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

Heart rate variability [HRV] in young healthy females with primary dysmenorrhea

Primary dysmenorrhea affects more than 70% of young women. It may be associated with some degree of autonomic disturbances. Heart rate variability [HRV] is noninvasive technique to assess the cardiac autonomic balance. Low HRV reflects reduced parasympathetic [vagal] activity and/or elevated sympathetic tone and is considered an important cardiovascular risk factor. Was to investigate whether, in young healthy females with primary dysmenorrhea, alterations of cardiac autonomic function can be observed and, if so, whether these alternations affect their blood pressure and/or influenced by the body mass index BMI or the waist hip ratio WHR [visceral adiposity]. Twenty healthy young women participated in this study divided into two groups according to the results of The Menstrual Distress Questionnaire [MDQ]. Group 1 consisted of ten volunteers with primary dysmanorrhea. Group 2 [control] consisted often young females who where free from premenstrual symptoms. All subjects examined in the physiology laboratory, King Abdel Aziz University, 12 h post-prandial three times during a month-long screening period: menses [day 1-5]; ovulation [day 11-21] and luteal [day 21-34]. Anthropometric measurements height, weight, body mass index [BMI], waist, hip circumference, and waist hip ratio [WHR], in addition to arterial blood pressure [ABP] were evaluated each time. The ANS activity was assessed by means of HRV. Time domain [heart rate [HR], RR interval[RR], the standard deviation of the normal RR-interval [SDNN], the root-mean square of differences of successive normal RR intervals [rMSSD], and power spectral analysis [high frequency [0.15-0.40 Hz] [HF]; low frequency [0.04-0.15Hz] [LF], and LF/HF ratio]] during supine resting condition. The two groups matched as regard age, and BMI. However, the group 1 had higher WHR compared to group 2. The ANS activity significantly changed [reduced vagus and increased sympathetic activities] in the luteal phase compared to the menses and follicular phases in Group L In addition, Group 1 possessed lower parasympathetic nerve activity [rMSDD and HF] throughout the cycle and higher sympathetic nerve activity in the late luteal phase compared to Group 2. The present study have demonstrated that although young females with primary dysmenorrhea had no significant changes in their HR and mean ABP comparing with matched group "as regards age and BMI" females with painless cycle, however, they had significant alteration in their cardiac autonomic activity in a form of decreased HRV with manifested fluctuation during the menstrual cycle

influence of exposure to light and dark environment on platelet concentrates during storage

There is increased demand for stored platelet concentrates [PCs] for therapeutic transfusions. Despite all efforts to simulate the physiological environment Loss of the platelet functionality due to platelet activation occurs during preparation and storage of PCs "platelet storage lesion" [PSL]. Intensive investigations are currently undertaken to improve the storage of PCs however, the quality of the stored platelets is still questionable. Was to compare the influence of light and dark environment on the physiological function of routinely prepared random-donor PCs. And to teste the changes in platelet indices [platelet count [PLT count], and mean platelet volume [MPV]J, pH, lactic acid dehydrogenase [LDH] levels, the release of alpha-granule content through cell surface expression of specific activation-dependent antigens GPIIIa [CD 61], P- selectin [CD62] and, platelet membrane glycoprotein GP Ib [CD42 alpha] and GP IIb-IlIa [PAC1] in the PCs. Platelet concentrates were prepared using 450 ml of whole blood collected from 20 adult random volunteer male donors divide into two bags. The first one was left in continuous light exposure [light group]. The other one was raped in aluminum foil to avoid exposure to light [Dark Group]. Both bags were placed at room temperature for 5 days Platelet indices [PLT, MPV], pH, lactic acid dehydrogenase levels in addition to the expression of activation antigens CD61 and CD62 along with modulation of platelet membrane glycoproteins [GP] Ib [CD42 alpha] and IIb-IIIa [PAC1] in the PCs were measured on day 1 and day 5 of the storage period for both groups. The differences [delta] in these parameters for both groups were compared. The platelet indices [delta PLT count, and delta MPV "which reflects change in the platelet morphology"], delta pH, delta LDH, in addition to the activation markers [delta CD42alpha, CD61, CD62, and delta PAC1] were significantly lower in the dark Group compared with the Light group The most significant changes were in the level of the released LDH [P= .000] and the production of CD62 [[P= .00]. The PLT count significantly decreased in both groups after 5 days of storage. However, the platelets MPV significantly decreased in the light group only, which may be due loss of the large sized platelet during storage. There was statistically significant increase in LDH production in the light group [P= .000] "which is used as a marker for PLT lysis", in addition their pH also significantly decreased. In the dark Group, although there was a significant increase in the production of LDH, but it was statistically less significant than in the light group [P= .0] so that it may be buffered by the plasma and did not reflect on the changes in the pH in this group. There was a statistically significant influence of pH changes "as an independent variable" in the PCs on the changes in MPV "as a dependent variable" in both groups. However, there was no such influence regarding the PLT count. In the light group, the platelet activation markers CD61, CD62, and PAC1 were significantly increased in the PCs at day 5 compared to day 1. In addition, CD42alpha, was significantly decreased. While in the dark Group, there were no significant changes in those parameters, except for PAC1 which was significantly decreased although difference was less than that in the light group. In this study, platelets stored in light environment seemed to be more active with more platelet storage lesion [PSL], than platelets stored in dark environment. Platelet activation was associated with an increase in the, pH, LDH production and release of alpha-granule content and modulation of platelet surface glycoproteins. All these parameters may affect the post infusion quality of the stored platelets

Pathophysiological mechanism of renal injury induced by cardiopulmonary bypass [CPB]: is there a possible protective role of N-acetylcysteine [NAS] as a radical scavenger?

Despite improvements in surgical techniques, myocardial protection, and perioperative care, acute renal failure [ARF] after cardiopulmonary bypass [CPB] represents one of clinician problems as it associated with unacceptable high mortality. Oxygen free radicals are important components that may be involved in the pathophystological tissue alterations observed during ischemia/reperfusion [I/R]. we evaluated the possible renoprotective role of N-acetylcysteine [NAC] as a free radical scavenger against oxidative stress during I/R injury of the kidney induced by CPB in patients with normal renal function compared with placebo, a prospective randomized study where thirty patients of ischemic heart disease who underwent coronary artery bypass grafting [CABG] were divided into two groups. The study group [n=15] with mean age 61.20 +/- 8.01 received NAC intravenously in a dose of 50 mg/Kg/day, given as 25 mg/Kg' twice daily for successive 3 days, and the placebo group [n=15] with mean age 60.60 +/- 8.41 received 0.5 cc/kg saline twice in 24h for three days before CABG. Intraoperative as well as the clinical outcome in both groups such as the type of graft used perioperative myocardial infarction, pump time aortic cross clamp time, the need for intra-aortic balloon, incidence of arrhythmias, and the of ICU stay were evaluated. Arterial blood sampling were collected from both groups after induction of anesthesia, and, 241 after cessation of CPB to measure serum creatinine, creatinine clearance [as markers of glomerular function]. Biochemical assay performed to measure Myeloperoxidase activity [MPO], interlukin-6 [IL-6] as an indicator of inflammation, malondialdhyde [MDA] as an index of lipid peroxidation and C-reactive protein [CRP] level "acute phase protein level The blood sampling for those biochemical studies was withdrawn after induction of anesthesia [t[0]], them 10 min [t[10]], and 30 mm [t[30]] on bypass, at the end of surgery [t[end]] and after 6h [t[6h]] and 24h [t[24h]] after cessation of CPB. There was no significant differences between both group regarding operative, and post operative data except for the duration of ICU stay which was significantly longer in the placebo group MPO activity was significantly higher levels in placebo group compared with the study group starting from t[0] and throughout the study. P=0.001 at t[0]], [t[10]], [t[30]], t[end], t[6th] and t[24h] In addition, its activity had not returned to the preoperative level at 24h P=0.0, while in the study group there was no significant difference in MPO activity at and 24h after cessation of CPB. MDA value started to increase 10 min after commencement of CPB in the placebo compared with the study group, and remained significantly higher throughout the study. P=.03,.02, .001, .01, .01 at t[10], [t[30]], t[end], t[6th] and t[24h] respectively. Similar to the MPO, MAD value had not returned to the preoperative level at t 24h in the placebo group P=.00 Regarding IL-6 levels. The study group patients had significantly lower levels than the placebo at the periods of t30, tend, and t6h. P=.03,.00,.00 respectively. However, 24h after cessation of CPB, the IL-6 levels were similar in both groups. CRP also increased significantly in the placebo group starting 30 mm after commencement of CPB and throughout the study duration P=.001,. 001, .02, .001 at t[end], t[6th] and t[24h] time periods respectively. However CRP levels had not returned to the basal levels in both study and placebo groups after 24h of CPB cessation P=.001. In the placebo group, serum creatinine SC increased significantly from 0.69 +/- 0.32 mg/dL tol.25 +/- 0.33 mg/dL24h after cessation of CPB. P=.001. While the study group showed no significant ehange in its level. Moreover after 24h of CPB cessation the placebo group had significantly higher SC level than the study group .P=.001, In addition to SC elevation in the placebo group, creatinine clearance CC also significantly decreased after 24h compared to the basal value. P=.01, and similar to SC, CC decreased significantly in the placebo group after 24h compared to the study group P=.02. In conclusion, we believe that preioperative administration of NAC has a beneficial protective effect against renal injury induced by ischemia reperfusion due to CBP particularly in patients with normal preoperative renal function

Fecal calprotectin, novel index for assessing the pathophysiological mechanisms of inflammatory bowel disease in rats treated by glutathione

In this study, the role of fecal calprotectin [FC] as a recent non-invasive diagnostic aid of inflammatory bowel disease [IBD] was evaluated and the effect of glutathione as a preventive and therapeutic factor in acetic acid induced colitis has been studied. Forty albino rats were divided into four groups; group I: acetic acid induced colitis group. Group II: before the induction of colitis, rats were given a preventive dose of glutathione [200 mg/kg, i.p]. Group III: after colitis induction rats were treated with glutathione for one week [50 mg/kg,i.p.]. Group IV: control group. At the end of experimental period, rats were sacrificed and fecal caiprotectin was assessed in the different groups, the level of antioxidant system in the intestine was evaluated and the severity of inflammation was histopathologically scored. Colitis induction was associated with significant increase in the colonic level of FC, which was significantly reduced with glutathione prevention. Glutathione level was decreased significantly in the intestine after colitis induction, however, it was significantly high in the prevention 'group. There was significant reduction in the antioxidant enzyme system after colitis induction. However, glutathione prevention was associated with higher antioxidant enzymes compared to treatment. Various histopathological changes as inflammation, ulceration and dysplasia were detected after colitis induction, group III, however, showed no ulceration and mild inflammation. Fecal caiprotectin can be used as a non-invasive and early marker for IBD. Glutathione prevention appeared to be beneficial for the acute stage of IBD than glutathione treatment. Moreover, intestinal antioxidant enzymes were correlated negatively with FC level

possible role of visceral adiposity in development of pro-atherogenic lipid profile in normal overweight young Egyptian female adults [a possible involvement of adiponectin and leptin]

The metabolic abnormalities that often co-exist with overweight and obesity appear to be mediated largely by visceral fat accumulation. Visceral fat is very different from the subcutaneous fat, and may be responsible for pro-atherogenic lipid profile in apparently healthy people. to examine the influence of visceral fat and "not obesity" on the lipid profile. In addition, to test the relation between adipocytokines [leptin and adiponectin] and lipid profile in overweight young healthy Egyptian adult females. Forty healthy young overweight females participated in this prospective cohort study, their age ranged from 19-23 Y, and their body mass index [BMI] ranged from 25-30 Kg/rn2. All the participants were completely healthy with no history of thyroid dysfunction; diabetes; or cardiovascular, renal, or liver dysfunction. No participant had taken medication for at least 3 months before the study, and none were dieting or smoking. The anthropometric measurements were made be the same observer in the physiology laboratory, Alexandria University, they induced: height, weight, body mass index [BMI], waist, hip circumference and waist hip ratio [WHR]. Fasting venous blood was collected to measure adipocytokines [leptin and adiponectin] and lipid profile [total cholesterol [TC], total triglycerides [TG], high-density hpoprotein cholesterol HDL-C, low-density lip oprotein cholesterol [LDL-C] and the LDL-C/HDL-C ratio was calculated as the atherogenic index. Then the examined subjects were divided into two groups based on their Waist/hip ratio [WHR]. Group 1 [n 25 with WHR>0.8], and group2 [n=15 with WHR

Beneficial effects of angiotensin converting enzyme inhibitors captopril and enalapril on experimentally induced colitis in rats

Increasing evidence supports an association between inflammation and angiotensin converting enzyme [ACE]. The aim of this study was to examin the efficacy of ACE inhibitors [ACEIs] namely, captopril and enalapril on acetic acid induced colitis in rats. Colitis was induced by intracolonic injection of 2 ml of 3% acetic acid. Eighty rats were studied in this study, divided into: two main groups, group 1, 40 rats of long duration of inflammation and treatment and group II, 40 rats of short duration of inflammation and treatment. Each group was subdivided into 4 subgroups. 10 control rats, 10 rats injected intracolonic with acetic acid [acetic acid untreated rats], 10 rats injected intracolonic with acetic and plus oral administration of captopril [captopril treated rats], and 10 rats injected intracolonic with acetic acid plus oral administration of enalapril [enalapril treated rats]. Captopril and enalapril were given 2 days after induction of colitis and continued daily for 3 weeks in group I, and for 2 days before and 2 days after induction of colitis in group II. Intracolonic acetic acid injection produced a significant inflammation, assessed by the ulcer index score, the weight of the colon and the colonic tissue level of myeloperoxidase enzyme, in acetic acid untreated rats of both groups. These parameters were significantly improved by ACEIs administration. The effect of captopril in group I was more potent than enalapril, while in group II both ACEIs had the same effect. in group II captopril succeeded to inhibit the change in the weight of the colon or the tissue level of myeloperoxidase enzyme. The colonic tissue level of glutathione reductase was significantly reduced in acetic acid untreated rats of both groups. This reduction was significantly inhibited by ACEIs administration in both groups, with better results with captopril treated rats than enalapril ones in group I. Also the efficacy of captopril in group I was more significant than in group II in improving the glutathione reductase colonic tissue level. Captopril and enalapril also sigificantly improved the level of tissue lipid peroxides, which was significantly elevated in acetic acid untreated rats of both groups. However, the efficiency of captopril in reducing the lipid peroxides level was mor significant than enalapril in both groups. this study provides an evidence that the two ACEIs particularly captopril confers a good anti-inflammatory activity against colitis in rats leading to improvement of oxidative stress induced by the inflammatory insult