Biochemical characterization of a novel extended-spectrum beta-lactamase from Pseudomonas aeruginosa 802

Pseudomonas aeruginosa 802 was isolated at Rabta hospital in Tunis and was resistant to extended-spectrum cephalosporins and aztreonam. It produced a pI 7.6 extended-spectrum beta-lactamase (ESBL). The ESBL, named LBT 802, was purified to homogeneity by filtration on Sephadex G-75 followed by CM-Sepharose chromatography and high-performance liquid chromatography (HPLC) on a TSK-gel SP-5PW column. The LBT 802 enzyme had a molecular mass of 30 kDa. It showed a broad-substrate profile by hydrolyzing benzylpenicillin, ampicillin, cephalothin, cephaloridine, cefotaxime, ceftriaxone, and cefpirome but not ceftazidime, cefoxitin, imipenem, or aztreonam. The highest hydrolytic efficiency (Vmax/Km) was obtained for ampicillin, cephalothin, cephaloridine, and benzylpenicillin. Among extended-spectrum cephalosporins the best substrate was ceftriaxone followed by cefotaxime and cefpirome. LBT 802 activity was inhibited by clavulanic acid, sulbactam, imipenem, cefoxitin, and aztreonam. It showed its lowest Ki values for clavulanic acid, imipenem and sulbactam.     

Streptococcus pneumoniae purulent pleurisy and hemolytic uremic syndrome. A case report

A 22-month-old infant developed purulent pleurisy caused by Streptococcus pneumoniae and a hemolytic uremic syndrome. The diagnosis was suggested by the classical triad: hemolytic anemia, renal failure and thrombocytemia confirmed by renal biopsy which demonstrated extensive cortical necrosis. Renal involvement was severe, justifying an indication for renal transplantation.     

High-fat diet induced an oxidative stress in white adipose tissue and disturbed plasma transition metals in rat: prevention by grape seed and skin extract

Obesity is a public health problem characterized by increased accumulation of fat into adipose tissues leading to oxidative stress, dyslipidemia, and chronic inflammatory status. We used an experimental model of high-fat diet-induced obesity to analyze the link between dyslipidemia, oxidative stress, and fat accumulation into adipose tissue of rats, as well as the involvement of intracellular mediators such as transition metals on signal transduction. We also looked at the ability of a grape seed and skin extract (GSSE) from a Tunisian cultivar to prevent fat-induced disturbances. Data showed that a high-fat diet (HFD) provoked dyslipidemia into plasma which is linked to an oxidative stress, an accumulation of transition metals such as manganese, copper, and zinc and a depletion of iron. GSSE prevented dyslipidemia by modulating lipase activity, together with increased antioxidant capacity and depletion of transition metals as well as of free radicals such as O₂ ^? and OH. These data indicated that GSSE has important preventive effects on HFD-induced obesity and oxidative stress whose transduction seems to involve transition metals. GSSE should be used as a safe anti-obesity agent that could find potential applications in metabolic disorders involving transition metals dyshomeostasis.     

Tracking of cardiovascular risk factors among school children: a four-year population surveillance in Susa, Tunisia

In order to confirm the phenomenon of tracking of cardiovascular risk factors among school children, we undertook in 2003, a prospective survey of a population of 789 pupils aged 13 to 15 years who had participated in a first investigation on cardiovascular risk factors in 1999. We were able to follow and study 453 pupils (57.4% of the initial population). Prevalences of hypertension and obesity were respectively 11.3% and 6.1% without significant difference between sexes. On the other hand, hypercholesterolemia was significantly more elevated among girls than boys (16.1% versus 9.3%, p = 0.039). Children classified initially as hypertensive, obese or having a hypercholesterolemia were identified 4 years later at a subsequent exam as hypertensive, obese or having a hypercholesterolemia in respectively 25%, 48.9% and 59%. The stability of cardiovascular risk factors among children imposes an early screening for a better management and a policy of cardiovascular health promotion since childhood based essentially on prevention of risk factors in order to reduce the cardiovascular disease burden in adulthood.     

Engrafted bone marrow-derived flk-(1+) mesenchymal stem cells regenerate skin tissue

Stem cell plasticity has created great interest because of its potential therapeutic application in degenerative or inherited diseases. Transplantation of bone marrow-derived stem cells was shown to give rise to cells of muscle, liver, nerve, endothelium, epithelium, and so on. But there are still disputes about stem cell plasticity, especially concerning the contribution of bone marrow-derived cells to skin cells. In this study, CM-DiI fluorescence-labeled Flk-(1+) bone marrow mesenchymal stem cells (bMSCs) of BALB/c mice (H-2Kd, white) were transplanted into lethally irradiated C57BL/6 mice (H-2Kb, black). By fluorescence tracing, we found that donor cells could migrate and take residency at the skin, which was confirmed by Y chromosome-specific PCR and Southern blot. The recipient mice grew white hairs about 40 days later and white hairs could spread over the body. Immunochemistry staining and RT-PCR demonstrated that skin tissue within the white hair regions was largely composed of donor-derived H-2Kd cells, including stem cells and committed cells. Furthermore, most skin cells cultured from white hair skin originated from the donor. Thus, our findings provide direct evidence that bone marrow-derived cells can give rise to functional skin cells and regenerate skin tissue. These may have important scientific implications in stem cell biology and transplantation therapy for skin tissue injury.     

Incidence, clinical features and subtypes of delirium in elderly patients treated for hip fractures

OBJECTIVE: To describe the incidence, risk factors and clinical features (subtypes) of delirium during the postoperative period after hip fracture surgery in elderly patients. DESIGN: Prospective study. METHODS: Thirty-four consecutive patients (9 men and 25 women) were included in this study between June 16 to July 14, 2003. All patients underwent surgery for a fractured neck of femur and were pre- and postoperatively cared for at a combined geriatric/orthopedic ward. ASSESSMENT: The diagnosis of delirium was based on the criteria of the DSM-IV and the Confusion Assessment Method Scale. Subtypes of delirium were classified according to the criteria proposed by Lipowski: hyperactive-hyperalert (or agitated), hypoactive-hypoalert (somnolent) and mixed delirium. Results: Fifty-five percent (n = 19) of the 34 patients developed delirium after surgery. The development of delirium was associated with the medication midazolam taken perioperatively. Nine (47%) of the delirious patients had a hyperactive type of delirium; 5 (26%) developed a hypoactive delirium, and 5 (26%) had a mixed type. We did not find any association among subtypes of delirium and clinical features. CONCLUSIONS: Delirium is a common complication in the postoperative period of elderly patients treated for hip fractures. The use of midazolam in the perioperative period increased the risk of developing postoperative delirium. The hyperactive type of delirium was the most common subtype of delirium.     

Helminth regulation of host IL-4Ralpha/Stat6 signaling: mechanism underlying NOS-2 inhibition by Trichinella spiralis

Gastrointestinal nematode infection is known to alter host T cell activation and has been used to study immune and inflammatory reactions in which nitric oxide (NO) is a versatile player. We previously demonstrated that Trichinella spiralis infection inhibits host inducible NO synthase (NOS-2) expression. We now demonstrate that (i) an IL-4 receptor alpha-subunit (IL-4Ralpha)/Stat6-dependent but T cell-independent pathway is the key for the nematode-induced host NOS-2 inhibition; (ii) endogenous IL-4 and IL-13, the only known IL-4Ralpha ligands, are not required for activating the pathway; and (iii) treatment of RAW264.7 cells with parasite-cultured medium inhibits NOS-2 expression but not cyclooxygenase 2 expression. We propose that a yet-unidentified substance is released by the nematode during the host-parasite interaction.     

Epidemiology of cardiovascular risk factors among schoolchildren in Sousse, Tunisia

BACKGROUND: In Tunisia, where the epidemiological transition phenomenon is well established, there are no data available at the population level on the cardiovascular disease (CVD) risk profile for children, although it is well known that risk factor development takes place in childhood. METHODS: We report an epidemiological survey based on a representative sample of 1569 urban schoolchildren of Sousse in Tunisia to assess the following CVD risk factors: hypertension, hypercholesterolaemia and other lipid disorders, obesity and tobacco consumption. RESULTS: The main results showed that girls had significantly higher levels of body mass index (BMI), diastolic blood pressure (DBP), total cholesterol, low-density lipoprotein (LDL) cholesterol and high-density lipoprotein (HDL) cholesterol than boys, who however had significantly higher levels of systolic blood pressure (SBP). Total cholesterol was significantly correlated to BMI and decreased with age. Obesity (BMI = 27) was found in 7.9% of the study population and was significantly higher for girls (9.7%) than for boys (6%): chi 2 = 9.02, DF = 2, P = 0.011. Overweight (BMI = 25) was also significantly higher for girls (16%) than for boys (11.1%): chi 2 = 8.21, DF = 1, P = 0.0041. Smoking habit concerned 7.6% of the study population; it was significantly higher for boys (14.7%) than for girls (1.1%): chi 2 = 103.4, DF = 1, P < 0.00001. CONCLUSION: This study showed to some extent that Tunisia's urban population of schoolchildren is exposed early to CVD risk factors and all should be done to avoid the worsening of this profile. These results will serve as a baseline for assessment of future trends in the risk factors studied.