In vivo Assessment of Combined Effects of Glibenclamide and Losartan in Diabetic Rats.

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-1ß, 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.

Molecular epidemiology of vancomycin resistant enterococci in a tertiary care hospital in Saudi Arabia.

AIM: Vancomycin-resistant enterococci (VRE) are a major cause of nosocomial infections with high mortality and morbidity. There is limited data on the molecular characterization of VRE in Saudi Arabia. This study was carried out to investigate the premise that a shift in VRE epidemiology is occurring in our setting. METHODS: Enterococcus species identification and susceptibility testing plus VRE phenotypic confirmation by vancomycin and teicoplanin E-test were carried out. Vancomycin resistance genes were detected by PCR. Strain typing was conducted using PFGE. RESULTS: Among the strains of Enterococcus spp. investigated in this study, 17 (4.5%) were VRE. With the exception of one isolate from rectal swab, all others were clinical specimens with blood being the commonest source (n = 11; 64.7%), followed by urine (n = 3; 17.6%). The 17 VRE isolates were Enterococcus faecium (n/N = 13/17) and Enterococcus gallinarum (n/N = 4/17). Among E. faecium isolates, vanA(+)/vanB(+) (n/N = 8/13; 62%) exhibiting VanB phenotype were predominant. One of the five vanA(+)E. faecium isolates exhibited a VanB phenotype indicative of vanA genotype-VanB phenotype incongruence. E. gallinarum isolates exhibited a Van C phenotype although two were vanA(+)/vanC1(+). PFGE revealed a polyclonal distribution with eight pulsotypes. CONCLUSION: These findings indicate an evolving VRE epidemiology with vanA(+)/vanB(+) isolates and vanA genotype-VanB phenotype incongruence isolates, which were previously described as colonizers, are now causing clinical infection.

Lutein dietary supplementation attenuates streptozotocin-induced testicular damage and oxidative stress in diabetic rats.

BACKGROUND: Diabetes mellitus with the successive generation of reactive oxygen species signifies a major risk factor for testicular dysfunction. Antioxidant supplements are one of the best options to prevent such disorder. In the present study, lutein as dietary supplement has been used to explore its potential protective effects against diabetes-induced oxidative stress in testicular cells. METHODS: Diabetes was induced using a single i.p. injection of streptozotocin (STZ). Lutein was mixed with rat chow powder and supplemented to diabetic rats for 5 weeks. Serum testosterone levels were estimated. In testicular cells, thiobarbituric acid reactive substances (TBARS), total sulfhydryl groups (T-GSH), non-protein sulfhydryl groups (NP-SH), superoxide dismutase (SOD) and catalase (CAT) activities were measured. Pro-inflammatory mediators like tumor necrosis factor α (TNF-α) and interleukin 1ß (IL-1ß) were measured in the testis. Nucleic acids and total protein (TP) levels were also estimated in testicular cells. Histopathological changes were evaluated in testis. RESULTS: Serum testosterone level was significantly decreased in diabetic animals compared to controls. Diabetes markedly reduced T-GSH, NP-SH, CAT and SOD, while TBARS, TNF-α and IL-1ß levels were increased in the diabetic testis compared to non-diabetic controls. Lutein supplementation, significantly and dose dependently increased the serum testosterone level. The elevated TBARS levels were significantly decreased compared to diabetic group, while the decreased levels of T-GSH and NP-SH and activities of CAT and SOD were found increased by lutein treatments in dose dependent manner. Lutein pretreatment also inhibited the TNF-α and IL-1ß levels compared to diabetic group. The decreased values of nucleic acids and total protein in diabetic group were also significantly increased in lutein supplemented groups. The histopathological evaluation revealed protection the damaged testicular cells in the diabetic rats by lutein supplementation. CONCLUSION: These findings showed that lutein has potential beneficial effects in diabetes-induced testicular damage, probably through its antioxidant and anti-inflammatory properties.

Carvedilol attenuates inflammatory biomarkers and oxidative stress in a rat model of ulcerative colitis.

Preclinical Research This study evaluated the effects of the carvedilol, a nonselective ß-adrenoceptor anatgonist with α1-adrenoceptor antagonist activity, in a rat model of experimentally induced ulcerative colitis (UC). UC was produced using acetic acid (AA) in animals previously treated with carvedilol (30 mg/kg po, qd) for seven days. Mucus content, lipid peroxidation (LPO) products, sulfhydryl groups, antioxidant enzyme activities, proinflammatory cytokines, prostaglandin E2 and nitric oxide levels were measured in colonic tissues and histopathological changes were assessed. LPO and proinflammatory biomarkers were markedly increased, while mucus content, sulfhydryl groups and enzymatic activities were inhibited in animals administered AA. Pretreatment with carvedilol attenuated LPO elevation, mucus content and sulfhydryl group inhibitions. Antioxidant enzymatic activity and proinflammatory biomarker levels were also restored in carvedilol-pretreated animals. Colonic protection associated with carvedilol pretreatment was further confirmed by histopathological assessment and found to be similar to the standard therapy of mesalazine (100 mg/kg po qd), suggesting that the effects of carvedilol action may be attributable to its anti-inflammatory and antioxidant properties.

Antimicrobial susceptibility patterns of multidrug-resistant Pseudomonas aeruginosa and Acinetobacter baumannii against carbapenems, colistin, and tigecycline.

OBJECTIVE: To examine susceptibility of Pseudomonas aeruginosa (P. aeruginosa) and Acinetobacter baumannii (A. baumannii ) against carbapenems along with colistin and tigecycline as alternative therapeutic options. METHODS: A total of 117 strains of multidrug-resistant (MDR) non-fermenting Gram negative bacteria isolated from non-duplicate samples were collected consecutively. We included one sample from each patient (84 isolates of A. baumannii and 33 isolates of P. aeruginosa isolated from patients seen at King Khalid University Hospital, Riyadh, Saudi Arabia, from June to December 2010). Isolates were identified by the MicroScan WalkAway 96 Plus system. The minimum inhibitory concentrations (MICs) were determined by E-test following the Clinical and Laboratory Standards Institute breakpoint recommendations. RESULTS: Most A. baumannii strains were resistant to imipenem (90.5%), meropenem (90.5%), and doripenem (77.4%). Whereas, a higher percentage of P. aeruginosa was resistant to imipenem (90.9%), and meropenem (81.8%), only 39.4% were resistant to doripenem. Colistin had excellent activity against both A. baumannii (100%) and P. aeruginosa (93.9%), while 89.3% of A. baumannii strains were susceptible to tigecycline. CONCLUSION: Among the carbapenems, doripenem was found to be the most potent antimicrobial agent against P. aeruginosa, whereas colistin proved to be an effective alternative antimicrobial agent for treatment of A. baumannii or P. aeruginosa. Tigecycline remains the best therapeutic option for MDR A. baumannii.

Role of quercetin and arginine in ameliorating nano zinc oxide-induced nephrotoxicity in rats.

BACKGROUND: Nanoparticles are small-scale substances (<100 nm) with unique properties. Therefore, nanoparticles pose complex health risk implications. The objective of this study was to detect whether treatment with quercetin (Qur) and/or arginine (Arg) ameliorated nephrotoxicity induced by two different doses of nano zinc oxide (n-ZnO) particles. 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.

Carnitine deficiency and oxidative stress provoke cardiotoxicity in an ifosfamide-induced Fanconi Syndrome rat model.

In addition to hemorrhagic cystitis, Fanconi Syndrome is a serious clinical side effect during ifosfamide (IFO) therapy. Fanconi syndrome is a generalized dysfunction of the proximal tubule which is characterized by excessive urinary excretion of glucose, phosphate, bicarbonate, amino acids and other solutes excreted by this segment of the nephron including L-carnitine. Carnitine is essential cofactor for ß-oxidation of long-chain fatty acids in the myocardium. IFO therapy is associated with increased urinary carnitine excretion with subsequent secondary deficiency of the molecule. Cardiac abnormalities in IFO-treated cancer patients were reported as isolated clinical cases. This study examined whether carnitine deficiency and oxidative stress, secondary to Fanconi Syndrome, provoke IFO-induced cardiomyopathy as well as exploring if carnitine supplementation using Propionyl-L-carnitine (PLC) could offer protection against this toxicity. In the current study, an animal model of carnitine deficiency was developed in rats by D-carnitine-mildronate treatment Adult male Wistar albino rats were assigned to one of six treatment groups: the first three groups were injected intraperitoneally with normal saline, D-carnitine (DC, 250 mg/kg/day) combined with mildronate (MD, 200 mg/kg/day) and PLC (250 mg/kg/day), respectively, for 10 successive days. The 4(th), 5(th) and 6(th) groups were injected with the same doses of normal saline, DC-MD and PLC, respectively for 5 successive days before and 5 days concomitant with IFO (50 mg/kg/day). IFO significantly increased serum creatinine, blood urea nitrogen (BUN), urinary carnitine excretion and clearance, creatine phosphokinase isoenzyme (CK-MB), lactate dehydrogenase (LDH), intramitochondrial acetyl-CoA/CoA-SH and thiobarbituric acid reactive substances (TBARS) in cardiac tissues and significantly decreased adenosine triphosphate (ATP) and total carnitine and reduced glutathione (GSH) content in cardiac tissues. In carnitine-depleted rats, IFO induced dramatic increase in serum creatinine, BUN, CK-MB, LDH, carnitine clearance and intramitochondrial acetyl-CoA/CoA-SH, as well as progressive reduction in total carnitine and ATP in cardiac tissues. Interestingly, PLC supplementation completely reversed the biochemical changes-induced by IFO to the control values. In conclusion, data from the present study suggest that: Carnitine deficiency and oxidative stress, secondary to Fanconi Syndrome, constitute risk factors and should be viewed as mechanisms during development of IFO-induced cardiotoxicity. Carnitine supplementation, using PLC, prevents the development of IFO-induced cardiotoxicity through antioxidant signalling and improving mitochondrial function.

Nitric oxide pros and cons: The role of L-arginine, a nitric oxide precursor, and idebenone, a coenzyme-Q analogue in ameliorating cerebral hypoxia in rat.

Evidence exists that nitric oxide (NO) may mediate both protective and pathological responses during brain hypoxia (HP). Reactive oxygen species have also been implicated in the pathophysiological response of the brain tissues to HP. Therefore, this study investigated whether a NO precursor, l-arginine (l-arg), a free radical scavenger, idebenone (ID), and their combination would reduce neurological injury resulting from hemic hypoxia (HP) in rats. Adult male Wistar albino rats were injected with sodium nitrite (60 mg/kg, s.c.) to establish hemic hypoxia. ID (100 mg kg(-1), i.p.) and/or l-arg (100 mg kg(-1), i.p.) were administrated 24 and 1h prior to sodium nitrite intoxication, respectively. Hypoxia significantly decreased hemoglobin concentration, while significantly increased serum lactate dehydrogenase (LDH), creatine phosphokinase (CPK), total nitrate/nitrite, sialic, and uric acids concentrations. Moreover, brain lipid peroxides were significantly enhanced, while reduced glutathione, l-ascorbic acids, adenosine triphosphate (ATP) contents, and the activities of catalase and superoxide dismutase, were significantly reduced in the brain tissue. Pretreatment with either ID or l-arg altered the majority of the above-mentioned biochemical changes in hypoxic rats. Additionally, the combination of these two agents significantly reduced injury marker enzyme activities as well as serum sialic, and uric acids level (P>0.05 vs. control). Moreover, this combination exerted a synergistic antioxidant effect by blocking the induction of lipid peroxidation, preserving brain energy (ATP) content, and greatly reducing the hypoxic alterations in brain enzymatic and non-enzymatic antioxidants. Histopathological examination of the brain tissue supported these biochemical findings. This study showed that ID and l-arg were capable of reducing neurological injury following HP in rat, and support the idea of the usefulness of l-arg and ID as prophylaxis from hypoxic brain injury.

Comparative study between the protective effects of Saudi and Egyptian antivenoms, alone or in combination with ion channel modulators, against deleterious actions of Leiurus quinquestriatus scorpion venom.

This study compared efficacy of two polyvalent antivenoms (Saudi Arabian and Egyptian), against lethality and pathophysiological changes of Leiurus quinquestriatus quinquestriatus (LQQ) scorpion venom in mice. Additionally, the study examined whether treatment with selected ion channel modulators, lidocaine, nimodipine or amiodarone would be effective, alone or combined with the antivenoms. The protein concentration of the Saudi antivenom was 1/3 of Egyptian, indicating lesser immunogenicity, while both preservative contents were within limits. In immunodiffusion experiments, both exhibited prominent precipitin bands indicating high concentrations of specific antibodies. Neutralizing capacities (60-70 LD(50)) stated on labels were confirmed. Both antivenoms significantly (P < 0.001) prolonged survival time (from 26.9 +/- 1.18 min, 100% dead with venom to 224-300 min, 0-30% dead) of envenomed mice, whether injected iv before or 5 min after venom. Injection of either antivenom plus ion channel modulators, gave comparable results to that observed in mice treated with antivenoms alone. The Na(+) channel blocker lidocaine and the Ca(2+) channel blocker nimodipine on their own significantly protected the animals (P < 0.05), but to a lesser extent. The two antivenoms, significantly ameliorated the venom-evoked changes in serum LDH (P < 0.001) and CKMB (P < 0.01) plus cardiac TNFalpha and nitrate/nitrite levels (P < 0.001). When combined with lidocaine or nimodipine, the effects were not greater than antivenom alone. Moreover, the antivenoms ameliorated characteristic venom-evoked changes in the isolated perfused Langendorff hearts. Lidocaine and amiodarone were more effective than nimodipine. In Conclusion both Saudi and Egyptian antivenoms protected mice from the pathological and lethal effects of LQQ scorpion. Sodium and calcium channel blockers, lidocaine and nimodipine, may be useful when antivenoms are not available.

Comparative study between peripherally and centrally acting sublethal and lethal doses of Leiurus quinquestriatus scorpion venom in rabbits: The usefulness of the sodium channel blocker lidocaine.

BACKGROUND: Scorpion envenomation is common among desert dwellers, affecting several systems and resulting in multiple organ dysfunction (MOD) or failure (MOF), mainly due to their action on Na(+) channels. Although scorpion venoms toxins do not pass the blood brain barrier, their CNS effects are prominent, occurring in conjunction with, or as an aftermath of peripheral actions of the venom. OBJECTIVE: To determine the ability of venom of the common scorpion Leiurus quinquestriatus (LQQ) to induce MOD or MOF when injected into rabbits in micro quantities centrally (intracerebroventricularly, i.c.v.) or macro amounts peripherally (s.c. or i.v.). Also, to assess if the Na(+) channel blocker lidocaine can protect rabbits from the resultant manifestations. METHODS: Rabbits were injected with LQQ venom centrally or peripherally, in either sublethal or lethal doses, and MOD or MOF determined by assessing: cardiac output (CO), estimated hepatic blood flow (EHBF), biochemical parameters indicative of cardiac/hepatic/renal and pancreatic functions, blood pressure (BP), survival, lung/body index (LBI, indicative of pulmonary edema), and/or histological changes in hearts, lungs, livers plus kidneys. In pre-treatment experiments, lidocaine was injected 40 min before venom and protective ability examined. RESULTS: LQQ venom in sublethal doses caused comparable significant reductions (vs control) in CO and EHBF when injected i.c.v. (2 µg kg(-1)) or s.c. (0.2 mg kg(-1)). Both routes caused gradual dose-related enhanced levels of creatine kinase, lactate dehydrogenase, aspartate aminotransferase, alanine aminotransferase, creatinine, glucose and amylase, indicating MOD. Also, characteristic venom-induced changes in BP were evident after lethal doses of venom i.v. (0.5 mg kg(-1)) or i.c.v. (3 µg kg(-1)). Histological changes in the organs plus LBI were comparable after i.c.v. and i.v. venom injection, with animals ultimately exhibiting MOF. Lidocaine (1 mg kg(-1) i.v., then infusion 50 µg kg(-1) min(-1), 30 min before venom), protected the animals from MOF evoked by lethal doses of the venom (whether injected centrally or peripherally), as evidenced by the amelioration of the venom's effects on blood pressure, LBI, survival and multiple organ histopathological manifestations. CONCLUSION: LQQ venom, whether injected centrally or peripherally caused comparable systemic dose-dependent MOD or MOF, with the latter attenuated by the Na(+) channel blocker lidocaine, indicating a role for Na(+) channels.

Correlation between blood pressure, cytokines and nitric oxide in conscious rabbits injected with Leiurus quinquestriatus quinquestriatus scorpion venom.

Activation of the inflammatory response with the release and activation of pro-inflammatory cytokines is among the factors thought to be important in the pathogenesis of many deleterious inflammatory effects seen in case of scorpion envenomation. The released inflammatory mediators interact in the body with a large number of proteins and receptors; this interaction determines the eventual inflammatory effect of the venom. Thus, in the present study an attempt was made to map the time course of scorpion envenomation and correlate the effects observed on the cardiovascular and respiratory systems with the changes that could take place in the levels of selected cytokines and nitric oxide during the course of experimental envenomation. New Zealand white male conscious rabbits were prepared for blood pressure recording. Arterial blood pressure was measured from the left central ear artery while a cannula was inserted into the right central ear artery and blood samples collected at different time interval after venom injection for biochemical and hematological analyses. In general, subcutaneous injection of Leiurus quinquestriatus quinquestriatus venom caused a significant (P+/-0.05) triphasic effect on BP consisting of an initial transient reduction, followed by an increase that peaked 2h after venom injection, and a gradual terminal hypotensive phase. The significantly high serum level of IL8, TNFalpha (P<0.001) and nitric oxide (P<0.0001) observed in the present study supports the evidence for the role of these potent vasodilators in the terminal hypotension that is usually observed in humans and animals after envenomation.

Oral colon targeted delivery systems for treatment of inflammatory bowel diseases: synthesis, in vitro and in vivo assessment.

The aim of this study was to investigate the potential of prodrugs of some non-steroidal anti-inflammatory drugs (NSAIDs) as colon targeted delivery systems for treatment of inflammatory bowel diseases. Naproxen, sulindac and flurbiprofen (Fbp) were used. The carboxylic group of those drugs was conjugated onto the amino group of l-aspartic acid or the hydroxyl group of alpha- or beta-cyclodextrin (CyD). Prodrugs hydrolysis in buffers of pH range 1.2-7.2 and in rat gastrointestinal tract homogenates and the effect of oral pretreatment of rats with clindamycin on the hydrolysis of the prodrugs was examined. Additionally, the effect of oral administration of Fbp-beta-CyD prodrug on the experimentally induced colitis in rats was evaluated. The in vivo inflammatory response was assessed macroscopically, histologically and by measurement of reduced glutathione (GSH) levels in colon tissues. No significant hydrolysis of the proposed seven prodrugs in buffers having pH range of 1.2-7.2 was observed over 72h. Negligible % of drug released from Fbp-alpha-CyD or Fbp-beta-CyD prodrugs was detected in rat stomach contents, intestinal tissues and intestinal contents homogenates. On the other hand, Fbp-alpha-CyD and Fbp-beta-CyD prodrugs released about 60% Fbp within 4h in rat colon homogenate. Oral pretreatment of rats with clindamycin significantly reduced % Fbp released from Fbp-alpha-CyD or Fbp-beta-CyD prodrugs. Oral administration of Fbp-beta-CyD to rats after induction of colitis significantly attenuated the severity of the colonic injury and reduced the score of the macroscopic and microscopic damage. Additionally, there was a significant increase in the level of GSH. The present study provided an evidence that Fbp-beta-CyD prodrug may be beneficial in treatment of inflammatory bowel disease.

Amelioration of the cardiovascular manifestations of the yellow scorpion Leiurus quinquestriatus envenomation in rats by red grape seeds proanthocyanidins.

The study attempts to determine the involvement of oxidative stress in cardiovascular manifestations during Leiurus quinquestriatus quinquestriatus (LQQ) scorpion envenomation and to examine the possible protective role of red grape seed proanthocyanidins (GSP) against such effects. Lethality studies conducted in mice demonstrated a significant (p<0.01) protection of GSP against venom lethality. Pretreatment with GSP (200 mg kg(-1), p.o., 10 days) prior to venom injection (350 microg kg(-1), s.c.) resulted in a significant decrease in percent mortality as well as in significant prolongation of the animal's survival time (p<0.01). Monitoring the cardiovascular effects elicited by venom injection in anesthetized rats revealed a marked protection of GSP against the increase in mean arterial blood pressure evoked by LQQ venom. Moreover, pretreatment with GSP reduced the characteristic signs of conduction defects, myocardial ischemia, and infarction observed by venom injection. Biochemical analyses showed that scorpion envenomation caused significant (p<0.001) elevation in serum lactate dehydrogenase as well as creatine kinase-MB activities. Such elevation was ameliorated by GSP (p<0.001). Oxidative stress parameters revealed that scorpion venom significantly increased (p<0.001) the level of lipid peroxidative damage in cardiac tissues and reduced the activity of both glutathione reductase and glutathione peroxidase enzymes in cardiac tissues (p<0.05). In the meantime, GSP offered significant protection against lipid peroxidative damage (p<0.05) and enhanced cardiac glutathione reductase activity (p<0.001). In summary, the current study demonstrates that pretreatment with GSP offers significant protection against LQQ envenomation possibly via enhancement of the antioxidant defense systems.

Molecular epidemiology of methicillin-resistant Staphylococcus aureus (MRSA) isolates from major hospitals in Riyadh, Saudi Arabia.

The few studies that have reported the incidence of methicillin-resistant Staphylococcus aureus (MRSA) in Saudi Arabia have indicated that a diverse number of circulating MRSA strains have been detected in several major hospitals. Thus, this study was designed to track the presence of MRSA strains in major hospitals in Riyadh, Saudi Arabia, and perform comparative chromosomal DNA analysis of MRSA strains for epidemiological investigation using pulsed-field gel electrophoresis (PFGE). Correlation of the PFGE types generated with microbiological and clinical data of the isolates was attempted. Screening for decreased susceptibility to vancomycin among the isolates was also done. A dendogram was generated using PFGE macrorestriction fragments and 6 types were identified (M1-M6) with M1 being predominant and widespread. A clear link between PFGE types and some clinical and microbiological data available for the strains was found. For example, M1 was statistically associated with male patients, whereas the unique types were associated with female patients, M2 was associated with isolates from wounds and age group <5 years, and M4 was associated with isolates from patients admitted to intensive care units. M5 was highly correlated with low sensitivity to linezolid. No vancomycin-resistant isolates were detected.

Trends in antibiotic susceptibility patterns and epidemiology of MRSA isolates from several hospitals in Riyadh, Saudi Arabia.

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.

Protective effect of red grape seeds proanthocyanidins against induction of diabetes by alloxan in rats.

It has been documented that impaired homeostasis in diabetes mellitus is associated with increased production of reactive oxygen species and depletion of the antioxidant defense systems. Natural grape seed proanthocyanidins (GSP) are potent free radical scavengers and hence provide significant protection against oxidative stress. Accordingly, the present study focused on investigating the possible protective role of GSP against free radical-mediated damage in pancreatic tissues of alloxan-induced diabetes in rats. The results revealed that oral administration of 50 and 100 mg kg(-1) (body weight) of GSP for 72 h significantly increased pancreatic glutathione (GSH) levels and inhibited the increase in lipid peroxidation caused by alloxan (p < 0.001). On the other hand, a significant reduction in pancreatic total nitrate/nitrite content (p < 0.001) was observed. Furthermore, GSP caused significant decline in the hyperglycemia induced by alloxan (p < 0.001). Such antihyperglycemic effect of GSP was accompanied by a significant increase in serum insulin levels in diabetic rats following 72 h of administration (p < 0.001). In conclusion, the study suggests that GSP are effective in ameliorating the damage to pancreatic tissue in experimental diabetes mellitus. Such effect may be related to their potent antioxidant properties as evidenced by the increase in pancreatic GSH and reduction of lipid peroxidation as well as total nitrate/nitrite levels.