Abnormal Neurovascular Control in Anabolic Androgenic Steroids Users

NUNES ALVES, M. J. N., M. R. DOS SANTOS, R. G. DIAS, C. A. AKIHO, M. C. LATERZA, M. U. P. B. RONDON, R. L. DE MORAES MOREAU, and C. E. NEGRAO. Abnormal Neurovascular Control in Anabolic Androgenic Steroids Users. Med. Sci. Sports Exerc., Vol. 42, No. 5, pp. 865-871, 2010. Purpose: Previous studies showed that anabolic androgenic steroids (AAS) increase vascular resistance and blood pressure (BP) in humans. In this study, we tested the hypotheses 1) that AAS users would have increased muscle sympathetic nerve activity (MSNA) and reduced forearm blood flow (FBF) compared with AAS nonusers and 2) that there would be an association between MSNA and 24-h BP. Methods: Twelve AAS users aged 31 +/- 2 yr (means +/- SE) and nine age-matched AAS nonusers aged 29 T 2 yr participated in the study. All individuals were involved in strength training for at least 2 yr. AAS was determined by urine test (chromatography-mass spectrometry). MSNA was directly measured by microneurography technique. FBF was measured by venous occlusion plethysmography. BP monitoring consisted of measures of BP for 24 h. Results: MSNA was significantly higher in AAS users than that in AAS nonusers (29 +/- 3 vs 20 +/- 1 bursts per minute, P = 0.01). FBF (1.92 +/- 0.17 vs 2.77 +/- 0.24 mL.min(-1).100 mL(-1), P = 0.01) and forearm vascular conductance (2.01 +/- 0.17 vs 2.86 +/- 0.31 U, P = 0.02) were significantly lower in AAS users than that in AAS nonusers. Systolic (131 +/- 4 vs 120 +/- 3 mm Hg, P = 0.001), diastolic (74 +/- 4 vs 68 +/- 3 mm Hg, P = 0.02), and mean BP (93 +/- 4 vs 86 +/- 3 mm Hg, P = 0.005) and heart rate (74 +/- 3 vs 68 +/- 3 bpm, P = 0.02) were significantly higher in AAS users when compared with AAS nonusers. Further analysis showed that there was a significant correlation between MSNA and 24-h mean BP (r = 0.75, P = 0.002). Conclusions: AAS increases MSNA and reduces muscle blood flow in young individuals. In addition, the increase in BP levels in AAS users is associated with augmented sympathetic outflow. These findings suggest that AAS increases the susceptibility for cardiovascular disease in humans.

Influence of a probiotic soy product on fecal microbiota and its association with cardiovascular risk factors in an animal model

Background: Previous work showed that daily ingestion of an aqueous soy extract fermented with Enterococcus faecium CRL 183 and Lactobacillus helveticus 416, supplemented or not with isoflavones, reduced the total cholesterol and non-HDL-cholesterol levels, increased the high-density lipoprotein (HDL) concentration and inhibited the raising of autoantibody against oxidized low-density lipoprotein (ox-LDL Ab) and the development of atherosclerotic lesions. Objective: The aim of this study was to characterize the fecal microbiota in order to investigate the possible correlation between fecal microbiota, serum lipid parameters and atherosclerotic lesion development in rabbits with induced hypercholesterolemia, that ingested the aqueous soy extract fermented with Enterococcus faecium CRL 183 and Lactobacillus helveticus 416. Methods: The rabbits were randomly allocated to five experimental groups (n = 6): control (C), hypercholesterolemic (H), hypercholesterolemic plus unfermented soy product (HUF), hypercholesterolemic plus fermented soy product (HF) and hypercholesterolemic plus isoflavone-supplemented fermented soy product (HIF). Lipid parameters and microbiota composition were analyzed on days 0 and 60 of the treatment and the atherosclerotic lesions were quantified at the end of the experiment. The fecal microbiota was characterized by enumerating the Lactobacillus spp., Bifidobacterium spp., Enterococcus spp., Enterobacteria and Clostridium spp. populations. Results: After 60 days of the experiment, intake of the probiotic soy product was correlated with significant increases (P < 0.05) on Lactobacillus spp., Bifidobacterium spp. and Enterococcus spp. and a decrease in the Enterobacteria population. A strong correlation was observed between microbiota composition and lipid profile. Populations of Enterococcus spp., Lactobacillus spp. and Bifidobacterium spp. were negatively correlated with total cholesterol, non-HDL-cholesterol, autoantibodies against oxidized LDL (ox-LDL Ab) and lesion size. HDL-C levels were positively correlated with Lactobacillus spp., Bifidobacterium spp., and Enterococcus spp. populations. Conclusion: In conclusion, daily ingestion of the probiotic soy product, supplemented or not with isoflavones, may contribute to a beneficial balance of the fecal microbiota and this modulation is associated with an improved cholesterol profile and inhibition of atherosclerotic lesion development.

Delivery of daunorubicin to cancer cells with decreased toxicity by association with a lipidic nanoemulsion that binds to LDL receptors

A lipidic nanoemulsion termed LDE concentrates in neoplastic cells after injection into the bloodstream and thus can be used as a drug carrier to tumour sites. The chemotherapeutic agent daunorubicin associates poorly with LDE; the aim of this study was to clarify whether the derivatization of daunorubicin by the attachment of an oleyl group increases the association with LDE, and to test the cytotoxicity and animal toxicity of the new preparation. The association of oleyl-daunorubicin (oDNR) to LDE showed high yield (93 +/- 2% and 84 +/- 4% at 1:10 and 1:5 drug:lipid mass, respectively) and was stable for at least 20 days. Association with oDNR increased the LDE particle diameter from 42 +/- 4 nm to 75 +/- 6 nm. Cytotoxicity of LDE-oDNR was reduced two-fold in HL-60 and K-562 cell lines, fourteen-fold in B16 cells and nine-fold in L1210 cells when compared with commercial daunorubicin. When tested in mice, LDE-oDNR showed remarkable reduced toxicity (maximum tolerated dose > 253 mu mol kg(-1), compared with <3 mu mol kg(-1) for commercial daunorubicin). At high doses, the cardiac tissue of LDE-oDNR-treated animals had much smaller structural lesions than with commercial daunorubicin. LDE-oDNR is therefore a promising new preparation that may offer superior tolerability compared with commercial daunorubicin.

Association between decreased vitamin levels and MTHFR, MTR and MTRR gene polymorphisms as determinants for elevated total homocysteine concentrations in pregnant women

Objectives: To examine the association between methylenetetrahydrofolate reductase (MTHFR) (C677T and A1298C), methionine synthase (MTR) A2756G and methionine synthase reductase (MTRR) A66G gene polymorphisms and total homocysteine (tHcy), methylmalonic acid (MMA) and S-adenosylmethionine/ S-adenosylhomocysteine (SAM/SAH) levels; and to evaluate the potential interactions with folate or cobalamin (Cbl) status. Subjects/ Methods: Two hundred seventy-five healthy women at labor who delivered full-term normal babies. Cbl, folate, tHcy, MMA, SAM and SAH were measured in serum specimens. The genotypes for polymorphisms were determined by PCR-restriction fragment length polymorphism ( RFLP). Results: Serum folate, MTHFR 677T allele and MTR 2756AA genotypes were the predictors of tHcy levels in pregnant women. Serum Cbl and creatinine were the predictors of SAM/SAH ratio and MMA levels, respectively. The gene polymorphisms were not determinants for MMA levels and SAM/SAH ratios. Low levels of serum folate were associated with elevated tHcy in pregnant women, independently of the gene polymorphisms. In pregnant women carrying MTHFR 677T allele, or MTHFR 1298AA or MTRR 66AA genotypes, lower Cbl levels were associated with higher levels of tHcy. Lower SAM/SAH ratio was found in MTHFR 677CC or MTRR A2756AA genotypes carriers when Cbl levels were lower than 142 pmol/l. Conclusions: Serum folate and MTHFR C677T and MTR A2576G gene polymorphisms were the determinants for tHcy levels. The interaction between low levels of serum Cbl and MTHFR (C677T or A1298C) or MTRR A66G gene polymorphisms was associated with increased tHcy.

Rutin association with ethylhexyl methoxycinnamate and benzophenone-3: In vitro evaluation of the photoprotection effectiveness by reflectance spectrophotometry

There is a world tendency to the development of sunscreens possessing reduced concentration of UV filters and, yet, with high UVA-UVB protection. This research work proposes the development and in vitro efficacy evaluation of sunscreens containing rutin, an antioxidant flavonol, associated or not to UVA (benzophenone-3) and UVB (ethylhexyl methoxycinnamate) filters. Formulations were in vitro assayed by reflectance spectrophotometry with integrated sphere, regarding the following parameters: estimated sun protection factor (SPF), critical wavelength (nm) and UVA/UVB ratio. Rutin 0.1% w/w photoprotection efficacy presented dependent of the concentration and presence of the UVA and UVB filters, and it was verified synergism on the SPF elevation, from 7.34 +/- 0.24 to 9.97 +/- 0.18, when the flavonoid was associated with the filters in minimum concentrations. Isolated rutin exerted UVA protection superior to the formulation not added to UV filters and their associations.

Diketopiperazines produced by endophytic fungi found in association with two Asteraceae species

Diketopiperazine (DKP) derivatives, named colletopiperazine, fusaperazine C and E as well as four known DKPs were isolated from cultures of Colletotrichum gloeosporioides, Penicillium crustosum, both endophytic fungi isolated from Viguiera robusta, and a Fusarium spp., an endophyte of Viguiera arenaria, respectively. Their structures were established on the basis of their spectroscopic data. Conformational analysis of two known DKPs showed that folded conformations were as energetically stable as the extended one. (C) 2010 Elsevier Ltd. All rights reserved.

Endophytic fungi found in association with Smallanthus sonchifolius (Asteraceae) as resourceful producers of cytotoxic bioactive natural products

Smallanthus sonchifolius is a traditional Andean plant which has been cultured mainly in Brazil, Japan and New Zealand due to its medicinal properties. A study of the endophytic fungi associated to the plant was carried out in order to characterize new cytotoxic agents. Thirty two fungal strains were isolated and submitted to cultivation and extraction producing 186 extracts. Of these, 12% displayed moderate to high cytotoxic activities and were considered promising anticancer compound sources. The ethyl acetate fractions of Nigrospora sphaerica and Phoma betae liquid fermentations contained the synergistic compounds 8-hydroxy-6-methoxy-3-methylisocoumarin and (22E,24R)-ergosta-4,6,8(14),22-tetraen-3-one which are potential compounds for drug discovery. Another isolated compound, pimara-7,15-dien-3-beta-ol diterpene is being characterized for the first time through a detailed spectroscopic analysis including GC/MS, homo- and hetero-nuclear correlated NMR experiments (HMQC, HMBC, COSY and NOEdiff) along with its optical rotation.

Influence of Plasma Protein Binding on Pharmacodynamics: Estimation of In Vivo Receptor Affinities of beta Blockers Using a New Mechanism-Based PK-PD Modelling Approach

The objective of this investigation was to examine in a systematic manner the influence of plasma protein binding on in vivo pharmacodynamics. Comparative pharmacokinetic-pharmacodynamic studies with four beta blockers were performed in conscious rats, using heart rate under isoprenaline-induced tachycardia as a pharmacodynamic endpoint. A recently proposed mechanism-based agonist-antagonist interaction model was used to obtain in vivo estimates of receptor affinities (K(B),(vivo)). These values were compared with in vitro affinities (K(B),(vitro)) on the basis of both total and free drug concentrations. For the total drug concentrations, the K(B),(vivo) estimates were 26, 13, 6.5 and 0.89 nM for S(-)-atenolol, S(-)-propranolol, S(-)-metoprolol and timolol. The K(B),(vivo) estimates on the basis of the free concentrations were 25, 2.0, 5.2 and 0.56 nM, respectively. The K(B),(vivo)-K(B),(vitro) correlation for total drug concentrations clearly deviated from the line of identity, especially for the most highly bound drug S(-)-propranolol (ratio K(B),(vivo)/K(B),(vitro) similar to 6.8). For the free drug, the correlation approximated the line of identity. Using this model, for beta-blockers the free plasma concentration appears to be the best predictor of in vivo pharmacodynamics. (C) 2008 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 98:3816-3828, 2009

Association Among Microalbuminuria and Oxidative Stress Biomarkers in Patients With Type 2 Diabetes

Aim: Hyperglycemia in diabetes mellitus (DM) may be one of the most important factors responsible for the development of oxidative stress, which promotes the main complications in DM patients. Therefore, this study evaluated if the hyperglycemia could be related to oxidative stress biomarkers, lipid profile, and renal function in type 2 diabetes patients without clinic complications. Methods: Plasmatic malondialdehyde (MDA), serum protein carbonyl (PCO), serum creatinine levels, microalbuminuria, glycated hemoglobin, and lipid profile were analyzed in 37 type 2 diabetic patients and 25 subjects with no diabetes. Results: Serum creatinine levels were within the reference values, but microalbuminuria presented increased levels in all the patients compared with controls (P G 0.05) and above of the reference values. The MDA, PCO, low- density lipoprotein, and triglyceride levels showed positive correlation with microalbuminuria levels. Moreover, glycated hemoglobin presented positive correlation with MDA, PCO, and microalbuminuria levels. Conclusions: The hyperglycemia could be responsible for the increase of the microalbuminuria levels and for the oxidation process in lipids and proteins in DM patients. Therefore, we suggested that the microvascular lesion is a direct consequence from hyperglycemia and an indirect one from the increased oxidative stress. Malondialdehyde and protein carbonyl levels could be suggested as additional biochemical evaluation to verify tissue damage in type 2 DM patients.

Biological features of a puzzling symbiotic association between the hermit crab Dardanus insignis and the porcellanid crab Porcellana Sayana (Crustacea)

The symbiotic lifestyle is widespread among porcellanid crabs, which maintain ecological and co-evolutionary associations with annelid polychaetes, poriferans, cnidarians, echinoderms, gastropod. mollusks, and other crustaceans such as shrimps and hermit crabs, among others. We investigated the ecological association between the hermit crab Dardanus insignis and the porcellanid Porcellana sayana, in southeastern Brazil. Porcellanid crabs, hermit crabs, and available shells were collected monthly from July 2001 to June 2003, with a shrimp boat equipped with two double-rig trawl nets. The majority of P. sayana specimens were collected in shells occupied by D. insignis (96.6%); a few were found in empty shells (3.4%). The catch of both symbionts and hosts increased with increasing depth, with the highest occurrence at 35 m. The F. sayana crabs of various sizes could be found solitary or forming aggregations of up to 14 individuals per host, showing no sex or size segregation. In spite of the high diversity of shell species occupied by the hermit crabs and also available in the field, only a few of them were also utilized by P. sayana. The majority (93%) of shells utilized by P. sayana also hosted other symbiont species, constituting the basis of extensive symbiotic complexes. Thus, the ecological relationship between D. insignis and P. sayana may be classified as a non-obligate and non-specific symbiosis that may also involve other facultative organisms such as sea anemones. (C) 2008 Elsevier B.V. All rights reserved.

Shelter association between the hermit crab Sympagurus dimorphus and the zoanthid Epizoanthus paguricola in the southwestern Atlantic Ocean

Schejter, L. and Mantelatto, F.L. 2011. Shelter association between the hermit crab Sympagurus dimorphus and the zoanthid Epizoanthus paguricola in the southwestern Atlantic Ocean. -Acta Zoologica (Stockholm) 92: 141-149. The available literature on zoanthid-hermit crab associations deals only with records of this phenomenon, providing no detailed information. We describe, for the first time, the shell-like colonies of Epizoanthus paguricola associated with the hermit crab Sympagurus dimorphus from benthic samples taken in the Argentine Sea, between 85 and 131 m depth, and provide information about morphometric relationships between the hermits and the zoanthids. In total, 260 specimens (137 males and 123 females) of S. dimorphus were collected, 240 (92.3%) of which were living in symbiosis with E. paguricola. The remaining 20 (7.7%) were living inside gastropod shells. As the initial structure of the pseudoshell, 12 different gastropod species were found (all were almost totally covered with colonies of E. paguricola). The hermit crab lives in the spiral cavity inside the soft colony, which seemed to be slightly different depending on the initial gastropod. Aperture pseudoshell morphology did not seem to be related to the sex of the hermit crab host, although males showed larger apertures for a given colony size. This fact is probably related to a larger size of male`s cheliped (sexual dimorphic character) used like a gastropod operculum and that may serve as a template for the growing of the aperture pseudoshell edge. The number of epizoanthid polyps per colony increased in relation to the weight of the colony and to the size of the hermit crab. A process of selection of the initial shell was evident, because species of Naticidae were not the most common gastropods in this benthic community, but were those most used by hermit crabs (> 60%). The puzzling association between hermit crab, shell and zoanthid presumably occurs during the hermit juvenile phase, when the crab occupies a small shell, and a zoanthid larva settles on it. Given the close relationship between S. dimorphus and E. paguricola found in this region, we support the idea that due to the low availability of adequate gastropod shells for hermit life cycle, this association allows the establishment and the continuity of the hermit crab population in the studied area.

The association of Na,K-ATPase subunits studied by circular dichroism, surface tension and dilatational elasticity

Different stoichiometries are observed between alpha and beta subunits of Na,K-ATPase that depend on the method employed to solubilize and purify the enzyme. It is not known whether this variability is due to loss of protein-protein association, or is a result of the replacement of essential phospholipids by detergent molecules. With the aim of understanding the effect of enzyme/surfactant ratio on both the catalytic activity and the enzyme structure, we have investigated the bulk and surface properties of the enzyme. The circular dichroism (CD) spectra, surface tension and dilatational surface elasticity results were compared with the residual ATPase activity of the Na,K-ATPase in different surfactant and protein concentrations. Na,K-ATPase in the (alpha beta)(2) form dissociated to the alpha beta form on dilution, and associated to the (alpha beta)(4) form when concentrated. These different stoichiometries have similar ATPase activities and are in equilibrium at C(12)E(8) concentrations below the CIVIC (0.053 mg mL(-1)). At detergent concentrations above the CIVIC the ATPase activity of all forms was abolished, which is concomitant with the dissociation of the a and subunits. (C) 2008 Elsevier Inc. All rights reserved.

A Statistical Study of the Association of Seven Dental Anomalies in the Brazilian Population

The objective of this study was to show the association patterns among seven types of dental anomalies (second pre-molar agenesis, upper side incisive reduced in size, lower first molar infra-ochlesis, enamel hypoplasia, first molar ectopic eruption, supra numerous teeth and upper canine ectopic eruption) in a population sample without dental treatment ranging in age from 7 to 14. A total of 172 patients were attended and underwent the clinical examination at the Clinica Infantil da Fundacao Educacional de Barretos. Eleven patients from this total were selected according to a first dental anomaly diagnosis and submitted to panoramic radiography. A significant association (p < 0.05) was detected among six pairs of anomalies (second pre-molar agenesis x first pre-molar ectopic eruption; second pre-molar agenesis x lower first molar infra-ochlesis; second pre-molar agenesis x upper side incisive reduced in size; supra numerous teeth x reduced size upper side incisive; first pre-molar ectopic eruption x enamel hypoplasia; lower first molar infra-ochlesis x upper side incisive reduced in size) suggesting a common genetic origin for these conditions. The association was not significant in only one case where there was anomaly sharing by the patients. The existence of an anomaly is clinically relevant for early diagnosis of a possible association and an anomaly can indicate an increased risk of other anomalies.

Association of haplotypes in the IL8 gene with susceptibility to chronic periodontitis in a Brazilian population

Background: Interleukin 8 (IL-8) is a chemokine related to the initiation and amplification of acute and chronic inflammatory processes. Polymorphisms in the IL8 gene have been associated with inflammatory diseases. We investigated whether the - 845(T/C) and - 738(T/A) single nucleotide polymorphisms (SNPs) in the IL8 gene, as well as the haplotypes they form together with the previously investigated -353(A/T), are associated with susceptibility to chronic periodontitis. Methods: DNA was extracted from buccal epithelial cells of 400 Brazilian individuals (control n =182, periodontitis n=218). SNPs were genotyped by the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. Disease associations were analyzed by the chi(2) test, Exact Fisher test and Clump program. Haplotypes were reconstructed using the expectation-maximization algorithm and differences in haplotype distribution between the groups were analyzed to estimate genetic susceptibility for chronic periodontitis development. Results: When analyzed individually, no SNPs showed different distributions between the control and chronic periodontitis groups. Although, nonsmokers carrying the TTA/CAT (OR = 2.35, 95% CI = 1.03-5.36) and TAT/CTA (OR= 6.05, 95% CI = 1.32-27.7) haplotypes were genetically susceptible to chronic periodontitis. The ITT/TAA haplotype was associated with protection against the development of periodontitis (for nonsmokers OR= 0.22, 95% CI = 0.10-0.46). Conclusion: Although none of the investigated SNPs in the IL8 gene was individually associated with periodontitis, some haplotypes showed significant association with susceptibility to, or protection against, chronic periodontitis in a Brazilian population. (C) 2010 Elsevier B.V. All rights reserved.

ASSOCIATION BETWEEN SADDLE NOSE DEFORMITY AND RETRO-ORBITAL MASS IN WEGENER`S GRANULOMATOSIS

Objectives: The relationship between saddle nose deformity (SND) in Wegener`s granulomatosis (WG) and other clinical features, including retro-orbital mass formation (ROM), has been poor described. Therefore, this relationship was analyzed retrospectively from 2000 to 2010. Patients and Methods: Eighteen consecutive WG patients with SND diagnosed by computed tomography were matched to 36 WG patients without SND (control group) for gender, age at WG diagnosis and disease duration. Results: No difference was found between the two groups in relation to WG type (limited and systemic forms), ethnicity, laboratory features, constitutional symptoms or clinical manifestations, including upper respiratory tract, and treatment, except for ROM (33.3 vs. 2.8% in SND(+) and SND(-) groups, respectively; p=0.004) and subglottic stenosis (22.2 vs. 2.8%; p=0.038). However, on multivariate analysis, only ROM (OR 17.15; 95% CI 1.11-265.52) was statistically associated to SND. In addition, in more than half of the cases, SND manifested prior to ROM. Conclusions: Results of this prospective analysis showed that SND was strongly associated to ROM in WG. Since early diagnosis and aggressive treatment of orbital involvement could lead to better prognosis, the presence of SND warrants additional vigilance.