Regulation of hunger-driven behaviors by neural ribosomal S6 kinase in Drosophila

Hunger elicits diverse, yet coordinated, adaptive responses across species, but the underlying signaling mechanism remains poorly understood. Here, we report on the function and mechanism of the Drosophila insulin-like system in the central regulation of different hunger-driven behaviors. We found that overexpression of Drosophila insulin-like peptides (DILPs) in the nervous system of fasted larvae suppressed the hunger-driven increase of ingestion rate and intake of nonpreferred foods (e.g., a less accessible solid food). Moreover, up-regulation of Drosophila p70/S6 kinase activity in DILP neurons led to attenuated hunger response by fasted larvae, whereas its down-regulation triggered fed larvae to display motivated foraging and feeding. Finally, we provide evidence that neural regulation of food preference but not ingestion rate may involve direct signaling by DILPs to neurons expressing neuropeptide F receptor 1, a receptor for neuropeptide Y-like neuropeptide F. Our study reveals a prominent role of neural Drosophila p70/S6 kinase in the modulation of hunger response by insulin-like and neuropeptide Y-like signaling pathways.     

Clearance of theophylline by hemodialysis in one patient with chronic renal failure.

The clearance of theophylline by hemodialysis was determined in one patient who had polycystic kidney with chronic renal failure and bronchial asthma. The serum levels of theophylline were determined by enzymatic immunoassay on two consecutive days, once on a dialysis day and again on a nondialysis day. Clearance of theophylline by hemodialysis was 119 ml/min, and the extraction efficiency was 0.56. The elimination half-life of theophylline shortened from 5.7 h to 1.6 h during hemodialysis. The dialysis rate constant (Kd) was 0.32/h, and 79 percent of the total body store of the drug was removed during a 4-h dialysis. Patients receiving theophylline who are maintained on hemodialysis should be closely monitored for bronchospasm during and after the hemodialysis procedure. Measurement of serum concentrations of theophylline should be employed to facilitate increases in dosage during hemodialysis.     

内质网分子伴侣糖调节蛋白94在非酒精性脂肪肝中的表达及意义

目的:检测非酒精性脂肪肝患者肝组织中糖调节蛋白94的表达情况,探讨非酒精性脂肪肝病(nonalcoholic fattyliver disease,NAFLD)的发病机制.方法:应用半定量逆转录聚合酶链反应(RTPCR)法和免疫组化法检测脂肪肝组和正常对照组肝组织中糖调节蛋白94基因和蛋白表达,HE染色观察肝脏脂肪变性、炎性活动和坏死,并进行相关分析.结果:非酒精性脂肪肝组脂肪变性、炎症评分及坏死评分较正常对照组明显增加,差异具有统计学意义(3.89±0.32 VS 0.20±0.4;3.67±0.49 VS 0:0.44±0.51 VS 0,P＜0.01或0.05).与正常组比较,脂肪肝患者肝组织糖调节蛋白94mRNA和蛋白表达明显增强(0.86±0.02 VS 0.37±0.03;0.34±0.01 VS 0.31±0.01,均P＜0.01).糖调节蛋白94 mRNA和蛋白表达与脂肪变性、炎症评分及坏死评分明显呈正相关(P＜0.01).结论:非酒精脂肪肝引起的肝脏损害可能与糖调节蛋白94表达有关.     

Collagenous pouchitis

Collagenous colitis is characterised by watery diarrhoea, normal colonic mucosa on endoscopy, diffuse colitis with surface epithelial injury, and a distinctive thickening of the subepithelial collagen table on histology. Some patients can develop medically refractory collagenous colitis, in which case they may require surgical intervention. This is the first report of collagenous pouchitis in a collagenous colitis patient with proctocolectomy and ileal pouch-anal anastomosis. A patient with medically refractory collagenous colitis who underwent a total proctocolectomy and ileal pouch-anal anastomosis was sequentially evaluated with an endoscopy and histology of the colon, distal small intestine, and ileal pouch. A 58-year-old female had a 10-year history of collagenous colitis before having a total proctocolectomy and ileal pouch-anal anastomosis for medically refractory disease. The histologic features of collagenous colitis were present in all colon and rectum biopsy or resection specimens, but were absent in the distal ileum specimen. The post-operative course was complicated by persistent increase of stool frequency, abdominal cramps, and incontinence. A pouch endoscopy was performed 3 years after ileal pouch-anal anastomosis which showed the histologic features of collagenous colitis in the ileal pouch, collagenous pouchitis, while the pre-pouch neo-terminal ileum had no pathologic changes. After antibiotic therapy, the histologic changes of collagenous pouchitis resolved. This is the first reported case of collagenous pouchitis. Since the abnormal collagen table and its associated features were only present in the pouch and absent in the neo-terminal ileum, and the patient had histologic improvement after antibiotic therapy, it would suggest that faecal stasis and bacterial load may play a role in the pathogenesis.     

Human immunodeficiency virus type 1-infected women exhibit reduced interferon-gamma secretion after Chlamydia trachomatis stimulation of peripheral blood lymphocytes

Epidemiologic, animal, and in vitro models suggest an important role for interferon (IFN)-gamma in the clearance of Chlamydia trachomatis infection. IFN-gamma in the supernatants of in vitro-stimulated peripheral blood mononuclear cells (PBMC) from 22 human immunodeficiency virus type 1 (HIV-1)-infected and 73 uninfected women at high risk for C. trachomatis acute pelvic inflammatory disease (PID) was studied. PBMC were stimulated with C. trachomatis purified major outer membrane protein (MOMP) and whole elementary bodies (EBs) from the 4 predominant serovars (E, F, K, and L2) that circulate in Nairobi. PBMC IFN-gamma secretion after stimulation with C. trachomatis EBs was significantly decreased in HIV-1-infected women. Among HIV-1-infected women, CD4 T cell depletion was associated with lower IFN-gamma secretion from PBMC stimulated with either C. trachomatis MOMP or EB antigen. Decreased antigen-specific IFN-gamma production may enhance the susceptibility of HIV-1-infected women to C. trachomatis PID.     

Gene cloning, expression and vaccine testing of Schistosoma japonicum SjFABP

A 600 bp DNA fragment was amplified by PCR from an adult Schistosoma japonicum cDNA library. Sequence analysis confirmed that this fragment contained an S. japonicum Chinese mainland strain fatty acid binding protein (Sj14FABP) gene. This gene was subsequently expressed in Escherichia coli (E. coli) and in Baculovirus/silkworm systems. The recombinant protein from E. coli was a 41 kDa GST fusion protein (rSj14/GST), which could be purified by glutathione agarose affinity chromatography, with a yield of 25 mg/L E. coli culture. The recombinant protein from the Baculovirus/silkworm system was an 18 kDa fusion protein (rSj14/His), which could be purified by Ni-NTA resin chromatography column with a yield of 3.5 mg per silkworm larva. Both rSj14/GST and rSj14/His could be recognized by S. japonicum-infected mouse sera and anti-rSj14/GST mouse sera in Western blotting. The purified recombinant protein was immunogenic in mice, rats and sheep, and 34.3%, 31.9% and 59.2% worm reductions, respectively, were obtained in vaccinated Kunming mice, Wistar rats and sheep vaccinated with Sj14/GST, compared to non-vaccinated control groups. Worm reductions of 48.8% and 49.0% were recorded in Balb/c mice immunized with Sj14/His, compared to non-vaccinated and BCG-vaccinated groups, respectively. These results indicate that rSj14FABP is a promising candidate vaccine for schistosomiasis japonica, particularly as in the rat and sheep vaccination experiments, no adjuvant was used.     

Segmental analysis of antidepressant and antipsychotic drugs in the hair of schizophrenic patients

Hair analysis is useful for documenting long‐term exposure to drugs. The potential of hair analysis for therapeutic drug monitoring within the forensic field has been studied, but reference values for some antidepressants and antipsychotics in the hair of individuals undergoing chronic therapy are still lacking. In the present study, a method was developed and validated for the determination of 23 analytes, including antidepressants, antipsychotics, and related metabolites, in human hair by liquid chromatography–tandem mass spectrometry (LC–MS/MS). Hair samples (10 mg) were extracted with a 25:25:50 (v/v/v) mixture of methanol/acetonitrile/2 mM ammonium formate (8% acetonitrile, pH 5.3) utilizing cryogenic grinding. The present method demonstrated sufficient selectivity, robustness, and accuracy. Sixteen analytes in hair were reported in 46 psychiatric patients receiving fixed drug dosages. To the best of our knowledge, the hair concentrations of perphenazine and norolanzapine, as well as the concentrations of amisulpride, aripiprazole and its metabolite dehydroaripiprazole, olanzapine, and sulpiride, in hair from individuals receiving fixed dosages is reported for the first time. A significant relationship between the administered dose and the concentration in the proximal hair segment was found only for clozapine, norclozapine, and chlorpromazine. The results confirmed that the idea of using hair concentrations to monitor a daily dose is inapplicable.     

Simultaneous analysis of 29 synthetic cannabinoids and metabolites,amphetamines, and cannabinoids in human whole blood by liquid chromatography–tandem mass spectrometry – A New Zealand perspective of use in 2018

We describe the validation of a method for the simultaneous analysis of 29 synthetic cannabinoids (SCs) and metabolites, 4 amphetamines, and 2 cannabinoids in human whole blood. This method enables one analysis to cover what previously required multiple analyses for these classic and novel drugs‐of‐abuse with diverse physicochemical properties. The scope of targeted analytes was based on the most prevalent drugs‐of‐abuse and SCs encountered at the New Zealand border in 2017 and included parent compounds and metabolites belonging to the indole and indazole carboxamide, quinolinyl indole carboxylate, and naphthoylindole classifications. Samples were prepared by supported‐liquid‐extraction (SLE) followed by liquid chromatography?tandem mass spectrometry (LC?MS/MS) analysis with positive electrospray ionization (ESI). The method was validated with respect to selectivity, matrix effects, process efficiency, sensitivity, repeatability, extract stability, and carryover for qualitative confirmation. Linearity as well as accuracy and precision data at target decision concentrations were also evaluated. The limits of detection and confirmation ranged from 0.1 to 6.0 ng/mL and 1.0 to 6.0 ng/mL, respectively. The described method was successfully applied to the analysis of 564 ante‐ and post‐mortem blood samples in 2018. There were 132 cases (23%) with positive findings of at least one SC, with the five most commonly detected SCs being AMB‐FUBINACA and/or acid (61%), 5F‐ADB and/or acid (40%), ADB‐FUBINACA (11%), 5F‐MDMB‐PICA acid (6%), and MDMB‐FUBINACA acid (6%). The results also demonstrate the predominant presence of metabolites at higher levels than the unchanged parent SCs in blood, highlighting the need to maintain forensic screening methods capable of the simultaneous detection of both parent compounds and metabolites.     

A new prenatal sonographic sign of epidermolysis bullosa

We report on the prenatal sonographic appearance of epidermolysis bullosa (EB). The third viable pregnancy of a consanguineous couple was found at 23 weeks to have dysplastic external ears and nose. The neonate was born at 33 weeks and was found to have junctional EB with pyloric atresia. On reviewing the 23‐week ultrasound images, skin denudation was evident. This is a report of visualization of skin denudation in EB. When EB is suspected prenatally, special attention should be given to the visualization of skin surfaces.     

Rapid Changes in Serum Testosterone in Men With Newly Diagnosed Type 2 Diabetes With Intensive Insulin and Metformin

OBJECTIVETo investigate the effect of metformin on testosterone levels in men with type 2 diabetes mellitus (T2DM).RESEARCH DESIGN AND METHODSSeventy men with newly diagnosed drug-naive T2DM and HbA_1c >9.0% (75 mmol/mol) were treated with intensive insulin pump therapy for 5 days to achieve glucose normalization. They were randomized to control (continued on intensive insulin only) and metformin (plus metformin) groups (1:1) for 1 month. Testosterone was measured at baseline, randomization, and after 1-month treatment.RESULTSTotal, free, and bioavailable testosterone increased significantly within 5 days (all P < 0.001). After 1 month, compared with the control group, the metformin group had lower total (12.7 vs. 15.3 nmol/L), free (0.20 vs. 0.24 nmol/L), and bioavailable (4.56 vs. 5.31 nmol/L) testosterone (all P < 0.05).CONCLUSIONSIn men with T2DM, 1-month oral metformin may decrease serum testosterone levels independent of blood glucose control. The effects of long-term metformin on testosterone in men need further study.