Ca2+ leakage rate from agonist-sensitive intracellular pools is altered in platelets from patients with type 2 diabetes

Platelets from patients with type 2 diabetes show abnormalities in intracellular Ca(2+) homeostasis that are involved in platelet hyperaggregability and the development of thrombotic complications. Different Ca(2+) transport mechanisms have been reported to be altered in platelets from patients with type 2 diabetes, including the sarcoendoplasmic and plasma membrane Ca(2+)-ATPases, plasma membrane Ca(2+) channels, or the Na(+)/Ca(2+) exchanger. Here, we have investigated whether passive Ca(2+) leak from the stores is altered in platelets from patients with type 2 diabetes. Resting cytosolic Ca(2+) concentration ([Ca(2+)](i)) was found to be greater in platelets from patients with type 2 diabetes than in healthy controls. In a Ca(2+)-free medium, platelet stimulation with thrombin or ADP evokes a rapid and transient increase in [Ca(2+)](i) that was found to be greater in patients with diabetes than in healthy controls. Sequential or combined inhibition of Ca(2+) extrusion and Ca(2+) sequestration into the stores reduced the difference between the responses to agonists in patients with diabetes and healthy controls, although agonist-induced Ca(2+) efflux from the stores was still significantly greater in patients with diabetes. Ca(2+) leak from the dense tubular system or the acidic stores, induced by a low concentration of thapsigargin or 2,5-di-(t-butyl)-1,4-hydroquinone (TBHQ), respectively, was clearly greater in patients with diabetes than in controls, and was not significantly modified by treatment with 2-APB. These findings indicate that passive Ca(2+) leakage rate from the intracellular stores in platelets is significantly enhanced in patients with type 2 diabetes mellitus and this might explain the increased resting [Ca(2+)](i).     

Epidemiologic profile of Haemophilus influenzae infection in Tunisia

Haemophilus influenzae, a commensal bacteria, is frequently incriminated in broncho--pulmonary surinfections and severe diseases as meningitis, pneumonia and septic arthritis, particularly in young children. A multicenter study was conducted to establish the epidemiological profile of Haemophilus influenzae diseases, to determine the rate of antibiotics resistance for guide therapeutic and preventive strategies. The identification was based on the requirements for X and V factors, and the serotype b determined by agglutination. The betalactamase production was done by nitrocefin test. Antimicrobial susceptibility testing was determined on Muller Hinton chocolate agar with isovitalex. During the two year period, (January 1998 December 1999), 192 isolates of H. Influenzae were collected, 61% were recovered from invasive infections (44 meningitis, 8 bacteremia, 2 arthritis). The serotype b was identified in 55.7% of cases, 67.3% were invasive strains. 24.5% of isolates were producing betalactamase particularly invasive serotype b strains. All isolates of H. influenzae were susceptible to cefotaxim and to ofloxacin. Resistance rates to other antibiotics were: erythromycin 56.2%, tetracyclin 10.3%, rifampin 12%, chloramphénicol 1%, cotrimoxazole 16.5%, 11.5% amikacin and 20% gentamicin. The incidence of meningitis remained frequent in our country, involving the introduction of the vaccination in official calendar. Nevertheless, the surveillance of H. influenzae invasives infections and the serotyping of isolates were necessary to evaluate the impact of the immunization.     

Clinicopathological significance of cancer stem cell markers CD44 and ALDH1 expression in breast cancer

Background

CD44 and aldehyde dehydrogenase 1 (ALDH1) has been reputed to be cancer stem cell (CSC) markers in breast cancer. Yet, the clinicopathologic and prognostic significance of these markers remain unclear. In this study, we have investigated the expression of these markers and their relation with conventional clinicopathologic tumor characteristic including molecular subtype.

Methods

CD44 and ALDH1 expression were investigated by immunohistochemistry in a series of 157 formalin-fixed paraffin-embedded breast cancer tissues.

Results

Overall, CD44 and ALDH1 are, respectively, detected in 33% (52 of 157) and 7% (10 of 157) of breast cancer cases. We also observed that CD44 expression was associated with histological grade (p?=?0.005). For ALDH1, we found that its expression is more frequent with elderly women (>?50 years, p?=?0.03). The investigation of relationship between the stem cell phenotype and breast cancer molecular subtype, revealed that CD44 and ALDH1 expression was more frequent in basal-like tumors (p?=?0.005). Among the two cancer stem cell markers tested, ALDH1 showed a strong association with the basal marker EGFR (p?=?0.05).

Conclusions

These findings suggest that CD44 and ALDH1 play a role in the clinical behavior in breast cancer and might be interesting biomarkers and therapeutic targets.

     

Renal biopsy findings in diabetes mellitus

BACKGROUND: The prevalence of diabetic patients with endstage renal disease is increased overall the word. Renal biopsy is sometimes necessary to precise the type of renal damage. AIM: To precise the type and the frequency of non diabetic nephropathy in diabetic patients. METHODS: We enrolled retrospectively during 17 years, 72 diabetic patients who had a renal biopsy. RESULTS: A non diabetic nephropathy was found in 69.5 % of them. Its presence was correlate to the presence of hematuria and the absence of diabetic retinopathy. We can successfully treated nine patients with minimal-change nephrotic syndrome and one patient with crescentic glomerulonephritis. CONCLUSION: Renal biopsy must be done in diabetic patient with hematuria or in the absence of diabetic retinopathy.     

Total absence of ST-segment resolution after failed thrombolysis is correlated with unfavorable short- and long-term outcomes despite successful rescue angioplasty

Introduction

ST-segment resolution (STR) is a well-established and simple tool for assessing the efficacy of reperfusion therapy in myocardial infarction. An incomplete (<50%) STR is a recognized marker of failed thrombolysis and a suitable recruitment criterion for rescue angioplasty.

Objective

We sought to determine the predictive value of the total absence of STR after thrombolysis in rescue angioplasty (percutaneous coronary intervention [PCI]).

Methods

Eighty-one consecutive patients who underwent a rescue angioplasty for failed thrombolysis in our institution from 2001 to 2007 were included. Two groups of patients were defined according to their STR extent, 90 minutes after lysis: partial resolution group 1 (10%-50% STR) vs absence of resolution group 2 (<10% STR) and compared in terms of in-hospital and long-term outcomes.

Results

Patients of group 2 were more likely to experience hemodynamic deterioration (50% vs 24%; odds ratio [OR] = 3.17; P = .017), to have a Thrombolysis in Myocardial Infarction 0 flow on the culprit artery (62.3% vs 42%; OR = 2.24; P = .045), to have a multivessel disease (66.7% vs 40%; OR = 3; P = .018), and to die during index hospitalization (26.7% vs 6%; OR = 5.69; P = .013) despite statistically similar rates of PCI failure in both groups (10% vs 7%; P = .402) and similar post-PCI STR (72% ± 18.25% vs 75% ± 11.62%; P = .36). In multivariate analysis, total absence of STR proved to be an independent predictor of in-hospital mortality (HR = 7.02; P = .032; 95% confidence interval, 1.18-41.58). Long-term major adverse cardiac events occurred more frequently in group 2 (log rank, P = .004) and were (on the Cox regression model) independently predicted by total absence of STR (HR = 6.21; P = .023; 95% confidence interval, 1.28-29.1).

Conclusions

The STR assessment before rescue PCI proved to be a good and simple means to predict the short- and long-term prognosis in these patients.     

Pharmacology of carbon nanotubes: Toxicokinetics,excretion and tissue accumulation

Carbon nanotubes (CNT) are increasingly being investigated for their use in biomedical applications and nanomedicine. An emergent need for the understanding of their in vivo biodistribution and pharmacokinetics is therefore needed to establish the essential properties and criteria for their further development as targeted CNT delivery systems to specific tissues for diagnostics and therapeutic purposes. Until their biodistribution and toxicoketic profiles are fully understood, their translation into the clinic will be hindered. This review will highlight the important factors affecting the biodistribution and pharmacokinetic profile of CNT and address their toxicokinetics following systemic, pulmonary and dermal exposure.     

Musculoskeletal disorders among Tunisian hospital staff: Prevalence and risk factors

Aim of the workMusculoskeletal disorders (MSD) represent a significant occupational problem among hospital staff; however, data on musculoskeletal health of hospital staff are sparse. This study sought to determine the prevalence of MSD, their epidemiologic data and the associated risk factors.MethodsA previously self administered questionnaire sought information on demographics, prevalence and pattern of MSD, associated risk factors was employed as the survey instrument. A total of 520 questionnaires were distributed to hospital staff but only 433 questionnaires was valid. Eighty-seven of the returned questionnaires were excluded because of incomplete data.ResultsThe prevalence of MSD among hospital staff was 65.4%. Musculoskeletal disorders occurred mostly in low back (74.5%), neck (38.1%), and knees (31.1%).Factors associated to MSD were age (P < 0.001), female gender (P < 0.001), years of service (P < 0.001) as well as prolonged standing or sitting (P = 0.016 and 0.023, respectively). No significant association was found between repetitive movement, uncomfortable postures, heavy load handling, working on night shifts, stress and the presence of MSD.ConclusionA high proportion of hospital staff reported MSD at some body site with the low back being injured most often. Education programs on prevention and coping strategies for musculoskeletal disorders are recommended for hospital staff in order to reduce the rate of occupational hazards and also promote efficiency in patient care.