Synthesis, evaluation, and molecular docking studies of cycloalkyl/aryl-3,4,5-trimethylgallates as potent non-ulcerogenic and gastroprotective anti-inflammatory agents

In our effort to identify the effective gastric sparing and protective anti-inflammatory agents, a series of cycloalkyl/aryl-3,4,5-trimethylgallates were synthesized and characterized. The physicochemical properties were studied to assess the lipophilicity and chemical stability. Subsequently, the compounds were evaluated for their anti-inflammatory activity and effect on gastric mucosa by most active compounds. All the compounds exhibited promising anti-inflammatory activity. In particular, 4a, 4b, 4g, and 4h emerged as the most active compounds in the series. The results of gastric mucosal studies and biochemical estimations suggested that these compounds are non-ulcerogenic and gastroprotective. The molecular docking analysis was performed to understand the binding interactions of these compounds to cyclooxygenase isoenzyme (COX-1 and COX-2). The results from this investigation suggests cycloalkyl/aryl-3,4,5-trimethylgallates as potent safer gastrosparing and protective anti-inflammatory agents.     

Gastrocnemius tightness: A population based observational study

BackgroundGastrocnemius tightness is believed to be associated with multiple musculoskeletal pathologies such as back pain, plantar fasciitis and metatarsalgia. Although surgical treatment of gastrocnemius tightness is gaining popularity the objective definition of a gastrocnemius contracture has not been determined. The aim of our study was therefore to quantify gastrocnemius tightness in a normal population.MethodsAdult participants with no obvious foot and ankle pathology were recruited. Gastrocnemius tightness was quantified using a weightbearing lunge test. Maximal ankle-foot dorsiflexion was measured on participants with the knee in full extension and flexed to 20° using a digital inclinometer. The ankle-foot dorsiflexion index or ADI (difference in ankle dorsiflexion with the knee extended and flexed) was calculated. The ADI values were plotted on a histogram to identify the distribution of values and were compared according to participant demographics.Results800 limbs from 400 participants were examined. There was a wide distribution of absolute values of maximal ankle-foot dorsiflexion ranging from 8 to 52°. The ADI ranged from 0 to19° and approximated to a normal distribution. The mean ADI was 6.04 ± 3.49° and was positively correlated with age (r = 0.132, P < 0.001) and negatively correlated with physical activity (r = ?0.88, P = 0.015).Conclusion(s)Our study is the first to quantify gastrocnemius tightness in a large healthy adult population with differences observed by age and physical activity. We have defined an easy and reproducible weightbearing test that can be used in both research and clinical settings. The majority of the population have some degree of gastrocnemius tightness and values of ADI greater than 13° (>2 SD of the mean), as measured by the lunge test, may be considered abnormal.     

骨髓间充质干细胞移植后脑梗死大鼠脑电图的变化

目的:对比观察骨髓间充质干细胞移植前后脑梗死大鼠脑电图的变化。方法:实验于2002-09/12在解放军第三军医大学中心实验室及西南医院神经内科肌电图室完成。①实验分组:选取清洁级健康成年Wistar大鼠15只,随机数字表法分为干细胞移植组、模型对照组、假手术组,5只/组。②实验方法:另取2只健康幼年Wistar大鼠用于骨髓间充质干细胞的提取,联合采用密度梯度离心及贴壁法分离培养大鼠骨髓间充质干细胞,选取生长良好的1～3代细胞用于移植实验。干细胞移植组、模型对照组大鼠建立大脑中动脉栓塞模型。假手术组仅分离颈总动脉、颈外动脉和颈内动脉,不予结扎和放置线栓。造模后1周,干细胞移植组、假手术组大鼠行细胞移植,在立体定向仪定位下于脑梗死区(壳核)直接注射骨髓间充质干细胞悬液5μL,细胞浓度1×104μL-1,移植坐标为前囟前1.0mm,右旁开3.0mm,硬膜下5.0mm。模型对照组大鼠于相同部位注射等量不含细胞的磷酸盐缓冲液。③实验评估:采用脑电图机分别于造模前、造模后1周(移植前)、细胞移植后4周对各组大鼠进行脑电图检测。结果:15只大鼠均进入结果分析。①造模前基本节律为8～11Hz、15～30μV的α波,间或少量θ波,双侧对称。②造模后1周,假手术组异常率为0;模型对照组20%(1/5)轻度异常,80%(4/5)中度异常;干细胞移植组20%(1/5)轻度异常,60%(3/5)中度异常,20%(1/5)重度异常。③细胞移植后4周,假手术组脑电图恢复正常;模型对照组随术后时间的延长慢波有所减少,但仍可见到δ波、棘波、棘慢波的发放,至细胞移植后4周60%(3/5)轻度异常,40%(2/5)中度异常;干细胞移植组术后局限性慢波逐渐减少,基本节律全部恢复为α波,不对称的情况明显好转,至细胞移植后4周60%(3/5)轻度异常,以病灶侧局限性θ波较多为主,另外40%(2/5)基本正常。结论:动物实验显示骨髓间充质干细胞移植对脑梗死大鼠的脑电图背景节律有改善作用,一定程度上促进了神经系统功能的恢复。     

Periodontal disease and type 1 diabetes mellitus: Associations with glycemic control and complications: An Indian perspective

AimTo evaluate the frequency of periodontal disease in a group of patients with type 1 diabetes mellitus and its relationship with diabetic metabolic control, duration and complications.Materials and methodsA comparison was made of periodontal parameters (plaque index, bleeding index, pocket depth and attachment loss) in a group of diabetic patients versus a group of non-diabetics (n = 20). Statistical analysis was performed to evaluate the relationship between periodontal parameters and degree of metabolic control, the duration of the disease and the appearance of complications.ResultsDiabetics had greater bleeding index (p < 0.001), probing pocket depth (p < 0.001) and clinical attachment level (p = 0.001). Patients diagnosed for diabetes for shorter duration of time (4–7 years) showed bleeding index-disease severity correlation to be 1.760 ± 0.434.ConclusionPatients with type 1 diabetes have increased periodontal disease susceptibility. Periodontal inflammation is greatly increased in subjects with longer disease course, poor metabolic control and diabetic complications.     

Prevalence of Usutu and West Nile virus antibodies in human sera,Modena, Italy, 2012

A collection of 3069 human sera collected in the area of the municipality of Modena, Emilia Romagna, Italy, was retrospectively investigated for specific antibodies against Usutu (USUV) and West Nile viruses (WNV). All the samples resulting positive using a preliminary screening test were analyzed with the plaque reduction neutralization test. Overall, 24 sera were confirmed as positive for USUV (0.78%) and 13 for WNV (0.42%). The results suggest that in 2012, USUV was circulating more than WNV in North‐eastern Italy.     

EMG classification using wavelet functions to determine muscle contraction

Surface electromyogram (SEMG) is a complex signal and is influenced by several external factors/artifacts. The electromyogram signal from the stump of the subject is picked up through surface electrodes. It is amplified and artifacts are removed before digitising it in a controlled manner so that minimum signal loss occurs due to processing. As removing these artifacts is not easy, feature extraction to obtain useful information hidden inside the signal becomes a different process. This paper presents methods of analysing SEMG signals using discrete wavelet Transform (DWT) for extracting accurate patterns of the signals and the performance of the used algorithms is being analysed rigorously. The obtained results suggest a root mean square difference (RMSD) value for the denoising and quality of reconstruction of the SEMG signal. The result shows that the best mother wavelets for tolerance of noise are second order of symmlets and bior6.8. Results inferred that bior6.8 suitable for the classification and analysis of SEMG signals of different arm motions results in a classification accuracy of 88.90%.     

A novel SRY missense mutation affecting nuclear import in a 46,XY female patient with bilateral gonadoblastoma

Patients with disorders of sex development (DSD), especially those with gonadal dysgenesis and hypovirilization, are at risk of developing the so-called type II germ cell tumors (GCTs). Both carcinoma in situ and gonadoblastoma (GB) can be the precursor lesion, resulting in a seminomatous or non-seminomatous invasive cancer. SRY mutations residing in the HMG domain are found in 10–15% of 46,XY gonadal dysgenesis cases. This domain contains two nuclear localization signals (NLSs). In this study, we report a unique case of a phenotypical normal woman, diagnosed as a patient with 46,XY gonadal dysgenesis, with an NLS missense mutation, on the basis of the histological diagnosis of a unilateral GB. The normal role of SRY in gonadal development is the upregulation of SOX9 expression. The premalignant lesion of the initially removed gonad was positive for OCT3/4, TSPY and stem cell factor in germ cells, and for FOXL2 in the stromal component (ie, granulosa cells), but not for SOX9. On the basis of these findings, prophylactical gonadectomy of the other gonad was performed, also showing a GB lesion positive for both FOXL2 (ovary) and SOX9 (testis). The identified W70L mutation in the SRY gene resulted in a 50% reduction in the nuclear accumulation of the mutant protein compared with wild type. This likely explains the diminished SOX9 expression, and therefore the lack of proper Sertoli cell differentiation during development. This case shows the value of the proper diagnosis of human GCTs in identification of patients with DSD, which allows subsequent early diagnosis and prevention of the development of an invasive cancer, likely to be treated by chemotherapy at young age.