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IJMS, Vol. 17, Pages 1727: Effects of Mutations on Structure–Function Relationships of Matrix Metalloproteinase-1

Matrix metalloproteinase-1 (MMP-1) is one of the most widely studied enzymes involved in collagen degradation. Mutations of specific residues in the MMP-1 hemopexin-like (HPX) domain have been shown to modulate activity of the MMP-1 catalytic (CAT) domain. In order to reveal the structural and conformational effects of such mutations, a molecular dynamics (MD) study was performed of in silico mutated residues in the X-ray crystallographic structure of MMP-1 complexed with a collagen-model triple-helical peptide (THP). The results indicate an important role of the mutated residues in MMP-1 interactions with the THP and communication between the CAT and the HPX domains. Each mutation has a distinct impact on the correlated motions in the MMP-1•THP. An increased collagenase activity corresponded to the appearance of a unique anti-correlated motion and decreased correlated motions, while decreased collagenase activity corresponded both to increased and decreased anti-correlated motions.

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IJMS, Vol. 17, Pages 1730: Assessment of Amino Acid/Drug Transporters for Renal Transport of [18F]Fluciclovine (anti-[18F]FACBC) in Vitro

[18F]Fluciclovine (trans-1-amino-3-[18F]fluorocyclobutanecarboxylic acid; anti-[18F]FACBC), a positron emission tomography tracer used for the diagnosis of recurrent prostate cancer, is transported via amino acid transporters (AATs) with high affinity (Km: 97–230 μM). However, the mechanism underlying urinary excretion is unknown. In this study, we investigated the involvement of AATs and drug transporters in renal [18F]fluciclovine reuptake. [14C]Fluciclovine (trans-1-amino-3-fluoro[1-14C]cyclobutanecarboxylic acid) was used because of its long half-life. The involvement of AATs in [14C]fluciclovine transport was measured by apical-to-basal transport using an LLC-PK1 monolayer as model for renal proximal tubules. The contribution of drug transporters herein was assessed using vesicles/cells expressing the drug transporters P-glycoprotein (P-gp), breast cancer resistance protein (BCRP), multidrug resistance-associated protein 4 (MRP4), organic anion transporter 1 (OAT1), organic anion transporter 3 (OAT3) , organic cation transporter 2 (OCT2), organic anion transporting polypeptide 1B1 (OATP1B1), and organic anion transporting polypeptide 1B3 (OATP1B3). The apical-to-basal transport of [14C]fluciclovine was attenuated by l-threonine, the substrate for system alanine-serine-cysteine (ASC) AATs. [14C]Fluciclovine uptake by drug transporter-expressing vesicles/cells was not significantly different from that of control vesicles/cells. Fluciclovine inhibited P-gp, MRP4, OAT1, OCT2, and OATP1B1 (IC50 > 2.95 mM). Therefore, system ASC AATs may be partly involved in the renal reuptake of [18F]fluciclovine. Further, given that [18F]fluciclovine is recognized as an inhibitor with millimolar affinity for the tested drug transporters, slow urinary excretion of [18F]fluciclovine may be mediated by system ASC AATs, but not by drug transporters.

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Epithelial abnormalities on Pap smear in Postmenopausal Women: A two-year hospital-based study

2016-10-13T10-00-37Z
Source: International Journal of Medical Science and Public Health
Juhi D Mahadik, Sharmishtha Patel, Swati Gupta, Avani S Patel, Pankaj R Ramani.
Background: Cervical cancer is the commonest cancer causing death among women in developing countries. In India, the peak age for cervical cancer incidence is 5559 years. However, older and poor women who are at the highest risk of developing cancer are least likely to undergo screening. Pap smear being the most cost-effective, non-invasive and a technically easy screening tool for cervical cancer detection should be carried out in the older population, at regular intervals, if the morbidity and mortality resulting from cervical cancer have to be brought down. Objectives: To study the incidence of epithelial abnormalities on pap smear in postmenopausal women. Materials and Methods: The study was carried out on pap smears of 700 postmenopausal women attending the department of Obstetrics and Gynecology, New Civil Hospital, Surat, during January 2014 to December 2015. The pap smears were reported in the Department of Pathology using The Bethesda System. Results: The incidence of epithelial abnormalities was 5.36%. The age group of 51-60 years showed the highest incidence of epithelial abnormalities. The incidence of epithelial abnormalities in asymptomatic women was 6.46%. Conclusion: The findings of our study indicate the need to increase awareness regarding the risk of cervical cancer in postmenopausal women, along with efforts to include even asymptomatic women in the screening for cervical cytology.


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Prevalence of refractive errors among dental scholars and supporting auxiliary staff in a Government Hospital of Kashmir- A cross-sectional study

2016-10-13T10-00-37Z
Source: International Journal of Medical Science and Public Health
Aasim Farooq Shah, Asif Yousuf, Rayees Ahmed, Suhail Majid Jan, Mohsin Siddiq, Irfan Ashraf Baba.
Background: The untreated refractive errors have a substantial effect on learning and academic achievement of students other than being a personal issue. Visual disorders due to refractive errors are the most common diseases among the students and the second principal cause of blindness worldwide. The literature available reporting refractive errors in dental students in India is inadequate. Objectives: The aim of this study was to determine the prevalence of refractive errors among dental students in Kashmir, a city in the North of India. Material and Methods: This cross-sectional institutional based study was conducted in June 2016 among dental students and interns. Students and Interns at Government Dental College and Hospital, Srinagar, Jammu and Kashmir, India were examined. All the subjects were assessed for refractive errors using auto-refractometer (TOPCON RM-8000B, TOPCON Corporation, Tokyo, Japan). The ophthalmologic examination was carried by an Ophthalmologist. SPSS Statistical Software 20.0 was used and significance of differences between the groups (gender and age) was sought using Mann-Whitney U-tests. Results: A total of 432 available subjects which including 155 males and 277 females were examined, of whom only 14.59% did not show any type of refectory error. Myopia was highly prevalent followed by Hypermetropia (Hyperopia) and Astigmatism. Conclusion: The results of the present study showed more than 75% students had refractive errors. Most of these students were unaware of the defects. Thus, more attention must be given to students for the treatment of these refractive errors.


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One-way traffic investigation of a case: a bane in Indian scenario

2016-10-13T06-51-28Z
Source: The Southeast Asian Journal of Case Report and Review
Senthil Kumaran, Vinod A Chaudhari, Kusa K Shaha, Nisreen A Rahman.
In this article, we report an unusual case of natural death due to infective endocarditis, which created suspicion as there is an alleged history of physical aggression by her husband a month back. A 19-year-old female succumbed to death after one month of admission to a hospital. The victim had been on treatment in hospital for infective endocarditis. Forensic autopsy revealed no significant injury. There were signs of infective endocarditis, corresponding to the data available from the clinical history. The cause of death was established as infective endocarditis. We discuss the cause and manner of death and contributing factors of the medico-legal aspects of the death.


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Spontaneous neonatal rectal perforation: A case for primary closure.

2016-10-13T03-49-34Z
Source: The Southeast Asian Journal of Case Report and Review
Yogender Singh Kadian,Anjali Verma.
Spontaneous perforation of the gastrointestinal tract in the neonate is rare. When it occurs it usually involves the stomach or the ileocaecal region. Perforation of the rectum in the neonate is usually caused by instruments being passed into it. We are hereby reporting a rare case of idiopathic rectal perforation and was successfully managed by primary closure.


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