Serum interleukin levels in asthmatic patients with eosinophilia

The incidence, morbidity and mortality of bronchial asthma have increased over the last two decades. Immune and inflammatory responses mediated by cytokines are essential in the pathophysiology of bronchial asthma. Substantial evidence has implicated Th2 cytokines, IL-4 and IL-5, in the pathology of allergic asthma and demonstrated protective effects of Th1 cells. This work was conducted to study the serum levels of IL-4, IL-5, IL-12 and IL-18, in patients with allergic asthma associated with eosinophilia. Interleukins levels were correlated with IgE level and the degree of eosinophilia in these patients. The study included 25 asthmatic patients with acute attack of bronchial asthma, associated with history of allergy and eosinophilia; and 25 normal healthy controls. All patients and controls were subjected to full medical history, clinical examination, and laboratory investigations for assessment of the eosinophil count and measurement of serum levels of IgE and interleukins [IL-4, IL-5, IL-12 and IL-18]. The correlation between interleukin [IL] levels, and degree of eosinophilia and IgE levels were also examined in these patients. Measurement of serum levels of interleukins showed significant elevation of IL-4, IL-5 and IL-18 levels in asthmatic patients as compared with the control group [p<0.0001], whereas IL-12 levels did not show any significant change [p>0.05]. Marked elevation in the IgE level and eosinophil count were also detected in asthmatic patients as compared with the control group [p<0.0001]. Significant positive correlations were observed between serum levels of IL-4, IL-5 and IL-18 and the degree of eosinophilia in asthmatic patients. A significant positive correlation was also detected between level of IL-18 and the IgE level in asthmatic patients. Patients with allergic bronchial asthma have elevated levels of IL-4, IL-5 as well as IL-18; and these levels correlated significantly with degree of eosinophilia in these patients. Further studies are needed to clarify the signaling cascade involved in allergic responses mediated by these ILs. This may help in developing new therapeutic modalities, as blockade of IL receptors, for these conditions

Human peroxisome proliferator-activated receptor 2 [PPAR 2] pro 12 Ala polymorphism: a possible association with risk of diabetic nephropathy in type 2 diabetes

Mutations of the nuclear receptors PPAR-gamma confer an extreme phenotype of partial lipodystrophy, early-onset severe insulin resistance, type 2 diabetes, dyslipidemia, hypertension, and hepatic steatosis. The association between the Pro 12 Ala polymorphism in PPAR-gamma and obesity, insulin sensitivity, and type 2 diabetes was studied. It appears that the Ala 12 allele confers modest protection against the onset of type 2 diabetes and is also associated with an increased BMI in overweight individuals. This study was conducted to investigate an association between Pro 12 Ala polymorphism and the incidence of diabetic nephropathy in obese patients with long-lasting type 2 diabetes. The study was carried on sixty patients with type 2 diabetes mellitus, they were divided to 2 groups, group 1 included 30 patients with diabetic nephropathy and group 2 include 30 patients without diabetic nephropathy. Thirty healthy subjects of matched age and sex were included as controls [group 3]. Pro 12 Ala polymorphism was statistically significant more frequent in the diabetic group without nephropathy [group 2] in comparison to diabetic patients with nephropathy [group 1] p<0.0001, and the control group [group 3], p<0.0001. but there was no significant difference between the diabetic nephropathy group [group 1] and control group [group 3]. PPAR gamma receptor polymorphism was positive in 7 patients [23.33%] and negative in 23 patients [76.67%] of the diabetic nephropathy group [group 1]. In the diabetic group without diabetic nephropathy, it was positive in 24 patients [80%], negative in 6 patients [20%]. On the other hand, patient with diabetic nephropathy [group 1] associated with hypertension [21 patients] were all negative regarding PPAR gamma Pro 12 Ala polymorphism. Whereas, those without hypertension only 2 out of 9 patient were negative and the remaining 7 cases were positive regarding polymorphism. There were no significant differences between the two diabetic groups of patients regarding BMI, lipid profile and duration of diabetes. There was also no association between PPAR polymorphism and duration of diabetes, BMI and any of the biochemical parameters measured. In conclusion, the presence of the Ala allele of the PPAR gamma Pro 12 Ala polymorphism seems to be associated with a decreased risk of diabetic nephropathy in patients with type 2 diabetes. This association needs to be confirmed in other patient populations. More basic studies will be required to uncover the molecular mechanisms underlying the association between PPAR gamma Pro 12 Ala polymorphism and diabetic nephropathy risk

Expression of wild p53, mutated p53 and hypoxia inducible factor-1 alpha in hepatocellular carcinoma

To investigate the expression of wild p53, mutated p53 and hypoxia inducible factor-1 alpha [HIF-1 alpha] genes in hepatocellular carcinoma and correlate their expression with clinicopathological data. Liver biopsy samples of 30 hepatocellular carcinoma [HCC] subjects. 20 chronic hepatitis C [CHC] and 20 liver biopsy samples from non cancerous tissue [i.e control samples] of HCC were assessed by polymerase chain reaction [RT-PCR] and restriction enzyme analysis for the three genes; wild p53 gene, mutations in p53 at codon 249, exon 7 and hypoxia inducible factor-1 alpha gene. Wild p53 gene was detected in 18/30cases of HCC [60%], 16/20 cases of CHC [80%] and 15/20 cases of control samples [75%] with no significant difference between the studied groups. Mutated p53 gene was detected in 12/30 cases of HCC [40%], 4/20 cases of CHC [20%] and 5/20 cases of control samples [25%], also with no statistically significant difference between the studied groups while HIF-lalpha gene was expressed in 20/30 cases of HCC [66.7%] in comparison to 2/20 cases of CHC [10%] and 3/20 of control samples [15%] with a highly statistically significant difference [p<0.001]. The expression of both wild p53 and the mutated p53 correlated with tumor size but did not correlate with grade of malignancy nor serum alpha fetoprotein level, while the expression of HIF-1 alpha correlated with grade of malignancy and alpha fetoprotein level but not with tumor size. No correlation between expression of all genes and capsule infiltration or presence of cirrhosis was found in all groups. HIF-1 alpha is highly expressed in HCC and is related to grade of malignancy and serum alpha fetoprotein level

Serum levels of soluble CD40 ligand in patients with chronic and acute coronary syndromes and its relation to angiographic extent of coronary arterial narrowing

The aim of this study was to determine serum levels of soluble CD4O ligand [sCD4OL] in patients with chronic and acute coronary syndromes [ACS] and to assess the relation between sCD4OL levels and extent of coronary arterial narrowing in patients with ACS. Acute coronary events commonly result from thrombosis triggered by disruption of an atherosclerotic plaque. Recent studies have localized the receptor CD4O and its ligand in human atheroma. The CD4OL on activated T cells and platelets, by inducing the expression of matrix- degrading proteinases and of tissue factor procoagulant, may contribute to the triggering of acute coronary events. To study the role of CD4OL-CD4O interaction in coronary artery disease, we analyzed serum levels of sCD4OL in the peripheral blood from 10 patients with stable angina [SA]. 26 patients with unstable angina [UA], 22 patients with acute ST-segment elevation myocardial infarction [Ml] and 20 healthy controls by enzyme-linked immunosorbent assay [ELISA]. Coronary angiograms of all the VA patients and 18 Ml patients were reviewed to determine the culprit vessel [CV], CV complexity score [CVCS] [a score of I is given to a simple stenosis, 2: complex stenosis, 3: intracoronary thrombus, 4: total occlusion], type of CV lesion [A, B or C according to the lesion morphology] and vessel score [number of vessels with >/= 50% diameter stenosis]. Both patients with UA and Ml showed significantly higher levels of serum sCD4OL compared to patients with SA and controls; particularly high levels occurred in patients with UA [F ratio 34.9, p <0.001]. No statistically significant difference in sCD4OL levels was noted between VA and Ml patients or between SA patients and controls. Levels of sCD4OL did not show any significant correlation to peak CK. CK-MB in Ml patients or troponin T serum levels in UA patients. Levels of sCD4OL did not also show any significant correlation to CVCS, type of CV lesion or vesset score in VA or Ml patients. This study shows enhanced levels of sCD4OL levels in patients with UA and MI patients suggesting that CD4OL-CD4O interaction plays a pathogenic role in the triggering of ACS. Serum levels of sCD4OL could not however, predict the angiographic extent of coronary arterial narrowing