Adiponectin and chronic kidney disease.

Enhanced chronic inflammation and reduced insulin sensitivity are often present in chronic kidney disease (CKD). Cardiovascular disease remains a major cause of morbidity and mortality in end-stage renal patients. Adiponectin (ADP) is a hormone exclusively produced by adipocytes and possesses anti-inflammatory and cardioprotective properties. Despite the high prevalence of insulin resistance and cardiovascular disease, levels of ADP are increased among end-stage renal disease patients on hemo or peritoneal dialysis but also among patients with moderate renal failure or with the nephrotic syndrome. Furthermore, lower ADP levels are associated with poor cardiovascular outcome. In this review, we examine ADP modifications in CKD and discuss the different factors that may have an impact on this adipokine metabolism in renal failure.     

Atazanavir / ritonavir versus Lopinavir / ritonavir-based combined antiretroviral therapy (cART) for HIV-1 infection: a systematic review and meta-analysis

BackgroundThis systematic review and meta-analysis was conducted to evaluate the safety and effectiveness of Atazanavir/ritonavir over lopinavir/ritonavir in human immunodeficiency virus-1 (HIV-1) infection.MethodsClinical trials with a head-to-head comparison of atazanavir/ritonavir and lopinavir/ritonavir in HIV-1 were included. Electronic databases: PubMed/Medline CENTRAL, Embase, Scopus, and Web of Science were searched. Viral suppression below 50 copies/ml at the longest follow-up period was the primary outcome measure. Grade 2–4 treatment-related adverse drug events, lipid profile changes and grade 3–4 bilirubin elevations were used as secondary outcome measures.ResultsA total of nine articles from seven trials with 1938 HIV-1 patients were included in the current study. Atazanavir/ritonavir has 13% lower overall risk of failure to suppress the virus level < 50 copies/ml than lopinavir/ritonavir in fixed effect model (pooled RR: 0.87; CI: 0.78, 0.96; P=0.006). The overall risk of hyperbilirubinemia is very high for atazanavir/ritonavir than lopinavir/ritonavir in the random effects model (pooled RR: 45.03; CI: 16.03, 126.47; P< 0.0001).ConclusionAtazanavir/ritonavir has a better viral suppression at lower risk of lipid abnormality than lopinavir/ritonavir. The risk and development of hyperbilirubinemia from atazanavir-based regimens should be taken into consideration both at the time of prescribing and patient follow-up.     

Molecular-cytogenetic analysis of HER-2/neu gene in BRCA1-associated breast cancers

The BRCA1 tumor suppressor gene and the HER-2/neu oncogene are located in close proximity on the long arm of chromosome 17 (17q11-21). Absence of BRCA1 or functional overexpression of the HER-2/neu gene presumably contributes to the somatic phenotype of breast cancer in premenopausal women, characterized by unfavorable prognostic features such as high tumor grade, hormone receptor negativity, and high proliferation rate. To examine whether amplification of HER-2/neu contributes to the aggressive biology of BRCA1-associated tumors, we have performed fluorescence in situ hybridization on formalin-fixed paraffin-embedded breast tumor tissue sections from 53 BRCA1 mutation carriers and 41 randomly selected, age-matched sporadic breast cancer cases. Although BRCA1-associated and sporadic tumors were equally likely (19% versus 22%) to exhibit HER-2/neu amplification [defined as a ratio of HER-2/neu copies to chromosome 17 centromere (CEP17) copies > or = 2], 6 (15%) of the sporadic tumors were highly amplified (defined as a ratio greater-than-or-equal 5) versus none of the BRCA1-associated tumors (P = 0.048). HER-2 protein overexpression as measured by immunohistochemical analysis was not observed among the BRCA1-associated cases (P = 0.042). Four of 21 (19%) sporadic tumors exhibited strong membranous staining of HER-2 (intensity level of 3+) as compared with 0 of 39 BRCA1-associated tumors. Our data suggest that a germ-line mutation in the BRCA1 tumor suppressor gene is associated with a significantly lower level of HER-2/neu amplification. Thus, it is possible that BRCA1-associated and HER-2/neu-highly amplified tumors progress through distinct molecular pathways, and the aggressive pathological features of BRCA1-associated tumors appear unrelated to amplification of the adjacent HER-2/neu oncogene.     

Reduced activation of phosphatidylinositol-3 kinase and increased serine 636 phosphorylation of insulin receptor substrate-1 in primary culture of skeletal muscle cells from patients with type 2 diabetes

To understand better the defects in the proximal steps of insulin signaling during type 2 diabetes, we used differentiated human skeletal muscle cells in primary culture. When compared with cells from control subjects, myotubes established from patients with type 2 diabetes presented the same defects as those previously evidenced in vivo in muscle biopsies, including defective stimulation of phosphatidylinositol (PI) 3-kinase activity, decreased association of PI 3-kinase with insulin receptor substrate (IRS)-1 and reduced IRS-1 tyrosine phosphorylation during insulin stimulation. In contrast to IRS-1, the signaling through IRS-2 was not altered. Investigating the causes of the reduced tyrosine phosphorylation of IRS-1, we found a more than twofold increase in the basal phosphorylation of IRS-1 on serine 636 in myotubes from patients with diabetes. Concomitantly, there was a higher basal mitogen-activated protein kinase (MAPK) activity in these cells, and inhibition of the MAPKs with PD98059 strongly reduced the level of serine 636 phosphorylation. These results suggest that IRS-1 phosphorylation on serine 636 might be involved in the reduced phosphorylation of IRS-1 on tyrosine and in the subsequent alteration of insulin-induced PI 3-kinase activation. Moreover, increased MAPK activity seems to play a role in the phosphorylation of IRS-1 on serine residue in human muscle cells.     

Anaerobic infections. The basics for primary care physicians

Anaerobic bacteria constitute a major portion of the normal human microflora, and some of them can cause disease in contiguous body parts, especially if there is a mucosal break. Most anaerobic infections are polymicrobial. Because anaerobes are difficult to culture, diagnosis is often made on the basis of clinical clues. Thus, knowledge of the common sites, predisposing conditions, and other representative features of anaerobic infections is critical. For anaerobic infections above the diaphragm, where Bacteroides fragilis is not a common isolate, high-dose penicillin G therapy is usually sufficient. Addition of clindamycin (Cleocin) or metronidazole (Flagyl, Metryl, Protostat) may be necessary for serious infections. Cefoxitin sodium (Mefoxin) or clindamycin is adequate for most anaerobic infections occurring outside the central nervous system. Metronidazole, chloramphenicol, imipenem, or beta-lactam antibiotics combined with beta-lactamase inhibitors may be preferable for serious infections. Appropriate coverage for aerobic bacteria must be included in the treatment regimen. Drainage of abscesses, decompression of infected spaces, debridement of necrotic tissue, and removal of foreign bodies are critical in management of many anaerobic infections.     

Genetic Characterization of Foot-and-Mouth Disease Viruses, Ethiopia, 1981�C2007

Foot-and-mouth disease (FMD) is endemic to sub-Saharan Africa. To further understand its complex epidemiology, which involves multiple virus serotypes and host species, we characterized the viruses recovered from FMD outbreaks in Ethiopia during 1981–2007. We detected 5 of the 7 FMDV serotypes (O, A, C, Southern African Territories [SAT] 1, and SAT 2). Serotype O predominated, followed by serotype A; type C was not recognized after 1983. Phylogenetic analysis of virus protein 1 sequences indicated emergence of a new topotype within serotype O, East Africa 4. In 2007, serotype SAT 1 was detected in Ethiopia and formed a new distinct topotype (IX), and serotype SAT 2 reappeared after an apparent gap of 16 years. The diversity of viruses highlights the role of this region as a reservoir for FMD virus, and their continuing emergence in Ethiopia will greatly affect spread and consequent control strategy of the disease on this continent.     

Smoking, HIV and non-fatal tuberculosis in an urban African population.

Most previous studies on smoking and tuberculosis (TB) have not considered the role of human immunodeficiency virus (HIV) infection, and very few have been conducted in sub-Saharan Africa. We conducted a case-control study on smoking and TB in Addis Ababa, Ethiopia. Men aged 18-65 years with TB (n = 72) were compared to men with no history of TB (n = 81). Forty-three per cent of cases smoked vs. 25% of controls (OR 2.3, adjusted for age, education and self-reported HIV status). Given that HIV appears to increase TB transmission in Africa, our finding that smoking also increases the risk of TB in Africa is of special concern.     

Efficacy of mebendazole and albendazole for Ascaris lumbricoides and hookworm infections in an area with long time exposure for antihelminthes, Northwest Ethiopia

OBJECTIVE: The efficacy of mebendazole and albendazole in the treatment of Ascaris lumbricoides and hookworm infections was evaluated in school children in an area with long time exposure for broad spectrum anthelminthic drugs. RESULTS: Mebendazole exhibited cure rates of 90.6% and 83.5%; egg reduction rates of 96.7% and 94.2% against Ascaris lumbricoides and hookworm infections respectively. Albendazole showed a cure rate of 83.9% and egg reduction rate of 96.3% against Ascaris lumbricoides and a cure rate of 84.2% and egg reduction rate of 95% against hookworm infection. Albendazole appeared to be more effective against hookworm infection (egg reduction rate of 95% versus 94.2%, p = 0.04). CONCLUSIONS: Mebendazole and albendazole showed reduced efficacy against Ascaris lumbricoides and hookworm infections at the recommended doses. This may be a sign for emergence of drug resistance in this region. Care in routine use of the anthelminthes and continuous drug efficacy surveillance is recommended.     

Cost of hospitalization of diabetic patients admitted at Tikur Anbessa Specialized Hospital, Addis Ababa, Ethiopia

OBJECTIVE: In Ethiopia the problems passed by diabetes is increasing for the last two to three decades. This indicates that diabetes is becoming a major economic factor in drug use and bed occupancy. So far there has been no study conducted to evaluate the cost of care among Ethiopian diabetic patients. This study aimed at assessing the cost of hospitalization of diabetic patients. METHODS: A case control study was conducted on consecutive 146 diabetic patients and 142 non diabetic controls admitted to the medical wards of Tikur Anbessa Specialized Hospital. Every first non-diabetic patient who was admitted to the same ward on the same day or in the subsequent days was taken as a control group. RESULTS: The average total cost of hospitalization of cases was significantly higher than the controls with mean cost of 1109.7 +/- 1026.4 for cases and 872.9 +/- 828.3 Birr for controls respectively, (p < 0.03). A large proportion (57%) of the total cost was utilized for treatment of acute and chronic complications of diabetes. The average treatment and laboratory cost were significantly higher among cases compared to controls (p = 0.013 and p = < 0.001 respectively). However, when adjusted by age, sex, address and history of hypertension and renal diseases, the average cost of laboratory investigation remained significantly higher for cases. CONCLUSION: The current study demonstrated that the direct cost of hospitalization of diabetic patient is significantly higher than non diabetics. The study showed that substantial proportion of the total cost of admission is utilized for treating acute and long term complications. This study warrants further research, attention of the health policy makers and health providers for future planning of prevention, diagnosis and treatment of diabetes.