Chronic kidney disease (CKD) is known to involve inflammation, oxidative stress and apoptosis. Here, we investigated the impact of curcumin (diferuloyl methane, a phenolic turmeric pigment), which has strong antioxidant, anti-inflammatory and anti-apoptotic activities on kidney structure and function in rats with adenine-induced CKD. Rats were treated for 5 weeks with adenine to induce CKD-like renal damage and combined with three doses of curcumin. Markers of kidney function and oxidative stress were quantified in plasma, urine, renal homogenates and on kidney tissue. Curcumin was found to significantly abate adenine-induced toxic effects such as reduced creatinine clearance, elevated neutrophil gelatinase-associated lipocalin levels and raised urinary N-acetyl-b-D-glucosaminidase activities. Curcumin markedly reduced renal morphological damage and histopathological markers of inflammation, fibrosis and apoptosis. Curcumin further reduced adenine-induced hypertension, urinary albumin, the inflammatory cytokines IL-1b, IL-6 and TNF-a, cystatin C and adiponectin. It restored plasma sclerostin concentrations and lowered oxidative stress in renal homogenates. In animals treated with the two higher curcumin concentrations, alone or in combination with adenine, an increased expression of the antioxidative transcription factor Nrf2 was found as well as up-regulation of the activity of its direct target glutathione reductase, and of an indirect target, the glutathione level. In conclusion, curcumin exhibits salutary effects against adenine-induced CKD in rats by reducing inflammation and oxidative stress via up-regulation of the transcription factor Nrf2.Chronic kidney disease (CKD) is a major and growing public health problem in both developed [1] and developing countries [2]. CKD is considered a key determinant of the poor health outcome of major non-communicable diseases [3] because of the high prevalence of morbidity and mortality associated with it, mainly due to cardiovascular dysfunction. Till now, there is no drug to improve kidney function in patients with CKD. The current therapeutic approaches to slow down its progression are limited to normalization of insulin, glucose and blood pressure [4]. Therefore, the development of novel therapies to either slow or reverse the deterioration in kidney function is highly needed. In particular, interesting for this are natural products with proven safety profiles.The pathophysiological basis of CKD and its complications include inflammation, oxidative stress and apoptosis [5]. These features consistently occur in human beings and animals. They are also major mediators of the disease, exerting similar effects in chronic renal failure models in rats [6,7]. Patients and laboratory animals with CKD have high plasma concentrations of inflammatory mediators (such as C-reactive protein, tumour necrosis factor and other cytokines) and several markers of nitrosative and oxidative stress [8,9]. Turmeric (Curcuma longa) is a popular Asian spice that has been utilized for...

Abstract:The aminoglycoside antibiotic gentamicin (GM) is still widely used against infections by Gram-positive and Gram-negative aerobic bacteria. Its therapeutic efficacy, however, is limited by renal impairment that occurs in up to 30% of treated patients. The drug may accumulate in epithelial tubular cells causing a range of effects starting with loss of the brush border in epithelial cells and ending in overt tubular necrosis, activation of apoptosis and massive proteolysis. GM also causes cell death by generation of free radicals, phospholipidosis, extracellular calcium-sensing receptor stimulation and energetic catastrophe, reduced renal blood flow and inflammation. Many drugs have been shown to either ameliorate or potentiate GM nephrotoxicity. This article aims at updating the literature that has been published in the past decade on the effects of agents that either ameliorate or augment the nephrotoxicity of this aminoglycoside. Notable among the new ameliorating procedures are gene therapy, such as intravenous cell therapy with serum amyloid A protein-programmed cells, and the use of some novel antioxidant agents and oils of natural origin. These include, for example, green tea, garlic saffron, grape seed extracts as well as sesame and oleanolic oils. Agents that may augment GM nephrotoxicity include indomethacin, cyclosporin, uric acid and the Ca ++ -channel blocker verapamil. Most of the nephroprotective agents mentioned here have not been tested in large controlled clinical trials. Because of their relative safety and effectiveness, antioxidant agents seem to be good candidates for testing in humans.The aminoglycoside antibiotics are used, either alone or in combination with cell wall-active agents, for the treatment of severe ⁄ life-threatening infections caused by Gram-positive and Gram-negative aerobes [1]. Gentamicin (GM) is probably the most commonly used and studied of all the aminoglycosides [2]. One serious limitation to the use of this antibiotic is that it can cause ototoxicity and nephrotoxicity, and, in some situations, these side effects are so severe that the use of the drug must be discontinued. It has been estimated that up to 30% of patients treated with GM for more than 7 days show some signs of renal impairment [3]. GM nephrotoxicity has been investigated in several experimental models in rabbits, mice and rats [4][5][6], and several strategies and agents have been used, with various degrees of success, in an attempt to protect or reverse renal GM damage [3,7,8]. This would be expected to have important clinical implications in increasing the safety of the drug. Because the pharmaceutical industry, in general, is not investing adequately in the development of new antibiotics, and antimicrobial resistance is on the increase, revival of older antibiotics for use might be a viable option. Some reviews have been published recently on specific aspects of GM nephrotoxicity. For example, Zorov [9] wrote about the role of renal mitochondria on protection against GM nephrotoxicity. Koyner...

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Background Adverse drug events from preventable medication errors can result in patient morbidity and mortality, and in cost to the healthcare system. Medication reconciliation can improve communication and reduce medication errors at transitions in care. Objective Evaluate the impact of medication reconciliation and counselling intervention delivered by a pharmacist for medical patients on clinical outcomes 30 days after discharge. Setting Sultan Qaboos University Hospital, Muscat, Oman. Methods A randomized controlled study comparing standard care with an intervention delivered by a pharmacist and comprising medication reconciliation on admission and discharge, a medication review, a bedside medication counselling, and a take-home medication list. Medication discrepancies during hospitalization were identified and reconciled. Clinical outcomes were evaluated by reviewing electronic health records and telephone interviews. Main outcome measures Rates of preventable adverse drug events as primary outcome and healthcare resource utilization as secondary outcome at 30 days post discharge. Results A total of 587 patients were recruited (56 ± 17 years, 57% female); 286 randomized to intervention; 301 in the standard care group. In intervention arm, 74 (26%) patients had at least one discrepancy on admission and 100 (35%) on discharge. Rates of preventable adverse drug events were significantly lower in intervention arm compared to standard care arm (9.1 vs. 16%, p = 0.009). No significant difference was found in healthcare resource use. Conclusion The implementation of an intervention comprising medication reconciliation and counselling by a pharmacist has significantly reduced the rate of preventable ADEs 30 days post discharge, compared to the standard care. The effect of the intervention on healthcare resource use was insignificant. Pharmacists should be included in decentralized, patient-centred roles. The findings should be interpreted in the context of the study's limitations.

Gum Arabic (GA [Acacia senegal]) is reputed, in Arabian medicinal practices, to be useful in treating patients with chronic renal failure (CRF), albeit without strong scientific evidence. We have previously shown that GA had no significant effect in rats with CRF induced by surgical nephrectomy. Here, we used another animal model of human CRF (feeding adenine at a concentration of 0.75%(w/w) for four weeks) to test the effect of GA on CRF. Renal morphology and measurements of plasma concentrations of urea and creatinine (Cr), and Cr clearance, in addition to urinary volume, osmolarity and protein concentrations, and N-acetylglucosamine and lactate dehydrogenase activities were performed. Interleukin-6 and the total antioxidant levels in urine, as well as the activity of superoxide dismutase in renal tissues, were estimated. Adenine feeding resulted in marked renal damage. GA (6%(w/v) and 12%(w/v) in drinking water for four consecutive weeks) significantly ameliorated the adverse biochemical alterations indicative of renal failure, abated the decrease in body weight and reduced the glomerular, tubular and interstitial lesions induced by adenine. Our study provides evidence that GA attenuated renal dysfunction in this model of CRF, suggesting a promising potential for it in protecting against renal failure progression. The mechanism(s) of this nephroprotection is uncertain but may involve anti-oxidant and/or anti-inflammatory actions.

Background/Aim:Due to epidemic levels of obesity and type 2 diabetes mellitus (DM), nonalcoholic fatty liver disease (NAFLD) and resulting nonalcoholic steatohepatitis (NASH) will be driving factors in liver disease burden in the coming years in Saudi Arabia and United Arab Emirates (UAE).Materials and Methods:Models were used to estimate NAFLD and NASH disease progression, primarily based on changes in adult prevalence rates of adult obesity and DM. The published estimates and expert interviews were used to build and validate the model projections.Results:In both countries, the prevalence of NAFLD increased through 2030 parallel to projected increases in the prevalence of obesity and DM. By 2030, there were an estimated 12,534,000 NAFLD cases in Saudi Arabia and 372,000 cases in UAE. Increases in NASH cases were relatively greater than the NAFLD cases due to aging of the population and disease progression. Likewise, prevalent cases of compensated cirrhosis and advanced liver disease are projected to at least double by 2030, while annual incident liver deaths increase in both countries to 4800 deaths in Saudi Arabia and 140 deaths in UAE.Conclusions:Continued high rates of adult obesity and DM, in combination with aging populations, suggest that advanced liver disease and mortality attributable to NAFLD/NASH will increase across both countries. Reducing the growth of the NAFLD population, along with potential therapeutic options, will be needed to reduce liver disease burden.

Chrysin (5, 7- dihydroxyflavone) is a flavonoid with several pharmacological properties that include antioxidant, anti-inflammatory and antiapoptotic activities. in this work, we investigated some effects of three graded oral doses of chrysin (10, 50 and 250 mg/kg) on kidney structure and function in rats with experimental chronic renal disease (CKD) induced by adenine (0.25% w/w in feed for 35 days), which is known to involve inflammation and oxidative stress. Using several indices in plasma, urine and kidney homogenates, adenine was found to impair kidney function as it lowered creatinine clearance and increased plasma concentrations of creatinine, urea, neutrophil gelatinase-associated lipocalin and N-Acetyl-beta-D-glucosaminidase activity. Furthermore, it raised plasma concentrations of the uremic toxin indoxyl sulfate, some inflammatory cytokines and urinary albumin concentration. Renal morphology was severely damaged and histopathological markers of inflammation and fibrosis were especially increased. In renal homogenates, antioxidant indices, including superoxide dismutase and catalase activities, total antioxidant capacity and reduced glutathione were all adversely affected. Most of these adenine – induced actions were moderately and dose -dependently mitigated by chrysin, especially at the highest dose. Chrysin did not cause any overt adverse effect on the treated rats. The results suggest that different doses of chrysin produce variable salutary effects against adenine-induced CKD in rats, and that, pending further pharmacological and toxicological studies, its usability as a possible ameliorative agent in human CKD should be considered.

Background: Medication errors occur frequently at transitions in care and can result in morbidity and mortality. Medication reconciliation is a recognized hospital accreditation requirement and designed to limit errors in transitions in care. Objectives: To identify beliefs, perceived roles and responsibilities of physicians, pharmacists and nurses prior to the implementation of a standardized medication reconciliation process. Methods: A survey was distributed to the three professions: pharmacists in the pharmacy and physicians and nurses in hospital in-patient units. It contained questions about the current level of medication reconciliation practices, as well as perceived roles and responsibilities of each profession when a standardized process is implemented. Value, barriers to implementing medication reconciliation and the role of information technology were also assessed. Analyses were performed using univariate statistics. Results: There was a lack of clarity of current medication reconciliation practices as well as lack of agreement between the three professions. Physicians and pharmacists considered their professions as the main providers while nurses considered physicians followed by themselves as the main providers with limited roles for pharmacists. The three professions recognize the values and benefits of medication reconciliation yet pharmacists, more than others, stated limited time to implement reconciliation is a major barrier. Obstacles such as unreliable sources of medication history, patient knowledge and lack of coordination and communication between the three professions were expressed. Conclusions: The three health care professions recognize the value of medication reconciliation and want to see it implemented in the hospital, yet there is a lack of agreement with regard to roles and responsibilities of each profession within the process. This needs to be addressed by the hospital administration to design clear procedures and defined roles for each profession within a standardized medication reconciliation process.