Feasibility and outcomes of living-donor liver transplantation utilizing the right hemi-liver graft with portal vein anatomical variations.

PURPOSE: Portal vein (PV) reconstruction is a key factor for successful living-donor liver transplantation (LDLT). Anatomical variations of right PV (RPV) are encountered among potential donors. METHODS: To evaluate a single center experience of reconstruction techniques for the right hemi-liver grafts with PV variations during the period between May 2004 and 2022. RESULTS: A total of 915 recipients underwent LDLT, among them 52 (5.8%) had RPV anatomical variations. Type II PV was found in 7 cases (13.5%), which were reconstructed by direct venoplasty. Type III PV was found in 27 cases (51.9%). They were reconstructed by direct venoplasty in 2 cases (3.8%), Y graft interposition in 2 cases (3.8%), and in situ double PV anastomoses in 23 cases (44.2%). Type IV PV was found in 18 cases (34.6%) and was reconstructed by Y graft interposition in 9 cases (17.3%), and in situ double PV anastomoses in 9 cases (17.3%). Early right posterior PV stenosis occurred in 2 recipients (3.8%). Early PV thrombosis occurred in 3 recipients (5.8%). The median follow-up duration was 54.5 months (4 - 185). The 1-, 3-, and 5-years survival rates were 91.9%, 86%, and 81.2%, respectively. Late PV stenosis occurred in 2 recipients (3.8%) and was managed conservatively. CONCLUSION: Utilization of potential living donors with RPV anatomic variations may help to expand the donor pool. We found that direct venoplasty and in situ dual PV anastomoses techniques were safe, feasible, and associated with successful outcomes.

Influence of dietary mannan-oligosaccharides supplementation on hematological characteristics, blood biochemical parameters, immune response and histological state of laying hens.

This study aimed to determine the influence of dietary mannan-oligosaccharides (MOS) on the immune system, hematological traits, blood biochemical parameters, and histological state of laying hens. At 34 wk of age, The Mandarah chicken strain's 120 laying hens and 12 cocks were divided into 4 groups, each with 30 hens and 3 cocks. The first group performed as a control group, which nourished on a basal diet. The second, third, and fourth experimental groups received 0.1, 0.2, and 0.5 g/kg of MOS and a base diet, respectively. Birds obtained MOS at numerous doses significantly (P ˂ 0.05) raised serum levels of immunoglobulin Y (IgY), immunoglobulin M (IgM), and avian influenza (AI) antibodies compared to control birds. Furthermore, adding MOS at a level of 0.1 g/kg diet significantly improved the immune response of the control group. Additionally, compared to the control group, treated birds with MOS at various dosages did not significantly enhance hematological parameters such as red blood cells (RBCs), white blood cells (WBCs), hemoglobin, and hematocrit. Compared to control birds, birds fed MOS at all levels exhibited considerably lower serum cholesterol, alanine aminotransferase (ALT), and aspartate aminotransferase (AST) values. Also, compared to other treated birds, MOS-treated birds displayed improved histological examination of the small intestine, isthmus, and testis compared to the control group, particularly in birds fed MOS at 0.1 and 0.2 g/kg diet. It could be concluded that using MOS at 0.1 or 2 g/kg diet can successfully improve the physiological performance and overall health of laying hens.

The Gulf Achievement of Cholesterol Targets in Out-Patients Study (GULF ACTION): Design, Rationale, and Preliminary Results.

AIM: To assess the current dyslipidemia management in the Arabian Gulf region by describing the demographics, study design, and preliminary results of out-patients who achieved low-density lipoprotein cholesterol (LDL-C) goals at the time of the survey. BACKGROUND: The Arabian Gulf population is at high risk for atherosclerotic cardiovascular disease at younger ages. There is no up-to-date study regarding dyslipidemia management in this region, especially given the recent guideline-recommended LDL-C targets. OBJECTIVE: Up-to-date comprehensive assessment of the current dyslipidemia management in the Arabian Gulf region, particularly in view of the recent evidence of the additive beneficial effects of ezetimibe and proprotein convertase subtilisin/kexin-9 (PCSK-9) inhibitors on LDL-C levels and cardiovascular outcomes. METHODS: The Gulf Achievement of Cholesterol Targets in Out-Patients (GULF ACTION) is an ongoing national observational longitudinal registry of 3000 patients. In this study, adults ≥18 years on lipidlowering drugs for over three months from out-patients of five Gulf countries were enrolled between January 2020 and May 2022 with planned six-month and one-year follow-ups. RESULTS: Of the 1015 patients enrolled, 71% were male, aged 57.9±12 years. In addition, 68% had atherosclerotic cardiovascular disease (ASCVD), 25% of these patients achieved the LDL-C target, and 26% of the cohort were treated using combined lipid-lowering drugs, including statins. CONCLUSION: The preliminary results of this cohort revealed that only one-fourth of ASCVD patients achieved LDL-C targets. Therefore, GULF ACTION shall improve our understanding of current dyslipidemia management and "guideline gaps" in the Arabian Gulf region.

Immune response, hematological traits, biochemical blood parameters, and histological status of laying hens influenced by dietary chitosan-oligosaccharides.

This experiment aimed to examine the effect of chitosan-oligosaccharides (COS) supplementation in laying hens' diets affected their immune response, hematological characteristics, blood biochemical parameters, and histological status. At the age of 34 wk, 200 laying hens and 20 cocks of the Mandarah chicken strain were allotted into four groups, each consisting of 50 hens and five cocks. The first group acted as a control group, fed on a basal diet. The second, third, and fourth experimental groups each received 0.1, 0.2, and 0.5 g/kg of COS in addition to a base diet. Birds received COS at various dosages had significantly (P ˂ 0.05) increased serum concentration of immunoglobulins, avian influenza, and Newcastle disease antibodies compared with the control birds. Moreover, adding COS at level 0.2 g/kg diet insignificantly enhanced immune response than the rest of the treatment groups. Also, treated birds with COS at different levels had insignificantly improved hematological parameters such as red blood cells, white blood cells, hemoglobin and hematocrit compared to the control group. Birds fed COS at all levels had significantly decreased serum cholesterol, triglycerides, Ca++ and alanine aminotransferase concentrations compared with control birds. In addition, compared to the control group, chitosan-treated birds showed enhanced histological examination of the small intestine, isthmus, and testis, notably in birds given COS at 0.1 g/kg diet compared to other treated birds. Cocks fed COS at all levels improved testicular tissues and increased the number and diameter of seminiferous tubules compared with control birds Morphological examination of the ileum showed increased villi number, height, and crypt depth. It is possible to conclude that laying hens' physiological performance and general health can be effectively improved by using chitosan at 0.1 or 2 g/kg diet levels enhanced immune response.

Antibacterial and molecular docking studies of newly synthesized nucleosides and Schiff bases derived from sulfadimidines.

A new series of nucleosides, moieties, and Schiff bases were synthesized from sulfadimidine. Infrared (IR), 1HNMR, 13C NMR, and mass spectrometry techniques and elemental analysis were employed to elucidate the synthesized compounds. The prepared analogues were purified by different chromatographic techniques (preparative TLC and column chromatography). Molecular docking studies of synthesized compounds 3a, 4b, 6a, and 6e demonstrated the binding mode involved in the active site of DNA gyrase. Finally, all synthesized compounds were tested against selected bacterial strains. The most effective synthesized compounds against S. aureus were 3a, 4d, 4b, 3b, 3c, 4c, and 6f, which exhibited inhibition zones of inhibition of 24.33 ± 1.528, 24.67 ± 0.577, 23.67 ± 0.577, 22.33 ± 1.528, 18.67 ± 1.528 and 19.33 ± 0.577, respectively. Notably, the smallest zones were observed for 4a, 6d, 6e and 6g (6.33 ± 1.528, 11.33 ± 1.528, 11.67 ± 1.528 and 14.66 ± 1.155, respectively). Finally, 6b and 6c gave negative zone values. K. pneumoniae was treated with the same compounds and the following results were obtained. The most effective compounds were 4d, 4c, 4b and 3c, which showed inhibition zones of 29.67 ± 1.528, 24.67 ± 0.577, 23.67 ± 1.155 and 19.33 ± 1.528, respectively, followed by 4a and 3d (15.33 ± 1.528 for both), while moderate results (13.67 ± 1.155 and 11.33 ± 1.528) were obtained for 6f and 6g, respectively. Finally, 6a, 6b, 6c, 3a, and 3b did not show any inhibition. The most effective compounds observed for the treatment of E. coli were 4d, 4b, 4c, 3d, 6e and 6f (inhibition zones of 26.33 ± 0.577, 21.67 ± 1.528, 21.67 ± 1.528, 19.67 ± 1.528, 17.67 ± 1.155 and 16.67 ± 1.155, respectively). Compounds 3b, 3c, 6a, 6c, and 6g gave moderate results (13.67 ± 1.528, 12.67 ± 1.528, 11.33 ± 0.577, 15.33 ± 1.528 and 12.67 ± 1.528, respectively), while 6b showed no effect. The MIC values against S. aureus ranged from 50 to 3.125 mg, while those against E. coli and K. pneumoniae ranged from 50 to 1562 mg. In vitro, the antibacterial effects were promising. Further research is required to study the in vivo antibacterial effects of these compounds and determine therapeutic doses.

Genotype-phenotype correlation of 33 patients with maple syrup urine disease.

Maple syrup urine disease (MSUD) is a rare autosomal recessive inherited disorder due to defects in the branched-chain α-ketoacid dehydrogenase complex (BCKDC). MSUD varies in severity and its clinical spectrum is quite broad, ranging from mild to severe phenotypes. Thirty-three MSUD patients were recruited into this study for molecular genetic variant profiling and genotype-phenotype correlation. Except for one patient, all other patients presented with the classic neonatal form of the disease. Seventeen different variants were detected where nine were novel. The detected variants spanned across the entire BCKDHA, BCKDHB and DBT genes. All variants were in homozygous forms. The commonest alterations were nonsense and frameshift variants, followed by missense variants. For the prediction of variant's pathogenicity, we used molecular modeling and several in silico tools including SIFT, Polyphen2, Condel, and Provean. In addition, six other tools were used for the prediction of the conservation of the variants' sites including Eigen-PC, GERP++, SiPhy, PhastCons vertebrates and primates, and PhyloP100 rank scores. Herein, we presented a comprehensive characterization of a large cohort of patients with MSUD. The clinical severity of the variants' phenotypes was well correlated with the genotypes. The study underscores the importance of the use of in silico analysis of MSUD genotypes for the prediction of the clinical outcomes in patients with MSUD.

Susceptibility Assessment of Multidrug Resistant Bacteria to Natural Products.

OBJECTIVE: The aim of this study was to examine the effect of some natural compounds against multidrug-resistant bacteria. METHODS: Forty-three bacterial strains were collected. Disc diffusion and minimum inhibitory concentration (MIC) tests were carried out for natural compounds including quercetin, Acacia nilotica, Syzygium aromaticum, and Holothuria atra. Scanning electron microscope analysis and bacterial DNA apoptosis assays were performed. RESULTS: Staphylococcus aureus strains were resistant to imipenim, ampicillin, and penicillin. Most Escherichia coli strains were resistant to amoxicillin, clavulanat, and ampicillin. Finally, tigecycline was effective with Klebsiella pneumoniae and was resistant to all antibiotics. Only S aromaticum had an antibacterial effect on K pneumoniae. Most S aureus strains were sensitive to S aromaticum, A nilotica, and quercetin. All examined natural extracts had no effect on E coli. Holothuria atra had no effect on any of the strains tested. Minimum inhibitory concentration and minimum bactericidal concentration values for examined plants against S aureus were 6.25 to 12, 1.6 to 3.2, and 9.12 to 18.24 mg/mL, respectively. Syzygium aromaticum was active against K pneumoniae with an MIC of 12.5 mg/mL. Scanning electron microscope analysis performed after 24 and 48 hours of incubation showed bacterial strains with distorted shapes and severe cell wall damage. Syzygium aromaticum, quercetin, and A nilotica showed clear fragmentations of S aureus DNA. CONCLUSIONS: Current findings confirmed the beneficial effect of using natural products such as clove (S aromaticum), quercetin, and A nilotica as a promising therapy to overcome multidrug resistant bacteria.

Evaluation of the functional outcome of a percutaneous technique in correction of excessive anteversion in cerebral palsy.

In cerebral palsy, patients' excessive femoral anteversion is one of the most common skeletal abnormalities. The general agreement is concurrent correction of both soft tissue and bony deformities during the same operative setting by combining open femoral derotation osteotomy (FDO) with soft tissue releases. Fifty-one children (75 lower limbs) with cerebral palsy with a mean age of 10.7 years (range 6-16 years) fulfilling the inclusion criteria who underwent percutaneous FDO and when needed customized soft tissue releases. Derotation was maintained by a pin-in-cast technique. The mean follow-up was 24 m (range 14-36 m) and gross motor function classification system, functional mobility scale (FMS) and anteversion angle using the Staheli rotational profile were evaluated. Femoral anteversion was accurately measured by hip ultrasonography followed by a preoperative three-dimensional gait analysis. Preoperative and postoperative data were statistically analyzed to reveal the validity of this method. Internal and external hip rotation improved significantly (P < 0.001, respectively). Mean cast and Schanz screw application time was 49 days and all patients achieved independent walking for at least 5 m within 7 weeks. FMS, ultrasonography measured hip anteversion and gait kinematics also improved significantly (P < 0.01, respectively). Two patients (3.92%) developed a mild knee flexion contracture which resolved completely with physiotherapy at 12 m. The pins-in-fiberglass cast provides sufficient rigid fixation to constitute a reliable and reproducible method permitting early weight bearing. It is versatile enough to allow concomitant soft tissue procedures and correction of other accompanying bony deformities.

Calcaneal lengthening for the pes planovalgus foot deformity in children with cerebral palsy.

PURPOSE: The objective of this study was to evaluate the operative management of pes planovalgus deformity in ambulatory cerebral palsy (CP) children by calcaneal lengthening osteotomy described by Evans. METHOD: Fifteen children (10 girls and 5 boys) with average age 11 years 6 months (range, 8 years 4 months-14 years 6 months) with 22 feet with pes planovalgus (PPV) deformity were included in this study. Clinical evaluation was made according to Dogan's scale and graded as perfect, good, fair and poor. Preoperative and postoperative radiological assessment of anteroposterior talo-first metatarsal angle (AP-T1MT), anteroposterior talo-calcaneal angle (AP-TC), laterl Talo-first metatarsal angle (Lat. T1MT), lateral Talo-calcaneal angle (Lat. TC), and lateral Calcaneal pitch angle (Lat. CP) had been done for all feet. All feet were corrected with the modification of the calcaneal lengthening osteotomy described by Mosca. RESULT: Clinical results were perfect in 18 feet (82%), good in 2 feet (9%) and fair in 2 feet (9%). Radiological results showed improvement in 20 feet, while 2 feet showed no improvement. The improvement was significant in Lat. T1MT (P < 0.001), AP-T1MT (P < 0.05)., AP-TC and Lat. CP (P < 0.001, <0.001 respectively) whereas it was insignificant in Lat. TC (P > 0.05). CONCLUSION: The results of the present study showed that the procedure reliably relieves pain in PPV foot in CP children and proved effective in addressing all components of the deformity in both hindfoot and forefoot clinically and Radiologically.

Closed reduction with or without adductor tenotomy for developmental dysplasia of the hip presenting at walking age.

BACKGROUND: Many children with developmental dislocation of the hip especially in underdeveloped countries reach walking age and still remain undiagnosed, which can be detrimental to their growth and development. Because of the lack medical services often encountered in these regions, it would be attractive to find a cheap and effective treatment. Our work evaluated the results of treatment of these children by closed reduction with or without adductor tenotomy in a prospective study. METHODS: We included 20 patients in this study with 29 affected hips (15 right and 14 left). Nine patients (45%) had bilateral DDH and 11 (55%) had unilateral DDH. There were 18 girls (90%) and two boys (10%) who were followed up for a mean of 21 mo (18-24 mo). Ages ranged from 9 to 36 mo (mean age 18.3 mo). Patients were divided according to age into two groups: between 9-18 mo and from 19-36 mo. The first group included nine patients (14 hips) while the second had 11 patients (15 hips). RESULTS: In the first group, closed reduction failed in two patients (two hips) during the follow-up period (14.3%) and this necessitated shift to open reduction, while in the second group only one patient (bilateral DDH) had a similar failure (13.3%). We identified four hips with avascular necrosis. Three of them required no further treatment, the remaining hip was openly reduced. CONCLUSIONS: Closed reduction in older children offers a valid and reproducible treatment modality in the hands of an experienced pediatric orthopaedic surgeon as long as there is close follow-up and thorough knowledge of possible complications and their management including the ability to shift timely to open reduction.

Severe neurological manifestations in an Egyptian patient with a novel frameshift mutation in the Glutaryl-CoA dehydrogenase gene.

To characterize an Egyptian patient with glutaric acidemia type I (GA I) and to identify the causative mutation(s) that may be responsible for the disease phenotype. MRI was performed on the patient using the 1.5 T magnet, biochemical analysis was carried out using gas chromatography/mass spectrometry on the patient's dried blood spot, and the patient's organic acids were measured in dried blood and a urine sample using MS/MS and GC/MS, respectively. Total RNA was isolated from the patient's peripheral blood, and the synthesized cDNA was bi-directionally sequenced. The patient exhibited clinical features and MRI findings compatible with a diagnosis of GA I. The abnormal elevation of organic acids in the urine supported the presence of glutaryl-CoA dehydrogenase deficiency. Gene sequencing revealed a novel homozygous frameshift mutation, c.644_645insCTCG; p.(Pro217Leufs*14), in exon 8 of the GCDH gene. The present study revealed a novel frameshift mutation responsible for a severe GA I phenotype in an Egyptian patient. This novel mutation will ultimately contribute to a better understanding of the molecular pathology of the disease and shed light on the intricacies of the genotype-phenotype correlation of GA I disease.

Protective effects of camel milk against pathogenicity induced by Escherichia coli and Staphylococcus aureus in Wistar rats.

The aim of the present study was to investigate the protective effects of camel milk on hepatic pathogenicity induced by experimental infection with Escherichia (E. coli) and Staphylococcus aureus (S. aureus) in Wistar rats. The rats were divided into six groups: The control and camel milk groups received water and camel milk, respectively; two groups received camel milk for 2 weeks prior to intraperitoneal injection of either E. coli or S. aureus; and two groups were injected intraperitoneally with E. coli and S. aureus, respectively. All animals were maintained under observation for 7 days prior to biochemical and gene expression analyses. The rats treated with camel milk alone exhibited no changes in expression levels of glutamic­pyruvate transaminase (GPT) or glutamic­oxaloacetic transaminase (GOT), compared with the water­treated group. The E. coli­ and S. aureus­injected rats exhibited a significant increase in oxidative stress, and prior treatment with camel milk normalized the observed changes in the expression levels of GPT, GOT and malondialdehyde (MDA). Treatment with camel milk decreased the total bacterial count in liver tissue samples obtained from the rats injected with E. coli and S. aureus. Camel milk administration increased the expression levels of glutathione­S­transferase and superoxide dismutase, which were downregulated following E. coli and S. aureus injection. In addition, camel milk downregulated the increased expression of interleukin­6 and apoptosis­associated genes. Of note, administration of camel milk alone increased the expression levels of the B cell lymphoma 2­associated X protein and survivin anti­apoptotic genes, and supplementation prior to the injection of E. coli and S. aureus induced further upregulation, In conclusion, camel milk exerted protective effects against E. coli and S. aureus pathogenicity, by modulating the extent of lipid peroxidation, together with the antioxidant defense system, immune cytokines, apoptosis and the expression of anti-apoptotic genes in the liver of Wistar rats.

Female genital mutilation/cutting: will it continue?

INTRODUCTION: Female genital mutilation/cutting (FGM/C) is a prevalent, deeply rooted traditional practice in Egypt. AIMS: Specification of the motives behind the continuation of FGM/C in Egyptian community and evaluation of the sexual function in women with FGM/C. METHODS: This cross-sectional study, involved 2,106 sexually active female participants with FGM/C. Full history-taking and general examination to evaluate the type of FGM/C were conducted. Sexual function was assessed by using the Female Sexual Function Index (FSFI) questionnaire. MAIN OUTCOME MEASURES: Enumerate and specify the motivational factors and its percent among the participants. The correlation between FGM/C and FSFI domain scores was done with Pearson's correlation. RESULTS: Tradition, cleanliness, and virginity were the most common motives empowering the continuation of FGM/C (100%), followed by men's wish, esthetic factors, marriage, and religion factors (45.2-100%). Type I FGM/C was the most common, followed by type II. There was only negative correlation between the type II FGM/C and sexual satisfaction. No statistically significant difference between type I and non-FGM/C was found. CONCLUSIONS: FGM/C remains high. A variety of socio-cultural myths, religious misbelievers, and hygienic and esthetic concerns were behind the FGM/C. Overall, a large proportion of the participants supported the continuation of FGM/C in spite of adverse effect and sexual dysfunction associated with FGM/C.

Sildenafil Ameliorates Gentamicin-Induced Nephrotoxicity in Rats: Role of iNOS and eNOS.

Gentamicin, an aminoglycoside antibiotic, is used for the treatment of serious Gram-negative infections. However, its usefulness is limited by its nephrotoxicity. Sildenafil, a selective phosphodiesterase-5 inhibitor, was reported to prevent or decrease tissue injury. The aim of this study is to evaluate the potential protective effects of sildenafil on gentamicin-induced nephrotoxicity in rats. Male Wistar rats were injected with gentamicin (100 mg/kg/day, i.p.) for 6 days with and without sildenafil. Sildenafil administration resulted in nephroprotective effect in gentamicin-intoxicated rats as it significantly decreased serum creatinine and urea, urinary albumin, and renal malondialdehyde and nitrite/nitrate levels, with a concomitant increase in renal catalase and superoxide dismutase activities compared to gentamicin-treated rats. Moreover, immunohistochemical examination revealed that sildenafil treatment markedly reduced inducible nitric oxide synthase (iNOS) expression, while expression of endothelial nitric oxide synthase (eNOS) was markedly enhanced. The protective effects of sildenafil were verified histopathologically. In conclusion, sildenafil protects rats against gentamicin-induced nephrotoxicity possibly, in part, through its antioxidant activity, inhibition of iNOS expression, and induction of eNOS production.

Carvedilol ameliorates early diabetic nephropathy in streptozotocin-induced diabetic rats.

Diabetic nephropathy results in end-stage renal disease. On the other hand, carvedilol has been reported to have various pharmacological properties. The aim of this study therefore is to evaluate the possible protective effect of carvedilol on streptozotocin-induced early diabetic nephropathy and various mechanisms underlie this effect in rats. Single i.p. injection of streptozotocin (65 mg/kg) was administered to induce early diabetic nephropathy in Wistar rats. Oral administration of carvedilol at a dose level of 1 and 10 mg/kg daily for 4 weeks resulted in nephroprotective effect as evident by significant decrease in serum creatinine level, urinary albumin/creatinine ratio, and kidney index as well as renal levels of malondialdehyde, nitric oxide, tumor necrosis factor- α , and cyclooxygenase-2 with a concurrent increase in creatinine clearance and renal reduced glutathione level compared to diabetic untreated rats. The protective effect of carvedilol was confirmed by renal histopathological examination. The electron microscopic examination indicated that carvedilol could effectively ameliorate glomerular basement membrane thickening and podocyte injury. In conclusion, carvedilol protects rats against streptozotocin-induced early diabetic nephropathy possibly, in part, through its antioxidant as well as anti-inflammatory activities, and ameliorating podocyte injury.

Maternal-Fetal Hepatitis E Transmission: Is It Underestimated?

Hepatitis E virus (HEV) is an enterically transmitted virus; and several modes of transmission have been proposed, including blood transfusion, person to person transmission, and transplacental transmission. HEV during pregnancy is associated with an unfavorable prognosis for mothers and in severe cases can cause acute fulminate hepatitis and death. Transplacental transmission of HEV usually results in unfavorable outcomes of pregnancy, mainly fetal loss, preterm labor, and hepatic dysfunction in neonates. In this review, we will summarize the effects of HEV on maternal-fetal health in various clinical situations.

Protective effect of hydrogen sulfide against cold restraint stress-induced gastric mucosal injury in rats.

Hydrogen sulfide (H2S) is an endogenous gaseous mediator plays a potential role in modulating gastric inflammatory responses. However, its putative protective role remains to be defined. The present study aimed to evaluate role of the exogenously released and endogenously synthesized H2S in cold restraint stress (CRS)-induced oxidative gastric damage in rats. Rats were restrained, and maintained at 4 °C for 3 h. The H2S donor, sodium hydrosulfide (NaHS) (60 µmol/kg) was injected intraperitoneally (i.p.) before CRS. Our results revealed that NaHS pretreatment significantly attenuated ulcer index, free and total acid output, and pepsin activity in gastric juice along with decreased gastric mucosal carbonyl content and reactive oxygen species production. This was accompanied by increased gastric juice pH and mucin concentration in addition to restoring the deficits in the gastric reduced glutathione, catalase as well as superoxide dismutase enzyme activities. NaHS pretreatment markedly reduced the serum level of tumor necrosis factor (TNF-α) and myeloperoxidase activity compared to CRS-non-treated. Moreover, NaHS preadministration significantly abrogated the inflammatory and the deleterious responses of gastric mucosa in CRS. The protective effects of H2S were confirmed by gastric histopathological examination. However, pretreatment with the H2S-synthesizing enzyme, cystathionine-gamma-lyase inhibitor, beta-cyano-L-alanine (50 mg/kg, i.p.) reversed the gastroprotection afforded by the endogenous H2S. Collectively, our results suggest that H2S can protect rat gastric mucosa against CRS-induced gastric ulceration possibly through mechanisms that involve anti-oxidant and anti-inflammatory actions alongside enhancement of gastric mucosal barrier and reduction in acid secretory parameters.

Curcumin ameliorates methotrexate-induced nephrotoxicity in rats.

Methotrexate is an effective anticancer and immunosuppressive agent. However, nephrotoxicity is one of the complications of its use. On the other hand, curcumin, a naturally occurring polyphenolic compound, is reported to have antioxidant and anti-inflammatory properties. Those two properties are likely to prevent methotrexate-induced nephrotoxicity. The aim of this study is to evaluate the possible protective effect of curcumin against methotrexate-induced nephrotoxicity and delineate various mechanism(s) underlies this effect in rats. Nephrotoxicity was induced in Wistar rats by intraperitoneal administration of methotrexate (7 mg/kg/day) for three consecutive days. Curcumin administration in methotrexate-intoxicated rats resulted in nephroprotective effects as evidenced by the significant decrease in levels of serum creatinine and urea as well as renal malondialdehyde, nitric oxide, and tumor necrosis factor- α with a concurrent increase in renal glutathione peroxidase and superoxide dismutase activities compared to nephrotoxic untreated rats. Additionally, immunohistochemical analysis demonstrated that curcumin treatment markedly reduced cyclooxygenase-2 expression. Histopathological examination confirmed the protective effects of curcumin. In conclusion, curcumin protected rats from methotrexate nephrotoxicity, at least in part, through its antioxidant and anti-inflammatory activities.

Inhibition of endogenous CO by ZnPP protects against stress-induced gastric lesion in adult male albino rats.

Carbon monoxide (CO) has been found to be produced in every living cell in a biochemical reaction catalyzed by heme-oxygenase (HO) enzyme which degrades heme into biliverdin, CO, and iron. Endogenous CO is not a waste product, but acts as a chemical messenger mediating and modulating many intracellular biochemical reactions that regulate physiological functions. This study was designed to investigate the effect of inhibition of endogenous CO production by zinc protoporphyrin (ZnPP), an HO inhibitor, on the gastric secretion and ulceration induced by cold-restraint stress (CRS) in adult male albino rats. Rats were pylorically ligated and divided randomly into the following groups (six rats each): control, ZnPP treated (50 µmol/kg/day, s.c. for 10 days), CRS, and stressed ZnPP treated groups. Blood samples were collected from the retro-orbital sinus of anesthetized rats for determination of CO concentration. We found that ZnPP pretreatment significantly decreased HO-1 level, CO level, and volume of gastric juice as compared to the control non-stressed rats. In the present study, ZnPP pretreatment proved to be protective against development of ulcerative lesions in CRS model as evidenced by reduction of the ulcer index, and this could be mediated through reduction of free and total acidity of gastric secretion and decreased lipid peroxidation but with significantly decreased gastric protective nitric oxide and prostaglandin E(2) levels. In conclusion and according to our results, the protective effect of ZnPP on CRS-induced gastric ulcers despite of inhibition of endogenous CO could be attributed to the presence of zinc which is known to have a protective anti-ulcer effect.