Relation between apelin-36 and arginine vasopressin in male rats subjected to water deprivation and volume expansion

The closed anatomical localization in supraoptic and paraventricular nuclei and tissue distribution of apelin-36 and arginine vasopressin [AVP] suggest a role for the peptide apelin-36 in body fluid homeostasis and regulation of AVP release. However, conflicting reports make the precise role of apelin-36 remains to be clarified. To investigate the effect of water deprivation and acute volume expansion on plasma and brain tissue levels of apelin-36 and AVP in an attempt to clarify the interaction between the two peptides in control of body fluid homeostasis. The study was conducted on 40 male albino rats divided into 4 groups. Group I: 10 control rats, group II: 10 rats subjected to 24h-water deprivation [WD], group III: 10 rats subjected to 48h-WD and group IV: 10 rats subjected to acute volume expansion 10% of body weight by infusion of isotonic saline over 40 minutes. The following parameters were measured in all rats; plasma and brain tissue apelin -36 and AVP, plasma Na[+] and K[+] concentrations, urinary excretion rates of Na[+] and K[+] and urine flow rate per minute. Hematocrite value and plasma protein concentrations were measured to investigate the state of dehydration and hydration. Water deprivation induced significant decrease in plasma apelin-36 level associated with an increase in its brain tissue contents. This was mirrored by increased plasma AVP level and decreased brain tissue content. The reverse was detected after acute volume expansion. Moreover, increased apelin-36 concentration in plasma after acute VE was associated with diuresis and natriuresis. A significant negative correlation was detected between plasma as well as brain tissue concentrations of both apelin-36 and AVP. Apelin-36 may be implicated in the control of body fluid homeostasis and exerts opposite action to AVP in this regard. Furthermore it may be an inhibitor of AVP and the two peptides may play complementary roles in maintenance of water balance

effect of combined rheumatoid arthritis and metabolic syndrome on endothelial dysfunction and the reliability of platelet endothelial cell adhesion molecule-I and matrix metalloproteinase-8 as markers for this dysfunction

Patients with rheumatoid arthritis [RA] and patients with metabolic syndrome [MetS] both are at increased risk for cardiovascular disease [CVD]. The present study aimed to evaluate the effect of association of RA with MetS on endothelial function measured by flow mediated dilatation [FMD] in females, as well as to find the possible role of platelet endothelial cell adhesion molecule-1 [PECAM-1] and matrix metalloproteinase-8 [MMP-8] on this function. forty eight female patients with RA, 21 of them had metabolic syndrome [RAMetS]. Forty nine female cases were enrolled as control cases, 25 of them had MetS [ContMetS]. C-reactive protein [CRP], MMP-8, Cartilage oligomeric matrix protein [COMP] and PECAM-i were assayed. Measurement of brachial artery FMD was performed using ultrasonography. RAMetS group had the highest level of MMP-8, PECAM-1 and CRP but it had the lowest FMD value than the other groups. FMD was found to correlate inversely with the severity of MetS as well as homeostasis model assessment-insulin resistance [HOMA-IR], CRP, MMP8, PECAM-1, rheumatoid factor [RF] and disease activity score in 28 joints [DAS28]. Endothelial cell dysfunction [ECD] proved by FMD impairment could be considered to be a common feature of RA as well as MetS. ECD was aggravated if both conditions were associated. Elevated MMP-8, PECAM-1 and CRP in RA patients and their correlation to FMD, point them to be contributing factors in the pathogenesis of ECD and the possibility to use them as biochemical markers for assessment of ECD in RA and/or MetS

Relationship between adiponectin, resistin and visceral obesity in type 2 diabetes mellitus in female Egyptians

The aim of this work was to study the possible physiological role of adiponectin and resistin as mediators linking obesity and insulin resistance in type 2 diabetes mellitus. Seventy-five female Egyptian subjects were enrolled in this study. They were divided into four groups as follows: obese nondiabetics [ONDM], obese diabetic type 2 [0DM], nonobese nondiabetic [NONDM] and nonobese diabetic [NODM]. Anthropometric measurements were taken. Abdominal ultrasound was also done to measure visceral fat [VF], subcutaneous fat [SCF] and visceral fat index [VFI]. Fasting blood samples were taken for analysis of serum insulin, blood glucose, plasma adiponectin and resistin. In the diabetic group adiponectin had an inverse correlation with resistin,VF and VFI [P < 0.01, P < 0.05, P < 0.01]. Resistin had a weak positive correlation only with VF, [P = 0.05] and RAI [resistin /adiponectin index] showed a positive correlation with VFI and SCF. In the nondiabetics adiponectin had no correlation with resistin, but had negative correlation with HOMA, age, VF and VFI, whereas resistin had no correlation with the same variables. RAI had a positive correlation with HOMA and SCF. In conclusion it can be said that resistin has no direct relation to insulin resistance either in diabetics or non diabetics. However, it may have a weak relation to visceral obesity only in diabetics. Hypoadiponectinemia is related to visceral obesity and increased resistin level in diabetics, while in non diabetics it is related to visceral obesity, insulin resistance and age. RAI is more informative than resistin which indicates a possible interaction between resistin and adiponectin especially in diabetics. RAI correlates positively with some anthropometrics but not to insulin resistance in diabetics, while it correlates positively with both variables in non diabetics

Study of the relationship between type-1 diabetes mellitus, prolactin hormone and immune system in rats

The effects of prolactin [PRL] on lactation and reproductive organs are well known. However, its effects on other target organs and its physiological consequences remain poorly understood. Prolactin was shown earlier to act as a stimulating factor for the immune system and thus it might influence the development of autoimmune diseases, as in type-I diabetes mellitus [DM]. The aim of the present work was to clarify the role of PRL in the development of autoimmune type-1 DM aiming to answer the question of whether PRL may have a beneficial effect in type-1 DM or not. The study was conducted on sixty male albino rats matched for age and weight. Rats were divided into six groups each of ten rats; group 1: a control group [C], group 2: a vehicle-treated group [V], group 3: Streptozotocin [STZ] treated group [STZ was given intraperitoneally [i.p.] in a dose of 40 mg/kg body weight [b.w] daily for 5 consequetive days], group 4: a group of STZ + PRL [PRL was given i.p. in a dose of 4 mg/Kg b.w starting with STZ and continuing for 21 days, group 5: a group of STZ + Bromocriptine [BC], a PRL antagonist. BC was given i.p. in a dose of 10 mg/kg b.w for 21 days and group 6: a group of STZ + PRL + BC. The study showed significant elevations of serum glucose, glycosylated Hb, [HAlc], serum Interleukin-1 beta [IL-1 beta], and interferon-gamma [IFN-gamma] levels in STZ treated rats, compared to the control and vehicle treated groups. Administration of PRL with STZ induced a significant decrease in the mean values of the previous parameters compared to STZ-only treated rats, still these parameters were not close to the mean control values. BC administration with STZ and PRL prevented the induced changes found with STZ and PRL. The results of the present study indicated that PRL might affect the associated immunological changes occurring in the early phases of developing type-1 DM. The partial protective effect of PRL was suggested to be due to suppression of autoimmune mechanisms as indicated by the significant reduction of IL-1 beta and IFN-gamma in PRL + STZ treated group as compared to control mean values

Metabolic derangements of skeletal muscle by aging and zymosan-induced critical illness in rats at rest and after electrical stimulation

The present work aimed to study the metabolic derangements of skeletal muscles in critically ill rats in relation to two different physiological factors, namely, age and electrical stimulation. The study was conducted on 80 male albino rats. Two study protocols A and B, each of 40 rats, were used. Each protocol consisted of 4 groups;10 rats each. Control young group [I]: consisted of 12 months old rats [vehicle-treated], Control old group[II]: consisted of 24 months old rats [vehicle-treated], Zymosan-treated young group[III]: consisted of 12 months old rats that were given zymosan [50 mg/100g body weight] by intra peritoneal [i.p.] route and Zymosan-treated old group[IV]: consisted of 24 months old rats, that were given zymosan [50mg/100g body weight] by i.p. route. Gastrocnemius muscles were prepared and excised from rats in resting state [protocol A] or after electrical stimulation [protocol B], then quickly frozen. The measured parameters included cytochrome c oxidase activity; as a mitochondrial content index, glycogen content, adenosine triphosphate [ATP], phosphocreatine [PCr], adenosine diphosphate [ADP], creatine, pyruvate and lactate concentrations as well as pH values in skeletal muscles of all rats of the study. At rest, the aging process was associated with significant decrease in ATP, glycogen and pH in normal control rats. However, after electrical stimulation, the aged control rats had significant lower cytochrome c oxidase activity and ATP, ADP, PCr, glycogen and pH values as compared to electrically stimulated young counterparts. Zymosan injection into young rats caused significant decrease in ADP, PCr, glycogen, pyruvate and pH at rest but with additional significant decrease in cytochrome c oxidase activity and ATP levels after electrical stimulation as compared to their corresponding control groups. Generally, zymosan-treated old group had the worst metabolic derangements especially after electrical stimulation. The young-aged rats could maintain ATP levels after electrical stimulation by effective anaerobic energy-producing pathways either with apparently well-acting aerobic pathway in control rats or with partially impaired aerobic pathway in zymosan-treated rats. However, old-aged rats can't maintain ATP levels after electrical stimulation even by enhanced anaerobic pathways possibly due to improper action of oxidative pathway. Zymosan injection produced metabolic derangements in skeletal muscles of rats by causing bioenergetic alterations which was more apparent after electrical stimulation especially in old-aged group

Aldehyde dehydrogenase 2 polymorphism: possibly a predisposing factor to hepatocellular carcinoma in hepatitis C cirrhotics?

Hepatocellular carcinoma [HCC] is considered as a long term multistage disease with multiple genetic alteration. Aldehyde dehydrogenase 2 [ALDH2] polymorphism may modify the risk of HCC. The aim of the present work was to evaluate the role of ALDH2 polymorphism as a predisposing factor for HCC in chronic hepatitis C virus [HCV] infected patients with cirrhosis for early detection. This study included fifty five subjects divided into three groups; twenty chronic hepatitis C patients with cirrhosis [group A], twenty chronic hepatitis C patients with cirrhosis and HCC [group B] and fifteen control subjects [group C]. The included patients were subjected to history taking, clinical examination, abdominal ultrasonography and liver biopsy [whenever possible]. All the subjects enrolled in this study were analysed for ALDH2 gene polymorphism. Genomic DNA prepared from leucocytes were used for polymerase chain reaction-restriction fragment length polymorphism [PCR-RFLP] technique. In addition, mitöchondrial ALDH activity was estimated in leucocytes. Of all fifty five subjects included in this study, six were heterozygous for ALDH2 gene mutation [ALDH2*1/*2] representing 10.9%, and the others were homozygous for the normal allele [ALDH2*11*1]. Non was detected to have homozygous mutant allele. The distribution among the patients groups was the same; three patients out of twenty in each group were heterozogous for the mutant gene [15%]. All the control subjects had normal homnozygous gene [ALDH2*1/*1]. The two patients' groups showed significantly higher percent of heterozygous mutant; ALDH2*1/*2 [X[2]=11.92,P=0.0027] and lower mitochondrial ALDH activity towards acetaldehyde [F=24.32, P=0.0002] in comparison to control group. However, non significant changes in both parameters were observed between the two patients' groups [P>0.05]. ALDH2 gene mutation could not be considered as a possible predictor for HCC in non alcoholic HCV-cirrhotic patients. However, these data did not exclude completely the relation to HCV infection and/or cirrhosis. Follow-up large scale studies are needed to investigate the exact link between ALDH2 mutation and cancer

Effect of quercetin on brain protein kinase C-alpha expression and serotonin level in streptozotocin-induced diabetic rats

Hyperglycemia is a key factor in diabetic complications. However, the mechanism of hyperglycemia-induced brain changes remains poorly understood. The aim of the present study was to investigate the effect of diabetes on serotonin [5-hydroxytryptamine; 5-HT] levels and protein kinase C-alpha [PKC-alpha] expression in brain. The potential protective effect of quercetin [QE]; as phytochemical on diabetic brain was additionally studied. This study was carried out on 60 adult male albino rats divided into three main groups; group I [control] included 20 vehicle-treated rats, group II [diabetic] consisted of 20 rats injected once intraperitonially with streptozotocin [STZ; 50mg/kb body weight] amid group III [insulin-treated diabetic] comprised 20 diabetic rats injected subcutaneously with insulin [SIU/kg/day]. Each group was subdivided into 2 subgroups; subgroup I [non-QE treated] and subgroup 2[QE-treated]. QE was administered orally [10mg/kg/day]. At the end of the implemental period, all rats were sacrificed, blood samples were withdrawn and their brains were rapidly removed and dissected. 5-HT was extracted from brain samlples and their concentrations were estimated fluorophotometrically. PKC-alpha expression was quantitated by immunoblot from extracted brain samples. The STZ-induced diabetic rats showed significant marked hyperglycemia and higher brain PKC-alpha expression as compared to both control and insulin-treated diabetic groups. However, brain 5-HT concentrations did not differ significantly between the three studied groups. Only in diabetic rats, QE administration produced a significant increase in 5-HT concentrations and a decrease in PKC-alpha expression but with no effect on blood glucose levels. A highly significant direct correlation was found between blood glucose and PKC-alpha expression levels. However, 5-HT did not correlate with either blood glucose or PKC-alpha expression. it could be concluded that STZ-induced chronically hyperglycemic rats were associated with enhanced PKC-alpha expression as well as unaltered neurotransmitter; 5-HT in brain. QE seems to act perfectly in diabetic rats by mechanisms other than antihyperglycemic action. The neuroprotective effect of QE in diabetics was suggested to be through both elevating 5-HT and lowering PKC-alpha expression. Consequently, controlling hyperglycemia is still the most essential approach for primary prevention of diabetic complications

Effect of l-carnitine and deferoxamine on hepatotoxicity, erythrocyte ergothioneine and testicular testosterone synthesis in sodiumvalproate-treated rats

The aim of the present study was to evaluate the effect of sodium valproate [VPA] as anantiepileptic drug on liver and erythrocyte oxidative state and on testicular testosterone synthesis. The therapeuticefficacy of either L-carnitine or deferoxamine [DFO] was assessed in such situations. This study included 108 albino rats divided into control groups, single dose VPA treated groups withand without L-carnitine or DFO treatment and repeated dose VPA treated groups with and without L-carnitine orDFO treatment. Liver triglycerides and malondialdehyde levels and catalase and glutathione S transferaseactivities as well as erythrocyte ergothioneine were estimated. In testes, P450cl7 and 17/3 hydroxysteroiddehydrogenase activities were measured as testosterone synthesis. Single and repeated VPA administration caused an increase in liver triglycerides, malondialdehyde,catalase and glutathione S transferase and a decrease in erythrocyte ergothioneine. Only repeated VPAadministration could decrease testicular testosterone synthesis. Co-administration of L-carnitine or DFO withVPA resulted in improvement of all the studied parameters. These data support the oxidative stress as a possible mechanism implicated in VPA-induced liver anderythrocyte damage. Moreover, VPA could alter testosterone synthesis giving a possible link between malereproductive function and VPA. The protective influence of L-carnitine and DFO may be partly mediated by theirantioxidant effects and by improving gonadal testosterone synthesi

role of reduced nicotinamide adenine dinucleotide dehydrogenase activity, nitric oxide, malondialdehyde and vitamin E in Parkinson's disease

The aim of the present work was to study the role of NADH dehydrogenase enzyme [complex I] activity, nitric oxide [NO], malondialdehyde [MDA] and vitamin E [vit. E] in the etiogenesis of Parkinson's disease [PD]. This study included 20 PD patients [group I] and 20 healthy subjects [group II]. Mitochondria from platelets were isolated to detect complex I activity. Plasma nitrite and nitrate together with their platelets homogenate levels were estimated. Plasma and platelets homogenate MDA, and plasma vit. E levels were also measured. The results of the present work showed: -Significant decrease of complex I activity [n mol/min/mg protein] as compared to healthy control subjects [t=4.03, p<0.001]. -Non-significant difference between the 2 studied groups as regard plasma nitrite and nitrate and their platelets homogenate levels [micro mol/L] [P>0.05]. -Non-significant difference between the 2 groups as regard the level of MDA in both plasma [n mol/L] and platelets homogenate [n mol/mg protein] [p>0.05]. -Significant increase of plasma vit. E level [ng/ml] in group I as compared to group II [t=3.6, p<0.001]. Age, age at onset and sex of PD patients showed non-significant correlation with complex I activity, plasma nitrate, plasma and platelets MDA and plasma vit. E [p>0.05]. However, plasma nitrite levels showed significant correlation with age [r=0.467, p<0.05]. These results suggest that complex I defect is a contributing factor in the pathogenesis of PD, To be considered as a biochemical marker, it should be measured repeatedly to detect progressive decrease in activity. Nitrite, nitrate, MDA and vit. E are apparently not related to the risk for PD