Mitigation of acute lipopolysaccharide-induced renal injury by hydrogen sulfide in adult male rats

Sepsis is one of the leading causes of acute kidney injury [AKI] and increases risk of death. Bused on the hemodynamic effects and anti-inflammatory properties of the hydrogen sulfide [H[2]S], this study aimed to examine its effects on renal damage using a rat model of lipopolysaccharide [LPS]-induced AKI where LPS promotes inflammation-mediated kidney damage. A total of forty adult male Wistar albino rats were included in the study. The rats were randomly divided into 4 groups: [I] control group was treated with saline. [2] H[2]S group received a single intravenous [i.v.] bolus of sodium hydrosulfide [NaHS] as H[2]S donor in ci dose of 0.2 mg/kg. [3] LPS group in which endoloxemic shock was induced through the intraperitoneal [i.p.] injection of 20 mg/kg LPS. [4] LPS H[2]S group received LPS with the same dose as the previous group, then 5 minutes later NaHS, in a single dose [0.2 mg/kg] was injected. Administration of NaHS as H[2]S donor in LPS + H[2]S group significantly abrogated kidney inflammation as evident by significant decrease of renal intercellular adhesion molecule- 1 [ICAM- 1], myeloperoxidase [MPO] and attenuated kidney cellular damage as observed by the increase of the Na -K- ATPase activity as compared with LPS group. These renoprotective effects were accompanied by improvement of hemodynamic with increase of the mean arterial blood pressure [MAP] via reduction of nitric oxide [NO] level. Kidney functions were also effectively enhanced where glomerular filtration rate [GFR], renal blood flow [RBF], filtration fraction [FF.], renal vascular resistance [RVR], urine flow rate and urinary sodium excretion [U[Na]V] were significantly increased while proteinuria, serum urea and serum creatnine were significantly decreased. Urinary kidney injury molecule-1 [KIM-1] which is a specific tubular biomarker was greatly attenuated. Consistent with these observations, H[2]S treatment significantly alleviated renal hitopatholgical changes of LPS-induced AKI. Taken together, our results indicated the enhanced renal inflamination during LPS-induced AKI and the improvement of renal hemodynamic and functions as well as suppression of both renal cellular damage and inflammation by H[2]S which may signify its renoprotective effects in septic AKI

Effect of ghrelin on heat-induced testicular dysfunction in adult rats

Background: Scrotal hyperthermia has been known as a cause of male infertility with impaired spermatogenesis

Objectives: This study was designed to investigate the heat-induced alterations in spermatogenesis, and the accompanied testicular dysfunction in adult rats, and the effect of ghrelin and its possible mechanism of action in averting such reproductive damage

Materials and Methods: Ninety six adult male rats were randomly divided into four experimental groups 24 animal each]: control, ghrelin, heated and ghrelin-heated groups. The scrota of heated-designed rats were submerged once in water bath at 43 Degree C for 30 min. Immediately upon heating, 2 ng/Kg of ghrelin were given subcutaneously to ghrelin-heated animals every other day up to the end of the experiment [day 60]. The animals were sacrificed at days 15, 30 and 60 after heat treatment. The epididymis were removed for evaluation of epididymal sperm characteristics. Serum levels of luteinizing hormone [LH], follicle stimulating hormone [FSH], as well as serum and testicular testosterone concentration as a biomarker of testicular functions were measured. Anti-apoptotic protein: heat shock protein-70 [HSP-70] was also evaluated. In addition testicular histopathology was clone

Results: The heated group showed significant testicular dysfunction in the form reduced weight of the testis, impaired spermatogenesis [decreased sperm count, motility, viability and sperm membrane integrity,], higher levels of serum LH and FSH, whereas decreased serum and testicular testosterone and HSP-70 levels in comparison to control animals. Testicular histopathology revealed significant reduction in the means of seminiferous tubules diameters [MSTD] with obvious germ cells apoptosis, degeneration of spermatogenic cells and small sized and number of interstitial cells of Leydig up to day 60 of the experiment. Notably, in ghrelin-heated group, ghrelin induced partial recovery in all of the above-mentioned parameters and improved testicular regeneration process by day 30 compared to the heated group. On day, 60 of the experiment, ghrelin restored spermatogenesis and attenuated the heat-induced testicular dysfunction to the levels observed in the control animals

Conclusion: Findings of the present study indicate the ghrelin ability in attenuation of heat-induced testicular dysfunction probably by activating testicular endocrine systems and anti- apoptotic effect

Interleukin-12 and interferon gamma levels in infants with post BCG lymphadenitis

Bacille Calmette Guerin [BCG] is a live bacterial vaccine used in many countries to prevent tuberculosis [TB]. However, because the vaccine consists of live attenuated bacteria, there is still a risk that inoculation with this Mycobacterium bovis strain in immunodeficent infant will cause localized [BCGitis] or disseminated infection, referred to as 'BCG-osis'[1,2] This was prospective hospital based study aiming to determine the serum levels of interleukin-12 and interferon-y among infants with post BCG lymphadenitis. The study included 20 cases [mean +/- SD of age was 4.2 +/- 1.7 months] with newly diagnosed post BCG lymphadenitis group in addition to 20 apparently healthy infants age and sex matched [mean +/- SD of age was 3.9 +/- 1.9 months] as a control group. The study was conducted during the period from March 2008 to November 2010. Both patients and controls were recruited from Paediatric Outpatients Clinics and Paediatric Emergency Department in Assiut University Children Hospital, Egypt. Written informed consents were obtained from the parents of both patients and controls. All cases were subjected to a thorough history, full clinical examinations and investigations which include routine blood tests, immunological studies and serum levels of Interleukin -12 and interferon- gamma. In the post BCG lymphadenitis group, 85% of cases came from rural areas, 45% have positive consanguinity, while 20% of the same group have positive family history of post BCG lymphadenitis. Serum IL-12 and IFN-gamma levels were significantly deceased in cases of post BCG lymphadenitis compared with control group [P< 0.01]. Serum IL-12 and IFN-gamma levels were significantly and positively correlated with age in studied cases. In addition, IL-12 was positively and significantly correlated with IFN-gamma. Serum IL-12 and IFN-gamma levels should be assessed in infants with post BCG lymphadenitis to detect IL-12/ IFN-gamma axis abnormalities. BCG vaccination should be delayed in every newborn and infant with a family history of post BCG lymphadenitis until immunodeficiency diseases and IL-12/IFN-gamma axis abnormalities have been ruled out

Serum leptin levels in type-I diabetic children and adolescents versus healthy controls: relationship to age, gender, body mass index, gonadal hormones and pubertal stages

Since childhood and puberty are periods of major metabolic and endocrine changes, the present study was conducted to: [I] Evaluate developmental changes of serum leptin levels in children and adolescents with type-1 diabetes mellitus in comparison with matched healthy controls in respect with chronological age and pubertal stages [2] Evaluate if leptin concentration would be related to obesity observed in children and adolescents with type-1 diabetes during puberty. The study included 60 children diagnosed as type-1 diabetes mellitus by the criteria of American Diabetes Association [ADA] as well as 48 healthy children with matchable age and sex with diabetic patients. The patient and control children were grouped according to their chronological age into 4 groups [6-7yr, 8-10yr, 11-13 yr and 14-16yr] and according to stages of puberty into 3 groups: pre puberty P[1] early puberty P[2] and overt puberty P[3]. Serum leptin levels and BMI were measured to all patients and controls. Also, serum testosterone in boys and serum estradiol in girls were measured by ELISA method. Serum leptin levels significantly increased parallel with age and with pubertal stages both in control and diabetic girls. The maximum levels were observed at 14-16yr age group and at overt stage of puberty. Serum leptin levels were significantly higher in diabetic girls than controls at all studied groups. In control boys, leptin levels were significantly higher at 8-10yr and during P[1] stage then a significant decline occurred thereafter. In contrast, the diabetic boys showed no such decline either with age or with pubertal staging. Diabetic boys had significantly higher leptin levels than control boys at all studied groups. Serum leptin levels in girls were significantly higher than boys either in control or diabetic children. Diabetic children [girls and boys] were significantly older than controls during P[2] and P[3] stage. BMI was significantly increased In diabetic children [girls and boys] than controls during P[1], P[2] and P[3] stage whereas serum estradiol in diabetic girls and testosterone in diabetic boys were significantly lower than controls during P[2] and P[3] stages. Significant positive correlations were observed between serum leptin levels versus age, BMI and estradiol hormone in control girls. Also significant positive correlations were found in diabetic girls between serum leptin levels and each of age, BMI and estradiol hormone. In control boys significant negative correlations were observed between serum leptin level and each of age and testosterone hormone whereas non significant with BMI. Significant positive correlations were found in diabetic boys between serum leptin levels and each of age and BMI, while the correlation with testosterone was non significant. In conclusion leptin appears to participate in various endocrinological and physiological process in human body. Among the more notable are obesity and pubertal delay-associated diabetes. Thus, it may be involved in regulation of body weight and signaling the onset of puberty and maintenance of reproductive function thereafter

Adiponectin serum level among children with nephrotic syndrome in relation to right ventricular functions

Adiponectin [ADPN], a protein hormone, is exclusively expressed on and secreted from adipocyte. ADPN is a particularly interesting compound because it may have a protective influence on the cardiovascular system. This study was a prospective hospital based study aiming to evaluate ADPN serum level among children with nephrotic syndrome [NS], right ventricular functions by Echocardiography and finding any correlation between ADPN as a protective hormone and right ventricular function. The study included 47 patients [28 boys and 19 girls] with steroid responsive nephrotic syndrome [SRNS]. Cases included two groups: Group A: Included 25 patients with SRNS in relapse. Group B: Included 22 patients with SRNS in remission for periods ranging from 3-9 months and with no steroid therapy. In addition to control group which included 28 children with matched age and sex. A thorough history and full clinical examinations and echocardiography measuring right and left ventricular wall functions and other abnormalities if present were done. Blood samples were collected for measuring serum levels of total cholesterol, triglycerides, high density lipoprotein [HDL], low density lipoprotein [LDL], very low density lipoprotein [VLDL] by Enzymatic Colorimetric kits, in addition to ADPN by ELISA method. Serum ADPN level was significantly higher in patients with SRNS in relapse [33.4 +/- 15.60 micro g/ml] in comparison with patients with SRNS in remission [12.54 +/- 8.76 micro g/ml] and with control group [10.54 +/- 6.43 micro g/ml] with P value<0.001 for both. Right ventricular end diastolic diameter [RVEDD], right ventricular peak pressure[RVPP] and pulmonary artery pressure [PAP] were significantly higher while right ventricular ejection fraction [RVEF%] was significantly lower among cases in relapse [group A] than in cases in remission [group B] or children in control group. During relapse of SRNS, ADPN serum level is higher than its level in SRNS in remission and also, right ventricular dysfunction occurs in relapsed SRNS reflected by decrease of RVEF% and increase in RVEDD, RVPP and PAP

Importance of inflammatory cytokines and endothelial peptides in predicting hypertensive left ventricular hypertrophy

Although it has been hypothesized that hypertension in part is an inflammatory disorder, the link between inflammation and endothelial disorders with hypertensive complications as left ventricle hypertrophy [LVH] is still marginal. This study was designed to investigate the role of inflammatory markers as interleukin-6 [IL-6], high sensitivity C reactive protein [Hs-CRP], endothelial peptides as endothelin-1 [EDN -1] and nitric oxide [NO] as well as serum lipid profile in predicting LVH. It also focused on the pathophysiological responsibility of inflammation and endothelial dysfunction in developing hypertensive LYH. To examine these hypotheses forty hypertensive patients were enrolled and divided by using echocardiography into hypertensive patients with normal left ventricular mass [Group I] and hypertensive patients with LVH [Group II]. Ten normotensive subjects were also included and considered as control group [C]. ELISA technique was used for measuring plasma concentrations of IL-6, Hs-CRP, EDN-1 by special kits, while serum NO and lipid profile were measured by spectrophotometer. Both hypertensive groups were relatively matched with each other regarding age, gender, body surface area and body mass index [BMI], however they were significantly greater than control. Serum levels of IL-6, Hs-CRP and END-1, were significantly higher and those of NO were significantly lower in both hypertensive groups compared to normotensives. Moreover, these changes were more obvious in hypertensive patients with LVK Additionally, estimation of serum lipid profile showed that levels of total cholesterol triglycerides, and low density lipoproteins [LDL-C] were significantly elevated and that of high density lipoproteins [HDL-C] were significantly reduced in group [II] compared to other groups. Among both hypertensive patients, LY mass index was significantly positively correlated with serum levels of IL-6, Hs-CRP, EDN-1, cholesterol, triglyceride, LDL-C and significantly negatively correlated with HDL-C hut not with age and NO levels. However, the slope of these relations was steeper in the hypertensive group with LVH. Besides, levels of IL-6 and EDN-1 were the most predictors [r= 0.849, P<0.0001, r= 0.889, P<0.0001 respectively] for LYH. The inflammatory markers are significantly increased in hypertensive patients with LVH. Increased EDN-l and lowered NO are also concerned to a greater extent in hypertensive LYH and this confirms a key pathophysiological role of inflammation and endothelium dysfunction in developing and progression of hypertension and LVH which is vital for recommending prophylactic and therapeutic strategies

Changes in lung functions among patients with s mellitus

Clear decrements in lung function have been reported in patients with diabetes mellitus over the past two decades. However, at the present time, there are no reports of functional imitations of activity of daily living ascribable to pulmonary disease in patients with diabetes. To examine the impact of type 1 and type 2 diabetes on pulmonary functions including spirometry, diffusion and lung volumes, also correlation of these functions with blood glucose level and duration of diabetes. 40 patients with diabetes mellitus 20 with type 1 and 20 with type 2 attending the outpatient clinic in Assiut university hospital were recruited in this study. They were subjected to through history and clinical examination and evaluation to exclude any air way diseases. Lung functions including spirometry, lung volumes and diffusion capacity were performed to these patients compared with 40 healthy age- matched volunteers as a control group. For spirometric study, the mean value of FVC, FEV1, PEF25-75 were significantly reduced in both males and females in both types of diabetes, while FEV1/FVC was reduced significantly only in females with type 1 diabetes. For lung volumes, there was significant increase in RV, FRC RV/TLC and significant reduction in TLC in male patients in both types of diabetes. In females, there was no significant difference in mean values of RV, FRC, but significant reduction in TLC and significant increase in RV/TLC in type 1. In type 2, there was significant increase in RV, RV/TLC and significant increase in TLC with no significant difference in FRC. For diffusion capacity, the mean values of DLCO and KCO were significantly decreased in both males and females with type 1diabetes, while this reduction in type 2 was not statistically significant. Spirometric functions and lung volumes were significantly affected in both types of diabetes mellitus, while the diffusion capacity of CO and transfer coefficient were only significantly decreased in type 1. There is a negative correlation of pulmonary functions with blood glucose level and duration of diabetes

Neurophysiological and intellectual evaluation of patients with beta-thalassemia major

Anemia and its complications represent a major health problem in children. Beta-Thalassemia major [BTM] is a chronic genetically determined hematological disorder characterized by ineffective erythropoiesis, peripheral hemolysis and severe anemia and they require regular blood transfusions. The aim of the present study is to evaluate the neurophysiological and intellectual aspects of patients with BTM who are clinically have no CNS affection. The study included 33 patients with BTM 23 males and 10 females, their mean age was [8.00 +/- 3.02 years], who attended hematology unit of pediatric hospital, Assiut university in the period between January and April 2006. In addition to 30 apparently healthy children of cross matched age and sex as a control. A thorough history full clinical examination and detailed neurological history and examination were carried out. Evaluation of the hemoglobin level, serum Iron and serum ferritin were done as well as EEG and IQ. In the present study, Hb level was significantly lower in patients [6.9 +/- 1.2 gm/dl] than controls [11.4 +/- 0.7 gm/dl] with P<0.001, serum iron was significantly higher in patients [186.3 +/- 60.9 micro g/dl] than controls [91.9 +/- 22.1 micro g/dl] with P<0.001 and serum ferritin was significantly higher in patients [2580.00 +/- 576.9 micro g/dl] than controls [435.6 +/- 112.9 micro g/dl] with P<0.001. Total as well as performance I.Q were significantly lower in patients than controls with p-value <0.001 for each, Mean value of total I.Q were 88.3 +/- 8.1 for patients and 98.7 +/- 6.4 for controls. Performance I.Q were 81.7 +/- 9.1 for patients and 97.8 +/- 6.1 for controls. A significant negative correlations was present between serum iron and total I.Q [r=-0.67 and p<0.001] as well as performance I.Q [r=-0.45 and p<0.01]. There were no significant correlations between serum ferritin and I.Q [total, verbal or performance]. A significant positive correlation between mean Hb level in the last 2 years and total I.Q [r=0.68 and P<0.001], performance I.Q [r=0.47 and p<0.01] and verbal I.Q [r=0.41 and p< 0.05]. EEG background activity was normal in 48.5% and shows different grades of slowing in the rest of cases. There were a significant increase in slow waves as theta waves [39.7 +/- 23.4 and controls 11.8 +/- 6.9 with P-value <0.001] and delta waves [9.6 +/- 8.8 and controls 4.4 +/- 4.6 with p-value <0.05]. While fast waves of EEG were significantly decreased as alpha waves [12.12 +/- 9.28 and controls 19.7 +/- 6.7 with p-value <0.001] and beta waves [38.48 +/- 22.24 and controls 64.1 +/- 12.28 with p-value <0.001]. A significant positive correlation was present between Hb level and alpha waves [r=0.74 and P<0.001], significant-ve correlation between Hb and theta waves [r=0.65 and P<0.001] and a significant positive correlation between Hb and beta waves [r=0.66 and P<0.001]. C.N.S. is one of the important systems affected by repeated blood transfusions in BTM patients leading to lowering of I.Q scores especially performance skills and also affect EEG and these effects starts silently and progress and so, early detection of CNS affection in BTM patients is recommended for early intervention and to maintain good quality of life as well as to reach a satisfactory levels in learning

study of some oxidants/antioxidants and trace elements in children with bronchial asthma

Asthma is a chronic inflammatory disorder of the airways involving variable airflow obstruction and increased airway responsiveness to a variety of stimuli. The rise in prevalence of asthma and allergic diseases among children is a matter of worldwide concern. Epidemiological evidence suggests that changes in diet, in particular reduced antioxidant intake have contributed to the increased asthma prevalence and severity and raises the possibility that dietary interventions may improve asthma. To evaluate the oxidants/antioxidants, and trace elements status in children with bronchial asthma this study was conducted on 39 asthmatic patients [mean age of 8.5 +/- 2.1 years] as well as 20 apparently healthy controls of matched age and sex recruited from Assiut Pediatric University hospital. Beside thorough history-taking, and meticulous clinical examination for all cases and controls, lung function tests and a chest x-ray were done for each asthmatic child. Fifteen patients had mild bronchial asthma, twelve had moderate, and twelve had severe asthma according to the National Asthma Education and Prevention program. The following investigations were done to all studied children: plasma lipid peroxide level expressed in terms of malondialdhyde [MDA]; red blood cell enzyme activity of each of glutathione peroxidase [GSH-Px], and superoxide dismutase [SOD]; plasma levels of vitamins [A, E, and C], zinc [Zn], copper [Cu], selenium [Se] and magnesium [Mg]. Asthmatic children showed significantly higher plasma level of MDA than controls. Red blood cell enzyme activity of each of GSH-Px, and SOD, also, plasma levels of vitamins A, and C, Zn, Se, and Mg showed significantly lower values in asthmatic children than controls. The changes observed in the studied parameters were more apparent in patients with severe asthma than those with mild degree. Significant positive correlations were observed between the values of forced expiratory volume 1 [FEV 1], and each of GSH-Px, SOD, and vitamin A, Zn, and Se, while significant negative correlation was found between FEV 1 and MDA. Also, significant negative correlations were detected between MDA, and each of GSH-Px, SOD, vitamin C and Zn. Oxidative stress and disturbed antioxidants and trace elements status are present in asthmatic children, and may have important consequences for the pathogenesis, and severity of asthma. Special attention must be given to the assessment of dietary intake of vitamins and trace elements. So, good dietetic intakes of high biological value protein, and supplements of vitamins, and trace elements are recommended as an adjuvant therapy. Long term prospective trials are recommended to determine whether modification of dietary intake will be beneficial in prevention, or reduction of the severity and or morbidity of the disease

study of anticonvulsant effect of some steroids on induced seizures in adult male mice

Hormones influence brain functions throughout life and might alter seizures susceptibility by affecting neuronal excitability. Alterations in gamma amino butyric acid [GABA,] ergic neurotransmission are associated with seizures disorders and consequently much of antiepileptic therapy is directed towards the GABA A receptor complex. In humans, seizures patterns are affected by some factors such as the onset of puberty, pregnancy and stress suggesting that there is an underlying hormonal component. the present study was conducted to evaluate the anticonvulsant effect and the possible mechanism of action of some steroid hormones. Progesterone, deoxycorticosterone [DOC] and dehydroepiandrosterone [DHEA] in experimentally induced seizures in male mice. This study was carried out on adult albino male mice weighing 24-26gm and included two experiments: experiment I, in which two models of seizures were used; pentylenetetrazol [PTZ] model and maximal electro-convulsive shock seizures [MES] model. In each model, the animals were divided into 5 groups. The first group was kept as a control group and each of the other 4 groups was subdivided into 3 subgroups, 20 animal each. The treated groups included: diazepam, progesterone, DOC and DHEA treated groups at different doses. In PTZ model, PTZ was given in a dose of 70 mg/kg by intraperifoneal [i.p.] injection to induce chemoconvulsant seizures while in MES model, the animal received a stimulus train of electric current 25 mA, 50 Hz through the brain via ear electric clip. Diazepam and hormones were given 30 mm prior to PTZ injection or MES induced seizures. Experiment II in which bicuculline, a GABA A receptor antagonist was used in a dose of 1 mg/kg subcutaneously [s.c] 15 mm prior to administration of hormones. The ictal activity [latency, duration of myoclonic seizures and percent of protection against seizures and mortality] was recorded in either experiment. It was observed that progesterone suppressed PTZ induced seizures where it significantly [P<0. 001] prolonged the latency and shortened the duration of myoclonic seizures as compared to control with median effective dose [ED 50] of about 20 mg/kg s.c. The protection against seizures was 60, 70 and 75% and against mortality was 100%. Also, DOC administration exhibited a potent significant anticonvulsant activity in PTZ model in comparison to control and nearly equal to diazepam treatment. The ED 50 of DOC was 5 mg/kg and complete protection against seizures and mortality was observed at 20 and 80 mg/kg. In MES model, administration of progesterone at.20 and 80 mg/kg induced no significant anticonvulsant effect and ED 50 war observed at a higher dose [160 mg/kg]. Treatment with DOC 5 mg/kg produced no anticonvulsant activity, ED 50 was 20 mg/kg and complete protection against seizures was reached at 80 mg/kg. Both in PTZ and MES model, diazepam at the all tested doses induced a significant anhiconvulsant effect, while DHEA lacked any anticonvulsant activity, even it has a convulsant effect. Pretreatment with. bicuculline prior to progesterone and DOC administration caused a significant reversal of the anticonvulsant activity of these hormones. These findings indicate that the steroid hormones; progesterone and DOC have a broad spectrum anticonvulsant activity in animal seizures models [especially PTZ model] mediated by GABA A receptor modulation. Therefore, they might be involved in the modification of seizures frequency and epilepsy and might have a clinical importance in the future treatment of seizures disorders in conjunction with the usual antiepileptic drugs. On the other hand, DHEA has no anti convulsant effect