Decreased cerebrospinal fluid neuropeptide Y (NPY) in patients with treatment refractory unipolar major depression: preliminary evidence for association with preproNPY gene polymorphism

Extensive animal studies suggest neuropeptide Y (NPY) to be involved in coping with a wide range of stressors, and that impaired central NPY signalling could be involved in the pathophysiology of anxiety and depression. Human studies of central NPY levels in depression have, however, been inconclusive. Here, we examined levels of NPY-like immunoreactivity (NPY-LI) in the cerebrospinal fluid (CSF) of medication-free subjects with treatment refractory unipolar depression. Patients were admitted to a research inpatient unit, examined under standardized conditions, and compared with a sample of volunteers in whom psychiatric morbidity was excluded. A robust suppression of NPY levels in patient CSF was found, while other putative CSF markers (monoamine metabolites, somatostatin) did not differ between the groups. We then explored whether this finding might be related to a recently described T1128C coding polymorphism which results in a Leu7-> Pro7 substitution of the signal peptide, and a previously not described T -399C polymorphism in the promoter region of the preproNPY gene. Preliminary evidence was found for an association of both markers with a diagnosis of depression, indicating the possibility of an underlying haplotype influencing the vulnerability for developing depressive illness. Our present findings are in line with an extensive animal literature, and further support the notion that impaired NPY function could contribute to depressive illness.     

Effect of β-endorphin on the contractile responses in mouse skeletal muscle

Tension development in response to direct and indirect electrical stimulation was studied in an isolated phrenic nerve hemidiaphragm preparation of the mouse. β-Endorphin (β-EP) caused an increase in the preparation of the mouse. β-Endorphin (β-EP) caused an increase in the response to low frequency stimulation of the nerve. Upon direct stimulation of the muscle the peptide had no effect. The actions of β-EP were abolished in the presence of the opioid antagonist naloxone and mimicked by β opioid agonists. Upon high frequency stimulation of the nerve, β-EP caused an increase in the initial, maximum, and mean tension. It also prevented the fall in the final tension seen in the control preparations with repeated periods of stimulation. The findings are consistent with β-EP having a role to improve neuromuscular function and deley fatigue, and indicate the possible therapeutic potential of opioid substances in conditions where muscle weakness is present. © John Wiley & Sons, Inc.     

Major Adverse Limb Events and Mortality in Patients With Peripheral Artery Disease: The COMPASS Trial

Background

Patients with lower extremity peripheral artery disease (PAD) are at increased risk of major adverse cardiovascular events (MACE) and major adverse limb events (MALE). There is limited information on the prognosis of patients who experience MALE.

Gold nanoparticles ameliorate acetaminophen induced hepato-renal injury in rats

Valuable effects of gold particles have been reported and used in complementary medicine for decades. The aim of this study was to evaluate the therapeutic efficacy of gold nanoparticles (AuNPs) against acetaminophen (APAP) induced toxicity. Albino rats were administered APAP at a dose of 2 g/kg p.o. once only. After 24 h of APAP intoxication, animals were treated with three different doses of AuNPs (50 μg/kg, 100 μg/kg, 150 μg/kg) orally or silymarin at a dose of 50 mg/kg p.o., once only. Animals of all the groups were sacrificed after 24 h of last treatment. APAP administered group showed a significant rise in the AST, ALT, SALP, LDH, cholesterol, bilirubin, albumin, urea and creatinine in serum which indicated the hepato-renal damage. A significantly enhanced LPO and a depleted level of GSH were observed in APAP intoxicated rats. Declined activities of SOD and Catalase, after acetaminophen exposure indicated oxidative stress in liver and kidney. The activities of ATPase and glucose-6-Phosphatase were significantly inhibited after APAP administration. AuNPs treatment reversed all variables significantly towards normal level and was found nontoxic. Thus it is concluded that gold nanoparticles played a beneficial role in reducing acetaminophen induced toxicity and can be used in the development of drug against hepatic as well as renal diseases, after further preclinical and clinical studies.     

Serum and hair zinc in severely malnourished Bangladeshi children associated with or without acute lower respiratory infection

Objective  To assess the zinc status in Bangladeshi children suffering from severe protein energy malnutrition (severe PEM), acute lower respiratory infection (ALRI), PEM presented with ALRI and to evaluate the relationship of zinc status with aforementioned clinical conditions. Methods  We assessed zinc status by simultaneous estimation of serum and hair zinc of Bangladeshi children less than 5 yr of age suffering from severe PEM, ALRI, severe PEM presented with ALRI and compared them with zinc status of well-nourished healthy children (control) in a hospital based cross sectional four cell study. Zinc concentration was estimated by Flame atomic absorption spectrophotometry. Results  Total one hundred and fifty two children were enrolled and number of children enrolled in severe PEM, ALRI, ALRI with PEM and control were 47, 35, 32 and 38 respectively. Both serum and hair zinc in univariate analysis were found significantly (p<0.05) low in severe PEM, ALRI and severe PEM associated with ALRI. However, in multivariate analysis, when serum and hair zinc were included in the same model, both serum and hair zinc were found to have significant negative association with PEM (p=0.002 & 0.013 respectively) and with ALRI only when ALRI was associated with PEM (p=0.043 and 0.034 respectively). Conclusion  Severe PEM and PEM with ALRI were significantly associated with low zinc status.     

Assessment of nitrite oxide and maternal–fetal Doppler parameters during pregnancy

Objective: The objective was to evaluate and compare the whole blood nitrite concentration in the three trimesters of pregnancy. Additionally, we investigate whether there is any relation between nitrite concentrations and Doppler ultrasound analysis of some maternal and fetal vessels.

Methods: Thirty-three healthy pregnant women were examined at the first (11–14 weeks), second (20–24 weeks) and third trimester (34–36 weeks) of pregnancy. In the three exams, we determined the maternal whole blood nitrite concentration and uterine arteries Doppler analysis to determine pulsatility index (PI), and resistance index (RI). In the second and third trimester we also performed fetal umbilical and middle cerebral arteries PI and RI. We compared the concentrations of nitrite in three trimesters and correlated with Doppler parameters.

Results: No difference was observed in the whole blood nitrite concentrations across trimesters: 151.70?±?77.90?nmol/ml, 142.10?±?73.50?nmol/ml and 147.10?±?87.30?nmol/ml; first, second and third trimesters, respectively. We found no difference in correlation between whole blood nitrite concentration and Doppler parameters from the evaluated vessels.

Conclusions: In healthy pregnant women, the nitrite concentrations did not change across gestational trimesters and there was also no strong correlation with Doppler impedance indices from maternal uterine arteries and fetal umbilical and middle cerebral arteries.     

Group A rotavirus-associated diarrhea in children seeking treatment in Indonesia

BACKGROUND: Globally, group A rotavirus causes significant morbidity and mortality among children. Limited data exist on the epidemiology of rotavirus disease among Indonesian children. OBJECTIVES: We describe the epidemiology of rotavirus-associated diarrhea among Indonesian children <6 years of age, including clinical symptoms and genotypes. STUDY DESIGN: We conducted a hospital-based, case series study at four referral hospitals between February 2004 and February 2005 among children with diarrhea. Rotavirus positivity was defined by a positive result from either EIA or RT-PCR. A semi-nested RT-PCR was used to determine specific rotavirus genotypes. RESULTS: 1660 stools were tested for pathogens. The overall rotavirus prevalence was 45.5%. Children with rotavirus-associated diarrhea were significantly younger (p<0.0001) and more likely to be hospitalized (81.3% versus 72.2%; p<0.0001). Symptoms associated with rotavirus included, vomiting, fever, nausea, fatigue and dehydration, while bloody stool was significantly less common with rotavirus-associated diarrhea. CONCLUSION: Rotavirus was an important contributor of morbidity to our study sample. Rotavirus genotyping demonstrated a temporal shift from G1-G4 to G9, but this was highly associated with the P[8] gene, suggesting that a multivalent rotavirus vaccine, incorporating G9 P[8] antigen, may reduce the burden of diarrheal illnesses among Indonesian children.     

A study of the killer cell immunoglobulin-like receptor gene KIR2DS1 in a Caucasoid Brazilian population with psoriasis vulgaris

Psoriasis is a chronic inflammatory skin disease whose pathogenesis and genetic background remain unclear. Considering that previous studies have suggested an association of psoriasis vulgaris (PV) and killer cell immunoglobulin-like receptors (KIRs), we typed 15 KIR genes and human leukocyte antigen (HLA)-Cw in 79 Brazilian Caucasoid patients with PV and 110 healthy controls by polymerase chain reaction (PCR) using sequence-specific oligonucleotides and sequence-specific primers. We did not observe a relevant increase in the frequency of the activating KIR2DS1 gene in the PV group [KIR2DS1, 46 of 79 cases (58.2%) vs 40 of 110 controls (36.4%)]. However, an association of KIR2DS1 with Cw*0602+ in 26.5% of PV patients was observed, while it was present in only 5.4% of controls. These results suggest that activating KIR2DS1 gene may not confer susceptibility to PV, and an association of KIR2DS1 gene with the HLA-Cw*0602+ was observed in these patients.