Adipocytokines in pre-pubertal children with type 1 diabetes: relation to some risk factors

Adipose tissue represents an active endocrine organ secreting a variety of factors that regulate energy metabolism and insulin sensitivity. The aim of this study is to evaluate adipocytokines in pre-pubertal children with type I diabetes mellitus and its relation to some risk factors. The study included 20 cases newly diagnosed with type 1 diabetes, 30 cases with long duration of diabetes, and 20 healthy matching children as controls. Cases and controls were subjected to full history taking and physical examination, estimation of BMI, blood glucose level and glycated hemoglobin. Non fasting blood samples were withdrawn from all cases and controls for estimation of serum adiponectin, resistin, leptin, TNF-alpha and IL-6. Results showed that newly diagnosed cases with type I diabetes had significantly lower BMI, serum adiponectin, and serum leptin levels and had significantly higher levels of TNf-alpha and lL-6 than cases with long duration of diabetes. No significant difference in resistin levels was observed between either studied cases or controls. Significant negative correlations were found between adiponectin with both lL-6 and TNF alpha serum levels in the whole studied cases. Also a positive correlation was found between resistin levels and duration of illness. In conclusion adipocytokines may play a role in metabolic adaptation of type I diabetes

role of Bcl2 and oxidative stress in juvenile diabetes mellitus

Diabetes mellitus is on of the most common non-communicable diseases, and if uncontrolled, targets multiorgan systems with serious debilitating and life threatening sequelae. Most diabetic cases fall under the type-2 category, characterized by relatively late onset, development of insulin resistance and for deficiency. Type-I diabetes on the other hand, manifest early during childhood and has an autoimmune component to it, that causes a severe deficiency in the circulating levels of insulin. The study included 32 diabetic child [17 males and 15 females] their age ranged from 3 to 14 years and 20 apparently healthy control of matching age and sex. All patients subjects for the following investigations: fasting glucose level, glycated hemoglopin[HBA[1]c],nitric oxide[NO], thiobarbituric acid [TBARS], hydrogen peroxide[H[2]O[2]], total antioxidant [TAO]and Bcl-2. Serum levels of glucose, HBA[1]c, NO[2], H[2]O[2] and TBARS were significantly higher in diabetic patients than in controls while serum levels of TAO and Bcl-2 were significantly lower in diabetic patients than in controls. Also there were positive correlations between serum glucose level with H[2]O[2], TBARS and NO serum levels and negative correlations between serum glucose level with TAO and Bcl-2 serum levels. In conclusion, Bcl-2 [as an anti-apoptotic factor] and oxidative stress state imbalance play an important role in the pathogenesis of diabetes mellitus

Pro-inflammatory cytokines, oxidative stress and intelligent quotient [IQ] in malnourished pediatric patients

Protein energy malnutrition [PEM] is one of the most common health problems among children of developing countries. Children with PEM lose their resistance to infection because of a disordered immune system. Protein energy malnutrition produces changes in inflammation related proteins characteristic off a low grade systemic inflammatory response and, thus, can serve as an inflammatory stimulus. Antioxidant status of PEM patients is significantly reduced. An increasing body of evidence indicates a link between malnutrition and poor cognitive ability in children [in particularly in early onset malnutrition]. This study included 28 children having malnutrition [17 patients had marasmus [loss of subcutaneous fat over the thigh or over the abdomen or loss the buccal bad of fat] and 11 patients had kwashiorkor[presented by generalized edema, sparse easily detachable hair, flag sign, cracky paint dermatosis and apathy], 15 males 13 females, their ages ranged from 4 months to 24 months, admitted to Gastroenterology Unit, Assuit University Children Hospital from April 2007 to December 2007 as well as 15 apparently healthy children of matchable ageand sex. All patients subjected to full history, complete clinical examination and the following investigations: serum levels of TNF-alpha, lL-6, nitric oxide [NO], lipid peroxide and zinc as well as Intelligent Quotient [IQ] were done. Serum levels TNF-alpha, lL-6, NO were significantly higher in patients with kwashiorkor and in patients with marasmus than in controls as well as higher in patient with kwashiorkor than in patients with marasmus. Serum levels of peroxide, was only significantly higher in patients with kwashiorkor and in patients with marasmus than in control. Also serum zinc level and I.Q were significantly lower in patients with kwashiorkor and in patients with marasmus than in controls as well as in patients with kwashiothor than in patients with marasmus. There are negative correlations between serum levels of TNF-alpha, lL-6 and lipid peroxide with I.Q in patients with marasums and patients with kwashiorkor. Also there is a positive correlation between serum level of zinc with IQ in patients with marasmus and in patients with kwashiorkor. in conclusion, oxidative stress imbalance and zinc deficiency in children with PEM play an important role in their neurocognitive development

Increased serum and cardiac acyl-carnitine/free carnitine ratio during development of doxorubicin-induced cardiotoxicity

This study has been initiated to investigate whether cumulative doxorubicin [DOX] therapy alters serum and cardiac carnitine levels and if so, whether these alterations should be viewed as a mechanism and /or as an index during development of DOX-induced cardiotoxicity. To achieve the ultimate goal of this study, a total of 40 adult male Wistar albino rats were divided into 4 groups. In the first group, animals were injected intraperitoneally [I. P.] with normal saline [0.5 ml/200 gm body weight] and served as a normal control. Animals in the second to the fourth groups were injected every other day with DOX [3 mg/kg, I.P.], to obtain treatments with cumulative doses of 6 mg/kg [group 2], 12 mg/kg [group 3] and 18 mg/kg [group 4]. At 24 hours after receiving the last dose of DOX, animals were sacrificed serum as well as hearts were isolated and analyzed. DOX induced a significant and dose-dependent increase in serum creatine phosphokinase isoenzyme [CK-MB], lactate dehydrogenase [LDH], acyl-carnitine [AC]/free carnitine [FC] ratio and a significant decrease in serum free FC. In cardiac tissues, DOX induced a significant 46% and 63% decrease in FC after cumulative doses of 12 and 18 mg/kg, respectively. In contrast to FC, DOX induced a significant 70% and 81% increase in AC after cumulative doses of 12 and 18 mg/kg, respectively. Moreover, DOX treatment showed significant and dose-dependent decrease in adenosine triphosphate [ATP] level in cardiac tissues. In conclusion, data from this study suggest that: [1] Decreased myocardial carnitine level should be viewed as a mechanism during development of DOX cardiotoxicity, and [2] the parallel increase of serum AC/FC ratio and cardiotoxicity enzymatic indices, may point to the possible consideration of AC/FC ratio as a marker during development of DOX cardiotoxicity

frequency of celiac disease, TB enteritis and giardiasis among children with chronic diarrhea

Chronic diarrhea is one of the most common causes of referral to a gastroenterology clinic. Chronic diarrhea may result from many different causes; celiac disease is one of them. Other important causes in our locality are infections such as TB and Giardiasis. This work was planned to determine the frequency of celiac disease, TB enteritis and Giardiasis among children referred to the gastroenterology unit with the complaint of chronic diarrhea and to evaluate the different methods used in the diagnosis of each disease. The study included 92 patients with chronic diarrhea. Their ages ranged from 6 months to 15 years. They were 56 males and 36 females, admitted to the Pediatric gastroenterology unit, Assiut University Hospital during the period from January 2005 to December 2006. Besides full history and thorough clinical examination, the following investigations were done for all cases: stool analysis for three consecutive days, CBC, ESR, total proteins and serum albumin, tuberculin test, accelerated BCG test [in tuberculin negative cases], serum antiendomysial antibodies. Upper GIT endoscopy with duodenal biopsy and aspiration and tissue staining by H and E and by immuno-histochemistry [anti-tTG moAbs] to detect tTG antigens in biopsy specimens. Lower GIT endoscopy with biopsy sampling and histopathological examination of biopsy specimens was also done. Out of the total patients, 18 cases [19.5%] were positive for celiac disease by AEM antibodies while 16 were positive by tTG immunostaining of biopsy specimens. Fourteen patients [15.2%] had tuberculous enterocolitis while 12 [13%] had biopsy proven Giardiasis. On the other hand 48 patients [52.1%] had other undiagnosed causes of chronic diarrhea. A very high index of suspicion for celiac disease should be maintained for patients who present with chronic diarrhea or iron deficiency anemia. The best method for diagnosis of celiac disease in such patients is serological testing followed by a small-bowel biopsy. The diagnosis of intestinal tuberculosis is difficult due to the lack of specific symptoms and signs. Colonoscopy with ileoscopy is a useful method for diagnosis of intestinal TB. Gastrointestinal endoscopy with biopsy examination is an important method of diagnosis and follows up of children with Giardiasis

Cardiac troponins in children with chronic renal failure

Cardiac troponins T and I [cTnT, cTnI] are highly sensitive biomarkers for the detection of myocardial damage. Patients with chronic renal failure [CRF]on regular hcmodialysis [HD] often have increased serum concentrations of cardiac troponins and left ventricular hypertrophy [LVH] with or without evidence of acute myocardial injury. Thirty eight pediatric patients [23 males and 15 females], aged 4-18 years, suffering from CRF and on regular HD for more than one year were prospectively included in this study as well as 15 apparently healthy children matched for age and sex as controls. All patients and controls had detailed history and full clinical examination. Serum levels of Na, K, cTnT, cTnI, creatinin kinase [CK] and creatinin kinase MB [CK-MB] and hematocrit were estimated. Echocardiographic estimation of left ventricular [LV] dimensions, FS, EF, LV mass index [LVMI] and relative wall thickness [RWT] was done. Patients were classified into three subgroups according to presence or absence of LVH, congestive heart failure [CHF] and anurea. Serum levels of cTnT, cTnI and CK-MB were significantly higher in the patient group [0.086 +/- 0.054, 0.357+0.17, 5.65 +/- 3.94ng/ml] compared to controls [0.052 +/- 0.036, 0.26 +/- 0.12, 4.2 +/- 2.88ng/ml] respectively [p<0.05 for all]. In the patient group, cTnT was elevated in 58% [22/38], cTnI was elevated in 15.7% [6/38], while CK-MB was elevated in only 8% [3/38]. Significantly higher cTnT was detected in patients with LVH, CHF and anurea [0.126 +/- 0.11, 0.132 +/- 0.123, 0.134 +/- 0.13ng/ml] than those-without [0.054 +/- 0.034, 0.062 +/- 0.048, 0.071 +/- 0.049ng/ml], [p<0.01, 0.025, 0.05] respectively. Also, cTnI was significantly higher in patients with LVH, CHF and anurea [0.381 +/- 0.05, 0.391 +/- 0.12, 0.389 +/- 0.13ng/ml] than those without [0.337 +/- 0.07, 0.339 +/- 0.014, 0.323 +/- 0.019ng/ml] p<0.05 for all. LVH was found in 58% of patients who had significantly higher LVMI than controls [39.9 +/- 14.2 Vs. 24.3 +/- 6.3g/m[2.7], p<0.001]. Concentric LVH was found in 8 [36%] of them. LVMI correlated significantly, with systolic BP [r=0.72, p=0.011], diastolic BP [r=0.83, p=0.002], indexed end diastolic LV dimension [r=0.68, p=0.010]. In addition, a highly significant positive correlation was detected between LVMI and cTnT serum level [r=0.591, p<0,001]. Serum levels of cardiac troponins [cTnT and cTnI] and LVMI are increased in pediatric patients with chronic renal failure on regular hemodialysis particularly those with cardiac complications. Cardiac troponins and LVH appear to predict cardiac complications in this group of patients

Serum antioxidant and pro-oxidant trace elements: relationship with oxidative stress in children with chronic renal failure on regular hemodialysis

There is a good evidence indicating that uremia, in general, is associated with enhanced oxidative stress and treatment of uremic patients with hemodialysis [HD] or peritoneal dialysis [PD] has been suggested to particularly contribute to oxidative stress and reduced antioxidant levels in those patients. Also uremic patients have abnormalities in trace elements which maybe caused by the uremia itself and/or enhanced or modified by the dialysis procedures. The aim of this study was to evaluate the oxidative stress imbalance and its relationship to the trace elements in children with chronic renal failure [CRF] on regular HD. This study was conducted on 36 children with CRF on regular HD and in 25 age and sex matched normal control children. Thiobarbituric acid [TBARS], total antioxidant [TAO], and hydrogen peroxide [H[2] O[2]] were measured by colorimetric assays. Trace elements [selenium [Se[+2]], zinc[zn[+2]], copper [Cu[+2]], manganese [Mn[+2]], lead [Pb[+2]] and cadmium [Cd[+2]] were measured by atom absorption/flame emission spectrophotometry. The results showed that the serum concentrations of TBARS, H[2]O[2], Cd and Pb were significantly higher in the studied cases [2.498 +/- 0.29, 2.967 +/- 0.414, 21.74 +/- 2.37 and 38.01 +/- 4.18 respectively] than in the controls [1.649 +/- 0.093, 0.311 +/- 0.032, 5.83 +/- 0.68 and 12.67 +/- 0.85 respectively] P<0.05 and P<0.001 for the others. The serum concentration of TAO, selenium, zinc and copper were significantly lower in the studied cases [1.379 +/- 0.017, 2.411 +/- 0.138, 91.07 +/- 2.979 and 84.89 +/- 3.145 respectively] than in the controls [2.049 +/- 0.014, 4.012 +/- 0.203, 128.7 +/- 4.924 and 128.7 +/- 3.904 respectively] [P<0.001 for each]. A significantly positive correlations were found between serum levels of cadmium and TBARS and between serum levels of selenium and TAO [r=0.359 P<0.05, and r=0.398, P<0.05 respectively]. Also a significant negative correlation was found between serum levels of zinc and serum level of TBARS [r=-0.392 P<0.05]. Our data suggest an enhanced oxidative stress and significant changes in trace elements in end stage renal disease [ESRD] patients undergoing HD. Also there is a significant relationship between the oxygen stress imbalance and the changes in the trace elements in these patients

Celiac disease, TB enterocolitis and giardiasis among children with chronic diarrhea: the accuracy of ANT-EMA and tTG expression in the diagnosis of celiac disease

Chronic diarrhea is one of the most common causes of referral to a gastroenterology clinic. Chronic diarrhea may result from many different causes; celiac disease is one of them. Other important causes in our locality are infections such as TB and Giardiasis. This work was planned to: 1-Determine the frequency of celiac disease, TB enteritis and Giardiasis among children referred to the gastroenterology unit with the complaint of chronic diarrhea and to evaluate the different methods used in the diagnosis of each disease. 2- Verifying the diagnostic accuracy of immunohistochemical tTG expression versus serum anti-endomysial antibodies [EMA] in celiac disease [CD] diagnosis. The study included 92 patients with chronic diarrhea. Their ages ranged from 6 months to 15 years. They were 56 males and 36 females, admitted to the Pediatric Gastroenterology Unit, Assiut University Hospital during the period from January 2005 to December 2006. Besides full history and thorough clinical examination, the following investigations were done for all cases: stool analysis for three consecutive days, CBC, ESR, total proteins and serum albumin, tuberculin test, accelerated BCG test [in tuberculin negative cases], serum anti-EMA. Upper GIT endoscopy with duodenal biopsy and aspiration and tissue staining by H and E and by Immunohistochemical [anti-tTG moAbs] to detect tTG antigens in biopsy specimens. Lower GIT endoscopy with biopsy sampling and histopathological examination of biopsy specimens was also done. Out of the total patients, 18 cases [19.5%] were positive for celiac disease AEM antibodies while 16 were positive by tTG immunostaining of biopsy specimens. Fourteen patients [15.2%] had tuberculous enterocolitis while 12 [13%] had biopsy proven Giardiasis. On the other hand 48 patients [52.1%] had other undiagnosed causes of chronic diarrhea. A very high index of suspicion for CD should be maintained for patients who present with chronic diarrhea or iron deficiency anemia. The best method for diagnosis of celiac disease in such patients is serological testing followed by a small-bowel biopsy. The diagnosis of intestinal tuberculosis is difficult due to the lack of specific symptoms and signs. Colonoscopy with ileoscopy is a useful method for diagnosis of intestinal TB. Gastrointestinal endoscopy with biopsy examination is an important method of diagnosis and follows up of children with Giardiasis

postulated protective role of lacidipine and verapamil against cyclosporin A-induced nephrotoxicity and its relation to P-glycoprotein expression in rat kidney

Cyclosporin-A [CsA] has markedly improved the results of transplantation and its use is extended to include autoimmune and primary renal diseases. However, the major limitation of its use is its nephrotoxicity. P-glycoprotein [P-gp] is a transmembrane efflux pump for hydrophobic, potentially toxic compounds, including CsA. CsA has been shown to increase P-gp expression in tubular and endothelial cells. Aim of Work: The aim of the present study was to elucidate the protective effect of the calcium channel blockers lacidipine and verapamil against CsA-induced nephrotoxicity and the relation of this protective effect to P-gp expression in rat kidney. This study included 7 groups, each containing 7 rats: oral saline group. intraperitoneal [IP] saline group, CsA [25 mg/kg/] group: rats received CsA IP for 14 days, lacidipine [1 mg/kg/d] group: rats received lacidipine orally for 17 days, concomitant lacidipine and CsA group: rats received lacidipine for 3 days and concomitant with CsA for another 14 days, yerapamil [0.1 mg/kg/d] group: rats received erapamil i.p for 17 days and concomitant verapamil and CsA group: rats received verapamil for 3 days and concomitant with CsA for another 14 days Serum creatinine, histopathological and immunostaining for P-gp for rat kidneys were done for all rats. This study revealed that CsA significantly raised serum creatinine, produced vacuolization and necrosis in tubular cells and increased P-gp expression. Kidneys treated with lacidipine alone revealed no significant changes biochemically and histologically. When lacidipine was given with CsA, it significantly protected the kidneys against CsA-induced nephrotoxicity and increased expression of P-gp in kidneys. Verapamil alone caused mild nephrotoxicity in the form of vacuolization and increased serum creatinine level. It also inhibited P-gp expression in rat kidneys. Verapamil given with CsA significantly ameliorated CsA nephrotoxicity and decreased P-gp expression. lacidipine had protective effect against CsA nephrotoxicity more than verapamil. Hemodynamic effect is the main effect and moreover, lacidipine may protect via P-gp over- expression

possible protective role of lisinopril as a pro-apoptotic agent in cyclosporin A induced nephrotoxicity in rats

The study was carried out on 40 male albino rats, which were divided into five groups: Group 1, normal control group, group 2, saline treated group, group 3, cyclosporin A treated group [rats received saline 0.2 ml for one week orally daily, then received cyclosporin A [20 mg/kg/day] intraperitoneally daily for another week], group 4, lisinopril plus cyclosporin A treated group [treatment with lisinopril [10 mg/kg/day] orally for one week, then co-administration, of both lisinopril and cyclosporin A for another one week using the aforementioned doses] and group 5, lisinopril-treated group [rats received lisinopril [10 mg/kg/day] orally for two weeks]. At the end of the study, blood samples were withdrawn from rats of all groups for determination of serum creatinine. Afterwards, rats were sacrificed and the kidneys were obtained. Sections from the kidney were stained by hematoxylin and oesin and immunohistochemically using anti-Bcl-2 antibodies for assessment of both necrosis and apoptosis, respectively. Cyclosporin A administration for one week significantly raised the serum creatinine level. Also, it produced histopathological changes confined to the proximal convoluted tubules in the form of moderate to severe focal necrosis, and produced strong Bcl-2 cytoplasm immunostaining. Treatment with lisinopril for one week, then co-administration, of both lisinopril and cyclosporin A, decreased significantly the cyclosporin A-induced elevation of serum creatinine, decreased the focal necrosis in the proximal convoluted tubules [Chi square=13.3], and produced weak Bcl-2 cytoplasm immunostaining [Chi square=7.27]. This denotes that the ACE inhibitor ameliorated the toxic insult induced by CsA by favoring induction of apoptosis as denoted by diminishing the Rcl-2 cytoplasmnostaining. From the above data, it could be concluded that lisinopril has a proapoptotic effect in the kidney after cyclosporin A-induced nephrotoxicity

Hypoglycemic effect of two mixtures of plant extracts on diabetic rats

Seeds of eight plant extracts, widely grown in Egypt were assessed for their hypoglycemic action on diabetic rats. Mixture [I] composed of Trigonella foenurn [Hulba], Lupinis albus [Termis], Gernum robertianum [Dahrnia], Ambrosia maritima [Damsisa] and Aloe ferox [Sabir], [5g each]. Mixture [II] composed of Nigella sativa [Habet el-baraka], Peganum harmala [Harmal] and Centaur/urn spicatum [Hashishet el-acrab], [5 g each]. Each mixture was extracted separately with boiled distilled water, then 2 ml from each extracted mixture were administrated, separately to the diabetic rats for 10 days [two days intervals]. The physiological capability of each extract was demonstrated, including the estimation of blood glucose, urea, creatinine, AST, ALT, insulin levels, beside liver protein content and hexokinase activity. The results revealed that the extract of mixture [I] exerted hypoglycemic and hyperinsulinemic effects on diabetic rats, meanwhile the extract of mixture [II] exerted hypoglycemic effect on the diabetic rats with no effect on the insulin level

Effects of trichloroacetate, water chlorination by-product, on liver peroxisomes and antioxidant status in rats and mice

Seven groups of each of male Fischer 344 rats and B6C3F1 mice were provided with drinking water containing distilled water 0.05 g/L trichloroacetate [TCA], 0.5 g/L TCA, 1.0 g/L TCA, 4.5 g/L TCA; distilled water + vitamin E and 4.5 g/L TCA + vitamin E, respectively, for 30 days. Liver palmitoyl Co-A oxidase [PCOA] and glycolate oxidase were estimated as peroxisomal enzymes. In addition, the liver content of water-soluble antioxidants, antioxidant enzymes and alpha- tocopherol were measured. These results demonstrated that the mouse is more sensitive than the rat with respect to the enhancement of liver peroxisome proliferation by TCA. A condition of oxidative stress produced by TCA exposure in drinking water was conducted. The possible role of oxidative damage in the hepatic carcinogenicity of TCA may be involved

Modulation of induced cardiocytotoxicity and genotoxicity of doxorubicin in rat by L-carnitine

Doxorubicin [DOX] is an anthracycline antibiotic with broad-spectrum antitumor activity. Its effectiveness has been limited by the occurrence of dose related myocardial and bone marrow toxicity. L-carnitine is tested in this study to evaluate its protective effect against DOX induced cytotoxicity and genotoxicity. Four groups of adult female rats, each of 15 animals were used; one is used as control receiving 0.5 ml of saline, the other groups received either DOX [3mg/kg], L-carnitine [100mg/kg] or a combination of the two drugs. The treatment was continued i.p. every other day for two weeks. Five animals of each group were injected with 0.2ml of colchicine 2 h before sacrifice, which took place 24 h after the last treatment. Cardiotoxicity was assessed by measuring the serum levels of lactic acid dehydrogenase [LDH], creatine phosphokinase [CPK], glutamic oxaloacetic transaminase [GOT]. Reduced glutathione [GSH], malonaldehyde [MDA] and mitochondrial palmitoyl Co-A and octanoate oxidation were also, determined in cardiac tissue homogenate. The femurs were removed and bone marrow was processed for the preparation of metaphase chromosomes and determination of mitotic activity. DOX significantly increased LDH, CPK, GOT and MDA and significantly decreased GSH and palmitoyl Co-A. Administration of L-carnitine one hour before DOX treatment caused significant recovery for the serum enzymes LDH, CPK, GOT, and MDA, GSH and palmitoyl Co-A. Cytogenetic analysis showed that DOX increased the incidence of chromosomal aberration 18.4% in bone marrow cells and inhibited mitosis to about 50% of its normal rate. Administration of L-carnitine one hour before treatment with DOX significantly decreased the incidence of chromosomal aberrations [14.8%] and increased mitotic activity [10.4]. The results suggest that the cardiotoxicity and genotoxicity induced by DOX took place via a number of possible mechanisms. The results obtained suggest that L-carnitine could be used together with DOX as an adjuvant therapy

Potentiation of the chemotherapeutic effect of methotrexate by hyperthermia in experimental animal tumor model

Evidence was obtained for the augmentation of cytotoxic effect of methotrexate [MTX] when combined with hyperthermia [HPT] in vivo. Results showed that Ehrlich tumor bearing mice injected i.p. with a single dose of MTX [1 mg/kg] 1 hour prior to local treatment with HPT [43C for 30 minutes] produced 2-fold enhancement of the tumor growth delay induced by MTX alone. Treatment of HPT alone for 3 times every other day produced 41.5% tumor regression, however, combined treatment of MTX and HPT produced 76.3% decrease in tumor volume compared to their volume before the treatment. The molecular mechanisms responsible for this potentiation were investigated by assaying tumor tissue contents of DNA, RNA and protein, and their rate of synthesis. Total lipid, cholesterol as well as activities of acid phosphatase and acid ribonuclease were also determined