Subclinical central neuropathy in type II diabetes mellitus

To evaluate central nervous system neuropathic changes in patients with type 2 DM with and without peripheral neuropathy. Thirty patients with type 2 DM were included. They were equally divided into two groups: those with clinical and electrophysiological findings of peripheral neuropathy [Group 1], and those without [group 2]. Fifteen healthy individuals were included as a control [group 3]. All groups were subjected to fasting plasma glucose, glycated hemoglobin [HbA1c] and other necessary tests, in addition to the electrophysiological study including: Somatosensory evoked potentials [SEP], motor evoked potentials [MEP], visual evoked potentials [VEP] and brainstem auditory evoked potentials [BAEP]. Group 1 had statistically significant higher mean values of fasting plasma glucose, HbA1c, urinary albumin excretion [UAE] and serum creatinine compared with group 2. Both diabetic groups had similar changes in VEP P100 latency and its amplitude, MEP central motor conduction time, amplitude percentage quotient and duration of the MEP, and BAEP wave II latency, with statistically significant differences compared to healthy controls. There was a statistically significant delay in all of the BAEP waves' interpeak latencies only in group 1. The other tested parameters of central neuropathy showed statistically significant differences between all studied groups. A statistically significant positive correlation was observed between some of the studied parameters of central neuropathy in diabetic patients and each of the patient age, duration of diabetes, HbA1c, serum total cholesterol, serum triglycerides and UAE. Central neuropathy in type 2 diabetics is not uncommon even in absence of peripheral neuropathy. It is related to the patient's age, duration of diabetes, glycated hemoglobin value, dyslipidemia and diabetic nephropathy. The use of more than one modality of the electrophysiological tests can buffer the fallacies of a single mode

Subclinical central nuropathy in thype 2 diabetes mellitus

Involvement of the peripheral and autonomic nervous systems is frequently encountered in diabetes mellitus [DM]. However, there is a paucity of data regarding central neuropathy in DM. To evaluate central nervous system neuropathic changes in patients with type 2 DM with and without peripheral neuropathy. The study included three groups; group 1: Fifteen patients with type 2 DM with clinical and electrophysiological findings of peripheral neuropathy, group 2: Fifteen patients with type 2 DM without any clinical or electrophysiological evidence of peripheral neuropathy and group 3: Fifteen healthy subjects as a control group. All groups were age and sex matched and subjected to physical examination, laboratory investigations including: Complete blood cell count, fasting plasma glucose. glycated hemoglobin [HbAlc], serum lipid profile, renal fitnctions and other necessary tests, in addition to the electrophysiological study including: Somatosensory evoked potentials [SEP], motor evoked potentials [MEP], visual evoked potentials [VEP] and brainstein auditory evoked potentials [BAEP]. Group I had a statistically significant higher mean values of fasting plasma glucose, HbAlc, urinary albumin excretion [UAE] and serum creatinine compared with group 2. Both diabetic groups had similar changes in VEP P100 latency and its amplitude, MEF central motor conduction time, amplitude percentage quotient and duration of the MEP, and BAEP wave II latency, with statistically significant differences compared to healthy controls. There was a statistically significant delay in all of the BAEP waves interpeak latency only in group 1. The other tested parameters of central neuropathy showed statisticasly signficant differences between all studied groups. A statistically significant positive correlation was observed between some of the studied parameters of central neuropathy in diabetic patients and each of the patient age, duration of diabetes, HbA1c, serum total cholesterol, serum triglycerides and UAE. Central neuropathy in type 2 diabetics is not uncommon even in absence of peripheral neuropathy. It is related to the patient age, duration of diabetes, glycated hemoglobin value, dyslipidemia and diabetic nephropathy. The use of more than one modality of the electrophysiological tests [multimodal evoked potential studies] can buffer the fallacies of a single mode and is advisable in evaluating central neuropathy in patients with type 2 DM. Early diagnosis of central neuropathy is recommended to offer an early opportunity for a proper management

Study of serum and urinary vascular cell adhesion molecule-1 in patients with lupus nephritis

Systemic lupus erythenwtosus [SLE] is a chronic multisystem autoimmune disease. Renal involvement [lupus nephritis; LN] is a frequent and potentially serious complication that worsens morbidity and mortality. LN is a chronic disease with remissions and relapses, and this is important to predict aiming for optimal management. However, a consistent approach still has not been adopted. To study serum and urinary' soluble vascular cell adhesion molecule-I [sVCAM-1] levels in patients with lupus nephr itis and their correlation with the disease activity, laboratory data and renal pathology. Twenty three patients with lupus nephritis and twenty age, sex and ethnic matched healthy controls were subjected to physical examination, abdominal ultrasound, laboratory investigations including: Complete blood cell count, eiythrocyte sedimentation rate [ESR], renal functions, urine analysis, 24-hour urinary protein excretion, liver functions, serum antinuclear antibody [ANA], anti-double stranded deoxyribonucleic acid [anti-dsDNA], serum and urinaly soluble VCAM-1 [sVCAM-1] and other necessary investigations. Percutaneous renal biopsy, with histopathological assessment and determination of activity and chronicity indices, was done for all patients. LN patients had a statistically sign[ficantly higher serum [S] and urinary sVCAM-1, S. ANA, S. antidsDNA, ESR, blood urea, S.creatinine, S.uric acid, 24-hour urinary protein excretion and S. alanine and aspartate aminotransferases, and a statistically significantly lower hemoglobin concentration, S. albumin and creatinine clearance tjian healthy controls. Renal biopsy assessment showed World Health Organization [WHO] class 11 LN in 3 patients, class iii in 4 patients, class IV in 13 patients and class V in 3 patients. S. sVCAM-1 was statistically significantly higher in classes III, IV and V LN than controls and in class IV LN than class II. Urinary sVCAM-1 was statistically signficantly higher in classes II, III, IV and V LN than controls and in classes III and IV LN than class II. Anti-dsDNA was statistically significantly higher in classes III and IV LN than controls, with no statistically significant differences in between the WHO classes. S. and urinary sVCAM-1 showed a statistically wreianon with the total SLEDAI score, pathologic activity index and urinary protein excretion, with a significantly positive correlation between S. and urinary sVCAM-1. A significantly negative correlation was present between S. sVCAM-1 and hemoglobin concentration, and between urinary sVCAM-1 and S. albumin. As regards anti-dsDNA, no statistically significant correlations were observed. In patients with LN, serum and urinary sVCAM-1 are positively correlated with the total SLEDAI score, pathologic activity index and urinary protein excretion. Measurement of their levels, specially urinary sVCAM-1, seems to be valuable in evaluating LNpatients. Further studies are recommended to assess the role of repeated measurements. Whether a blockade of soluble VCAM-1 could have a therapeutic implication in LN remains to be investigated

Expression of apoptotic markers BCL-2 and bax chronic hepatitis C virus patients

Despite advances in the knowledge of the molecular virology of hepatitis C virus [HCV], the mechanisms of hepatocellular injury in HCV infection are not completely understood. The available reports are in favor of a destructive mechanism mediated by the host immune system rather than a direct cytopathic effect of the virus. Some viral infections influence the susceptibility of peripheral blood mononuclear cells [PBMC] to apoprosis. This could lead to insufficient antiviral immune response, persistent viral infection and disease progression. To evaluate the expression of apoptotic markers Bcl-2 and Bax in PBMC in chronic HCV patients. The study included three groups; group 1. Fifteen chronic HCV patients with biopsy-proven liver cirrhosis and ascites; among this group, five patients had cryoglobulinemia [group la] and the remaining ten patients had no cryoglobulinemia; group lb. Group 2: Ffteen chronic HCV patients without any suspected evidence of liver cirrhosis and group 3: Fifteen healthy subjects as a control group. All groups were age and sex matched and subjected to physical examination, abdominal ultrasound, laboratory investigations including: Complete blood cell count, liver and renal functions, Hepatitis B suiface antigen, anti-HCV antibodies, serum cryoglobulins, detection of apoptotic markers Bcl-2 and Box in peripheral blood lymphocytes, other necessary tests and in addition serum HCV RNA levels in the patient groups, by quantitative polymerase chain reaction [PCR] assay, and peritonealfluid analysis in group 1 patients. Group 1 chronic HCV patients [with cirrhosis and ascites] had a statistically significantly low Bcl-2 percentage expression in peripheral blood lymphocytes, a significantly high Bax expression and a significantly decreased Bcl-2/Bax ratio compared than healthy controls, with a statistically significant difference between group la [cryoglobulinemic] and group lb [non-cryoglobulinemic]. Group 2 patients had a statistically significantly increased Bcl-2 percentage expression, a signcantly decreased Bax expression and a significantly increased Bcl-2/Bax ratio than controls. In chronic hepatitis C virus patients [group 1 and 2] Bcl-2 expression showed a statistically significant positive correlation with S. albumin, prothrombin activity, ALT and the Bcl-2/Bax ratio and a significantly negative correlation with S. total blirubin, blood urea and the Bax expression. Bax expression showed a statistically significant positive correlation with S. total blirubin, blood urea and S. creatinine and a significantly negative correlation with S. albumin, prothromhin activity, ALT and the Bcl-2/Bcvc ratio. Bcl-2/Bax ratio showed a statistically significant positive correlation with S. albumin, prothrombin activity and ALT and a significantly negative correlation with S. total blirubin, blood urea and S. creatinine. Chronic HCV patients exhibit a dysregulation of apoptosis, in the form of a down regulation of Bcl-2 expression together with an increasd Bax expression and, a decreased Bcl-2/Bax ratio in peripheral blood lymphocytes, with the disease pro gression. This provides an insight into the pathogenesis of chronic HCV infection and may open new avenues in the management of the disease

Evaluation of some platelet functions and platelet membrane glycoproteins in uremic, hemodialysis and renal transplant patients

The hemostatic defect of chronic renal failure [CRF] is well recognized. Increased bleeding has been attributed to platelet dysfunction. However, the available reports are controversial. To study platelet aggregation and glycoprotein receptors' [GP] expression in a well identified population with CRF. 25 patients with advanced CRF on conservative treatment [CRF group], 25 patients on regular hemodialysis [HD group], 25 renal transplant patients [Tx group], and 20 age-, race- and sex-matched healthy controls [control group] were subjected to complete physical examination, complete blood count, bleeding time [BT], renal functional parameters and other necessary laboratory tests, in addition to estimation of platelet aggregation in response to adenosine 5-diphosphate [ADP] and ristocetin as well as GPIb, GPIIb, and GPIIIa receptors' expression using fluorescein isothiocyanate-conjugated monoclonal antibodies CD42b, CD41 and CD62, respectively and a flow cytometer. BT was prolonged in both CRF and HD groups [P<0.001], and was not attributed to a decrease in platelet count. Both CRF and HD patients had similar, but significantly decreased maximum percentage of platelet aggregation induced by either ADP or ristocetin compared with Tx and healthy control groups [P<0.001]. GPIb expression was significantly decreased in the CRF group than the Tx and healthy control groups [P<0.05], while HD group showed non significant difference when compared with CRF, Tx or control groups. GPIIb and GPIIIa showed a highly significant decreased expression in both CRF and HD groups compared with Tx and healthy control groups [P<0.001], with no significant difference in between both uremic groups. An inverse correlation was observed between serum creatinine and GPIIb [r=-0.641, P=0.023] and GPIIIa [r=-0.545, P=0.031] receptors' expression in CRF patients versus no correlation in HD patients. The results of the studied parameters in Tx group were comparable to healthy controls. Uremic patients have decreased platelet aggregability and decreased GP receptors' expression [mainly GPIIb and GPIIIa], denoting that platelet dysfunction is at least partially contributing to their hemorrhagic problem. The observed defects were not corrected by regular HD. Renal transplantation seemed to be a better choice

Study of serum activin a and follistatin in post renal transplant patients: correlation with renal hemodynamics, graft function and survival

Chronic allograft nephropathy [CAN] is a devasting long-term complication of kidney transplantation that is responsible for a significant proportion of graft loss. Activin A, a member of the transforming growth factor-beta [TGF- beta] superfamily of proteins, has a pro-fibrotic activity. The biologic effects of activin A are countered by follistatin, which is a high affinity extracellular binding protein for activin A. To study serum activin A and follistatin levels in the post-renal transplant patients and their correlation to renal hemodynamics, graft function and survival. The study included 20 post-renal transplant patients [Group I] and 20 age and sex matched healthy subjects [Group II] as controls. Serum activin A and serum follistatin were measured by enzyme linked immunosorbent assay [ELISA]. Serum C-reactive protein [S.CRP] was measured by turbidimetry. Serum and urinary alkaline phosphatase [S.ALP, U.ALP] were measured by spectrophotometry. Renal henwdynamics were evaluated by duplex Doppler ultrasonography; resistive and pulsatility indices [RI, PI] were calculated. Ten patients were categorized as chronic allograft nephropathy [CAN; group Ia]. The other ten patients had a stable renal function [non-CAN; group Ib]. There was a statistically significant increase in serum activin A [S.activin A], S.ALP, S.CRP, RI and PI and a statistically significant decrease in U.ALP and follistarin/activin ratio in patients with CAN than healthy controls, versus a statistically significant difference only in S. activin A and follistatin/activin ratio between non-CAN and controls. There was no statistically significant differences in S. follistatin between the studied groups. In post-renal transplant patients, S.activin A showed a statistically significant positive correlation with S. creatinine, S.CRP, RI and PI versus a statistically significant negative correlation with creatinine clearance, U.ALP and follistatin/Activin ratio. U.ALP showed a statistically significant positive correlation with creatinine clearance versus a statistically significant negative correlation with S. creatinine, S. activin A, S.CRP, RI and PI. Enhanced activin A activity together with normal follistatin level and the decrease in follistatin/activin ratio in post-renal transplant patients, showed that there is a dysregulation of activin-follistatin axis with the increase of the unbound biologically active activin A with deterioration of renal function. Also, there is an increased activity of ongoing inflammation accompanied by impaired renal function among renal allograft recipients that led to enhanced renal fibrosis and a degree of tubular dysfunction

Study of pro-hepcidin level and renal functions in nephrotic syndrome, chronic renal failure and hemodialysis patients

Anemia is associated with worse outcomes in patients with chronic kidney disease [CKD]. Hepcidin is a recently discovered protein produced mainly by the hepatocytes as a pre-prohormone, pre-prohepcidin. It is a key regulator of iron metabolism in different iron disorders. To study serum pro-hepcidin levels in nephrotic syndrome [NS], chronic renal failure [CRF], and hemodialysis [HD] patients. The study included 4 groups. Group I: 20 patients with NS, group II: 20 patients with CRF on conservative treatment, group III: 20 patients on regular HD, and group IV: 20 healthy subjects as a control group. All groups were age and sex matched, and subjected to physical examination, abdominal ultrasound, and laboratory investigations including: Complete blood cell count, serum iron, iron indices, serum pro-hepcidin, serum high sensitivity C-reactive protein [hs-CRP], renal functions, liver functions, and other necessary tests. CRF and HD patients had a statistically significant higher mean serum pro-hepcidin than NS patients and controls [P <0.001], with no statistically significant difference between the NS and control groups. All patient groups had a statistically significant higher serum hs-CRP, and a significantly lower hemoglobin concentration, serum iron, and transferrin saturation compared with controls [P<0.001]. The mean serum ferritin was statistically significantly increased in the HD group only [P <0.001]. Serum pro-hepcidin showed a statistically significant positive correlation with serum hs-CRP [a marker of inflammation], serum ferritin, blood urea and serum creatinine in all patient groups, with serum uric acid in NS and CRE patients, and with serum albumin only in NS patients. It showed a statistically significant inverse correlation with serum iron and transferrin saturation in all patient groups, with hemoglobin concentration and creatinine clearance in NS and CRF patients [HD patients were anuric], and with urinary albumin excretion only in NS patients probably due to increased pro-hepcidin loss with the proteinuria. In patients with CKD, the presence of a chronic inflammatory status offsets the inhibitory effect of anemia on pro-hepcidin production with a net increase in serum pro-hepcidin levels. This inflammation related dysregulation of pro-hepcidin might result in a functional iron deficiency, thus aggravating the anemia. Pro-hepcidin is unlikely to be beneficial in monitoring anemia of CKD. However, it could be a future therapeutic target in managing anemia in these patients

Evaluation of calcitonin gene- related peptide in hypertension: a clinical and experimental study

Calcitonin gene-related peptide [CGRP] is an extremely potent vasodilator neuropeptide that is widely distributed in the perivascular sensory nerves. To clarify the exact role of CGRP in hypertension in both essential hypertension patients and experimentally induced hypertension in rats. 15 patients with untreated essential hypertension and 15 age and sex matched healthy controls were subjected to physical examination, resting ECG, two-dimensional echocardiography, abdominal ultrasound, Doppler study of renal vessels, and laboratory tests including estimation of serum CGRP, malondialdehyde [MDA; as an oxidative stress marker], renal functional parameters and other essential investigations. In the experimental study, hypertension was induced in 15 male albino rats by uninephrectomy and 0.9% saline in drinking water for 6 weeks [uninephrectomy-salt model]. 15 matched healthy male albino rats [controls] were sham operated and given tap water. Rats were subjected to mean arterial pressure [MAP] measurement, using a pressure transducer, and laboratory tests including serum CGRP, MDA and renal function tests. Compared with normotensive controls, essential hypertension patients had a significantly higher mean serum creatinine [P= 0.011], urinary albumin excretion [UAE], and serum MDA versus a significantly reduced CGRP [P<0.001]. Echocardiography revealed subtle hypertensive findings in only 3 patients. All ECGs were normal. Hypertensive rats showed a significantly higher mean blood urea, serum creatinine, UAE, serum MDA, and also CGRP than control rats [P<0.001]. In hypertensive patients, the only observed correlation was a positive correlation between the systolic blood pressure and serum MDA [r =0.52, P =0.037]. In hypertensive rats, a positive correlation was observed between each of MAP, UAE and serum MDA [r =0.65, P =0.008 and r =0.62, P = 0.012] and also between MAP and serum CGRP [r =0.59, P =0.017], versus an inverse correlation between UAE and CGRP [r = -0.54, P =0.026]. In addition, a strongly positive correlation was observed between serum MDA and CGRP in the hypertensive rats [r =0.77, P<0.001]. Patients with essential hypertension have diminished CGRP levels. Hypertension is associated with increased oxidative stress. CGRP is important in protection against hypertension-induced renal damage. These data shed light on a potentially therapeutic role of CGRP and may be antioxidants in the management of hypertension, including the use of medications that can enhance CGRP release, or increase the vascular sensitivity to this neuropeptide

Study of plasma adiponectin in type 2 diabetes mellitus ; relation to non-alcoholic fatty liver disease

Subdying possible link between adiponectin, plasma insulin and biochemical parameters of liver injury in type 2 Diabetic patients with and without non-alcoholic fatty liver disease [NAFLD]. Thirty type 2 diabetics [group I], 30 type 2 diabetics with NAFLD [group II] and 30 healthy controls [group III] were subjected to complete clinical examination, anthropometric measurements, determination of fasting plasma insulin and fasting adiponectin, fasting and 2-hours postprandial plasma glucose, glycated hemoglobin [HbA[1c]%] lipid profile, liver enzymes and abdominal ultrasound examination. Diabetic patients had significantly increased mean fasting plasma insulin and decreased mean fasting plasma adiponectin values compared with the controls, especially group II with NAFLD [p < 0.001]. There was a significantly negative correlation between fasting adiponectin and insulin values in both diabetic groups [p < 0.001]. Adiponectin did not correlate with lipid parameters nor liver enzyme in diabetics with and without NAFLD. In conclusion, this study demonstrated a low plasma adiponectin level in type 2 diabetes especially those with NAFLD that is inversely correlated with hyperinsulinemia. These data support a role for .adiponectin in protection against liver injury, in keeping with the hypothesis that an imbalance between proinflammatory and antiinflammatory cytokines may have a pathogenic role in the development of liver damage in diabetics with NAFLD. Finally, a novel cross-talk between the adipose tissue and liver is emerging that may act as a major player in the link between the metabolic syndrome and non alcoholic fatty liver disease [NAFLD].Future studies are recommended to evaluate the role of adiponectin in the management of patients with type 2 diabetes and those with NAFLD