Peculiarities of vasomotor reaction of cerebral vessels in arterial hypertension

We studied vasomotor activity of rat cerebral vessels. Peculiarities of endothelium-dependent reactions of cerebral arteries in induced arterial hypertension were revealed. Quantitative and qualitative relationships between the parameters of the vasomotor apparatus of cerebral arteries and parameters of circulatory homeostasis were determined. __________ Translated from Byulleten’ Eksperimental’noi Biologii i Meditsiny, Vol. 144, No. 7, pp. 36–38, July, 2007     

Reversal of HIV-1-associated osteoporosis with once-weekly alendronate

HIV-1-infected patients with osteoporosis were randomly assigned to alendronate 70 mg once-weekly plus dietary counselling (n = 11) or diet counselling alone (n = 14). At week 96, 27% of patients on alendronate versus 96% of controls presented with osteoporosis. Spine bone mineral density (BMD) increases were detected at week 48, and progressed thereafter. Improvements in trochanter BMD were obtained after 2 years. Once-weekly oral alendronate may be an effective and safe treatment for HIV-1-associated osteoporosis.     

Tumour CD133 mRNA expression and clinical outcome in surgically resected colorectal cancer patients

BackgroundHuman prominin-1 (CD133) is a novel pentaspan membrane protein which was originally classified as a marker of primitive haematopoietic and neural stem cells. Cancer stem cells have been isolated and expanded from leukaemia and several solid tumours, and have been associated with metastasis, chemoresistance and relapse. CD133 is recognised as a stem cell marker and is capable of identifying a tumour-initiating subpopulation in brain, colon, melanoma and other solid tumours.MethodsWe assessed CD133 mRNA expression levels by RT-QPCR in tumour and matched normal tissue from 64 stages I–III colorectal cancer (CRC) patients and correlated tumour CD133 levels with clinicopathological characteristics and clinical outcome.ResultsIn four patients, CD133 mRNA was not expressed in tumour or in normal tissue. In the remaining 60 patients, expression levels were higher in tumour than in normal tissue (p = 0.001). Higher levels of CD133 expression were associated with shorter relapse-free interval (RFI) (p = 0.004) and overall survival (OS) (p < 0.0001). In the multivariate analyses, CD133 levels emerged as a prognostic marker for RFI and OS.ConclusionsWe have observed longer RFI and OS in patients with lower levels of CD133, regardless of adjuvant treatment and other clinical characteristics. If these findings are confirmed in larger prospective studies, CD133 assessment may prove useful for new diagnostic and therapeutic procedures for CRC patients.     

Transplantation of SNAP-treated adipose tissue-derived stem cells improves cardiac function and induces neovascularization after myocardium infarct in rats

Stem cell therapy has been considered a promise for damaged myocardial tissue. We have previously shown that S-nitroso-N-acetyl-D,L-penicillamine (SNAP) increases the expression of several muscular markers and VEGF in mesenchymal stem cells, indicating that transplantation of SNAP-treated cells could provide better functional outcomes. Here, we transplanted SNAP-treated adipose tissue-derived stem cells (ADSCs) in rat infarcted myocardium. After 30 days, we observed a significant improvement of the ejection fraction in rats that received SNAP-treated ADSCs, compared with those that received untreated cells (p = 0.008). Immunohistochemical reactions showed an increased expression of troponin T–C and von Willebrand factor, and organized vascular units in the infarcted area of tissue transplanted with treated ADSCs. SNAP exposure induced intracellular S-nitrosation, a decreased GSH/GSSG ratio, but did not increase cGMP levels. Collectively, these results indicate that SNAP alters the redox environment of ADSCs, possibly associated with a pre-differentiation state, which may improve cardiac function after transplantation.     

Lipid-lowering drugs in the MPTP mouse model of Parkinson's disease: fenofibrate has a neuroprotective effect, whereas bezafibrate and HMG-CoA reductase inhibitors do not

We tested the ability of simvastatin, atorvastatin, fenofibrate and bezafibrate (two synthetic peroxisome proliferator-activated receptor-alpha (PPAR-alpha) agonists) to prevent dopaminergic cell death in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) mouse model of Parkinson's disease. Tyrosine hydroxylase (TH) immunochemistry was performed 8 days after acute MPTP intoxication. When orally administered for the week prior to intoxication and a week thereafter, fenofibrate prevented the MPTP-induced dopaminergic cell loss in the substantia nigra pars compacta (SNpc) and attenuated the loss of tyrosine hydroxylase immunoreactivity in the striatum. The dosage of 1-methyl-4-phenyl pyridinium (MPP+) in the striatum by high-performance liquid chromatography indicated that fenofibrate did not affect MPTP metabolism. Bezafibrate had no effect and, strikingly, simvastatin and atorvastatin had a negative effect. We also demonstrated the presence of PPAR-alpha in the dopaminergic neurons of the murine substantia nigra. Our data suggest that PPAR-alpha activation by fenofibrate could have a neuroprotective effect in PD through inhibition of inflammation, oxidative stress and/or apoptosis.     

The PPARalpha activator fenofibrate slows down the progression of the left ventricular dysfunction in porcine tachycardia-induced cardiomyopathy

It has been reported that high intramyocardial peroxisome proliferator-activated receptor alpha (PPARalpha) stimulation or overexpression altered cardiac contractile function in mouse models of cardiac hypertrophy and heart failure. Nevertheless, it has never been demonstrated that clinically relevant doses of drugs stimulating PPARalpha activity such as fenofibrate increase the risk to develop heart failure in humans. To determine if fenofibrate accelerates the development of heart failure in large mammals, we have tested its effects on the progression of left ventricular dysfunction in pacing-induced heart failure in pigs. Fenofibrate treatment blunted reduction in left ventricular ejection fraction, reduced cardiac hypertrophy, and attenuated clinical signs of heart failure. Fenofibrate impeded the increase in atrial natriuretic peptide, brain natriuretic peptide, and endothelin-1 plasma levels. The expression of PPARalpha, fatty acyl-CoA-oxidase, and carnitine palmitoyltransferase-Ibeta was reduced at mRNA levels in the left ventricle from untreated heart failure pigs but maintained near normal values with fenofibrate. Fenofibrate prevented heart failure-induced overexpression of TNFalpha mRNA and enhanced catalase activity in left ventricle compared to placebo. These data suggest that a clinically relevant dose of fenofibrate does not accelerate but slows down heart failure development in the model of pacing-induced heart failure in large mammals.     

Pridominant isolates of urinary tract pathogens and their antimicrobial susceptiblity patterns in Gondar University Teaching Hospital, nothwest Ethiopia

BACKGROUND: Urinary tract infection (UTI) is one of the most common bacterial infections encountered by clinicians in developing countries. Although UTI seldom leads to complications, it can cause significant morbidity and mortality. OBJECTIVE: To identify the etiologic agents of UTIs and to assess their antimicrobial susceptibility pattern. METHODS: A retrospective analysis of 1420 mid-stream urine specimens processed fobr culture and antimicrobial susceptibility testing in the bacteriology laboratory of Gondar University Teaching Hospital between September 2002 and August 2003 was conducted RESULTS: Significant bacteriuria (cultures with > 10(5) colony forming units of bacteria per ml of urine) was observed in 399 (28.1%) of the specimens. Two bacteria each were isolated from 14 specimens, making the number of bacteria isolated to be 413 with the isolation rate of 29.1%. The most commonly isolated bacteria were Escherichia coli 166 (40.2%), Staphylococcus aureus 60 (14.5%), Klebisella species 42 (10.2%) and Citrobacter species 34 (8.2%). Among Gram-positive organisms S. aureus showed high level qf drug resistance for tetracycline 48 (80%), corimoxazole 32 (53.3%), chloramphenicol 32 (53.3%), amnpicillin 26 (43.3%) and penicillin 22 (36.7%). Of the Gram-negative bacteria, extremely high resistance patterns were found in Salmonella species for ampicillin 5 (100%), erythromycin 5 (100%), penicillin 5 (100%), co-trimoxazole 3 (60%), tetracycline 3 (60%) and 3 chloramphenicol (60%). Multiple drug resistance was observed in 85.7% of the isolates. Only 5.1% of the isolates were found to be sensitive to all antibiotics tested. CONCLUSION: Resistance to the commonly used antibiotics was found to be very high among the isolates leaving clinicians with very few choices of drugs or the treatment of UTIs. It is therefore, critical that the use of antimicrobial agents with in a hospital and all other responsible institutions he reviewed