Optimal duration of treatment for HCV genotype 1 infection in slow responders: a meta-analysis

Background

A head-to-head comparison of the 72-week and 48-week anti-HCV therapies in slow responders with genotype 1 infection has been performed in several randomized clinical trials (RCTs).

Objectives

This review aimed at summarizing and pooling the results of these studies.

Materials and Methods

RCTs that had evaluated the 72-week vs. 48-week anti-HCV therapy (peginterferon and ribavirin) in slow responders with HCV genotype 1 infection were systematically identified. A meta-analysis was performed using the random effects model. Heterogeneity in results was assessed on the basis of the Q statistics, and publication bias was evaluated by using Harbord’s modified test. The end point was set as a sustained virological response (SVR).

Results

Data of 1206 subjects were retrieved from 7 studies. A total of 631 patients had received extended therapy. Slow virological responders who received the 72-week therapy had a significantly higher probability of achieving SVR than their counterpartswho received the 48-week therapy [RR = 1.44 (95% CI, 1.20–1.73)]. With regard to publication biases, the heterogeneity in funnel plots was not significant (P = 0.19, I2 = 30%, PHarbord = 0.1).

Conclusion

Our meta-analysis showed that the 72-week therapy with peginterferon and ibavirin is significantly superior to the standard 48-week therapy in slow responders th HCV genotype 1 infection.     

The Ki-67/MIB-1 index level and recurrence of papillary thyroid carcinoma

Thyroid Neoplasms, papillary and follicular carcinomas, are a heterogeneous group of tumors, which combined make up almost 95% of all endocrine tumors and accounts for about 1% of all malignancies. Papillary thyroid carcinoma is associated with the expression of multiple cell proliferating markers such as Ki-67/MIB-1, cyclin D1, p27, which were linked to the biological features and clinical behavior of the tumors. It is important to determine prognostic factors for survival in patients with clinical recurrence of PTMC, to more clearly determine optimal management regimens. Emerging epidemiological and clinical evidences suggest that Ki-67/MIB-1 may positivity confers a higher risk of recurrence and a worse survival in patients with PTC. This leads to the hypothesis that, it is possible to use Ki-67/MIB-1 as a prognostic marker in the thyroid tumors especially in papillary thyroid micro-carcinoma, and defined its index values closed to the papillary thyroid carcinoma as a cutoff for detection of the tumor recurrence. It is our hope that use this genes as a defined marker of cell proliferation to better understand cancer pathogenesis to prevent the recurrence or to improve the survival, and ultimately to expand therapeutics.     

Effects of oleuropein on pentylenetetrazol-induced seizures in mice: involvement of opioidergic and nitrergic systems

Oleuropein, a well-known olive polyphenol, has been shown to mediate neuroprotection in Alzheimer’s disease and cerebral ischemia. We investigated the effects of oleuropein on pentylenetetrazole (PTZ)-induced seizures in male NMRI mice, with diazepam as the standard drug. We also examined the possible involvement of opioidergic/nitrergic pathways in the probable effects of oleuropein. Intraperitoneal (i.p.) administration of different doses of oleuropein (10, 20 and 30 mg/kg) significantly increased the seizure threshold 60 min prior to induction of seizure, in a dose-dependent manner. Administration of naltrexone (10 mg/kg, i.p.), an opioid receptor antagonist, completely reversed the anticonvulsant effects of oleuropein (10 mg/kg). On the other hand, the anticonvulsant effect of oleuropein (10 mg/kg) was blocked by a non-effective dose of nonspecific inhibitor of nitric oxide synthase (NOS), L-NAME (1 and 10 mg/kg, i.p) and a selective inhibitor of neuronal NOS, 7-nitroindazole (30 mg/kg, i.p.). However, the nitric oxide precursor, l-arginine (30 and 60 mg/kg, i.p.) potentiated the anticonvulsant activity of oleuropein (10 mg/kg). A selective inducible NOS inhibitor, aminoguanidine (100 mg/kg, i.p.) did not change the anticonvulsant activity of oleuropein. It seems that the opioidergic system and constitutive neuronal NOS may be involved in the anticonvulsant properties of oleuropein.     

Matrix metalloproteinase 2 secretion in WEHI 164 fibrosarcoma cells is nitric oxide-related and modified by morphine

Matrix metalloproteinases (MMP) are ubiquitous enzymes involved in extracellular matrix remodeling, and as a consequence in a number of physiological and pathological states, including development, wound healing and cancer. A crucial feature of cancer progression and metastasis is the disruption of extracellular matrix, and spreading of proliferating cancer cells. Modulation of MMP is a main target of cancer research. Using the mouse fibrosarcoma cell line WEHI 164, producing high amounts of MMP-2, we investigated whether we could modulate its production. We report that MMP-2 is under the control of nitric oxide (NO)/nitric oxide synthase (NOS) system. In addition, we show that NOS activity is controlled by opioids in a non-opioid receptor-related manner. Finally, we provide evidence that morphine, when administrated at low, non-toxic concentrations (<10(-9) M) attenuates MMP-2 activity. We conclude that, as morphine is able to decrease metalloproteinase activity via the NO/NOS system, it may have a place in the treatment of several sarcomas including fibrosarcoma.     

Assessment of indirect hemagglutination and zymography procedures in evaluation of gelatinase a in patients with benign and malignant prostate hyperplasia

There are increasing data on novel tumor markers such as gelatinase A, which play a key role in tissue invasion and metastasis. Since prostate cancer is one of the common malignancies, we designed a simple and applicable Indirect Hemagglutination (IHA) test for determination of total gelatinase A in serum samples. In this study, we have analyzed the circulating form of gelatinase A (MMP-2) in patients suffering from either benign prostate hyperplasia (n= 54) or prostate cancer (n= 26) and normal individuals as control (n= 26). The gelatinolytic activity was determined by zymography followed by densitometric analysis. PSA was quantified by using a standard ELISA technique. Correlation of densitometric analysis of gelatinase A activity and IHA titer was significant at 0.01 level (p< 0.01, r = 0.916). Correlation of PSA and IHA titer was significant at 0.01 level (p< 0.01, r = 0.746). Border line IHA titer in patients with prostate cancer was 512 +/- 1 tube titer, in benign prostate hyperplasia patients was 128 +/- 1 tube titer, and the titer in normal individuals was 8 +/- 1 tube titer. These results demonstrate that IHA compared to zymography may be a better and simpler procedure in monitoring and screening patients with prostate cancer.     

Lethal area 50 percent (LA50) or standardized mortality ratio (SMR): Which one is more conclusive?

Background

Burn injuries impose a considerable burden on healthcare systems. It is among the top ten causes of mortality and a major cause of disability. This study aimed to calculate and compare the lethal area fifty percent (LA50) and standardized mortality ratio (SMR) in patients with burns.

Reliable prediction of n-heptane isomerization over Pt/(CrOx/ZrO2)-HMS via comparative assessment of regularization networks and surface response methodologies

Novel Pt–Cr/Zr(x)-HMS catalysts with different molar ratios of Cr/Zr were synthesized. These catalysts were characterized by necessary techniques including XRD, XRF, NH₃-TPD, FTIR, H₂ chemisorption, nitrogen sorption and TGA. Moreover, generalization performances of an optimized in-house regularization network and an RSM were compared for the prediction of activity and selectivity versus various molar ratios, feed temperatures and time on stream. The results indicated that the incorporation of Cr promotes the catalyst activity, in which a high amount of 63% conversion was obtained at Cr/Zr = 30 and T = 200 °C. Increasing temperature has an adverse effect on i-C₇ and mono plus multi-branch isomer selectivity nearly in all amounts of molar ratios. The best i-C₇ selectivity (66%), MOB (29.6%) and MUB (32%) were observed at 200 °C and Cr/Zr = 30. Although both modeling methods exhibited outstanding performances, statistical analysis revealed that optimized RN has slightly better performances than RSM.

Novel Pt–Cr/Zr(x)-HMS catalysts with different molar ratios of Cr/Zr were synthesized.     

Rosai‐Dorfman disease: A case report of asymptomatic isolated renal involvement

A possible diagnosis of RDD should be kept in mind when encountering a patient with raised plasma creatinine levels and renal mass. Timely diagnosis and management of RDD will help prevent future kidney loss.