Evaluation of Guinea pig models of the acute phase of allergic rhinitis

Allergic rhinitis is an allergen-IgE complex mediated inflammation of the nasal mucosa characterized by the symptoms of sneezing, nasal itchiness, rhinorrhea, and nasal congestion. The economical and social impact of allergic rhinitis is substantial. The effectiveness of currently available medications is limited. Investigation of more effective medications with fewer side effects is essential. Therefore, this study was intended to establish a model of allergic rhinitis in guinea pigs that can be utilized for further investigation of new medications. Furthermore, this study was also aimed to systematically evaluate the role of some inflammatory mediators of acute allergic reactions in guinea pigs in vivo. Male Dunkin Hartley guinea pigs were intranasally sensitized to, and challenged with, ovalbumin. Sneezing (SN) and nose rubbing (NR) were evaluated on day 21 post initiation of sensitization dose. From day 23 after first sensitization, the animals were anaesthetized with intraperitoneal pentobarbital (30-35mg/kg). The trachea was cannulated in both directions, caudally for measurement of nasal airway pressure (NAP) using a ventilator flow method (8ml/beat, 72beats/min) and rostrally for measurement of lung inflation pressure (LIP). Drugs were administered prior to ovalbumin challenge. SN and NR were evaluated for 30 minutes and NAP was evaluated within 30 minutes post challenge. Cellular infiltration (CI) was assessed from nasal lavage collected 60 minutes post challenge. Sensitized guinea pigs produced symptoms of SN, NR and nasal blockade (NB) in addition to eosinophil infiltration following ovalbumin challenge. A first generation H1 antihistamine, mepyramine, inhibited SN only, whereas later H1 antihistamine, cetirizine, inhibited SN, NR and NB. Montelukast, a leukotriene D4 receptor antagonist, and heparin prevented NB and CI. L-NAME , a non specific nitric oxide synthase inhibitor, inhibited NB and stimulated neutrophil infiltration. In non-sensitized guinea pigs, histamine and acetylcholine introduced intravenously caused dose-dependent decreases in NAP (by the action of histamine on H1 , M2 and perhaps M5 receptors, and acetylcholine on Ml receptors) and increases in LIP (by the action of histamine on H1 receptors, and acetylcholine on Ml receptors). In conclusion pathophysiological changes due to allergic rhinitis in guinea pigs resemble to some extent those in humans. The models reported here reflect the effectiveness of some drugs currently used to treat allergic rhinitis. The models can be used in investigating new potential drugs for the treatment of allergic rhinitis.Medicine, Faculty ofAnesthesiology, Pharmacology and Therapeutics, Department ofGraduat

Potentially Harmful Drug–Drug Interactions and Their Associated Factors Among Hospitalized Cardiac Patients: A Cross-Sectional Study

Abstract Background Cardiovascular diseases are responsible for a significant proportion of mortalities worldwide. Elderly patients are the most affected by cardiovascular diseases, and because of factors such as polypharmacy, multimorbidity, and age-related changes in drug availability and metabolism, they are highly susceptible to the occurrence of drug–drug interactions. Drug–drug interactions are among the many drug-related problems leading to negative outcomes among inpatients and outpatients. Thus, it is important to investigate the prevalence, involved drugs, and factors related to potential drug–drug interactions (pDDIs) to properly optimize pharmacotherapy regimens for these patients. Objective We aimed to determine the prevalence of pDDIs, drugs most frequently implicated, and significant predictors associated with these interactions among hospitalized patients in the Cardiology Unit at Sultan Qaboos University Hospital in Muscat, Oman. Methods This retrospective cross-sectional study included 215 patients. Micromedex Drug-Reax® was used to identify pDDIs. Data extracted from patients’ medical records were collected and analyzed. Univariable and multivariable linear regression was applied to determine the predictors associated with the observed pDDIs. Results A total of 2057 pDDIs were identified, with a median of nine (5–12) pDDIs per patient. Patients with at least one pDDI accounted for 97.2% of all the included patients. The majority of pDDIs were of major severity (52.6%), fair level of documentation (45.5%), and pharmacodynamic basis (55.9%). Potential drug–drug interactions between atorvastatin and clopidogrel were the most frequently observed (9%). Of all the detected pDDIs, around 79.6% of them included at least one antiplatelet drug. Having diabetes mellitus as a comorbidity (B = 2.564, p < 0.001) and the number of drugs taken during the hospitalization period (B = 0.562, p < 0.001) were factors positively associated with the frequency of pDDIs. Conclusions Potential drug–drug interactions were highly prevalent among hospitalized cardiac patients at Sultan Qaboos University Hospital, Muscat, Oman. Patients having diabetes as a comorbidity and with a high number of administered drugs were at a higher risk of an increased number of pDDIs

Antibiotics utilization patterns and dosage appropriateness among patients receiving hemodialysis

Chronic kidney disease (CKD) is a global health challenge, with a reported prevalence of around 10%. Prescribing for patients receiving hemodialysis (HD) is challenging and complicated by polypharmacy, comorbidities, and changes in clearance of medications. The aim of this study was to evaluate antibiotics utilization patterns and dosage appropriateness in patients receiving HD at a tertiary hospital. A retrospective study was carried on 287 adult inpatients, who received HD and at least one antibiotic in a tertiary hospital in Oman. Data were extracted using the hospital’s electronic patient information system. Dosage appropriateness was assessed by identifying the dosage and frequency of prescribed antibiotics and comparing them with international guidelines. The main outcome measures were antibiotics utilization patterns and dosing inappropriateness. The most commonly prescribed parenteral antibiotic was piperacillin + tazobactam (20%), while the most common prescribed oral antibiotic was azithromycin (41.7%). For prophylaxis, cefazolin (54.6%) was the main antibiotic prescribed. The most commonly used antibiotic for external use was mupirocin ointment (38.5%). The overall dosing inappropriateness was 29.5%. Vancomycin was the most common parenteral antibiotic subjected to dosing inappropriateness (19.8%). However, trimethoprim + sulfamethoxazole was more inappropriately prescribed among the oral route (28.6%).In conclusion, the most utilized antibiotic was piperacillin + tazobactam followed by vancomycin. The study reported some inappropriate dosing of antibiotics. Such a study opens the door for the establishment of local guidelines for the improved practice of antibiotics use in HD patients

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

The effect of sildenafil on rats with adenine-Induced chronic kidney disease

Karaca, Turan (Trakya author)The erectile dysfunction drug sildenafil has cardiopulmonary protective actions, and a nephroprotective action in cisplatin and ischemia-reperfusion- induced acute kidney injury. Here, we assessed its possible ameliorative action in a model of chronic kidney disease (CKD) using adenine feeding. Eight groups of rats were treated with saline (controls), adenine (0.25% w/w in feed daily for 5 weeks), and oral sildenafil (0.1, 0.5 or 2.5 mg/kg), either alone, or concomitantly with adenine. Urine was collected 24 h after the end of the treatments from all rats and blood pressure measured, followed by collection of blood and kidneys for the measurement of several functional, biochemical and histopathological parameters. Adenine treatment reduced body weight, creatinine renal clearance, and increased water intake and urine output, as well as the plasma concentrations of urea and creatinine, neutrophil gelatinase-associated lipocalin, and N-acetyl-beta-D-glucosaminidase activity, and albumin in urine. Adenine also increased the concentrations of the uremic toxins indoxyl sulfate, uric acid and phosphate, and a number of proteins and inflammatory cytokines, and decreased that of several anti - oxidant indices. Renal histopathological markers of damage (inflammation and fibrosis) were significantly increased by adenine. Sildenafil, given simultaneously with adenine, induced a dose - dependent improvements in most of the above parameters, suggesting its possible use as adjunct treatment for CKD in humans

The Effect of Metformin in Diabetic and Non-Diabetic Rats with Experimentally-Induced Chronic Kidney Disease

This work aimed to investigate whether treatment with the antidiabetic drug metformin would affect adenine-induced chronic kidney disease (CKD) in non-diabetic rats and rats with streptozotocin (STZ)-induced diabetes. Rats were randomly divided into eight groups, and given either normal feed, or feed mixed with adenine (0.25% w/w, for five weeks) to induce CKD. Some of these groups were also simultaneously treated orally with metformin (200 mg/kg/day). Rats given adenine showed the typical signs of CKD that included detrimental changes in several physiological and traditional and novel biochemical biomarkers in plasma urine and kidney homogenates such as albumin/creatinine ratio, N-acetyl-beta-D-glucosaminidase, neutrophil gelatinase-associated lipocalin, 8-isoprostane, adiponectin, cystatin C, as well as plasma urea, creatinine, uric acid, indoxyl sulfate, calcium, and phosphorus. Several indices of inflammation and oxidative stress, and renal nuclear factor-κB and nuclear factor erythroid 2-related factor 2 levels were also measured. Histopathologically, adenine caused renal tubular necrosis and fibrosis. The activation of the intracellular mitogen-activated protein kinase signaling pathway was inhibited in the groups that received metformin and STZ together, with or without adenine induced-CKD. Induction of diabetes worsened most of the actions induced by adenine. Metformin significantly ameliorated the renal actions induced by adenine and STZ when these were given singly, and more so when given together. The results suggest that metformin can be a useful drug in attenuating the progression of CKD in both diabetic and non-diabetic rats

The effect of swimming exercise on adenine-induced kidney disease in rats, and the influence of curcumin or lisinopril thereon

<div><p>Patients with chronic kidney disease (CKD) have been reported to benefit from different types of exercises. It has also been shown that the ACE inhibitor lisinopril, and the natural product curcumin are also beneficial in different models of CKD in rats. We assessed the influence of moderate swimming exercise (SE) on rats with adenine-induced CKD, and tested the possible effects of lisinopril and/or curcumin thereon using several physiological, biochemical, histopathological and immunohistochemical parameters. Rats (either sedentary or subjected to SE) were randomly divided into several groups, and given for five weeks either normal food or food mixed with adenine (0.25% w/w) to induce CKD. Some of these groups were also concomitantly treated orally with curcumin (75 mg/kg), or lisinopril (10 mg/kg) and were subjected to moderate SE (45 min/day three days each week). Rats fed adenine showed the typical biochemical, histopathological signs of CKD such as elevations in blood pressure, urinary albumin / creatinine ratio, and plasma urea, creatinine, indoxyl sulfate and phosphorus. SE, curcumin or lisinopril, given singly, significantly ameliorated all the adenine-induced actions. Administering curcumin or lisinopril with SE improved the histopathology of the kidneys, a salutary effect not seen with SE alone. Combining SE to the nephroprotective agents’ curcumin or lisinopril might offer additional nephroprotection.</p></div