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The current study aimed to investigate the cardiotoxic effect of dexamethasone-high-dose in rats, the therapeutic effect of carvedilol and the role of α1-adrenergic receptor (α1AR). The experiment involved 6 groups: control, dexamethasone (10 mg/kg), carvedilol (10 mg/kg), phenylephrine (1 mg/kg), phenylephrine plus carvedilol and propranolol (30 mg/kg). Drugs and vehicles were given for 7 days. Dexamethasone was given with the drugs in the last 4 groups. On the 8th-day and after overnight fasting, serum and cardiac samples were collected. Serum levels of cardiac troponin I and creatine kinase–myoglobin as well as cardiac levels of diacylglycerol, malondialdehyde, kinase activity of Akt, transforming growth factor-β, Smad3 and alpha smooth muscle actin were measured. Cardiac samples were also used for histopathological examination using hematoxylin–eosin and Sirius red stains, in addition to immunohistochemical examination using β-arrestin2 antibody. Dexamethasone induced cardiac injury via increasing oxidative stress, apoptosis and profibrotic signals. Carvedilol significantly reduced the dexamethasone-induced cardiotoxicity. Using phenylephrine, a competitive α1-agonist, with carvedilol potentiated the cardioprotective actions of carvedilol. Propranolol, a β-blocker without activity on α1ARs, showed higher cardiac protection than carvedilol. Dexamethasone-high-dose upregulates cardiac oxidative stress, apoptotic and profibrotic signals and induces cardiac injury. Blocking the α1-adrenergic receptor by carvedilol attenuates its cardioprotective effects against dexamethasone-induced cardiotoxicity.

The aim of the work was to determine the best beams number and segments in order to improve the plans conformity and homogeneity that generate low monitor units (MUs) and faster irradiated time for different types of head and neck cancer (HNC).  Methods This study includes 30 patients with different HNC. Intensity modulated radiotherapy (IMRT) treatment planning techniques were done with step and shoot delivery technique, 5, 7 and 9 beams IMRT were carried out for each patient. The treatment plans for all patients were calculated and optimized using fast superposition algorithm. All plans were generated using equal spaced odd beam number around the target. 6 MV were used in all beams. Multiple segments were created for each beam. Typically maximum iteration was carried out to achieve optimized plans. The beam weight optimized to generate the plan, then the segment weight optimized for all plans by using sliding window methods. The final optimization maps were converted into a way of step and shoot sequence map which delivered by linear accelerator using multi leaf collimator (MLC). IMRT plans were compared based on several criteria: Isodose distributions, the mean and standard deviation with pvalues for planning target volume (PTV) 95%, conformity index (CI), homogeneity index (HI), organs at risk (OARs), number of segments, MUs and total irradiated time were presented and compared in all patients. Statically analyses were compared for all patients used ANOVA testes.

Background Acinetobacter baumannii (A. baumannii) is one of the most important nosocomial pathogens responsible for a wide range of infections. Aim This study aimed to investigate the existence of the plasmidic genes encoding for aminoglycoside modifying enzymes (AMEs), 16S rRNA methyltransferases (RMT), and the altered dihydropetroate synthase (DHPS) encoded by the sul1 gene among A. baumannii clinical isolates collected from Taif, Kingdom of Saudi Arabia (KSA). The mutations in aac(6ʹ)-Ib and sul1 genes were also investigated. Methods Forty A. baumannii clinical isolates were investigated for their susceptibility to ten antibiotics. The plasmid DNA was extracted and screened for nine genes encoding for aminoglycoside resistance in addition to the sul1 gene. The clonal relatedness was determined by random amplified polymorphic DNA (RAPD)-PCR. Mutation in aac(6ʹ)-Ib and the sul1 genes were detected by capillary electrophoresis sequencing (CES). Results All isolates were A. baumannii in which 42.5% of them exhibited a high level of aminoglycoside resistance (HLAR). The most prevalent AMEs and RMT encoding genes were aph(3ʹ)-VI, the two aac(6ʹ) gene variants [aac(6ʹ)-Ib and aac(6ʹ)-SL], ant(3ʹʹ)-I, and armA in which 90%, 87.5%, 85%, and 45% of isolates tested positive, respectively. The other investigated aminoglycoside resistant encoding genes, namely aac(3)-II, aac(6ʹ)-II, and rmtB, were not detected. Only 15% of isolates harbored the sul1 gene. RAPD-PCR classified the 40 isolates into three clusters in which cluster II was the main cluster. DNA sequencing revealed that 34.29% (12/35) of isolates tested positive for aac(6ʹ)-Ib were found to harbor a common missense mutation in position 102 indicating a novel allelic variant named aac(6ʹ)-SL. Also, DNA sequencing revealed three missense mutations in the sul1 gene. Conclusion This is the first Saudi study to investigate the plasmid borne aminoglycoside and sulfonamide resistance genes among A. baumannii clinical isolates. A novel allelic variant for aac(6ʹ)-Ib was detected in addition to novel mutations in the sul1 gene.

The present study aimed to investigate the role of α and β-adrenergic receptors (βARs) in mediation or modulation of the dexamethasone-induced nephrotoxicity by using different pharmacological interventions. Nephrotoxicity was induced by subcutaneous injection of dexamethasone (10 mg/kg) for 7 days in Wistar albino rats. Eight groups were used: control; dexamethasone; carvedilol; phenylephrine; carvedilol and phenylephrine; propranolol; doxazosin; propranolol and doxazosin. At the end of experiment, rats were euthanized and blood, urine and kidney samples were collected. Serum and urinary creatinine and urinary total protein levels were measured. Also, the renal tissue levels of diacylglycerol (DAG); Akt kinase activity, malondialdehyde (MDA), NADPH oxidase 2 (NOX2), transforming growth factor-β (TGF-β), Wnt3A and β-catenin were recorded. Furthermore, histopathological and β-arrestin2-immunohistochemical examinations of renal tissues were performed. Results: Dexamethasone induced glomerular damage, proteinuria, renal oxidative stress and upregulated the renal Wnt/β-arrestin2/β-catenin pathway and the profibrotic signals. Blocking the α1 and βARs by carvedilol reduced the dexamethasone-induced nephrotoxicity. Pre-injection of phenylephrine did not reduce the reno-protective action of carvedilol. Blocking the βARs only by propranolol reduced the dexamethasone-induced nephrotoxicity to the same extent of carvedilol group. Blocking the α1ARs only by doxazosin reduced dexamethasone-induced nephrotoxicity to a higher extent than other treatments. However, combined use of propranolol and doxazosin did not synergize the reno-protective effects of doxazosin. Conclusion: Dexamethasone induces nephrotoxicity, possibly, by upregulating the Wnt/β-arrestin2/β-catenin pathway. Blocking either α1ARs or βARs can effectively protect against the dexamethasone-induced nephrotoxicity. However, combined blocking of α1ARs and βARs does not synergize the reno-protective effects.

Anxiety disorders are among the most prevalent mental disorders in the general population. Nearly 30 million persons are affected in the United States, with women affected nearly twice as frequently as men. These disorders are frequently treated using benzodiazepines (Diazepam) and non-benzodiazepines (Zaleplon). Non-benzodiazepines have replaced the benzodiazepines for anxiety treatment due to low risk of dependence and CNS effects encouraging drug abuse. This work was designed to investigate the toxicological overdose effect of zaleplon and diazepam on behavior, blood pressure, heart rate, brain neurotransmitter content and liver & kidney functions in rats. Rats were divided into five groups: 1% Tween 80, p.o. (control), diazepam (1 & 4 mg/kg, p.o.) and zaleplon (1 & 4 mg/kg, p.o.). All groups were injected daily for four weeks to perform the following: behavioral study (assessment of motor co-ordination and anxiety performance), measurement of blood pressure & heart rate, determination of the free amino acid and monoamine contents in the whole brain, determination of serum aminotransferases activity, total protein, total and direct billirubin, creatinine & blood urea nitrogen of experimental rats. Zaleplon decreased motor co-ordination, blood pressure and heart rate with extent lesser than diazepam. However, it decreased anxiety performance and brain monoamine content with extent more than diazepam. While, diazepam increased brain amino acid content, serum aminotransferases activity, total protein, total & direct billirubin, creatinine and blood urea nitrogen by magnitude more than zaleplon.

Objectives The best developmental stage and the best thawing protocol suitable for cryopreservation of the early embryos are not well documented. The present study aimed at evaluating the effect of the ultra rapid cryopreservation (vitrification) technique, followed by slow or fast thawing protocol, on the fertilized ova, 4-cell embryos and morula. Methods The vitrification method included equilibrating the ova in the vitrification solution (EFS40; consisted of 40% ethylene glycol, 30% Ficoll, 0.5 M sucrose in D-PBS) for 2 minutes before immersion in liquid nitrogen. Slow and fast thawing were done and the cryoprotectants were withdrawn by a hyperosmolar sucrose solution, which was then gradually diluted and replaced by culture medium. Results The best results were obtained with vitrification of the 4-cell embryos both with slow and fast thawing, which gave survival rate of 86% and 94%, and in vitro development rate of 74% and 80%, respectively. Fast thawing showed better survival rates (80%, 94%, 77%) and better in vitro development rates (60%, 80%, 63%) than those of slow thawing, following vitrification of the fertilized ova, 4-cell embryos and morula, respectively. Conclusion These criteria of vitrification/ thawing could be inferred to the human 4-cell embryos in the IVF protocol.

Cyclosporine A (CsA), a potent immunosuppressive drug, has been found to induce glucose intolerance through its toxic effect on the endocrine pancreas. It is not exactly known whether CsA has a direct effect on the endocrine pancreas or induces its effect indirectly. The present study was therefore undertaken to examine the function and morphology of isolated pancreatic islets when they are directly exposed in vitro to CsA. Pancreatic islets were isolated from adult male Lewis rats using collagenase ductal perfusion technique. The islets were separated with the discontinuous Ficoll gradient technique and further purified by hand picking of the non-islet tissue. The islets were cultured in RPMI-1640, pH 7.4 and maintained at 37 degrees C in a humid atmosphere of 5% (v/v) carbon dioxide in air. Cyclosporine was added to the culture medium to give a final concentration of 1 microg/ml (therapeutic dose), 5 microg/ml (toxic dose), or vehicle (control). Islets were harvested at 1, 4 and 10 days of culture and processed for functional or histological study. The functional study of the islets cultured with 1 microg/ml CsA showed insulin and C-peptide contents similar to those of the control islets. The islets cultured with 5 microg/ml CsA showed a marked decrease in insulin and C-peptide contents. Glucose-dependent insulin release was variable. C-peptide release was lower than that of the control following both the therapeutic and toxic doses of CsA. Phase contrast microscopy showed that the islets cultured with 1 microg/ml CsA were mostly normal looking with a well-defined regular periphery; a few islets had ill-defined or irregular peripheries. The islets cultured with 5 microg/ml CsA had ill-defined irregular peripheries at 1 day, and were dense and forming clumps at 4 and 10 days following culture. There was a decrease in the islet number following the therapeutic dose; the decrease was more following the toxic dose of CsA. The islet diameters increased after the therapeutic dose, but slightly decreased following the toxic dose of CsA. Islets showed a weakly positive immunoperoxidase reaction for insulin that was weaker following the toxic dose of CsA. It is concluded that CsA has a direct effect on B-cells that was proved by the functional and morphological changes seen in the pancreatic islets cultured in vitro.

Zoonotic cutaneous leishmaniasis (ZCL) is endemic in Sinai Peninsula. The sand fly and reservoirs were investigated in Suez G., since new settlements and land reclamation programs are ongoing. The results showed that Phlebotomus papatasi reached its highest density in September. The successfully colonized P. papatasi facilitated its biology and competence study. An autogenous trait was proven within P. papatasi population indicating its ability to survive and breed during adverse conditions. The vector competence was carried out under laboratory condition through feeding on lesion of a L. major experimentally infected hamster and by membrane feeding technique. Both hamsters and BALB-c mice inoculated with L. major developed ZCL lesions.

The distribution of rodents was studied in three different habitats. Seven rodent species were identified: Rattus norvegicus, R. alexandrinus, R. frugivorous, Mus musculus, Acomys russatus, Meriones sacramenti and Gerbillus pyramidum. The species distribution varied with the habitat type. The highest density of rodents was in July and August and the lowest one was in January. However, some species were collected all the year round. The rodents were investigated for the endo- and ecto-parasites. No Leishmania parasites were found. The ectoparasites were: Xenopsylla cheopis, Leptopsylla segnis and Ctenocephalides felis, Polyplax spinulos, Hyalomma dromedarii (nymph) and Echinolaelaps echidninus and Hemolaelaps glassgowi. Ecto-parasites were on rodents all year-round in domestic habitat and peridomestic habitats. In wild one, ecto-parasites activity was from March to December. The rodents' role as reservoir for L. major was experimentally studied. Rodents inoculated with L. major together with hamster and BALB-c mice developed cutaneous lesions. The active lesions, the rodents' ecological habitats and the presence of insect-vector may pave the way to an epidemic zoonotic leishmaniasis role.

The ability of the fetal pancreatic islet cells to multiply rendered them a potential tissue for transplantation studies to cure diabetes. A bank of fetal islets could be created with proper storage in liquid nitrogen. The aim of this study is to evaluate the effect of thawing rate and post-thaw culture on the structural and functional integrity of isolated cryopreserved islets of rat fetuses. Fetal rat islets were isolated by the collagenase digestion, cultured for three days, and then cryopreserved using dimethylsulphoxide as cryoprotectant and the step-rate cooling to -40 degrees C before immersing them in liquid nitrogen. The islets were thawed by the slow or fast warming rates using hyperosmolar sucrose solution and then cultured for 1 or 2 days. Insulin and C-peptide contents of the slow thawed islets were higher than those of the control. In the fast thawed islets the contents were similar to those of the control. Insulin and C-peptide release in response to glucose for the slow thawed islets were lower than those of the control and in the fast thawed islets they were similar to that of the control. Histological examination showed irregular periphery and fragmented central part of the large slowly thawed islets, which showed also variable immunohistochemical reaction to anti-insulin serum, ranging from strongly positive reaction to markedly weak reaction. Fast thawed islets showed mostly regular periphery and their reaction to the anti-insulin serum was slightly weaker than that of the control islets. It was concluded that fast thawing and post-thaw culture is much better than slow thawing, as indicated by nearly normal insulin and C-peptide content and release and intact structural integrity.

To perform a morphometric and structural study of the cultured isolated fetal rat pancreatic islets.Islets of the fetal rat pancreas, aged 22 days were isolated by the standard procedure of collagenase digestion and culture technique. The islets were cultured for 1, 2, 3, 4 and 5 days. The islets were counted under a dissecting microscope and islet diameter and purity were measured under a phase contrast microscope fitted with a calibrated grid. The islet specimens were fixed in buffered neutral formalin, dehydrated in alcohol and embedded in parablast. Sections were stained with hematoxylin and eosin. This study was conducted in King Fahd Medical Research Center, Faculty of Medicine, King Abdul-Aziz University, Kingdom of Saudi Arabia, during 2003 and 2004.The purity of the cultured islets gradually increased with time and was significantly different between the cultured groups. The number of the cultured islets gradually decreased with time. The islet diameter gradually increased with culture period. The islet purity and diameter were significantly different between the cultured groups. Parablast sections stained with hematoxylin and eosin showed that the shape and histological structure of the cultured islets were intact.The results of the present work represent an extensive morphometric structural study of isolated cultured fetal islets. The culture islet diameter and purity showed gradual increase with culture period, while the islet number showed gradual decrease.

This case report documents a variation in the insertion of the coracobrachialis muscle of the right arm of an adult male cadaver of unknown age. In addition to the normal insertion of the coracobrachialis muscle into the middle of the medial border of the humerus, an additional slender tendon passed inferiorly, crossing anterior to the median nerve and brachial artery before attaching to the medial epicondyle of the humerus. Most of the proximal part of the tendon gave rise to an aponeurotic expansion that inserted into the distal medial border of the humerus. The tendinous insertion and aponeurotic expansion may represent a variant of the coracobrachialis longus (Wood's) muscle and the internal brachial ligament, respectively. The median nerve and brachial artery traversed a tunnel bounded by the additional tendon and aponeurotic expansion as well as the usual humeral insertion of the coracobrachialis muscle. The clinical implication of this variation is that it may be a cause of median nerve entrapment and brachial artery compression.

Reports that describe the abnormalities and complexities of the anatomy of the arm are important with regard to surgical approaches. This case study reports a combined abnormal form of the coracobrachialis and biceps brachii muscles of the left arm of an adult male cadaver that was detected during the educational gross anatomy dissections of embalmed cadavers. The coracobrachialis muscle demonstrated two bellies which formed shortly inferior to its origin from the coracoid process of the scapula. One belly inserted into the middle of the antero-medial surface of the humerus, whereas the other belly inserted into the medial head of the triceps brachii muscle. The musculocutaneous nerve passed between the two bellies, giving a separate branch to each. We suggest that the two bellies of the coracobrachialis muscle may represent the incompletely fused short heads of the ancestral muscle. The biceps brachii muscle showed a third head, which originated mainly from the antero-medial surface of the humerus and partially from an aponeurosis belonging to the medial head of the triceps brachii muscle. These observations were confined to the left upper limb and were not accompanied by any other abnormality.

Objective The aim of this study was to evaluate the role of kidney injury molecule-1 (KIM-1) as an early marker for acute kidney injury (AKI) in critically ill patients as compared with conventional markers (e.g. serum creatinine). Background Depending on traditional markers for renal functions, namely, blood urea and serum creatinine, has led to unacceptable delay in the diagnosis of AKI and in initiating treatment. Materials and methods This study included 89 individuals: 79 critically ill patients and 10 healthy individuals who served as controls. All patients were prospectively followed up from the time of ICU admission. Blood and urine samples were collected simultaneously at predetermined time points: at the time of ICU admission, 6 h after arriving, 12 h after arriving, and daily thereafter for a minimum of the next 2 days and a maximum of 5 days. Results KIM-1 can detect AKI as early as 6 h from its occurrence and before the elevation of conventional markers. KIM-1 is (unlike conventional markers) not influenced by age, sex, and BMI. Conclusion KIM-1 is a reliable indicator for early detection of AKI in critically ill patients.

Although there is a recent increase in the use of the isolated pancreatic islets of the rat in the transplantation and functional studies, there has been no detailed quantitative assessment on the size and cellular constituents of islets after the isolation procedure. The present work was undertaken to study the size classes of the isolated islets and the morphometry of their cellular populations. Islets of the rat pancreas were isolated by using the intraductal collagenase digestion technique, the most commonly used procedure for the isolation of pancreatic islets. Different endocrine cells of the isolated islets were stained by immunoperoxidase staining techniques. The distribution of the cellular constituents of the isolated islets was similar to that of the intact islets of the normal pancreas; A, D, and PP cells were peripherally arranged around the centrally located B cells. However, morphometric quantitative study showed that the percent volume and percent number of A, D, and PP cells of the isolated islets were lower than those of the corresponding intact ones. Further, the mean true diameter of the isolated islets was lower than that of the intact ones. These data indicate loss of islet cells during the process of isolation. Most of the lost cells were from the periphery of islets. This may provide an explanation for the incomplete metabolic control and recurrence of hyperglycemia encountered after isolated islet transplantation in the treatment of diabetes mellitus. It seems that further refinements of the isolation techniques are necessary to obtain islet tissue with total cellular integrity, before a complete success in transplantation could be achieved.