pathophysiology of hemodialysis-induced hypotension in end stage renal [ESRD] disease patients

The upsurge in the renal failure patients undergoing haemodyalisis has attracted the researcher to figure out the possible mechanism of the haemodyalysis associated with hypotension. the purpose of this study was to determine plasma levels of ghrelin, leptin, insulin, and nitric oxide in renal failure patients with and without haemodialysis-induced hypotension, and to examine the potential correlation between these parameters and mean blood pressure in those patients. Sixty-four renal patients were included in the study and, were divided into three groups The first group consisted of 21 patients with renal insufficiency who were not on dialysis [NHD], the second group consisted of 23 patients on regular maintenance hemodialysis with normal blood pressure [HDNT] and, the third group consisted of 20 patients on regular maintenance hemodialysis with hypotension [HDHT]. The control group consisted of 20 healthy volunteers. Body mass index [BMI] and waist-hip ratio [WHR] were assessed. Blood pressure was measured three times within an interval of 5 min and the average was estimated. Mean blood pressure [MBP] was calculated. Nitric oxide metabolites [nitrates + nitrites, NO[X]], plasma ghrelin, leptin and insulin levels were assayed. BMI was significantly lower in HDHT group than the control, NHD, and HDNT groups. While the waist/hip ratio was significantly higher in HDHT group than NDH group. Both systolic and diastolic blood pressures were significantly lower in HDHT group than the other groups. Regarding the HDNT group, the systolic blood pressure was significantly lower than control and NHD group, while the diastolic one was significantly lower than the NDH group. Serum albumin was significantly lower in both HDHT and HDNT groups compared with NHD and control groups, however, it was significantly lower in HDHT compared with HDNT group. In addition, serum urea and creatinine, were significantly higher in the both HDHT, and HDNT groups compared with NHD and control groups, and it was significantly lower in HDHT compared with HDNT group. Plasma levels of Ghrelin, nitrate/nitrite [NO[X]] and leptin were significantly higher in patients compared with the control groups. Moreover, they were significantly higher in HDHT than HDNT and NHD groups, and in HDNT than NHD group. Regarding plasma levels of insulin it was significantly higher in the renal patients compared with the control group. However, there was no significant difference in insulin level between NHD and DHNT groups, while it was significantly higher in HDHT group compared with the two other renal patient groups [NHD, and HDNT. There was a significant negative correlation between changes of mean artrial blood pressure and ghrelin, leptin, insulin levels in both HDNT and HDHT patients. Our data suggest that excessive production of ghrelin, leptin, insulin and NOX contributes to HD-related hypotension in renal dialysis patients. The significantly elevated plasma levels of leptin and ghrelin is probably, at least in part, caused by impairment of their clearance by the kidney. Although being produced by the kidney, the physiological role of ghrelin in the kidney under normal and pathological conditions remains not fully elucidated. The elevated plasma insulin level may be caused by impaired glucose metabolism in uremic patients with alterations in insulin degradation and insulin secretion. The elevated NO[X] may be due to elevated serum leptin that modulates endothelial NO production, and /or elevated serum insulin that enhances NO release. However, we need to study the correlation between NO production and leptin and insulin levels in HD-related hypotension in renal dialysis patients to confirm this hypothesis

Role of histamine in ovariectomy-induced osteoporosis in rats

It has been reported that histamine increases osteoclast activity and number through H1 and H2 receptors, respectively, whereas other studies indicated that the histamine effects on bone resorption were indirect. The present study was designed to assess the possible effect of the H1 receptor antagonist [promethazine] and the H2 receptor antagonist [ranitidine], alone and in combination compared with the bisphosphonate [alendronate], as a standard treatment of osteoporosis, on ovariectomy-induced osteoporosis in rats. The present study was conducted on 60 female albino rats that were divided into 6 groups, each of JO rats. Group I: sham-operated, Group II: non-treated ovariectomized [OVX] rats, while groups III, 1V V and VI were OVX rats treated with alendronate, promethazine, ranitidine and combination ofpromethazine and ranitidine, respectively. The results of the present study demonstrated that urinary deoxypyridinoline [DPY]/creatinine and serum osteocalcin concentration significantly increased in the OVX non-treated group compared to the sham-operated group, indicating an increased bone turnover. In addition, serum alkaline phosphatase [ALP] activity and serum phosphorus [F] concentration were significantly higher in the OVX non-treated group than in the sham-operated group. Meanwhile, no significant dfference among groups I to VI was observed in the mean serum calcium [Ca] concentration. Treatment of OVX rats with alendronate significantly decreased urinary DPY/creatinine as compared to the OVX non-treated group. Moreover, alendronate significantly decreased serum osteocalcin and F concentrations and serum ALP activity as compared to the OVX non-treated group. Similarly, treatment of OVX rats with promethazine, ranitidine or their combination significantly deceased urinary DPY/creatinine as compared to the OVX non-treated group. Furthermore, the combination of both drugs .reased urinary DPY/creatinine at a higher significant level when compared to each drug alone. In addition, e was no significant difference, regarding this parameter, between the combination, alendronate and shamyrerated groups. Moreover, treatment of OVX rats with promethazine, ranitidine or their combination sigi4ficantly serum osteocalcin and F concentrations and serum ALP activity as compared to the OVX non-treated-group. Furthermore, there was no statistically significant difference, regarding these parameters, between the pnethazine, ranitidine, their combination and alendronate-treated groups. However, there were statistically significant differences, regarding these parameters, between all the drug-treated groups and the sham-operated. It may be concluded from the findings of the present study that the use of the H1 and H2 receptor agonists [promethazine and ranitidine] could be effective in decreasing bone resorption, increasing bone formation and diminishing ovariectomy-induced osteoporotic changes. These findings might be of help in developing therapeutic regimens to protect against postmenopausal osteoporosis in women

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

Role of modulation of vascular endothelial growth factor and tumor necrosis factor-alpha in gastric ulcer healing in diabetic rats

To assess the role of modulation of vascular endothelial growth factor and tumor necrosis factor-alpha in gastric ulcer healing in streptozotocin [STZ]- induced diabetic rats. forty male rats were made diabetic by intraperitoneal [i.p] STZ infection and ten rats were injected i.p. by a single dose of saline and served as a control for group II Six weeks following STZ or saline injection, gastric ulcers were induced by serosal application of acetic acid. Three days after acetic acid application, rats were divided into: group I[normal control], group II [STZ-injected rats], groups III. IV and V [STZ-injected rats treated with insulin, insulin and phosphodiesterase [PDE] inhibitor [pentoxifylline] [PTX] and insulin and Hydroxymethylglutaryl Coenzyme A [HMG-CoA] reductase inhibitor [simvastatin] respectively, for seven days following acetic acid application. At the end of the experimental period, plasma glucose was measured. Gastric ulcer area as well as gastric tumor necrosis factor- alpha [TNF-alpha], vascular endothelial growth factor [VEGF] and haemoglobin [Hb] concentrations were determined. STZ-injection induced diabetes, evidenced by significant higher mean value in plasma glucose concentration in group II compared to that of the control group [I] Significant delay in ulcer healing could be observed, in the form of significant increase in gastric ulcer area in group II compared to the control group I. STZ-injection resulted in significant increase in gastric TNF-alpha as well as a significant decrease in gastric VEGF concentrations together with a significant decrease in gastric angiogenic response evidenced by a significant decrease in gastric Hb concentration in group II compared to the control group I. The use of insulin, as well as combinations of insulin and PTX or simvastatin caused a significant decrease in plasma glucose concentration as well as a significant increase in gastric ulcer healing [evidenced by a significant decrease in ulcer area], gastric VEGF and gastric Hb concentration as well as significant decrease in gastric TNF-alpha compared to group II. A significant difference in gastric ulcer area and gastric TNF-alpha could be observed between rat that received combinations of insulin and PTX or simvastatin compared to rats that received insulin only. A significant difference in gastric VEGF and Hb was also found between the group that received combination of insulin and simvastatin compared to the group that received insulin only. Experimental DM impairs ulcer healing, depending upon the increased release of proinflammatory cytokines [e.g. TNF-alpha] and the attenuation of angiogenesis Insulin reversed this impairment of ulcer healing in diabetic rats, mainly due to the enhancement of angiogenesis and reduction in expression of TNF-alpha in the ulcer area. Phosphodiesterase [PDE] inhibitor [pentoxifylline], via suppressing TNF-alpha and hydroxymethylglutaryl coenzyme A [HMG-CoA] reductase inhibitor [simvastatin]. via suppressing TNF-alpha and increasing VEGF, are beneficial in enhancing gastric ulcer healing. These findings support the notion that impairment of healing of gastric ulcers in DM results from impairment of angiogenic response of the gastric mucosa to injury together with upregulotion of gastric TNF-alpha and suggest the feasibility of a novel treatment strategy for patients in whom impairment of ulcer healing complication of DM

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

possible cytoprotective effect of vitamin E in aluminium-induced liver damage in rats

The aim of the present work was to assess the possible pro-oxidant effects of Al on rat liver, as well as the possible protective role of exogenous vitamin E. 40 male Sprague Dawley rats were divided into 4 groups each including ten animals: group I served as a control, group II treated with Al alone, group ill treated with Al and vitamin E, and group IV treated with vitamin E alone. For 4 weeks, Al and vitamin E were given in a dose of 20 mg/kg body weight. After 4 weeks, blood samples were collected for estimation of Al, vitamin E, and liver enzymes ALT and AST. Liver tissue homogenates were used for determining ROS and All. After 4 weeks of Al administration, Al levels increased in both plasma and liver. Treatment with Al alone significantly increased plasma levels of liver enzymes AST and ALT. On the other hand, the presence of vitamin E with Al caused a decrease in these elevated plasma liver enzymes yet it did not reach the control value. ROS was increased in liver homogenates from rats treated with Al compared to controls. This effect was attenuated by exogenous vitamin E administration. Oxidative stress clearly played a key role in Al-induced liver pathogenesis .Moreover; vitamin E supplementation alleviated the harmful effects of Al on all the measured parameters and improved liver functions

Respiratory chain activity in myopathies

Aim: The present study was conducted to find out whether disturbances of respiratory chain enzymes were involved in the pathogenesis of three types of myopathy: Duchenne muscle dystrophy [DMD], limb girdle muscular dystrophy, and steroid-induced myopathies; to assess the extent and nature of these deficits among the three myopathic groups, and to investigate the relation between the severity of muscular disorders- assessed by creatine phosphokinase [CPK] level- and the extent of respiratory chain impairment. Subjects and Fourty myopathic patients as group I [GI]; 10 DMD [GIA], 16 limb girdle dystrophy [GIB], and 14 steroid-induced myopathy [GIC]; and 20 healthy controls as group II [GII] that matches the general features of GI. Cases and controls were subjected to history taking as well as physical examination. Diagnosis of myopathy was established using routine motor and sensory conduction study and concentric needle EMG. Cases and controls were subjected to estimation of respiratory chain complexes; RCI, RCII, RCIII, and RCIV, in neutrophil mitochondria. Results were analysed using t-test between GI and II and F test in between GIA, GIB and GIC. The results revealed a significant decrease of all respiratory chain complexes; RCI, RCII, RCIII, and RCIV; in GI as compared to controls [2878.04 +/- 1085.96 versus 5867.93 +/- 1000.03 micro mol/min/mg protein for RCII, 549.7 +/- 21574 versus 80382+/=119.41 micro mol/min/mg of protein for RCIV, 60654 +/- 162.35 versus 95949 +/- 136.14 micro mol/min/mg of protein for RCIII, and 58.73 +/- 18.08 versus 97.88 +/- 19.06 micro mol/min/mg protein for RCIV. On comparing the 3 subgroups; IA, IB, and IC; the following was found [1] A significant decrease of GIC when compared to GIA and when compared to GIB and when compared to GIB as regards RCI [3234.526 +/- 716.363, 3385.13 +/- 218.603, and 2043.894 +/- 631.967 micro mol/min/mg protein for GIA. GIB, and GIC, respectively, F - 4.331, and P = 0.03]; [2] A significant decrease of GIA when compared to GIB and when compared to GIC as regards RCIV [42.584 +/- 22,9177, 66.947 +/- 10.861, and 60.88 +/- 1532 micro mol/min/mg protein for GIA, GIB, and GIC, respectively, F = 3.67 and P = 0.47]. [3] Nonsignificant difference between GIA, GIB and GIC as regards RCII, and RCIII. Using multiple linear regression analysis between respiratory chain enzymes and CPK, only RCIV showed a statistically significant correlation with CPK. Conclusions: Myopathy could be associated with alterations in respiratory chain enzyme complexes that result in effort intolerance. Such an alteration could be detected in neutrophil mitochondria by an easier noninvasive technique. RCIV could be used as a predictive marker for the occurrence of muscle damage in myopathy

Altered serum leptin and lipoproteins pattern in Egyptian patients with liver cirrhosis

Aim: Leptin is implicated in the regulation of several body functions including liver metabolism, in addition, the liver plays a key role in serum lipoproteins synthesis and metabolism. This study aimed to assess serum leptin levels, serum lipids and lipoproteins pattern in Egyptian patients with liver cirrhosis, and to relate the findings with the body composition and the severity of liver disease. Subjects and Thirty male patients with liver cirrhosis, together with 15 age and sex-matched control subjects were enrolled in the study. Clinical and biochemical investigations included: clinical examination, ultrasonic scanning and /or liver biopsy, liver function profile, viral markers, measurement of serum leptin, serum lipids, and serum apolipoproteins B and A-1. Sixteen patients were positive for hepatitis C antibodies, 9 were positive for hepatitis B surface antigen, and 5 were positive for both viral markers, while schistosomal hepatic fibrosis was present in 22 patients. Serum leptin was significantly decreased in patients compared to controls [mean +/- SD= 1.34 +/- 0.16 and 3.94 +/- 0.55 ng/ ml respectively; P< 0.05], it correlated directly with BMI in both patients and controls [r= 0.60; P< 0.01 and r= 0.337; P< 0.05 respectively] and with the triceps skinfold thickness in both groups [r= 0.384 and 0.376 respectively; P< 0.05], but did not correlate with the severity of liver disease. Serum lipids showed a significant decreased levels in both TC and TG in cirrhotic patients compared to controls [mean +/- SD = 172.00 +/- 17.24 and 86.60 +/- 64.51 mg/dl in patients versus 192.27 +/- 32.33 and 136.13 +/- 70.86 mg/dl in controls; P < 0.05], serum HDL-C and LDL-C levels showed non significant differences between the two groups, while apo A-1 and apo B were significantly lower in patients than controls [mean +/- SD= 130.84 +/- 40.64 and 38.37 +/- 15.34 mg/dl in patients versus 197.00 +/- 42.05 and 53.39 +/- 3.79 mg/dl in controls; P< 0.001]. Serum lipids did not correlate with the severity of liver disease, however, apo A-1 correlated directly with both prothrombin activity and serum albumin [r= 0.368 and 0.372 respectively; P< 0.05], and inversely with both ALT and AST [r= -0.472; P< 0.01 and r= -0.448; P< 0.05 respectively]. Conclusions: It was concluded that in Egyptian patients with liver cirrhosis, serum leptin level was decreased and did not correlate with serum lipids nor with the severity of liver disease, however it correlated directly with BMI and triceps skinfold thickness in both patients and controls. Serum TC, TG, apo B, and apo A-1 levels were decreased significantly in patients than controls. Although no correlation was found between serum lipids and the degree of liver function, yet, apo A-1 correlated directly with both prothrombin activity and serum albumin, thus it could be regarded as a good parameter for synthetic liver function