Diacerein niosomal gel for topical delivery: development,in vitro and in vivo assessment

The purpose of this study was to load diacerein (DCR) in niosomes by applying response surface methodology and incorporate these niosomes in gel base for topical delivery. Box–Behnken design was used to investigate the effect of charge-inducing agent (X₁), surfactant HLB (X₂) and sonication time (X₃) on the vesicle size (Y₁), entrapment efficiency (Y₂) and cumulative drug released (Y₃). DCR niosomal formulations were prepared by thin film hydration method. The optimized formula was incorporated in different gel bases. DCR niosomal gels were evaluated for homogeneity, rheological behavior; in vitro release and pharmacodynamic activity by carrageenan-induced hind paw edema method in the rat compared with DCR commercial gel. The results revealed that the mean vesicle sizes of the prepared niosomes ranged from 7.33 to 23.72?µm and the entrapment efficiency ranged from 9.52% to 58.43% with controlled release pattern over 8?h. DCR niosomal gels exhibited pseudoplastic flow with thixotropic behavior. The pharmacodynamic activity of DCR niosomal gel in 3% HPMC showed significant, 37.66%, maximum inhibition of edema size in comparison with 20.83% for the commercial gel (p?相似文献   

Investigating the effects of subthalamic Nucleus–Deep brain stimulation on the voice quality

Abstract

Introduction: Deep brain stimulation (DBS) is a standard surgical treatment method which is generally applied to subthalamic nucleus in Parkinson’s patients in cases where medical treatment is insufficient in treating the motor symptoms. It is known that Subthalamic Nucleus Deep Brain Stimulation (STN-DBS) treats many motor symptoms. However, the results of studies on speech and voice vary. The aim of the study is analysing the effect of STN-DBS on the characteristics of voice.

Materials/methods: A total of 12 patients, (8 male–4 female) with an age average of 58.8?±?9.6, who have been applied DBS surgery on STN included in the study. The voice recordings of the patients have been done prior to surgery and 6?months after the surgery. The evaluation of voice has been carried out through the instrumental method. The patients’ voice recordings of the /a,e,i/ vowels have been done. The obtained recordings were evaluated by the Praat programme and the effects on jhitter, shimmer, fundamental frequency (F0) and noise harmonic rate (NHR) were analysed.

Results: Numerical values of F0 of all female participants have been decreased for all of the vowels postoperatively. In the females; jhitter and fraction parameters were found to be significantly different (0.056 and 0.017, perspectively) for the vowel /e/. In addition, p values in the shimmer for vowels /e,i/ were thought to be clinically significant (.087, .079 and .076) respectively. All these changes in second measurements were found to indicate worsening vocal quality after the DBS in females. In males, there is not any significant difference observed between two measures in any of the parameters of any vowels.

Conclusions: Acoustic voice quality deteriorated after STN-DBS predominantly for females however this deterioration was not prominent audio-perceptually. This finding commented as a result of the fact that that voice quality deviance of the participants was not severe.     

Metabolite Profiling by Hyphenated Liquid Chromatographic Mass Spectrometric Technique (HPLC‐DAD‐ESI‐Q‐TOF‐MS/MS) and Neurobiological Potential of Haplophyllum sahinii and H. vulcanicum Extracts

In the current study, the ethanol extracts of flower, stem, and root parts of two endemic Turkish species, e. g., Haplophyllum sahinii O. Tugay & D. Uluku? and H. vulcanicum Boiss . & Heldr ., were screened against acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) associated with Alzheimer's disease as well as tyrosinase (TYR) linked to Parkinson's disease using ELISA microplate assay at 200 μg/mL. Among the extracts, the highest inhibition was caused by the stem extract of H. sahinii against BChE (IC₅₀=64.93±1.38 μg/mL). Consistently, all of the extracts were found to exert a selective inhibition towards BChE to some extent. It was only the root extract of H. vulcanicum that could inhibit AChE at low level (IC₅₀=203.18±5.33 μg/mL). None of the extracts displayed an inhibition over 50 % against TYR. Metabolite profiling of the extracts was achieved by a highly hyphenated liquid chromatographic mass spectrometric technique (HPLC‐DAD‐ESI‐Q‐TOF‐MS/MS), which revealed the presence of furoquinoline (β‐fagarine, γ‐fagarine) and amide (tubasenicine, tubacetine) alkaloids; furano‐ (rutamarin), pyrano‐ (xanthyletine), and geranyloxy coumarins; phenylpropanoid (secoisolariciresinol), arylnaphthalene (mono‐O‐acetyldiphyllin apioside), and dibenzylbutyrolactone (kusunokinin, haplomyrfolin) lignans. Several important differences were observed between the extracts analyzed. β‐Fagarine was the major alkaloid in H. vulcanicum, whereas γ‐fagarine was present only in the roots of both Haplophyllum species; moreover, secoisolariciresinol and secoisolariciresinol dimethyl ether were the main lignans in the stems and flowers. This is the first study identifying ChE and TYR inhibitory effect and metabolic profiles of H. vulcanicum and H. sahinii.     

Design,synthesis and pharmacological evaluation of omeprazole-like agents with anti-inflammatory activity

A new series of novel benzimidazole derivatives containing substituted pyrid-2-yl moiety and polyhydroxy sugar conjugated to the N-benzimidazole moiety has been synthesized and evaluated as orally bioavailable anti-inflammatory agents with anti-ulcerogenic activity. The anti-inflammatory and anti-ulcerogenic activities of these compounds were compared to diclofenac and omeprazole, respectively. In carrageenan-induced paw oedema assay, 2-methyl-N-((3,4-dimethoxypyridin-2-yl)methyl)-1H-benzimidazol-5-amine (12d) and 1-(1,2,3,5-tetrahydroxy-α-d-mannofuranose)-5-(((3,4-dimethoxypyridin-2yl)methyl)amino)-2-methyl-1H-benzimidazole (15d) displayed dose-dependent anti-inflammatory activities by decreasing the inflammation by 62% and 72%, respectively which is comparable to that of diclofenac (73%). In contrast to diclofenac, the anti-inflammatory activity of these compounds was not only free from any side effects on the gastric mucosa but also showed significant anti-ulcerogenic activity in rat pyloric ligation and ethanol-induced gastric ulcer models similar to that of omeprazole. Together, these findings suggest that 12d and 15d are potent anti-inflammatory agents with concurrent anti-ulcerogenic activity and support its clinical promise as a component of therapeutic strategies for inflammation, for which the gastric side effects are always a major limitation.     

Breast cancer in the eastern province of Saudi Arabia

In the Kingdom of Saudi Arabia (KSA), hospital and population based statistics have shown that breast cancer has the highest crude frequency rate among Saudi women. The scarcity of reports about the disease in the KSA has been the impetus to this analysis about breast cancer in the eastem province of KSA. Data on female patients with invasive breast carcinoma seen at King Fahd Hospital of the University in the eastern province of KSA, were retrospectively reviewed. The analysis intended to examine the pattern of the disease and the outcome for patients. Between 1985 and 1995, 292 patients were identified. Their median age±SD (standard deviation) was 42±10.5 years. Most patients were younger than 50 years (78%) and were predominantly premenopausals (79%). Only 25 (9%) of patients had stage I cancer, whilst 130 (44%), 90 (30%), and 47 (16%) had stage II, III, and IV, respectively. Among patients with known axillary nodal status (242 patients), only 37% were node-negative whilst 32% and 31% had 1–3, and ≥4 positive nodes, respectively. Adjuvant chemotherapy and tamoxifen were commonly offered; nonetheless, other adjuvant modalities were rarely utilised. The median follow-up ±SD of all patients was 62.3±8.9 months: 152 patients (52%) were alive with no evidence of disease, 25 (9%) were alive with evidence of disease, and 115 (39%) were dead from breast cancer or its related complications. The median survival of the entire group was not obtained, but the 10-year projected survival was 55%. For stage I and II patients, 118 (76%) were alive with a projected 10-year actuarial survival of 64%. On the other hand, only 51 (57%) of patients with stage III disease were alive with a median survival of 41.5 months (95% Confidence interval (CI), 18.9 to 51.3). Patients with stage IV disease demonstrated a poor outcome with a median survival of 23.5 (95%, CI 12.2 to 31.4). Multivariate analyses were performed to explore the influence of independent variables on overall survival (OS) for patients with non-metastatic disease. Besides the expected adverse effect of disease progression, the favourable influence of adjuvant chemotherapy and tamoxifen prevailed. The amount of benefit gained from tamoxifen, however, was small. Similar analyses were undertaken to determine the influence of independent variables on progression-free survival (PFS). These analyses ascertained the adverse effects of advanced stage and the favourable impact of adjuvant chemotherapy. Breast cancer in the KSA has features that are distinctive from those of industrialised countries. Survival data, however, were comparable. The favourable influence of adjuvant chemotherapy was evident on both OS and PFS. Adjuvant tamoxifen, however, had little effect. Due to its infrequent use, the role of other adjuvant modalities could not be asserted.     

Biomarkers of oxidative stress in Biomphalaria alexandrina snails for assessing the effects of certain inorganic fertilisers

Freshwater snails are often used to monitor aquatic pollution. The present study aims to use Biomphalaria alexandrina snails as bio-indicators for three types of NPK fertilisers (high nitrogen, high phosphorus and balanced). Data showed that high phosphorus and high nitrogen fertilisers have a negative impact on the growth rate of juvenile snails. Such observations were supported by determining antioxidant parameters in the digestive gland. Results indicated a significant increase in the catalase activity of snails that were exposed to ½ LC₅₀ concentrations of balanced and high phosphorus fertilisers. Meanwhile, the glutathione S-transferase, glutathione peroxidase and reduced glutathione parameters showed varying results representing an increase or decrease in the activities of all treated groups after both the first and second weeks, according to the type of fertiliser the snails were exposed to.     

The effect of N‐acetylcysteine supplementation on the oxidative stress levels,apoptosis, DNA damage,and hematopoietic effect in pesticide‐exposed fish blood

Cysteine is important for protein synthesis, detoxification, and diverse metabolic functions. However, cysteine metabolism has been poorly described in fish, and the role of the therapeutic effect in pesticide toxicology on aquatic organisms is unknown. The aim of this study was to determine the effects of regular cysteine treatment on the hematology, biochemistry, apoptosis, oxidative DNA damage, and antioxidant parameters in fish blood after chemical application. Therefore, fish were exposed to cypermethrin for 2 weeks. Then two different concentrations of N‐acetylcysteine (NAC) were applied for a 4‐day treatment period and compared with the group of the self‐healing process. At the end of the treatment, the hematological index, blood biochemical parameters, paraoxonase (PON), arylesterase (ARE), and myeloperoxidase (MPO) activities in the fish blood samples were investigated. With regard to the hematological parameters, statistical differences were obtained except for mean corpuscular hemoglobin (MCH) and mean corpuscular hemoglobin concentration (MCHC) (P < 0.05). Enzyme activities (ARE, PON, and MPO), as well as some biochemical parameters (creatinin [Cre], alanine amino transferase, total glyceride, alkaline phosphatase, iron, calcium, low density lipoprotein‐cholesterol [LDL‐C], sodium, and potassium), were found to be importantly different among all groups at the P < 0.05 level, while 8‐hydroxydeoxyguanosine and caspase‐3 levels were determined to be high in the pesticide group but decreased significantly in NAC‐treated groups ( P < 0.05). According to the results of the study, acute cysteine treatment showed an ameliorative effect on the hematological index, biochemical parameters, PON, MPO, and ARE in the blood in the all the treatment group fish. The positive effect of NAC on protein synthesis, detoxification, and diverse metabolic functions against cypermethrin toxicity was more effective in 1.0 mM NAC. NAC has an important therapeutic effect on pesticide‐induced hematoxicity for fish in terms of all the data.