Structure-activity relationship, molecular docking, and molecular dynamic studies of diterpenes from marine natural products with anti-HIV activity.

HIV-1 infection is a global epidemic whose treatment is limited majorly by viral resistance and adverse effects. Natural products from algae have been studied for many years, including antiviral, being an alternative to anti-HIV drug design. Since the isolation of natural products can be a hurdle, molecular modeling is an important tool to study these compounds. Herein, structure-activity relationship, molecular docking, and molecular dynamic studies were performed to direct the studies of ten marine natural products with anti-HIV activity. In the structure-activity relationship, descriptors were identified associating the anti-HIV activity of five diterpenes with possible action on the reverse transcriptase allosteric site. These diterpenes were evaluated by molecular docking, and it was identified that only dolabelladienetriol interacted in the allosteric site. Molecular dynamics suggested that the dolabelladienetriol might interfere with the viral RNA binding to HIV-1 RT by inducing a conformational change of the enzyme. Also, in silico ADMET simulations predicts that the dolabelladienetriol present a high potential to be successfully developed as a drug. Thus, applying in silico approaches was possible to suggest potential anti-HIV compounds derived from marine natural products.Communicated by Ramaswamy H. Sarma.

Experimental cryptorchidism enhances testicular susceptibility to dibutyl phthalate or acrylamide in Sprague-Dawley rats.

Cryptorchidism (CPT), the most common male congenital abnormality, is variably associated with other male reproductive tract problems. We evaluated if cryptorchid rats develop enhanced testicular susceptibility to dibutyl phthalate (DBP) or acrylamide (AA) after extended exposure. Three studies with rats were performed: (1) in utero and postnatal exposure to DBP or AA; (2) establishment of CPT and orchiopexy; and (3) in utero and postnatal exposures to DBP or AA associated with CPT/orchiopexy. Seminiferous tubules were histologically scored according to the severity of lesions: (1) Rats exposed to DBP (score 1.5) or AA (score 1.1) presented mostly preserved spermatogenesis. Some seminiferous tubules showed vacuolated germinative epithelium, germ cell apoptosis, and a Sertoli cell-only (SCO) pattern. (2) CPT (score 3.3) resulted in decreased absolute testes weights, degenerated and SCO tubules, and spermatogenesis arrest that were reversed by orchiopexy (score 1.1). (3) Exposure to DBP or AA with CPT/orchiopexy led to atrophic testes, spermatogenesis arrest, germ cell exfoliation/multinucleation, and SCO tubules (both chemicals score 2.5). Exposure to chemicals such as DBP or AA prevented the recovery of cryptorchid testes by orchiopexy. The possible role of environmental contaminants should be considered when looking for factors that modulate human testicular disorders associated with CPT.

Exploring pathways for sustained melanogenesis in facial melasma: an immunofluorescence study.

BACKGROUND: The physiopathology of epidermal hypermelanization in melasma is not completely understood. Several cytokines and growth factors are increased in skin with melasma, nevertheless, nor the pathways involved in the increased αMSH expression have been adequately evaluated, nor a model for sustained focal melanogenesis is available. OBJECTIVE: To explore stimulatory pathways for epidermal pigmentation in facial melasma related to αMSH: those linked to ultraviolet radiation, oxidative stress, inflammation, neural crest pigmentation cell differentiation and antagonism of αMSH. METHODS: Paired skin biopsies (3 mm) from 26 women with facial melasma and from normal adjacent skin (<2 cm far) were processed for immunofluorescence with markers for p53, p38, αMSH, MC1R, Melan-A, IL-1α, COX2, Wnt1, WIF-1 and ASIP. RESULTS: The fluorescence intensity in the skin from melasma was higher for MC1R, αMSH at epidermis as at melanocytes (P < 0.05). There were no differences between the sites in epidermal protein expression of COX2, IL-1α, p53, WIF-1 and ASIP (P > 0.1). P53 was expressed only in epidermis, without difference between sites (P = 0.92). WNT1 was remarkable in the epidermis of melasma (P < 0.01), but not in dermis. Positive p38 cells were prominent in the upper dermis of melasma (P < 0.01), despite no marking in epidermis. CONCLUSION: Melanogenesis in melasma involves epithelial secretion of αMSH and activation of the Wnt pathway; nevertheless, it seems to be independent of the stimulation by ultraviolet radiation/p53, IL-1α, COX2/PgE2 , WIF-1 and ASIP. Damaged cells at upper dermis suggest the role of senescence/autophagy in sustained pigmentation in melasma.

Knowledge, attitude and behaviour regarding hepatitis C virus infection amongst Brazilian dental students.

AIM: Dental health professionals, including dental students, are at high risk of exposure to infection with the hepatitis C virus (HCV) through occupational percutaneous injuries and eye exposure. Further, fear of HCV infection is associated with discriminatory attitudes. The current study aimed to evaluate the knowledge about HCV infection amongst dental students and their attitudes towards patients infected with HCV. METHODS: A cross-sectional survey was conducted amongst 340 Brazilian dental students from two public universities using an instrument containing information regarding demographic characteristics, knowledge of HCV and attitudes towards patients with HCV infection. Descriptive statistics, Fisher's exact test, Student's t-tests, Mann-Whitney U-test and multiple logistic regression (MLR) were carried out (P < 0.05 was considered significant). RESULTS: Response rate was 90% (n = 306), and more than half (54%, n = 165) of participants had high knowledge level (above the mean); 97.7% (n = 299) demonstrated positive attitudes. MLR showed that high knowledge of dental students regarding HCV was substantially influenced by advancement in year of study (last year; P < 0.001) and type of university (federal; P = 0.049). Positive attitude towards HCV-infected patients was mainly influenced by age (P = 0.004) and male gender (P = 0.022). CONCLUSIONS: These results demonstrated a satisfactory knowledge about HCV infection amongst dental students, but some gaps were observed, suggesting the importance of continuous education about HCV in this population to prevent HCV infection as well as discrimination and prejudice towards patients with hepatitis C.

Estradiol and progesterone fecal metabolites analysis in crab-eating-fox (Cerdocyoun thous) / Análise de metabólitos fecais de estradiol e progesterona em cachorro-do-mato (Cerdocyoun thous)

In this study, four crab-eating fox females (Cerdocyon thous) maintained at the Federal University of Mato Grosso Zoo, Cuiabá, Brazil, were investigated for 12 months, using feces measurement of estradiol and progesterone concentrations. Fecal collections were performed three times a week for hormone extraction. Two methods of analysis, Elisa (EIA) and Radioimmunoassay (RIA), were used in the measurement of progesterone (P4) and estradiol (E2) metabolites. The aim of this study was to compare and validate two different methods of hormone measurement for C. thous. There were no differences regarding the method used. The Radioimmunoassay technique proved to be more sensitive, however, both showed similar results.(AU)

Neste estudo, quatro fêmeas de cachorros-do-mato (Cerdocyon thous) mantidas no Zoológico da Universidade Federal de Mato Grosso, Cuiabá, MT, Brasil, foram investigadas pelo período de 12 meses, mediante a mensuração de concentrações de estradiol e progesterona em fezes. Coletas de fezes foram realizadas três vezes por semana para posterior extração hormonal. Dois métodos de análise de metabólitos fecais, elisaimunoensaio (EIA) e radioimunoensaio (RIA), foram utilizados na mensuração dos metabólitos de progesterona (P4) e estradiol (E2). O objetivo deste estudo foi comparar e validar dois diferentes métodos de mensuração hormonal para C. thous. Não houve diferença significativa com relação ao método empregado. A técnica de radioimunoensaio demonstrou ser mais sensível, no entanto ambas apresentaram resultados semelhantes.(AU)

Dosagem hormonal e avaliação testicular em cachorro-do-mato (Cerdocyun thous) utilizando diferentes protocolos anestésicos / Hormonal analyses and testicular evaluation in Cerdocyun thous using different anesthetic protocols

Tree Cerdocyon thous males received different anesthesia protocols: tiletamine-zolazepan (7mg/kg); ketamine-xylazine (12 and 1mg/kg); ketamine-xylazine-atropin (12, 1.0 and 0.04mg/kg), ketamine-midazolam (12 and 0.5mg/kg) and ketamine-acepromazine (12 and 0.1mg/kg) for semen collection by electroejaculation, testosterone hormonal dosages, fine needle aspiration cytology (FNAC), testicular manual evaluation, biometry by caliper and ultrassonography (US). The ejaculates collected by electroejaculation showed urine contamination making impossible the semen evaluation. The M±PD of serum testosterone was 0.74±0.2ng/mL. The cell types found in FNAC were: spermatogonia 13.3±11.5 percent, primary spermatocytes 5.5±1.1 percent, secondary spermatocytes 5.5±3.9 percent, early spermatids 12.8±6.2 percent, late spermatids 26.2±11.2 percent, sperm 14.5±4.7 percent and Sertoli cells 21.8±2.7 percent. Manual testicular evaluation showed normal consistency of testicles. The M±PD of testicular biometry by caliper was 3.8±1.5cm³ and by US was 1.1±0.3cm³. The animals showed normal spermatogenesis with normal spermatozoa observed in FNAC and normal testicular US.

Analysis of the use of imipenem at a University Hospital following the restructuring of an antimicrobial audit system

This study analyzed the use pattern of imipenem following the restructuring of the antimicrobial audit system at a University Hospital. It was an observational study before and after the restructuring of the antimicrobial audit system in a University Hospital from May to August and then from September to December 2006. The criteria of the rational use of imipenem were obtained from a non-systematic revision of the literature. The collection of data on the general characteristics and clinical state of the patient, the infection and the established therapy was carried out in a previously tested instrument. Data was recorded, revised and analyzed in a database built with the software SPSS® for Windows® PC, version 10.0. The statistical analysis had a descriptive character: frequencies, mean, median and standard deviation. No differences were encountered in relation to the appropriate indication, consumption and clinical outcomes of patients. However, there was a reduction of 4 to 1 (75.0 percent) in the number of associations with spectrum superposition and an increase of 4 to 8 (50.0 percent) in the change of therapy. The restructuring of the antimicrobial audit system in the studied hospital did not reflect significantly the increase of the appropriate indication of imipenem. It contributed, however, to the reduction of the inappropriate associations of this antibiotic and to changes of therapy, without, however, compromising the quality of services rendered to patients.

Analysis of the use of imipenem at a university hospital following the restructuring of an antimicrobial audit system.

This study analyzed the use pattern of imipenem following the restructuring of the antimicrobial audit system at a University Hospital. It was an observational study before and after the restructuring of the antimicrobial audit system in a University Hospital from May to August and then from September to December 2006. The criteria of the rational use of imipenem were obtained from a non-systematic revision of the literature. The collection of data on the general characteristics and clinical state of the patient, the infection and the established therapy was carried out in a previously tested instrument. Data was recorded, revised and analyzed in a database built with the software SPSS for Windows PC, version 10.0. The statistical analysis had a descriptive character: frequencies, mean, median and standard deviation. No differences were encountered in relation to the appropriate indication, consumption and clinical outcomes of patients. However, there was a reduction of 4 to 1 (75.0%) in the number of associations with spectrum superposition and an increase of 4 to 8 (50.0%) in the change of therapy. The restructuring of the antimicrobial audit system in the studied hospital did not reflect significantly the increase of the appropriate indication of imipenem. It contributed, however, to the reduction of the inappropriate associations of this antibiotic and to changes of therapy, without, however, compromising the quality of services rendered to patients.