Bioactive peptide carnosin protects against lead acetate-induced hepatotoxicity by abrogation of oxidative stress in rats

Context Oxidative stress is a common mechanism of liver injury. Carnosine is a dipeptide having strong antioxidant effects.

Objectives We investigated the effects of carnosine on lead-induced hepatotoxicity and oxidative stress in rats.

Materials and methods Animals received an aqueous solution of lead acetate (500?mg Pb/L in the drinking water) and/or daily oral gavage of carnosine (10?mg/kg) for 8 weeks. Rats were then weighed and used for the biochemical (commercial kits), molecular (standard chemical methods) and histological (microscopic) evaluations.

Results Lead-induced oxidative stress in liver tissue was indicated by a significant increase in the level of malondialdehyde (MDA) (8.25?±?0.15?nmol/mg) as well as decrease in the level of total antioxidant capacity (TAC) (1.72?±?0.25?μmol/g) and total thiol (SH) groups) 1.9?±?0.22?μmol/g). Carnosine treatment decreased MDA (4?±?0.08?nmol/mg), whereas it increased the contents of total thiol (3.25?±?0.04?μmol/g) and TAC (3.44?±?0.32?μmol/g) in the lead group. Carnosine also prevented the decreased body weight (p?<?0.001), albumin (p?<?0.05) and total protein levels (p?<?0.001) and increased liver weight (p?<?0.05) and activates of hepatic enzymes (p’s?<?0.001) (alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase and lactate dehydrogenase) in the lead group. Furthermore, histopathological study showed that carnosine attenuates liver damage by decreasing necrosis and infiltration of inflammatory cells.

Conclusion Carnosine prevented lead-induced hepatotoxicity, indicated by molecular, biochemical and histopathological analyses through inhibiting lipid peroxidation and enhancing antioxidant defence systems. Therefore, carnosine makes a good candidate to protect against the deleterious effect of chronic lead intoxication.     

Effect of isotretinoin treatment on the inflammatory markers in patients with acne vulgaris: can monocyte/HDL be a new indicator for inflammatory activity of isotretinoin treatment?

Abstract

Background: Oral isotretinoin (ISO) can effect markers of inflammation in patients with acne vulgaris. To our knowledge, there are no data on the relationship between ISO and monocyte to HDL cholesterol ratio (MHR). In this study, it is aimed to examine the effect of the ISO treatment on the MHR and other inflammatory markers in patients with acne vulgaris.

Materials and methods: In this study, 89 out of 120 patients with severe/very severe acne vulgaris according to the Global Acne Grading Scale who received at least 3 months of ISO treatment were evaluated. The complete blood counts including mean levels of mean platelet volume, plateletcrit (PTC), neutrophil to lymphocyte ratio (NLR), platelet to lymphocyte ratio (PLR), MHR, and serum biochemistry panel were evaluated before and after ISO treatment.

Results: The mean platelet value, NLR, and PLR levels underwent a statistically significant decrease after ISO treatment (p?<?0.05) while MHR increased significantly 3 months after ISO treatment (p?=?0.017). The mean platelet value, NLR, and PLR levels were 9.56?±?1.05, 2.15?±?0.81, and 142.45?±?48.33 before treatment while were 9.32?±?1.45, 1.90?±?0.99, and 127.94?±?41.38 after treatment, respectively. On the other hand, MHR was 9.76?±?4.27 and 10.86?±?4.12 before and after treatment, respectively.

Conclusions: In this study, we found that ISO may have both inflammatory and anti-inflammatory effects by using MPV, PTC, NLR, PLR, and MHR. The inflammatory effects of ISO may be associated with possible inflammatory diseases. MHR can be used as a novel marker to investigate the inflammatory effect of the ISO.     

Vitamin D status in patients with rosacea

Background: Rosacea is a common chronic skin condition affecting the face. In recent years, significant evidence shows that vitamin D plays an important role in modulating the immune system. Vitamin D and its analogues via these mechanisms are playing an increasing role in the management of atopic dermatitis, psoriasis, vitiligo, acne and rosacea.

Objectives: In our study, we aimed to investigate the relationship between serum vitamin D levels in patients with rosacea and analyze the association of vitamin D with clinical features.

Methods: Forty-four rosacea patients and 32 healthy control subjects were included into the study. 25-hydroxyvitamin D (25(OH)D), calcium and intact parathyroid hormone were measured. Deficiency of vitamin D is defined as the level of 25(OH)D being less than 20?ng/ml.

Results: Thirty-three female and 11 male patients were included in the study. The mean age of patients was 48.6?±?11.5. The mean levels of vitamin D levels were found as 21.4?±?9.9 and 17.1?±?7.9 in patients and controls, respectively. The difference was statistically significant (p?=?0.04). The prevalence of vitamin D deficiency in patients with rosacea was 38.6% and 28.1% in healthy controls (p?=?0.34).

Conclusions: To the best of our knowledge, our study is the first study for evaluating serum vitamin D levels of patients with rosacea in the literature. Patients with rosacea have relatively high serum vitamin D levels compared to control groups. The result of our study suggests that increased vitamin D levels may lead to the development of rosacea. To confirm status of vitamin D levels in patients with rosacea, larger epidemiological studies are needed.     

Chemometrics models for assessment of oxidative stress risk in chrome-electroplating workers

Oxidative stress is the main cause of hexavalant chromium-induced damage in chrome electroplating workers. The main goal of this study is toxicity analysis and the possibility of toxicity risk categorizing in the chrome electroplating workers based on oxidative stress parameters as prognostic variables. We assessed blood chromium levels and biomarkers of oxidative stress such as lipid peroxidation, thiol (SH) groups and antioxidant capacity of plasma. Data were subjected to principle component analysis (PCA) and artificial neuronal network (ANN) to obtain oxidative stress pattern for chrome electroplating workers. Blood chromium levels increased from 4.42?ppb to 10.6?ppb. Induction of oxidative stress was observed by increased in lipid peroxidation (22.38?±?10.47?μM versus 14.74?±?4.82?μM, p?p?p?相似文献   

Effects of vildagliptin versus saxagliptin on daily acute glucose fluctuations in Chinese patients with T2DM inadequately controlled with a combination of metformin and sulfonylurea

Objective The present study aimed to compare the effects of the dipeptidyl peptidase-4 (DPP-4) inhibitors vildagliptin and saxagliptin on 24?hour acute glucose fluctuations in Chinese patients with type 2 diabetes mellitus (T2DM) inadequately controlled with a combination of metformin and sulfonylurea.

Research design and methods This was a 24 week, prospective, randomized, open-label, active-controlled study. Patients (N?=?73) with T2DM who had inadequate glycemic control (HbA1c 7.0%–10.0%) with a stable dosage of metformin plus gliclazide for more than 3 months were randomized to receive either vildagliptin 50?mg twice daily (BID, n?=?37) or saxagliptin 5?mg once daily (QD, n?=?36). Change in mean amplitude of glycemic excursions (MAGE) was assessed at the end of 24 weeks.

Results At baseline, the mean (±SD) age was 62.9?±?6.55 years, disease duration was 7.0?±?2.33 years, and HbA1c was 8.4?±?0.68%. After 24 weeks of treatment, the MAGE decreased from 5.81?±?1.16?mmol/L to 4.06?±?0.86?mmol/L (p<0.001) in the vildagliptin group and from 5.66?±?1.14?mmol/L to 4.79?±?1.25?mmol/L (p?=?0.003) in the saxagliptin group. The mean change in MAGE in the vildagliptin group was significantly greater than that in the saxagliptin group (1.74?±?0.48?mmol/L vs. 0.87?±?0.40?mmol/L, p<0.001). The mean change in HbA1c, from baseline to the study endpoint, in the vildagliptin and saxagliptin groups, was 1.22?±?0.40% and 1.07?±?0.36%, respectively, with no significant difference between the groups (p?=?0.091). The overall safety and tolerability of vildagliptin and saxagliptin were similar. The limitations of the study were a small number of patients and open-label administration of the study drug.

Conclusion Vildagliptin produced a significantly greater reduction in acute glucose fluctuations compared with saxagliptin when added to a dual combination of metformin and sulfonylurea in Chinese patients with T2DM.

Chinese clinical trial registration number ChiCTR-TRC-13003858.     

Hepatoprotective effects of cod liver oil against sodium nitrite toxicity in rats

Abstract

Context: Exposure to high levels of nitrites for a prolonged time have adverse health effects on several organs especially the liver due to oxidative properties. Meanwhile, cod liver oil has been reported to ameliorate organ dysfunction in animal models that involve oxidative stress.

Objective: Examine the impact of dietary cod liver oil on sodium nitrite-induced liver damage.

Materials and methods: Thirty-two adult male Sprague-Dawely rats were daily treated with sodium nitrite (80?mg/kg) in presence or absence of cod liver oil (5?ml/kg). Morphological changes were assessed in liver sections. Oxidative stress and antioxidant markers were measured in serum and liver homogenates. Liver samples were used for measurements of MCP-1, DNA fragmentation and mitochondrial function.

Results: The hepatoprotective effect of cod liver oil was proved by significant reduction of elevated liver enzymes and normal appearance of hepatocytes. Cod liver oil significantly reduced hepatic malondialdehyde, hydrogen peroxide and superoxide anion (224.3?±?18.9?nmol/g, 59.3?±?5.1 and 62.5?±?5.1?µmol/g, respectively) compared with sodium nitrite (332.5?±?25.5?nmol/g, 83.1?±?8.1 and 93.9?±?6.5?µmol/g, respectively). Cod liver oil restored hepatic cytochrome c oxidase activity after 38% reduction by sodium nitrite. Furthermore, cod liver oil significantly reduced hepatic MCP-1 (79.8?pg/mg) and DNA fragmentation (13.8%) compared with sodium nitrite (168.7?pg/mg and 41.3%, respectively).

Discussion and conclusion: Cod liver oil ameliorates sodium nitrite induced hepatic impairment through several mechanisms including attenuation of oxidative stress, blocking MCP-1, reactivation of mitochondrial function and reduction of DNA fragmentation.     

Effects of rosmarinic acid on acetaminophen-induced hepatotoxicity in male Wistar rats

Context: Drug-induced liver injury is a significant worldwide clinical problem. Rosmarinic acid (RA), a natural phenol, has antioxidant effects.

Objective: The effects of RA against acetaminophen (N-acetyl-p-amino-phenol (APAP))-induced oxidative damage and hepatotoxicity in rats were investigated.

Materials and methods: Male Wistar rats were pretreated with RA (10, 50 and 100?mg/kg, i.g.) for one week. On day 7, rats received APAP (500?mg/kg, i.p.). Then aspartate aminotransferase (AST), alanine aminotransferase (ALT), albumin, total protein, malondialdehyde (MDA), glutathione (GSH), total antioxidant capacity (TAC), glutathione S-transferase (GST), cytochrome CYP450 and histopathological changes were determined.

Results: APAP-induced oxidative stress in liver by a significant increase in the level of MDA (7.6?±?0.21?nmol/mg) as well as a decrease in the contents of TAC (1.75?±?0.14?μmol/g), GSH (1.9?±?0.22?μmol/g) and GST) 3.2?±?0.28?U/mg). RA treatment decreased MDA (4.32?±?0.35?nmol/mg) but increased the contents of TAC (3.51?±?0.34?μmol/g), GSH (3.42?±?0.16?μmol/g) and GST (5.71?±?0.71?μmol/g) in APAP group. RA 100?mg/kg decreased ALT (91.5?±?1.5?U/L), AST (169?±?8.8?U/L) and CYP450 (3?±?0.2?nmol/min/mg) in APAP group. Histologically RA attenuated hepatic damage by decreasing necrosis, inflammation, and haemorrhage in liver sections of APAP group.

Discussion and conclusions: This is the first report that oral administration of RA dose-dependently elicited significant hepatoprotective effects in rats through inhibition of hepatic CYP2E1 activity and lipid peroxidation. RA-protected hepatic GSH and GST reserves and total tissue antioxidant capacity.     

Mechanism of ginsenoside Rg1 renal protection in a mouse model of d-galactose-induced subacute damage

Context Ginseng is a widely used herbal medicine in China but its mechanism of action remains unclear.

Objective The objectives of this work were to study the protective effect of ginsenoside Rg1 on subacute murine renal damage induced by d-galactose and its mechanism.

Materials and methods C57BL/6J mice were injected with 120?mg/kg/d (sc) d-galactose for 1 week, followed by a combined treatment of Rg1 20?mg/kg/d (ip) and 120?mg/kg/d d-galactose (sc) for 5 weeks. Mice were injected with the 0.9% saline 0.2?mL/d (sc) and 120?mg/kg/d d-galactose (sc) for 6 weeks in the control group and the d-galactose group, respectively. After 6 weeks, urea, creatinine, uric acid, cystatin (Cys-C), senescence-associated β-galactosidase (SA-β-gal) staining positive kidney cells, superoxide dismutase (SOD), glutathione peroxidase (GSH-PX), malondialdehyde (MDA), glycation end products (AGEs) and 8-hydroxy-2 deoxyguanosine (8-OH-dG) were measured.

Results Treatment with Rg1 ameliorated kidney function and aging state (urea from 17.19?±?1.09 to 15.77?±?1.22?mmol·L?^??¹, creatinine from 29.40?±?5.72 to 22.60?±?3.97?μmol·L?^??¹, uric acid from 86.80?±?5.97 to 72.80?±?10.61?μmol·L?^??¹, Cys-C from 0.23?±?0.03 to 0.18?±?0.05?mg·L?^??¹, ROD of SA-β-gal from 56.32?±?10.48 to 26.78?±?7.34, SOD from 150.22?±?19.07 to 190.56?±?15.83 U·(mg·prot)?^?1, MDA from 9.28?±?1.59 to 3.17?±?0.82?nmol·(mg·prot)?^?1, GSH-PX from 15.68?±?2.11 to 20.32?±?2.96 U·(mg·prot)?^?1 as well as regulated glomerulus morphology (glomerulus diameter from 775.77?±?18.41 to 695.04?±?14.61?μm, renal capsule width from 39.56?±?3.51 to 31.42?±?2.70?μm, glomerulus basement membrane from 206.03?±?16.22 to 157.27?±?15.70?nm, podocyte slit from 55.21?±?8.55 to 37.63?±?6.65?nm).

Conclusions Ginsenoside Rg1 can antagonise d-galactose subacute renal damage in mice and this may occur due to alleviating oxidative stress injury.     

Protective mechanism of turmeric (Curcuma longa) on carbofuran-induced hematological and hepatic toxicities in a rat model

Context: Turmeric (Curcuma longa L. [Zingiberaceae]) is used in the treatment of a variety of conditions including pesticide-induced toxicity.

Objective: The study reports the antioxidant properties and the protective effects of turmeric against carbofuran (CF)-induced toxicity in rats.

Materials and methods: The antioxidant potential was determined by using free radicals scavenging activity and ferric reducing antioxidant power values. Male Wistar rats were randomly divided into four groups, designated as control, turmeric (100?mg/kg/day), CF (1?mg/kg/day) and turmeric (100?mg/kg/day)?+?CF (1?mg/kg/day) treatments. All of the doses were administered orally for 28 consecutive days. The biological activity of the turmeric and CF was determined by using several standard biochemical methods.

Results: Turmeric contains high concentrations of polyphenols (8.97?±?0.15?g GAEs), flavonoids (5.46?±?0.29?g CEs), ascorbic acid (0.06?±?0.00?mg AEs) and FRAP value (1972.66?±?104.78?μM Fe²⁺) per 100?g of sample. Oral administration of CF caused significant changes in some of the blood indices, such as, mean corpuscular volume, corpuscular hemoglobin, white blood cell, platelet distribution width and induced severe hepatic injuries associated with oxidative stress, as observed by the significantly higher lipid peroxidation (LPO) levels when compared to control, while the activities of cellular antioxidant enzymes (including superoxide dismutase and glutathione peroxidase) were significantly suppressed in the liver tissue.

Discussion and conclusion: Turmeric supplementation could protect against CF-induced hematological perturbations and hepatic injuries in rats, plausibly by the up-regulation of antioxidant enzymes and inhibition of LPO to confer the protective effect.     

Short-term pharmacokinetic comparison of a novel testosterone buccal system and a testosterone gel in testosterone deficient men

SUMMARY

Objective: The primary objective of the study was to compare the percentage of men with mean serum total T (Cave(0–24)) within normal range during the 24-h pharmacokinetic (PK) sampling period on Days 14 and 15.

Methods: Treatment with a new testosterone (T) buccal system, (Striant), 30mg twice daily was compared to a transdermal gel delivery system, (T-gel) [AndroGel 5?g containing 1% (50?mg) T] daily for 14days in T-deficient men. Safety parameters included laboratory assessments and collection of adverse events. Patients were otherwise healthy T-deficient men with total T?<?8.7 nmol/L (< 2.5?ng/mL).

Results: Twenty-six of the 28 patients enrolled completed the 24-h PK assessment. Of the evaluable patients, 92.3% of T buccal system and 83.3% of T-gel patients had Cave(0–24) within the normal range of 10.4-36.4 nmol/L (3.0–10.5?ng/mL). Mean total T values were not different in the T buccal system group (Cave(0–24) 16.7?±?4.7?nmol/L; 4.8?±?1.4?ng/mL) compared to the T-gel group (Cave(0–24) 15.9?±?4.8?nmol/L; 4.6?±?1.4?ng/mL). All T values returned to baseline levels after the study drug was stopped. Serum LH and FSH levels decreased, and E2 increased as expected following T administration. Differences in DHT concentrations between treatment groups were significant (p?=?0.012) with mean DHT levels on Day 14 of 1.9?±?1.4 nmol/L (0.55?±?0.42?ng/mL) for the T buccal system and 3.2?±?1.3?nmol/L (0.93?±?0.38ng/mL) for T-gel, which was greater than the upper level of normal (2.9?nmol/L; 0.85?ng/mL). Statistically significant differences were seen in the mean T/DHT ratio on Days 14     

Real-life behaviour of direct oral anticoagulants in a Spanish cohort with non-valvular atrial fibrillation: Refase Registry

Abstract

Aim: To analyse the effectiveness and safety of DOAC (direct oral anticoagulants) in non-valvular atrial fibrillation (NVAF) patients attending clinical practice.

Methods: Retrospective study of AF patients who started treatment with DOAC from January 1, 2013 to December 31, 2016 in three Spanish hospitals. Mean follow-up was 1.6?years. The primary outcomes were rates of all-cause death, ischaemic stroke, and bleeding. These outcomes were also studied depending on correct dosage adjustment and standard/adjusted dose.

Results: The study included 2494 patients (age = 76.0?±?9.5?years, CHA₂DS₂-VASc = 4.0?±?1.6). The most prescribed DOAC was rivaroxaban (41.1%). Patients taking dabigatran were the youngest (mean age = 73.1?±?10.3 years), with better kidney function (mean CrCl = 80.6?±?35.8?ml/min) and lower CHA₂DS₂-VASc (3.7?±?1.4) and HAS-BLED (2.1?±?0.9) scores. Patients taking apixaban were the oldest, and had the highest CHA2DS2-VASc and HAS-BLED scores (4.3?±?1.6 and 2.6?±?0.9, respectively). Rates of stroke/major bleeding/intracranial bleeding were 1.8/3.0/0.3 events per 100 patient-years, respectively, with no differences among DOAC. Based on dose adjustment according to technical data, it was observed that 517 patients (23.5%) received DOAC doses inconsistent with labelling (p?<?.001) and, within this group, under-dosed patients had a higher death rate although it did not reach a significant result after multivariate adjustment.

Conclusions: The results of safety and efficacy are very similar to those of other previously published national registries. There were no differences among the different types of DOAC regarding outcomes. However, it was found that people taking the adjusted dose of the drug seemed to have a higher risk of death. A non-negligible proportion of patients received DOAC doses inconsistent with labelling (mostly underdose).     

The association effect of insulin and clonazepam on oxidative stress in liver of an experimental animal model of diabetes and depression

Abstract

Context: It is known that oxidative stress occurs in peripheral blood in an experimental animal model of diabetes and depression, and acute treatment with insulin and clonazepam (CNZ) has a protective effect on oxidative stress in this model.

Objective: This study evaluated the effect of insulin plus CNZ on oxidative stress parameters in the liver of diabetic male rats induced with streptozotocin (STZ) and subjected to forced swimming test (FST).

Materials and methods: Diabetes was induced by a single intraperitoneal (i.p.) dose of STZ 60?mg/kg in male Wistar rats. Insulin (4?IU/kg) plus CNZ acute i.p. treatment (0.25?mg/kg) was administered 24, 5 and 1?h before the FST. Nondiabetic control rats received i.p. injections of saline (1?mL/kg). Protein oxidative damage was evaluated by carbonyl formation and the antioxidant redox parameters were analyzed by the measurements of enzymatic activities of the superoxide dismutase (SOD), catalase and glyoxalase I (GLO). Glycemia levels also were determined.

Results: Our present study has shown an increase in carbonyl content from diabetic rats subjected to FST (2.04?±?0.55), while the activity of catalase (51.83?±?19.02) and SOD (2.30?±?1.23) were significantly decreased in liver from these animals, which were reverted by the treatment. Also, the activity of GLO (0.15?±?0.02) in the liver of the animals was decreased.

Discussion and conclusion: Our findings showed that insulin plus CNZ acute treatment ameliorate the antioxidant redox parameters and protect against protein oxidative damage in the liver of diabetic rats subjected to FST.     

Results of a real-world study on vortioxetine in patients with major depressive disorder in South East Asia (REVIDA)

Objective: The REVIDA study aimed to assess the evolution of major depression symptoms in South East Asian (SEA) patients treated with vortioxetine for major depression in real-world clinical practice.

Methods: This non-interventional study was conducted from August 2016 to April 2017. A total of 138 patients (aged 18–65 years) with an active episode of major depression were recruited from Malaysia, Philippines, Singapore and Thailand. Vortioxetine was initiated on the first visit and patients were followed for 3 months. Depression severity was assessed using the PHQ-9 questionnaire (patient assessed) and CGI-S scale (physician assessed); cognitive function was assessed with the PDQ-D questionnaire; work productivity and activity impairment (WPAI) was assessed with the WPAI questionnaire.

Results: At baseline, 89.9% of patients were moderately to severely depressed (PHQ-9 score ≥10). During the 3 month treatment period, mean?±?SD PHQ-9 score decreased from 18.7?±?5.7 to 5.0?±?5.3, mean?±?SD CGI-S score decreased from 4.4?±?0.7 to 2.2?±?1.1 and mean?±?SD PDQ-D score decreased from 42.1?±?18.8 to 13.4?±?13.0. By Month 3, response and remission rates reached 80.8% and 59.0%, respectively. Work productivity loss decreased from 73.6% to 30.5%, while activity impairment decreased from 71.5% to 24.6%. Positive correlations were observed between PHQ-9, PDQ-D, and WPAI work productivity loss and activity impairment. By Month 3, 82.0% of patients were either not depressed or only mildly depressed (PHQ-9 score ≤9).

Conclusion: In real-world clinical settings, vortioxetine was effective in reducing depression severity and improving cognitive function and work productivity in SEA patients with major depression.     

Isolation of major phenolics from Launaea spinosa and their protective effect on HepG2 cells damaged with t-BHP

Context: Some Launaea species (Asteraceae) are used traditionally to treat liver oxidative stress.

Objective: The present study investigates the protective effects of isolated compounds from Launaea spinosa Sch. Bip. (Asteraceae) against oxidative stress on t-BHP-induced HepG2 cells.

Materials and methods: Major phenolic content from flowering aerial parts of L. spinosa was isolated and identified. The protective effects of isolated compounds (10 and 20?μM) against oxidative stress induced by tert-butyl hydroperoxide (t-BHP) in HepG2 cells were investigated through the measurement of aspartate aminotransferase (AST), alanine transaminase (ALT), and superoxide dismutase (SOD) levels.

Results: A new phenolic compound identified as 2,3-diferulyl R,R-(+) methyl tartrate (6), in addition to five known metabolites, esculetin (1), esculetin-7-O-d-glucoside (cichoriin) (2), fertaric acid (3), acacetin-7-O-d-glucoside (4), and acacetin-7-O-d-glucuronic acid (5), were isolated. Oxidant-induced damage by 200?μM t-BHP in HepG2 cells was inhibited by compounds 1, 4, and 5 (10 and 20?μM), or quercetin (10?μM; positive control). The protective effects of compounds 1, 4, and 5 were associated with decreasing in AST, ALT, and SOD levels. Compound 4 (20?μM) decreased the AST level from 128.5?±?13.9 to 7.9 ±1.8?U/mL. Meanwhile, compound 1 (20?μM) decreased ALT activity from 20.3?±?7.0 to 7.6?±?2.4?U/mL, while compound 5 decreased SOD levels from 41.6?±?9.0 to 28.3?±?3.4?mU/mg.

Conclusion: The major phenolic compounds isolated from L. spinosa displayed a significant cytoprotective effect against oxidative stress, leading to maintenance of the normal redox status of the cell.     

Insulin delivery through nasal route using thiolated microspheres

Abstract

The aim of the present study was to investigate the potential of developed thiolated microspheres for insulin delivery through nasal route. In the present study, cysteine was immobilized on carbopol using EDAC. A total of 269.93?µmol free thiol groups per gram polymer were determined. The prepared nonthiolated and thiolated microspheres were studied for particle shape, size, drug content, swellability, mucoadhesion and in vitro insulin release. The thiolated microspheres exhibited higher mucoadhesion due to formation of covalent bonds via disulfide bridges with the mucus gel layer. Drug permeation through goat nasal mucosa of nonthiolated and thiolated microspheres were found as 52.62?±?2.4% and 78.85?±?3.1% in 6?h, respectively. Thiolated microspheres bearing insulin showed better reduction in blood glucose level (BGL) in comparison to nonthiolated microspheres as 31.23?±?2.12% and 75.25?±?0.93% blood glucose of initial BGL were observed at 6?h after nasal delivery of thiolated and nonthiolated microspheres in streptozotocin-induced diabetic rabbits.     

Co-administration of walnut (Juglans regia) prevents systemic hypertension induced by long-term use of dexamethasone: a promising strategy for steroid consumers

Context: The long-term consumption of glucocorticoids (GCs) may induce serious adverse effects such as hypertension. There is sufficient evidence related to the benefit of walnuts on the cardiovascular system.

Objective: This study assesses the effect of methanol extract of walnut [Juglans regia L. (Juglandaceae)] on dexamethasone-induced hypertension and the possible mechanisms in Wistar rats.

Material and methods: Animals were randomized into control, kernel extract (100 and 200?mg/kg/d, orally), dexamethasone (0.03?mg/kg/d, subcutaneously), dexamethasone?+?kernel (100 and 200?mg/kg/d, separately), and dexamethasone?+?captopril (25?mg/kg/d, orally) groups. Animals were treated with water, kernel extract or captopril by gavage 4 d before and during 11 d of saline or dexamethasone treatment. On the 16th day, blood pressure (BP) was recorded and blood samples were collected to measure nitric oxide (NO). Animal hearts were frozen for measurement of malondialdehyde (MDA) and glutathione peroxidase (GPX).

Results: Dexamethasone increased the diastolic BP and MDA/GPX ratio in comparison with control group (128?±?7 vs. 105?±?3?mmHg, p?p?p?p?Conclusion: Similar to captopril, walnut extract normalized dexamethasone-induced hypertension. A part of this beneficial effect apparently involves maintaining balance of the redox system and NO production.     

Hesperidin,a citrus flavonoid,protects against l-methionine-induced hyperhomocysteinemia by abrogation of oxidative stress,endothelial dysfunction and neurotoxicity in Wistar rats

Context: Hesperidin (HSP), a flavanoglycone found in citrus fruits, has antioxidant, anti-inflammatory and neuroprotective properties.

Objective: This study evaluates the protective effect of HSP on l-methionine-induced hyperhomocysteinemia (HHcy) in rats.

Materials and methods: Male Wistar rats were randomly divided into seven groups as DMSO, l-methionine, HSP (25, 50 and 100?mg/kg), HSP-per se (100?mg/kg) and donepezil (0.1?mg/kg). HHcy was induced by oral administration of l-methionine (1.7?g/kg) for 32 days. From the 14^th day of study HSP (25, 50 and 100?mg/kg) and donepezil was administered orally to l-methionine-treated rats. Cognitive impairment induced by HHcy was determined using the Morris water maze (MWM) and Y-maze on video tracking system (28^th–32^nd day). Different biomarkers of HHcy in serum and brain and vascular reactivity were evaluated and histopathology (thoracic aorta and brain) was done.

Results: HSP (100?mg/kg) treatment in l-methionine-treated rats exhibited significant (p?p?l-methionine on acetylcholine-induced endothelial-dependent relaxation and increased serum nitrite and vascular nitric oxide bioavailability along with the restoration of histological aberrations.

Conclusion: HSP exerts a protective effect on HHcy by abrogating oxidative stress, ED and neurotoxicity.     

Additional therapy for cholesterol lowering in ezetimibe-treated,statin-intolerant patients in clinical practice: results from an internal audit of a university lipid clinic

Objective: The aim of our study was to evaluate the tolerability and efficacy of alternative approaches to improve cholesterolemia control in patients with statin-related myalgia treated with ezetimibe.

Research design and methods: We retrospectively evaluated 3534 Clinical Report Forms (CRFs) filled in the period June 2012–June 2015 for first visits to the lipid clinic of the University of Bologna. For this study, we selected 252 CRFs based on the following criteria: statin-related myalgia, previous failed treatment with at least two low-dosed statins, well tolerated treatment with ezetimibe. Then, the following lipid-lowering treatments were added in order to improve the ezetimibe low density lipoprotein cholesterol (LDL-C) lowering efficacy, based on clinical judgment: fenofibrate 145?mg, rosuvastatin 5?mg 1 tablet/week, rosuvastatin 5?mg 2 tablets/week, red yeast rice (standardized in monacolin K 3?mg) + berberine 500?mg, berberine 500?mg b.i.d., phytosterols 900?mg?+?psyllium fiber 3.5?g b.i.d. Patients continuing to claim a tolerable myalgia were then treated with coenzyme Q10 nanoemulsions 200?mg/day.

Results: The treatment with standard lipid-lowering diet plus ezetimibe alone was associated with a mean LDL-C reduction of 17?±?2%. The additive LDL-lowering effect with the various tested treatment was: ?16?±?2% with fenofibrate 145?mg/day, ?13?±?1% with rosuvastatin 5?mg 1 tablet/week, ?17?±?3% with rosuvastatin 5?mg 2 tablets/week, ?19?±?4% with red yeast rice?+?berberine, ?17?±?4% with berberine b.i.d. and ?10?±?3% with phytosterols?+?psyllium b.i.d.; 11% of the patients treated with fenofibrate required treatment modification because of myalgia recurrence, while the percentage was negligible for the other tested treatments. In patients with residual tolerable myalgia, treatment with coenzyme Q10 for 8 weeks was associated with a mean improvement of the graduated myalgia score from 4.8?±?1.9 to 2.9?±?1.3 (p?=?0.013).

Conclusions: Some alternative treatments seems to be effective and well tolerated, thus improving the ezetimibe effect on cholesterolemia.     

Status and trend analysis of prophylactic usage of recombinant factor VIII in Chinese pediatric patients with hemophilia A: ReCare – a retrospective,phase IV,non-interventional study

Background: No study has reported the status and chronological trend of prophylactic recombinant factor VIII (rFVIII) use in Chinese pediatric patients with hemophilia A (HA).

Objective: We aimed to analyze the status and trend of rFVIII-containing prophylaxis in Chinese pediatric patients with HA.

Methods: ReCARE (Retrospective study in Chinese pediatric hemophilia A patients with rFVIII contained REgular prophylaxis) was a retrospective study conducted in 12 hemophilia treatment centers across China. The trend of prophylaxis was evaluated by determining the mean duration of prophylaxis, mean injection frequency (per week), mean dose of each injection (IU/kg), mean total dose injected/week (IU) and proportion of rFVIII consumption relative to factor VIII (FVIII) consumption over the study period.

Results: We analyzed 183 male pediatric patients with HA (mean age, 7.1?±?4.23 years), who received intermittent prophylaxis between 1 November 2007 and 31 May 2013. The mean duration of prophylaxis with rFVIII increased from 16.72 weeks in 2008 to 32.77 in 2012. Per injection dose of rFVIII increased significantly from 2008 to 2013 (25.89 to 28.31?IU/kg, p?Conclusion: Our data revealed an overall improvement in treatment dosage and duration with an increase in the number of patients receiving prophylaxis. The total proportion of rFVIII also increased gradually indicating the development of economy and safety awareness.

Trial Registration: The trial is registered at ClinicalTrials.gov (CT.gov identifier: NCT02263066).