Plasma free metanephrine, normetanephrine, and 3-methoxytyramine for the diagnosis of pheochromocytoma/paraganglioma.

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.

Clinical profile and inheritance pattern of CYP21A2 gene mutations in patients with classical congenital adrenal hyperplasia from 10 families.

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.

Phenotype, genotype and gender identity in a large cohort of patients from India with 5α-reductase 2 deficiency.

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.

A survey of nutritional practices for children with cancer in India.

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.

Influence of cadmium on dry matter yield, micronutrient content and its uptake in some crops.

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.

Effect of farm yard manure on chemical fractionation of cadmium and its bio-availability to maize crop grown on sewage irrigated coarse textured soil.

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.

Plasma testosterone in adult normoglycaemic men: impact of hyperinsulinaemia.

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.

Presentation and clinical course of Wolfram (DIDMOAD) syndrome from North India.

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.

Implications of obesity for drug therapy: limitations and challenges.

Obesity has become a worldwide challenge with significant health and socioeconomic implications. One of the major implications is its impact on drug therapy. In order to gain a better understanding of this impact, we surveyed the regulatory guidances, the newly approved molecular entity drug products, and drug product labels in the Physician's Desk Reference. This review summarizes the findings of the survey along with the existing knowledge on pharmacokinetic and pharmacodynamic changes associated with obesity.

Association of subclinical hypothyroidism and phenotype, insulin resistance, and lipid parameters in young women with polycystic ovary syndrome.

OBJECTIVE: To determine whether subclinical hypothyroidism (SCH) alters the phenotype, insulin resistance, or lipid parameters in young women with polycystic ovary syndrome (PCOS). DESIGN: Prospective case-control study. SETTING: Tertiary care setting. PATIENT(S): Sixty-two young women with PCOS and SCH (group I) and 291 euthyroid women with PCOS (group II). INTERVENTION(S): Recording of clinical, biochemical, hormonal profile, and parameters of insulin resistance. MAIN OUTCOME MEASURE(S): Whether SCH has any association with clinical parameters like hirsutism, menstrual disturbances, lipid profile, and parameters of insulin sensitivity. RESULT(S): Mean (±SD) TSH was 7.13±1.28 IU/L in group I and 2.51±1.21 IU/L in group II, with comparable free triiodothyronine and free thyroxine. The two groups were comparable in age, weight, and body mass index. Parameters like blood pressure, menstrual pattern, and degree and duration of hirsutism did not differ between the two groups. Serum concentrations of triglycerides were significantly higher in the SCH group compared with controls. Plasma glucose concentrations both in fasting and after oral glucose tolerance test were similar between the two groups. Fasting insulin and other parameters of insulin resistance were not altered by SCH. CONCLUSION(S): Mild TSH elevation in the face of normal serum free triiodothyronine and free thyroxine results in a mild increase in serum lipids. Subclinical hypothyroidism is not associated with alteration in phenotypic expression and insulin resistance in young women with PCOS.

Spatial and seasonal distribution of nitrate-N in groundwater beneath the rice-wheat cropping system of India: a geospatial analysis.

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.

Suitability of village pond waters for irrigation-a case study from district Ludhiana, India.

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.

Phenotype, hormonal profile and genotype of subjects with partial androgen insensitivity syndrome: report of a family with four adult males and one child with disorder of sexual differentiation.

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.

Vitamin D nutritional status of exclusively breast fed infants and their mothers.

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.

Gender identity of children and young adults with 5alpha-reductase deficiency.

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.

Impact of sewage irrigation on speciation of nickel in soils and its accumulation in crops of industrial towns of Punjab.

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.

A test method to monitor in vitro storage and degradation effects on a skin substitute.

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.

Bacillus lehensis sp. nov., an alkalitolerant bacterium isolated from soil.

A Gram-positive, endospore-forming, alkalitolerant bacterial strain, designated MLB2T, was isolated from soil from Leh, India, and was subjected to a polyphasic taxonomic study. The strain exhibited phenotypic properties that included chemotaxonomic characteristics consistent with its classification in the genus Bacillus. Growth was observed at pH 7.0-11.0, but not at pH 6.0. The DNA G+C content was 41.4 mol%. The highest level of 16S rRNA gene sequence similarity was with Bacillus oshimensis JCM 12663T (98.8 %). However, DNA-DNA hybridization experiments indicated low levels of genomic relatedness with the type strains of B. oshimensis (62 %), Bacillus patagoniensis (55 %), Bacillus clausii (51 %) and Bacillus gibsonii (34 %), the species with which strain MLB2T formed a coherent cluster (based on the results of the phylogenetic analysis). On the basis of the phenotypic characteristics and genotypic distinctiveness of strain MLB2T, it should be classified within a novel species of Bacillus, for which the name Bacillus lehensis sp. nov. is proposed. The type strain is MLB2T (=MTCC 7633T=JCM 13820T).

Antiremodeling agents influence osteoblast activity differently in modeling and remodeling sites of canine rib.

Antiremodeling agents reduce bone loss in part through direct actions on osteoclasts. Their effects on osteoblasts and bone formation activity are less clear and may differ at sites undergoing modeling vs. remodeling. Skeletally mature intact beagles, 1-2 years old at the start of the study, were treated daily with clinically relevant doses of alendronate (0.10 or 0.20 mg/kg), risedronate (0.05 or 0.10 mg/kg), raloxifene (0.50 mg/kg), or vehicle (1 mL/kg). Dynamic bone formation parameters were histologically assessed on periosteal, endocortical/trabecular, and intracortical bone envelopes of the rib. Raloxifene significantly increased periosteal surface mineral apposition rate (MAR), a measure of osteoblast activity, compared to all other treatments (+108 to +175%, P < 0.02), while having no significant effect on MAR at either the endocortical/trabecular or intracortical envelope. Alendronate (both 0.10 and 0.20 doses) and risedronate (only the 0.10 dose) significantly (P < or = 0.05) suppressed MAR on the endocortical/trabecular envelope, while none of the bisphosphonate doses significantly altered MAR at either the periosteal or intracortical envelopes compared to vehicle. Based on these results, we conclude that (1) at clinically relevant doses the two classes of antiremodeling agents, bisphosphonates and selective estrogen receptor modulators, exert differential effects on osteoblast activity in the canine rib and (2) this effect depends on whether modeling or remodeling is the predominant mechanism of bone formation.

Comparison of efficacy of spironolactone with metformin in the management of polycystic ovary syndrome: an open-labeled study.

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.