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Abstract Background Nanoparticles are small-scale substances ( Method ZnO nanoparticles were administered orally in two doses (either 600 mg or 1 g/Kg body weight/day for 5 conscutive days) to Wister albino rats. In order to detect the protective effects of the studied antioxidants against n-ZnO induced nepherotoxicity, different biochemical parameters were investigated. Moreover, histopathological examination of kidney tissue was performed. Results Nano zinc oxide-induced nephrotoxicity was confirmed by the elevation in serum inflammatory markers including: tumor necrosis factor alpha (TNF-α), interleukin-6 (IL-6); and C-reactive protein (CRP). Moreover, immunoglobulin (IGg), vascular endothelium growth factor (VEGF), and nitric oxide (NO) were significantly increased in rat serum. Serum urea and creatinine levels were also significantly increased in rats intoxicated with n-ZnO particles compared with the control group. Additionally, a significant decrease in the non-enzymatic antioxidant reduced glutathione (GSH) was shown in kidney tissues and serum glucose levels were increased. These biochemical findings were supported by a histopathological examination of kidney tissues, which showed that in the animals that received a high dose of n-ZnO, numerous kidney glomeruli underwent atrophy and fragmentation. Moreover, the renal tubules showed epithelial desquamation, degeneration and necrosis. Some renal tubules showed casts in their lumina. Severe congestion was also observed in renal interstitium. These effects were dose dependent. Cotreatment of rats with Qur and/or Arg along with n-ZnO significantly improved most of the deviated tested parameters. Conclusions The data show that Qur has a beneficial effect against n-ZnO oxidative stress and related vascular complications. Also, its combination with Arg proved to be even more effective in ameliorating nano zinc oxide nephrotoxicity.

Objective: Diabetic complications involve multiple pathological pathways, including hyperglycemia-induced oxidative stress and inflammation. Combination therapy is usually employed to improve treatment outcomes and to lower potential adverse effects. In this study, we evaluated the effects of antidiabetic and antihypertensive agents, glibenclamide (GLI) and losartan (LT), on diabetes mellitus (DM)-associated metabolic changes in rats.Materials and Methods: Streptozotocin-induced diabetic animals were orally treated with GLI 5 mg/kg and/or LT 25 mg/kg for 4 weeks. Blood glucose, insulin, aspartate aminotransferase, alanine aminotransferase, urinary creatinine, and urea levels were measured. Serum, liver, and kidney values of inflammatory markers, such as interleukin-1β, tumor necrosis factor alpha, and interleukin-6 were assessed, along with lipid peroxidation products (e.g., thiobarbituric acid reactive substances), endogenous antioxidants (e.g., glutathione), as well as antioxidant enzyme activities (e.g., catalase, superoxide dismutase, and glutathione peroxidase). Finally, histological changes in liver and kidney tissues were evaluated.Results: DM markedly induced systemic, hepatic, and renal inflammation and lowered antioxidant defense mechanisms. Treatment of diabetic rats with either GLI or LT significantly improved liver and kidney functions and histological structure. Moreover, both medications reduced signs of oxidative stress and inflammation in blood, liver, and kidney samples. Combining GLI and LT showed similar protective potential against systemic, hepatic, and renal oxidative stress and inflammation.Conclusion: Adding LT to GLI therapy revealed prospective antioxidant and anti-inflammatory action, while no synergistic or additive effects were observed. [ABSTRACT FROM AUTHOR]

Abstract Background Methicillin-resistant Staphylococcus aureus (MRSA), is associated with high morbidity and mortality rates with rapid development of resistance. Methods A total of 512 MRSA isolates were procured from 6 major hospitals in Riyadh, Saudi Arabia and antibiotic susceptibilities and MICs were documented against several antibiotics and vancomycin. SPSS version 10 was used for statistical analysis. Results The prevalence of MRSA in the study hospitals ranged from 12% to 49.4%. Mean patient age was 44 years with males constituting 64.4% and females 35.6%. Approximately 41.5% of the isolates came from patients in the extreme age groups. MIC for vancomycin was in the susceptible range for all isolates ranging from 0.25 to 3 ug/ml. The overall susceptibility of MRSA to the various antibiotics tested was: fusidic acid 4.3%, sulfamethoxazole/trimethoprim 33.8%, gentamicin 39.6%, mupirocin 77.0%, gatifloxacin 78.9%, chloramphenicl 80.7%, linezolid 95.1%, quinupristin/dalfopristin 100%. Some differences were noted in the resistance of isolates among the participating hospitals reflecting antibiotic usage. On the whole, inpatient isolates (accounting for 77.5% of the isolates) were more resistant than outpatient isolates (22.5%) except for linezolid. Quinupristin-dalfopristin and linezolid are the most effective antibiotics tested against inpatient isolates while quinupristin-dalfopristin and gatifloxacin seem to be the most effective against outpatient isolates. Approximately one forth of the isolates are no longer susceptible to mupirocin used for eradication of the carrier state reflecting resistance developing after widespread use. Trends over time show a tendency towards decreased susceptibility to gatifloxacin and linezolid with increasing susceptibility to gentamicin and sulfamethoxazole/trimethoprim. Conclusion Quinupristin/dalfopristin and linezolid are two valuable additions to our antimicrobial armamentarium, but resistance has already been described. To preserve their value, their use should be limited to those rare cases where they are clearly needed. Fusidic acid, the local antibiotic, gentamicin and trimethoprim/sulfamethoxazole should not be relied upon for treatment of MRSA infections, at least empirically as the percentage of susceptible isolates is very low.

OBJECTIVES: Potential health hazard is associated with the wide use of nanoparticles. The prophylactic role of either α- lipoic acid (α -lip) or vitamin E (vit E) against the toxic effect of zinc oxide nano-particles (ZnONPs) induced metabolic disorder, inflammation and DNA damage in rat livers was studied. MATERIALS AND METHODS: ZnO-NPs were administered orally using two doses (600 mg and 1 g/kg body weight/day for 5 consecutive days). Some biomarkers of tissue damage, metabolic disorder, and DNA damage were investigated to explore the protective mechanisms of α -lip or vit E against ZnO-NPs induced hepatotoxicity. RESULTS: Co-administration of either α -lip (200 mg/kg body weight) or vit E (100 mg/kg body weight) daily for three weeks to ZnO-NPs intoxicated rats, significantly down-modulated the marked increase in serum ALT (marker of liver damage) and also serum glucose level (marker of metabolic disorder) as well as the pro-inflammatory biomarkers including nitric oxide (NO), tumor necrosis factor-α (TNF- α), interleukin- 6 (IL-6), C-reactive protein (CRP), and immunoglobin G (IGg). Reduced glutathione level was decreased while caspase3 level was elevated in liver tissues of ZnO-NPs treated group compared with intoxicated one. Moreover histopathological examination of liver tissue supported the previous biochemical markers. Furthermore, ZnO-NPs induced hepatic oxidative DNA damage. CONCLUSIONS: Either α -lip or vit E proved to be hepatoprotective agents against ZnONPs toxicity because they ameliorated metabolic and immune disorders related to liver damage and modulated the previous measured parameters. [ABSTRACT FROM AUTHOR]

Background: Methicillin-resistant Staphylococcus aureus (MRSA), is associated with high morbidity and mortality rates with rapid development of resistance. Methods: A total of 512 MRSA isolates were procured from 6 major hospitals in Riyadh, Saudi Arabia and antibiotic susceptibilities and MICs were documented against several antibiotics and vancomycin. SPSS version 10 was used for statistical analysis. Results: The prevalence of MRSA in the study hospitals ranged from 12% to 49.4%. Mean patient age was 44 years with males constituting 64.4% and females 35.6%. Approximately 41.5% of the isolates came from patients in the extreme age groups. MIC for vancomycin was in the susceptible range for all isolates ranging from 0.25 to 3 ug/ml. The overall susceptibility of MRSA to the various antibiotics tested was: fusidic acid 4.3%, sulfamethoxazole/trimethoprim 33.8%, gentamicin 39.6%, mupirocin 77.0%, gatifloxacin 78.9%, chloramphenicl 80.7%, linezolid 95.1%, quinupristin/ dalfopristin 100%. Some differences were noted in the resistance of isolates among the participating hospitals reflecting antibiotic usage. On the whole, inpatient isolates (accounting for 77.5% of the isolates) were more resistant than outpatient isolates (22.5%) except for linezolid. Quinupristindalfopristin and linezolid are the most effective antibiotics tested against inpatient isolates while quinupristin-dalfopristin and gatifloxacin seem to be the most effective against outpatient isolates. Approximately one forth of the isolates are no longer susceptible to mupirocin used for eradication of the carrier state reflecting resistance developing after widespread use. Trends over time show a tendency towards decreased susceptibility to gatifloxacin and linezolid with increasing susceptibility to gentamicin and sulfamethoxazole/trimethoprim. Conclusion: Quinupristin/dalfopristin and linezolid are two valuable additions to our antimicrobial armamentarium, but resistance has already been described. To preserve their value, their use should be limited to those rare cases where they are clearly needed. Fusidic acid, the local antibiotic, gentamicin and trimethoprim/sulfamethoxazole should not be relied upon for treatment of MRSA infections, at least empirically as the percentage of susceptible isolates is very low. [ABSTRACT FROM AUTHOR]

Tuberculosis (TB) represents a significant challenge to public health authorities, especially with the emergence of drug-resistant (DR) and multidrug-resistant (MDR) isolates of Mycobacterium tuberculosis. We sought to examine the genomic variations among recently isolated strains of M. tuberculosis in two closely related countries with different population demography in the Middle East. Clinical isolates of M. tuberculosis from both Egypt and Saudi Arabia were subjected to phenotypic and genotypic analysis on gene and genome-wide levels. Isolates with MDR phenotypes were highly prevalent in Egypt (up to 35%) despite its relatively stable population structure (sympatric pattern). MDR-TB isolates were not identified in the isolates from Saudi Arabia despite its active guest worker program (allopatric pattern). However, tuberculosis isolates from Saudi Arabia, where lineage 4 was more prevalent (>65%), showed more diversity than isolates from Egypt, where lineage 3 was the most prevalent (>75%). Phylogenetic and molecular dating analyses indicated that lineages from Egypt were recently diverged (~78 years), whereas those from Saudi Arabia were diverged by over 200 years. Interestingly, DR isolates did not appear to cluster together or spread more widely than drug-sensitive isolates, suggesting poor treatment as the main cause for emergence of drug resistance rather than more virulence or more capacity to persist. [ABSTRACT FROM AUTHOR]

Two new analogues of lidocaine were synthesized at the College of Pharmacy, King Saud University: compound I (Methyl-2-[2-(N,N-diethylamino) acetamido]-3-cyano-4,5-dimethylbenzoate) and compound II (Methyl-2-[2-(piperidino) acetamido]-3-cyano-4,5-dimethylbenzoate). Their influence on the arterial blood pressure and the heart rate of urethane-anaesthetized rats was studied and compared with the actions of lidocaine. Compounds I, II and lidocaine induced significant dose-dependent decreases in the arterial blood pressure and heart rate, which usually returned to basal values within 3-5 min. There were significant differences in the potency of the three compounds in producing their effects on blood pressure and heart rate (P< 0.0001, ANOVA). Compound II was 14 and 6 times more potent in reducing blood pressure and 8 and 2 times more capable of reducing the heart rate than lidocaine and compound I, respectively. The results of this study also indicated the ineffectiveness of antagonists of autonomic, histaminergic and 5-HT receptor, and various vasodilators in blocking the actions of the three compounds on blood pressure and heart rate. Pretreatment with CaCl(2)significantly reduced the hypotension and bradycardia induced by the three compounds, suggesting the involvement of calcium channels, probably of the L type. Several possible mechanisms are postulated. In conclusion, the results direct attention to the capability of the two new compounds to decrease blood pressure and heart rate; affects that may have clinical potential., (Copyright 2001 Academic Press.)

Many toxins from scorpion venoms activate sodium channels, thereby enhancing neurotransmitter release. The aim of the present work was to determine if the in vivo and in vitro effects of Leiurus quinquestriatus venom (LQQ) could be ameliorated by lignocaine, a sodium channel blocker. In urethane anaesthetised rabbits, LQQ venom (0.5 mg kg(-1), i.v.) caused initial hypotension and bradycardia followed by hypertension, pulmonary oedema, electrocardiographic changes indicating conduction defects, ischaemia, infarction, and then hypotension and death. Lignocaine (1 mg kg(-1) i.v. bolus initially, followed by i.v. infusion of 50 microg kg(-1) min(-1)) significantly attenuated the majority of the venom-evoked effects and reduced mortality. Addition of LQQ venom (1, 3 and 10 microg ml(-1)) to chick biventer cervicis, guinea pig ileum, and rat vas deferens preparations, increased the height of electrically-induced twitches, elevated resting tension, and caused autorhythmic oscillations. Lignocaine (3 x 10(-4)-1.2 x 10(-3) M) greatly attenuated these venom-evoked actions in the three preparations. Antagonists of appropriate neurotransmitters were also tested to determine the contribution of released transmitters to LQQ effects. Atropine significantly decreased the venom-elicited effects on guinea pig ileum preparations, while prazosin and guanethidine significantly reduced the venom's actions on rat vas deferens. In chick biventer cervicis preparations, tubocurarine and hexamethonium significantly attenuated the venom-induced effects. This study supports the hypothesis that many effects of LQQ venom involve the release of neurotransmitters and may be ameliorated by treatment with lignocaine.

The present study was undertaken to investigate the involvement of kinins in the cardiovascular- and respiratory effects of LQQ venom. Blood pressure, heart rate, electrocardiogram (ECG) and respiration were studied in anaesthetised rabbits, in the presence and absence of aprotinin and icatibant, a B2 bradykinin antagonist. Plasma bradykinin concentrations were also measured following venom injection. LQQ venom caused a triphasic effect on blood pressure comprising an immediate fall, a pronounced rise and a progressive decline until death. Bradycardia, myocardial damage, arrhythmias, respiratory distress and pulmonary oedema were also exhibited. Pretreatment with aprotinin attenuated the venom-induced hypotension, bradycardia, ECG and respiratory changes and prolonged survival. Pretreatment of atropinized animals with icatibant gave similar protection. In animals treated with LQQ venom, plasma bradykinin was significantly higher than controls, although there was considerable inter-animal variation in plasma kinin concentrations and the elevation was seen relatively late after venom administration. The data provides some support for the hypothesis that kinins are involved in the cardiovascular and lethal effects of LQQ venom in rabbits.

Nine fatal cases from the sting of the scorpion Leiurus quinquestriatus are presented. All victims showed association of CNS and cardiovascular manifestations. Either the CNS or the cardiovascular effects could occur first in the early phases of the scorpion envenoming syndrome; the CNS manifestations, however, always preceded the terminal hypotension and cardiac arrest. Pharmacokinetic studies in rabbits following s.c. injection of the labelled venom showed that rapid absorption took place with about 70% of the maximum blood concentration reached within 15 min. Intramuscular injection of antivenom did not significantly affect the absorption of the venom or the other pharmacokinetic parameters. The total area under concentration time curve was not significantly different from that following i.v. injection, showing that nearly complete absorption of the venom from the s.c. site would occur in 7-8 hr. The i.v. infusion of venom into anaesthetized rats, at a rate comparable to the absorption rate from s.c. sites, allowed the determination of the minimum lethal dose (MLD) with reasonable accuracy. In rescue experiments, anaesthetized rats were injected s.c. with multiple MLD of venom and infused i.v. with drugs commonly used in the treatment of scorpion envenomation. The prepared potent specific antivenoms, but not the commercial polyvalent antivenom, rescued all animals from the lethal effect of the venom, even when injected late. Atropine, atropine+phentolamine, chlorpromazine, hydrocortisone and indomethacin were able, in varying degrees, to rescue some rats injected with 2 MLD of venom. Phentolamine, propranolol, hydralazine and calcium gluconate significantly prolonged the survival time, but did not rescue any animals. Chlorpheniramine, saline and 1/4 saline + 5% dextrose were without any effect. Aprotinin, the kallikrein-kinin inhibitor, was able to rescue half of the animals from the lethal action of the venom. Electrocardiographic studies showed that L. quinquestriatus venom, irrespective of the route of administration, causes myocardial ischaemia and either inferior or anterior wall infarction. This was associated with an initial moderate and a terminal severe bradycardia together with a variety of rhythm and conduction defects. Except for minor and transient electrocardiographic changes, either the prepared antivenoms or aprotinin protected rabbits and rats from the cardiac effects of the venom.