Plasma levels of transforming growth factor -B[1], connective tissue growth factor; soluble factor related apoptosis and urinary levels of desmosine in childhood interstitial lung diseases

This study aimed to evaluate fibrosis and elastin destruction in childhood interstitial lung disease [chILD] patients and to correlate findings with clinical characteristics. Fifty-six patients and apparently healthy twenty children were recruited in this study. Participants were subjected to thorough history taking and clinical examination. All participants provided midstream urine and venus blood samples. Plasma levels of transforming growth factor [TGF]-/ll, connective tissue growth factor [CCN2] and soluble factor related apoptosis [sFas] and urinary desmosome /urinary creatinine [UDes/UCr] were measured by ELISA kits. In patients, clinical findings were crepitation [1.00 %], tachypnea [67. 90%], cardiomegaly [46.40%], digital clubbing [44.60%], cough [33.90%], cyanosis [28.60%], hepatomegaly [28.60%] and wheezes [23.30%]. Fan chILD clinical score was mostly score 3 [n= 20, 35.70%] then score 5 [n= 16, 28.60%], score 2 [n = 9, 16.10%], score 1 [n =8, 14.30% and score [4] [n=3, 5.40%]. TGF-PI, CCN2, sFas and UDes/UCr levels were significantly higher in patients than controls [P =0.0001]. In patients, significant positive correlations were found between TGF-PI and CCN2, sFas and UDes/UCr; between CCN2 and both sFas and UDes/UCr; between UDes/UCr and both sFas and mortality rate. Morbidity and mortality rates were 48.20% and 10.70%.Conclusions: Markers of fibrosis [TGF-B sFas, CCN2] and elastin destruction [UDes/UCr] were increased in chILD. So blockage of their pathways signals may offer novel therapeutic targets

Effects of tramadol versus indomethacin on gastric mucosa in rat model of nociception: a structural, immunohistochemical and hormonal study

Background: Tramadol is centrally acting analgesic that is frequently used clinically but its mechanism of action is still unclear

Aim of work: To evaluate tramadol analgesic activity, and its effect on gastric mucosa and hormones

Material and Methods: Thirty two adult male albino rats were used. Rats were divided into three groups: group [I] was injected with 3 doses of physiological saline [2ml kg[-1] every 12 h, i.p.], served as control; group [II] was injected with 3 doses of indomethacin [10 mg kg[-1] every 12 h, i.p.]; and group [III] was injected with 3 doses of tramadol [10 m kg[-1] every 12 h, i.p.]. 30 min after the first dose of injections, all groups were given 10 ml k[-1] of 1% acetic acid-saline i.p. to induce writhing. After 10 min following acetic acid injection, writhes numbers were counted over 20 min. Gastric mucosa was examined macroscopically and microscopically. Gastrin expression was detected by immunohistochemistry. Serum prostaglandin [PG], E2, ghrelin, and histamine concentrations were measured using ELISA kits

Results: Tramadol has lower analgesic effect compared to indomethacin. The gastric ulcer index was significantly lower in tramadol- versus indomethacin-treated group [P <0.0001]. Immunohistochemistry demonstrated higher gastrin immunoreactivity in indomethacin- and tramadol-treated groups versus control. Ghrelin serum levels were significantly suppressed by tramadol and indomethacin versus control that were coincident with gastric mucosal lesions. No significant changes in serum levels of PGE2 and histamine were obtained

Conclusion: Our results suggested that tramadol-induced gastric lesions are probably mediated by reduction of ghrelin and increase in gastrin expression. The antinociceptive and gastric effects of tramadol suggest that tramadol is relatively safe clinically in pain therapy

Role of RANKL/OPG and L-carnitine systems in osteopenia/osteoporosis in children with B-thalassemia major

Bone disease in beta TM in the form of low bone mass remains a frequent, debilitating and poorly understood problem, even among well transfused and chelated patients. Receptor activator of nuclear factor kB ligand [RANKL] is a regulator of osteoclast formation and function, the activity of which appears to be a balance between interaction with its receptor and with antagonist binding protein osteoprotegerin [OPG]. L-carnitine enhanced osteoblasric activity as well. The objective is to define the role of RANKUOPG and L-carnitine systems-related bone loss in attempt for better management of osteopenialosteoporosis in beta TM children. The study included 69 I3TM children [45 males and 24 females, mean age 8.72 +/- 3. 70 ys and weight 22.84 +/- 7.04kg] attended the Children University Hospital [January-September 2008]. The patients were subdivided into 2 groups; one [n=34] received iron chelating [DFO] and the other group [n=35] did not receive any chelating drug. Fifteen healthy matched age, sex and BMI were included as controls. Serum OPG, sRANKL, L-carnitine, calcium, inorganic phosphorus and free fatty acids were measured by ELIZA and spectrophotometer. BMD, BMC and Z-score were measured by DEXA in 25 patients. There was a significantly lower serum level of OPG, L-carnitine and significantly higher sRANKL, sRANKL/OPG ratio, FFAs in patients than controls and in patients receiving DFO than those not receiving chelation. DEXA bone scanning detected osteopenia/osteoporosis in 12%and 88%of patients [mean Z score-3.38 +/- 1.19] with significantly higher osteoporosis in patients receiving DFO; more obvious in pelvis, L-spine, and femoral neck. L-carnitine correlated negatively with sRANKL, and positively with OPG. sRANKL correlated negatively with OPG. Z-score correlated negatively with age and positively with OPG. In conclusion, Reduced osteoblas tic activity and enhancing osteoclastic resorption are the basic mechanisms of bone loss in beta TM through decrease in L-carnitine and disturbed RANKL/OPG pathway. Recombinant OPG, L-carnitine and anti-RANKL supplement may be future agents that help in management of beta TM osteopenia/osteoporosis. Chelation with DFO seems to affect the bone density in such patients

Trace elements and flapping tremors in patients with liver cirrhosis. Is there a relationship?

To investigate the possible correlation between hepatic flapping tremors and serum manganese Mn, iron Fe, zinc Zn, and copper Cu. This case control study was carried out in Assiut University Hospital, Assiut, Egypt from June 2006 to June 2007. It included 100 patients with liver cirrhosis, 78 had flapping tremor, and 22 had not, and 60 healthy controls. All patients were subjected to assessment of serum Mn, total Fe, total iron binding capacity TIBC, Zn, and Cu. Assessment of hepatic encephalopathy was carried out using a battery of cognitive function tests. All patients had electroencephalography and MRI of the brain.Compared to healthy controls, patients showed increase in Mn p<0.0001, Cu p<0.05 and decrease in TIBC p<0.000, Zn p<0.05. Eighty-two percent of patients had minimal hepatic encephalopathy mHE. In 85%, MRI-brain showed bilateral hyperintense substantia nigra and globus pallidus on T1-weighted images. A significant positive correlation was present between tremors and severity of liver dysfunction, mHE and serum Cu, and negative correlation with total Fe, TIBC, and Zn. Altered homeostasis of Mn and other minerals could be responsible for the pathophysiology of cognitive deficits associated with liver cirrhosis, but not with flapping tremors. The exact pathogenic role and possibilities for therapeutic implications need further study

Dyslipidemia, oxidative stress and cardiac dysfunction in children with chronic renal failure: effects of l-carnitine supplementation

Secondary carnitine deficiency may develop in chronic renal failure [CRF] patients undergoing long-term hemodialysis [HD], with a resulting higher incidence of cardiovascular diseases, dyslipidemia and oxidative stress. We studied the efficacy of 12 months of L-carnitine supplementation on the amelioration of dyslipidemia, oxidative stress and cardiac dysfunction in 24 CRF children undergoing long-term HD compared with 24 age- and sex-matched controls. Plasma samples were analyzed spectrophotometerically before and after dialysis sessions and after 2-month supplementation with oral L-carnitine [50 mg/kg/day] for free carnitine [FC], the lipid profile, and oxidative stress markers. Echocardiography the day following dialysis measured cardiac diameters, wall thicknesses, left ventricular mass index [MI], end diastole and systole volume indices and functions. The pre-dialysis FC concentration was substantially lower than controls and decreased significantly at the end of the dialysis session. Pre- and post-dialysis plasma levels of free fatty acids [FFAs], trigyleride [TG], total cholesterol [TC] and oxidative stress markers significantly increased while high-density lipoprotein cholesterol [HDL-C] and phospholipids significantly decreased compared to controls. Echocardiography detected a significant increase in cardiac diameters and thickness, and systolic and diastolic cardiac dysfunction. After L-carnitine supplementation, plasma levels of FC increased to normal levels. FFAs, TC and HDL-C returned to control levels while TG, phospholipids, and the oxidative stress markers decreased but remained significantly higher than controls. There was a significant decrease in cardiac diameters and an increase in left ventricular diastolic function [E/A ratio], but no correlation between FC levels and echocardiographic parameters. Pre-dialysis, post-dialysis and after treatment, plasma FC level showed a significant positive correlation with HDL-C and phospholipids and a significant negative correlation with each of oxidative stress markers, FFAs, TG and TC. On the other hand, FFAs showed a significant positive correlation with TG, TC, DC, NO and a significant negative correlation with HDL-C and phospholipids. This study demonstrates that CRF children under regular HD suffer from a decrease in the level of plasma FC, dyslipidemia, oxidative stress, and an increase in cardiac diameters and thickness with impairment of cardiac functions. Oral L-carnitine supplementation at a dose of 50 mg/kg for 2 months can increase plasma FC level, improve dyslipidemia, decrease oxidative stress with reduction of cardiac diameters and increase in diastolic function

effects of passive cigarette smoking on the respiratory system among the healthy wives of active smokers

This study included 50 adult healthy volunteers; 20 currently smokers, 20 wives of active smokers spouse [passive smokers] and the remaining 10 subjects were nonsmokers controls. Ventilatory pulmonary function tests [FVC% predicted, FEV1/FVC ratio, FEV1% predicted and FEF25-7.5% predicted] were made to all subjects. Urinary cotinine, serum cotinine and lipid peroxides levels were assessed using spectrophotometric method. Data demonstrated that passive smokers are at risk to develop subsequent destructive lung disease, which was evident by an increase in the level of lipid peroxides [marker of oxidative stress] and a decline in the spirometric indices [especially a decline in FEV1% predictive which is the most strongly predictive index of chronic obstructive lung diseases in adults]. The decline in FEF25-75% predictive indicated the possibility of small airway diseases. The benefit of the use of urinary and serum cotinine as cheap biomarkers of exposure to cigarette smoke was clarified