Complementary and alternative medicine: practice and perspective of allopathic doctors at a tertiary care hospital

2016-09-23T23-25-50Z
Source: International Journal of Basic & Clinical Pharmacology
Dharani Sundarmurthy, Vijayalakshmi Devarashetty, Narayana Reddy S..
Background: Complementary and alternative medicine (CAM) has been defined as a group of diverse healthcare systems, not considered to be a part of conventional (allopathic) medicine. Approximately 80% of general population use traditional medicines (WHO). Thus, patients using CAM and its associated adverse effects may be encountered in practice of modern medicine. Hence it is necessary to assess the knowledge, attitude and practices of CAM among health care professionals (HCPs). Methods: After obtaining IEC approval, the cross-sectional study was conducted in doctors at Bangalore Medical College and its attached hospitals. 200 doctors who gave informed consent were included in the study. Results: 61.5% of the HCPs were aware that CAM includes AYUSH. 53% of the HCPs used CAM for self, especially for respiratory disorders (28.3%) and chronic painful conditions (21.6%). The common adverse effects attributed to use of CAM among patients which required consultation of the HCPs were hepatic (42.5%) and renal impairment (32.5%), allergy (10%), relapse (10%), and metal intoxication (5%). 71% didnt prefer suggesting CAM for patients. 70% opined that CAM therapies be subjected to clinical trials. Conclusions: HCPs had used CAM therapy for self at least once especially for respiratory disorders and chronic painful conditions. However majority of the HCPs didnt prefer suggesting CAM to patients and as many as 70% of the HCPs insisted that CAM therapies be subjected to scientific evaluation including clinical trials in view of patient safety before integrating them with conventional medicine.


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Price analysis of antianginal drugs available in Indian market

2016-09-23T23-25-50Z
Source: International Journal of Basic & Clinical Pharmacology
Vihang S. Chawan, Sagar V. Badwane, Kalpesh V. Gawand, Maheshi U. Chhaya.
Background: Coronary artery disease (CAD) is one of the most common causes of cardiovascular mortality and morbidity in developing countries like India. Initial management includes use of many antianginal drugs. There is wide variation in market prices of these drugs. This study was planned to analyse the percentage variation in prices amongst monotherapy and combination therapy of antianginal drugs manufactured and sold under different brand names in Indian market. Methods: Price of antianginal drugs manufactured by different pharmaceutical companies, in the same strength and dosage forms was obtained from "Current Index of Medical Specialties (CIMS)" January-April 2016 and "Indian Drug Review (IDR)" Vol. XXII, Issue No.1, 2016. The difference in the maximum and minimum price of the same drug manufactured by different pharmaceutical companies and percentage variation in price per 10 tablets was calculated. Results: Percentage variation in price for antianginal drugs marketed in India was found to be amlodipine (5 mg) 1128.57% followed by amlodipine (10 mg) 1040% and amlodipine (2.5 mg) 780% as a monotherapy. Whereas atenolol (25 mg), atenolol (50 mg) and nicorandil (10 mg) also showed significant percentage variation in prices 525%, 426.66% and 350.84% respectively. For combination therapy, percentage variation in prices were seen with amlodipine + atenolol (5 + 50 mg) 700%, followed by atenolol + hydrochlorothiazide (50 + 12.5 mg) 362.5% and Isosorbide dinitrate + aspirin (5 + 75 mg) 300%. Conclusions: There is a wide variation in the price of different brands of antianginal drugs available in India. The clinicians prescribing these drugs should be aware of these variations to reduce the financial burden of drug therapy.


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A prospective cohort study to evaluate the correlates of polypharmacy and its association with depression among elderly patients

2016-09-23T23-25-50Z
Source: International Journal of Basic & Clinical Pharmacology
Shweta Srivatsa, Debdipta Bose, Sushma M, Jayanthi C.R..
Background: Polypharmacy is a reliable indicator of irrational prescribing particularly among elderly. Polypharmacy increases the risk of adverse drug reactions (ADRs) exponentially imposing higher economic burden. Addressing and evaluating the prescribing practices in elderly will rationalize the drug utilization leading to improvement in quality of health care. The present study was taken to evaluate the determinants of polypharmacy and its association with depression, defined as a 15 item geriatric depression scale (GDS) >6, in elderly patients. Methods: This prospective cohort study was conducted at department of medicine, Victoria hospital, Bengaluru 100 patients aged 60 and above years was enrolled. Relevant data regarding patients demographic details, smoking and alcohol consumption, medical diagnosis and drug details were collected. Geriatric Depression Scale was used to diagnose depression. Results: Out of 100 patients screened, 36% were males and 64% were females. Polypharmacy was noted in 73% of the elderly, of which 43% had cumulative co morbidity (≥4 diagnoses). 68% were found to have a GDS score of ≥6, which corresponded to Depression. Patients with depression (GDS score ≥6) had 1.54 (OR-1.54, 95% CI-0.59-4.01) times more risk of encountering polypharmacy (≥4 drugs). Cumulative co-morbidity (OR-1.52, 95% CI-1.082.11, p


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Study to assess knowledge, attitude and practice regarding swine flu vaccine amongst medical students

2016-09-23T23-25-50Z
Source: International Journal of Basic & Clinical Pharmacology
Rajvardhan R. Solunke, Shrikant C. Dharmadhikari, Jugalkishore B. Jaju, Ganesh R. Pawar, Aruna Gurung.
Background: Due to recurrent outbreak and associated high mortality of swine flu there is panic amongst medical students also because of higher risk of getting infected. Vaccination for swine flu is the best preventive measure. So this study was undertaken. The aim of the present study was to assess the knowledge, attitude and practice regarding swine flu vaccine amongst medical students of government medical college and provide data to improve awareness about swine flu vaccine Methods: This was a cross sectional observational study carried out amongst 250 medical students during period of April-June 2015. A pre designed and pre tested, multiple choice questionnaires was used to assess KAP regarding swine flu vaccine and descriptive analysis was done. Results: Knowledge of participants regarding Swine flu vaccine was high as the mean score of correct answers marked was 152.5. But Only 21.8% participants had knowledge about cost of vaccine and 33.2% about the adverse drug reactions to the vaccine. Internet was the most common source of information amongst participants. Attitude of participants toward vaccination was favourable (mean score -128.4) but attitude for vaccination during pregnancy (30.8%) and with other vaccines (32.8%) was unfavourable. Only 30(12%) candidates have taken the vaccine which shows very poor practice. Conclusions: This study shows high knowledge, favourable attitude but poor practice towards Swine flu vaccination amongst medical students. So there is need to increase awareness for vaccination of swine flu amongst medical students by continuous health education and also need to increase the availability of vaccine in government hospitals.


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To study the pattern of adverse drug reactions among patients hospitalized in the medical wards of a tertiary care hospital

2016-09-23T23-25-50Z
Source: International Journal of Basic & Clinical Pharmacology
Anup Kumar, Dinesh Kansal, Parveen Kumar Sharma, Amit Bhardwaj, Sushma Sawaraj.
Background: ADRs have a major impact on public health, quality of life. ADRs are a recognized hazard of drug therapy. Although some ADRs are minor and resolve without squeal, others can cause permanent disability or death. Despite the methodological rigor of clinical trials, it is generally not possible to identify all safety issues associated with drugs during the pre-marketing research phase. The only way to find out such occurrences is to be on active-look out for adverse events over a long time horizon in large population and in different host conditions. The information may be useful in identifying and minimizing preventable ADRs, while generally enhancing the knowledge of the prescribers to deal with them more efficiently. Methods: This retro-prospective study was conducted in a tertiary care hospital for one year. Data of those patients who experienced ADRs was recorded in detail from internal Medicine ward. An assessment of causality was done. Data was evaluated to determine the class of drugs and the organ systems frequently associated with ADR within the settings of the institute. Results: The total incidence of ADRs was 7.59% in hospitalized patients with male predominance. Most common system involved was GIT followed by CNS and CVS. Antibiotics were most common culprits for ADRs followed by NSAIDS and hypoglycemic agents. In causality assessment probable ADRs were much more than possible ADRs. Severity of reaction in most of the patients was moderate. Majority of ADRs were Type A and maximum were probably preventable. Conclusions: There is need to explore the reasons for this relatively low incidence rate of ADRs in the Indian population. Under­reporting is one of the major factors with a lack of proper pharmacovigilance system which is still in budding state in India.


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Single dose metronidazole, tinidazole and ornidazole in the treatment of bacterial vaginosis - a comparative study

2016-09-23T23-25-50Z
Source: International Journal of Basic & Clinical Pharmacology
Banapura Ambika, Mamatha K. R., Geetha Shivamurthy.
Background: Bacterial vaginosis (BV) is the most common cause of abnormal vaginal discharge. There is a lack of consensus on the etiologic agents or agents associated with BV, due to polymicrobial nature. There is high recurrence rate of BV and it is difficult to treat. Metronidazole is the drug of choice but newer nitroimidazoles are better alternatives with long half-lives and better tolerability. Methods: This was a prospective, comparative, randomized, single blinded study on 120 diagnosed cases of bacterial vaginosis, with symptomatic or asymptomatic abnormal vaginal discharge. Amsel's criteria were used to diagnose bacterial vaginosis as well as to assess the response and classify the patients as cured, partially cured and not cured. Statistical analysis was done by Chi square test. The cure rate was compared considering metronidazole cure rate as gold standard. Results: At 1 week, the cure rate of tinidazole and ornidazole was 89.5% in both the groups, and at 4 weeks, it was 84.5% for both drugs (P


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Comparative assessment of the pattern of anti-hypertensive drugs prescribed in medicine and cardiology outpatient department

2016-09-23T23-25-50Z
Source: International Journal of Basic & Clinical Pharmacology
Bhargav Gaikwad, Sagar Bhagat, Ketaki Patil.
Background:Hypertension or High blood pressure is one of the strongest modifiable risk factors for cardiovascular and renal diseases and is a condition that afflicts almost 1 billion people worldwide Objective: To compare the prescribing pattern of antihypertensive drugs in patient attending medicine and cardiology OPD Methodology: observational, cross sectional study conducted in the department of pharmacology in collaboration with the medicine and the cardiology department. Results :The present study which was conducted for a period of 6 months in the medicine and cardiology OPD showed unequal distribution of the patients in the medicine and cardiology OPD, with 223 patients attended medicine OPD while 434 patients attended cardiology OPD. Amongst the patients attending medicine OPD, majority of the patients (61.88%) were stage 1 hypertensive (>140/90mmHg) according to JNC VII classification whereas majority (69.38%) of those attending cardiology OPD were stage II hypertensive (>160/100). calcium channel blockers (CCB) were the most commonly prescribed drug in medicine OPD followed by angiotensin converting enzyme inhibitors (ACEI) whereas beta blockers (BB) were most commonly prescribed in cardiology OPD followed by ACEI.


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A comparative prospective study to assess the clinical efficacy and safety of pantoprazole monotherapy versus pantoprazole and itopride dual therapy in patients with gastroesophageal reflux disease in a tertiary care hospital

2016-09-23T23-25-50Z
Source: International Journal of Basic & Clinical Pharmacology
Pradeep Kumar BT, Mamatha KR, Nagesh NS, Jayanthi CR, Bharath Kumar VD.
Background: Gastroesophageal reflux disease (GERD) is a common chronic, relapsing condition that carries a risk of significant morbidity and potential mortality from resultant complications. Proton pump inhibitors (PPIs) remained as the main stay in the therapy of GERD but they do not have any role in increasing the tone of lower esophageal sphincter which is the main pathophysiology of GERD. In this regard addition of prokinetic agent like Itopride may be beneficial in improving the symptoms associated with GERD. So the present study has been taken to compare the healing rates of esophagitis and reduction in symptom scores associated with GERD between Pantoprazole monotherapy and Pantoprazole plus Itopride combination. Methods: 100 patients diagnosed with GERD were randomly assigned into two groups, Group A and Group B. Group A received tablet Pantoprazole 40 mg twice daily alone and group B received tablet Pantoprazole 40 mg twice daily and tablet Itopride 50 mg thrice daily 30 minutes before food for 4 weeks. The patients were followed up at the end of 4 weeks and were given the questionnaire to assess the FSSG scores. Endoscopy and FSSG scores were recorded and then the percentage of responders in both groups was compared. Results: Endoscopic evidence of healing of esophagitis was similar in both the groups, 72% in Group A and 74% in Group B. The symptom relief was significantly more in Pantaprozole plus Itopride group 74.5% (4.2±1.6) than Pantaprozole alone 62.5% (6.4±1.1) after 4 weeks (p

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To evaluate and compare antidepressant activity of Rosa damascena in mice by using forced swimming test

2016-09-23T23-25-50Z
Source: International Journal of Basic & Clinical Pharmacology
Hemapriya Tirupathi, Padmavathi Golla.
Background: Rosa damascene mill L (R. damascena) is an ornamental plant that has several therapeutic (such as sedative and hypnotic) effects. It also heals depression, grief, nervous stress and tension. In the present study we evaluated antidepressant-like effect of R. damascena using forced swimming test (FST). The forced swim test is a commonly used stressor test, where mice are forced to swim in specially constructed tanks for a particular period and looked for behavioural activation characterized by vigorous swimming and diving to search for alternate routes to escape. Animal health including human has been shown to be affected by the stressful events of the life inducing situation which alters cognition, learning memory and emotional responses, causing mental disorders like depression and anxiety and stress in mice. Methods: The experiment was carried out with 24 healthy albino mice of either sex weighing about 25-30 gm. These were acclimatized to their environment for one week prior to experimentation. Two doses of aqueous extract (20 and 40 mg/kg) were injected intraperitoneally. After 30 min of injection, immobility and swimming times were measured and compared with control (negative control) and imipramine (positive control). Results: In the present study R. damascena in the doses of 20 mg and 40 mg/kg significantly decreased the immobility time compared to the control than standard, thereby proving that it has antidepresssant activity. The dose of 40 mg/kg body weight showed anti-depressant activity almost similar to the standard dug imipramine (10 mg/kg). Conclusions: Antidepressant activity of R. damascena was studied by forced swimming test in mice in the doses of 20 mg/kg and 40 mg/kg .This test shows that R. damascena significantly decreased the immobility time in mice. The results suggest that R. damascena has dose dependent antidepressant activity comparable with imipramine.


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To evaluate the creatinine clearance and compare nephrotoxic potential of Amikacin and Gentamicin, in post operative patients with normal baseline renal function

2016-09-23T23-25-50Z
Source: International Journal of Basic & Clinical Pharmacology
Subarna Bajracharya, Krishna Pandey, Ataul Haque.
Background: The majority of infections on any surgical ward are usually due to one or more of the gram-negative bacilli. Among the different groups of antimicrobials that have been used to treat these infections, Aminoglycoside antibiotics such as Amikacin and Gentamicin are the most commonly used. Methods: The study is 1 year, non-interventional, prospective study of patients administered either Amikacin or Gentamicin following surgery carried out in surgery ward in co-ordination with department of Pharmacology, Teerthanker Mahaveer Medical College and Research Centre Moradabad. Results: The mean difference in final and initial serum creatinine values were observed to be 0.32 and 0.52 with a standard deviation of 0.228 and 0.387 in AM and GM group respectively. This difference was statistically significant with p value of 0.007. The mean difference in final and initial creatinine clearance values were observed to be 18.82 and 24.76 with a standard deviation of 10.14 and 11.93 in AM and GM group respectively. This difference was also statistically significant with p-value of 0.013. Nephrotoxicity occurred in 9 out of 50 patients (18%) in AM group out of which 12% were male and 6% were female whereas in case of GM group nephrotoxicity occurred in 16 out of 50 patients (32%) in which 26% were male and 6% were female. Conclusions: From this study we can conclude that Gentamicin is more nephrotoxic and causes greater fall in creatinine clearance although the dose of Gentamicin administered is much lower compared to Amikacin.


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A study of serum psedocholinesterase levels following diazinon poisoning in relation to liver function-prognostic and therapeutic value

2016-09-23T23-25-50Z
Source: International Journal of Basic & Clinical Pharmacology
K. Swarnalatha, B. Surya Prakasa Rao, S. Sharon Sonia.
Background: To study serum pseudo-cholinesterase (PChE) levels as an index of liver injury in individuals with diazinon poisoning with or without alcoholism. It gives the knowledge of the therapeutic efficacy and severity of liver dysfunction. Methods: Blood samples were taken from normal male adults as control and PChE is estimated. Blood samples were taken from diazinon poisoning patients from local hospitals on the 1st day and on 5th day for pseudocholinesterase estimation. Another group of blood samples were taken on the 1st day and on the 5th day from diazinon poisoning patients with history of alcoholism serum PChE is estimated. Results: Serum PChE was estimated among the normal healthy male adults as the normal value of enzyme for the various levels for comparison. Among 30 normal adults, the control value of PChE ranged between 125 and 321 µmol/ml with 212 as the mean. Following the treatment with atropine, PAM and blood transfusion, blood samples were estimated by 5th day among patients with diazinon. Their mean value was found to be 200 µmol/ml. Among individuals with alcohol and diazinon poisoning, following the treatment, the serum PChE levels were raised comparatively on 1st day. The value is 100 µmol/ml. Conclusions: In diazinon poisoning without alcoholism, the prognostic and therapeutic efficacy of the drugs is better unlike in alcoholics. Hence a scope of necessitating the hepatoprotective measures is of consideration in the organophosphorous poisoning cases.


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Knowledge towards antibiotic usage among paramedics and non-medical personnels of a tertiary care hospital

2016-09-23T23-25-50Z
Source: International Journal of Basic & Clinical Pharmacology
Pranjit Narzaree, M. C. Gupta.
Background: The aim of this study was to assess the knowledge, self-medication behaviour and attitudes toward antibiotic usage among paramedics and non-medical working staff of a tertiary care hospital. Methods: A cross-sectional study was designed using a self-administered questionnaire to access the knowledge, self-medication behaviour and attitude towards antibiotics usages among the two groups of participants from paramedics and non- medical working staff of PGIMS Rohtak administration. Results: All the participants from paramedics (100%) were aware of the term antibiotics and antibiotic resistance compared to the non-medical personnels. Non-medical staffs (86%) were aware of the term antibiotics but their understanding about antibacterial resistance was only 44 %. Majority of participants have self-medication experiences (86% and 84% for paramedics and non-medical staff respectively). Antibiotics were used by both the groups for symptomatic treatment of various clinical conditions without any rationale justifications. The major reason for not visiting medical practitioner was cost saving and convenience (non-medical staff 80% and paramedics 60%. Antibiotics were mainly obtained from the community pharmacist (non-medical staff 100% and paramedics 68%). Conclusions: Self-medication practice was prevalent among the participants and lack of up-to-date knowledge was the major areas of concern. Antibiotic awareness should reach every corner of our society for prevention of antibiotic resistance.


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A comparative study of efficacy of atorvastatin, rosuvastatin, and atorvastatin + fibrates as lipid lowering agents

2016-09-23T23-25-50Z
Source: International Journal of Basic & Clinical Pharmacology
Karunasree Nagarur, Yamini Vadlamannati, Narasimha Rao Raja.
Background: Hypercholesterolemia patients are at high risk of coronary heart disease. National cholesterol education programme (NCEP) Adult Treatment Panel III guidelines provide the option of aggressively lowering Low-density cholesterol in them. Presently the standard therapy of hypercholesterolemia is by HMG co-A reductase inhibitors. Present study shows that Rosuvastatin is better than Atorvastatin, Atorvastatin and Fibrate is better than Atorvastatin monotherapy in management of hypercholesterolemia. Methods: The present research was an observational study conducted at Government general hospital, Nizamabad. A total of 150 patients on treatment for hypercholesterolemia for more than one year were enrolled in our study. They were divided into three groups. Group I: Atorvastatin (20 mg) (n=96; 64%); Group II: Rosuvastatin 10 mg (n= 41; 27.33%); Group III: Atorvastatin (20 mg) + Fibrate (145 mg) (n=13; 8.66%). Results: Rosuvastatin is better than Atorvastatin and Atorvastatin with fibrates reduces LDL, TG more than Atorvastatin alone. Conclusions: Rosuvastatin is better than Atorvastatin and Combination of atorvastatin with fibrates reduces LDL-Cholesterol and triglycerides more than atorvastatin alone.


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Evaluation of antimicrobial activity of orange peel extract against oral biofilm forming organisms: an in vitro microbial study and scanning electron microscopic assessment

2016-09-23T23-25-50Z
Source: International Journal of Basic & Clinical Pharmacology
Chetana Dilip Mankar, Mona Udayan Shah, Yogesh Sharad Doshi, Monika Bajaj, Vidhi Kevadia, Roshini Vinod.
Background: To evaluate in vitro antimicrobial activity of orange peel extract, 0.2% chlorhexidine (CHX) and saline against dental biofilm-forming bacteria and their effect on plaque structure under SEM. Methods: Present study included 3 groups; Group A: Orange peel extract; Group B: 0.2% CHX and Group C: Saline. MIC of each group was determined by broth and well diffusion method. Reference strains of Porphyromonas gingivalis (P.g.), Prevotella intermedia (P.i.) and Aggregatibacter actinomycetemcomitans (A.a.) were selected as being colonizers in dental biofilm. For SEM analysis, plaque retained orthodontic e-chains were subjected to each group for 60s and studied under SEM. Results: The MIC of Group A by broth diffusion method is 66.66 µg/ml for P. intermedia, 75 µg/ml for P. gingivalis and 33.33 µg/ml for A.a. MIC of Group B was 14.58 µg/ml for P.i., 7.29 µg/ml for P.g. and 20.83 µg/ml for A.a. MIC of Group C was 83.33 µg/ml for A.a. while P.i. and P.g. showed resistance to Group C. The determination of MIC by well diffusion showed increase in clear zone diameter with increasing concentrations. Greater zone of inhibition was seen in Group B with statistical significance for all 3 microorganisms. Morphologic changes in the SEM study showed maximum change in the surface characteristics and loss of adhesion of the clusters of microorganisms subjected to Group B. Conclusions: CHX and orange peel extract exhibited notable anti-microbial activity against biofilm organisms, but at varying concentrations. The plaque samples subjected to orange peel extract showed slightly shrunken and coarse form indicating its ability to disrupt the plaque biofilm.


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Paradoxical nocturnal agitation associated with mirtazapine therapy

2016-09-23T23-25-50Z
Source: International Journal of Basic & Clinical Pharmacology
Olayinka A. Ogundipe, Zubaidat M. Oduniyi.
This report describes an 85 year old woman presenting with a mixed delirium with risk factors of hyponatraemia, polypharmacy, and bilateral frontal lobe atrophy with small vessel cerebrovascular disease. Treatment for depression with oral citalopram had been revised to oral mirtazapine, with the aim of reducing the risks of recurrent hyponatraemia noted with the former. She developed an evolving adverse drug reaction (ADR) symptom profile of insomnia, and later severe paradoxical nocturnal agitation. These symptoms were subsequently noted to correlate with both the night-time dosing pattern, and the increased dosing regimen of the mirtazapine. The symptoms settled rapidly following withdrawal of the mirtazapine. The report briefly reviews the relevant literature, and two previously validated causality assessment systems are applied to the index case to support the pharmacovigilance process. This is aimed at promoting objectivity in assessing for the likelihood that the suspected medication (mirtazapine) was the cause for the noted adverse drug reaction.


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Evaluation of eslicarbazepine for its antidiuretic effect in albino wistar rats

2016-09-23T23-25-50Z
Source: International Journal of Basic & Clinical Pharmacology
Satish AM, Mohammed Sibgatullah, Lokraj Subedee, Shashi Kumar, Umme Salma, Varun Gupta.
Background: Diabetes insipidus is characterized by polyuria, polydipsia with hyposthenuria, causing dehydration and hypernatremia if the patient is deprived of water. Vasopressin analogues and drugs causing water retention are used in this condition. The aim of the present study was to evaluate the antidiuretic effect of eslicarbazepine in albino rats. Methods: The animals were divided into 3 groups each containing 6 animals. The first group was constituted by the control group which received distilled water. The second was the standard group which received vasopressin. The third group was constituted by the test group which received the test drug eslicarbazepine. The test drug was given for a period of 5 days. On 5th day, one hour after administration of respective drugs in different groups, diuresis was induced in all groups of animals by Furosemide after they were loaded with normal saline after overnight fasting. The volume of urine collected was measured at the end of 5 hours from each of the group along with sodium, potassium and chloride concentrations. Results: There was significant water retention and urine was concentrated in the test group which received eslicarbazepine when compared to the control group. Conclusions: Eslicarbazepine has significant water retaining capacity in albino wistar rats. Further evaluation is required before using it in diabetes insipidus.


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A comparative study of antinociceptive effect of fluoxetine with pentazocine in rodent model

2016-09-23T23-25-50Z
Source: International Journal of Basic & Clinical Pharmacology
Manjunatha C. H., Jagadishchandra S. Ratnakar.
Background: Chronic pain affects millions of people across the globe, commonly coexisting with depression. Antidepressants like fluoxetine have shown potential to have analgesic activity with superior safety profile and hence might be better suited in the treatment of chronic pain. The objective of this study was to evaluate the antinociceptive activity of fluoxetine and to compare the antinociceptive effect of fluoxetine with pentazocine. Methods: Adult albino rats weighing 150-200 grams were used in this study. Screening method used was Acetic acid induced writhing method in rats. Rats were divided into three groups of 5 animals and drugs administered as follows: group-1: distilled water (control), group-2: Fluoxetine, group-3: Pentazocine. All drugs were administered 30 minutes before the onset of pain stimulus. Statistical analysis was done by using one way-analysis of variance (one way ANOVA) followed by Tukey-Kramer test. Results: Fluoxetine failed to show significant antinociceptive activity in Acetic acid induced writhing method. Conclusions: Fluoxetine is an SSRI and one of the most commonly prescribed drug for depression. It is proven to act at multiple sites like serotonin transporter and opioid µ receptor, both of which may play a role in its analgesic activity.


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Evaluation of medication adherence patterns amongst anti-hypertensive drug users in a tertiary care hospital in north India

2016-09-23T23-25-50Z
Source: International Journal of Basic & Clinical Pharmacology
Mahesh Chander Gupta, Ankita Bhattacharjee, Harpreet Singh.
Background: Non-adherence to prescribed medications is a major barrier in management of chronic diseases like hypertension, which can lead to treatment failure and can increase morbidity, mortality and health care costs. The objective of this study was to assess the level of adherence of hypertensive patients to their anti-hypertensive medications and various factors influencing the adherence among these patients. Methods: A cross sectional, observational, questionnaire based study was carried out amongst 70 patients diagnosed with hypertension. Adherence was measured using Morisky medication adherence score questionnaire (MMAS-8). Co-relation of various factors like age, sex, education level, number of drugs taken, presence of concomitant diseases etc. were assessed. Univariate and multivariate analysis was done to determine the factors associated with adherence. Results: The mean age of 70 patients (35 male, 35 female) were 52.29±11.39 years. Using MMAS-8, high, medium and low adherence was seen in 58.6%, 20.0% and 21.4% patients respectively. Middle age group patients were more adherent (60.8%) than younger age group and elderly (37.5%) (p-value


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Studies on the concept, knowledge and attitude of the rational use of medicines among the sixth semester 2nd MBBS student of Jawaharlal Nehru Institute of Medical Sciences, Porompat, Imphal, Manipur, India

2016-09-23T23-25-50Z
Source: International Journal of Basic & Clinical Pharmacology
Varkung Valte, Premchand M. Singh, Indira Raleng.
Background: The present study was designed to accesses the concept, knowledge and attitude of rational use of medicine among the sixth semester 2nd MBBS students with the aim to install rational use of medicine amongst the prescriber right from the grass root level. Methods: The study has been conducted in Jawaharlal Nehru Institute of Medical Sciences Porompat, Imphal, Manipur during 2015-2016 session. The studies has been organised in accordance with World Health Organisation (WHO) Good Prescribing Guide. The students were subjected to presented questionnaire on concept, knowledge and attitude on the rational use of medicine. The design of the study is simple cross sectional study. Percentage, proportions and means are used for descriptive statistics while the associations are calculated using corresponding tests for the associations. Results: The majority of the students have a clear cut concept in the present studies (96.7%); integration with other subject (80.3%); usefulness in the future practice (98.3%); initiative and willingness (91.0%); learning the topic in the MBBS course (95.0%); out of the total questionnaire of 61, only 7 questions on concept, knowledge and attitude have been selected for further analysis. 3.2% do not have the knowledge of RUMs; 13.1% do not feel necessary to integrate with other subjects; 8.1% are indecisive, 4.91% do not feel necessary to learn RUMs; 16.3% do not have any idea about the role of evaluation. Conclusions: The present study will enlightened the young energetic medical students to practice rational use of medicine and improves WHO Good prescribing method and rational pharmacotherapy skills in the future.


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Antihypertensive and antiatherogenic effects of Tanopati a traditional recipe used for the treatment of high blood pressure

2016-09-23T23-25-50Z
Source: International Journal of Basic & Clinical Pharmacology
Amani Komenan Nazaire, Djyh Bernard Nazaire, Boga Gogo Lucien, Kouassi Konan, Severin Kouakou Konan, NGuessan Jean David.
Background: The objective of the present study was to investigate the possible effect of Tanopati on induced hypercholesterolemia in rats and hypertension in rabbits. Methods: Twenty wistar rats were divided into 4 groups each and then subjected to different treatments. Hypercholesterolemia was induced by induced dietary cholesterol; the rats are then treated with Tanopati and Questran®) Sixteen rabbits males, divided in four lots with four rabbits each, were used in this study. Hypertension was induced by adrenalin (1 mg/ml for 2 weeks intramuscularly) in the lots 2 to 4. After induction of hypertension in animals, they were treated with the extract of Tanopati. The cardiovascular parameters of rabbits (systolic blood pressure (SBP), diastolic blood pressure (DBP) and heart rate (HR) was taken with an electric manometer. These three cardiovascular parameters were then compared to the witness group. Results: The treatment with the Tanopati and with Questran® significantly improved (p


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Serum Iron, Zinc and its relationship with Blood lead levels among lead exposed worker from lead battery plant.

2016-09-23T14-47-06Z
Source: Journal of Molecular Pathophysiology
Bhavani Shankara Bagepally, Ravibabu Kalahasthi, Tapu Barman.
Objective: Present study was conceived to examine the relationship between blood lead level (BLL) and serum Iron (Fe) and Zinc (Zn) in lead-exposed workers from lead Battery plant. Methods: The study design was cross-sectional. Ninety seven male workers involved in the lead battery manufacturing plant were considered as study subjects. BLL, serum Zn and Fe were estimated using Atomic Absorption Spectrophotometer. Haematological parameters were determined by using an Fx-19E haematology analyser. The renal function tests - creatinine and blood urea nitrogen (BUN) determined by standard methods. The statistical analysis was performed on SPSS version 16. Results: The body mass index (BMI) of subjects was 25.8±3.0. The systolic blood Pressure (SBP) was 127.8±14.5 mm Hg while diastolic blood Pressure (DBP) was 77.8±10.8 mm Hg. The workers with >30 µg/dL BLL (Fe 1745 ± 723 µg/L) had significantly (P


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Hypothyroidism and anemia in pregnancy

2016-09-23T08-52-31Z
Source: International Journal of Advances in Medicine
Usha Agrawal, Preshant Shrivastava, Shweta Shrivastava.
Background: Hypothyroidism and anemia are widely prevalent in pregnant women. Due to better diagnostic facilities and increased awareness, more cases of hypothyroidism are seen. Using ATA trimester specific guidelines for diagnosis of hypothyroidism has also resulted in increased prevalence of hypothyroidism in pregnancy. This study was undertaken to evaluate the prevalence of hypothyroidism among pregnant women, and to study the correlation between the prevalence of hypothyroidism and anemia in pregnant women. Methods: A total of 110 consecutive antenatal women attending the antenatal clinic were included in our study. A detailed clinical and obstetric history was obtained from them. The cases underwent routine clinical and obstetric examination. Blood samples were sent to lab for routine haematology and fasting serum TSH testing. Results: Out of 110 cases, Raised S. TSH (>2.5mIU/L) suggestive of thyroid dysfunction was seen in 35 (31.81%) cases. Hb 2.5 mIU/L) was seen in 35 (31.81%) cases. Amongst the cases with anemia, 42.86% had S.TSH >2.5 mIU/L. Anemia and Hypothyroidism are very common in our country in pregnancy. It is likely, that hypothyroidism may add on to the severity of anemia. Early diagnosis and treatment of hypothyroidism during pregnancy will help in reducing anemia and adverse maternal and fetal outcomes


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Myeloid sarcomas of the head and neck in pediatric patients with myeloid leukemia.

Related Articles

Myeloid sarcomas of the head and neck in pediatric patients with myeloid leukemia.

Ear Nose Throat J. 2016 Sep;95(9):405-407

Authors: Cuthbertson DW, Punia JN, Owczarzak VL

Abstract
Myeloid sarcoma is a rare extramedullary tumor composed of malignant myeloid cells that occur in the presence of myeloid leukemia. We report a case series of pediatric head and neck myeloid sarcomas representative of the epidemiology, symptomatology, laboratorial correlations, prognoses, and treatment of extramedullary leukemia. Presented are 3 cases involving patients ranging from 17 months to 11 years of age. Two patients were successfully treated with chemotherapy, and in the third patient, a large lytic lesion was treated palliatively with proton beam therapy. Knowledge and recognition of myeloid sarcomas is important as they can be locally invasive, and they may also be used as a diagnostic tool or a prognostic indicator for leukemia.

PMID: 27657319 [PubMed - as supplied by publisher]

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Molecular cloning, characterization and expression analysis of TGF-β and receptor genes in the woodchuck model

Publication date: 20 December 2016
Source:Gene, Volume 595, Issue 1
Author(s): Lu Wang, Junzhong Wang, Yana Liu, Baoju Wang, Shangqing Yang, Qing Yu, Michael Roggendorf, Mengji Lu, Jia Liu, Dongliang Yang
Transforming growth factor beta (TGF-β) is an important cytokine with pleiotropic regulatory functions in the immune system and in the responses against viral infections. TGF-β acts on a variety of immune cells through the cell surface TGF-β receptor (University of Duisburg-EssenTGFBR). The woodchuck has been used as a biomedical model for studies of obesity and energy balance, endocrine and metabolic function, cardiovascular, cerebrovascular and neoplastic disease. Woodchucks infected with woodchuck hepatitis virus (WHV) represent an informative animal model to study hepatitis B virus (HBV) infection. In this study, the cDNA sequences of woodchuck TGF-β1, TGF-β2, TGFBR1 and TGFBR2 were cloned, sequenced and characterized. The full-length TGFBR1 cDNA sequence consisted of 1305bp coding sequence (CDS) that encoded 434 amino acids with a molecular weight of 48.9kDa. The phylogenetic tree analysis revealed that the woodchuck TGF-β family genes had a closer genetic relationship with Ictidomys tridecemlineatus. One antibody with cross-reactivity to woodchuck TGFBR1 was identified by flow cytometry. Moreover, the expression of these genes were analyzed at the transcriptional level. The quantitative PCR analysis showed that the TGF-β family transcripts were constitutively expressed in many tissues tested. Altered expression levels of the TGF-β family transcripts in the liver of WHV infected woodchucks were observed. These results serve as a foundation for further insight into the role of the TGF-β family in viral hepatitis in woodchuck model. Our work also possesses the potential value for characterizing the TGF-β family in other related diseases, such as obesity-related diseases, metabolic disorder, cardiovascular disease and cancer.



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Scientists demand halt to damming of Europe’s last wild river

More than 200 researchers from 33 countries are urging the Albanian government to save the Vjosë, the continent’s last surviving unexplored waterway

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High incidence and persistence of airborne allergen sensitization up to age 19 years

Abstract

Background

Longitudinal population-based studies about the natural history of allergic sensitization are rare. The aim was to study incidence and persistence of airborne allergen sensitization up to young adulthood, and risk factors for early and late onset of sensitization.

Methods

All children aged 7-8 years in two municipalities in Northern Sweden were invited to a parental questionnaire and skin prick tests (SPT) to ten airborne allergens, and 2,148 (88%) participated. The protocol was repeated at age 11-12 and 19 years, and 1,516 participated in all three examinations.

Results

Prevalence of any positive SPT increased from 20.6% at age 7-8y to 30.6% at 11-12y, and 42.1% at 19y. Animals were the primary sensitizers at age 7-8y, 16.3%, followed by pollen, 12.4%. Mite and mold sensitization was low. Mean annual incidence of any positive SPT varied between 2.8-3.4/100/year, decreased by age for animal and was stable for pollen. Sensitization before age 7-8y was independently associated with family history of allergy, OR 2.1(95%CI 1.6-2.8), urban living, OR 1.9(95%CI 1.2-2.9), and male sex, OR 1.3(95%CI 1.0-1.7), and negatively associated with birth order, OR 0.8(95%CI 0.7-1.0) and furry animals at home, OR 0.7(95%CI 0.7-0.9). Incidence after age 11-12y was associated only with family history of allergy. Multi-sensitization at age 19y was significantly associated with early age at sensitization. Remission of sensitization was uncommon.

Conclusion

The increasing prevalence of allergic sensitization by age was explained by high incidence and persistence. After age 11-12y the factors urban living, number of siblings and male sex lost their importance.

This article is protected by copyright. All rights reserved.

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Asthma is associated with reduced fibrinolytic activity, abnormal clot architecture and decreased clot retraction rate

Abstract

The aim of this study was to assess whether steroid-naïve asthma modulates hemostasis. We evaluated the clot retraction rate (CRR), fibrinolysis rate (FR), clot density (CD) (by confocal microscopy), plasma levels of plasminogen activator inhibitor (PAI-1), and factor XIII (FXIII), NO in exhaled breath (FE_NO), spirometry (FEV₁) and eosinophil count (EOS), in 36 patients with allergic, steroid-naïve asthma and in 34 healthy controls. We observed significantly (p<0.001) reduced CRR, FR, FEV₁; and increased FE_NO, EOS, PAI-1, FXIII, and CD in asthmatic patients compared with controls. In asthmatic patients FR negatively correlated with CD, FXIII, PAI-1, FE_NO and EOS, and positively with FEV₁. FXIII positively correlated with CD. CRR negatively correlated with FE_NO and positively with FEV₁ (all p<0.001). These novel findings suggest that asthma itself is associated with decreased CRR and reduced fibrinolytic potential resulting from alterations in clot architecture and elevated levels of plasma FXIII and PAI-1.

This article is protected by copyright. All rights reserved.

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Assessment of children's nutritional attitudes before oral food challenges to identify patients at risk of food reintroduction failure: a prospective study

Abstract

Background

Inappropriate dietary eliminations may impair quality of life, affect children's growth, and unnecessarily impact on healthcare costs. Previous retrospective studies reported that around 25% of children continue a food-avoidance diet despite a negative oral food challenge (OFC). A definite pattern has not been found yet for patients not reintroducing the food. The present study aimed to examine the role of child's nutritional attitudes and maternal anxiety in reintroducing food after a negative OFC.

Methods

A prospective study was conducted involving 81 mothers of children with IgE-mediated food allergy. They completed a survey on nutritional behaviour and attitudes and the State-Trait-Anxiety Inventory on the day of OFC and 6 months later.

Results

11.1% of children never or rarely ate the food after a negative OFC. Consumption of the reintroduced food is positively correlated to child's interest in tasting new foods before and after OFC and to changes in child's nutritional habits after OFC. It is negatively correlated to monotony of the diet after OFC. No correlations were found with other participants’ characteristics, or maternal anxiety. State anxiety significantly decreased after the OFC. A correlation was found between trait and state anxiety and the degree of change in nutritional habits after OFC.

Conclusions

Evaluating child's approach toward food before the OFC is a promising approach to identify patients at risk of food reintroduction failure. Furthermore, it underlined the importance of reassessing food consumption in all patients after a negative OFC and supporting patients in the reintroduction of food.

This article is protected by copyright. All rights reserved.

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Scientists demand halt to damming of Europe’s last wild river

More than 200 researchers from 33 countries are urging the Albanian government to save the Vjosë, the continent’s last surviving unexplored waterway

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Awakening tumour suppressors with CRISPR

Researchers have used an exciting new technology to successfully switch on dormant tumour suppressor genes in multiple cancer types. Dr Benjamin Garcia Bloj, along with his labmates from the Harry Perkins Medical Centre Cancer Epigenetics Laboratory...

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Comment on: “The Cost Effectiveness of High-Dose Versus Conventional Haemodialysis: A Systematic Review”

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Hemophagocytic lymphohistiocytosis responding to withdrawal of gluten: a case report

This is the first documented case of a patient with hemophagocytic lymphohistiocytosis in association with coeliac disease. There was complete clinical and biochemical remission of hemophagocytic lymphohistioc...

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Toxoplasma gondii pseudocyst in a transbronchial biopsy: a case report

We herein present a case in which a Toxoplasma cyst was found in a transbronchial biopsy specimen from an immunocompetent patient with negative serology for the parasite.

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Papillon–Lefèvre syndrome: a series of five cases among siblings

Papillon–Lefèvre syndrome is a rare autosomal recessive disorder characterized by palmoplantar hyperkeratosis and aggressively progressing periodontitis leading to premature loss of deciduous and permanent den...

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Amyand’s hernia with appendicitis masquerading as Fournier’s gangrene: a case report and review of the literature

The incarceration of an appendix within an inguinal hernia sac is known as Amyand’s hernia. Appendicitis in Amyand’s hernia accounts for 0.1 % of the cases. An aggressive necrotizing infection of the genitalia...

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The peri-esophageal connective tissue layers and related compartments: visualization by histology and magnetic resonance imaging

Abstract

An organized layer of connective tissue coursing from aorta to esophagus was recently discovered in the mediastinum. The relations with other peri-esophageal fascias have not been described and it is unclear whether this layer can be visualized by non-invasive imaging. This study aimed to provide a comprehensive description of the peri-esophageal fascias and determine whether the connective tissue layer between aorta and esophagus can be visualized by magnetic resonance imaging (MRI). First, T2-weighted MRI scanning of the thoracic region of a human cadaver was performed, followed by histological examination of transverse sections of the peri-esophageal tissue between the thyroid gland and the diaphragm. Secondly, pretreatment motion-triggered MRI scans were prospectively obtained from 34 patients with esophageal cancer and independently assessed by two radiologists for the presence and location of the connective tissue layer coursing from aorta to esophagus. A layer of connective tissue coursing from the anterior aspect of the descending aorta to the left lateral aspect of the esophagus, with a thin extension coursing to the right pleural reflection, was visualized ex vivo in the cadaver on MR images, macroscopic tissue sections, and after histologic staining, as well as on in vivo MR images. The layer connecting esophagus and aorta was named ‘aorto-esophageal ligament’ and the layer connecting aorta to the right pleural reflection ‘aorto-pleural ligament’. These connective tissue layers divides the posterior mediastinum in an anterior compartment containing the esophagus, (carinal) lymph nodes and vagus nerve, and a posterior compartment, containing the azygos vein, thoracic duct and occasionally lymph nodes. The anterior compartment was named ‘peri-esophageal compartment’ and the posterior compartment ‘para-aortic compartment’. The connective tissue layers superior to the aortic arch and at the diaphragm corresponded with the currently available anatomic descriptions. This study confirms the existence of the previously described connective tissue layer coursing from aorta to esophagus, challenging the long-standing paradigm that no such structure exists. A comprehensive, detailed description of the peri-esophageal fascias is provided and, furthermore, it is shown that the connective tissue layer coursing from aorta to esophagus can be visualized in vivo by MRI.

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TIP150-Cortactin Interaction Orchestrates Cell Migration [Signal Transduction]

Cell migration is orchestrated by dynamic interactions of microtubules with the plasma membrane cortex. How these interactions facilitate these dynamic processes is still being actively investigated. TIP150 is a newly characterized microtubule plus end tracking protein essential for mitosis and entosis (Ward, T., Wang, M., Liu, X., Wang, Z., Xia, P., Chu, Y., Wang, X., Liu, L., Jiang, K., Yu, H., Yan, M., Wang, J., Hill, D. L., Huang, Y., Zhu, T., and Yao, X. (2013) Regulation of a dynamic interaction between two microtubule-binding proteins, EB1 and TIP150, by the mitotic p300/CBP-associated factor (PCAF) orchestrates kinetochore microtubule plasticity and chromosome stability during mitosis. J. Biol. Chem. 288, 15771–15785; Xia, P., Zhou, J., Song, X., Wu, B., Liu, X., Li, D., Zhang, S., Wang, Z., Yu, H., Ward, T., Zhang, J., Li, Y., Wang, X., Chen, Y., Guo, Z., and Yao, X. (2014) Aurora A orchestrates entosis by regulating a dynamic MCAK-TIP150 interaction. J. Mol. Cell Biol. 6, 240–254). Here we show that TIP150 links dynamic microtubules to steer cell migration by interacting with cortactin. Mechanistically, TIP150 binds to cortactin via its C-terminal tail. Interestingly, the C-terminal TIP150 proline-rich region (CT150) binds to the Src homology 3 domain of cortactin specifically, and such an interaction is negatively regulated by EGF-elicited tyrosine phosphorylation of cortactin. Importantly, suppression of TIP150 or overexpression of phospho-mimicking cortactin inhibits polarized cell migration. In addition, CT150 disrupts the biochemical interaction between TIP150 and cortactin in vitro, and perturbation of the TIP150-cortactin interaction in vivo using a membrane-permeable TAT-CT150 peptide results in an inhibition of directional cell migration. We reason that a dynamic TIP150-cortactin interaction orchestrates directional cell migration via coupling dynamic microtubule plus ends to the cortical cytoskeleton.

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Kinesin-5 Mechanochemistry [Enzymology]

Single-molecule microscopy and stopped-flow kinetics assays were carried out to understand the microtubule polymerase activity of kinesin-5 (Eg5). Four lines of evidence argue that the motor primarily resides in a two-heads-bound (2HB) state. First, upon microtubule binding, dimeric Eg5 releases both bound ADPs. Second, microtubule dissociation in saturating ADP is 20-fold slower for the dimer than for the monomer. Third, ATP-triggered mant-ADP release is 5-fold faster than the stepping rate. Fourth, ATP binding is relatively fast when the motor is locked in a 2HB state. Shortening the neck-linker does not facilitate rear-head detachment, suggesting a minimal role for rear-head-gating. This 2HB state may enable Eg5 to stabilize incoming tubulin at the growing microtubule plus-end. The finding that slowly hydrolyzable ATP analogs trigger slower nucleotide release than ATP suggests that ATP hydrolysis in the bound head precedes stepping by the tethered head, leading to a mechanochemical cycle in which processivity is determined by the race between unbinding of the bound head and attachment of the tethered head.

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Activated G{alpha}s Samples Intracellular Membrane Compartments [Membrane Biology]

Heterotrimeric G proteins are localized to the plasma membrane where they transduce extracellular signals to intracellular effectors. G proteins also act at intracellular locations, and can translocate between cellular compartments. For example, Gαs can leave the plasma membrane and move to the cell interior after activation. However, the mechanism of Gαs translocation and its intracellular destination are not known. Here we use bioluminescence resonance energy transfer (BRET) to show that after activation, Gαs rapidly associates with the endoplasmic reticulum, mitochondria, and endosomes, consistent with indiscriminate sampling of intracellular membranes from the cytosol rather than transport via a specific vesicular pathway. The primary source of Gαs for endosomal compartments is constitutive endocytosis rather than activity-dependent internalization. Recycling of Gαs to the plasma membrane is complete 25 min after stimulation is discontinued. We also show that an acylation-deacylation cycle is important for the steady-state localization of Gαs at the plasma membrane, but our results do not support a role for deacylation in activity-dependent Gαs internalization.

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Regulation of Neuronal Viability by NPM1 [Cell Biology]

NPM1 (nucleophosmin 1) is a nucleolar phosphoprotein that regulates many cellular processes, including ribosome biogenesis, proliferation, and genomic integrity. Although its role in proliferating cell types and tissues has been extensively investigated, little is known about its function in neurons and in the brain where it is highly expressed. We report that NPM1 protein expression is increased selectively in the striatum in both the R6/2 transgenic and 3-nitropropionic acid-injected mouse models of Huntington's disease. Examination of the effect of ectopic expression on cultured neurons revealed that increasing NPM1 is toxic to otherwise healthy cerebellar granule and cortical neurons. Toxicity is dependent on its cytoplasmic localization and oligomerization status. Forced retention of NPM1 in the nucleus, as well as inhibiting its ability to oligomerize, not only neutralizes NPM1 toxicity but also renders it protective against apoptosis. Although not blocked by pharmacological inhibition of the pro-apoptotic molecules, JNK, glycogen synthase kinase 3 beta, or caspases, toxicity is blocked by compounds targeting cyclin-dependent kinases (CDKs), as well as by dominant-negative forms of CDK1 and CDK2 and the pan-CDK inhibitor, p21Cip1/Waf1. Although induced in in vivo Huntington's disease models, NPM1 protein levels are unchanged in cultured cerebellar granule and cortical neurons induced to die by low potassium or homocysteic acid treatment, respectively. Moreover, and counterintuitively, knockdown of its expression or inhibition of endogenous NPM1 oligomerization in these cultured neurons is toxic. Taken together, our study suggests that although neurons need NPM1 for survival, an increase in its expression beyond physiological levels and its translocation to the cytoplasm leads to death through abortive cell cycle induction.

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PC4 Affects Memory Processes [Gene Regulation]

Although the elaborate combination of histone and non-histone protein complexes defines chromatin organization and hence regulates numerous nuclear processes, the role of chromatin organizing proteins remains unexplored at the organismal level. The highly abundant, multifunctional, chromatin-associated protein and transcriptional coactivator positive coactivator 4 (PC4/Sub1) is absolutely critical for life, because its absence leads to embryonic lethality. Here, we report results obtained with conditional PC4 knock-out (PC4f/f Nestin-Cre) mice where PC4 is knocked out specifically in the brain. Compared with the control (PC4+/+ Nestin-Cre) mice, PC4f/f Nestin-Cre mice are smaller with decreased nocturnal activity but are fertile and show no motor dysfunction. Neurons in different areas of the brains of these mice show sensitivity to hypoxia/anoxia, and decreased adult neurogenesis was observed in the dentate gyrus. Interestingly, PC4f/f Nestin-Cre mice exhibit a severe deficit in spatial memory extinction, whereas acquisition and long term retention were unaffected. Gene expression analysis of the dorsal hippocampus of PC4f/f Nestin-Cre mice revealed dysregulated expression of several neural function-associated genes, and PC4 was consistently found to localize on the promoters of these genes, indicating that PC4 regulates their expression. These observations indicate that non-histone chromatin-associated proteins like PC4 play a significant role in neuronal plasticity.

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Identification of a Single {alpha}-Helix Motif in MLV [Microbiology]

The assembly of immature retroviral particles is initiated in the cytoplasm by the binding of the structural polyprotein precursor Gag with viral genomic RNA. The protein interactions necessary for assembly are mediated predominantly by the capsid (CA) and nucleocapsid (NC) domains, which have conserved structures. In contrast, the structural arrangement of the CA-NC connecting region differs between retroviral species. In HIV-1 and Rous sarcoma virus, this region forms a rod-like structure that separates the CA and NC domains, whereas in Mason-Pfizer monkey virus, this region is densely packed, thus holding the CA and NC domains in close proximity. Interestingly, the sequence connecting the CA and NC domains in gammaretroviruses, such as murine leukemia virus (MLV), is unique. The sequence is called a charged assembly helix (CAH) due to a high number of positively and negatively charged residues. Although both computational and deletion analyses suggested that the MLV CAH forms a helical conformation, no structural or biochemical data supporting this hypothesis have been published. Using an in vitro assembly assay, alanine scanning mutagenesis, and biophysical techniques (circular dichroism, NMR, microcalorimetry, and electrophoretic mobility shift assay), we have characterized the structure and function of the MLV CAH. We provide experimental evidence that the MLV CAH belongs to a group of charged, E(R/K)-rich, single α-helices. This is the first single α-helix motif identified in viral proteins.

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Roles of PKA Subunits in Lipolysis [Cell Biology]

Protein kinase A (PKA) is a cyclic AMP (cAMP)-dependent protein kinase composed of catalytic and regulatory subunits and involved in various physiological phenomena, including lipid metabolism. Here we demonstrated that the stoichiometric balance between catalytic and regulatory subunits is crucial for maintaining basal PKA activity and lipid homeostasis. To uncover the potential roles of each PKA subunit, Caenorhabditis elegans was used to investigate the effects of PKA subunit deficiency. In worms, suppression of PKA via RNAi resulted in severe phenotypes, including shortened life span, decreased egg laying, reduced locomotion, and altered lipid distribution. Similarly, in mammalian adipocytes, suppression of PKA regulatory subunits RIα and RIIβ via siRNAs potently stimulated PKA activity, leading to potentiated lipolysis without increasing cAMP levels. Nevertheless, insulin exerted anti-lipolytic effects and restored lipid droplet integrity by antagonizing PKA action. Together, these data implicate the importance of subunit stoichiometry as another regulatory mechanism of PKA activity and lipid metabolism.

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I{kappa}B{zeta} Ankyrin Repeats Bind to NF-{kappa}B p50 and Promoter DNA [Signal Transduction]

The nuclear protein IκBζ, comprising the N-terminal trans-activation domain and the C-terminal ankyrin repeat (ANK) domain composed of seven ANK motifs, activates transcription of a subset of nuclear factor-κB (NF-κB)-dependent innate immune genes such as Lcn2 encoding the antibacterial protein lipocalin-2. Lcn2 activation requires formation of a complex containing IκBζ and NF-κB p50, a transcription factor that harbors the DNA-binding Rel homology region but lacks a trans-activation domain, on the promoter with the canonical NF-κB-binding site (κB site) and its downstream cytosine-rich element. Here we show that IκBζ productively interacts with p50 via Asp-451 in the N terminus of ANK1, a residue that is evolutionarily conserved among IκBζ and the related nuclear IκB proteins Bcl-3 and IκBNS. Threonine substitution for Asp-451 abrogates direct association with the κB-site-binding protein p50, complex formation with the Lcn2 promoter DNA, and activation of Lcn2 transcription. The basic residues Lys-717 and Lys-719 in the C-terminal region of ANK7 contribute to IκBζ binding to the Lcn2 promoter, probably via interaction with the cytosine-rich element required for Lcn2 activation; glutamate substitution for both lysines results in a loss of transcriptionally active complex formation without affecting direct contact of IκBζ with p50. Both termini of the ANK domain in Bcl-3 and IκBNS function in a manner similar to that of IκBζ to interact with promoter DNA, indicating a common mechanism in which the nuclear IκBs form a regulatory complex with NF-κB and promoter DNA via the invariant aspartate in ANK1 and the conserved basic residues in ANK7.

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Fis1 Activity in Yeast Mitochondrial Fission [Protein Structure and Folding]

The tail-anchored protein Fis1 is implicated as a passive tether in yeast mitochondrial fission. We probed the functional role of Fis1 Glu-78, whose elevated side chain pKa suggests participation in protein interactions. Fis1 binds partners Mdv1 or Dnm1 tightly, but mutation E78A weakens Fis1 interaction with Mdv1, alters mitochondrial morphology, and abolishes fission in a growth assay. In fis1Δ rescue experiments, Fis1-E78A causes a novel localization pattern in which Dnm1 uniformly coats the mitochondria. By contrast, Fis1-E78A at lower expression levels recruits Dnm1 into mitochondrial punctate structures but fails to support normal fission. Thus, Fis1 makes multiple interactions that support Dnm1 puncta formation and may be essential after this step, supporting a revised model for assembly of the mitochondrial fission machinery. The insights gained by mutating a residue with a perturbed pKa suggest that side chain pKa values inferred from routine NMR sample pH optimization could provide useful leads for functional investigations.

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Multiple cyclin kinase inhibitors promote bile acid-induced apoptosis and autophagy in primary hepatocytes via p53-CD95-dependent signaling. [Additions and Corrections]

VOLUME 283 (2008) PAGES 24343–24358PAGE 24348:In Fig. 3A, the image of mouse hepatocytes overexpressing p21 and treated with PD184352 (PD) and deoxycholic acid (DCA) was duplicated from the image of mouse hepatocytes infected with control virus and treated with PD184352 and deoxycholic acid. This error has now been corrected. This error does not affect the results or conclusions of this work.jbc;291/39/20823/FU1F1FU1

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TMEM16A Regulates Pancreatic Luminal pH [Signal Transduction]

The identification of ANO1/TMEM16A as the likely calcium-dependent chloride channel of exocrine glands has led to a more detailed understanding of its biophysical properties. This includes a calcium-dependent change in channel selectivity and evidence that HCO3− permeability can be significant. Here we use freshly isolated pancreatic acini that preserve the luminal structure to measure intraluminal pH and test the idea that ANO1/TMEM16A contributes to luminal pH balance. Our data show that, under physiologically relevant stimulation with 10 pm cholesystokinin, the luminal acid load that results from the exocytic fusion of zymogen granules is significantly blunted by HCO3− buffer in comparison with HEPES, and that this is blocked by the specific TMEM16A inhibitor T16inh-A01. Furthermore, in a model of acute pancreatitis, we observed substantive luminal acidification and provide evidence that ANO1/TMEM16A acts to attenuate this pH shift. We conclude that ANO1/TMEM16A is a significant pathway in pancreatic acinar cells for HCO3− secretion into the lumen.

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Myeloid Cell Plasticity in the Oral Barrier Tissue and ONJ [Immunology]

Injury to the barrier tissue initiates a rapid distribution of myeloid immune cells from bone marrow, which guide sound wound healing. Bisphosphonates, a widely used anti-bone resorptive drug with minimal systemic side effects, have been linked to an abnormal wound healing in the oral barrier tissue leading to, in some cases, osteonecrosis of the jaw (ONJ). Here we report that the development of ONJ may involve abnormal phenotypic plasticity of Ly6G+/Gr1+ myeloid cells in the oral barrier tissue undergoing tooth extraction wound healing. A bolus intravenous zoledronate (ZOL) injection to female C57Bl/6 mice followed by maxillary first molar extraction resulted in the development of ONJ-like lesion during the second week of wound healing. The multiplex assay of dissociated oral barrier cells exhibited the secretion of cytokines and chemokines, which was significantly modulated in ZOL mice. Tooth extraction-induced distribution of Ly6G+/Gr1+ cells in the oral barrier tissue increased in ZOL mice at week 2. ONJ-like lesion in ZOL mice contained Ly6G+/Gr1+ cells with abnormal size and morphology as well as different flow cytometric staining intensity. When anti-Ly6G (Gr1) antibody was intraperitoneally injected for 5 days during the second week of tooth extraction, CD11b+GR1hi cells in bone marrow and Ly6G+ cells in the oral barrier tissue were depleted, and the development of ONJ-like lesion was significantly attenuated. This study suggests that local modulation of myeloid cell plasticity in the oral barrier tissue may provide the basis for pathogenesis and thus therapeutic as well as preventive strategy of ONJ.

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Molecular Basis of the RHOGAP Family Proteins [Molecular Biophysics]

RHO GTPase-activating proteins (RHOGAPs) are one of the major classes of regulators of the RHO-related protein family that are crucial in many cellular processes, motility, contractility, growth, differentiation, and development. Using database searches, we extracted 66 distinct human RHOGAPs, from which 57 have a common catalytic domain capable of terminating RHO protein signaling by stimulating the slow intrinsic GTP hydrolysis (GTPase) reaction. The specificity of the majority of the members of RHOGAP family is largely uncharacterized. Here, we comprehensively investigated the sequence-structure-function relationship between RHOGAPs and RHO proteins by combining our in vitro data with in silico data. The activity of 14 representatives of the RHOGAP family toward 12 RHO family proteins was determined in real time. We identified and structurally verified hot spots in the interface between RHOGAPs and RHO proteins as critical determinants for binding and catalysis. We have found that the RHOGAP domain itself is nonselective and in some cases rather inefficient under cell-free conditions. Thus, we propose that other domains of RHOGAPs confer substrate specificity and fine-tune their catalytic efficiency in cells.

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Transcriptional Regulation via HIF Hydroxylase Inhibition [Genomics and Proteomics]

The hypoxia-inducible factor (HIF) system orchestrates cellular responses to hypoxia in animals. HIF is an α/β-heterodimeric transcription factor that regulates the expression of hundreds of genes in a tissue context-dependent manner. The major hypoxia-sensing component of the HIF system involves oxygen-dependent catalysis by the HIF hydroxylases; in humans there are three HIF prolyl hydroxylases (PHD1–3) and an asparaginyl hydroxylase (factor-inhibiting HIF (FIH)). PHD catalysis regulates HIFα levels, and FIH catalysis regulates HIF activity. How differences in HIFα hydroxylation status relate to variations in the induction of specific HIF target gene transcription is unknown. We report studies using small molecule HIF hydroxylase inhibitors that investigate the extent to which HIF target gene expression is induced by PHD or FIH inhibition. The results reveal substantial differences in the role of prolyl and asparaginyl hydroxylation in regulating hypoxia-responsive genes in cells. PHD inhibitors with different structural scaffolds behave similarly. Under the tested conditions, a broad-spectrum 2-oxoglutarate dioxygenase inhibitor is a better mimic of the overall transcriptional response to hypoxia than the selective PHD inhibitors, consistent with an important role for FIH in the hypoxic transcriptional response. Indeed, combined application of selective PHD and FIH inhibitors resulted in the transcriptional induction of a subset of genes not fully responsive to PHD inhibition alone. Thus, for the therapeutic regulation of HIF target genes, it is important to consider both PHD and FIH activity, and in the case of some sets of target genes, simultaneous inhibition of the PHDs and FIH catalysis may be preferable.

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Coiled-coil Initiation in Kinesin Motors [Protein Structure and Folding]

Kinesin-1, -2, -5, and -7 generate processive hand-over-hand 8-nm steps to transport intracellular cargoes toward the microtubule plus end. This processive motility requires gating mechanisms to coordinate the mechanochemical cycles of the two motor heads to sustain the processive run. A key structural element believed to regulate the degree of processivity is the neck-linker, a short peptide of 12–18 residues, which connects the motor domain to its coiled-coil stalk. Although a shorter neck-linker has been correlated with longer run lengths, the structural data to support this hypothesis have been lacking. To test this hypothesis, seven kinesin structures were determined by x-ray crystallography. Each included the neck-linker motif, followed by helix α7 that constitutes the start of the coiled-coil stalk. In the majority of the structures, the neck-linker length differed from predictions because helix α7, which initiates the coiled-coil, started earlier in the sequence than predicted. A further examination of structures in the Protein Data Bank reveals that there is a great disparity between the predicted and observed starting residues. This suggests that an accurate prediction of the start of a coiled-coil is currently difficult to achieve. These results are significant because they now exclude simple comparisons between members of the kinesin superfamily and add a further layer of complexity when interpreting the results of mutagenesis or protein fusion. They also re-emphasize the need to consider factors beyond the kinesin neck-linker motif when attempting to understand how inter-head communication is tuned to achieve the degree of processivity required for cellular function.

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AMY3 Interferes with Starch Granule Initiation [Metabolism]

Arabidopsis leaf chloroplasts typically contain five to seven semicrystalline starch granules. It is not understood how the synthesis of each granule is initiated or how starch granule number is determined within each chloroplast. An Arabidopsis mutant lacking the glucosyl-transferase, STARCH SYNTHASE 4 (SS4) is impaired in its ability to initiate starch granules; its chloroplasts rarely contain more than one large granule, and the plants have a pale appearance and reduced growth. Here we report that the chloroplastic α-amylase AMY3, a starch-degrading enzyme, interferes with granule initiation in the ss4 mutant background. The amy3 single mutant is similar in phenotype to the wild type under normal growth conditions, with comparable numbers of starch granules per chloroplast. Interestingly, the ss4 mutant displays a pleiotropic reduction in the activity of AMY3. Remarkably, complete abolition of AMY3 (in the amy3 ss4 double mutant) increases the number of starch granules produced in each chloroplast, suppresses the pale phenotype of ss4, and nearly restores normal growth. The amy3 mutation also restores starch synthesis in the ss3 ss4 double mutant, which lacks STARCH SYNTHASE 3 (SS3) in addition to SS4. The ss3 ss4 line is unable to initiate any starch granules and is thus starchless. We suggest that SS4 plays a key role in granule initiation, allowing it to proceed in a way that avoids premature degradation of primers by starch hydrolases, such as AMY3.

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Protease-mediated Damage of hERG [Molecular Bases of Disease]

The human ether-a-go-go-related gene (hERG) encodes the pore-forming subunit of the rapidly activating delayed rectifier potassium channel (IKr), which is important for cardiac repolarization. Dysfunction of hERG causes long QT syndrome and sudden death, which occur in patients with cardiac ischemia. Cardiac ischemia is also associated with activation, up-regulation, and secretion of various proteolytic enzymes. Here, using whole-cell patch clamp and Western blotting analysis, we demonstrate that the hERG/IKr channel was selectively cleaved by the serine protease, proteinase K (PK). Using molecular biology techniques including making a chimeric channel between protease-sensitive hERG and insensitive human ether-a-go-go (hEAG), as well as application of the scorpion toxin BeKm-1, we identified that the S5-pore linker of hERG is the target domain for proteinase K cleavage. To investigate the physiological relevance of the unique susceptibility of hERG to proteases, we show that cardiac ischemia in a rabbit model was associated with a reduction in mature ERG expression and an increase in the expression of several proteases, including calpain. Using cell biology approaches, we found that calpain-1 was actively released into the extracellular milieu and cleaved hERG at the S5-pore linker. Using protease cleavage-predicting software and site-directed mutagenesis, we identified that calpain-1 cleaves hERG at position Gly-603 in the S5-pore linker of hERG. Clarification of protease-mediated damage of hERG extends our understanding of hERG regulation. Damage of hERG mediated by proteases such as calpain may contribute to ischemia-associated QT prolongation and sudden cardiac death.

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N-terminal Myristoylated Cargo Interaction with Unc119a/b [Signal Transduction]

Primary cilia are highly specialized small antenna-like cellular protrusions that extend from the cell surface of many eukaryotic cell types. The protein content inside cilia and cytoplasm is very different, but details of the sorting process are not understood for most ciliary proteins. Recently, we have shown that prenylated proteins are sorted according to their affinity to the carrier protein PDE6δ and the ability of Arl3 but not Arl2 to release high affinity cargo inside the cilia (Fansa, E. K., Kösling, S. K., Zent, E., Wittinghofer, A., and Ismail, S. (2016) Nat. Commun. 7, 11366). Here we address the question whether a similar principle governs the transport of myristoylated cargo by the carrier proteins Unc119a and Unc119b. We thus analyzed the binding strength of N-terminal myristoylated cargo peptides (GNAT1, NPHP3, Cystin1, RP2, and Src) to Unc119a and Unc119b proteins. The affinity between myristoylated cargo and carrier protein, Unc119, varies between subnanomolar and micromolar. Peptides derived from ciliary localizing proteins (GNAT1, NPHP3, and Cystin1) bind with high affinity to Unc119 proteins, whereas a peptide derived from a non-ciliary localizing protein (Src) has low affinity. The peptide with intermediate affinity (RP2) is localized at the ciliary transition zone as a gate keeper. We show that the low affinity peptides are released by both Arl2·GppNHp and Arl3·GppNHp, whereas the high affinity peptides are exclusively released by only Arl3·GppNHp. Determination of the x-ray structure of myristoylated NPHP3 peptide in complex with Unc119a reveals the molecular details of high affinity binding and suggests the importance of the residues at the +2 and +3 positions relative to the myristoylated glycine for high and low affinities. The mutational analysis of swapping the residues at the +2 and +3 positions between high and low affinity peptides results in reversing their affinities for Unc119a and leads to a partial mislocalization of a low affinity mutant of NPHP3.

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Ubiquitination and Degradation of the CaV Channel I-II Loop [Protein Synthesis and Degradation]

CaVβ subunits interact with the voltage-gated calcium channel CaV2.2 on a site in the intracellular loop between domains I and II (the I-II loop). This interaction influences the biophysical properties of the channel and leads to an increase in its trafficking to the plasma membrane. We have shown previously that a mutant CaV2.2 channel that is unable to bind CaVβ subunits (CaV2.2 W391A) was rapidly degraded (Waithe, D., Ferron, L., Page, K. M., Chaggar, K., and Dolphin, A. C. (2011) J. Biol. Chem. 286, 9598–9611). Here we show that, in the absence of CaVβ subunits, a construct consisting of the I-II loop of CaV2.2 was directly ubiquitinated and degraded by the proteasome system. Ubiquitination could be prevented by mutation of all 12 lysine residues in the I-II loop to arginines. Including a palmitoylation motif at the N terminus of CaV2.2 I-II loop was insufficient to target it to the plasma membrane in the absence of CaVβ subunits even when proteasomal degradation was inhibited with MG132 or ubiquitination was prevented by the lysine-to-arginine mutations. In the presence of CaVβ subunit, the palmitoylated CaV2.2 I-II loop was protected from degradation, although oligoubiquitination could still occur, and was efficiently trafficked to the plasma membrane. We propose that targeting to the plasma membrane requires a conformational change in the I-II loop that is induced by binding of the CaVβ subunit.

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Discovery of Dual Inhibitors of MDM2 and XIAP for Cancer Treatment

Publication date: Available online 22 September 2016
Source:Cancer Cell
Author(s): Lubing Gu, Hailong Zhang, Tao Liu, Sheng Zhou, Yuhong Du, Jing Xiong, Sha Yi, Cheng-Kui Qu, Haian Fu, Muxiang Zhou
MDM2 and XIAP are mutually regulated. Binding of MDM2 RING protein to the IRES region on XIAP mRNA results in MDM2 protein stabilization and enhanced XIAP translation. In this study, we developed a protein-RNA fluorescence polarization (FP) assay for high-throughput screening (HTS) of chemical libraries. Our FP-HTS identified eight inhibitors that blocked the MDM2 protein-XIAP RNA interaction, leading to MDM2 degradation. The compound-induced MDM2 downregulation resulted not only in inhibition of XIAP expression, but also in activation of p53, which contributed to cancer cell apoptosis in vitro and inhibition of cancer cell proliferation in vivo. Importantly, one of the MDM2/XIAP inhibitors, MX69, showed minimal inhibitory effect on normal human hematopoiesis in vitro and was very well tolerated in animal models.

Graphical abstract

Teaser

Gu et al. use chemical screening to identify inhibitors of the MDM2 protein-XIAP mRNA interaction and show these inhibitors lead to apoptosis by reducing XIAP protein, decreasing MDM2 stability, and increasing p53 levels. Animal testing of one of these compounds shows antitumor efficacy and minimal toxicity.


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IJERPH, Vol. 13, Pages 939: Polymorphisms in GEMIN4 and AGO1 Genes Are Associated with the Risk of Lung Cancer: A Case-Control Study in Chinese Female Non-Smokers

MicroRNA biosynthesis genes can affect the regulatory effect of global microRNAs to target mRNA and hence influence the genesis and development of human cancer. Here, we selected five single nucleotide polymorphisms (SNPs) (rs7813, rs2740349, rs2291778, rs910924, rs595961) in two key microRNA biosynthesis genes (GEMIN4 and AGO1) and systematically evaluated the association between these SNPs, the gene-environment interaction and lung cancer risk. To control the impact of cigarette smoking on lung cancer, we recruited Chinese female non-smokers for the study. The total number of lung cancer cases and cancer-free controls were 473 and 395 in the case-control study. Four SNPs showed statistically significant associations with lung cancer risk. After Bonferroni correction, rs7813 and rs595961 were evidently still associated with lung cancer risk. In the stratified analysis, our results revealed that all five SNPs were associated with the risk of lung adenocarcinoma; after Bonferroni correction, significant association was maintained for rs7813, rs910924 and rs595961. Haplotype analysis showed GEMIN4 haplotype C-A-G-T was a protective haplotype for lung cancer. In the combined unfavorable genotype analysis, with the increasing number of unfavorable genotypes, a progressively increased gene-dose effect was observed in lung adenocarcinoma. We also found that individuals exposed to cooking oil fumes showed a relatively high risk of lung cancer, but no interactions were found between cooking oil fume exposure or passive smoking exposure with these SNPs, either on an additive scale or a multiplicative scale. Overall, this is the first study showing that rs7813 and rs595961 could be meaningful as genetic markers for lung cancer risk.

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IJERPH, Vol. 13, Pages 941: The Use of Exenatide in Managing Markers of Cardiovascular Risk in Patients with Type 2 Diabetes: A Systematic Review

Objective: This review examines the use of exenatide twice daily in managing changes in markers of cardiovascular risk in patients with type 2 diabetes. Background: Type 2 diabetes is a progressive metabolic disorder, which results from defects in insulin secretion and/or insulin action leading to chronic hyperglycaemia and associated cardiovascular complications. Despite the use of diet, exercise, oral antihyperglycaemic agents and insulin, the progressive nature of the condition means that the levels of the preventive and treatment measures would have to be increased and/or new therapies have to be developed in order to address the long term impact of type 2 diabetes. The advent of exenatide, a glucagon-like peptide-1 receptor agonist provides a useful basis for managing type 2 diabetes and related cardiovascular complications without the side effects of regular diabetes therapies. However, exenatide twice daily is often used in combination with other therapies, although the mechanism of exenatide in managing diabetes and and associated cardiovascular risks and complications remain complex and still evolving. Method: A range of databases including EBSCOhost online research database were used to access articles based on PICO (Population, Interventions, Comparative Interventions, Outcomes) framework and Boolean operators. Results: Eleven randomised controlled studies which met the inclusion criteria were selected for this review. Nine of the eleven studies showed significant decrease in body weight among participants in the exenatide group compared with placebo or control group while the other two studies did not report statistically significant differences in body weight. In adition, all the studies showed statistically significant decrease in glycated haemoglobin (HbA1c) in the exenatide group compared to controls except in one study. In the present review, the seven studies, which looked at the effect of exenatide twice daily on lipid profile, did not find any significant difference between the exenatide group and the control group except for High density lipoprotein-cholesterol in two of the studies. However, statistically significant decrease was observed between exenatide group and controls with respect to blood pressure (systolic and/or diastolic) in these studies. Discussion: It would appear that exenatide is more effective in reducing body weight in patients with type 2 diabetes when used in combination with metformin than when used alone or in combination with thiazolidinedione. The findings of this review would suggest that exenatide twice daily may be useful in managing cardiovascular risks and complications by reducing body weight, HbA1c and blood pressure.

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IJERPH, Vol. 13, Pages 943: Pesticide Residues on Three Cut Flower Species and Potential Exposure of Florists in Belgium

In order to assess the prevalence of pesticide contamination and the risk of florists’ exposure when handling cut flowers, sampling and analysis of 90 bouquets of the most commonly sold cut flowers in Belgium (50 bouquets of roses; 20 of gerberas, and 20 of chrysanthemums) were carried out. The bouquets were collected from 50 florists located in the seven largest cities of Belgium (Antwerp, Brussels, Charleroi, Ghent, Leuven, Liege, and Namur) and from five supermarkets located in the different regions. To have a better understanding of the route of exposure and professional practices a questionnaire was also addressed to a group of 25 florists who volunteered to take part in the survey. All florists were interviewed individually when collecting the questionnaire. The residual pesticide deposit values on cut flowers were determined in an accredited laboratory using a multi-residue (QuEChERS Quick Easy Cheap Effective Rugged Safe) method and a combination of gas chromatography (GC) and liquid chormatograhphy (LC) analysis. A total of 107 active substances were detected from all samples; i.e., an average of about 10 active substances per bouquet. The most severely contaminated bouquet accumulated a total concentration of residues up to 97 mg/kg. Results show that roses are the most contaminated cut flowers; with an average of 14 substances detected per sample and a total concentration per rose sample of 26 mg/kg. Some active substances present an acute toxicity (acephate, methiocarb, monocrotophos, methomyl, deltamethrin, etc.) and exposure can generate a direct effect on the nervous system of florists. Nevertheless, fungicides (dodemorph, propamocarb, and procymidone) were the most frequently detected in samples and had the highest maximum concentrations out of all the active substances analysed. Dodemorph was the most frequently detected substance with the highest maximum concentration (41.9 mg/kg) measured in the rose samples. It appears from the survey that, despite being exposed to high deposits of residues, florists usually do not protect themselves from contact with residues even if they spend several hours handling cut flowers and preparing bouquets (from 2 to 6 h/day, depending on the time of year and/or selling periods) daily. Bad habits (eating, drinking, or smoking at work) and absence of personal protective equipment of most florists also increase the risk of contact with pesticide residues.

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IJERPH, Vol. 13, Pages 938: Trace Elements Contamination and Human Health Risk Assessment in Drinking Water from the Agricultural and Pastoral Areas of Bay County, Xinjiang, China

Tap water samples were collected from 180 families in four agricultural (KYR: Keyir, KRW: Kariwak, YTR: Yatur, DW: Dawanqi) and two pastoral areas (B: Bulong and Y: Yangchang) in Bay County, Xinjiang, China, and levels of seven trace elements (Cd, Cr, As Ni, Pb, Zn, Se) were analyzed using inductively-coupled plasma mass spectrometry (ICP-MS) to assess potential health risks. Remarkable spatial variations of contamination were observed. Overall, the health risk was more severe for carcinogenic versus non-carcinogenic pollutants due to heavy metal. The risk index was greater for children overall (Cr > As > Cd and Zn > Se for carcinogenic and non-carcinogenic elements, respectively). The total risk index was greater in agricultural areas (DW > KYR > YTR > KRW > B > Y). Total risk indices were greater where well water was the source versus fountain water; for the latter, the total health risk index was greater versus glacier water. Main health risk factors were Cr and As in DW, KYR, YTR, KRW, and B, and Zn, Cr, and As in the Y region. Overall, total trace element–induced health risk (including for DW adults) was higher than acceptable (10−6) and lower than priority risk levels (10−4) (KYR, YTR, KRW, Y, and B). For DW children, total health risk reached 1.08 × 10−4, higher than acceptable and priority risk levels (10−4).

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IJERPH, Vol. 13, Pages 942: The Possibility of Decreasing 50-Hz Electric Field Exposure near 400-kV Power Lines with Arc Flash Personal Protective Equipment

Various guidelines for the protection of human beings against possible adverse effects resulting from exposure to electromagnetic fields (EMFs) have been published with a view towards continual improvement; therefore, decreasing exposure is an important research area. The aim of this study was to investigate the possibility of decreasing electric field exposure with arc flash rated personal protective equipment (PPE), which in this case was a set of coveralls, and to compare the measurement results to calculations using the helmet-mask measuring system. We collected the data under a 400-kV power line. The test person stood on isolated aluminum paper, and the current between the ground and the aluminum paper was measured. When the test subject wore the arc flash PPE, the current to the ground was only 9.5% of the current measured when wearing normal clothes, which represents a clear decrease in exposure.

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IJERPH, Vol. 13, Pages 940: Time Effectiveness of Ultraviolet C Light (UVC) Emitted by Light Emitting Diodes (LEDs) in Reducing Stethoscope Contamination

Today it is well demonstrated that stethoscopes can be as contaminated as hands, which are a recognized source of Health-Care Associated Infections (HCAIs). Ultraviolet C (UVC) light has proven disinfection capacity and the innovative UVC technology of Light Emitting Diode (LED) shows several potential benefits. To verify whether the use of UVC LEDs is effective and reliable in stethoscope membrane disinfection after prolonged use, a pre-post intervention study was conducted. A total of 1668 five-minute cycles were performed on two UVC LEDs to simulate their use; thereafter, their disinfection capacity was tested on stethoscope membranes used on a previously auscultated volunteer. Then, a further 1249 cycles were run and finally the LEDs were tested to assess performance in reducing experimental contamination by Staphylococcus aureus, Pseudomonas aeruginosa and Escherichia coli on the stethoscope membrane. Baseline volunteer contamination identified 104 Colony Forming Units (CFUs) while treated Petri dishes had 12 and 15 CFUs (p < 0.001). Statistically significant differences (p < 0.001) were also found relating to the reduction of specific bacteria: in particular, after treatment no CFU were observed for S. aureus and E. coli. UVC LEDs demonstrated the capacity to maintain high levels of disinfection after more than 240 h of use and they were effective against common microorganisms that are causative agents of HCAIs.

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Five wild lionesses grow a mane and start acting like males

The unusual characteristics of a few lionesses in Botswana may be down to excess testosterone, making them male-like as well as apparently infertile

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Five wild lionesses grow a mane and start acting like males

The unusual characteristics of a few lionesses in Botswana may be down to excess testosterone, making them male-like as well as apparently infertile

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Evaluation of bio medical waste management practices in select health care facilities of Karnataka

2016-09-23T00-30-08Z
Source: International Journal of Community Medicine and Public Health
Suman Gadicherla, Hemanth Thapsey, Lalitha Krishnappa, Shivaraj N. Somanna.
Background: Health care sector has expanded to a great extent in both private and public sectors to cater to the needs of the increasing population of the country. Mismanagement of bio medical waste can expose health care personnel and public to various potential hazards. Methods: Cross sectional study was conducted during September- November 2014 to assess current practices of Bio- Medical waste management (BMW) among the health care facilities (HCF) that had participated the selected districts level training program. Two stage sampling method was used to select eight districts and 15 HCFs in each district of Karnataka. An observational check list was used to observe macro and process areas of BMW. Results: Efficiency of each of the process of waste management was calculated by using a scoring system. A total of 116 HCF were observed-9 large, 17 medium and 90 small. Segregation efficiency was poor in 22 (24.4%) small HCFs. Disinfection was practiced in 50% of the locations observed in small HCFs. The storage efficiency was excellent in 56.3% and 57.7% among medium and small HCFs respectively. No containment of sharps was observed in 34.7%, 23.4%, 26.8% locations of small, medium and large HCFs respectively. Final disposal of waste was managed by common treatment facility in 88.8% of large and 88.2% of medium sized hospital respectively. Conclusions: Practices of bio medical waste management need to be improved at all levels.


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Resveratrol attenuates myocardial ischemia/reperfusion injury through up-regulation of vascular endothelial growth factor B

Publication date: Available online 22 September 2016
Source:Free Radical Biology and Medicine
Author(s): Lei Yang, Yan Zhang, Mengmeng Zhu, Qiong Zhang, Xiaoling Wang, Yanjiao Wang, Jincai Zhang, Jing Li, Liang Yang, Jie Liu, Fei Liu, Yinan Yang, Licheng Kang, Yanna Shen, Zhi Qi
The objective was to examine the protective effect of resveratrol (RSV) on myocardial ischemia/reperfusion (IR) injury and whether the mechanism was related to vascular endothelial growth factor B (VEGF-B) signaling pathway. Rat hearts were isolated for Langendorff perfusion test and H9c2 cells were used for in vitro assessments. RSV treatment significantly improved left ventricular function, inhibited CK-MB release, and reduced infarct size in comparison with IR group ex vivo. RSV treatment markedly decreased cell death and apoptosis of H9c2 cells during IR. We found that RSV was responsible for the up-regulation of VEGF-B mRNA and protein level, which caused the activation of Akt and the inhibition of GSK3β. Additionally, RSV prevented the generation of reactive oxygen species (ROS) by up-regulating the expression of MnSOD either in vitro or ex vivo. We also found that the inhibition of VEGF-B abolished the cardioprotective effect of RSV, increased apoptosis, and led to the down-regulation of phosphorylated Akt, GSK3β, and MnSOD in H9c2 cells. These results demonstrated that RSV was able to attenuate myocardial IR injury via promotion of VEGF-B/antioxidant signaling pathway. Therefore, the up-regulation of VEGF-B can be a promising modality for clinical myocardial IR injury therapy.



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