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Introduction: Curcumin is involved in erectile signaling via elevation of cyclic guanosine monophosphate (cGMP)., Aim: Assessment of the effects of water-soluble curcumin in erectile dysfunction (ED)., Methods: One hundred twenty male white albino rats were divided into: 1st and 2nd control groups with or without administration of Zinc protoporphyrin (ZnPP), 3rd and 4th diabetic groups with or without ZnPP, 5th diabetic group on single oral dose of pure curcumin, 6th diabetic group on pure curcumin administered daily for 12 weeks, 7th and 8th diabetic groups on single dose of water-soluble curcumin administered with or without ZnPP, 9th and 10th diabetic groups on water-soluble curcumin administered daily for 12 weeks with or without ZnPP. All curcumin dosage schedules were administered after induction of diabetes., Main Outcome Measures: Quantitative gene expression of endothelial nitric oxide synthase (eNOS), neuronal NOS (nNOS), inducible NOS (iNOS), heme oxygenase-1 (HO-1), nuclear transcription factor-erythroid2 (Nrf2), NF-Кβ, and p38. Cavernous tissue levels of HO and NOS enzyme activities, cGMP and intracavernosal pressure (ICP)., Results: Twelve weeks after induction of diabetes, ED was confirmed by the significant decrease in ICP. There was a significant decrease in cGMP, NOS, HO enzymes, a significant decrease in eNOS, nNOS, HO-1 genes and a significant elevation of NF-Кβ, p38, iNOS genes. Administration of pure curcumin or its water-soluble conjugate led to a significant elevation in ICP, cGMP levels, a significant increase in HO-1 and NOS enzymes, a significant increase in eNOS, nNOS, HO-1, and Nrf2 genes, and a significant decrease in NF-Кβ, p38, and iNOS genes. Water-soluble curcumin showed significant superiority and more prolonged duration of action. Repeated doses regimens were superior to single dose regimen. Administration of ZnPP significantly reduced HO enzyme, cGMP, ICP/ mean arterial pressure (MAP), HO-1 genes in diabetic groups., Conclusion: Water-soluble curcumin could enhance erectile function with more effectiveness and with more prolonged duration of action., (© 2012 International Society for Sexual Medicine.)

Objectives: The present study was undertaken to determine the clinical significance of serum levels of HGF, Bcl-2 and NO in the diagnosis and prognosis of breast cancer patients., Patients and Methods: Forty four primary invasive breast cancer patients and fifteen health control subjects were enrolled in the present study. Serum HGF, Bcl-2 and No levels were assayed and correlated with clinico pathological parameters. ROS curve analysis was also done for each biochemical marker., Results: The mean level of HGF was 1198.79 +/- 76.32 pg/ml versus 884.67 +/- 66.88 pg/ml for the control (p = 0.026). The HGF levels were significantly elevated in the patients with increasing the tumor stage (p = 0.036). In addition, HGF levels were markedly increased in negative estrogen receptor patients (p = 0.039). The mean level of Bcl-2 in patients was 12.83 +/- 1.97 ng/ml versus 5.09 +/- 0.40 ng/ml in control (p = 0.027). Levels of Bcl-2 were elevated but not statistically significant in patients with grade I (GI) tumors, negative nodes, ER negative tumors and postmenopausal patients (p = 0.4, 0.8, 0.7 and 0.5, respectively). The patients mean serum levels of NO were 63.07 +/- 4.14 micromol/L versus 43.99 +/- 4.21 micromol/L in control (p = 0.014). The levels of NO were elevated but also not statistically significant in patients with tumor size I, GI tumors, ER negative tumors, positive nodes, stage II tumors and postmenopausal patients (p = 0.3, 0.6, 0.3, 0.7, 0.3 and 0.2 respectively). From the ROC curve analysis, it was observed that the area under curve for HGF, Bcl-2 and NO was 0.695, 0.842 and 0.711, respectively. This result indicates the good validity of the above biomarkers especially Bcl-2 to discriminate the ER positive from the negative tumors in primary breast cancer patients., Conclusion: This study demonstrates that the serum levels of HGF, Bcl-2 or NO may help in the diagnosis of breast cancer patients and may aid in disease prognosis. However, larger study with more patients are required.

Objectives: To study the role of inflammatory chemokine; monocyte chemoattractant protein-1 (MCP-1), and fibrogenic markers [transforming growth factor beta-1 (TGF-β(1)), connective tissue growth factor (CTGF) and fibronectin (FN)] in diabetic nephropathy (DN)., Design and Methods: This study included 17 control and 65 type 2 diabetic subjects (18 normoalbuminuric, 22 microalbuminuric and 25 macroalbuminuric). Demographic characteristics, diabetic index and kidney function tests were monitored. Serum TGF-β(1), plasma CTGF, MCP-1 and FN levels were assayed., Results: Microalbuminuric and macroalbuminuric subjects showed a significant elevation in TGF-β(1), CTGF, MCP-1 and FN levels as compared with control and normoalbuminuric subjects. There was positive correlation between these markers and fasting plasma glucose, albumin excretion rate and with each other., Conclusion: This study revealed the importance of these markers in DN pathogenesis which is powered by their association and thus the possibility of their use as biochemical markers in DN was suggested., (Copyright © 2012 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.)

Background: Obesity, a worldwide health problem, is a metabolic disease currently associated with a cluster and progressive pathologies presenting several features of metabolic syndrome., Objectives: The present study was undertaken to investigate the effect of rimonabant, simvastatin and their combination on obesity associated metabolic disorder mediators in adult male rats., Materials and Methods: Fifty adult male Wistar rats weighing (120 +/- 10 g) were divided into five groups: Group 1 was kept on standard rodent chow and served as normal diet control. Group 2 was given high fat diet (HFD) for twenty weeks and served as HFD control. Groups 3, 4 and 5 administered HFD for ten weeks and then orally received rimonabant (2 mg/kg/day), simvastatin (10 mg/kg/day), combination of both drugs, respectively for another ten weeks with continuing feeding HFD., Results: The current results showed that the treatment of HFD rats with either rimonabant or simvastatin significantly reduced body mass index, total cholesterol, triacylglycerides, low density lipoproteins, tumor necrosis factor alpha and monocyte chemoattractant protein-1, while increased adiponectin serum levels. Rimonabant showed to be more effective than simvastatin. Moreover, concomitant administration of rimonabant and simvastatin achieved the highest effect which nearly normalized most of the studied parameters as compared to singular therapy., Conclusion: Rimonabant is the drug of primary choice as singular therapy for obesity. The adjunct therapy of rimonabant with simvastatin may be a novel and a promising therapeutic approach as it has a beneficial effect on the pathophysiological processes of obesity and its associated metabolic disorders.

Introduction: Cutaneous candidiasis is a disease that affects children as well as adults. The presentation may be localized or systemic, and with multiple etiological agents. The most prevalent infecting species in children differs from that of the adult., Objective: A case is presented where a congenital cutaneous candidiasis was transmitted to the child during birth., Materials and Methods: A full term newborn was exposed to a subclinical vaginal candidiasis infection, and 24 hr after birth, developed congenital cutaneous candidiasis. The etiological agent was Candida albicans, and was associated with sepsis and respiratory distress. Blood cultures, cutaneous biopsy of vesicular lesions, blood tests and lumbar puncture were performed., Results: Biochemistry and blood count showed a CRP of 5.7 mg/dl, leukocytosis with left shift and mild anemia. After 24 hr, the blood analyses showed an increase in a CRP (7.8 mg/dl) and increased progressively for three days; consequently, a lumbar puncture was performed. Blood culture was positive for Staphylococcus aureus. Cutaneous biopsy confirmed the cutaneous candidiasis., Conclusions: The early diagnosis is essential to prevent complications derived by the Candida albicans in newborns.

Poly(sodium 10-undecenyl sulfate) (poly-SUS), poly(sodium N-undecenyl leucinate) (poly-SUL) and their five molecular binary mixed micelles with varied SUS:SUL composition were prepared and used as pseudostationary phases in micellar electrokinetic chromatography (MEKC). Linear solvation energy relationships (LSERs) model and free energy of transfer studies were used to characterize the retention behavior and the selectivity differences among the seven surfactant systems. System constant differences and regression models for varied benzene derivative compounds are used to establish the selectivity differences of the seven pseudostationary phases. The cavity formation and dispersion interaction (the v system constant) and the hydrogen-bonding acidity (the b system constant) of the surfactant systems were found to have the most significant influence on selectivity and MEKC retention. The molecular micelle with sulfate head group, poly-SUS, was found to be more hydrogen-bond acidic than the molecular micelle with leucinate head group, poly-SUL. The other system constants (a, s and e) have modest effect on the retention and selectivity of the benzene derivatives. The model intercept coefficients (c system constants), which are negative for all surfactant systems have unusually large values. The free energy changes of transfer for the functional groups studied have all negative values except phenol and benzyl alcohol. Selectivity differences between pseudostationary phases were also compared by plotting the log k values against each other and were found to agree well with LSER results., (Copyright © 2012. Published by Elsevier B.V.)

Objective: This study was undertaken to investigate the anti-inflammatory role of fennel, carob, doum and mixture of them in improving the renal dysfunction induced in rats by the cyclosporine., Design: Sixty female albino rats were divided into six groups: healthy control rats, cyclosporine injected rats (positive control), other groups were injected by cyclosporine for 7 days and then diet was supplemented with either fennel, doum, carob or mixture of them. After 45 days of supplementation, rats were scarified. Serum and urinary samples were obtained for different biochemical analysis., Methods: The analysis included the determination of creatinine levels in serum and urinary samples, serum ammonia, transforming growth factor-beta1 (TGF-beta1) and tumor necrosis factor-alpha (TNF-alpha), urinary N-acetyl-beta D-glucosaminidase (NAG), beta2 microglobulin as well as calculating the creatinine clearance. Also, an histopathological examination for the kidney tissue was performed., Results: The present study showed that cyclosporine induced the nephrotoxicity as appeared by elevation of serum and urinary levels of creatinine, urinary level of beta2 microglobulin, serum levels of ammonia, TGF-beta1 and TNF-alpha and the NAG level while decreased the creatinine clearance. Addition of fennel, carob, doum or mixture of them significantly improved the kidney functions. Moreover, anti-inflammatory status of animals injected with cyclosporine and supplemented with fennel, carob, doum and mixture of them, showed a significant amelioration in the kidney functions as compared to animals injected with the cyclosporine only. Histopathological investigation of kidney tissue of rat treated with the cyclosporine showed a moderate degree of renal damages. While, groups fed on fennel, carob, doum or mixture of them showed a great improvement in the kidney morphological structure., Conclusions: Diet supplementation with fennel, carob, doum have a promising anti-inflammatory influence on attenuating the complications associated with the renal dysfunction.

The current study was undertaken to investigate the protective role of melatonin (MEL) and acetyl-L-carnitine (ALC) against dexamethasone (DM)-induced neurotoxicity. Adult female rats (60) were divided into: (1) control group, (2) DM-treated group, (3) MEL-treated group, (4) ALC-treated group, (5) MEL- and DM-treated, and (6) ALC- and DM-treated group. Serum acetylcholinesterase (AchE) activity, malondialdehyde (MDA), nitric oxide (NO) level, catalase (CAT), superoxide dismutase (SOD) and glutathione-S-transferase (GST) activities were estimated. Gene expression of the prooxidants (NO synthases NOS-1, NOS-2 and heme oxygenases HO-1, HO-2) and antioxidant enzyme (GST-P1) as well as deoxyribonucleic acid (DNA) fragmentation analysis of brain tissue were investigated. Histological examination of the brain tissue was carried out. DM administration caused significant increase in serum AchE activity, MDA and NO levels accompanied with significant decrease in the antioxidant enzymes activity. Pretreatment with MEL or ALC prior DM has been found to reverse all the former parameters. On the genetic level, DM administration significantly increased the expression level of NOS-1, NOS-2, HO-1, and HO-2 messenger ribonucleic acids (mRNAs) and decreased that GST-P1-mRNA in brain tissue. Also, DM produced DNA fragmentation in brain tissue. Treatment with MEL or ALC prior DM administration tend to normalize the above mentioned parameters. These results were documented by the histological examination of brain tissue. The present study suggests that oxidative stress is involved in the pathogenesis of DM-induced neurotoxicity. The inhibition of oxidative stress via stimulation of the antioxidant enzymes by MEL and ALC pretreatment plays a central protective role in modulation of neurotoxicity induced by DM.

Background: Dermatologists are regularly consulted in their place of work by patients without an official appointment (individuals accompanying other patients, doctors from other specialties, hospital workers, etc)., Objectives: To describe the characteristics of consulting patients, reasons for consultation, severity of complaint, diagnostic and therapeutic approach taken, and level of care provided by the consulted professionals., Results: The typical patient would be a middle-aged female nurse consulting for the first time for a benign melanocytic lesion. In general, the dermatologist will take an empirical or informative therapeutic approach and consider the care provided to be similar to that offered to patients with an official appointment., Conclusions: Unofficial appointments, although commonly for trivial complaints, represent an additional workload in daily clinical practice., (Copyright © 2010 Elsevier España, S.L. y AEDV. All rights reserved.)

The aim of this study was to determine serum concentrations of angiogenic factors including vascular endothelial growth factor (VEGF), interleukin 18 (IL-18) and nitric oxide (NO) in patients with breast cancer and to evaluate whether these factors will be correlated with CA 15.3, as a routine tumor marker for breast cancer or not. This study was conducted on 44 patients with breast cancer and 15 healthy individuals as a control group. The results demonstrated significant increase in serum IL-18, NO and CA 15.3 levels in sera of breast cancer patients when compared to those of the control group (P < 0.001, P = 0.016 and P < 0.001, respectively). However, the mean serum level of VEGF in patients as showed insignificant increase compared to that of the controls was not significant (P = 0.311). Sensitivity of CA 15.3, VEGF, IL-18 and NO to detect patients with disease was 52.2, 21.3, 77.2 and 70.4 %, respectively. In addition, positive status of serum CA 15.3 and/or IL-18 was found in 39 out of 44 (88.6 %) patients, and the positive status of serum CA 15.3 and/or NO was only found in 35 out of 44 (79.5 %). In conclusion, the simultaneous determination of IL-18 or NO in combination with the CA 15.3 may increase the sensitivity to diagnose breast cancer and may aid in disease prognosis.

Dibromoacetonitrile (DBAN) is water disinfectant by-product. Its broad-spectrum toxicity in different test systems in vivo and in vitro has been reported. However, there is a scanty of information regarding dibromoacetonitrile hepatotoxicity. Therefore, this study aimed to investigate the possible mechanisms for dibromoacetonitrile-induced tumor initiation in rat liver cells. Dibromoacetonitrile was orally administered to rats as an acute (60 mg/kg) and fractionated (7.5mg/kg) doses, weekly twice for 4 weeks and once weekly for 8 weeks. Significant increase in malondialdehyde level (approximately 7-, 6- and 4-folds) and extensive depletion in total antioxidant capacity were detected following acute and fractionated doses respectively. Alanine aminotransferase (about 2- and 1-folds) and aspartate aminotransferase (3- and 2-folds) were significantly increased after acute dose and fractionated doses for 4 weeks. Also, these doses of dibromoacetonitrile produced high levels of DNA fragmentation, micronucleated polychromatic erythrocytes and changes in the expression of hepatocyte growth factor gene and proto-oncogenes (c-met and c-myc) in liver tissues. Ability of dibromoacetonitrile to induce DNA damage and alterations in the expression of tumor-initiating genes was suggested to be due to hepatotoxicity, oxidative stress and disturbance in the oxidant/antioxidant status of rat liver., (Copyright © 2011 Elsevier Ltd. All rights reserved.)

Anti-cancer agents which combine two biologically active compounds in one such as steroidal heterocyclic derivatives attain both hormone and cytotoxic effects on cancer cells. The aim of the present study is to synthesize and evaluate new potential chemotherapeutic anti-breast cancer agents. Several pyridazino-, pyrimido-, quinazolo-, oxirano- and thiazolo-steroid derivatives were synthesized. The structure of the novel steroid derivatives was confirmed using the analytical and spectral data. The most structurally promising of the novel synthesized steroid derivatives, compounds 8, 12, 17, 20, 22c, 24c, 30a and 30b, were investigated individually as anti-breast cancer agents against human breast cancer cells (MCF-7) using sulforhodamine B (SRB) assay. The tested compounds 17, 20, 22c and 8 showed potent broad spectrum cytotoxic activity in vitro after 48 h incubation. Compound 17 (IC(50)=2.5 μM) exhibited more inhibitory influence on MCF-7 growth than the reference drug doxorubicin (Dox) (IC(50)=4.5 μM) after 48 h incubation. Also, the present study showed that all the tested steroid derivatives exhibited significant depletion with various intensities in gene expression of breast cancer related genes (VEGF, CYP19 and hAP-2γ). Noteworthy, compounds 17, 20 and 22c showed the most pronounced effect in this respect., (Copyright © 2011 Elsevier Ltd. All rights reserved.)

Background and Objectives: Alzheimer's disease (AD) is a neurological disorder associated with aging. The neuropathologic features of this disease are senile plaques and neurofibrillary tangles, which are present in memory structures and cerebral cortex. This study focuses on evaluation of estradiol administration in the management of neurological changes accompanied with AD in ovariectomized rats intoxicated with aluminum., Materials and Methods: Fifty adult female rats were classified into 5 main groups as follows: Group (1): gonad intact control, Group (2): ovariectomized control group, Group (3): ovariectomized rats were injected subcutaneously with estradiol for 18 weeks, Group (4): ovariectomized rats were injected intraperitoneally with aluminum chloride (AlCl3) daily for three months, Group (5): ovariectomized rats were injected intraperitoneally with AlCl3 for three months, then, they were injected subcutaneously with estradiol three times weekly for 18 weeks. Hydrogen peroxide (H2O2), malondialdehyde (MDA), total antioxidant capacity (TAC), superoxide dismutase (SOD), catalase (CAT), B cell lymphoma 2 (Bcl-2), brain derived neurotrophic factor (BDNF), acetylcholinesterase (AchE) and acetylcholine (Ach) were determined in brain tissue of all studied groups., Results: The results showed that brain TAC, SOD activity, Bcl-2 and BDNF levels were decreased significantly due to ovariectomy. Brain H2O2, MDA levels and AchE activity were increased significantly after AlCl3 administration to ovariectomized rats. Brain TAC, Bcl-2, BDNF and Ach levels were decreased significantly as a result of AlCl3 supplementation to ovariectomized rats. Treatment of rats with estradiol produced marked improvement in the most studied biomarkers and this finding was well documented by histological investigation of the brain which showed remarkable improvement in the feature of the neurons in addition to the disappearance of plaques., Conclusions: We could conclude that estradiol administration significantly ameliorates the neurodegeneration characteristic of Alzheimer's disease in experimental rat model. This may be attributed to its powerful antioxidant, antiapoptotic, neurotrophic as well as its antiamyloidogenic activities.

Context: Cisplatin (CP), a broadly used anticancer drug, is widely known to induce acute renal failure as a result of renal tubular injury., Objective: In this study, the effect of N-acetyl cysteine (NAC) or taurine (TAU) for protection against CP-induced nephrotoxicity was investigated., Materials and Methods: A single dose of CP 1 mg/kg b.wt. for 4 days was given IP to the rats, 10 days rest, and then the dose was repeated for other 4 days. After CP administration, NAC or TAU was given IP in a dose of 50 mg/kg b.wt. 3 times weekly for 8 weeks., Results: CP-induced nephrotoxicity is reflected in high values of blood urea and creatinine levels. In addition, the significant increase in the β(2)-MG and N-acetyl-β-glucosaminidase enzymes exhibited a strong correlation with histology scores of overall proximal tubule damage as compared with the normal control values. Treatment with TAU or NAC after CP administration significantly ameliorated CP-induced nephritic oxidation stress markers as compared with CP-treated group. On the other hand, treatment with TAU or NAC after CP administration significantly ameliorated CP-induced nephritic inflammation with possible attenuation of renal injury., Discussion: These data suggest that oxidative stress and inflammation are involved in the pathogenesis of CP-induced acute renal failure. The inhibition in oxidative stress and the elevation of the total antioxidant capacity as well as the inhibition of the inflammatory biomarkers by NAC or TAU after CP administration may play a central role in modulation of nephrotoxicity induced by CP., Conclusion: NAC and TAU have antioxidant and anti-inflammatory against CP-induced nephrotoxicity.

The antitumour activities of extracts from the Red Sea seaweeds Jania rubens, Sargassum subrepandum, and Ulva lactuca were investigated in an in vivo mice model based on intramuscular injection of Ehrlich ascites tumour cells. In parallel, antioxidant activities were measured. Tumour marker levels, liver biochemical parameters, and hepatic oxidant/antioxidant status were measured to prove the anticancer and antioxidant nature of the algal extracts. Significant decreases in carcinoembryonic antigen (CEA) and a-fetoprotein (AFP) levels, activities of liver enzymes, levels of nitric oxide (NO) and malondialdehyde (MDA), and an increase in total antioxidant capacity (TAC) were recorded in groups treated with the algal extracts. Jania rubens was selected for phytochemical screening of its phytoconstituents. In addition, carotenoids, halides, minerals, lipoidal matters, proteins, and carbohydrates were studied. Furthermore, 7-oxo-cholest-5(6)-en-3-ol (1) and cholesterol (2) were isolated from the dichloromethane fraction.

There is a great deal of interest in neurotrophin therapy to prevent neuronal degeneration. The present study aimed at synthesizing new functionalized indole derivatives with structures justifying neuroprotective activity using L-tryptophan (TRP) as starting material. The potential neuroprotective effect of these newly synthesized agents against acrylamide (ACR) induced neurotoxicity was investigated in adult female rats. The novel indole derivatives, indolylmethyl pyridine derivatives 9a,b, pyrimidinylindolyl propanone derivatives 12a-c, pyrazolylindolyl propanone derivatives 14a,b, and indolyl tetrazolopropanoic acid derivative 17 were synthesized and their chemical structures were confirmed by studying their analytical and spectral data. The administration of ACR [ip, 50mgkg(-1) body weight (b. wt.)] alone resulted in significant increase in brain malondialdehyde level (MDA) and lactate dehydrogenase (LDH) activity whereas it caused significant decrease in brain monoamines levels and antioxidant enzymes activity. Treatment with the indole derivatives 9b, 12c, 14a, and 17 (ip, 50mgkg(-1) b. wt.) prior to ACR produced neuroprotective activity with various intensities depending on the structure of each compound. Compound 17 in which the tetrazole ring was attached to the TRP moiety ranked as the strongest neuroprotective agent. All the tested compounds have been shown to possess antioxidant properties offering promising efficacy against oxidative stress induced by ACR administration., (Copyright © 2011 Elsevier Ltd. All rights reserved.)

Background: While continuous positive airway pressure (CPAP) effectively treats obstructive sleep apnea (OSA), adherence to CPAP is suboptimal. The short-term efficacy of and adherence with a convenient expiratory positive airway pressure (EPAP) nasal device was evaluated in OSA patients non-adherent with CPAP., Methods: Participants were OSA patients who refused CPAP or used CPAP less than 3 h per night. After demonstrating tolerability to the EPAP device during approximately 1 week of home use, patients underwent a screening/baseline polysomnogram (PSG1) and a treatment PSG (PSG2). Patients meeting prespecified efficacy criteria underwent PSG3 after about 5 weeks of EPAP treatment., Results: Forty-seven of 59 eligible patients (80%) tolerated the device and underwent PSG1. Forty-three patients (27 m, 16f; 53.7±10.9 years) met AHI entry criteria and underwent PSG2. Mean AHI decreased from 43.3±29.0 at baseline to 27.0±26.7 (p<0.001) at PSG2. Twenty-four patients (56%) met efficacy criteria; their mean AHI was 31.9±19.8, 11.0±7.9, 16.4±12.2 at PSG1, PSG2, and PSG3, respectively (p<0.001, PSG1 vs. both PSG2 and PSG3). Mean Epworth Sleepiness Scale (ESS) scores were 12.3±4.8 at baseline, 11.1±5.1 at PSG1, and 8.7±4.4 at PSG3 (p=0.001 compared to baseline). Device use was reported an average of 92% of all sleep hours., Conclusions: The improvements in AHI and ESS, combined with the high degree of treatment adherence observed, suggest that the convenient EPAP device tested may become a useful therapeutic option for OSA., (Copyright © 2010 Elsevier B.V. All rights reserved.)

The current study was undertaken to elucidate a possible neuroprotective role of dehydroepiandrosterone (DHEA) against the development of Alzheimer's disease in experimental rat model. Alzheimer's disease was produced in young female ovariectomized rats by intraperitoneal administration of AlCl(3) (4.2 mg/kg body weight) daily for 12 weeks. Half of these animals also received orally DHEA (250 mg/kg body weight, three times weekly) for 18 weeks. Control groups of animals received either DHAE alone, or no DHEA, or were not ovariectomized. After such treatment the animals were analyzed for oxidative stress biomarkers such as hydrogen peroxide, nitric oxide and malondialdehyde, total antioxidant capacity, reduced glutathione, glutathione peroxidase, glutathione reductase, superoxide dismutase and catalase activities, antiapoptotic marker Bcl-2 and brain derived neurotrophic factor. Also brain cholinergic markers (acetylcholinesterase and acetylcholine) were determined. The results revealed significant increase in oxidative stress parameters associated with significant decrease in the antioxidant enzyme activities in Al-intoxicated ovariectomized rats. Significant depletion in brain Bcl-2 and brain-derived neurotrophic factor levels were also detected. Moreover, significant elevations in brain acetylcholinesterase activity accompanied with significant reduction in acetylcholine level were recorded. Significant amelioration in all investigated parameters was detected as a result of treatment of Al-intoxicated ovariectomized rats with DHEA. These results were confirmed by histological examination of brain sections. These results clearly indicate a neuroprotective effect of DHEA against Alzheimer's disease.

Acrylamide (ACR) has been shown to be a neurotoxic agent for both laboratory animals and human. The present study aimed at synthesizing new functionalized melatonin derivatives bearing promising heterocyclic moiety that could be expected to have protective effect against ACR-induced neurotoxicity in adult female rats. The novel melatonin derivatives 4, 6, 7 and 11 were synthesized and their chemical structures were confirmed by studying their analytical and spectral data. The administration of ACR [i.p., 50 mg kg(-1) body weight (b. wt.)] alone resulted in significant increase in brain malondialdehyde level (MDA) and lactate dehydrogenase (LDH) activity whereas it caused significant decrease in brain monoamines levels and antioxidant enzymes activity. Treatment with melatonin derivatives 4, 6, 7 and 11 (i.p., 50 mg kg(-1) b. wt) prior to ACR produced significant decrease in brain MDA level and LDH activity with concomitant significant increase in brain monoamines and antioxidant enzymes activity. It could be concluded that the new synthesized melatonin derivatives exhibited promising protective activity against ACR-induced neurotoxicity., (Copyright © 2010 Elsevier Masson SAS. All rights reserved.)

Objective: To assess homocysteine, folic acid and vitamin B12, trace element levels and oxidant/antioxidant status in Down syndrome (DS) mothers and children., Design and Methods: 42 mothers with previous history of bearing DS baby with karyotypically confirmed full trisomy 21 were included. 48 healthy mothers with their healthy children were considered as control. Serum B12, folic acid, total homocysteine (tHcy), vitamins E and C, TBARS and trace elements were estimated., Results: DS mothers showed higher levels of tHCy, lower levels of folic acid and vitamin B12 than controls. tHCy and folic acid concentrations were significantly decreased, while vitamin B12 exhibited a slight decrease in DS children versus control. Vitamins E and C, zinc and copper levels were markedly reduced in DS mothers. By contrast, TBARS showed significant elevation in them. Furthermore, DS children had severe reduction of vitamin C and zinc levels relative to healthy children. However, vitamin E showed slight reduction and TBARS displayed a slight rise in DS children., Conclusion: Abnormal folic acid-homocysteine metabolism is a potent marker to identify women at risk for having DS child and it also exposes them to oxidant/antioxidant imbalance., (2010 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.)

Curcumin exerts a hypoglycemic action and induces heme-oxygenase-1 (HO-1). We evaluated the effect of curcumin on isolated islets of Langerhans and studied whether its action on insulin secretion is mediated by inducible HO-1. Islets were isolated from rats and divided into control islets, islets incubated in different curcumin concentrations, islets incubated in hemin, islets incubated in curcumin and HO inhibitor, stannous mesoporphyrin (SnMP), islets incubated in hemin and SnMP, islets incubated in SnMP only, and islets incubated in 16.7 mmol/L glucose. Heme-oxygenase activity, HO-1 expression, and insulin estimation was assessed. Insulin secretion, HO-1 gene expression and HO activity were significantly increased in islets incubated in curcumin, hemin, and glucose compared with controls. This increase in insulin secretion was significantly decreased by incubation of islets in SnMP. The action of curcumin on insulin secretion from the isolated islets may be, in part, mediated through increased HO-1 gene expression.

Objectives: To investigate the possibility of depending on adiponectin and leptin as early predictors of microvascular complications in type 1 diabetic subjects., Design and Methods: We studied 63 type 1 diabetic subjects from the National Institute of Diabetes (30 normoalbuminuric and 33 microalbuminuric). Clinical, demographic characteristics and kidney function tests were monitored. Plasma levels of adiponectin, leptin, interlukein-6 (IL-6), and the high sensitive C-reactive protein (CRP) were measured in these subjects., Results: Microalbuminuric subjects showed a significant elevation in adiponectin levels and a significant decrease in leptin levels as compared to normoalbuminuric subjects. Adiponectin showed a significant positive correlation with microalbuminuria concentrations while leptin showed a significant negative correlation with both fasting blood glucose and glycated hemoglobin A(1c)., Conclusion: The results of this study introduced the possibility of depending on adiponectin and leptin as early, reliable, and sensitive predictors for the microvascular complications monitored by microalbuminuria concentration and glycemic control indices.

Background: Adipose tissue is known to produce and secrete a variety of bioactive substances known as adipocytokines. Adiponectin and leptin are considered to be among the most important adipocytokines:, Objectives: We sought to explore the relationships between adipocytokines (adiponectin and leptin), plasma lipoprotein lipid, and diabetic control indices in type 1 diabetic subjects., Subjects and Methods: In this study 63 clinically diagnosed type 1 diabetic subjects and 30 age- and sex-matched healthy control subjects were analyzed. Age, sex, diabetic duration, family history of diabetes, daily insulin dose, weight, height, body mass index, and systolic and diastolic blood pressure were recorded. Fasting blood glucose, glycated hemoglobin A(1c), total hemoglobin, plasma lipoprotein, lipid and plasma concentrations of adiponectin and leptin were measured in type 1 diabetic subjects and control subjects., Results: In this study a significant increase in triglycerides and high-density lipoprotein cholesterol in plasma of type 1 diabetics was found as compared with normal control subjects. In type 1diabetic subjects, plasma adiponectin was significantly elevated, whereas leptin showed a significant decrease as compared to a normal control group. Leptin concentrations showed a positive correlation with body mass index and systolic blood pressure but a negative correlation with both fasting blood glucose and glycated hemoglobinA(1c)., Conclusion: The results of this study suggest that blood leptin but not adiponectin concentrations have a significant correlation with indices of glycemic control.

Background: Nipple discharge causes discomfort and anxiety to many women. Nipple discharge is most commonly associated with endocrine alterations and/or medications. These often result in duct ectasia and/or fibrocystic changes that may lead to discharge from one or several ducts. The most common cause of clinically significant discharge is intraductal growth of the ductal epithelium, due to hyperplasia, micropapillary proliferation, solitary papillomas and/or ductal carcinoma (both in situ and invasive). The aim of the study was to evaluate the role of the gray-scale ultrasound and colour Doppler in the diagnosis of intraductal pathology in patients with nipple discharge., Patients and Methods: One hundred & seven patients were included in the study, (age range 23-65years). Standard mammographic views were taken. Ultrasound evaluation was performed for all cases; ductography for 20 cases and ductoscopy for 3 cases. US guided fine needle biopsy was done in 7 cases; microducectomy of affected duct was done in 20 cases and major duct excision in 5cases. Fibro-optic Ductoscopy is performed for 3 cases., Results: Revision of biopsy specimens of 17 cases with intraluminal masses detected by US revealed: Six cases with intraductal carcinoma, intraductal papilloma in 7 cases, 1 case of ductal papillomatosis. Three cases showed atypical cells: Intraductal papilloma with atypia in 2 cases, proliferative hyperplasia with atypia in one case. Eighty eight cases had simple duct ectasia (51 bilateral multiple and 37 focal duct ectasia). No dilated ducts were detected in 2 cases. Fibro-optic Ductoscopy confirmed the presence of intraductal papilloma in one case, carcinoma in one case, no intraductal masses in the third case. A 6 months follow-up was requested for all cases with no detected intra luminal pathology. Ultrasound examination is highly sensitive (100%) but less specific (82.4%) in diagnosis of intraductal pathology. Colour & power Doppler are sensitive (94%) in detecting flow in intraductal echogenic masses to differentiate them from insipissated secretions. Colour and power Doppler raises specificity and diagnostic accuracy to 100%. Ductography is an underused procedure that is sensitive (100%) but less specific (60%) in characterization of intraductal filling defects., Conclusion: Ultrasonography is a mandatory complement to mammography in these cases, US guided fine needle biopsy is minimally invasive technique in confirming the diagnosis of suspicious mass. Ultrasound may also be a guide to fibro-optic ductoscope., Key Words: Ductography - Nipple discharge - Intraductal carcinoma - Intraductal papilloma - In situ ductal carcinoma - Invasive ductal carcinoma - Duct ectasia - Breast ductoscopy.

Objective: To assess the role of HO-1 in HCC progression and to study the expression of apoptotic factors represented by TNF-alpha, and Fas-L versus antiapoptotic and angiogenic factors represented by HO-1, TGF-beta, HGF, and VEGF in HCC compared to non cancerous cirrhotic liver., Design and Methods: Liver biopsies were taken from twelve patients with grade II HCC confined to the liver and twelve patients with non cancerous liver cirrhosis (served as control). RT-PCR of previous genes was evaluated., Results: HO-1, VEGF, HGF, and TNF-alpha genes were significantly increased (P<0.05) in HCC compared to control. Fas-L showed a significant decrease (P<0.05) in HCC compared to control. TGF-beta was higher in HCC than control but the difference was not statistically significant (P>0.05). HGF showed significant positive correlation with HO-1 (r=0.8217, P=0.001)., Conclusion: HCC is associated with increased expression of VEGF, HGF, and TGF-beta, and with suppression of Fas-L. In addition, HO-1 is highly significantly expressed in HCC. The significant positive correlation between HO-1 and HGF was first reported in Egyptian human liver biopsies, and this suggests that it may play a role in the progression of hepatocellular carcinoma.

The use of nitrofurans as veterinary drugs has been banned in the EU since 1993 due to doubts on the safety of the protein-bound residues of these drugs in edible products. Furazolidone (FUZ) is a nitrofuran drug, which has been used for many years as an antibacterial drug in veterinary practice. The aim of the current study is to investigate the role of L-cysteine and L-methionine in the protection against hormonal imbalance and the genotoxicity induced by FUZ using the micronucleus (MN) assay and random amplified polymorphism DNA (RAPD-PCR) analysis in female rats. Forty female Sprague-Dawley rats were divided into four groups included the untreated control group; a group treated with FUZ (300 mg/kg b.w.); a group treated with a mixture of L-cysteine (300 mg/kg b.w.) and L-methionine (42.8 mg/kg b.w.) and a group treated with FUZ plus the mixture of L-cysteine and L-methionine for 10 days. The results indicated that FUZ induced hormonal disturbances involving thyroid, ovarian and adrenal hormones. Moreover, FUZ increased the micronucleus formation and induced changes in polymorphic band patterns. The combined treatment with FUZ and the mixture of L-cysteine and L-methionine succeeded to prevent or diminish the endocrine disturbance and the clastogenic effects of FUZ. The current study is casting new light on the complex mechanisms underlying the ameliorating action of dietary L-cysteine and L-methionine against FUZ toxicity in experimental animals.

Objective: To study the effect of mesenchymal stem cells (MSC) on experimental liver fibrosis in rats., Design and Method: MSC were derived from bone marrow obtained from femoral and tibial bones of male albino rats. MSC were separated, grown, and propagated in culture for 4 weeks and were characterized morphologically and by detection of CD29 by RT-PCR. They were then infused into the tail vein of female rats that received CCl4 injection to induce liver fibrosis. Rats were divided into 4 groups: control, CCl4, CCl4 plus MSC, and MSC. Liver tissue was examined histopathologically and liver functions (ALT and serum albumin) were estimated for all groups. Y-chromosome gene (sry) was assessed by PCR in liver tissue of the female rats to confirm uptake of the male stem cells. Hydroxyproline content in liver tissue was assessed by chemical methods and expression of the collagen gene (type I) was detected as a marker for liver fibrosis. Results of the present study showed that MSC have a significant antifibrotic effect as evidenced by the significant decrease in liver collagen gene expression as well as the decrease in hydroxyproline content in the CCl4/MSC group (p<0.001) compared to the CCl4 group. The Y-chromosome gene (sry) was detected by RT-PCR in the CCl4/MSC group, but was not detected in control group and other groups. The CD29 gene was expressed in MSC culture, and this confirmed the efficiency of isolation and propagation of MSC in culture. With regard to liver function, there was also a significant improvement and elevation of serum albumin in the CCl4/MSC group compared to the CCl4 group (p<0.05). As regard to the liver enzyme ALT, there was a decrease of its level in the CCl4/MSC group compared to the CCl4 group. However, this was statistically nonsignificant (p>0.05). In conclusion, MSC have a potential therapeutic effect against the fibrotic process through their effect in minimizing collagen deposition in addition to their capacity to differentiate into hepatocytes.

Aim: To investigate the association between serum insulin-like growth factor 1 (IGF-1), osteocalcin, and parathyroid hormone (PTH) levels with the etiology and clinical condition of patients with chronic liver disease., Methods: Eighty children with hepatocellular damage were divided into 3 groups according to the etiology of disease infection: bilharziasis (9 patients), hepatitis B virus (HBV, 12 patients) and hepatitis C virus (HCV, 29 patients). The Child score index was found as A in 24 patients, B in 22 patients, C in 4 patients. Thirty healthy children served as control group. HBsAg, HBcAbIgM, HBcAbIgG, and anti-HCV were detected using ELISA technique. HCV-RNA was measured by reverse transcription polymerase chain reaction (RT-PCR). Anti-bilharzial antibodies were detected by indirect haem- agglutination test. Liver function tests were performed using autoanalyser. Serum IGF-1, osteocalcin and PTH levels were measured by ELISA technique. Abdominal ultrasonography was also conducted., Results: Serum IGF-1 level was significantly lower in all patient groups with liver diseases, while serum osteocalcin and PTH levels were significantly elevated in patients with HBV and HCV infections compared with the control group. Serum osteocalcin and PTH concentrations were measured with the severity of liver disease from Child A to C. Child A patients unexpectedly showed significantly reduced IGF-1 levels in comparison to patients staged as Child B or C. Serum osteocalcin level was negatively correlated with albumin (14.7 +/- 0.54 vs 3.6 +/- 0.10, P < 0.05), while that for PTH was positively correlated with total protein (70.1 +/- 2.17 vs 6.7 +/- 0.10, P < 0.05) in patients with HCV infection., Conclusion: Low serum IGF-1 level seems to play a critical role in the bone loss in patients with chronic liver disease. Elevated biochemical markers of bone remodeling suggest high-turnover in patients with viral infection and reflect severity of the clinical stage.

Objectives: Both heme oxygenase-1 (HO-1) and vascular endothelial growth factor (VEGF) have been shown to be involved in the progression of atherosclerosis. The relationship between HO-1 and VEGF gene expression and their proteins in endothelial cells from human atherosclerotic arterial specimens was investigated., Design and Methods: The study included seventeen human arterial specimens with early and six specimens with advanced atherosclerotic lesions. Ten specimens were obtained from healthy young adults undergoing arterial reconstruction for trauma and were considered as non-atherosclerotic control. HO-1 and VEGF expressions as well as HO activity and VEGF protein content were measured in isolated endothelial cells (ECs)., Results: HO-1 expression and activity (5.3+/-2.1 nmol bilirubin/mg protein/h) were only present in ECs from advanced atherosclerotic lesions. VEGF expression was more strongly expressed in ECs from advanced lesion compared with early lesions and was absent in healthy arteries. VEGF protein (1.35+/-0.69 ng/mg) was only detected in advanced lesions. A significant positive correlation (r=0.9, p<0.01) exists between HO activity and VEGF protein content in ECs of advanced lesions., Conclusions: This study demonstrated that HO-1 expression and activity in ECs are present only in advanced atherosclerosis whereas, VEGF expression is present in early as well as in advanced atherosclerosis and the degree of its expression increases with severity of atherosclerosis. This study suggests an association between HO activity and VEGF protein in human ECs from advanced atherosclerotic lesions.

Background: HPV infection is the main cause of cervical cancer and cervical intraepithelial neoplasia worldwide. The second-generation HC II test is a liquid hybridization assay designed to detect 18 HPV types. The aim of the present study was to detect the rate of HPV infection and its various genotypes among Egyptian women., Material/methods: We evaluated 166 Egyptian women. They were classified according to cytology into those with normal cytology, chronic nonspecific cervicitis, and squamous intraepithelial lesions (SILs)., Results: The overall prevalence of HPV DNA in the studied groups was 15.06% (25/166). Among the 25 HPV-positive women, 16 (64%) were infected with high-risk HPV types, 4 (16%) with low risk HPV types, while 5 (20%) had both types. Twenty-one (84%) of the infected women harbored at least one high-risk HPV type, while 9 (36%) harbored at least one low-risk HPV type. Values of HPV viral load for low-risk HPV infection showed no significant difference in the normal and chronic nonspecific cervicitis groups. But when HPV viral load of high-risk HPV infection was compared in the normal, chronic nonspecific cervicitis, and SIL groups, a significant difference was found. The same was detected between chronic nonspecific cervicitis and SIL and between normal cytology and SIL, suggesting an association between viral load and risk of SIL and, accordingly, cancer., Conclusions: It may be concluded that HPV testing using the HC II assay is a useful tool when combined with cytology in the diagnosis of high-risk HPV viral types in apparently normal tissues.

Chemoprevention by extracts of Laurencia obtusa (E1) and Caulerpa prolifera (E2) collected from the Egyptian coast of the Red Sea against aflatoxin B(1) (AFB(1))-initiated hepatotoxicity in female Sprague-Dawley rats has been studied. Animals were fed aflatoxin-contaminated diet (3 mg kg(-1) diet) for 6 days then treated orally with pure aflatoxin B(1) (AFB(1)) (200 microg kg(-1) b.w.) for 4 days either in combination with or before E1 or E2 administration (50 mg kg(-1) b.w.). AFB(1) resulted in a signicant increase in serum alpha fetoprotein, carcinoembryonic antigen, tumor necrosis factor alpha, nitric oxide, interleukin-1alpha, procollagen III and lipid peroxidation level in the liver. It caused a signicant decrease in food intake, body weight, serum leptin, the activities of glutathione peroxidase, superoxide dismutase and DNA and RNA concentrations in the liver. Cotreatment with AFB(1) and E1 or E2 resulted in an obvious improvement in all tested parameters. Noteworthy, E2 was more effective than E1 in the protection against AFB(1)-induced hepatotoxicity., (Copyright 2006 John Wiley & Sons, Ltd.)

Acrylamide (ACR) is an industrial neurotoxic chemical that has been recently found in carbohydrate-rich foods cooked at high temperatures. ACR was designated as a probable human carcinogen by IARC (1994) and USEPA (1988). Panax ginseng extract has efficacies such as anticancer, antihypertension, antidiabetes and antinociception. The objective of the current study is to evaluate the protective effects of Panax ginseng extract against ACR-induced toxicity in rats. Sixty adult Sprague Dawley female rats were divided into six groups included a control group, a group treated orally with ACR (50 mg kg(-1) body weight; b.w.) for 11 days, a group treated orally with Panax ginseng extract (20 mg kg(-1) b.w.) for 11 days and groups treated orally with Panax ginseng for 11 days before, during or after 11 days of ACR treatment. The results indicated that treatment with ACR alone resulted in a significant increase in lipid peroxidation level and LDH activity in brain homogenate as well as in serum CK activity, whereas it caused a significant decrease in SOD activity and a small but statistically insignificant decrease in Na(+)K(+)-ATPase activity in brain homogenate. Serum serotonin, corticosterone, T3, T4, TSH, estradiol, progesterone and plasma adrenaline were significantly decreased in ACR-treated rats. Treatment with Panax ginseng before, during or after ACR treatment reduced or partially antagonized the effects induced by ACR towards the normal values of controls. It could be concluded that Panax ginseng extract exhibited a protective action against ACR toxicity and it is worth noting that treatment with Panax ginseng extract before or at the same time as ACR treatment was more effective than when administered after ACR treatment., (Copyright 2006 John Wiley & Sons, Ltd.)

The objective of this study was to elucidate the potential role of novel synthesized aminosteroidal heterocyclic compounds 2, 5, 9b and 10c against iron-induced oxidative stress with particular insight on erythrocyte ghosts in male rats. Chronic iron supplementation (3000 mg kg(-1) diet) for 6 weeks significantly increased plasma iron and ferritin levels. It also produced significant increase in plasma TNF-alpha and NO levels. Lipid metabolism was also affected by excess iron, so that plasma and erythrocyte membrane total cholesterol, triglycerides, phospholipids and total lipid levels were significantly elevated. In consequence, a significant increase in plasma leptin level was detected. Iron overload clearly induces oxidative stress as indicated by the significant increase in both plasma and erythrocyte membrane lipid peroxidation levels. Noteworthy, excess iron not only decreased the mean value of erythrocyte membrane protein but also caused marked alterations in the membrane protein fractions with concomitant inhibition in erythrocyte membrane ATPases activity. On the other hand, treatment with the aminosteriodal heterocyclic compounds especially compounds 5, 2, and 10c in an oral dose of 5 mg kg(-1) B.W. per day could ameliorate almost all of the changes in plasma and erythrocyte ghosts components induced by iron overload. The efficacious role of these novel synthesized aminosteriods in preventing iron-induced oxidative stress may be mediated through their iron chelating properties, anti-lipid peroxidation activities and membrane stabilizing actions. The encouraging results obtained in the present study lend credence to substantial investigation to assess the use of these compounds as a potent line of therapy to retard the pathogenesis of iron overload diseases.

The aim of this work was to investigate the protective role of baker's yeast Saccharomyces cerevisiae against the hepatotoxic effect of the drug flutamide that is widely used for treatment of metastatic prostate adenocarcinoma. Administration of flutamide to adult male rats in a dose of 100 mg/kg b.w. daily for 15 days resulted in serious hepatic injury. Highly significant increase in each of serum ALT, ALP, bilirubin, bile acids and cholesterol level, relative to the control group, was observed. Also, a highly significant increase in the serum glutathione-S-transferase isoforms: alpha-GST and pi-GST and each of TNF-alpha and NO levels was recorded. Moreover, highly significant decrease in hepatic glutathione peroxidase and superoxide dismutase activities was observed. In addition, the authors noticed a significant increase in serum testosterone levels with concomitant highly significant increase in serum acid phosphatase activity. Prophylactic treatment of male rats with baker's yeast in a dose of 4.8 mg/kg b.w. daily for 15 days, followed by a combination of flutamide (100 mg/kg b.w.) and yeast (4.8 mg/kg b.w.) daily for other 15 days resulted in marked improvement in rat's liver function, whereas the serum testosterone and acid phosphatase levels retained values parallel to those recorded for the flutamide-treated rats. Histological examination of liver tissues showed that flutamide caused hydropic degeneration, necrotic areas and marked increase in Kupffer cells. The central vein is congested with blood and signs of apoptosis appeared in the hepatocytes in the form of fragmentation of the nuclei and blebbing of the cytoplasm. On the other hand, in the rats treated with both yeast and flutamide, the hepatic cords were more regularly arranged, signs of degeneration or apoptosis were less pronounced and some hepatocytes appeared binucleated. The authors postulate that each one of the powerful antioxidative components in S. cerevisiae effectively participated in attenuation of the oxidative stress caused by flutamide metabolites, and in promoting regeneration of new hepatocytes and meanwhile could restore liver function beyond normal status.

This study aimed at evaluation of melatonin and some of its novel synthesized derivatives 3, 4, 9 and 10b as cardioprotective agents against doxorubicin-induced acute cardiac toxicity in rats. Also, this work was extended to study the potential role of each synthesized derivative in comparison with the parent compound melatonin. Intraperitoneal injection of a single dose (15mg/kg B.W.) of doxorubicin resulted in significant increase in serum troponin I, leptin, triglycerides, cholesterol and LDL-cholesterol levels with concomitant decrease in serum T(3), T(4) and IL-1alpha levels. In contrast, intraperitoneal injection of melatonin or its synthesized derivatives especially compounds 3 and 10b in a dose of 5mg/kg B.W./day for 10days reversed doxorubicin-induced changes in the above mentioned parameters towards the normal values. The present data revealed that doxorubicin exerts its action mainly through the oxidative stress. This appeared from the significant elevation in serum nitric oxide level and cardiac lipid peroxidation level with concomitant decrease in cardiac antioxidative enzymes activity. Treatment with melatonin and its derivatives 3 and 10b could reduce the markers of oxidative stress and restore the activity of the antioxidative enzymes in the heart tissue. In conclusion, the cardioprotective effect of melatonin and its derivatives may be mediated through the antioxidant and free radical scavenging activity of these compounds.

Objective: To determine the clinical value of assaying serum levels of neopterin, tumor necrosis factor-alpha (TNF-alpha) and soluble tumor necrosis factor receptor II (p75) (sTNFRII) in patients with systemic lupus erythematosus (SLE), manifested clinically with lupus nephritis (LN), neuropsychiatric lupus erythematosus (NPLE), and/or vasculitis compared with established parameters (complements C3 and C4)., Patients and Methods: Serum concentrations of neopterin, TNF-alpha and sTNFRII were studied in 40 female patients with SLE at various degrees of disease activity and in 10 healthy controls, matched for age and sex, using an ELISA kit. Disease activity was assessed by the SLE disease activity index (SLEDAI) score. Thirty-five, 30 and 28 of our patients presented with LN, NPLE and/or vasculitis, respectively, as the main clinical manifestation., Results: Serum levels of neopterin, TNF-alpha and sTNFRII were significantly increased, while the TNF-alpha/sTNFRII ratio, C3 and C4 levels of SLE patients were significantly lower than those of healthy controls. Neopterin and sTNFRII were the only parameters that showed significantly higher levels in SLE patients with mild activity compared to normal subjects and were the only parameters that showed a significant elevation in membranous nephritis and in mild NPLE compared to patients without nephritis and NPLE. Patients with vasculitis had significant elevation of serum neopterin, TNF-alpha and sTNFRII levels compared to patients without vasculitis. We found significant correlations between all measured variables and the SLEDAI score. Also, serum neopterin levels showed significant positive correlation with serum TNF-alpha, sTNFRII and TNF-alpha/sTNFRII levels. Serum neopterin and sTNFRII could be used to identify SLE patients from normals with a sensitivity and specificity of 100%. Multivariate linear regression analysis showed that serum sTNFRII was the only significant independent variable among parameters for prediction of SLE disease activity., Conclusion: We suggest that serum sTNFRII and neopterin are more sensitive markers of disease activity than TNF-alpha, C3 or C4. However, sTNFRII may be a clinically useful independent marker for prediction of SLE disease activity and to differentiate normal subjects from those having mild SLE.

This study was conducted to assess the frequency of gastroesophageal reflux disease (GERD) and Barrett's esophagus among Sudanese patients with clinical symptoms of heartburn. One hundred and five patients were included in the study; forty seven patients had evidence of reflux oesophagitis, 61.7% of whom had grade B oesophagitis according to the modified Los Angeles classification and 10.6% had Barrett's oesophagus. 78.7% of the biopsies from the esophageal cardia revealed presenced of inflammation (Carditis). Dysplasia was documented in 21.3% of these biopsies. Helicobacter pylori was detected 59.6% of gastrooesophageal reflux disease patients and 56.8% of patients with carditis. However, 80% of patients with Barrett oesophagus were positive for Helicobacter pylori. It was concluded that gastro-oesophageal reflux disease affects all age groups with males being affected more than females and Helicobacter pylori infection did not play a major role in gastro-oesophageal reflux disease orits complications.

Studies were conducted into the effects on pituitary gonadotrophic hormones in ovariectomized rats of butorphanol, a synthetic morphine derivative which was claimed to be a potent analgesic with few side-effects, in comparison to effects of the naturally occurring alkaloid morphine. For this purpose, 3 groups of ovariectomized rats were used. Rats of the 1st group were injected butorphanol at 2 dose levels (1 or 2 mg/kg body weight [b.w.]. Those of the 2nd group were injected morphine sulphate (10 or 20 mg/kg b.w.). The 3rd group was injected saline and served as control. Blood samples were collected by orbital sinus punctures, just before treatment and 1 hour post injection. Luteinizing hormone (LH) and follicle-stimulation hormone levels were determined in the sera of rats by radio-immuno-assay. The results revealed that morphine, at the 2 dose levels used, produced more than 90% decrease in serum LH concentration, whereas butorphanol produced more than 70% decrease in serum LH levels. Both morphine and butorphanol, at the 2 doses used, produced more than 76% decrease in serum follicle stimulating hormone concentration. It is concluded that butorphanol, the morphinic derivative, has a depressive effect on the synthesis and/or release of gonadotrophic hormones. This inhibitory effect, however, was nearly as potent as that produced by morphine sulphate.

A single iv injection of 0.31, 0.62, 1.25, 2.5, 5, 10, or 20 mg/kg body wt of a phenothiazine derivative, propiomazine (PP), into male rats significantly (P less than 0.05) increased plasma prolactin concentrations. The higher doses (5, 10, and 20 mg/kg body wt) produced increases that were greater in both magnitude and duration than those produced by the lower doses. The higher doses of PP, along with the elevations in plasma prolactin, also produced concomitant decreases in plasma luteinizing hormone (LH) levels. Pretreatment with L-dopa (100 mg/kg body wt) completely blocked the PP-induced stimulation of prolactin release, indicating that antidopaminergic action of PP either at the hypothalamic or anterior pituitary level was responsible for its effects on the release of prolactin.

A single iv injection of 15 or 30 but not 7.5 mg/kg BW of an antiviral drug, amantadine, significantly (P less than 0.05) decreased plasma prolactin (PRL) concentrations in male rats. This effect was dose-dependent, with the highest dose producing a longer-lasting decrease in plasma PRL. The amantadine-induced decrease was unaffected by a simultaneous injection of 5-hydroxytryptophan (30 mg/kg BW) but was completely blocked by a simultaneous injection of haloperidol (0.05 mg/kg BW). It is concluded that this novel effect of amantadine on PRL is produced by an interaction with the dopaminergic system.

In this study the effects of the major tranquilizer, xylazine, on serum prolactin level were studied in male rats. The results showed that, unlike all other tranquilizers, xylazine produced significant decrease (P less than 0.05) in serum prolactin levels. Xylazine at doses of 2.5, 5, and 10 mg/kg body weight (b.w.) induced significant decrease in serum prolactin levels 1 h after its intramuscular injection which remained significantly low for 4 h. The inhibition produced by 5 mg/kg and the 10 mg/kg b.w. doses was observed to be stronger in both magnitude and duration than that produced by the lower dose (2.5 mg/kg). This inhibitory effect of xylazine on prolactin levels may be attributable to its dopaminergic and/or alpha adrenergic antagonist activity. However, this point needs further investigation.