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 the relationship between adiponectin, myeloperoxidase enzyme activity and severity of coronary artery disease

The aim of the present work was to study the possible relationships between each of plasma adiponectin level, myeloperoxidase [MPO] activity, serum nitric oxide [NO] metabolites and the occurrence and the severity of coronary atherosclerosis. It also aimed to detect potential interaction among these factors and to find if there is relationship between these factors and some of the traditional CAD risk factors. In order to achieve this goal, 48 male subjects were evaluated and divided into 4 groups who had coronary angiography to evaluate the severity of coronary atherosclerosis if present; group I consisted of 12 CAD patients with single vessel disease, group II consisted of 12 CAD patients with double vessel disease, group III consisted of 12 CAD patients with multivessel disease, and group IV [control group] consisted of 12 individuals of matched age and sex presented with chest pain with normal coronary angiography. Following proper selection of patients and control subjects, the following laboratory tests were performed for all of them: determination of plasma adiponectin concentration, estimation of MPO activity, determination of serum NO metabolites concentrations [nitrite / nitrate] and determination of serum lipids concentration [total cholesterol, triglycerides [TG], high density lipoprotein-cholesterol [HDL-ch], and low density lipoprotein-cholesterol [LDL-ch]]. The result of the present study showed significant association between the occurrence of CAD and each of low adiponectin level, high MPO activity, low nitrite level, low nitrate level, high total cholesterol level, high TG level, high LDL-ch level, low HDL-ch level and high LDL/HDL-ch ratio. They may all be regarded as predictors or risk factors for CAD. Furthermore, adiponectin, MPO activity, nitrite, total cholesterol, LDL-ch and LDLJHDL-ch ratio were the factors that affected the severity of coronary atherosclerosis. Significant correlation was found between low adiponectin level and atherogenic lipid profile. Moreover, the present study showed significant decrease in adiponectin level in hypertensive and cigarette smoking CAD patients compared to normotensive and non cigarette smoking CAD patients suggesting that low adiponectin level might interact with these traditional risk factors to induce oxidative stress and endothelial dysfunction, thereby promoting atherosclerosis. Furthermore, significant correlation was found between high MPO activity and each of cigarette smoking and atherogenic lipid profile in CAD patients suggesting a possible interaction between MPO and these risk factors to induce and promote oxidative stress and vascular inflammatory process in coronary atherosclerosis. However, there was no significant correlation between MPO activity and hypertension. Another point of interest in the results of the present study was the significant correlation of both low adiponectin level and high MPO activity with NO metabolites [nitrite / nitrate] level. Such correlation suggests that NO could be a link parameter and a common mediator for the action of adiponectin and MPO activity. The latter result highlights the importance of NO as both diagnostic tool and therapeutic target in atherosclerosis. The present study supports the hypothesis that endothelial dysfunction, vascular inflammation, and oxidative stress are primary interacting mediators in the pathogenesis of coronary atherosclerosis. It also highlights the importance of adiponectin as a marker for the presence and extent of CAD. MPO might serve as a marker of a general capacity for oxidative damage to the vasculature rather than functioning solely through direct consumption of NO. Furthermore, NO can act as a predictor of CAD severity, a mediator of coronary atherosclerosis and a common mediator of the action of adeponectin and MPO

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

Modification of angiogenesis factors in cancer patients under bisphosphonate

Recently, new experimental data suggested that, besides inhibiting osteoclasts, bisphosphonate may also have an antitumor effect. Antiangiogenic activity is one of the possible mechanisms of anticancer activity attributed to zoledronic acid; an amino-bisphosphonate. The aim of this study was to evaluate the modifications in angiogenic cytokines levels after zoledronic acid infusion. Sixteen cancer patients with bone metastases were intravenously infused with zoledronic acid. They were evaluated prospectively for circulating levels of calcium, vascular endothelial growth factor [VEGF], transforming growth factor beta1 [TGF-beta1] and interferon-gamma [IFN-gamma] at different time points: just before and after 1 and 7 days of zoledronic acid infusion. Basal VEGF serum levels were decreased significantly on the 1[st] and 7[th] day after zoledronic acid infusion, more pronounced on the 7[th] day. TGF-beta1 serum levels were significantly decreased on the 7[th] day of infusion, while IFN-gamma serum levels were significantly increased 1 day after the infusion. Moreover, the present data showed a statistically significant negative correlation between serum levels of VEGF and of both TGF-beta1 on the 7[th] day of infusion and IFN-gamma on the 1[st] day. This study confirms that the amino-bisphosphonate; zoledronic acid appears to modulate serum levels of proangiogenic growth factors such as VEGF, TGF-beta1 and IFN-gamma in cancer patients. It may have antiangiogenic properties through a significant and lasting decrease in serum levels of VEGF and TGF-beta1. In addition, it may activate the gamma delta T cell population as evidenced by increased INF-gamma level, which shows potential cytotoxic activity toward a broad spectrum of tumors

Role of orexin-A in obesity and type 2 diabetes in male patients and its correlation with leptin hormone

To study role of orexin-A in obesity, type 2 diabetes as well as combined obesity and type2 diabetes in male patients and its correlation with leptin hormone. The study was conducted on 30 male patients and 10 healthy age and sex matched control subjects. The patients were divided into 3 groups each of ten as follow: obese normoglycemic, nonobese type 2 diabetic and obese type 2 diabetic patients. All patients and controls were subjected to full history taking and complete clinical examination with determination of BMI. The following parameters were measured: fasting serum levels of glucose, insulin, triglycerides and glycosylated hemoglobin. Serum orexin-A and leptin concentrations were determined. The results of the study revealed that, serum orexin-A was significantly low in all the studied patient groups as compared to control subjects. Significant high serum leptin levels were detected in all patient groups compared to normal ones. An inverse correlation was found between serum orexin-A and BMJ, leptin, glucose and insulin levels. On the other hand, serum leptin was positively correlated with BMI and insulin levels. Orexin-A is implicated in the pathogenesis of both obesity and type 2 diabetes. Leptin may be an important negative regulator of orexin-A

Toxic effects of trichloroethylene on the lung

This study aimed to investigate the effect of trichloroethylene on the lung ofalbino rats histopathologically and ultrastructurally. The experimentalanimals were divided into three treated groups. One group was administeredtrichloroethylene as a single dose [2000 mg/kg] intraperitoneally. The secondand third treated groups received trichloroethylene as repeated doses [1000mg/kg] intraperitoneally every other day for two and four weeks, respectively. Light microscopy of lungs of the first group exhibited variable degenerativechanges including lining epithelium of bronchioles. Electron microscopicexamination revealed a dilatation of endoplasmic reticulum, distension ofperinuclear cisternae and disorientation of mitochondria. Lung of the secondand third groups exhibited variable necrotic changes including bronchiolarepithelium and diffuse interstitial fibrosis in the alveolar zone resulting ina thickening of alveolar septa and distortion of lung structure. Electronmicroscopy revealed cellular changes similar to those in the first group, butof varying degrees. Additionally, there were parenchymal changes includingtype II alveolar cells, which had reduced the numbers of lamellar bodies anddistortion of the microvilli. These results demonstrated thattrichloroethylene is pneumotoxic and affects bronchiolar epithelial andalveolar type II cells