Mohammed Al Za’abi

Experimental gentamicin nephrotoxicity and agents that modify it: a mini-review of recent research.

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.

Ameliorative effect of chrysin on adenine-induced chronic kidney disease in rats

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.

Glycemic control among patients with type 2 diabetes at a primary health care center in Oman

AIMS To determine the status of blood sugar control by using fasting blood sugar (FBS) of ≤6.1 mmol/l and glycosyted hemoglobin A1c (HbAc1) of <7% as indictors of glycemic control and to assess the influence of demographic, blood pressure (BP) and lipid characteristics on glycemic control. METHODS This retrospective study included all Omani patients with type 2 diabetes (N=177) attended a primary health care center in Al-Dakhiliya region, Oman. RESULTS The overall mean age of the cohort was 53±12 years (range: 24-91) with females representing 60% (n=106) of the study sample. The study found that only 9.6% (n=17) and 35% (n=62) of the patients attained optimal FBS and HbAc1 levels, respectively. Higher HbA1c was significantly associated with higher diastolic BP (84 versus 80 mm Hg; p=0.006), higher total cholesterol (5.2 versus 4.7 mmol/l; p=0.002) and higher low-density lipoprotein cholesterol (3.8 versus 3.0 mmol/l; p=0.034). CONCLUSIONS The results demonstrated poor glycemic control in Oman type 2 diabetic patients comparable to local and global studies especially in those hypertensive and dyslipidemic patients. Implementation of early and aggressive management of diabetes mellitus at the primary care setting is warranted.

Whose responsibility is medication reconciliation : Physicians, pharmacists or nurses? A survey in an academic tertiary care hospital

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.

Sampling time and indications appropriateness for therapeutically monitored drugs at a teaching university hospital in Oman

Objective: To evaluate prospectively the appropriateness of indications, sampling time and outcome of TDM requests at a teaching university hospital in Oman. Methods: A prospective cross-sectional study was conducted over a four months period; October 2013–January 2014 at the Sultan Qaboos University Hospital (SQUH), an 855 bed university teaching hospital. Appropriateness criteria for indications and sampling time were defined a priori. The evaluated drug’s requests were for carbamazepine, phenytoin, phenobarbital, valproic acid, digoxin, gentamicin, amikacin, vancomycin, tobramycin, theophylline, lithium, and cyclosporine. Results: Of 733 evaluated TDM requisitions, the majority were for antibiotics (75.0%) followed by antiepileptics (10.5%) and cyclosporine (8.9%). Most of the requests had appropriate indication (78.2%), however, only 28.5% had appropriate sampling time. Results were applied by dosage adjustments in 65.8% of requests and some of the inappropriately sampled requests (15.3%) were used as a basis for modifying the dosage regimen. Of all the reported plasma concentrations 42.3%, 41.2%, and 16.5% were within, below and above the reference range, respectively. Conclusion: TDM service is much less than optimal in SQUH. A lot of effort needs to be carried out to improve TDM use in the developing countries as adjusting the doses on results that are based on wrong sampling time might expose patients to toxicity or therapeutic failure.

Mechanistic Approaches of PHE and PPF Columns for Separation of Rasberry Ketone and Caffeine

High-Performance Liquid Chromatography (HPLC) separation mechanisms of raspberry ketone and caffeine on phenyl columns (PhE and PPF) are described. The π–π interactions played major role in separation phenomenon. PhE column resulted into better separation than PPF due poor π–π interactions in later column. Fast, reproducible, selective, and effective HPLC method was developed for analyses of ketone and caffeine in pharmaceutical preparation. The columns used were Sunniest PhE (phenyl) (250 × 4.6 mm, 5.0 µm) and Sunshell PFP (100 × 4.6 mm, 2.6 µm) of Chromanik Japan. The mobile phase used was water–acetonitrile (60:40, v/v, at different pH values) at 1.0 mL/min flow rate. The detection was at 280 nm with 27 ± 1°C as working temperature. The ranges of capacity (k), separation (α), and resolution (Rs) factors at different pH values on both columns were 2.60–5.10, 1.32–1.60, and 3.22–4.28, respectively. The values of limit of detection (LOD) and limit of quantitation (LOQ) of raspberry ketone and caffeine on both columns ranged from 5.0 to 20.0 and 7.0 to 25.0, respectively. The developed mechanistic aspect is useful for designing separation strategies of other molecules on these phenyl columns. The reported method may be used for quality control in industries and government organizations. Besides, fast analyses may be carried out in various food products.

Gum Acacia Improves Renal Function and Ameliorates Systemic Inflammation, Oxidative and Nitrosative Stress in Streptozotocin-Induced Diabetes in Rats with Adenine-Induced Chronic Kidney Disease

Background/Aims: The effect of treatment with gum acacia (GA), a prebiotic shown previously to ameliorate chronic kidney disease (CKD), in diabetic and non – diabetic rats with adenine – induced CKD has been investigated using several conventional and novel physiological, biochemical, and histopathological parameters. Methods: Diabetes mellitus was induced in rats by a single injection of streptozotocin (STZ). Diabetic and non – diabetic rats were randomly divided into several groups, and given either normal food or food mixed with adenine (0.25% w/w, for five weeks) to induce CKD. Some of these groups were also concomitantly treated orally with GA in the drinking water (15% w/w). Results: Rats fed adenine alone exhibited physiological (decreased body weight, increased food and water intake and urine output), biochemical (increase in urinary albumin/creatinine ratio, plasma urea and, creatinine, indoxyl sulfate and phosphorus), inflammatory biomarkers (increased in neutrophil gelatinase-associated lipocalin, transforming growth factor beta -1, tumor necrosis factor alpha, adiponectin, cystatin C and interleukin-1β), oxidative biomarkers (8-isoprostane, 8 -hydroxy -2-deoxy guanosine), nitrosative stress biomarkers (nitrite and nitrate) and histopathological (increase in tubular necrosis and fibrosis) signs of CKD. STZ - induced diabetes alone worsened most of the renal function tests measured. Administration of adenine in STZ – diabetic rats further worsened the renal damage induced by adenine alone. GA significantly ameliorated the renal actions of adenine and STZ, given either singly or in combination, especially with regards to the histopathological damage. Conclusion: GA is a useful dietary agent in attenuating the progression of CKD in rats with streptozotocin-induced diabetes.