The Effect of an Extract and Fractions of Date Pits on Some Plasma Constituents, Reproductive Hormones, and Testicular Histology in Male Mice.

Pits of dates (Phoenix dactylifera L.) have numerous nutritional benefits that could have wide-ranging applications. This study aimed to examine the effects of administering three extracts from powdered date pits on some basic physiological parameters, plasma constituents, reproductive hormones, and testicular histology in CD1 male mice. Three groups received doses of 100 mg/kg/day of lyophilized extract, a nonpolar fraction, and a polar fraction of date pits by oral gavage for 28 consecutive days. For the control, one group was administered a 1 mL/kg concentration of distilled water. The three different extracts significantly increased the plasma testosterone level but showed no significant effect on estradiol or luteinizing hormone levels, except for estradiol reduction in the polar extract group. The measured physiological or biochemical parameters or testicular histology also demonstrated no significant differences between the control mice and those mice treated with the three extracts, except for reductions in plasma urea in all extracts and in total protein in the nonpolar extract. Therefore, date pit extracts may potentially be used as a safe and effective dietary supplement. However, further investigation is needed.

Effects of the SGLT-2 Inhibitor Canagliflozin on Adenine-Induced Chronic Kidney Disease in Rats.

BACKGROUND/AIMS: SGLT-2 inhibitors have been shown to be nephroprotective in diabetes. Here, we examined if one of these drugs (canagliflozin) could also ameliorate non-diabetic chronic kidney disease (CKD). METHODS: CKD was induced in rats by feeding them adenine (0.25%w/w for 35 days) and canagliflozin (10 or 25 mg/kg, by gavage) was given with or without adenine. Several conventional and novel plasma and urine biomarkers and tissues morphology were used to investigate the canagliflozin effect on kidney structure and function. RESULTS: Rats fed adenine showed the typical features of CKD that included elevation of blood pressure, decreased food intake and growth, increased water intake and urine output, decrease in creatinine clearance, and increase in urinary albumin/creatinine ratio, liver-type fatty acid binding protein, N-acetyl-beta-D-glucosaminidase, and plasma urea, creatinine, uric acid, calcium, indoxyl sulfate and phosphorus concentrations. Adenine also increased concentrations of several biomarkers of inflammation such as neutrophil gelatinase-associated lipocalin, interleukin-6, tumor necrosis factor alpha, clusterin, cystatin C and interleukin-1ß, and decreased some oxidative biomarkers in kidney homogenate, such as superoxide dismutase, catalase, glutathione reductase, total antioxidant activity, and also urinary 8-isoprostane and urinary 8-hydroxy-2-deoxy guanosine. Adenine significantly increased the renal protein content of Nrf2, caused renal tubular necrosis and fibrosis. Given alone, canagliflozin at the two doses used did not significantly alter any of the parameters mentioned above. When canagliflozin was given concomitantly with adenine, it significantly and dose - dependently ameliorated all the measured adenine - induced actions. CONCLUSION: Canagliflozin ameliorated adenine - induced CKD in rats, through reduction of several inflammatory and oxidative stress parameters, and other indices such as uremic toxins, and by antagonizing the increase in the renal content of the transcription factor Nrf2. The drug caused no overt or significant untoward effects, and its trial in patients with CKD may be warranted.

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-1ß), 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.

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.

Therapeutic Effect of Chrysin on Adenine-Induced Chronic Kidney Disease in Rats.

BACKGROUND/AIMS: To study the therapeutic effect of chrysin, a flavonoid with strong antioxidant and anti-inflammatory activities, on adenine-induced chronic kidney diseases (CKD) in rats. METHODS: Chrysin, in three graded oral doses (10, 50 and 250 mg/kg), was given for 10 consecutive days to rats after the induction of CKD by feeding them adenine (0.25%(w/w) for 35 days). Several plasma and urine biomarkers and tissues morphology were used the investigate chrysin effect on kidney structure and function. RESULTS: Adenine lowered creatinine clearance and elevated the concentrations of urea, creatinine, plasma neutrophil gelatinase-associated lipocalin and urinary N-Acetyl-beta-D-glucosaminidase activity, and increased the concentrations of the uremic toxin indoxyl sulfate, in addition to some inflammatory cytokines. Renal histopathological markers of inflammation and fibrosis were significantly increased. Renal catalase and superoxide dismutase activities, total antioxidant capacity and reduced glutathione were all adversely affected. Most of these adenine - induced actions were moderately mitigated by chrysin, especially at the highest dose. Compared to control, chrysin did not cause any overt adverse effects on the treated rats. CONCLUSION: Different doses of chrysin produce variable therapeutic salutary effects in rats with CKD, and that, pending further studies, its usability as a possible therapeutic agent in human CKD should be considered.

Analyses of acute kidney injury biomarkers by ultra-high performance liquid chromatography with mass spectrometry.

The newly developed acute kidney injury biomarkers are very important for the early and timely detection of kidney diseases. This review contains details of the analyses of several acute kidney injury biomarkers using ultra-high performance liquid chromatography-mass spectrometry in urine and plasma samples. In this review we attempt to discuss some aspects of the types of the biomarkers, patents, sample preparation, and the analyses. Besides, efforts were also made to discuss the possible uses of superficially porous (core-shell) columns in traditional and inexpensive high-performance liquid chromatography instruments. Additionally, the challenges and the future prospects are also highlighted. The present review will be useful for the academicians, scientists, and clinicians for the early detection of acute kidney injury biomarkers.

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.

Short-term effects of antimicrobial stewardship programs on antibiotics usage, clinical outcomes, and multidrug resistant organisms in the post COVID-19 era.

BACKGROUND: Antimicrobial resistance is associated with increasing mortality rates and the emergence of multidrug-resistant (MDR) organisms. There is scarcity of data on the short-term impact of Antimicrobial Stewardship Programs (ASP) on antibiotic usage, clinical outcome and MDR organisms' pattern following the COVID-19 pandemic. This study evaluated the short-term effects of ASP on antibiotic usage, clinical outcomes and MDR organisms' pattern in the post COVID-19 era. METHODS: Conducted at a tertiary academic health center, this observational study involved adult patients (≥18 years) in the general medical unit, treated with oral or intravenous antibiotics from May 1, 2021, to April 30, 2022. The applied ASP strategy was a prospective audit and feedback where a weekly meeting was held to discuss the antimicrobial therapy of admitted patient, after which recommendations were made regarding antimicrobial use. RESULTS: The study included 301 patients with 166 (55.1%) pre-ASP and 135 (44.9%) post-ASP. The median (IQR) age was 69 (55-77) years with 56.1% were female. Antibiotic usage dropped by 25.2% post-ASP. The length of hospital stay (LOS) was longer post-ASP (7 days vs. 7.9 days, p = 0.001), with MDR infections being a significant predictor (OR: 0.486, p < 0.001). There were no significant differences in 28-day readmission, recurrence of infections and all-cause mortality. Post-ASP, MDR pathogens increased (17.0% vs. 6.6%, p = 0.013), however, after separating post-ASP into two three-months periods, MDROs numbers decreased slightly (13 vs. 10). CONCLUSION: Short-term ASP implementation post COVID-19 reduced antibiotic usage while other clinical outcomes remained unchanged. Nonetheless an increase in MDR pathogens and LOS was observed. Further research is required to assess ASP's long-term impact on MDR infections rates and specific patient group outcomes.

Analyses of anticancer drugs by capillary electrophoresis: a review.

Capillary electrophoresis is a fast, inexpensive and low detection limit technique for the analysis of anticancer drugs. It has been used to analyze various anticancer drugs in biological samples, pharmaceutical preparations and environmental matrices. It has also been used to detect various cancer biomarkers in cancer patients. The present article describes the state-of-the art of capillary electrophoresis for the analyses of anticancer drugs. Various drugs discussed belong to several groups such as antimitotic agents, nucleoside analogs, antibiotics, topoisomerase inhibitors and DNA intercalating agents. In addition, efforts have also been made to discuss sample preparation, applications of capillary electrophoresis in genomic research, optimization and future perspectives.

The Stability of Analytes of Ionized Magnesium Concentration and Its Reference Range in Healthy Volunteers.

This study aimed to determine the stability of refrigerated analytes of iMg concentration at different time intervals and to establish iMg reference range in a cohort of healthy Omani volunteers (≥18 years). The concentrations of iMg were measured using the direct ion-selective electrode technique. Pearson's and Lin's concordance correlation coefficients along with the Bland-Altman plot were used to assess the levels of agreement between iMg concentrations of fresh and refrigerated blood samples at different time intervals. The study included 167 volunteers (51% females) with a median age of 21 (range: 20-25) years. The median, 2.5th, and 97.5th percentiles for fresh iMg reference ranges were 0.55, 0.47, and 0.68 mmol/L, respectively. The overall agreement between the fresh and refrigerated iMg concentrations was poor (rho-c = 0.51; p < 0.001). However, according to Altman's definition, iMg concentrations of the refrigerated samples for a period of ≤1 h had an excellent correlation with the fresh iMg concentrations (Lin's rho-c = 0.80), with a small average bias difference of 0.009 (95%CI; -0.025-0.043). A cut-off refrigeration period within ≤1 h at 2-8 °C can be considered an alternate time frame for the gold standard measurement (fresh or within 0.5 h).

The Prevalence and Impact of Evidence-Based Medications on Cardiovascular and Cerebrovascular Outcomes in Patients with Acute Coronary Syndrome Post-Revascularization in Oman.

OBJECTIVES: International cardiovascular guidelines recommend prescribing a combination of five evidence-based medications (EBM) for acute coronary syndrome (ACS) patients post-revascularization. This study aims to assess the prevalence and impact of prescribing the full (five medications) versus partial (four medications or fewer) EBM combination on major adverse cardiovascular and cerebrovascular events (MACCE) in patients with ACS post-revascularization. METHODS: Data from patients with ACS who had revascularization between January 2016 and September 2021 were collected retrospectively. Patients were then followed up until March 2022 for MACCE. RESULTS: The full EBM combination was prescribed to 70% of the patients. However, after taking into account the presence of contraindications and clinical factors, the actual adherence to the guidelines was 95%. Patients who received the full EBM combination were younger (58 versus 62 years; p = 0.0 and 3) and had lower rates of chronic kidney disease (11% versus 41%; p < 0.001) and heart failure (9% versus 20%; p = 0.012) when compared to patients who received the partial EBM. Compared to the partial EBM group, the full EBM group was associated with lower MACCE rates (54% versus 37%, p = 0.012). After employing the propensity score technique utilizing the 1:1 nearest neighbor matching method without replacement, the univariate findings were further re-affirmed with those on full EBMs (compared to those on partial EBMs) associated with a significant reduction in the MACCE rate (average treatment effect of -25%; 95% confidence interval: -10--40%; p = 0.001). CONCLUSIONS: The full EBM utilization was significantly high in our setting and in line with international guidelines. The full EBM combination was predominantly prescribed in younger and less comorbid patients and was associated with lower MACCE rates. The findings were further reaffirmed by the propensity score matching method.

Impact of evidence-based cardiac medication on short- and long-term mortality in 7,567 acute coronary syndrome patients in the Gulf RACE-II registry.

OBJECTIVE: To evaluate the impact of evidence-based cardiac medications (EBMs) on 1-month and 1-year mortality among discharged acute coronary syndrome (ACS) patients in the Middle East. METHODS: Data were analyzed from 7,567 consecutive ACS patients admitted to 66 hospitals in 6 Middle Eastern countries enrolled in the Gulf RACE II in October 2008 to June 2009. Individual EBMs or concurrent use of the EBM combination consists of an anti-platelet therapy, angiotensin-converting enzyme inhibitor (ACEI) (or angiotensin II receptor blocker (ARB)), ß-blocker, and a statin at discharge, were evaluated. Analyses were performed using univariate and multivariate statistical techniques. RESULTS: The mean age of the cohort was 56 +/- 12 years with 79% being males. 65% of the patients received the concurrent EBM combination at discharge. Aspirin, clopidogrel, statins, b-blockers and ACEIs/ARBs use was 96%, 71%, 95%, 82% and 81%, respectively. 70% of the patients were prescribed both aspirin and clopidogrel concurrently at discharge. Adjusting for demographic, clinical, revascularization, and country characteristics, the multivariable logistic regression models demonstrated no differences in mortality at both 1-month (3.0 vs. 3.6%; p = 0.828) and 1-year (3.5 vs. 3.5%; p = 0.976) between the concurrent EBM combination users and non-users. CONCLUSION: The majority of the ACS patients in the Middle East were prescribed the guideline recommended EBM combination at discharge. However, potential still remains for further optimization of management. Further studies are required to examine the long term effect of concurrent use of the EBM combination on mortality in the region.

Superficially porous particles columns for super fast HPLC separations.

Superficially porous silica particles columns (SPSPCs) are manufactured by different companies. The most common have the brand names Halo, Ascentis Express and Kinetex. These columns provide super fast, sharp peaks and moderate sample loading and back pressure. These are available in different chemistries such as C8, C18, RP Amide and Hilic. Normally, the silica gel particles have 2.7 and 1.7 µm total and inner solid core diameters with 0.5 µm thick outer porous layer, 90 Å pore size and 150 m²/g surface area. They have been used for the separation and identification of low and high molecular weight compounds. The present article describes the state of the art of superficially porous silica particles based columns with special emphasis on their structures, mechanisms of separation, applications and comparison.

Appropriateness of antifungal prescribing in Oman.

Background: The inappropriate use of antimicrobials has substantially contributed to the development of antimicrobial drug resistance. Appropriate antibacterial prescribing has been emphasised, with minimal focus on appropriate prescribing of antifungals. Evaluation of antifungal use in the clinical setting is essential to prevent unnecessary drug exposure, development of resistance, adverse effects, and high hospitalisation costs. Objective: The purpose of this study was to assess the appropriateness of antifungal prescribing among adult patients at the Sultan Qaboos University Hospital (SQUH) in Oman. Methods: In this retrospective, observational study, the study population comprised adult patients treated with oral or intravenous antifungals between July 2018 and December 2019. The appropriateness of treatment was assessed using guidelines from the Infectious Diseases Society of America (IDSA) and the National Comprehensive Cancer Network (NCCN), as well as a set of literature-based criteria that were modified by SQUH infectious diseases team to suit local practices. These criteria included indication, dosage, and potential drug interactions. The primary outcome was the frequency of adherence to the treatment guidelines for fungal infections. Descriptive statistics were used for data analysis. Results: A total of 400 prescriptions were collected, of which 158 (39.5%) were for empirical therapy, 135 (33.8%) for targeted therapy, 69 (17.3%) for prophylactic therapy, and 38 (9.5%) for pre-emptive therapy. The overall appropriateness was 74.8%. The indication, dosage, and potential for antifungal-drug interactions were considered appropriate in 391 (97.8%), 314 (78.5%), and 381 (95.3%) prescriptions, respectively. Anidulafungin was the most prescribed antifungal agent, with 210 prescriptions (52.5%), followed by fluconazole with 102 prescriptions (25.5%), and voriconazole with 48 prescriptions (12%). Conclusion: In comparison with publised literature, our study revealed appropriate antifungal drug prescribing practices. However, studies with larger sample size in various hospital settings are necessary to confirm our findings on a national scale, and to obtain better statistical inferences and generalisability.

A Snapshot of Potentially Inappropriate Prescriptions upon Pediatric Discharge in Oman.

Background: Identifying and quantifying potentially inappropriate prescribing (PIP) practices remains a time-consuming and challenging task, particularly among the pediatric population. In recent years, several valuable tools have been developed and validated for assessing PIP. This study aimed to determine the prevalence of PIP and related risk factors in pediatric patients at a tertiary care hospital in Oman. Materials and Methods: A retrospective study was conducted by reviewing the medical records of pediatric patients (<18 years) from 1 October to 31 December 2019. Potentially inappropriate medication (PIM) and potential prescribing omission (PPO) were assessed using an internationally validated pediatric omission of prescriptions and inappropriate prescriptions (POPI) tool. Results: A total of 685 patients were included; 57.5% were male, and 30.5% had at least one comorbidity. Polypharmacy was identified in 70.2% of these patients, with a median of 2 (1−3) medications. PIM was observed in 20.4% of the cohort, with the highest in ENT-pulmonary disease (30.5%), followed by dermatological disorders (28.6%). PPO was identified in 6.9% of the patients with digestive and neuropsychiatric disorders, with the highest rate of 54% and 24%, respectively. Age (p = 0.006), number of medications (p = 0.034), and prescriber rank (p = 0.006) were identified as significant predictors of PIM, whereas age (p = 0.044) was the only significant predictor for PPO. Conclusions: The rates of PIM and PPO were high in this study population. In light of these findings, educational and interventional activities and programs are needed.

Effect of flaxseed on systemic inflammation and oxidative stress in diabetic rats with or without chronic kidney disease.

BACKGROUND: Diabetes mellitus (DM) and chronic kidney disease (CKD) are common causes of morbidity and mortality. Flaxseed contains several bioactive compounds that have been shown to possess anti-inflammatory and antioxidative properties. The aim of the present study was to investigate the possible effect of flaxseed in diabetic rats with adenine-induced CKD. METHODS: Male Wister rats (n = 48) were randomly divided into seven equal groups and treated for 33 consecutive days as follows: G1: control. G2 adenine, G3: streptozotocin (STZ), G4: flaxseed, G5: adenine+flaxseed, G6: STZ+flaxseed, G7: adenine+STZ+flaxseed). DM or CKD were experimentally induced by a single intraperitoneal injection of streptozotocin (STZ) or by adenine via oral gavage, respectively. RESULTS: Rats fed adenine alone exhibited several changes including decreased body weight, increased food and water intake and urine output, increased urinary albumin/creatinine ratio. They also showed an increase in plasma urea and, creatinine, indoxyl sulfate, neutrophil gelatinase-associated lipocalin and cystatin C, and a decrease in renalase activity. These were associated with significant changes in inflammatory and oxidative biomarkers, e.g., increase in 8-isoprostane, 8 -hydroxy -2-deoxy guanosine and decrease in antioxidant enzymes, as well as increase in interleukins 1ß and 6, and NF-κB, and a decrease in interlukin-10. Histopathologically, there was increased tubular necrosis and fibrosis. Concomitant administration of adenine and STZ further worsened the renal damage induced by adenine alone. Flaxseed significantly ameliorated the changes caused by adenine and STZ, given either singly or in combination. CONCLUSION: These findings suggest that flaxseed is a potential therapeutic agent in attenuating the progression of CKD in diabetes.

The salutary action of melatonin and betaine, given singly or concomitantly, on cisplatin-induced nephrotoxicity in mice.

Cisplatin (CP) is commonly used in the treatment of various solid tumors. Its use, however, is hampered by nephrotoxicity. In this study, we compared the effect of betaine and melatonin given singly, with that of a combination of these two agents on CP-induced nephrotoxicity in mice. CP (20 mg/kg, given intraperitoneally on the 8th day of 12 days of the experiment) showed the typical physiological, biochemical, and histologic features of nephrotoxicity. CP-treated mice showed a significant reduction in food intake, body weight, and urine and fecal output. It also induced significant increases in the plasma concentrations of urea, creatinine, uric acid, phosphorous, adiponectin, interleukin-1ß, interleukin-6, transforming growth factor -ß1, tumor necrosis factor-α, and cystatin C. All these effects were significantly reduced by daily administration of betaine or melatonin at oral doses of 200 mg/kg and 10 mg/kg, respectively. Furthermore, using the two agents in combination caused further significant reductions in the above parameters. These findings suggest that betaine and melatonin concomitant use is likely to provide greater protection against CP-induced nephrotoxicity than when they are given singly, rendering them potentially suitable and safe agents to use in clinical trials to assess their possible beneficial actions in cancer patients receiving CP.

The influence of the prebiotic gum acacia on the intestinal microbiome composition in rats with experimental chronic kidney disease.

Chronic kidney disease (CKD) is a globally common and important disease and there are evidence for a bidirectional relationship between microbiota and CKD. The aim of the study was to examine the influence of prebiotic - gum acacia (GA) on the intestinal microbiota in rats with adenine-induced CKD. Animals were randomly distributed into four equal groups (n = 6): control, adenine, GA and adenine + GA groups. CKD was induced by adenine (0.75% w/w) given in the diet daily for four weeks, and GA was administered in drinking water at a concentration of 15% w/v. The 16s rRNA analysis was performed on Illumina Miseq targeting V3-V4 region to characterize microbial composition. The abundance of Actinobacteria, Proteobacteria, Tenericutes and Verrucomicrobia bacteria was increased in adenine-induced CKD, and GA treatment successfully reversed those levels. Interestingly, alpha and beta diversity index were both reduced with GA treatment in rats with CKD. Short chain fatty acids (SCFAs) measurement and PICRUSt analysis have shown that GA treatment completely restored the depleted butyrate level and various perturbated functional pathways, respectively, in CKD rats. Taking together, our results suggest that GA supplementation has a beneficial role in treating CKD, through an increased production of butyrate, as well as its anti-inflammatory, antioxidant capacity and anti-nitrosative properties.

Effects of repeated increasing doses of cisplatin as models of acute kidney injury and chronic kidney disease in rats.

Cisplatin (CP) is nephrotoxic, and this side effect is used as an animal model for acute kidney injury (AKI). Earlier research has been focused on CP-induced AKI, with relatively little attention being paid to its ability to progress to chronic kidney disease (CKD) on repeated administration. We aimed here to test the dose dependency of its nephrotoxic actions by comparing various physiological, biochemical, molecular, and histopathological indices using repeated increasing doses of CP in rats. Furthermore, we investigated whether these doses of CP would result in the development of CKD. Biochemical, molecular, and histopathological measurements were conducted in plasma, urine, and/or kidneys of rats treated with increasing doses of CP at 1.6, 3.2, and 4.8 mg kg-1 weekly for four consecutive weeks. These doses induced significant and dose-dependent elevations in most of the measured renal indices. These included increased renal fibrosis, as suggested histopathologically and biochemically by the significant increase in transforming growth factor-ß1, significant decrease in actin alpha 2, and variable actions of collagen I and IV. CP also dose-dependently increased nuclear factor (erythroid-derived 2)-like 2 and caspase-3. Multiple repeated doses of CP (1.6 to 4.8 mg kg-1) induced multiple episodes of AKI, leading to CKD after the 4th weekly dose and confirmed that this dosage regimen could be used as an experimental animal model of AKI progressing to CKD. These actions were driven by inflammation, oxidative, and nitrosative stress.

The Effects of Furosemide on Behavioral and Hormonal Parameters in Male and Female Mice Subjected to Immobilization and Cold-Water Stress.

INTRODUCTION: The diuretic agent furosemide (FUR, 25 and 50 mg/kg) has been shown in a single report to act as an anti-stressor agent in two models of acute stress in mice, viz. electric foot-shock stress and immobilization (IMS). The present work aimed to investigate the possible anti-stressor action of FUR on two models of acute stress in mice, cold-water stress (CWS) and IMS, and tried to determine whether gender has any impact on the effect of FUR. METHODS: FUR (40 mg/kg) was injected intraperitoneally, and after 30 minutes, mice were subjected to CWS (4°C for three minutes) or IMS (fixing movement for two and a half hrs using adhesive tape). Motor and exploratory activities, neuromuscular coordination, and thermal nociception were then tested. Blood was collected from the mice and used to measure the concentrations of three stress hormones (corticosterone, epinephrine and prolactin). RESULTS: Mice subjected to CWS and IMS had significantly reduced motor and exploratory activities, neuromuscular coordination, and increased nociception. CWS and IMS also significantly increased the plasma concentrations of the three hormones. FUR pretreatment significantly mitigated these stress-induced hormonal changes. There was no significant sex difference when CWS or IMS was applied. DISCUSSION: IMS and CWS stimuli in male and female mice caused significant elevations in the plasma concentrations of corticosterone, epinephrine, and prolactin, accompanied by a significant reduction of motor and exploratory activities, neuromuscular coordination, and thermal nociception. There were no sex differences when IMS was applied. In stressed mice, prior administration of FUR (40 mg/kg) significantly decreased the concentrations of stress hormones, and this effect significantly mitigated the stress-induced behavioural and motor changes.