Biochemical and Histological Study of Aminoacylase-1 Purified from Amniotic Fluid in Rats with Oxidative Stress Induced by Lead Acetate

تضمن البحث فصل ودراسة إنزيم أمينواسيليز-1 (ACY1) من السائل الأمنيوني للحوامل  الاصحاء، إذ تم فصل حزمة رئيسية واحدة فقط ذات فعالية عالية بتقنية التبادل الايوني السالب نوع DEAE-cellulose للراسب البروتيني الناتج عن ترسيب البروتينات باستخدام كبريتات الامونيوم (65%) بعد عملية الفرز الغشائي، اذ وصلت عدد مرات التنقية الى (19) مرة, وعند استخدام عمود الترشيح الهلامي باستخدام سيفادكس من نوع G-100 تم الحصول على نقاوة عالية للإنزيم وصلت عدد مرات التنقية له الى (38), وقد وجد ان الوزن الجزيئي لإنزيم المعزولة كان بحدود 46698 دالتون عند استخدام تقنية كروماتوغرافي الترشيح الهلامي. درس تأثير إنزيم  ACY1المعزول على الجرذان المصابين بالإجهاد التأكسدي المستحدث بخلات الرصاص (LA) بجرعة 40 ملغم /كغم من وزن الجرذي وتمت مقارنتها مع الطبيعيين وذلك من خلال قياس المتغيرات الكيموحيوية المختارة والتي تضمنت: الكلوتاثايون (GSH) والمالوندايالديهايد(MDA) وإنزيم اسبارتيت أمينوترانسفريز (AST) وإنزيم ألانين أمينوترانسفريز(ALT) وكذلك من خلال الفحص النسيجي للكبد والكلية. اذ أظهرت النتائج ارتفاعاً معنوياً في مستويات (MDA وAST وِALT) وانخفاضها في مستوى (GSH) مقارنة مع مجموعة السيطرة السالبة، كما لوحظ ان هناك انخفاضاً معنوياً في مستويات (MDA وAST وِALT) وارتفاع في GSH عند حقن إنزيم ACY1 4  ملغم /كغم من وزن الجرذي مع LA بجرعة 40 ملغم /كغم. وأظهرت نتائج الفحص النسيجي وجود تغيرات مرضية عالية لأنسجة الكبد للجرذان المعاملة بمادة LA 40 ملغم /كغم من وزن الجرذان عند مقارنتها مع الطبيعيين، لقد حصل تحسن لأنسجة الكبد والكلية عند استخدام إنزيم ACY1 4  ملغم /كغم من وزن الجرذان مع LA، وهذه النتائج تثبت دور انزيم ACY1 في الحماية من الاجهاد التأكسدي والتقليل من حدة الأمراض المختلفة. درس تأثير إنزيم  ACY1المعزول على الجرذان المصابين بحالة الكرب التأكسدي المستحدث بواسطة خلات الرصاص بجرعة 40 ملغم /كغم من وزن الجسم ومقارنتها مع الجرذان الطبيعيين وذلك من خلال قياس المتغيرات الكيموحيوية المختارة والتي تضمنت: الكلوتاثايون (GSH) والمالوندايالديهايد(MDA) وإنزيم اسبارتيت أمينوترانسفريز (AST) وإنزيم ألانين أمينوترانسفريز(ALT) وكذلك من خلال الفحص النسيجي للكبد والكلية. اذ أظهرت النتائج ارتفاعاً معنوياً في مستويات (MDA وAST وِALT) وانخفاضها في مستوى (GSH) مقارنة مع مجموعة السيطرة، كما لوحظ ان هناك انخفاضاً معنوياً في مستويات (MDA وAST وِALT) وارتفاع مستوى GSH عند استخدام الإنزيم المعزول بجرع4  ملغم /كغم من وزن الجرذان مع خلات الرصاص بجرعة 40 ملغم /كغم. وأظهرت نتائج الفحص النسيجي وجود تغيرات مرضية عالية لأنسجة الكبد للجرذان المعاملة بخلات الرصاص بجرعة 40 ملغم /كغم من وزن الجرذان عند مقارنتها مع الجرذان الطبيعيين، وحصول حالة تحسن لأنسجة الكبد والكلية عند استخدام الإنزيم المعزول بجرع 4  ملغم /كغم من وزن الجرذان مع خلات الرصاص، وهذه النتائج تثبت دور الإنزيم المعزول في حماية الجسم من الكرب التأكسدي والتقليل من حدة الأمراض الناتجة عنه.This work involves separating and studying the aminoacylase-1 (ACY1) of amniotic fluid from healthy pregnant, mainly one peak with higher activity has been isolated by DEAE-Cellulose ion exchange from the proteinous supernatant produced by deposition of proteins using ammonium sulfate  (65%) after dialysis. The purification folds reaching to 19 folds also gave one protein peak when injected into the gel filtration column, a high ACY1 purity was obtained, with 38 folds of purification. It was found that the molecular weight of the isolated ACY1 was up to 46698 Dalton when using gel chromatography technique.The effect of ACY1 isolate was studied on rats with oxidative stress caused by lead acetate(LA) at 40 mg / kg body weight and compared with normal rats by measuring the selected biochemical parameters which included: Glutathione (GSH), malondialdehyde (MDA), aspartate aminotransferase (AST) and alanine aminotransferase (ALT) through liver and kidney tissue examination. The results showed a significant increase in the levels of (MDA, AST, ALT) and a decrease in the level of GSH compared with the control group, Also it has been observed there that was a significant decrease in the levels of (MDA, AST, ALT) and high level of GSH when injecting the ACY1 isolate in a dose of 4 mg / kg of rat weight with LA at 40 mg/kg. The results of the tissue examination demonstrated high pathological changes in the liver tissue of rats treated with LA at 40 mg/kg of rat weight when compared with normal rats. The liver and kidney tissue improved when treated with isolate at 4 mg / kg rat weight and LA. These results demonstrate the role of ACY1 in protecting from oxidative stress then can reduce the severity of various diseases. Studying the effect of ACY1 isolated on rats with oxidative stress caused by lead acetate at a dose of 40 mg / kg body weight and compared with normal rats by measuring the selected biochemical parameters which included: Glutathione (GSH), malondialdehyde (MDA), aspartate aminotransferase (AST) and alanine aminotransferase (ALT) as well as through liver and kidney tissue examination. The results showed a significant increase in the levels of (MDA, AST, ALT) and a decrease in the level of GSH compared with the control group, It was also observed that there was a significant decrease in the levels (MDA, AST, ALT) and high level of GSH when using the enzyme isolated in a dose of 4 mg / kg of rat weight with lead acetate at a dose of 40 mg/kg. The results of the tissue examination showed high pathological changes in the liver tissue of rats treated with lead acetate at a dose of 40 mg/kg of rat weight when compared with normal rats, and liver and kidney tissue improvement when isolated enzyme is administered at 4 mg / kg rat weight with lead acetate. These results demonstrate the role of isolated enzyme in protecting the body from oxidative stress then can reducing the severity of various diseases

Therapeutic concentrations of antidepressants inhibit pancreatic beta-cell function via mitochondrial complex inhibition

Diabetes mellitus risk is increased by prolonged usage of antidepressants (ADs). Although various mechanisms are suggested for their diabetogenic potential, whether a direct effect of ADs on pancreatic β-cells is involved is unclear. We examined this idea for 3 ADs: paroxetine, clomipramine and, with particular emphasis, fluoxetine, on insulin secretion, mitochondrial function, cellular bioenergetics, KATP channel activity, and caspase activity in murine and human cell-line models of pancreatic β-cells. Metabolic assays showed that these ADs decreased the redox, oxidative respiration, and energetic potential of β-cells in a time and concentration dependent manner, even at a concentration of 100 nM, well within the therapeutic window. These effects were related to inhibition of mitochondrial complex I and III. Consistent with impaired mitochondrial function, lactate output was increased and insulin secretion decreased. Neither fluoxetine, antimycin nor rotenone could reactivate KATP channel activity blocked by glucose unlike the mitochondrial uncoupler, FCCP. Chronic, but not acute, AD increased oxidative stress and activated caspases, 3, 8, and 9. A close agreement was found for the rates of oxidative respiration, lactate output and modulation of KATP channel activity in MIN6 cells with those of primary murine cells; data that supports MIN6 as a valid model to study beta-cell bioenergetics. To conclude, paroxetine, clomipramine and fluoxetine were all cytotoxic at therapeutic concentrations on pancreatic beta-cells; an action suggested to arise by inhibition of mitochondrial bioenergetics, oxidative stress and induction of apoptosis. These actions help explain the diabetogenic potential of these ADs in humans

Delineating groundwater and subsurface structures by using 2D resistivity, gravity and 3D magnetic data interpretation around Cairo–Belbies Desert road, Egypt

AbstractGeophysical tools such as magnetic, gravity and electric resistivity have been used to delineate subsurface structures, groundwater aquifer around Cairo–Belbies Desert road. A dipole–dipole section was measured at the central part of the study area with 2100m length and electrode spacing 50m for greater penetration depth. The results of the inverse resistivity data indicate that the study area includes two groundwater aquifers at different depths. The shallow aquifer water is near the surface and the deep aquifer lies at depth of about 115m and exhibits low resistivity values ranging from 20 to 100ohmm.One hundred and fifty-two gravity stations were measured using Autograv gravimeter (CG3), different gravity corrections (drift, elevation and latitude corrections) were applied. The corrected data represented by Bouguer anomaly map were filtered into regional and residual gravity anomaly maps. The residual gravity map indicates that the area is dissected by many faults with NW-SE, N-S, E-W and NE-SW trends.One hundred and fifty-three ground magnetic measurements are collected using two Proton magnetometers (Envimag). The corrected magnetic data are represented by total magnetic intensity map that was reduced to the magnetic pole. 3D magnetic modeling was applied to detect the depth of basaltic sheet and basement complex. The results indicated that the elevation of upper surface of basalt is ranging from 148 to −153m and the elevation of lower surface of basalt is ranging from 148 to 269m

Unconditionality of orthogonal bases in B0-algebras

The article contains no abstrac

BER performance of OFDM signals in presence of nonlinear distortion due to SSPA

Orthogonal frequency division multiplexed signals typically exhibit large dynamic ranges due to superposition of a large number of subcarrier signals. As a result, such signals are highly vulnerable to distortion caused by high power amplifier (HPA) nonlinearity, leading to degradation in bit error rate (BER). In turn, the HPA operating point should be backed off to compensate for such degradation at the expense of the HPA efficiency. In this paper, the considered amplifier chain is a solid state power amplifier of Rapp's model. We develop the factors contributing to BER degradation in terms of the input backoff (IBO) level assuming quadrature phase shift keying modulation. Consequently, the BER performance for such an amplifier model is developed as a function in IBO. Then, we show how this developed performance can be used to determine the required HPA operating point to achieve a certain required BER. Accordingly, an improvement in the amplifier efficiency is achieved. All developed analytic expressions are compared against simulationmeasurements, which show that good agreement exists

Factors affecting spectral regrowth in DS-CDMA signals due to PD-HPA nonlinear distortion

When passed through a high power amplifier (HPA), downlink direct sequence-code division multiple access (DS-CDMA) signals result in additional out-of-band emissions, or spectral regrowth, which could affect adjacent channels. In this paper, we explore which characteristics of the input CDMA signal, in relation to the amplifier characteristics, contribute to spectral regrowth. These characteristics represent the key features of the signal's interplay with the HPA, which give the system designer/operator the ability to minimize the spectral regrowth in the transmitted signal. The amplifier chain considered in this paper includes a predistorter (PD), namely PDHPA. Assuming that the baseband CDMA signal is characterized as a band-limited Gaussian process, we develop analytic expressions for the characteristics contributing to spectral regrowth. Finally, simulation experiments are presented to demonstrate the effect of the established signal characteristics on spectral regrowth

Pigmentosins from Gibellula sp. As antibiofilm agents and a new glycosylated asperfuran from Cordyceps javanica

n the course of our exploration of the Thai invertebrate-pathogenic fungi for biologically active metabolites, pigmentosin A (1) and a new bis(naphtho-α-pyrone) derivative, pigmentosin B (2), were isolated from the spider-associated fungus Gibellula sp. Furthermore, a new glycosylated asperfuran 3, together with one new (6) and two known (4 and 5) cyclodepsipeptides, was isolated from Cordyceps javanica. The pigmentosins 1 and 2 showed to be active against biofilm formation of Staphylococcus aureus DSM1104. The lack of toxicity toward the studied microorganism and cell lines of pigmentosin B (2), as well as the antimicrobial effect of pigmentosin A (1), made them good candidates for further development for use in combination therapy of infections involving biofilm-forming S. aureus. The structure elucidation and determination of the absolute configuration were accomplished using a combination of spectroscopy, including 1D and 2D NMR, HRMS, Mosher ester analysis, and comparison of calculated/experimental ECD spectra. A chemotaxonomic investigation of the secondary metabolite profiles using analytical HPLC coupled with diode array detection and mass spectrometry (HPLC–DAD–MS) revealed that the production of pigmentosin B (2) was apparently specific for Gibellula sp., while the glycoasperfuran 3 was specific for C. javanica