In vivo and in vitro Pharmacological Evaluation of Gymnosporia Royleana / Evaluación Farmacológica de Gymnosporia Royleana in vivo e in vitro

ABSTRACT Objective: Gymnosporia royleana (G royleana) Wall ex MA Lawson, locally known as (Sur Azghee), is traditionally used for the management of various diseases. In the current investigation, we made an effort to scientifically validate its traditional use in various pathological conditions, such as microbial infections and cancer, and to explore its additional pharmacological activities via random screening against locally accessible pharmacological methods, irrespective of its traditional uses like antidiabetic, haemagglutination and antioxidant assays. Methods: Extraction was carried out using a cold maceration methodology. Dilution method was used for antimicrobial susceptibility testing using different concentrations. Streptozocin (STZ) induced protocol was used to assess antidiabetic activity at a dose level of 200, 400 mg/ kg. Antioxidant activity, haemagglutination activity, and anticancer activities against HepG-2 and MCF-7 cell lines were determined as per established protocols. Similarly, the maximum amount of phenolic content (12.02 mg 100 g) was determined by using Folin Ciocalteu assay. Results: Promising antimicrobial activities in terms of minimum inhibitory concentration (MIC) were noted for crude extract (25-200 µg/mL), n-hexane (100-400 µg/mL), ethyl acetate (50-200 µg/mL) and aqueous (100-400 µg/mL). Antidiabetic potential was significant at a dose level of 200-400 mg/kg bodyweight by reducing the blood glucose level at days 10 and 15. The percentage of 2,2-diphenyl-1-picrylhydrazyl (DPPH) values increase by increasing the concentration of the plant extract (10-100 µg/mL). The methanol extract was found to possess high agglutination activity. Conclusion: It was concluded that this plant species possess significant antimicrobial, antidiabetic, antioxidant, anticancer and haemagglutination activities, which could be attributed to the phenolic content of the extract.

RESUMEN Objetivo: Gymnosporia royleana (G royleana) Wall ex MA Lawson, localmente conocida como "Sur Azghee", se utiliza tradicionalmente para el tratamiento de diversas enfermedades. En la investigación presente, tratamos de validar científicamente su uso tradicional en varias condiciones, tales como las infecciones microbianas y el cáncer, así como explorar sus actividades farmacológicas adicionales mediante el tamizado aleatorio frente a los métodos farmacológicos localmente accesibles, independientemente de sus usos tradicionales como ensayos antidiabéticos, hemaglutinantes, y antioxidantes. Métodos: La extracción se realizó mediante una metodología de maceración en frío. Un método de dilución se utilizó para la prueba de susceptibilidad antimicrobiana utilizando diferentes concentraciones. Se utilizó el protocolo inducido por estreptozotocina (STZ) para evaluar la actividad antidiabética a un nivel de dosis de 200, 400 mg/kg. La actividad antioxidante, la actividad de hemaglutinación, y las actividades anticancerígenas contra las líneas celulares HepG-2 y MCF-7, se determinaron según los protocolos establecidos. De modo similar. la cantidad máxima de contenido fenólico (12.02 mg 100 g) se determinó mediante el uso del ensayo Folin-Ciocalteu. Resultados: Se observaron actividades antimicrobianas prometedoras en términos de la concentración inhibitoria mínima (CIM) para el extracto crudo (25-200 μg/mL), el n-hexano (100-400 μg/mL), el acetato de etilo (50-200 μg/mL), y el extracto acuoso (100-400 μg/mL). El potencial antidiabético fue significativo a un nivel de dosis de 200-400 mg/kg de peso corporal mediante la reducción del nivel de glucosa en sangre a los 10 y 15 días. El porcentaje de los valores de 2,2-difenil-1-picrilhidracilo (DPPH) se incrementa al aumentar la concentración del extracto de la planta (10-100 μg/mL). Se halló que el extracto de metanol posee una alta actividad de aglutinación. Conclusión: Se concluyó que esta especie de planta posee importantes actividades antimicrobianas, antidiabéticas, antioxidantes, anticancerígenas y hemaglutinantes, que podrían atribuirse al contenido fenólico del extracto.

Mesothelioma in Sweden: Dose–Response Analysis for Exposure to 29 Potential Occupational Carcinogenic Agents

BACKGROUND: There is little information on the dose–response relationship between exposure to occupational carcinogenic agents and mesothelioma. This study aimed to investigate this association as well as the existence of agents other than asbestos that might cause mesothelioma. METHODS: The Swedish component of the Nordic Occupational Cancer (NOCCA) study consists of 6.78 million individuals with detailed information on occupation. Mesothelioma diagnoses recorded in 1961–2009 were identified through linkage to the Swedish Cancer Registry. We determined cumulative exposure, time of first exposure, and maximum exposure intensity by linking data on occupation to the Swedish NOCCA job-exposure matrix, which includes 29 carcinogenic agents and corresponding exposure for 283 occupations. To assess the risk of mesothelioma, we used conditional logistic regression models to estimate hazard ratiosand 95% confidence intervals. RESULTS: 2,757 mesothelioma cases were identified in males, including 1,416 who were exposed to asbestos. Univariate analyses showed not only a significant excess risk for maximum exposure intensity, with a hazard ratio of 4.81 at exposure levels 1.25–2.0fb/ml but also a clear dose–response effect for cumulative exposure with a 30-, 40-, and 50-year latency time. No convincing excess risk was revealed for any of the other carcinogenic agents included in the Swedish NOCCA job-exposure matrix. CONCLUSION: When considering asbestos exposure, past exposure, even for short periods, might be enough to cause mesothelioma of the pleura later in life.

Detection of autonomic nervous dysfunction by SL manoeuvre.

We have evaluated the immediate heart rate response to standing and lying and in 100 Diabetic subjects aged 43 +/- 10 years who underwent five other cardiovascular autonomic tests. Using a specially devised scoring system the patients were divided into three groups: a) 58 subjects without autonomic neuropathy, b) 15 borderliners, c) 27 with autonomic neuropathy. The results were compared with 50, sex and age matched controls. We studied SL1 = ratio between R-R mean before lying and R-R maximum between the 20th to 25th beat and R-R minimum over the first 5 beats after lying. In controls SL1 was 1.35 +/- 0.18 and SL2 was 1.52 +/- 0.23. In diabetic subjects without autonomic neuropathy SL1 was 1.20 +/- 0.86 (p < 0.01), SL2 1.50 +/- 0.02 (p < 0.001). In the group with autonomic neuropathy SL1 was 1.04 +/- 0.02 (p < 0.001) and SL2 was 1.20 +/- 0.09 (p < 0.001). We propose that the lowest normal and highest abnormal limits of SL1 are 1.12 and 1.08 respectively and that normal and highest abnormal limits of SL2 are 1.23 and 1.18 respectively. We suggest the use of SL1 as a pure parasympathetic test and SL2 as a mixed but predominantly sympathetic test in the diagnosis of autonomic neuropathy.