Kaliuresis and Intracellular Uptake of Potassium with Potassium Citrate and Potassium Chloride Supplements: A Randomized Controlled Trial.

BACKGROUND: A potassium replete diet is associated with lower cardiovascular risk but may increase the risk of hyperkalemia, particularly in people using renin-angiotensin-aldosterone system inhibitors. We investigated whether intracellular uptake and potassium excretion after an acute oral potassium load depend on the accompanying anion and/or aldosterone and whether this results in altered plasma potassium change. METHODS: In this placebo-controlled interventional cross-over trial including 18 healthy individuals, we studied the acute effects of one oral load of potassium citrate (40 mmol), potassium chloride (40 mmol), and placebo in random order after overnight fasting. Supplements were administered after a 6-week period with and without lisinopril pretreatment. Linear mixed effect models were used to compare blood and urine values before and after supplementation and between the interventions. Univariable linear regression was used to determine the association between baseline variables and change in blood and urine values after supplementation. RESULTS: During the 4-hour follow-up, the rise in plasma potassium was similar for all interventions. After potassium citrate, both red blood cell potassium-as measure of the intracellular potassium-and transtubular potassium gradient (TTKG)-reflecting potassium secretory capacity-were higher than after potassium chloride or potassium citrate with lisinopril pretreatment. Baseline aldosterone was significantly associated with TTKG after potassium citrate, but not after potassium chloride or potassium citrate with lisinopril pretreatment. The observed TTKG change after potassium citrate was significantly associated with urine pH change during this intervention ( R =0.60, P < 0.001). CONCLUSIONS: With similar plasma potassium increase, red blood cell potassium uptake and kaliuresis were higher after an acute load of potassium citrate as compared with potassium chloride alone or pretreatment with lisinopril. CLINICAL TRIAL REGISTRY NAME AND REGISTRATION NUMBER: Potassium supplementation in patients with chronic kidney disease and healthy subjects: effects on potassium and sodium balance, NL7618.

L-arginine and lisinopril supplementation protects against sodium fluoride-induced nephrotoxicity and hypertension by suppressing mineralocorticoid receptor and angiotensin-converting enzyme 3 activity.

Sodium fluoride (NaF) is one of the neglected environmental toxicants that has continued to silently cause toxicity to both humans and animals. NaF is universally present in water, soil, and atmosphere. The persistent and alarming rate of increase in cardiovascular and renal diseases caused by chemicals such as NaF in mammalian tissues has led to the use of various drugs for the treatment of these diseases. The present study aimed at evaluating the renoprotective and antihypertensive effects of L-arginine against NaF-induced nephrotoxicity. Thirty male Wistar rats (150-180 g) were used in this study. The rats were randomly divided into five groups of six rats each as follows: Control, NaF (300 ppm), NaF + L-arginine (100 mg/kg), NaF + L-arginine (200 mg/kg), and NaF + lisinopril (10 mg/kg). Histopathological examination and immunohistochemistry of renal angiotensin-converting enzyme (ACE) and mineralocorticoid receptor (MCR) were performed. Markers of renal damage, oxidative stress, antioxidant defense system, and blood pressure parameters were determined. L-arginine and lisinopril significantly (P < 0.05) ameliorated the hypertensive effects of NaF. The systolic, diastolic, and mean arterial blood pressure of the treated groups were significantly (P < 0.05) reduced compared with the hypertensive group. This finding was concurrent with significantly increased serum bioavailability of nitric oxide in the hypertensive rats treated with L-arginine and lisinopril. Also, there was a significant reduction in the level of blood urea nitrogen and creatinine of hypertensive rats treated with L-arginine and lisinopril. There was a significant (P < 0.05) reduction in markers of oxidative stress such as malondialdehyde and protein carbonyl and concurrent increase in the levels of antioxidant enzymes in the kidney of hypertensive rats treated with L-arginine and lisinopril. The results of this study suggest that L-arginine and lisinopril normalized blood pressure, reduced oxidative stress, and the expression of renal ACE and mineralocorticoid receptor, and improved nitric oxide production. Thus, L-arginine holds promise as a potential therapy against hypertension and renal damage.

Conservative therapy is associated with worse clinical features and biochemical derangements than renal replacement therapy: a retrospective study in Kumasi, Ghana.

BACKGROUND: The incidence of end stage kidney disease (ESKD) is increasing in Ghana as with the rest of the world. This study compared the sociodemographic, diagnostic characteristics (clinical, biochemical and imaging) and clinical outcomes of ESKD patients who chose either renal replacement therapy (RRT) or conservative therapy as well as the factors that influenced their choice. METHODS: We retrospectively reviewed the records of 382 ESKD patient from 2006 to 2018. The data was collected from the Nephrology Clinic at the Komfo Anokye Teaching Hospital (KATH). Sociodemographic, diagnostic (clinical, biochemical and imaging) and therapeutic data were obtained, organized and analyzed with Statistical Package for the Social Sciences (SPSS). RESULTS: Of the 382 patients, 321 had conservative therapy whiles 61 had renal replacement therapy. The mean age of participants was 47.71 ± 16.10 years. Bipedal swelling (16.8%), fatigue (10.4%) and facial swelling (9.2%) were the major clinical features. Chronic glomerulonephritis (31.4%), hypertension (30.3%) and diabetes mellitus nephropathy (28.2%) were the most frequent predisposing conditions. Nifedipine (82.0%), bisoprolol (32.8%), aspirin (19.7%), ranitidine (26.2%), metformin (13.1%) and lasix (78.7%) were commonly used by the RRT patients than their conservative therapy counterparts. Compared to their RRT counterparts, patients on conservative therapy were more on irbesartan/lisinopril (57.9%) and sodium hydro carbonate (NaHCO3) (52.0%). Diastolic blood pressure (DBP) (p = 0.047), uremic gastritis (p = 0.007), anaemia, uraemia, haematuria and hyperkalaemia (p < 0.001) were more common in conservative therapy patients than RRT patients with RRT patients showing better corticomedullary differentiation (38.1% vs. 27.7%, p < 0.001) and normal echotexture (15.0% vs. 11.6%, p = 0.005). Age, gender, occupation and duration of illness were significantly associated with the decision to opt for conservative therapy. CONCLUSION: Patients on conservative therapy have worse clinical outcomes than their RRT counterparts. Early referrals to nephrologist as well as subsidized RRT should be targeted.

Persea americana seed extract restores defective sperm quality and biochemical parameters relevant to reproduction in male wistar rats treated with cyclosporine A.

Studies have shown that some drugs impair spermatogenesis, thereby causing infertility. Thus, this study aims at investigating the effect of Persea americana seed extract on the male reproductive system in cyclosporine-induced rats. Thirty male albino rats were randomly divided into five groups; all groups were induced with cyclosporine except the control group. Group 3 was treated with 10 mg/kg of lisinopril, groups 4 and 5 received 50 and 100 mg/kg of PAE, respectively. The experiment lasted for 7 days. The antioxidant enzymes [superoxide dismutase (SOD) and catalase (CAT)], and arginase activities were evaluated, nitric oxide (NO) and malondialdehyde (MDA) level of the penile tissue homogenate were determined with serum hormonal (follicle stimulating hormone, luteinizing hormone and testosterone) concentration and sperm quality. This study showed that cyclosporine induction caused a significant (p < .05) decrease in the SOD, CAT, sperm quality, NO, and hormonal level as compared to the control group, with a simultaneous increase in arginase activity and MDA level. However, treatment with PAE and lisinopril significantly (p < .05) increase antioxidant enzyme activities, sperm quality, NO, and serum hormonal level, with a decrease MDA level and arginase activity when compared with cyclosporine-induced group. This study showed that P. americana seed extract could be useful in the management of hormonal disruption resulting from oxidative stress in male folks. PRACTICAL APPLICATIONS: Some pharmaco-agents have been reported to alter spermatogenesis, thereby causing infertility. Plants represent natural resources use in the management of several human diseases from time immemorial. Persea americana seed is a part of the fruit that most people do throw away after consuming the edible portion of the fruit. However, the therapeutic and pharmacological activities of P. americana seed have been reported. Therefore, this study sought to investigate the effects of P. americana seed extract on cyclosporine-induced reprotoxicity.

Long-acting PGE2 and Lisinopril Mitigate H-ARS.

Thrombocytopenia is a major complication in hematopoietic-acute radiation syndrome (H-ARS) that increases the risk of mortality from uncontrolled hemorrhage. There is a great demand for new therapies to improve survival and mitigate bleeding in H-ARS. Thrombopoiesis requires interactions between megakaryocytes (MKs) and endothelial cells. 16, 16-dimethyl prostaglandin E2 (dmPGE2), a longer-acting analogue of PGE2, promotes hematopoietic recovery after total-body irradiation (TBI), and various angiotensin-converting enzyme (ACE) inhibitors mitigate endothelial injury after radiation exposure. Here, we tested a combination therapy of dmPGE2 and lisinopril to mitigate thrombocytopenia in murine models of H-ARS following TBI. After 7.75 Gy TBI, dmPGE2 and lisinopril each increased survival relative to vehicle controls. Importantly, combined dmPGE2 and lisinopril therapy enhanced survival greater than either individual agent. Studies performed after 4 Gy TBI revealed reduced numbers of marrow MKs and circulating platelets. In addition, sublethal TBI induced abnormalities both in MK maturation and in in vitro and in vivo platelet function. dmPGE2, alone and in combination with lisinopril, improved recovery of marrow MKs and peripheral platelets. Finally, sublethal TBI transiently reduced the number of marrow Lin-CD45-CD31+Sca-1- sinusoidal endothelial cells, while combined dmPGE2 and lisinopril treatment, but not single-agent treatment, accelerated their recovery. Taken together, these data support the concept that combined dmPGE2 and lisinopril therapy improves thrombocytopenia and survival by promoting recovery of the MK lineage, as well as the MK niche, in the setting of H-ARS.

Antidiabetic Potential of Stem Bark Extract of Enantia chlorantha and Lack of Modulation of Its Therapeutic Efficacy in Diabetic Rats Co-Administered with Lisinopril.

This study validates the antidiabetic efficacy of Enantia chlorantha stem bark and the possible therapeutic implications of the co-administration of lisinopril and E. chlorantha in type 2 diabetic rats. E. chlorantha stem bark was extracted by cold maceration. The inhibitory effect of the plant on carbohydrate metabolizing enzymes and its antioxidative potentials were assessed in vitro. The extract exhibited α-amylase and α-glucosidase inhibitory activities and also showed antioxidative properties in vitro. Administration of the extract normalized fasting hyperglycemia in vivo by showing 47.24 % reduction in blood glucose levels relative to untreated diabetic rats. Co-administration of E. chlorantha and lisinopril restored serum glucose and serum lipid profile levels. E. chlorantha stem bark displayed antidiabetic potentials as compared with a standard antidiabetic drug (metformin). The study also showed that the plant contained some bioactive compounds which we hypothesize might be responsible for the observed activities. Co-administration of the plant with lisinopril conferred no significant therapeutic advantage on the serum glucose level and lipid profile.

Psychological Continuum of Elderly Patients Suffering from Arterial Hypertension with Metabolic Syndrome, Against the Background of Chronotherapy with a Fixed Combination of Amlodipine, Lisinopril and Rosuvastatin.

Aim        To study the psychological continuum in elderly patients with arterial hypertension associated with metabolic syndrome during the chronotherapy with a fixed combination (FC) of amlodipine, lisinopril, and rosuvastatin.Material and methods        In the inpatient conditions, 63 patients aged 60-74 years with arterial hypertension associated with metabolic syndrome were treated with chronotherapy with a FC of amlodipine, lisinopril, and rosuvastatin (5 / 10 / 10 mg/day in the evening). These patients composed the main group. The control group (58 patients aged 60-74 years with arterial hypertension associated with metabolic syndrome) was treated with the FC of amlodipine, lisinopril, and rosuvastatin at the same dose of 5 / 10 / 10 mg/day in the morning.Results   At one year, the disorders of psychological continuum were significantly decreased with the chronotherapy (evening dosing) with the antihypertensive FC of amlodipine, lisinopril, and rosuvastatin compared to the traditional treatment (morning dosing) at the same dose of 5 / 10 / 10 mg/day in both groups. With the chronotherapeutic approach, the dynamic of cognitive disorders in patients aged 60-74 years with arterial hypertension associated with metabolic syndrome was characterized by a significant increase in the Mini-Mental-State-Examination scale score from 17.8±0.3 at baseline to 23.5±0.4 with the evening dosing (р<0.001) vs. the increase from 16.9±0.3 to 20.4±0.4 (р<0.001) with the morning dosing. The situational anxiety score decreased from 40.0±2.2 to 30.6±1.8 (р<0.05) and from 40.8±2.5 to 33.5±1.9  (р<0.05), and the trait anxiety score decreased from 48.8±2.0 to 26.4±1.9 (р<0.001) and from 44.9±1.9 to 30.7±1.7  (р<0.01) with the evening and morning dosing, respectively. Depressive disorders slightly decreased with the chronotherapy by 14.1 % vs. 7.7 % with the traditional regimen; nevertheless, they were consistent with depressive spectrum disorders in both groups.Conclusion            The study results showed a higher effectiveness of the chronotherapeutic treatment compared to the traditional treatment with FC of amlodipine, lisinopril, and rosuvastatin in arterial hypertension with metabolic syndrome.

Impact of Green Tea Catechin Ingestion on the Pharmacokinetics of Lisinopril in Healthy Volunteers.

Lisinopril, a highly hydrophilic long-acting angiotensin-converting enzyme inhibitor, is frequently prescribed for the treatment of hypertension and congestive heart failure. Green tea consumption may reduce the risk of cardiovascular outcomes and total mortality, whereas green tea or its catechin components has been reported to decrease plasma concentrations of a hydrophilic ß blocker, nadolol, in humans. The aim of this study was to evaluate possible effects of green tea extract (GTE) on the lisinopril pharmacokinetics. In an open-label, randomized, single-center, 2-phase crossover study, 10 healthy subjects ingested 200 mL of an aqueous solution of GTE containing ~ 300 mg of (-)-epigallocatechin gallate, a major catechin component in green tea, or water (control) when receiving 10 mg of lisinopril after overnight fasting. The geometric mean ratio (GTE/control) for maximum plasma concentration and the area under the plasma concentration-time curve of lisinopril were 0.289 (90% confidence interval (CI) 0.226-0.352) and 0.337 (90% CI 0.269-0.405), respectively. In contrast, there were no significant differences in time to reach maximum lisinopril concentration (6 hours in both phases) and renal clearance of lisinopril (57.7 mL/minute in control vs. 56.9 mL/minute in GTE). These results suggest that the extent of intestinal absorption of lisinopril was significantly impaired in the presence of GTE, whereas it had no major effect on the absorption rate and renal excretion of lisinopril. Concomitant use of lisinopril and green tea may decrease oral exposure to lisinopril, and therefore result in reduced therapeutic efficacy.

Nutraceutical and pharmaceutical cocktails did not preserve diaphragm muscle function or reduce muscle damage in D2-mdx mice.

NEW FINDINGS: What is the central question of this study? We previously demonstrated that quercetin transiently preserved respiratory function in dystrophin-deficient mice. To gain lasting therapeutic benefits, we tested quercetin in combination with nicotinamide riboside, lisinopril and prednisolone in the D2-mdx model. What is the main finding and its importance? We demonstrated that these quercetin-based cocktails did not preserve respiratory or diaphragmatic function or reduce histological damage after 7 months of treatment starting at 4 months of age. ABSTRACT: Duchenne muscular dystrophy is characterized by the absence of dystrophin protein and causes muscle weakness and muscle injury, culminating in respiratory failure and cardiomyopathy. Quercetin transiently improved respiratory function but failed to maintain long-term therapeutic benefits in mdx mice. In this study, we combined quercetin with nicotinamide riboside (NR), lisinopril and prednisolone to assess the efficacy of quercetin-based cocktails. We hypothesized that quercetin, NR and lisinopril independently would improve respiratory function and decrease diaphragmatic injury and when combined would have additive effects. To address this hypothesis, in vivo respiratory function, in vitro diaphragmatic function and histological injury were assessed in DBA (healthy), D2-mdx (dystrophic) and D2-mdx mice treated with combinations of quercetin, NR and lisinopril from 4 to 11 months of age. Respiratory function, assessed using whole-body plethysmography, was largely similar between healthy and dystrophin-deficient mice. Diaphragm specific tension was decreased by ∼50% in dystrophic mice compared with healthy mice (P < 0.05), but fatigue resistance was similar between groups. Contractile area was decreased by ∼10% (P < 0.05) and fibrotic area increased from 3.5% in healthy diaphragms to 27% (P < 0.05) in dystrophic diaphragms. Contrary to expectations, these functional and histological parameters of disease were not offset by any intervention. These data suggest that quercetin, NR and lisinopril, independently and in combination, did not prevent diaphragmatic injury or preserve respiratory function.

Abdominal Wall Pain: A Common Clinical Problem.

Abdominal wall pain (AWP) is a common and underrecognized cause of chronic abdominal pain. The etiology of AWP varies. History and physical examination are critical to an accurate diagnosis of AWP. Trigger point injection using either a corticosteroid, a local anesthetic, or a combination of both often gives relief of pain and is of diagnostic and therapeutic value. Increased awareness of AWP as a cause of chronic, nonvisceral abdominal pain can prevent fruitless searches for intra-abdominal pathology and reduce medical costs.

Amelioration of Diabetes-Induced Diabetic Nephropathy by Aloe vera: Implication of Oxidative Stress and Hyperlipidemia.

This study investigated the effect of Aloe vera in diabetes-induced nephropathy in rats. As diabetes-associated hyperlipidemia and oxidative stress have been implicated in the pathogenesis of diabetic nephropathy, we evaluated the protective effect of whole leaf extract of Aloe vera on the basis of its hypolipidemic and antioxidative property. Aloe vera (300 mg/kg orally) has been noted to possess renoprotective effect in experimental diabetic nephropathy. However, its mechanism is not fully understood. Rats were administered streptozotocin (STZ) (55 mg/kg intraperitoneally once) to induce experimental diabetes mellitus. The development of diabetic nephropathy was assessed biochemically and histologically. In addition, the diabetes-induced lipid profile and renal oxidative stress were assessed. The single administration of STZ produced diabetes, which induced renal oxidative stress, altered the lipid profile, and subsequently produced nephropathy in eight weeks by increasing serum creatinine, blood urea nitrogen, proteinuria, and glomerular damage. Treatment with Aloe vera (300 mg/kg/day orally) was noted to be more effective against the diabetes-induced nephropathy and renal oxidative stress as compared to lisinopril (1 mg/kg/day orally), a reference agent. It may be concluded that diabetes-induced oxidative stress and lipid alterations may be accountable for the induction of nephropathy in diabetic rats. The treatment with Aloe vera (300 mg/kg/day orally) may have prevented the development of diabetes-induced nephropathy by reducing lipid alteration, decreasing renal oxidative stress, and providing direct renoprotective action.

Swallowing therapy for dysphagia in acute and subacute stroke.

BACKGROUND: Dysphagia (swallowing problems), which is common after stroke, is associated with increased risk of death or dependency, occurrence of pneumonia, poor quality of life, and longer hospital stay. Treatments provided to improve dysphagia are aimed at accelerating recovery of swallowing function and reducing these risks. This is an update of the review first published in 1999 and updated in 2012. OBJECTIVES: To assess the effects of swallowing therapy on death or dependency among stroke survivors with dysphagia within six months of stroke onset. SEARCH METHODS: We searched the Cochrane Stroke Group Trials Register (26 June 2018), the Cochrane Central Register of Controlled Trials (CENTRAL; 2018, Issue 6) in the Cochrane Library (searched 26 June 2018), MEDLINE (26 June 2018), Embase (26 June 2018), the Cumulative Index to Nursing and Allied Health Literature (CINAHL) (26 June 2018), Web of Science Core Collection (26 June 2018), SpeechBITE (28 June 2016), ClinicalTrials.Gov (26 June 2018), and the World Health Organization International Clinical Trials Registry Platform (26 June 2018). We also searched Google Scholar (7 June 2018) and the reference lists of relevant trials and review articles. SELECTION CRITERIA: We sought to include randomised controlled trials (RCTs) of interventions for people with dysphagia and recent stroke (within six months). DATA COLLECTION AND ANALYSIS: Two review authors independently applied the inclusion criteria, extracted data, assessed risk of bias, used the GRADE approach to assess the quality of evidence, and resolved disagreements through discussion with the third review author (PB). We used random-effects models to calculate odds ratios (ORs), mean differences (MDs), and standardised mean differences (SMDs), and provided 95% confidence intervals (CIs) for each.The primary outcome was functional outcome, defined as death or dependency (or death or disability), at the end of the trial. Secondary outcomes were case fatality at the end of the trial, length of inpatient stay, proportion of participants with dysphagia at the end of the trial, swallowing ability, penetration aspiration score, or pneumonia, pharyngeal transit time, institutionalisation, and nutrition. MAIN RESULTS: We added 27 new studies (1777 participants) to this update to include a total of 41 trials (2660 participants).We assessed the efficacy of swallowing therapy overall and in subgroups by type of intervention: acupuncture (11 studies), behavioural interventions (nine studies), drug therapy (three studies), neuromuscular electrical stimulation (NMES; six studies), pharyngeal electrical stimulation (PES; four studies), physical stimulation (three studies), transcranial direct current stimulation (tDCS; two studies), and transcranial magnetic stimulation (TMS; nine studies).Swallowing therapy had no effect on the primary outcome (death or dependency/disability at the end of the trial) based on data from one trial (two data sets) (OR 1.05, 95% CI 0.63 to 1.75; 306 participants; 2 studies; I² = 0%; P = 0.86; moderate-quality evidence). Swallowing therapy had no effect on case fatality at the end of the trial (OR 1.00, 95% CI 0.66 to 1.52; 766 participants; 14 studies; I² = 6%; P = 0.99; moderate-quality evidence). Swallowing therapy probably reduced length of inpatient stay (MD -2.9, 95% CI -5.65 to -0.15; 577 participants; 8 studies; I² = 11%; P = 0.04; moderate-quality evidence). Researchers found no evidence of a subgroup effect based on testing for subgroup differences (P = 0.54). Swallowing therapy may have reduced the proportion of participants with dysphagia at the end of the trial (OR 0.42, 95% CI 0.32 to 0.55; 1487 participants; 23 studies; I² = 0%; P = 0.00001; low-quality evidence). Trial results show no evidence of a subgroup effect based on testing for subgroup differences (P = 0.91). Swallowing therapy may improve swallowing ability (SMD -0.66, 95% CI -1.01 to -0.32; 1173 participants; 26 studies; I² = 86%; P = 0.0002; very low-quality evidence). We found no evidence of a subgroup effect based on testing for subgroup differences (P = 0.09). We noted moderate to substantial heterogeneity between trials for these interventions. Swallowing therapy did not reduce the penetration aspiration score (i.e. it did not reduce radiological aspiration) (SMD -0.37, 95% CI -0.74 to -0.00; 303 participants; 11 studies; I² = 46%; P = 0.05; low-quality evidence). Swallowing therapy may reduce the incidence of chest infection or pneumonia (OR 0.36, 95% CI 0.16 to 0.78; 618 participants; 9 studies; I² = 59%; P = 0.009; very low-quality evidence). AUTHORS' CONCLUSIONS: Moderate- and low-quality evidence suggests that swallowing therapy did not have a significant effect on the outcomes of death or dependency/disability, case fatality at the end of the trial, or penetration aspiration score. However, swallowing therapy may have reduced length of hospital stay, dysphagia, and chest infections, and may have improved swallowing ability. However, these results are based on evidence of variable quality, involving a variety of interventions. Further high-quality trials are needed to test whether specific interventions are effective.

Effect of aqueous extract and anthocyanins of calyces of Hibiscus sabdariffa (Malvaceae) in rats with adenine-induced chronic kidney disease.

OBJECTIVES: The aim of this work was to assess the possible beneficial effects of aqueous extracts of Hibiscus sabdariffa L. calyces and anthocyanins isolated therefrom in an adenine-induced chronic kidney disease (CKD) model. METHODS: Rats were orally given, for 28 consecutive days, either adenine alone or together with either aqueous extract of H. sabdariffa calyces (5 and 10%) or anthocyanins (50, 100 and 200 mg/kg of anthocyanin concentrate). For comparative purposes, two groups of rats were given lisinopril (10 mg/kg). KEY FINDINGS: When either H. sabdariffa aqueous extract or the anthocyanins isolated from it was administered along with adenine, the adverse effects of adenine-induced CKD were significantly lessened, mostly in a dose-dependent manner. The positive effects were similar to those obtained by administration of lisinopril. CONCLUSIONS: The results obtained show that both H. sabdariffa and its anthocyanins could be considered as possible promising safe dietary agents that could be used to attenuate the progression of human CKD. This could have added significance as H. sabdariffa tea is widely consumed in many parts of Africa and Asia and is thus readily available.

Betanin, isolated from fruits of Opuntia elatior Mill attenuates renal fibrosis in diabetic rats through regulating oxidative stress and TGF-ß pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: The fruits of Opuntia elatior Mill are being used traditionally in different disease condition like diabetes, obesity, asthma, inflammatory disorders, and anemia. Betanin, a compound isolated from fruits of Opuntia elatior Mill has potent anti-oxidative and anti-inflammatory activity. Recent study from our lab indicated the protective effect of betanin against high glucose induced rat renal epithelial cell fibrosis and matrix accumulation, major features of diabetic nephropathy (DN). However the molecular mechanism of betanin in DN has not yet been fully elucidated. AIM OF THE STUDY: The aim of the present study was to further investigate the anti-fibrotic mechanisms of betanin against streptozotocin (STZ) induced DN. MATERIALS AND METHODS: Betanin was isolated from fruits of Opuntia elatior Mill (Cactaceae) and structure was elucidated using spectroscopy (UV, IR, 1H-NMR and mass). STZ was injected intraperitoneally with single dose of 50mg/kg for diabetes induction. In order to develop DN the animals were left in diabetes condition without any treatment during the following 4 weeks. Betanin (25, 50 and 100mg/kg/day) and lisinopril (5mg/kg/day, reference compound) were orally administered for 8 weeks after the induction of DN. Renal function, blood glucose, serum creatinine, blood urea nitrogen (BUN) and antioxidant enzyme activities in the kidney tissue were measured. Kidney tissue samples were used for glomerulosclerosis, tubulointerstitial fibrosis and morphometric studies. The expression of transforming growth factor-beta (TGF-ß), type IV collagen, alpha-smooth muscle actin (α-SMA) and E-cadherin in kidney tissue were evaluated using reverse transcription-polymerase chain reaction, and immunohistochemistry. RESULTS: Betanin was successfully isolated from fruits of Opuntia elatior Mill (Cactaceae) and purified by column chromatography. The results showed that betanin attenuated diabetic kidney injury by significantly inhibiting proteinuria, blood glucose, serum creatinine and BUN levels and restored antioxidant enzyme activities in kidney tissue. Histological studies exhibited that betanin treatment reduced the glomerular surface area, glomerulosclerosis and tubulointerstitial fibrosis. Furthermore, betanin modulated mRNA and protein expression of TGF-ß, type IV collagen, α-SMA and E-cadherin in kidney. CONCLUSIONS: The results conclude that betanin can effectively suppress renal fibrosis in DN, and may slow down the progression to end-stage renal disease by regulating TGF-ß signal pathway.

Does consumption of an aqueous extract of Hibscus sabdariffa affect renal function in subjects with mild to moderate hypertension?

Hibiscus sabdariffa (HS) has been traditionally used as a herbal medicine in Nigeria mainly because of its antihypertensive action. In view of the recent increase in the prevalence of renal failure, we have investigated the effect of HS consumption on renal function in Nigerians with mild to moderate hypertension. A total of 78 newly diagnosed but untreated subjects with mild to moderate hypertension attending the medical outpatients unit of Enugu State University Teaching Hospital (Enugu, Nigeria) were recruited for the study. These subjects were randomly divided into three equally sized groups that received HS or lisinopril (treatment groups) or placebo (control group), once daily for 4 weeks. Indices of renal function (urine volume and creatinine clearance) were measured at baseline and weekly throughout the study period. HS and lisinopril significantly increased (P < 0.001) urine volume compared to placebo, and HS significantly (P < 0.001) increased urine volume more than lisinopril. HS significantly increased (P < 0.001) creatinine clearance compared to placebo whereas lisinopril did not. These results indicate that HS consumption improved indices of renal function in our study population of Nigerians with mild to moderate hypertension.

Haematopoietic effects of Angelica sinensis root cap polysaccharides against lisinopril-induced anaemia in albino rats.

CONTEXT: Angelica sinensis L. (Umbelliferae) has medicinal properties. OBJECTIVES: The present study evaluates the haematopoietic effects of A. sinensis polysaccharides (ASP) against lisinopril-induced anaemia. MATERIALS AND METHODS: Thirty healthy adult male albino rats were randomly divided into five groups (n = 6). Group I was control group. Group II was treated with angiotensin-converting enzyme inhibitor (ACEI, 20 mg/kg/day) to induce anaemia. In group III, erythropoietin (EPO, 100 IU/kg/each) was administered in combination with ACEI. Group IV was treated with ASP (1 g/kg/day), extracted from A. sinensis root caps. In Group V, ASP (1 g/kg/day) was treated with ACEI. After 28 days, blood and tissue samples were collected for haematological and histopathological analysis, respectively. RESULTS: The results showed that ACEI significantly reduced the haemoglobin (Hb, 10.0 g/dL), packed cell volume (PCV, 39.5%), red blood cells (RBCs, 6.2 million/mm3), mean corpuscular volume (MCV, 53.5 fL) and mean corpuscular haemoglobin (MCH, 16.2 pg/cell) values. In the group treated with ASP, the Hb (13.7 g/dL) and RBCs (7.8 million/mm3) increased significantly (p < 0.05). The combination of ASP and ACEI led to the significant (p < 0.05) reduction in Hb (10.7 g/dL), PCV (33.3%), RBCs (6.0 million/mm3), MCV (54.42 fL) and MCH (16.44 pg/cell) values. While histopathological examination of the liver and kidney cells showed a mild degree of toxicity in the ASP-treated group. CONCLUSION: ASP has a potentiating effect on haematological parameters when given alone. However, when administered simultaneously with lisinopril, it showed an unfavourable effect with more complicated anaemia so it should not be used with ACEIs.

Garlic capsule and selenium-vitamins ACE combination therapy modulate key antioxidant proteins and cellular adenosine triphosphate in lisinopril-induced lung damage in rats.

BACKGROUND: Garlic capsule (GAR) and/or selenium- vitamin A, C, E (S-VACE) might be useful in the treatment of lung diseases. The present study evaluated the toxicity of lisinopril (LIS) in the lungs of male rats and the reversal effect of GAR and/or selenium-vitamins A, C, and E (S-VACE). METHODS: Group I served as the control, whereas animals in groups II, III, IV, and V received 28 mg of LIS/kg body weight by gavage. Group III was co-treated with GAR at a therapeutic dosage of 250 mg/kg body weight per day. Group IV was co-treated with S-VACE at dosage of 500 mg/kg body weight per day. Lastly, group V was co-treated with GAR and S-VACE at dosages of 250 and 500 mg/kg body weight per day, respectively. The experiment lasted for 8 days (sub-acute exposure). RESULTS: Administration of therapeutic dose of LIS to male rats depleted enzymatic antioxidants (superoxide dismutase and catalase) and cellular adenosine triphosphate content with concomitant increase in lipid peroxidation. Histopathology examination showed damage to the epithelial cells of the airways. These effects were prevented by both single and combination treatment of GAR and S-VACE in male rats with LIS-induced lung toxicity. CONCLUSIONS: We therefore concluded that the combination of GAR and S-VACE can be a novel therapy for the management of lung diseases in humans.

Hypokalaemia and drinking green tea: a literature review and report of 2 cases.

We report the association between excessive consumption of green tea and hypokalaemia in an Oriental couple. Both patients were asymptomatic and the abnormal electrolyte level was only detected on routine blood tests. When they were advised to reduce the consumption of green tea, the abnormally low potassium level was reversed. We have not found such an association reported in the medical literature. The health benefits of green tea consumption are well publicised but the potential side-effects of overconsumption are less well known. We would like to report this association to alert clinicians about this potentially serious complication. This is especially relevant for those who are also taking prescribed medications that can lower potassium levels and/or sensitise patients to potential harm from hypokalaemia.

[Ramipril plus amlodipine and lisinopril plus amlodipine fixed dose combinations and patient's adherence]. / A ramipril/amlodipin és a lisinopril/amlodipin fix kombinációk a terápiahuség tükrében.

INTRODUCTION: Patient's adherence has a great significance to reach target blood pressure values. The risk of cardiovascular adverse events decreases when patients are on target blood pressure. AIM: The aim of the authors was to investigate the one-year persistence of the ramipril/amlodipine and lisinopril/amlodipine fixed dose combination in hypertensive patients. METHOD: National Health Insurance Found prescriptions database of Hungary on pharmacy-claims between October 1, 2012 and September 30, 2013 was analyzed. The authors identified patients who filled prescriptions for fixed dose combinations of ramipril and amlodipine, and lisinopril and amlodipine prescribed for the first time, for the therapeutic indication of hypertension. Patients have not received antihypertensive therapy with similar active substances during one year before the study. To model the persistence, the apparatus of survival analysis was used, where "survival" was the time to abandon the medication. As it was available to month precision, discrete time survival analysis was applied: a generalized linear model was estimated with complementary log-log link function with the kind of drug being the only explanatory variable. RESULTS: During the study period, fixed dose combination antihypertensive therapy with ramipril plus amlodipine and lisinopril plus amlodipine was started in 10,449 and 20,276 patients, respectively. One-year persistence rate in patients taking ramipril and amlodipine as a fixed dose combination was 54%, whereas 36% in those on the fixed lisinopril and amlodipine combination. Considering only the 360-day study period, the mean duration of persistence was 271 days in patients on the ramipril based and 211 days on lisinopril based fixed dose combination. Analyzing persistence on treatment with these combinations showed that the actual rate of discontinuation was about twice higher during treatment with the lisinopril and amlodipine fixed dose combination compared with the use of the ramipril and amlodipine fixed dose combination (hazard ratio = 1.79, p<0.001). CONCLUSIONS: There is a significant difference between the one-year persistence of ramipril plus amlodipine and lisinopril plus amlodipine fixed dose combination in patients with hypertension. The result demonstrated that ramipril and amlodipine fixed dose combination has a favourable patients' adherence as compared to lisinopril and amlodipine fixed dose combination.