Fungal transformation of androsta-1,4-diene-3,17-dione by Aspergillus brasiliensis

Background

The biotransformation of steroids by fungal biocatalysts has been recognized for many years. There are numerous fungi of the genus Aspergillus which have been shown to transform different steroid substances. The possibility of using filamentous fungi Aspergillus brasiliensis cells in the biotransformation of androsta-1,4-diene-3,17-dione, was evaluated.

Methods

The fungal strain was inoculated into the transformation medium which supplemented with androstadienedione as a substrate and fermentation continued for 5 days. The metabolites were extracted and isolated by thin layer chromatography. The structures of these metabolites were elucidated using ¹H-NMR, broadband decoupled ¹³C-NMR, EI Mass and IR spectroscopies.

Results

The fermentation yielded one reduced product: 17β-hydroxyandrost-1,4-dien-3-one and two hydroxylated metabolites: 11α-hydroxyandrost-1,4-diene-3,17-dione and 12β-hydroxyandrost-1,4-diene-3,17-dione.

Conclusions

The results obtained in this study show that A. brasiliendsis could be considered as a biocatalyst for producing important derivatives from androstadienedione.     

Raloxifene adjunctive therapy for postmenopausal women suffering from chronic schizophrenia: a randomized double-blind and placebo controlled trial

Background

Cumulative evidence from epidemiological, preclinical and clinical studies suggests estrogens may have psychoprotective effects in schizophrenic patients. Selective Estrogen Receptor Modulators could have therapeutic benefits in schizophrenia for both sexes without being hazardous to gynecological tissues or having feminizing effects. Few studies have been conducted regarding the effects of raloxifene on postmenopausal women suffering from schizophrenia. We conducted this placebo-controlled trial to compare the add-on effect of raloxifene to risperidone versus risperidone with placebo.

Methods

This was an 8-week, parallel-group, placebo-controlled trial undertaken at two universities affiliated psychiatric Hospitals in Iran. Forty-six postmenopausal women with the definite diagnosis of schizophrenia were enrolled in the study. Patients received risperidone (6 mg/day in 3 divided doses) combined with either placebo (N = 23) or 120 mg/day of raloxifene (N = 23) for 8 weeks. Patients were assessed by a psychiatrist at baseline and at 2 and 8 weeks after the start of medical therapy. Efficacy was defined as the change from baseline to endpoint in score on Positive and Negative Syndrome Scale (PANSS).

Results

For PANSS scores, the main effect comparing two types of intervention was not significant [F (1, 48) = 1.77, p = 0.18]. For positive subscale scores, there was marginal significant interaction between intervention type and time [F (2, 47) = 2.93, p = 0.06] and there was substantial main effect for time [F (2, 47) = 24.39, p = 0.001] within both groups showing reduction in positive subscale scores across the three time periods. In addition, the main effect comparing two types of intervention was significant [F (1, 48) = 3.78, p = 0.02]. On the other hand, for negative subscale scores, the main effect comparing two types of intervention was not significant [F (1, 48) = 1.43, p = 0.23]. For general subscale scores, the main effect comparing two types of intervention was not significant [F (1, 48) = 0.03, p = 0.86].

Conclusions

According to our findings, raloxifene as an adjunctive treatment to risperidone was only superior in improvement of positive symptoms and it was not effective in treating negative and general psychopathology symptoms.

Trial registration

The trial was registered at the Iranian registry of clinical trials: IRCT201205131556N42     

Synthesis of thioether derivatives of quinazoline-4-one-2-thione and evaluation of their antiplatelet aggregation activity

A series of 2-(arylmethylthio)-3-phenylquinazolin-4-one derivatives have been synthesized and their antiplatelet aggregation activities were assessed against ADP and arachidonic acid-induced platelet aggregation in human plasma. Among the tested thioethers, derivative 2, 3, 5 and 16 were the most potent compounds with satisfactory IC₅₀ for inhibition of platelet aggregation induced by ADP. Analysis of global physicochemical parameters shows some correlations between activities and molecular volume and also surface area of the studied derivatives.     

Concordance of PCR and Culture from Nasal Swabs for Detection of Methicillin-Resistant Staphylococcus aureus in a Setting of Concurrent Antistaphylococcal Antibiotics

The effect of concurrent administration of antibiotics on the detection of methicillin-resistant Staphylococcus aureus (MRSA) remains unresolved. Here, we assessed the concordance of paired nasal swabs processed using commercial PCR and culture and found high concordance in both the absence and presence of antibiotics with activity against MRSA (93.7% [95% confidence interval [CI], 88.1%, 96.8%] and 90.9% [95% CI, 84.8%, 94.7%], respectively), although PCR was more likely to be positive in the presence of antibiotics. (This study has been registered at ClinicalTrials.gov under registration no. {"type":"clinical-trial","attrs":{"text":"NCT01234831","term_id":"NCT01234831"}}NCT01234831.)     

Attenuation of inflammation in streptozotocin-induced diabetic rabbits by Matricaria chamomilla oil: A focus on targeting NF- κ B and NLRP3 signaling pathways

Objectives: The present study was conducted to investigate the protective effects of chamomile oil from Matricaria chamomilla against type 1 diabetes mellitus(T1 DM) and its potential mechanisms.Methods: T1 DM was established in male New Zealand white rabbits via a single intraperitoneal infusion of streptozotocin(STZ)(80 mg/kg body weight-1, dissolved in 0.2 m L of normal saline). Different doses of chamomile oil(25, 50 and 100 mg/kg) were orally administrated to STZ induced diabetic rabbits for 21 consecutive days. The expression of pro-inflammatory cytokines was determined using ELISA assay. The expression of NF-κB and NLRP3 was measured using Western blot assay.Results: Compared with normal rabbits, STZ-induced diabetic rabbits exhibited significant increased levels of blood glucose and decreased levels of serum insulin that were reversed using middle and high tested dose of chamomile oil. Likewise, STZ-induced diabetic rabbits showed a significant increased expression of NF-κB and NLRP3 proteins in the pancreas tissue that was reversed by high tested dose of chamomile oil.Conclusion: Collectively, our findings demonstrated that chamomile oil possesses anti-hyperglycemic, and anti-inflammatory activities in STZ-induced diabetic rabbits by targeting inflammatory cytokines and NF-κB and NLRP3 signaling pathways.     

Hereditary neuropathy with liability to pressure palsies

Journal of Neurology - Hereditary neuropathy with liability to pressure palsies (HNPP) is characterized by recurrent sensory and motor neuropathy in individual nerves starting in adolescence or...