study on angiotensin converting enzyme gene insertion/deletion polymorphism and serum cortisol among a sample of egyptian patients with major depression disorder

Angiotensin-converting enzyme [ACE] is assumed to influence the activity of the hypothalamic-pituitary-adrenocortical [HPA] system, which shows hyperactivity in the majority of patients with major depression. The ACE gene, known to be associated with cardiovascular disorders, which in turn are accompanied with an increased susceptibility for depression, is therefore a promising candidate gene for effective disorders. However, the results are conflicting, with no reported studies on Egyptian depressed patients. This study aimed to assess ACE insertion / deletion [I/D] gene polymorphism among Egyptian depressed patients in order to clarify HPA system dysregulation, and to determine its possible association with severity of depression. This case/control study was conducted on 42 adult depressed patients, and 37 healthy controls were screened to detect genetic associations with unipolar major depression. Determination of ACE genotypes was performed for all subjects by real time PCR. Total serum cortisol levels were measured by ELISA. The frequencies of the DD, ID and II genotypes were 26.2%, 45.2%,and 28.2%, respectively among the cases, and 17.49%, 25.2%, and 56.41%3 respectively among the controls. Significant differences in ACE gefiotype distribution were observed between cases and controls [p - 0.0384]. Serum cortisol in patients show the highest value in the ID polymorphism while II polymorphism shows the lowest value of a.m. cortisol. Data illustrated a significant association of ID polymorphism with the more severity of illness. Our findings support that ACE gene I/D polymorphism and high D allele frequency are associated with depression, also hypercortisolimia is significantly higher in individuals with major depression compared to control among Egyptian adults. ACE gene polymorphism might provide a common link between developing depressive episode and dysfunctional HPA-axis

Influence of ionizing radiation on Echis pyramidium snake venom: Biochemical and immunological aspects

The effect of a single LD[50] dose of native Echis pyramidum venom [27.69 micro g/mouse] on the activities of certain serum enzymes levels: aspartate aminotransferase [AST], alanine aminotransferase [ALT], alkaline phosphatase [ALP], urea, creatinine, lactate dehydrogenase [LDH], creatine phosphokinase [CPK], creatine kinase isoenzyme [CK-MB] were studied. Samples from the serum were collected 4hr following LD50 venom dose intraperitonealy injected in male Swiss albino mice. The activities of these enzymes showed significant elevation compared to the non-envenomated group. In contrast, an equivalent dose of 1.5 kGy gamma irradiated Echis pyramidum venom [27.69 micro g/mouse] did not cause any significant increase compared to non-envenomated group. The effect of a dose that is equivalent to ½ LD[50][13.8 micro g/50 micro l] of native Echis pyramidum venom on plasma creatine phosphokinase [CPK] induced a significant increase of creatine phosphokinase [CPK] level compared to normal control [P<0.01]. In contrast, an equivalent dose of 1.5 kGy gamma irradiated Echis pyramidum venom showed non significant difference in creatine phosphokinase activity when compared to the normal control. Light microscopic examinations of gastrocenemius muscles of mice injected with native Echis pyramidum venom [½ LD[50]; 13.8 micro g/50 micro l] showed fragmentation, disorganization, loss of myofibrils in some of the muscle fibers, hemorrhage in-between the muscle fibers and mononuclear cellular infiltration. While light microscopic examinations of gastrocenemius muscles of mice injected with 1.5 kGy gamma irradiated Echis pyramidum venom [13.8 micro g/50 micro l; a dose identical to that used from native venom] showed that most muscle fibers were of normal appearance except for small area of fragmentation and disorganized myofibrils and oedema of the intercellular connective tissue. Double immunodiffusion test revealed a similar reactivity for native, 1 kGy, 1.5 kGy and 3 kGy gamma irradiated Echis pyramidum venoms against a commercial polyvalent Egyptian antivenin. The visible lines obtained in the immunodiffusion reactions were identical and joined smoothly at the corners, indicating that there was no change in their antigenic reactivity. These results demonstrate that the ability of the venom antigens to react with its corresponding antibodies was maintained in spite of being exposed to radiation doses of 1 kGy, 1.5 kGy and 3 kGy. Both antivenins raised against native or 1.5 kGy gamma irradiated venoms recognized Echis pyramidum venom when submitted to protein blotting, but the anti 1.5 kGy gamma irradiated venom show a higher intensity bands than the antivenin raised against native Echis pyramidum venom, in spite of having less neutralizing activity [native neutralize 50 LD[50], 1.5 kGy gamma irradiated neutralize 40 LD[50]], this indicates that antibodies were formed not only for toxic fraction but also for non toxic fraction. Irradiation of the whole Echis Pyramidium Venom with 1.5KGy reduced its lethality 12.5 times though keeping its immunogenicity. The 1.5KGy dose was shown to be the best radiation dose to promote detoxification without significantly affecting its immunogenicity. Thus results of this study confirm the conclusion that gamma radiation is a suitable way to detoxify Echis Pyramidium Venom without affecting its immunogenicity provided that proper dose is used

Effect of moxonidine versus clonidine and lisinopril on blood pressure and expression of renin gene in two kidney/one clip [2K/1 C] hypertensive rats

It has been suggested that imidazoline receptors rather than alpha-2 adrenoceptors are implicated in the sympathoinhibitory action of centrally acting antihypertensive drugs. I[1] Imdazoline receptors [I[1]Rs] are important for regulation of sympathetic drive. They are concentrated in the rostral ventrolateral medulla [RVLM], a part of the brainstem vasomotor center. The control of arterial blood pressure is mainly regulated via the sympathetic and angiotensin/ aldosterone cascades. The purpose of the present study was focused to assess the effect of oral administration and abrupt withdrawal of moxonidine versus clonidine and lisinopril on systolic pressure, to investigate the role of moxonidine versus clonidine and lisinopril on plasma noradrenaline level and plasma renin activity and to determine the genometric effect of moxonidine versus clonidine and lisinopril oral administration on renin gene expression in 2K1C renovascular hypertensive rats. Rats were made hypertensive with a clip on the left renal artery. The operation was conducted under light ether anesthesia. Three weeks after renal clipping. 2 series of experiments on male rats were conducted to evaluate the effect of the test drugs on the following parameters. 1- Effect of oral administration of the test drugs for a period of three weeks on the systolic pressure in 2K1C hypertensive rats measured via indirect rat-tail method. 2-Biochemical tests to estimate plasma norepiphrine level and plasma renin activity. 3- Renin gene expression measured by quantified RT-PCR. All test drugs elicited a remarkable significant reduction in systolic pressure of renovascular hypertensive rats. Discontinued administration of moxonidine did not trigger rebound hypertension observed with clonidine. These findings suggest that both imidazoline receptors and alpha 2- adrenoceptors are involved in the central antihypertensive effect of moxonidine, but that activation of imidazoline receptors is more important for its renal sympathinhibitory action. Additionally imidazoline derivatives and ACEIs are very effective agents for treatment of renovascular hypertension. The antihypertensive effect of moxonidine was accompanied by decrease in plasma norepinephrine, renin levels and renin gene expression in the renal tissue. Whereas lisinopril decreased plasma norepinephrine level but increased plasma renin activity in parallel with renin gene expression compared to the untreated 2K1C hypertensive control. The data presented in this report indicate that moxonidine is an orally effective antiypertensive agent in 2KIC hypertensive rats without an accompanying rebound hypertension on abrupt dicontinuation of the drug, which makes it advantageous over clonidine. Moxonidine therefore allies antihypertensive efficacy with excellent tolerance without triggering central side-effects as moxonidine selectively binds at therapeutic doses to I[1] imidazoline receptors. ACEI, lisinopril produced a significantly pronounced reduction in systolic pressure in 2K1C hypertensive rats. Lisinopril may be of greater benefit in management of renovascular hypertension. In light of these findings moxonidine represents a unique profile among centrally acting antihypertensive agents. Moxonidine offers an advantageous hemodynamic activity over clonidine and lisinopril and probably it exerts its strong antihypertensive effect through its affinity for I[1] imidazoline receptors rather than alpha[2] adrenergic receptors

Fetal gender determination in early pregnancy using PCR analysis of maternal serum

Non-invasive methods using maternal plasma and serum for molecular genetic diagnosis have become an important field of interest in prenatal genetic diagnosis. Free fetal DNA in maternal plasma and serum has been shown to be useful for fetal gender determination, and seems to offer a new possibility to perform non-invasive prenatal genetic diagnosis. Peripheral blood samples were obtained from 25 pregnant women selected at random. All of the pregnant women underwent blood sampling at gestational ages ranging from 9 weeks + 2 days to 12 weeks + 4 days. Maternal serum was used to detect the Y-chromosome specific sequence DYS14. 40 cycles of PCR were carried out for each DNA extract. The PCR products were analyzed by 2.5% agarose gel electrophoresis and ethidium bromide staining and the results were compared with the results of ultrasound scanning at 21 weeks gestation. Ultrasound scan revealed that 13 of the pregnant women were carrying a male fetus and the remaining 12 pregnant women were carrying a female fetus. PCR analysis of maternal serum of all the women participating in the study was identical to the results obtained by Ultrasound scan PCR analysis of maternal serum can be used successfully with 100% accuracy to diagnose fetal gender in maternal serum in normal single pregnancies

Detection of human papilloma virus DNA in skin tags

Human papilloma virus [HPV] has been suggested to be one of the factors involved in the pathogenesis of skin tags. This study explored the presence of HPV-DNA by polymerase chain reaction [PCR] in biopsies from lesional and perilesional skin of 30 patients and the normal skin of 20 age- and sex-matched control. The results revealed the presence of HPV-DNA in 77% of skin tags, which was statistically significant compared to perilesional skin [53%] and controls [20%]. It was, therefore, concluded that HPV virus has an important role in the pathogenesis and progression of skin tags as previously reported for laryngeal papillomas

Cellular and humoral immunological changes in chronic renal failure associated with schistosomiasis

The changes that occur in cell mediated and humoral immunity in patients suffering from chronic renal failure associated with schistosomiasis were studied. There was a decrease in T3%, T4% and T4/T8 ratio. IgG, IgM and IgE levels were found to increase in such cases. It was concluded that there was a reciprocal relationship between cell mediated immunity and IgE levels in cases with chronic renal failure associated with bilharzial hepatosplenomegaly

Evaluation of dot elisa technique in the serodiagnosis of schistosomiasis in Egypt

A simplified dot enzyme linked immunosorbent assay [dot ELISA] was evaluated as a recent diagnostic test for schistosomiasis in Egypt. 160 individuals with early intestinal, urinary and mixed schistosomiasis were subjected to this study. Another 27 sera of patients suffering from other parasitosis were included for the cross activity reaction. The test was compared with 2 common serological tests for schistosomiasis in Egypt, circumoval precipitin test [COPT] and indirect haemagglutination test [IHAT]. The dot ELISA was shown to have a sensitivity of 99%, specificity of 98% and the highest diagnostic accuracy 98%. The data indicated that the dot ELISA is an accurate and rapid technique for the detection of antischistosomal antibodies

Evaluation of the DOT enzyme-linked immunosorbent assay in diagnosis of leishmaniasis

Human sera were collected from twenty patients of parasitologically proven cutaneous leishmaniasis, 35 cases of schistosomiasis mansoni and ten normal control sera. The antileishmanial antibodies were detected by the dot enzyme-linked immunosorbent assay [dot ELISA]. The results showed that the dot ELISA had high sensitivity. However, there was a marked deal of cross reactivity with the antisera of schistosomiasis mansoni infected patients, particularly those with splenomegaly and ascites

Cutaneous leishmaniasis in Ismailiya Governorate, Egypt

Out-patients attending the Public Health Center in Kantara Gharb [Ismailiya Governorate] were examined for any suspected lesion or papule suggesting cutaneous leishmaniasis. Twenty-eight out of 450 patients [6.2 per cent] had active cutaneous leishmaniasis.The diagnostic criteria was based on smear examination and culture on N.N.N. medium. The results are discussed