RESUMEN
The study was conducted to evaluate the accumulation pattern of cadmium (Cd) and its tolerance in different crops grown on sewage irrigated soils with differentCd levels. Growth, yield, uptake and tolerance of maize, raya, berseem and spinach were assessed to different levels of Cd ranging from 0-40 mg kg(-1) soil. Significant reduction in dry matter yield in raya was observed at 20 mg Cd kg(-1) soil where as for other crops it was 10 mg Cd kg(-1) soil. The quadratic models seem to give the best description of variation in dry matter yield with Cd levels as revealed by significant coefficient of determination (R2 > or = 90). Cadmium content and uptake varied in the following order: raya > spinach > maize > berseem. Raya could tolerate high levels of Cd as compared to other crops. Conversely, berseem and maize which showed reduced ability to absorb or translocate Cd for genetic reasons compared to raya and spinach be preferred for growing on sewage irrigated soils or area having increased Cd-levels. The relationship of Cd with other micronutrients was variable.
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Biomasa , Cadmio/metabolismo , Productos Agrícolas/metabolismo , Micronutrientes/metabolismo , Aguas del Alcantarillado , Riego Agrícola , Productos Agrícolas/crecimiento & desarrolloRESUMEN
Cadmium is a potentially toxic heavy metal that enters food chain from the soil through various anthropogenic sources. Availability of metal ions in contaminated soils can be reduced by the addition of organic amendments. In this study, effect of organic matter -farm yard manure (FYM) amendment on fractionation and availability of Cd to maize was evaluated. A green house experiment was conducted to determine the toxicity and uptake of Cd by maize in sandy loam soil with and without organic matter. Four levels of Cd (0, 10, 20 and 40 mg kg(-1) soil) and two levels of FYM (0 and 20 tonnes ha(-1)) with three replication in a completely randomized factorial design. Concentration of Cd in maize increased with increasing rate of Cd application. Application of organic matter increased the dry matter yield of maize while reduced the uptake of metal. All the fractions exhibited increase with Cd rates. The addition of organic amendment declined significantly the concentration of water soluble and exchangeable Cd, but increased the amounts of these metals into less mobile fractions (Fe/Mn oxide, organic matter and residual). Dominance of insoluble forms of Cd after the application of organic amendments may be ascribed to the increases of soil OM, pH, EC and available P contents which caused transformation or redistribution of the sorbed phases. This resulted in increasing Cd retention in the more persistent fractions with application of FYM at the expense of reductions in the loosely bound fractions. Thus FYM appears to be agronomically feasible way to off set the adverse effect of Cd toxicity.
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Cadmio/química , Estiércol , Contaminantes del Suelo/química , Suelo/química , Riego Agrícola , Animales , Ganado , Aguas del AlcantarilladoRESUMEN
This study analysed the relationship of plasma testosterone with ß-cell secretion, insulin sensitivity and other pituitary-target gland hormones in normoglycaemic adult men. The sample frame was the 'Offspring of individuals with diabetes study' database. A total of 358 offspring of individuals with type-2 diabetes (T2DM) and 287 individuals without known family history of T2DM were recruited for the study. Normoglycaemic men aged ≥18 years (maximum 55) were selected for this analysis. All participants underwent 75 g oral glucose tolerance test (OGTT); blood samples were collected at 0, 30, 60 and 120 min for plasma insulin and C-peptide. Total testosterone, cortisol, adrenocorticotropic hormone, thyroid stimulating hormone and thyroxine (T4) were measured in the fasting sample. A total of 164 men (age 28 ± 7.7 years) were included in analysis. Testosterone correlated negatively with BMI, waist to hip ratio (WHR), area under curve (AUC) of C-peptide and insulin (during OGTT) and was positively correlated with insulin sensitivity (r ~ 0.4). Cortisol and T4 positively correlated (weak) with testosterone (r ~ 0.2). In multivariate analysis, AUC C-peptide, BMI, WHR (negatively) and cortisol (positively) were related to testosterone. Concluding, testosterone correlated negatively with BMI and ß-cell secretion. There was a positive association of testosterone with insulin sensitivity, cortisol and T4.
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Hiperinsulinismo/sangre , Testosterona/sangre , Adulto , Índice de Masa Corporal , Péptido C/sangre , Diabetes Mellitus Tipo 2/sangre , Prueba de Tolerancia a la Glucosa , Humanos , Hidrocortisona/sangre , Insulina/sangre , Resistencia a la Insulina , Masculino , Persona de Mediana Edad , Tirotropina/sangre , Tiroxina/sangreRESUMEN
AIMS: Wolfram syndrome, also known as DIDMOAD, is a relatively rare inherited neurodegenerative disorder, first evident in childhood as an association of juvenile-onset diabetes mellitus and optic atrophy, followed by diabetes insipidus and deafness. The aim of the study was to examine the clinical profile of patients with DIDMOAD syndrome presenting to a tertiary care hospital in north India. METHODS: Clinical presentation of juvenile-onset diabetes mellitus fulfilling the diagnosis of Wolfram syndrome was studied using a prepared standardized form. RESULTS: Subjects with juvenile-onset non-autoimmune diabetes mellitus attending the diabetic clinic at a tertiary care centre in north India were followed for 10 years and a diagnosis of fully developed Wolfram syndrome was confirmed in seven individuals. The series consisted of five male and two female patients with a mean age of 17.5 ±7.34 years. Two subjects had consanguinity and none had any other family member affected. Optic atrophy was present in all, sensorineural hearing loss in 4/7, central diabetes insipidus in 4/7 and nephrogenic diabetes insipidus in 2/7 subjects. The new associations found were: spastic myoclonus, short stature with pancreatic malabsorption, nephrogenic diabetes insipidus, cyanotic heart disease and choledocholithiasis with cholangitis. Genetic analysis revealed mutation in exon 8 of the WFS1 gene in all the cases studied. CONCLUSIONS: The present clinical series of Wolfram syndrome reveals a varied clinical presentation of the syndrome and some new associations.
Asunto(s)
Pérdida Auditiva Sensorineural/diagnóstico , Proteínas de la Membrana/genética , Mutación , Atrofia Óptica/diagnóstico , Síndrome de Wolfram/diagnóstico , Adolescente , Adulto , Secuencia de Bases , Niño , Colangitis/diagnóstico , Coledocolitiasis/diagnóstico , Consanguinidad , Análisis Mutacional de ADN , Femenino , Trastornos del Crecimiento/diagnóstico , Pérdida Auditiva Sensorineural/epidemiología , Pérdida Auditiva Sensorineural/genética , Humanos , India/epidemiología , Imagen por Resonancia Magnética , Síndromes de Malabsorción/diagnóstico , Masculino , Mioclonía/diagnóstico , Atrofia Óptica/epidemiología , Atrofia Óptica/genética , Linaje , Síndrome de Wolfram/epidemiología , Síndrome de Wolfram/genética , Adulto JovenRESUMEN
Increased use of nitrogenous fertilizers in the intensively cultivated rice (Oryza sativa)-wheat (Triticum aestivum) cropping system (covers a 13.5-ha m area in South Asia) has led to the concentration of nitrates (NO(3)-N) in the groundwater (GW) in Haryana State of India. Six districts from the freshwater zone were selected to identify factors affecting NO(3)-N enrichment in GW. Water and soil samples were collected from 1,580 locations and analyzed for their chemical properties. About 3% (26,796, and 10,588 ha) of the area was estimated to be under moderately high (7.5-10 mg l( -1)) and high (>10 mg l( -1)) risk categories, respectively. The results revealed that NO(3)-N was 10-50% higher during the pre-monsoon season than in the monsoon season. Nitrate-N decreased with the increase in aquifer depth (r (2) = 0.99). Spatial and proximity analyses using ArcGIS (9.2) revealed that (1) clay material in surface and sub-surface texture restricts N leaching, (2) piedmont and rolling plains act as an N sink, and (3) perennial rivers bring a dilution effect whereas seasonal rivers provide favorable conditions for NO(3) (-) enrichment. The study concludes that chemical N fertilizers applied in agro-ecosystems are not the sole factor determining the NO(3) in groundwater; rather, it is an integrated process governed by several other factors including physical and chemical properties of soils, proximity and type of river, and geomorphologic and geographical aspects. Therefore, future studies should adopt larger area (at least watershed scale) to understand the mechanistic pathways of NO(3) enrichment in groundwater and interactive role of the natural drainage system and surrounding physical features. In addition, the study also presents a conceptual framework to describe the process of nitrate formation and leaching in piedmont plains and its transportation to the mid-plain zone.
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Agricultura/métodos , Agua Dulce/química , Nitratos/análisis , Oryza , Triticum , Contaminantes Químicos del Agua/análisis , Monitoreo del Ambiente , India , Estaciones del Año , Suelo/química , Contaminación Química del Agua/estadística & datos numéricos , Abastecimiento de Agua/análisis , Abastecimiento de Agua/estadística & datos numéricosRESUMEN
The village ponds were used for storing rainwater for animals and recharging of underground water. Recent developments like public water supply for household purpose, provision of household wastewater concrete channels, and toilet septic tanks have polluted the village ponds. The infiltration of water has decreased due to non-cleaning of silt from the pond beds. Increased discharge of wastewater from households, coupled with a low infiltration rate, has inundated these ponds. People have abandoned the use of this water for animals. An effort has been made to assess the suitability of this water for irrigation in the vicinity so as to clean these ponds. Seventy-eight water samples were collected from the village ponds in the Ludhiana district of Punjab. The samples were analyzed for total solids (TS), total dissolved solids (TDS), total suspended solids (TSS), biological oxygen demand (BOD), chemical oxygen demand (COD), electrical conductivity (EC), residual sodium carbonate (RSC), nitrogen, water soluble P and K, as well as micronutrients and pollutant elements. The total solids content of these waters were on the higher side. Considering TSS, BOD, and COD, some of these waters are unsafe for their disposal in river or water bodies. Electrical conductivity ranged from 693 to 5050 µmhos/cm, and RSC varied between -1.9 and 22.8 meq/l. The inorganic N (NH+4+ NO-3-N) and total Kjeldahl N ranged from 3 to 30 and 8 to 41 mg/l, respectively. The amount of micronutrients (Zn, Cu, Fe, and Mn) present in pond water indicated its high nutrient value. The content of the pollutant elements such as nickel, cadmium, and lead was below the maximum permissible limits, thereby indicating its suitability for irrigation. According to the EC and RSC criteria, 18% of the samples were fit, 31% were marginal, and 51% were unfit for irrigation. The data indicate that these waters are a good source of nutrients for agriculture.
Asunto(s)
Monitoreo del Ambiente/métodos , Agua Dulce/análisis , Contaminantes Químicos del Agua/análisis , Abastecimiento de Agua/análisis , Carbonatos/análisisRESUMEN
BACKGROUND: Vitamin D nutrition has a profound effect on the development of an infant. Vitamin D status of mothers and their infants are closely correlated. While hypovitaminosis D has emerged as a significant public health problem across all age groups, there is limited information of this condition in lactating mothers and their breast fed infants. AIM: To evaluate the vitamin D status of lactating mothers and their breast fed infants. SUBJECTS AND METHODS: 180 healthy lactating mothers and exclusively breast fed infants, 2-24 weeks old, were recruited for the study. The mother-infant pairs underwent concurrent clinical, biochemical and hormonal evaluation for calcium-vitamin D-PTH axis. RESULTS: The mean serum 25(OH)D values in lactating mothers was 27.2 +/- 14.6 nmol/l (10.9 +/- 5.8 ng/ml), while that of their infants was 28.9 +/- 20.8 nmol/l (11.6 +/- 8.3 ng/ml). Serum 25(OH)D levels <25 nmol/l (10 ng/ml) were found in 47.8% of the mothers and 43.2% of the infants. Among these, elevated PTH levels (>54 pg/ml) were seen in 59.3% of the mothers and 69.6% of the infants. A highly significant negative correlation was found between serum 25(OH)D and PTH in mothers (r = -0.480, p = 0.01) and their infants (r = -0.431, p = 0.01). A strong positive correlation was seen of 25(OH)D levels in mother-infant pairs (r = 0.324, p = 0.001). CONCLUSIONS: A high prevalence of vitamin D deficiency was found in lactating mothers and their exclusively breast fed infants. Infants born to mothers with hypovitaminosis D had 3.8 times higher risk of developing hypovitaminosis D as compared to those born to mothers with normal vitamin D levels.
Asunto(s)
Lactancia Materna , Trastornos de la Nutrición del Lactante/epidemiología , Lactancia/sangre , Estado Nutricional/fisiología , Deficiencia de Vitamina D/epidemiología , Vitamina D/análogos & derivados , Adulto , Femenino , Humanos , India/epidemiología , Lactante , Trastornos de la Nutrición del Lactante/etiología , Recién Nacido , Masculino , Vitamina D/sangre , Deficiencia de Vitamina D/etiología , Adulto JovenRESUMEN
There is little information on the molecular basis of intrafamilial and inter-familial phenotypic heterogeneity with the same androgen receptor (AR) mutation in patients with partial androgen insensitivity syndrome. A genetic analysis was performed in a large kindred with ambiguous genitalia and the genotype-phenotype correlations were analysed. The index case was brought for sex assignment. Family history revealed four other affected members who had hypospadias and varying degrees of virilisation. All the affected males had hemizygous mutations in the third exon of the AR gene (A596T). One was also found to have a heterozygous mutation in the fourth exon of the 5 alpha reductase type 2 gene (G196S). This affected male with double mutations was better virilised compared with the other affected members with a single mutation. The degree of virilisation correlated with serum testosterone levels. Gynaecomastia was not present in any of these subjects. It is concluded that the subject with dual gene defects also had higher levels of testosterone and pubertal virilsation. Testosterone levels possibly govern the degree of pubertal virilisation in subjects with A596T gene defects. It is not clear whether the better pubertal virilsation and higher testosterone are in any way causally related to the SRD5A2 gene defect.
Asunto(s)
Síndrome de Resistencia Androgénica/genética , Genotipo , Fenotipo , Receptores Androgénicos/genética , Diferenciación Sexual/genética , Testosterona/sangre , 3-Oxo-5-alfa-Esteroide 4-Deshidrogenasa/genética , Adulto , Humanos , Recién Nacido , MasculinoRESUMEN
Male pseudohermaphroditism (46,XY DSD) due to 5alpha-reductase deficiency has been recognized for the last few decades. There is scant literature on this entity in India. We compiled data on five patients with this disorder. Four of our five patients were reared as females. Our assessment of these children reveals that they had male gender identity from childhood. Three of the four reared as females chose to change gender role at adolescence, while the fourth is still prepubertal. We conclude that all these patients had male gender identity from early childhood. The parents took note of this only after the appearance of male secondary sexual characteristics at puberty, thereby giving an impression of change in gender identity and gender role.
Asunto(s)
3-Oxo-5-alfa-Esteroide 4-Deshidrogenasa/deficiencia , Trastornos del Desarrollo Sexual/enzimología , Trastornos del Desarrollo Sexual/psicología , Identidad de Género , Adolescente , Niño , Preescolar , Femenino , Hormonas/metabolismo , Humanos , India , MasculinoRESUMEN
We have investigated a potential test method to monitor changes through possible degradation of a collagen/glycosaminoglycan tissue engineering scaffold in vitro. The method used cyclic voltammetry where the degradation process was measured by determining changes in the apparent diffusion coefficients of thermodynamically reversible couples, ferrocyanide and 1,4-benzoquinone, through the scaffold before and after degradation at low pH and at different temperatures. Scaffold samples were degraded in vitro by exposure to pH 3 for 44 days and also stored in pH 7.4 phosphate saline buffer for one week. Sample temperatures used were 21 degrees C, 37 degrees C and 40 degrees C. The greatest apparent degradation was observed for scaffolds stored at 40 degrees C. Prior to storage, effective diffusion coefficients were 4.4x10(-6) cm2 s(-1) and 2.6x10(-10) cm2 s(-1) for ferrocyanide and 1,4-benzoquinone, respectively. For these respective compounds values changed to 1.2x10(-6) cm2 s(-1) and 1.0x10(-6) cm2 s(-1) after 37 degrees C degradation and 2.6x10(-6) cm2 s(-1) and 5.5x10(-8) cm2 s(-1) after pH 3 degradation.
Asunto(s)
Colágeno/metabolismo , Glicosaminoglicanos/metabolismo , Piel Artificial , Benzoquinonas/química , Colágeno/química , Difusión , Electroquímica , Ferricianuros/química , Ferrocianuros/química , Glicosaminoglicanos/química , Concentración de Iones de Hidrógeno , Temperatura , Termodinámica , Ingeniería de TejidosRESUMEN
Analysis of soil samples collected from sewage and tube well irrigated soils of Ludhiana, Amritsar Jalandhar and Mandi Gobindgarh, revealed that Diethylene triamine pentaacetic acid extractable nickel ( DTPA-Ni) was found to be higher in sewage fed soils. Sewage irrigation increased soil DTPA-Ni content by 3.04 times over the tube well irrigated soils. The content of DTPA-Ni showed decreasing trend with depth. Hydrogen concentration (pH) was negatively and significantly correlated with DTPA-Ni nickel whereas, organic carbon and total Ni show positive and significant correlation. Sequential fractionation was carried out to partition Ni in to fractions namely exchangeable and water soluble, organic bound, carbonate bound, Mn oxides bound, amorphous Fe oxides, crystalline Fe oxides bound and residual. Plant availability of these fractions is believed to decrease in the above order. Sequential fractionation indicated that every extracted fraction exhibited increase in Ni content with sewage irrigation with most prominent increases occurring in the organic and oxide fractions. The lowest amount of Ni in exchangeable and water soluble and the highest in residual pools testify that plants grown on these soils may not suffer from Ni toxicity. Though all the crops irrigated with sewage water had appreciably higher concentration of Ni as compared to the crops raised with tube-well water yet raya (Brassica juncea) and toria (Brassica campestris) accumulated higher content of heavy metals as compared to other crops, with higher content in roots than shoots. Transport index suggested that major part of taken up Ni is translocated to top parts of plant. Based on values of transport indices, different crops maybe arranged as toria > raya = maize > bajra > lady finger. As the plants take up nickel readily and there is danger of its excessive accumulation in plant organs and devaluation of the plant products. This is topical issue particularly in crops used for direct consumption.
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Ciudades , Productos Agrícolas/metabolismo , Contaminantes Ambientales/química , Níquel/química , Aguas del Alcantarillado , Suelo , Agricultura , Transporte Biológico , Carbono/análisis , Fraccionamiento Químico , Contaminantes Ambientales/análisis , Concentración de Iones de Hidrógeno , India , Residuos Industriales , Industrias , Níquel/análisis , SolubilidadRESUMEN
Mastoparan potently stimulated catalytic activity of guanylate cyclase-coupled atrial natriuretic factor receptor (GC-A/ANF-R), both in the plasma membranes and intact Leydig tumor (MA-10) cells. In plasma membrane preparations, a maximum of 5-fold GC catalytic activity was stimulated by 100 microM mastoparan and the half maximum stimulation (EC50) was achieved at 40 microM concentration. Mastoparan potentiated GC activity by more than 40%, above the level, stimulated by ANF. Mas 7, an active analog of mastoparan, stimulated the GC activity in a similar manner to mastoparan whereas Mas 17, an inactive analog, did not enhance GC activity. In membranes prepared from mastoparan-treated intact MA-10 cells, GC catalytic activity was enhanced by more than 4-fold as compared with untreated control cells. Pretreatment of membranes with either anti-Gs alpha or anti-Gi alpha antibodies had no effect on mastoparan-stimulated GC activity, however, anti-Go alpha antibodies inhibited the stimulatory effect of mastoparan by almost 50%. Agents known to modulate the effect of mastoparan such as EGTA (Ca2+ chelator), W7 (calmodulin inhibitor) and staurosporine (protein kinase C inhibitor) had no effect on the mastoparan-stimulated GC activity. Mastoparan enhanced the ANF-stimulated GC activity in detergent solubilized membrane preparations without a significant change in ANF-binding capacity. The data establish a role for mastoparan in the ANF-dependent stimulation of GC-A/ANF-R catalytic activity, both in the plasma membrane preparations and intact Leydig tumor (MA-10) cells. Furthermore, these findings provide new evidence that mastoparan (isolated from wasp venom) potently stimulates guanylate cyclase activity of GC-A/ANF-R by activating G-proteins.
Asunto(s)
Factor Natriurético Atrial/farmacología , Proteínas de Unión al GTP/fisiología , Guanilato Ciclasa/metabolismo , Tumor de Células de Leydig/metabolismo , Receptores del Factor Natriurético Atrial/efectos de los fármacos , Venenos de Avispas/farmacología , Animales , Línea Celular , Membrana Celular/metabolismo , Péptidos y Proteínas de Señalización Intercelular , Ratones , Péptidos , Receptores del Factor Natriurético Atrial/metabolismoRESUMEN
BACKGROUND: Assessing nutritional status and delivering optimal nutritional care is a part of modern day treatment of children with cancer. The nutritional practices in India for these children have not been previously described. AIMS: To describe the existing nutrition assessment and management practices for children with cancer in India. METHODS: Attendees of the First International Society of Pediatric Oncology-Pediatric Oncology in Developing Countries workshop on nutrition in children with cancer organized in September 2014 at Tata Memorial Hospital, Mumbai, India were invited to complete a self-administered questionnaire related to three domains: nutritional assessment, intervention, and education. RESULTS: Hundred and eight respondents from 42 health institutions and background in the health sector participated in the survey. There was variability in nutritional assessment, practice and education. Lack of resources and time are contributory. CONCLUSIONS: This assessment of nutritional services in India provided useful information to plan development of national guidelines, policy, and delivery of services.
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Neoplasias/epidemiología , Estado Nutricional , Pediatría , Adolescente , Niño , Preescolar , Humanos , India/epidemiología , Neoplasias/dietoterapia , Neoplasias/patología , Evaluación NutricionalRESUMEN
Deficiency of the 5α-reductase 2 enzyme impairs the conversion of testosterone to dihydrotestosterone (DHT) and differentiation of external genitalia, seminal vesicles and prostate in males. The present study describes the phenotype, genotype and gender identity in a large cohort of patients with 5αRD2. All patients underwent detailed clinical evaluation, hormonal profile, karyotyping and molecular analysis of the SRD5A2 gene. The molecular analysis of the SRD5A2 gene showed the presence of mutant alleles in 24 patients. We found 6 novel mutations IVS(1-2) T>C, p.A52T, 188-189insTA, 904-905ins A, p.A12T and p.E57X in our patients. All patients had ambiguous genitalia and the degrees of under-virilization ranged from penoscrotal hypospadias and microphallus to clitoromegaly. The position of gonads was variable in patients with same mutation. All the patients with mutations in the SRD5A2 gene had male gender identity. Those reared as female had gender dysphoria and underwent gender reassignment. Though a specific genotype-phenotype correlation could not be established in our patient but confirming the diagnosis of 5αRD2 with assessment of the SRD5A2 gene may help in appropriate gender assignment.
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3-Oxo-5-alfa-Esteroide 4-Deshidrogenasa/deficiencia , 3-Oxo-5-alfa-Esteroide 4-Deshidrogenasa/genética , Trastorno del Desarrollo Sexual 46,XY/genética , Disforia de Género/genética , Identidad de Género , Proteínas de la Membrana/deficiencia , Proteínas de la Membrana/genética , Mutación , Adolescente , Biomarcadores/sangre , Niño , Preescolar , Análisis Mutacional de ADN , Trastorno del Desarrollo Sexual 46,XY/enzimología , Trastorno del Desarrollo Sexual 46,XY/psicología , Trastorno del Desarrollo Sexual 46,XY/terapia , Femenino , Disforia de Género/enzimología , Disforia de Género/psicología , Disforia de Género/terapia , Predisposición Genética a la Enfermedad , Hormonas/sangre , Humanos , India , Lactante , Cariotipo , Cariotipificación , Masculino , Fenotipo , Procedimientos de Reasignación de Sexo , Encuestas y CuestionariosRESUMEN
CONTEXT: Congenital adrenal hyperplasia (CAH) is an autosomal recessive metabolic disorder caused by mutations in the CYP21A2 gene. Genetic diagnosis of 21-OH deficiency causing CAH is more complicated than any other monogenic disorder due to high variability of the locus. The disease has a wide spectrum of clinical variants making it difficult to establish a genotyp-phenotype correlation. Therefore, family studies are necessary to ascertain parental genotype and segregation of the mutant allele among the offspring. AIM: The present study aimed to identify CYP21A2 gene mutations and analyze the segregation pattern in CAH trios (patients and their parents). MATERIALS AND METHODS: A total of ten families having at least one CAH child were recruited. RESULTS: Out of 31 children from ten families, 15 were affected with CAH and 13 of/them (12 females and 1 male) were available for genetic testing. One family had all the children affected with CAH. Compound heterozygous mutations were identified in seven patients (53.8%) whereas p.P30L, In2 and Δ8 bp mutations were present in homozygous state in three (23.1%), two (15.3 %) and one (7.6%) patient respectively. CONCLUSIONS: In majority of the families, mutant alleles observed in the patients were inherited from the parents whereas three families showed sporadic mutations without any paternal or maternal origin. This indicated their novel occurrence due to misalignment of the parental genes and/or large deletion of the gene. Female preponderance was noted in the CAH families and also among the patients raising the possibility of survival advantage among females.
RESUMEN
BACKGROUND: Pheochromocytomas (PHEO) and paragangliomas (PGL) are derived from paraganglia of the sympathetic and parasympathetic nervous system. Most of the sympathetic PHEO/PGL secrete either catecholamine or their metabolites, metanephrines, whereas parasympathetic PHEO/PGL are nonsecretory. We assessed the utility of plasma free 3-methoxytyramine (3MT), normetanephrine (NM), and metanephrine (MN) for the diagnosis of PHEO/PGL. MATERIALS AND METHODS: Sixty-five patients referred to endocrine/ENT clinics were enrolled. Twelve patients with von Hippel-Lindau (VHL), neurofibromatosis type 1 (NF1) and multiple endocrine neoplasia type 2 (MEN2) syndromes were excluded. Remaining 53 patients (39 patients with adrenal, abdominal, cervical and thoracic PHEO/PGL and 14 patients with head and neck PGL (HNPGL) were taken for this study. Sixty-five age- and sex-matched subjects were taken as controls. Plasma levels 3MT, NM, and MN were measured using high-performance liquid chromatography. Receivers operating characteristics was plotted and cut-off levels were established. RESULTS: When compared with controls, there was a 36-, 8.7- and 9.5-fold increase in levels of NM, 3MT and MN in the patients with PHEO/PGL and 7.2- and 2.7-fold increase in 3MT and NM, in the patients with HNPGL, respectively. In malignant PHEO/PGL, there was a 99-, 16- and 20-fold increase and in benign PHEO/PGL, there was 19-, 6.8- and 6.4-fold increase in levels of NM, 3MT, and MN, respectively. NM in combination with MN was high in 97% of the patients with PHEO/PGL. All three metabolites in combination were high in 83% of patients with HNPGL. In malignant PHEO/PGL, 50% subjects had increased levels of both NM and 3MT. CONCLUSIONS: Measurement of plasma-free NM along with 3MT and MN provides a better tool for the diagnosis of PHEO/PGL as well as HNPGL. Further, NM in combination with 3MT can be used for the diagnosis of malignant PHEO/PGL.
RESUMEN
We have investigated the mechanism by which different natriuretic peptides stimulate steroidogenesis in purified mouse Leydig cells. In addition to atrial natriuretic factor (ANF), we show that brain natriuretic peptide (BNP) and C-type natriuretic peptide (CNP) also stimulate testosterone production in these cells. Testosterone production was increased dramatically to 14-fold with ANF (EC50 = 0.3 nM) and 15-fold with BNP (EC50 = 0.2 nM); however, the CNP-stimulated level of testosterone production was only 2.5-fold compared with controls. ANF and BNP enhanced the stimulatory effect of LH on testosterone production. The C-ANF(4-23) (a truncated form of ANF) had no effect on testosterone production in these cells. ANF, BNP, and CNP stimulated the production of intermediate precursors of testosterone biosynthesis, which included progesterone, 17 alpha-hydroxy progesterone, androstenedione, pregnenolone, 17 alpha-hydroxy pregnenolone, and dehydroepiandrosterone sulfate. The conversion of pregnenolone and progesterone to testosterone was also significantly enhanced after treatment of Leydig cells with these peptides. All three natriuretic peptides (ANF, BNP, and CNP) stimulated the activity of particulate guanylate cyclase by 8.4-, 8.5-, and 4.8-fold and the accumulation of intracellular cGMP by 52-, 58-, and 19-fold, respectively. The cGMP inhibitor LY83583 attenuated both the generation of cGMP as well as testosterone in response to these natriuretic peptides, suggesting the involvement of cGMP as a second messenger. Leydig cells were found to contain high affinity and low capacity binding sites for ANF [dissociation constant (Kd), 2.0 x 10(-10) M; maximum binding capacity (Bmax). 20 fmol/1 x 10(5) cells], BNP (Kd, 2.2 x 10(-10) M; Bmax, 19 fmol/1 x 10(5) cells), and CNP (Kd, 3.1 x 10(-10) M; Bmax, 8.6 fmol/1 x 10(5) cells). The results presented here document that a family of different natriuretic peptides stimulates Leydig cell steroidogenesis in receptor-mediated fashion, beginning at the cholesterol side-chain cleavage enzyme. The data also show that these peptide hormones induce testosterone production in mouse Leydig cells by involving both delta 4- and delta 5-pathways of steroidogenesis.
Asunto(s)
Factor Natriurético Atrial/farmacología , Enzima de Desdoblamiento de la Cadena Lateral del Colesterol/metabolismo , Células Intersticiales del Testículo/metabolismo , Proteínas del Tejido Nervioso/farmacología , Testosterona/biosíntesis , Animales , Factor Natriurético Atrial/metabolismo , Activación Enzimática/efectos de los fármacos , Células Intersticiales del Testículo/efectos de los fármacos , Hormona Luteinizante/farmacología , Masculino , Ratones , Péptido Natriurético Encefálico , Péptido Natriurético Tipo-C , Proteínas del Tejido Nervioso/metabolismo , Pregnenolona/metabolismo , Progesterona/metabolismoRESUMEN
Gender differences after treatment with streptozotocin (STZ) have been previously reported; however, differences in the glucose response to islet transplantation in STZ-induced diabetes in male and female rats after islet transplantation have not been examined. Male and female Wistar-Furth rats were made diabetic using STZ (55 mg/kg BW) and then given an intraportal islet transplant. Control animals received sham injections and sham transplant surgery; diabetic animals received STZ and sham surgery. In male animals, islet grafts contained 0 (diabetic), 250, 500, 1000, 1500, 2000, and 3000 islets; in female rats, grafts were made up of 0, 500 700, 750, 1000, or 2500 islets. STZ treatment had more dramatic effects on male than female rats. During the diabetic phase, body weights of male rats were significantly reduced compared to those of control male animals; this was not observed among females. Although all STZ-treated animals were hyperglycemic, plasma glucose levels in male diabetic rats were significantly higher than those in females during this phase (29.8 +/- 2.1 vs. 24.6 +/- 0.6 mM). After islet transplantation, body weight gain was positively associated with the number of islets transplanted in male rats (r2 = 0.59; P < 0.01), but not in females (r2 = 0.09; P > 0.8). In both male and female rats, animals that received 1000 islets or more were generally normoglycemic by 3 weeks posttransplant (males, 10.8 +/- 2.2 mM; females, 7.1 +/- 0.2 mM). Approximately 60% of male and female animals that received 500 islets achieved a reduction in plasma glucose levels. Mean plasma glucose levels were 17.2 +/- 2.3 in the females and 22.6 +/- 1.0 mM in males. However, a significantly larger proportion of female 500-islet animals (6 of 16) achieved a plasma glucose level of 9.5 mM or less compared with males receiving 500 islets (2 of 30). Multivariate regression analysis suggests that sex and islet number interact to affect glycemic normalization after islet transplantation. Gender differences appear to influence body weight and plasma glucose responses to islet transplantation. This finding may have particular relevance when a marginal number of functional islets are available.
Asunto(s)
Diabetes Mellitus Experimental/metabolismo , Trasplante de Islotes Pancreáticos , Caracteres Sexuales , Animales , Glucemia/análisis , Peso Corporal , Diabetes Mellitus Experimental/patología , Femenino , Trasplante de Islotes Pancreáticos/métodos , Masculino , Ratas , Ratas Endogámicas WF , Análisis de Regresión , Estudios Retrospectivos , Factores de TiempoRESUMEN
We compared the efficacy of spironolactone (50 mg/d) with metformin (1000 mg/d) after random allocation in 82 adolescent and young women with polycystic ovary syndrome (PCOS) on body mass index (BMI), waist-to-hip ratio, blood pressure, menstrual cyclicity, hirsutism, hormonal levels, glycemia, and insulin sensitivity at baseline and at the 3rd and 6th months of treatment. Sixty-nine women who completed the follow-up had a mean age of 22.6 +/- 5.0 yr and mean BMI of 26.8 +/- 4.0 kg/m2. The number of menstrual cycles in the spironolactone and metformin groups increased from 6.6 +/- 2.1 and 5.7 +/- 2.3 at baseline to 9.0 +/- 1.9 and 7.4 +/- 2.6 at 3rd month and to 10.2 +/- 1.9 and 9.1 +/- 2.0/ year at the 6th month (P = 0.0037), respectively. The hirsutism score decreased from 12.9 +/- 3.2 and 12.5 +/- 4.9 at baseline to 10.1 +/- 3.1 and 11.4 +/- 4.1 at the 3rd month and to 8.7 +/- 1.9 and 10.0 +/- 3.3 at the 6th month, respectively. Both groups showed improvement in glucose tolerance and insulin sensitivity, although the metformin effect was significant in the latter. Serum LH/FSH and testosterone decreased in both groups. BMI, waist-to-hip ratio, and blood pressure did not change with either drug. We conclude that both drugs are effective in the management of PCOS. Spironolactone appears better than metformin in the treatment of hirsutism, menstrual cycle frequency, and hormonal derangements and is associated with fewer adverse events.
Asunto(s)
Hipoglucemiantes/administración & dosificación , Metformina/administración & dosificación , Antagonistas de Receptores de Mineralocorticoides/administración & dosificación , Síndrome del Ovario Poliquístico/tratamiento farmacológico , Espironolactona/administración & dosificación , Adolescente , Adulto , Índice de Masa Corporal , Femenino , Estudios de Seguimiento , Humanos , Hipoglucemiantes/efectos adversos , Metformina/efectos adversos , Antagonistas de Receptores de Mineralocorticoides/efectos adversos , Espironolactona/efectos adversos , Resultado del TratamientoRESUMEN
The effect of thyrotrophin-releasing hormone (TRH) on the circulating plasma levels of tri-iodothyronine (T3) and thyroxine (T4) was determined in the same group of animals (four cattle and four Murrah buffaloes) during hot dry (HD), hot humid (HH) and cold environmental conditions. Plasma T3 and T4 concentrations were measured during 2 h before and up to 12 h after the administration of TRH (200 micrograms i.v.). In the preinjection period in both cattle and buffaloes T3 levels were significantly lower in HH conditions. No significant difference in basal (preinjection) T3 levels was observed during HD and cold seasons in cattle. The highest T3 levels were obtained in buffaloes during HD season with intermediate values during the cold months. Plasma T4 levels in these animals were reversed during HD and HH months. In both cattle and buffaloes there was a biphasic response of T3 and T4 to TRH treatment and this varied with time and in size. The season significantly affected the T3 response to TRH in cattle and buffaloes but the T4 response differed in the two species. The ratio of T4/T3 was higher during HH condition compared with other seasons in both cattle and buffaloes. The climate significantly affected the thyroidal response to TRH.