RESUMEN
Studies have reported a wide range of inflammatory responses in the nerve, skin and plasma of leprosy patients. The expression levels of each biomolecule was individualistic, however could be categorized as high and low based on their statistical mean level. Here we report for the first time, expression of a set of biomolecules relating with each other in a defined proportion. The hypothesis of this paper is that the segregation of high and low combinations of a set of biomolecules follows either classical Mendelian dihybrid ratio or epistatic ratios. This hypothesis was tested for 17 molecules in three tissues; nerve, skin and plasma and were confirmed to interact in 9:7, 9:3:4, 12:3:1, 13:3, 15:1 epistatic proportions. These findings suggest that there could be a significant role of networking of molecules in defined epistatic proportions and could be important in pathophysiology of peripheral nerve.
Asunto(s)
Epistasis Genética , Inflamación/genética , Lepra/patología , Algoritmos , Antígenos Bacterianos/inmunología , Genes Recesivos , Humanos , Inflamación/inmunología , Lepra/genética , Lepra/inmunología , Modelos Genéticos , Modelos Estadísticos , Neuronas/metabolismo , Nervios Periféricos/fisiopatología , Fenotipo , Plasma/metabolismo , Estudios Retrospectivos , Piel/metabolismo , Resultado del TratamientoRESUMEN
ETHNOPHARMACOLOGICAL RELEVANCE: Aegle marmelos (L.) Corr. Serr. (Aegle marmelos) leaves were extensively used in the Ayurvedic, Unani and Siddha systems of Indian medicine as an anti-diabetic agent, which serves as hypoglycemic agent. However, the significance of this plant on secondary complications of diabetes such as cataract remained unknown. The aim of the study was to investigate the possible anti-cataractous activity of Aegle marmelos against streptozotocin (STZ) induced diabetic cataract in rats. MATERIALS AND METHODS: Aegle marmelos leaf extract was prepared using three different solvents (petroleum ether, ethyl acetate and methanol) and tested for inhibition against rat lens aldose reductase (AR), a key enzyme of polyol pathway. Furthermore, the pharmacological potential of Aegle marmelos extract was investigated against osmotic stress induced opacification of lens in ex vivo organ culture and streptozotocin (STZ) induced diabetic cataract in rats. RESULTS: Ethyl acetate extract of Aegle marmelos inhibited rat lens AR in vitro with an IC50 value of ≈ 15 µg/ml. This extract also prevented the hyperglycemia induced increase in AR activity, sorbitol accumulation and opacification of rat lens in ex vivo lens organ culture. Supplementation of ethyl acetate extract of Aegle marmelos to STZ-induced diabetic rats decreased the blood glucose levels due to hyperglycemia and inhibited the AR activity and delayed cataract progression in dose dependent manner. α-crystallin isolated from diabetic rats fed with Aegle marmelos showed improved chaperone activity than that of isolated from rats naïve to Aegle marmelos. CONCLUSION: This study indicates that ethyl acetate extract of Aegle marmelos has pharmacologically active components with a potential to inhibit rat lens AR and consequential decrease in osmotic stress. Besides this, the present study also demonstrates that the extract prevented loss of antioxidants contributing to the integrity of α-crystallin's chaperone activity and thereby delaying cataract.
Asunto(s)
Aegle/química , Aldehído Reductasa/antagonistas & inhibidores , Catarata/prevención & control , Diabetes Mellitus Experimental/tratamiento farmacológico , Hipoglucemiantes/uso terapéutico , Extractos Vegetales/uso terapéutico , Animales , Catarata/enzimología , Catarata/etiología , Diabetes Mellitus Experimental/complicaciones , Diabetes Mellitus Experimental/enzimología , Etnofarmacología , Hipoglucemiantes/aislamiento & purificación , Hipoglucemiantes/farmacología , India , Cristalino/efectos de los fármacos , Cristalino/enzimología , Cristalino/patología , Masculino , Técnicas de Cultivo de Órganos , Extractos Vegetales/aislamiento & purificación , Extractos Vegetales/farmacología , Hojas de la Planta/química , Ratas , Ratas Sprague-Dawley , Estreptozocina/farmacologíaRESUMEN
BACKGROUND & OBJECTIVE: Automobile exhaust consists of many toxic components and is considered to be a major health concern in urban areas. Traffic policemen are occupationally exposed to vehicular exhaust during the traffic control. Hence, the present study was aimed to evaluate genotoxic effects of vehicular exhaust in traffic policemen in Hyderabad, south India. METHODS: Analysis of chromosomal aberrations was carried out in 136 traffic policemen, including 78 non smokers and 58 smokers who were exposed to vehicular exhaust for a period of 1-28 yr. For comparison, 115 healthy males including 69 non smokers and 46 smokers of the same age group and socio-economic status (who were not exposed to any chemical or radiation at their workplace) were studied. RESULTS: A significant increase (P<0.05) was observed in the mean frequency of chromosomal aberrations in non smoker and smoker traffic policemen (6.48 and 8.96 respectively) when compared to their respective control groups (3.35 and 4.30). According to the age a significant increase in the frequency of chromosomal aberrations was observed both in control and exposed groups (P<0.05). As the duration of exposure increased in traffic policemen, there was a corresponding increase in the frequency of chromosomal aberrations. INTERPRETATION & CONCLUSION: Cytogenetic damage was more pronounced in smokers when compared to non smokers. Age and duration of exposure also appear to play a vital role in causing cytogenetic damage. Thus the present study suggests that the induction of cytogenetic damage might be due to the cumulative effect of smoking, age and duration of exposure to vehicular exhaust.
Asunto(s)
Contaminantes Ocupacionales del Aire/toxicidad , Emisiones de Vehículos/toxicidad , Adulto , Estudios de Casos y Controles , Aberraciones Cromosómicas , Análisis Citogenético , Humanos , India , Masculino , Persona de Mediana Edad , Mutágenos/toxicidad , Exposición Profesional , Policia , Adulto JovenRESUMEN
Contiguous gene syndromes are characterized by deletions or duplications of specific chromosomal segments involving clusters of single genes. Although these syndromes are associated with distinct clinical phenotypes, these features are difficult to distinguish in the newborn and early childhood periods. In such cases, demonstration of chromosomal involvement through cytogenetic studies is of vital importance in arriving at an accurate diagnosis. In this article results of microdeletion analysis of 31 cases comprising 16 cases of Prader-Willi syndrome, 3 of Angelman syndrome, 7 of Miller-Dieker syndrome, and 5 of DiGeorge syndrome are reported. All patients were studied with both high-resolution chromosome analysis and fluorescence in situ hybridization. In the majority of cases there is 100% concordance between the two techniques. However, in one patient suspected of having DiGeorge syndrome with a normal karyotype at the 750 band level, fluorescence in situ hybridization identified a deletion within the critical region. Without fluorescence in situ hybridization studies on this patient, it would not have been possible to confirm the diagnosis of DiGeorge syndrome cytogenetically. Based on these results and other studies reported in the literature, it is recommended that all suspected cases of microdeletion syndromes should be studied using fluorescence in situ hybridization, irrespective of high-resolution chromosome results. However, because of the difficulties associated with clinical diagnosis of these syndromes, fluorescence in situ hybridization should not replace standard chromosome analysis.