Short- and long-term effects of Xuezhikang (血脂康), an extract of cholestin, on serum proprotein convertase subtilisin/kexin type 9 levels

Abstract

Objective

To investigate the short- and long-term effects of Xuezhikang (血脂康, XZK), an extract of cholestin, on proprotein convertase subtilisin/kexin type 9 (PCSK9) level.

Methods

Thirty rats were randomly divided into three groups and were given saline, XZK 1,200 mg/kg or lovastatin 10 mg/kg respectively by daily gavage for 3 days (n=10 for each). Sixteen patients without previous lipid-lowering drug treatment for dyslipidemia received XZK 1,200 mg daily for 8 weeks. Fasting blood samples and liver tissue were collected at day 3 for rats, while the blood samples were obtained at baseline and week 8 from patients. The serum PCSK9 and lipid profile were measured. The expression of hepatic low density lipoprotein (LDL) receptor and sterol regulatory element binding protein 2 (SREBP-2) were measured by real time-PCR.

Results

PCSK9 levels in rats were significantly increased in the XZK and lovastatin groups (P=0.002, P=0.003 vs. control) at day 3, while no significant differences were found in the levels of lipid parameters. PCSK9 levels in patients increased by 34% (P=0.006 vs. baseline) accompanied by total cholesterol and LDL-cholesterol decreased by 22% and 28% P=0.001, P=0.002 vs. baseline). The hepatic mRNA levels of LDL-receptor and SREBP-2 were significantly increased in the XZK and lovastatin groups.

Conclusion

XZK has significant impact on PCSK9 in a short- and long-term manner in both rats and humans. Moreover, the data indicated that as lovastatin, XZK increased PCSK9 levels through SREBP-2 pathway.

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Effects of Chinese Medicine Shen-Fu Injection (参附注射液) on the expression of inflammatory cytokines and complements during post-resuscitation immune dysfunction in a porcine model

Abstract

Objective

To investigate the action of Shen-Fu Injection (参附注射液, SFI) in regulating the expression of the serum complements and inflammatory cytokines synthesized and released in response to the stress of global ischemia accompanying cardiac arrest (CA) and resuscitation.

Methods

Thirty pigs were randomly divided into the sham (n=6) and 3 returns of spontaneous circulation (ROSC) groups (n=24). After 8-min untreated ventricular fibrillation and 2-min basic life support, 24 pigs of the ROSC groups were randomized into three groups (n=8 per group), which received central venous injection of SFI (SFI group), epinephrine (EP group), or saline (SA group). Hemodynamic status and blood samples were obtained at 0, 0.5, 1, 2, 4, 6, 12, and 24 h after ROSC.

Results

Serum concentrations of specific activation markers of the complement system C3, C4 and C5b-9 were increased during cardiopulmonary resuscitation throught 24 h after ROSC. There were intense changes of various pro-inflammatory cytokines and anti-inflammatory cytokines as early as 0.5 h after CA. Compared with the EP and SA groups, SFI treatment reduced the proinflammatory cytokines levels of interleukin (IL)-6, IL-8 and tumor necrosis factor α (TNF-α, P<0.05), and increased the anti-inflammatory cytokine levels of IL-4 and IL-10 (P<0.05). Further, SFI treatment decreased the values of C3, C4 and C5b-9 compared with the EP and SA groups.

Conclusions

SFI, derived from the ancient Chinese medicine, has significant effects in attenuating post-resuscitation immune dysfunction by modulating the expression of complements and cytokines levels. The current study provided an experimental basis for the clinical application of a potential pharmacologic target for post resuscitation immune dysfunction.

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A pragmatic observational feasibility study on integrated treatment for musculoskeletal disorders: Design and protocol

Abstract

Background

Musculoskeletal disorders (MSD) comprise a wide range of conditions, associated with an enormous pain and impaired mobility, and are affecting people’s lives and work. Management of musculoskeletal disorders typically involves a multidisciplinary team approach. Positive findings have been found in previous studies evaluating the effectiveness of complementary therapies, though little attention has been paid to evaluating of the effectiveness of integrated packages of care combining conventional and complementary approaches for musculoskeletal conditions in a National Health Service (NHS) setting.

Objective

To determine the feasibility of all aspects of a pragmatic observational study designed: (1) to evaluate the effectiveness and cost effectiveness of integrated treatments for MSDs in an integrated NHS hospital in the UK; (2) to determine the acceptability of the study design and research process to patients; (3) to explore patients’ expectation and experience of receiving integrated treatments.

Methods

This is an observational feasibility study, with 1-year recruitment and 1-year follow-up, conducted in Royal London Hospital for Integrated Medicine, University College London Hospital Trust, UK. All eligible patients with MSDs newly referred to the hospital were included in the study. Interventions are integrated packages of care (conventional and complementary) as currently provided in the hospital. SF-36™ Health Survey, short form Brief Pain Inventory, Visual Analogue Scale, and modified Client Service Receipt Inventory will be assessed at 4/5 time points. Semi-structured interview/focus group will be carried out before treatment, and 1 year after commence of treatment.

Discussion

We intend to conduct a pragmatic observational study of integrated medical treatment of MSDs at a public sector hospital. It will inform the design of a future trial including recruitment, retention, suitability of the outcome measures and patients experiences.

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Gushing and Gleeking - lareviewofbooks

lareviewofbooks

Gushing and Gleeking lareviewofbooks Fat-campers sit in the cafeteria awaiting their meal, “saliva glands audibly gushing and gleeking.” An official ... Their manifesto is a sly inversion of John Galt's: “We believe that the best way to cure society of its cancer is to remove its tumors ...

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Phosphatidic acid induces EHD3-containing membrane tubulation and is required for receptor recycling

Publication date: Available online 16 February 2016
Source:Experimental Cell Research
Author(s): Yuji Henmi, Natsuko Oe, Nozomu Kono, Tomohiko Taguchi, Kohji Takei, Kenji Tanabe
EHD3 is localized on the tubular structures of early endosomes, and it regulates their trafficking pathway. However, the regulatory mechanism of EHD3-containing tubular structures remains poorly understood. An in vitro liposome co-sedimentation assay revealed that EHD3 interacted with phosphatidic acid through its helical domain and this interaction induced liposomal tubulations. Additionally, inhibiting phosphatidic acid synthesis with diacylglycerol kinase inhibitor or lysophosphatidic acid acyltransferase inhibitor significantly reduced the number of EHD3-containing tubules and impaired their trafficking from early endosomes. These results suggest that EHD3 and phosphatidic acid cooperatively regulate membrane deformation and trafficking from early endosomes.



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Role of palliative radiotherapy in the management of mural cardiac metastases: who, when and how to treat? A case series of 10 patients

Abstract

Cardiac metastases (CM), although a rare manifestation of metastatic cancer, are increasing in incidence with the improved prognosis and increased longevity of many patients with cancer. This condition may be life-threatening, especially for bulky rapidly growing tumors. Such cancer presentations may be amenable to palliative radiotherapy to improve symptoms and to prevent further cardiac function decline. Here, we report on our experience with 10 patients with mural CM who received radiotherapy (RT) to the heart with palliative intent. The radiation treatment was given in different clinical situations using different dose and fractionation, and with a variety of outcomes. Palliative RT was a reasonably effective treatment, leading to good radiographic response in five patients who were evaluable for radiologic response. The mean duration of response in responding patients was 6.3 months (range: 3–11 months). This report describing clinical dilemmas around CM radiation therapy summarizes the previous experiences with radiation in treatment of CM and may assist in the considerations of palliative treatment for these patients.

The success of palliative radiotherapy in improving clinical symptoms and achieving good local control for mural cardiac metastases calls for further consideration of this modality either as a single modality or in combination with surgery and/or chemotherapy. Our experience shows that common palliative dose fractionation schemes (such as 8, 20, or 30 Gy in 1, 5, and 10 fractions, respectively) is safe and effective and should be considered early in the management of these patients.

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Is there a progression-free survival benefit of first-line crizotinib versus standard chemotherapy and second-line crizotinib in ALK-positive advanced lung adenocarcinoma? A retrospective study of Chinese patients

Abstract

Although crizotinib has demonstrated promising efficacy and acceptable toxicity in patients with advanced non-small cell lung cancer (NSCLC), the available evidence in Chinese populations is currently limited. This study compared the progression-free survival (PFS) of Chinese patients with anaplastic lymphoma kinase (ALK)-positive, advanced lung adenocarcinoma who received first-line crizotinib therapy with that of patients who received first-line standard chemotherapy, and also the PFS benefit of first-line versus second-line crizotinib treatment. Data on 80 patients with ALK-positive, advanced lung adenocarcinoma who received crizotinib or standard chemotherapy as first-line treatments between June 2013 and December 2014 were retrospectively collected; 26 of the patients received crizotinib as second-line therapy after progressive disease (PD) occurred on first-line chemotherapy. Tumor responses were assessed using Response Evaluation Criteria in Solid Tumors (RECIST), version 1.1. The median PFS was 13.3 months (95% CI: 6.5–20.0 months) in patients who received first-line crizotinib as compared with 5.4 months (95% CI: 4.4–6.5 months) in patients who received first-line standard chemotherapy (adjusted hazard ratio for progression or death with crizotinib, 0.20; 95% CI: 0.11–0.36; P < 0.001). In patients who received second-line crizotinib therapy, the median PFS was 9.9 months (95% CI: 6.4–13.4 months). The difference between first-line and second-line crizotinib treatment was not statistically significant (adjusted hazard ratio for progression, 0.56; 95% CI: 0.29–1.11; P = 0.092). Thus, there was a significant PFS benefit of first-line crizotinib versus first-line standard chemotherapy in Chinese patients with ALK-positive lung adenocarcinoma. Additionally, crizotinib showed promising efficacy in patients who received it as second-line therapy after PD had occurred on first-line chemotherapy.

There was a significant progression-free survival (PFS) benefit of first-line crizotinib versus first-line standard chemotherapy in Chinese patients with anaplastic lymphoma kinase (ALK)-positive lung adenocarcinoma. Additionally, crizotinib showed promising efficacy in patients who received it as second-line therapy after progressive disease (PD) had occurred on first-line chemotherapy.

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