Psychiatric morbidity and HIV in female drug dependants in Malaysia

Female drug dependants (n = 171) and controls (n = 1137) were studied to search for psychiatric morbidity in them. The psychiatric morbidity was found to be 36.3% and 6.9%, respectively. The most common psychiatric disorder found was dysthymic disorder followed by adjustment disorder, anxiety disorder and borderline personality disorder. The diagnosis was significantly dependent on the type of drug used (P < 0.001) and HIV seropositivtty status of the patients (P = 0.04). The findings highlight the relationship of the psychiatric morbidity to the HIV status and female drug users.     

小藤铃儿草的生物碱成分

自小藤铃儿草Dactylicapnos torulosa(Hook.f ct Thomas.)Hutchins中分得六个单体,通过UV,IR,MS,~1HNMR和~(13)CNMR解析,鉴定了四个,其中一个为新化合物,命名为紫金龙碱(zijinlongine,Ⅰ),其他三个为已知化合物:氯化1-甲氧基小檗碱(1-methoxylberberium chloride,Ⅱ),氯化三乙基苯胺(triethylphcnylamium chloride,Ⅲ)和异紫堇定(isocorydine,Ⅳ)。Ⅱ和Ⅲ系首次从植物中得到。     

Changes in symptom scores as a potential clinical endpoint for studies of cystic fibrosis pulmonary exacerbation treatment

Introduction: Symptom improvement was assessed as changes in the Chronic Respiratory Infection Symptom Score (CRISS) during intravenous antimicrobial exacerbation treatments among subjects from study NCT02109822.Methods: Median daily CRISS reduction (i.e., improvement) and covariates associated with CRISS reduction by Day 14 were assessed by logistic regression.Results: Among 173 subjects, median baseline CRISS was 49 [IQR 41, 56]; 93.6% had a CRISS reduction of ≥11 (minimal clinically important difference); median time to –11 reduction was 2 days [95% CI 2, 3]. The greatest median CRISS difference from baseline, on Day 17, was –26 [–29, –23]. Odds of –26 CRISS change by Day 14 were greater in subjects with higher baseline CRISS (P=.006) and younger ages (P=.041).Conclusions: CRISS response has good dynamic range and may be a useful efficacy endpoint for PEx interventional trials. The optimal use of CRISS change as an endpoint remains uncharacterized.     

Use of pulse oximetry for blood pressure measurement after cardiac surgery

Blood pressure measurement using pulse oximeter waveform change was compared with an oscillometric measurement and the gold standard, intra-arterial measurement, in children after cardiac surgery. Forty six patients were enrolled and divided into groups according to weight. Simultaneous blood pressure measurements were obtained from the arterial catheter, the oscillometric device, and the pulse oximeter. Pulse oximeter measurements were obtained with a blood pressure cuff proximal to the oximeter probe. The blood pressure measurements from the pulse oximeter method correlated better with intra-arterial measurements than those from the oscillometric device (0.77-0.96 v 0.42-0.83). The absolute differences between the pulse oximeter and intra-arterial measurements were significantly smaller than between the oscillometric and intra-arterial measurements in children less than 15.0 kg. The pulse oximeter waveform change is an accurate and reliable way to measure blood pressure in children non-invasively, and is superior to the oscillometric method for small patients.     

Protein restriction in chronic renal failure

The aim of the study was to investigate the effect of a protein restricted diet on renal function and growth of children with chronic renal failure. In a multicentre prospective study 56 children (aged 2-18 years) with chronic renal failure were randomly assigned to the protein restricted (0.8-1.1 g/kg/day) or the control group. All children were followed up by the same paediatrician and dietitian. After a follow up period of three years there was no significant difference in glomerular filtration rate between children on a protein restricted diet and children of the control group. There was no significant difference in weight with respect to height and height SD score between the protein restricted and the control group. Compliance with the protein restricted diet, as indicated by the prospective diet diaries and the serum urea:creatinine ratio, was good. This study shows that children with chronic renal failure do not benefit from a protein restricted diet.     

Relationship between clinical features of Parkinson's disease and presynaptic dopamine transporter binding assessed with [123I]IPT and single-photon emission tomography

IPT [N-(3-iodopropen-2-yl)-2-carbome-thoxy-3-(4-chlorophenyl) tropane] is a new cocain analogue which allows the presynaptic dopamine transporters to be imaged with single-photon emission tomography (SPET) as early as 1–2 h post injection. In the present study [¹²³I]IPT SPET was performed in patients with Parkinson's disease (PD) to analyse the relationship between specific dopamine tansporter binding and clinical features of the disease. Twenty-six PD patients (Hoehn and Yahr stages I-IV, age range 40–79 years) and eight age-matched controls were studied. SPET imaging was performed 90–120 min after injection of 160–185 MBq [¹²³I]IPT using a triple-head camera. For semiquantitative evaluation of specific [¹²³I]IPT binding, ratios between caudate, putamen and background regions were calculated. Specific [¹²³I]IPT uptake was significantly reduced in PD patients compared to controls. Most patients showed a marked asymmetry with a more pronounced decrease in [¹²³I]IPT binding on the side contralateral to the predominant clinical findings. The putamen was always more affected than the caudate. [¹²³I]IPT binding was significantly correlated with disease duration (r=–0.7,P<0.0001) but not with the age of PD patients (r=–0.10,P=0.61). Specific [¹²³I]IPT uptake in the caudate and putamen, and putamen to caudate ratios, decreased with increasing Hoehn and Yahr stage. Our findings indicate that [¹²³I]IPT SPET may be a useful technique to estimate the extent of nigrostriatal degeneration in PD patients. Close relationships between striatal [¹²³I]IPT binding and clinical features of the disease suggest that this method can be used to objectively follow the course and progression of PD. The reduced putamen to caudate ratios observed even in patients with mild, newly recognized symptoms indicate that particularly this parameter may help to establish the correct diagnosis in the early course of PD.     

Combined 1-Deoxynojirimycin and Ibuprofen Treatment Decreases Microglial Activation,Phagocytosis and Dopaminergic Degeneration in MPTP-Treated Mice

Inflammation is a predominant aspect of neurodegenerative diseases and experimental studies performed in animal models of Parkinson’s disease (PD) suggesting that a sustained neuroinflammation exacerbates the nigrostriatal degeneration pathway. The central role of microglia in neuroinflammation has been studied as a target for potential neuroprotective drugs for PD, for example nonsteroidal anti-inflammatory drugs (NSAIDs) and matrix metalloproteinases (MMP) inhibitors that regulates microglial activation and migration. The aim of this study was to investigate the neuroprotective response of the iminosugar 1-deoxynojirimycin (1-DNJ) and compare its effect with a combined treatment with ibuprofen. MPTP-treated mice were orally dosed with ibuprofen and/or 1-DNJ 1. Open-field test was used to evaluate behavioral changes. Immunohistochemistry for dopaminergic neurons marker (TH⁺) and microglia markers (Iba-1⁺; CD68⁺) were used to investigate neuronal integrity and microglial activation in the substantia nigra pars compacta (SNpc). The pro-inflammatory cytokines TNF-α and IL-6 were analysed by qPCR. Treatments with either 1-DNJ or Ibuprofen alone did not reduce the damage induced by MPTP intoxication. However, combined treatment with 1-DNJ and ibuprofen prevents loss of mesencephalic dopaminergic neurons, decreases the number of CD68⁺/ Iba-1⁺ cells, the microglia/neurons interactions, and the pro-inflammatory cytokines, and improves behavioral changes when compared with MPTP-treated animals. In conclusion, these data demonstrate that the combined treatment with a MMPs inhibitor (1-DNJ) plus an anti-inflammatory drug (ibuprofen) has neuroprotective effects open for future therapeutic interventions.

MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine) is a protoxicant that, after crossing the Blood Brain Barrier, is metabolized by astrocytic MAO-B to MPDP+, a pyridinium intermediate, which undergoes further two-electron oxidation to yield the toxic metabolite MPP+ (methyl-phenyltetrahydropyridinium) that is then selectively transported into nigral neurons via the mesencephalic dopamine transporter. In this study, we demonstrated that MPTP induced death of dopaminergic neurons, microgliosis, increase of gliapses, motor impairment and neuroinflammation in mice, which were inhibited by combined 1-deoxynojirimycin and ibuprofen treatment.

     

Metabolic actions of FGF21: molecular mechanisms and therapeutic implications

Fibroblast growth factor 21 (FGF21) is an atypical member of the FGF family that functions as an endocrine factor. In obese animals, elevation of plasma FGF21 levels by either pharmacological or genetic approaches reduces body weight, decreases hyperglycemia and hyperlipidemia, alleviates fatty liver and increases insulin sensitivity. FGF21 exerts its pleiotropic metabolic effects through its actions on multiple targets, including adipose tissue, liver, brain and pancreas. The expression of FGF21 is under the control of both peroxisome proliferator-activated receptor gamma (PPARγ) and peroxisome proliferator-activated receptor alpha (PPARα). A growing body of evidence suggests that the metabolic benefits of these two nuclear receptors are mediated in part by induction of FGF21. In humans, plasma levels of FGF21 are elevated in obese subjects and patients with type 2 diabetes, but are reduced in patients with autoimmune diabetes. This review summarizes recent advances in understanding the physiological roles of FGF21 and the molecular pathways underlying its actions, and also discusses the future prospective of developing FGF21 or its agonists as therapeutic agents for obesity-related medical complications.