Novel phenoxyalkylcarboxylic acid derivatives as hypolipidaemic agents

Novel phenoxyalkylcarboxylic acid derivatives based on the natural scaffolds, flavonoids, or resveratrol were designed, synthesized, and evaluated for hypolipidaemic activity. Among the compounds, 30b lowered the triglycerides by 48.5% (P?<?0.05) and total cholesterol by 44.2% (P?<?0.05), respectively, and was more effective than the reference drug fenofibric acid in a Triton WR-1339-induced hyperlipidaemic mice model orally (300?mg/kg body weight). 30b also showed 59.4% triglycerides lowering in an alloxan-induced diabetic mice model orally (150?mg/kg body weight). Receptor docking studies revealed that compound 30b could interact with the amino acid residues in the ligand-binding domain essential for the activation of the PPARα. The results indicate that resveratrol should be a better scaffold to derive a new class of hypolipidaemic agents in comparison with a flavonoid scaffold.     

Synthesis and in vivo anti-ulcer evaluation of some novel piperidine linked dihydropyrimidinone derivatives

Dihydropyrimidinone derivatives containing piperidine moiety were synthesised in a good yield. All the compounds were confirmed by elemental analysis and spectral data. Anti-ulcer activity of novel dihydropyrimidinone-piperidine hybrids (1–18) was evaluated. Among them, four compounds (3, 8, 11 and 15) were found to be most active in 80% ethanol-induced ulcer experimental animal model. All the potent compounds were further evaluated for anti-ulcer activity by different in vivo anti-ulcer models to study the effect of compounds on anti-secretory and cytoprotective activities. All the active compounds inhibited the formation of gastric ulcers and increased the formation of gastric mucin secretion. Compound 15 was found to be the most potent compound of the series as anti-ulcer agent. Additional experimental studies on lead compound 15 will result in a new class of orally active molecule for anti-ulcer activity.     

dl-3-正丁基苯酞对脑损伤大鼠的神经保护作用的实验研究

目的:研究dl-3-正丁基苯酞(NBP)对脑损伤大鼠的神经保护作用。方法:将100只7周龄清洁级雄性Sprague-Dawley(SD)大鼠随机分成5组,分别为假手术组、模型组、NBP低、中和高剂量组,每组20只。使用控制性皮层撞击损伤建立中型大鼠颅脑损伤模型。将NBP溶解在大豆油中,NBP低、中和高剂量组分别按照每天20、40和80 mg/kg的剂量灌胃,假手术组和模型组灌胃等体积的大豆油,共给药2周。采用改良神经功能缺损评分(m NSS)对大鼠的神经系统状况进行评价。检测各组大鼠治疗后的脑组织含水量以及脑组织中丙二醛(MDA)、超氧化物歧化酶(SOD)和谷胱甘肽过氧化物酶(GSH-Px)水平。TUNEL方法鉴定细胞的凋亡。通过RT-PCR、Western blot或免疫组化检测脑组织中Nrf2、NQO-1、HO-1、ApoJ、MMP9、AQP4、Caspase-3和AKT的表达。结果:NBP治疗2周后,NBP低、中和高剂量组大鼠的m NSS评分和神经元凋亡率以剂量依赖性方式显著降低(P0.05)。与模型组比较,NBP低、中和高剂量组大鼠的脑含水量均显著降低(P0.05)。与模型组比较,NBP低、中和高剂量组大鼠的MDA显著降低,而SOD和GSH-Px显著升高(P0.05)。与模型组比较,NBP低、中和高剂量组大鼠的细胞核Nrf2显著升高,而细胞质Nrf2显著降低(P0.05)。与模型组比较,NBP低、中和高剂量组大鼠的NQO-1和HO-1蛋白表达水平显著升高(P0.05)。与模型组比较,NBP低、中和高剂量组大鼠的AQP4、MMP-9、ApoJ和Caspase-3的m RNA和蛋白表达水平均显著降低,而AKT显著升高(P0.05)。结论:NBP对创伤性颅脑外伤大鼠具有一定的神经保护作用。     

Comparison of percutaneous vs oral infection of hamsters with the hookworm Ancylostoma ceylanicum: Parasite development,pathology and primary immune response

BackgroundHundreds of millions of people in poor countries continue to suffer from disease caused by bloodfeeding hookworms. While mice and rats are not reliably permissive hosts for any human hookworm species, adult Golden Syrian hamsters are fully permissive for the human and animal pathogen Ancylostoma ceylanicum. Similar to humans, hamsters may be infected with A. ceylanicum third-stage larvae orally or percutaneously. Oral infection typically leads to consistent worm yields in hamsters but may not accurately reflect the clinical and immunological manifestations of human infection resulting from skin penetration.Methodology/Principal findingsIn this study we compared host responses following percutaneous infection to those utilizing an established oral infection protocol. Infected hamsters exhibited a dose-dependent pathology, with 1000 percutaneous larvae (L3) causing anemia and adult worm recovery comparable to that of 50 orally administered L3. A delayed arrival and maturity of worms in the intestine was observed, as was variation in measured cellular immune responses. A long-term study found that the decline in blood hemoglobin was more gradual and did not reach levels as low, with the nadir of disease coming later in percutaneously infected hamsters. Both groups exhibited moderate growth delay, an effect that was more persistent in the percutaneously infected group. Fecal egg output also peaked later and at lower levels in the percutaneously infected animals. In contrast to orally infected hamsters, antibody titers to larval antigens continued to increase throughout the course of the experiment in the percutaneous group.Conclusions/SignificanceThese results demonstrate that the route of infection with A. ceylanicum impacts disease pathogenesis, as well as humoral and cellular immune responses in an experimental setting. These data further validate the utility of the Golden Syrian hamster as a model of both oral and percutaneous infection with human hookworms.     

Effect of Dexamethasone on Glucose Homeostasis In Normal and Prediabetic Subjects With A First-Degree Relative With Type 2 Diabetes Mellitus

ObjectiveTo determine the effect of a single 8-mg orally administered dose of dexamethasone or placebo on glucose and insulin homeostasis, during an oral glucose tolerance test (OGTT) performed before and 24 hours after the administered dose.MethodsIn a randomized, double-blind, placebo controlled study, we conducted experiments in subjects with normal glucose tolerance (NGT) or prediabetes, all of whom had at least one first-degree relative with type 2 dia betes mellitus. Measures of glucose and insulin homeosta sis derived from an OGTT before and 24 hours after admin istration of dexamethasone or placebo were compared in 21 placebo-treated versus 23 dexamethasone-treated sub jects with NGT as well as in 23 placebo-treated versus 20 dexamethasone-treated subjects with prediabetes.ResultsBefore administration of dexamethasone or placebo, area under the curve (AUC) for glucose and homeostasis model assessment of insulin resistance were higher, and the Matsuda and disposition indices were lower, in the prediabetic versus the NGT group. In both NGT and prediabetic groups treated with dexamethasone, glu cose and insulin values at fasting and during OGTT were increased in comparison with placebo-treated groups at 24 hours (P = .001). Dexamethasone treatment in both study groups increased homeostasis model assessment of insulin resistance and AUC glucose and decreased the Matsuda index (P = .001). No significant changes were observed in AUC insulin/AUC glucose or homeostasis model assess ment of beta-cell function after dexamethasone treatment in either the NGT or the prediabetic group. The disposition index decreased and was lowest in the prediabetic group after dexamethasone treatment.ConclusionIn a study population in which all sub jects had at least one first-degree relative with type 2 dia betes mellitus, those with prediabetes were more insulin resistant and had a lower disposition index than did sub jects with NGT. Subjects with prediabetes also had a pro nounced decrease in disposition index when challenged with a single 8-mg orally administered dose of dexametha sone. (Endocr Pract. 2012;18:855-863)     

Visceral Leishmaniasis on the Indian Subcontinent: Modelling the Dynamic Relationship between Vector Control Schemes and Vector Life Cycles

BackgroundVisceral leishmaniasis (VL) is a disease caused by two known vector-borne parasite species (Leishmania donovani, L. infantum), transmitted to man by phlebotomine sand flies (species: Phlebotomus and Lutzomyia), resulting in ≈50,000 human fatalities annually, ≈67% occurring on the Indian subcontinent. Indoor residual spraying is the current method of sand fly control in India, but alternative means of vector control, such as the treatment of livestock with systemic insecticide-based drugs, are being evaluated. We describe an individual-based, stochastic, life-stage-structured model that represents a sand fly vector population within a village in India and simulates the effects of vector control via fipronil-based drugs orally administered to cattle, which target both blood-feeding adults and larvae that feed on host feces.ConclusionsOur model should prove useful in a priori evaluation of the efficacy of fipronil-based drugs in controlling leishmaniasis on the Indian subcontinent and beyond.     

Involvement of asymmetric dimethylarginine (ADMA) in glomerular capillary loss and sclerosis in a rat model of chronic kidney disease (CKD)

AimsAsymmetric dimethylarginine (ADMA), an endogenous nitric oxide synthase inhibitor, has been reported to be a novel marker for the progression of chronic kidney disease (CKD). We have recently found that accumulation of ADMA could trigger peritubular capillary loss, thus contributing to tubulointerstitial ischemia and fibrosis in a rat model of CKD. However, effects of ADMA on glomerular capillary loss and sclerosis remain to be elucidated.Main methodsIn this study, we investigated whether lowering of ADMA by overexpression of dimethylarginine dimethylaminohydrolase (DDAH), a main enzyme that degrades ADMA, could ameliorate glomerular capillary loss and sclerosis in a rat model of CKD. Four weeks after 5/6 subtotal nephrectomy (Nx), animals were given tail vein injections with recombinant adenovirus vector encoding DDAH-I (Adv-DDAH) or control vector expressing bacterial β-galactosidase (Adv-LZ), or orally administered with 20 mg/kg/day of hydralazine (Hyz) which served as a blood pressure control model.Key findingsPlasma levels of ADMA were associated with decreased number of glomerular capillaries as well as severity of glomerular sclerosis in Nx-rats. These glomerular changes progressed in Adv-LZ- or Hyz-treated Nx-rats, while they were ameliorated by the treatment with DDAH overexpression.SignificanceOur present data suggest that ADMA may be involved in glomerular capillary loss and sclerosis, thus contributing to the progression of CKD. Substitution of DDAH protein or enhancement of its activity may become a novel therapeutic strategy for the treatment of CKD.     

Menthacarin attenuates experimental colitis

BackgroundPeppermint oil and caraway oil are established remedies in gastroenterological medicine because of their spasmolytic/analgesic effects.PurposeWe investigated whether Menthacarin, a combination of both oils, exerted anti-inflammatory effects in a dextran sodium sulphate (DSS, 2%) murine model of colitis.Study Design and MethodsC57BL/6 mice were orally administered Menthacarin in doses of 10, 30, 60, and 120 µg/g body weight (BW), and control mice received 0.2% agar, 10 µl/g BW, during 8 days of DSS-induced colitis. Colitis was monitored by BW measurements and colonoscopies. Colons of euthanised mice were excised for histological staining and ELISA measurements of the cytokines TNFα, IL-6, IL-10, IL-1β, and TGF-β.ResultsMenthacarin-treated mice compared to controls showed improved macroscopical and microscopical parameters and lower BW loss during the course of colitis. Menthacarin changed the colonic cytokine profile towards a regulatory/anti-inflammatory phenotype.ConclusionMenthacarin attenuates experimental colitis and may be a promising add-on therapy for the treatment of IBD.     

Manganese in toenails is associated with hearing loss at high frequencies in humans

Purpose: Elevated hearing thresholds from high frequencies are known to be one of the hallmarks of age-related hearing loss. Our recent study showed accumulation of manganese (Mn) in inner ears resulting in acceleration of age-related hearing loss in mice orally exposed to Mn. However, there is no evidence showing an association between Mn in non-invasive biological samples and hearing loss in humans evaluated by pure tone audiometry (PTA). In this study, we evaluated Mn in non-invasive biological samples as a possible biomarker for hearing loss in humans.

Materials and methods: We determined hearing levels by PTA and Mn levels in toenails, hair and urine with an inductively coupled plasma mass spectrometer (ICP-MS) in 145 healthy subjects in Bangladesh.

Results: Multivariable analyses showed that Mn levels in toenails, but not in hair and urine samples, were significantly associated with hearing loss at 8?kHz and 12?kHz. Moreover, our experimental study showed a significant correlation between Mn levels in inner ears and nails, but not hair, in mice orally exposed to Mn.

Conclusions: The results provide novel evidence that Mn in toenails is a possible biomarker for hearing loss at high frequencies in humans.     

Hesperidin attenuates inflammation and oxidative damage in pleural exudates and liver of rat model of pleurisy

Objectives: This study investigated the potential anti-inflammatory effect of hesperidin against carrageenan induced pleurisy in rat model.

Methods: Twenty-four adult female Wistar rats (350 - 450g) were grouped as follows: Group I: rats were administered saline solution only (Normal control group); Group II: rats were administered saline solution (NaCl 0.9%) orally and injected with carrageenan (Inflammation control group); Group III: rats were administered hesperidin only (Hesperidin group); Group IV: rats were administered hesperidin orally and intrapleurally injected with 2% carrageenan (Inflammation treated with hesperidin group). The exudate volume, total leukocyte count, reactive oxygen species (ROS), myeloperoxidase (MPO),δ–aminolevulinate dehydratase (δ-ALA-D), catalase (CAT), superoxide dismutase (SOD), activities as well as non-protein thiol group (NPSH) and thiobarbituric acid reactive substances (TBARS) levels were determined.

Results: Pretreatment with hesperidin at a dose of 80 mg/kg orally per day for 21 days, minimized the increase in pleural exudate volume and leucocyte count and modulated the activities of MPO, SOD and CAT, as well as the levels of ROS, NPSH and TBARS in carrageenan-induced rats.

Conclusion: Our results suggest that hesperidin can elicit its anti-inflammatory action by blocking exudate and leukocyte influx into pleural cavity, inhibiting MPO activity and preventing oxidative damage.     

Chemistry and Biological Activities of Cinnzeylanine and Cinnzeylanol,New Insecticidal Substances from Cinnamonum zeylanicum Nees

Cinnzeylanine (1) and cinnzeylanol (2) were isolated from barks of Cinnamonum zeylanicum Nees (ceylon cinnamon). Chemical properties and NMR spectra of the both compounds are disccused in terms of their structures which were determined by the X-ray analysis and chemical reactions. When administered orally with artificial diet, both 1 and 2 killed larvae of silkworm, Bombyx mori L. at a dose of 16 ppm and inhibited larval ecdysis at 2~ 4 ppm.     

Everolimu Resolving Hypoglycemia,Producing Hyperglycemia,and Necessitating Insulin Use in A Patient With Di Etes and Nonresectable Malignant Insulinoma

ObjectiveTo present a case of management of refractory hypoglycemia due to malignant insulinoma with use of everolimusresulting in recurrent insulin-requiring diabetes.MethodsThis report describes a case of a nonresectable malignant insulinoma in a 78-year-old patient with long-standing type 2 diabetes mellitus. Endogenous hyperinsulinism was confirmed by a fasting test, which revealed a glucose level of 35 mg/dL and an insulin value of 23.7 μIU/mL. Endoscopic ultrasonography, magnetic resonance imaging, and computed tomography identified a pancreatic mass, infiltration of the superior mesenteric vein, and metastatic lesions in the liver.ResultsAfter chemoembolization of the metastatic lesions, hypoglycemia recurred, despite combined treatment with somatostatin analogues, dexamethasone, and diazoxide. Everolimus, an orally administered mammalian target of rapamycin, was used at a daily dose of 5 mg. After 6 months, the hypoglycemia was controlled, and the patient presented with a C-peptide level of 0.2 ng/mL and secondary hyperglycemia that necessitated insulin treatment.ConclusionThe orally administered drug everolimus controlled hypoglycemia due to a malignant insulinoma in a patient with prior insulinrequiring diabetes. Secondary hyperglycemia was an acceptable drug effect (to the patient and managing physicians), in light of the complex and often poorly tolerated treatments available for this rare condition. (Endocr Pract. 2011;17:e17-e20)     

Up-regulation of Arl4a gene expression by broccoli aqueous extract is associated with improved spermatogenesis in mouse testes

Introduction: Broccoli (Brassica oleracea) is well known for its properties as an anticancer, antioxidant, and scavenger of free radicals. However, its benefits in enhancing spermatogenesis have not been well established.Objective: To study broccoli aqueous extract effects on sperm factors and the expression of genes Catsper1, Catsper2, Arl4a, Sox5, and Sox9 in sperm factors in mice.Material and methods: Male mice were divided randomly into six groups: (1) Control; (2) cadmium (3 mg/kg of mouse body weight); (3) orally treated with 200 µl broccoli aqueous extract (1 g ml^-1); (4) orally treated with 400 µl of broccoli aqueous extract; (5) orally treated with 200 broccoli aqueous extract plus cadmium, and (6) orally treated with 400 µl of broccoli aqueous extract plus cadmium. We analyzed the sperms factors and Catsper1, Catsper2, Arl4a, Sox5, and Sox9 gene expression.Results: An obvious improvement in sperm count and a slight enhancement in sperm motility were observed in mice treated with broccoli extract alone or with cadmium. Sperm viability was reduced by broccoli extract except for the 200 µl dose with cadmium, which significantly increased it. Interestingly, Arl4a gene expression increased in the 400 µl broccoli- treated group. Likewise, the Arl4a mRNA level in mice treated with cadmium and 200 µl of broccoli extract was higher than in the cadmium-treated mice. Furthermore, broccoli extract enhanced the mRNA level of Catsper2 and Sox5 genes in mice treated with 200 µl and 400 µl broccoli extract plus cadmium compared with the group treated solely with cadmium.Conclusion: The higher sperm count in broccoli-treated mice opens the way for the development of pharmaceutical products for infertile men.     

The effect of selective phosphodiesterase inhibitors,alone and in combination,on a murine model of allergic asthma

BackgroundThe anti-inflammatory effects of the selective phosphodiesterase (PDE) inhibitors cilostazol (PDE 3), RO 20-1724 (PDE 4) and sildenafil (PDE 5) were examined in a murine model of allergic asthma. These compounds were used alone and in combination to determine any potential synergism, with dexamethasone included as a positive control.MethodsControl and ovalbumin sensitised Balb/C mice were administered orally with each of the possible combinations of drugs at a dose of 3 mg/Kg for 10 days.ResultsWhen used alone, RO 20-1724 significantly reduced eosinophil influx into lungs and lowered tumour necrosis factor-α, interleukin-4 and interleukin-5 levels in the bronchoalveolar lavage fluid when compared to untreated mice. Treatment with cilostazol or sildenafil did not significantly inhibit any markers of inflammation measured. Combining any of these PDE inhibitors produced no additive or synergistic effects. Indeed, the anti-inflammatory effects of RO 20-1724 were attenuated by co-administration of either cilostazol or sildenafil.ConclusionsThese results suggest that concurrent treatment with a PDE 3 and/or PDE 5 inhibitor will reduce the anti-inflammatory effectiveness of a PDE 4 inhibitor.     

Hypocalcemia after Alendronate Therapy in a Patient with Celiac Disease

ObjectiveTo describe a patient with osteoporosis who was treated with alendronate and developed hypocalcemia, which ultimately led to the diagnosis of celiac sprue.MethodsWe present the clinical and laboratory findings in a patient with osteoporosis, in whom hypocalcemia developed after treatment with alendronate. This patient was subsequently diagnosed with celiac sprue. The pertinent literature regarding orally administered bisphosphonate-induced hypocalcemia is reviewed.ResultsA 79-year-old man who was diagnosed with osteoporosis was treated with alendronate. He was subsequently found to have asymptomatic hypocalcemia (serum calcium concentration, 8.3 mg/dL), which resolved after alendronate therapy was discontinued. He was then treated with calcium, vitamin D, and calcitonin nasal spray, which did not cause hypocalcemia. Because of his reduced bone density, however, he was subsequently referred for endocrine consultation. Evaluation at that time showed normal levels of serum calcium, phosphorus, creatinine, alkaline phosphatase, 25-hydroxyvitamin D, thyrotropin, and parathyroid hormone as well as 24-hour urine calcium excretion. An endomysial antibody titer was dramatically elevated. Upper endoscopy showed villous atrophy, and small bowel biopsy confirmed the presence of villous blunting and chronic inflammation, consistent with celiac sprue. He was treated with a gluten-free diet and then subsequently treated with orally administered risedronate, which he tolerated well without evidence of hypocalcemia.ConclusionTo the best of our knowledge, this is the first report of orally administered bisphosphonate-induced hypocalcemia, which subsequently led to the diagnosis of previously unrecognized, otherwise asymptomatic celiac sprue. Patients with unexplained hypocalcemia should be screened for celiac sprue, even in the absence of gastrointestinal symptoms. (Endocr Pract. 2007;13:403-407)     

Correlation between octanol/water and liposome/water distribution coefficients and drug absorption of a set of pharmacologically active compounds

Abstract

Absorption and consequent therapeutic action are key issues in the development of new drugs by the pharmaceutical industry. In this sense, different models can be used to simulate biological membranes to predict the absorption of a drug. This work compared the octanol/water and the liposome/water models. The parameters used to relate the two models were the distribution coefficients between liposomes and water and octanol and water and the fraction of drug orally absorbed. For this study, 66 drugs were collected from literature sources and divided into four groups according to charge and ionization degree: neutral; positively charged; negatively charged; and partially ionized/zwitterionic. The results show a satisfactory linear correlation between the octanol and liposome systems for the neutral (R^2?=?0.9324) and partially ionized compounds (R^2?=?0.9367), contrary to the positive (R^2?=?0.4684) and negatively charged compounds (R^2?=?0.1487). In the case of neutral drugs, results were similar in both models because of the high fraction orally absorbed. However, for the charged drugs (positively, negatively, and partially ionized/zwitterionic), the liposomal model has a more-appropriate correlation with absorption than the octanol model. These results show that the neutral compounds only interact with membranes through hydrophobic bonds, whereas charged drugs favor electrostatic interactions established with the liposomes. With this work, we concluded that liposomes may be a more-appropriate biomembrane model than octanol for charged compounds.     

Effect of fudosteine,a cysteine derivative,on airway hyperresponsiveness,inflammation, and remodeling in a murine model of asthma

AimsFudosteine is a cysteine derivative that is used as an expectorant in chronic bronchial inflammatory disorders. It has been shown to decrease the number of goblet cells in an animal model. This study examined the effects of fudosteine on airway inflammation and remodeling in a murine model of chronic asthma.Main methodsBALB/c mice were sensitized by an intraperitoneal injection of ovalbumin (OVA), and subsequently challenged with nebulized ovalbumin three days a week for four weeks. Seventy-two hours after the fourth challenge, airway hyperresponsiveness (AHR) and the cell composition of bronchoalveolar lavage (BAL) fluid were assessed. Fudosteine was administered orally at 10 mg/kg or 100 mg/kg body weight from the first to the fourth challenge.Key findingsWe investigated the effects of fudosteine on the development of allergic airway inflammation and airway hyperresponsiveness after chronic allergen challenges. The administration of fudosteine during the challenge with ovalbumin prevented the development of airway hyperresponsiveness and accumulation of lymphocytes in the airways. Eotaxin, IL-4, and TGF-β levels and the relative intensity of matrix metalloproteinase-2 and matrix metalloproteinase-9 (MMP-2 and MMP-9) in BAL fluid were reduced by the fudosteine treatment; however, the number of eosinophils in BAL fluid and serum IgE levels did not change. The expression of TGF-β, the development of goblet cell hyperplasia, subepithelial collagenization, and basement membrane thickening were also reduced by the fudosteine treatment.SignificanceThese results indicate that fudosteine is effective in reducing airway hyperresponsiveness, airway inflammation, and airway remodeling in a murine model of chronic asthma.     

Protective effect of rosemary (Rosmarinus officinalis) against diethylnitrosamine-induced renal injury in rats

Abstract

Context: The kidney plays a central role in detoxification and excretion of toxic metabolites, and therefore, is susceptible to toxicity by xenobiotics.

Objective: To investigate the protective effect of Rosmarinus officinalis (rosemary) powder and its essential (volatile) oil against diethylnitrosamine (DEN)-induced renal injury in rats.

Materials and methods: Phenolic and flavonoid components were characterised in rosemary powder using HPLC-UV instrument while rosemary essential oil (E.O) was investigated via GC-MS technique. In rat model, rosemary was administrated orally (in diet) for two months. Lipid profile, antioxidant biomarkers, kidney functions and histopathological examinations were assessed.

Results: Hesperidin (4878.88?ppm) and ellagic acid (403.57?ppm) are among the major phenolic and flavonoid constituents in rosemary powder. Camphor (18.36%) and α-pinene (12.74%) represent the main E.O active ingredients. Rats treated with rosemary E.O showed a significant elevation in serum HDL (28.28%) accompanied by a decrease in LDL (115.47%). A significant decrease in serum creatinine and urea was also reported (69.72 and 109.89%, respectively). Moreover, serum glutathione peroxidise (GSH-Px) activity has been significantly increased. Kidney histopathological examinations confirmed the protective effect against DEN-induced abnormalities.

Conclusion: Rosemary (powder/E.O) was able to reduce or even prevent the severity of diethylnitrosamine-induced renal dysfunction.     

Inpatient Medical Errors Involving Glucose-Lowering Medications and Their Impact on Patients: Review of 2,598 Incidents from a Voluntary Electronic Error-Reporting Database

ObjectiveTo describe characteristics of inpatient medical errors involving hypoglycemic medications and their impact on patient care.MethodsWe conducted a cross-sectional analysis of medical errors and associated adverse events voluntarily reported by hospital employees and staff in 21 nonprofit, nonfederal health-care organizations in the United States that implemented a Web-based electronic error-reporting system (e-ERS) between August 1, 2000, and December 31, 2005. Persons reporting the errors determined the level of impact on patient care.ResultsThe median duration of e-ERS use was 3.1 years, and 2,598 inpatient error reports involved insulin or orally administered hypoglycemic agents. Nursing staff provided 59% of the reports; physicians reported < 2%. Approximately two-thirds of the errors (1,693 of 2,598) reached the patient. Errors that caused temporary harm necessitating major treatment or that caused permanent harm accounted for 1.5% of reports (40 of 2,598). Insulin was involved in 82% of reports, and orally administered hypoglycemic agents were involved in 18% of all reports (473 of 2,598). Sulfonylureas were implicated in 51.8% of reports involving oral hypoglycemic agents (9.4% of all reports).ConclusionAn e-ERS provides an accessible venue for reporting and tracking inpatient medical errors involving glucose-lowering medications. Results are limited by potential underreporting of events, particularly by physicians, and variations in the reporter perception of patient harm. (Endocr Pract. 2008;14:535-542)     

Transcriptomic and biochemical effects of pycnogenol in ameliorating heat stress-related oxidative alterations in rats

BackgroundHeat stress is a condition that is due to extreme heat exposure. It occurs when the body cannot keep its temperature healthy in response to a hot climate and associated with oxidative stress. Testicular hyperthermia can induce apoptosis of sperm cells, affect sperm production and decrease sperm concentration, leading to sperm disorder, for this reason, we examined the protective impact of pycnogenol that it has a wide range of biological benefits, including antioxidant, anti-inflammatory and anti-cancer activities against the oxidative alterations that happen in testicular and brain tissues due to heat stress in rats.Study designForty-eight Wistar male rats, approximately around 6 weeks age were allocated randomly into four groups (12 in each) of control, HS (subjected to heat stress and supplemented orally with 50 mg of pycnogenol/kg b. w./day dissolved in saline for 21 days), and pycnogenol (rats supplemented orally with 50 mg of pycnogenol/kg b. w./day dissolved in saline for 21 days).ResultsData revealed a promising role of pycnogenol as an antioxidant, natural product to successfully reverse the heat-induced oxidative alterations in testicular and brain tissues of rats through significant upregulation of superoxide dismutase-2, catalase, reduced glutathione, and anti-apoptotic gene, while downregulating pro-apoptotic, and heat shock protein70. Pycnogenol treatment also reversed the reproductive hormone level and spermatogenesis to their normal values.ConclusionPycnogenol as a natural protective supplement could recover these heat stress-induced oxidative changes in testes and hypothalamus.