Chronic exposure of bisphenol S (BPS) affect hypothalamic-pituitary-testicular activities in adult male rats: possible in estrogenic mode of action

BACKGROUND@#The industrial revolution has resulted in increased synthesis and the introduction of a variety of compounds into the environment and their potentially hazardous effects have been observed in the biota. The present study was aimed to evaluate the potential endocrine-disrupting effects of chronic exposure to the low concentrations of bisphenol S (BPS) in male rats.@*METHODS@#Weaning male Sprague-Dawley rats (22 days old) were either exposed to water containing 0.1% ethanol for control or different concentrations of BPS (0.5, 5, and 50 μg/L) in drinking water for 48 weeks in the chronic exposure study. After completion of the experimental period, animals were dissected and different parameters (hormone concentrations, histology of testis and epididymis, oxidative stress and level of antioxidant enzymes in the testis, daily sperm production (DSP), and sperm parameters) were determined.@*RESULTS@#Results of the present study showed a significant alteration in the gonadosomatic index (GSI) and relative reproductive organ weights. Oxidative stress in the testis was significantly elevated while sperm motility, daily sperm production, and the number of sperm in epididymis were reduced. Plasma testosterone, luteinizing hormone (LH), and follicle-stimulating hormone (FSH) concentrations were reduced and estradiol levels were high in the 50 μg/L-exposed group. Histological observations involved a significant reduction in the epithelial height of the testis along with disrupted spermatogenesis, an empty lumen of the seminiferous tubules, and the caput region of the epididymis.@*CONCLUSION@#These results suggest that exposure to 5 and 50 μg/L of BPS for the chronic duration started from an early age can induce structural changes in testicular tissue architecture and endocrine alterations in the male reproductive system which may lead to infertility in males.

Effect of focal adhesion kinase inhibition on osteoblastic cells grown on titanium with different topographies

Abstract Objective The present study aimed to investigate the participation of focal adhesion kinases (FAK) in interactions between osteoblastic cells and titanium (Ti) surfaces with three different topographies, namely, untreated (US), microstructured (MS), and nanostructured (NS). Methodology Osteoblasts harvested from the calvarial bones of 3-day-old rats were cultured on US, MS and NS discs in the presence of PF-573228 (FAK inhibitor) to evaluate osteoblastic differentiation. After 24 h, we evaluated osteoblast morphology and vinculin expression, and on day 10, the following parameters: gene expression of osteoblastic markers and integrin signaling components, FAK protein expression and alkaline phosphatase (ALP) activity. A smooth surface, porosities at the microscale level, and nanocavities were observed in US, MS, and NS, respectively. Results FAK inhibition decreased the number of filopodia in cells grown on US and MS compared with that in NS. FAK inhibition decreased the gene expression of Alp, bone sialoprotein, osteocalcin, and ALP activity in cells grown on all evaluated surfaces. FAK inhibition did not affect the gene expression of Fak, integrin alpha 1 ( Itga1 ) and integrin beta 1 ( Itgb1 ) in cells grown on MS, increased the gene expression of Fak in cells grown on NS, and increased the gene expression of Itga1 and Itgb1 in cells grown on US and NS. Moreover, FAK protein expression decreased in cells cultured on US but increased in cells cultured on MS and NS after FAK inhibition; no difference in the expression of vinculin was observed among cells grown on all surfaces. Conclusions Our data demonstrate the relevance of FAK in the interactions between osteoblastic cells and Ti surfaces regardless of surface topography. Nanotopography positively regulated FAK expression and integrin signaling pathway components during osteoblast differentiation. In this context, the development of Ti surfaces with the ability to upregulate FAK activity could positively impact the process of implant osseointegration.

La leptina promueve la expresión de Hic-5 y la formación de puntos de actina por la vía dependiente de FAK-Src en células epiteliales mamarias MCF10A / Leptin induced Hic-5 expression and actin puncta formation by the FAK/Src-dependent pathway in MCF10A mammary epithelial cells

Resumen Introducción. La leptina es una hormona secretada por los adipocitos que se ha relacionado con el proceso de la transición de epitelio a mesénquima (Epithelial- Mesenchymal Transition, EMT). Promueve la migración e invasión de las células del epitelio mamario mediante la activación de las cinasas FAK y Src, un complejo regulador de vías de señalización que favorecen la expresión de las proteínas relacionadas con la formación de estructuras proteolíticas implicadas en la invasión y progresión del cáncer. Recientemente, se ha descrito que la sobreexpresión y activación de la proteína Hic-5 durante el mencionado proceso de transición, favorece la formación de los puntos de actina (indicativa de la formación y funcionalidad de los invadopodios), lo cual promueve la degradación local de los componentes de la matriz extracelular y la metástasis del cáncer. Objetivos. Evaluar el papel de las cinasas FAK y Src sobre la expresión y localización subcelular de Hic-5 y la formación de puntos de actina inducida por la leptina en la línea celular MCF10A de epitelio mamario no tumoral. Materiales y métodos. Se utilizaron los inhibidores específicos de la FAK (PF-573228) y la Src (PP2) para evaluar el papel de ambas cinasas en los niveles de expresión y localización subcelular de la proteína Hic-5 mediante Western blot e inmunofluorescencia, así como la formación de puntos de actina mediante la tinción con faloidina-TRITC en células MCF10A estimuladas con leptina. Resultados. La leptina indujo el incremento en la expresión de Hic-5 y la formación de puntos de actina. El tratamiento previo con los inhibidores de las cinasas FAK (PF-573228) y Src (PP2), promovió la disminución en la expresión de Hic-5 y de los puntos de actina en la línea celular MCF10A de epitelio mamario no tumoral. Conclusión. La leptina indujo la expresión y la localización perinuclear de Hic-5 y la formación de puntos de actina mediante un mecanismo dependiente de la actividad de las cinasas FAK y Src en las células MCF10A.

Abstract Introduction: Leptin is a hormone secreted by adipocytes that has been associated with the epithelial-mesenchymal transition (EMT). Additionally, leptin promotes the migration and invasion of mammary epithelial cells through the activation of FAK and Src kinases, which are part of a regulatory complex of signaling pathways that promotes the expression of proteins related to the formation of proteolytic structures involved in the invasion and progression of cancer. Recently, overexpression and activation of Hic-5 during the EMT have been shown to induce the formation of actin puncta; these structures are indicative of the formation and functionality of invadopodia, which promote the local degradation of extracellular matrix components and cancer metastasis. Objective: To evaluate the role of FAK and Src kinases in the expression of Hic-5 during the epithelial-mesenchymal transition induced by leptin in MCF10A cells. Materials and methods: We used specific inhibitors of FAK (PF-573228) and Src (PP2) to evaluate Hic-5 expression and subcellular localization by Western blot and immunofluorescence assays and to investigate the formation of actin puncta by epifluorescence in MCF10A cells stimulated with leptin. Results: Leptin induced an increase in Hic-5 expression and the formation of actin puncta. Pretreatment with inhibitors of FAK (PF-573228) and Src (PP2) promoted a decrease in Hic-5 expression and actin puncta formation in the non-tumorigenic mammary epithelial cell line MCF10A. Conclusion: In MCF10A cells, leptin-induced Hic-5 expression and perinuclear localization, as well as the formation of actin puncta through a mechanism dependent on the kinase activity of FAK and Src.

The tankyrase inhibitor G007-LK inhibits small intestine LGR5+ stem cell proliferation without altering tissue morphology

Abstract Background The WNT pathway regulates intestinal stem cells and is frequently disrupted in intestinal adenomas. The pathway contains several potential biotargets for interference, including the poly-ADP ribosyltransferase enzymes tankyrase1 and 2. LGR5 is a known WNT pathway target gene and marker of intestinal stem cells. The LGR5+ stem cells are located in the crypt base and capable of regenerating all intestinal epithelial cell lineages. Results We treated Lgr5-EGFP-Ires-CreERT2;R26R-Confetti mice with the tankyrase inhibitor G007-LK for up to 3 weeks to assess the effect on duodenal stem cell homeostasis and on the integrity of intestinal epithelium. At the administered doses, G007-LK treatment inhibited WNT signalling in LGR5+ stem cells and reduced the number and distribution of cells traced from duodenal LGR5+ stem cells. However, the gross morphology of the duodenum remained unaltered and G007-LK-treated mice showed no signs of weight loss or any other visible morphological changes. The inhibitory effect on LGR5+ stem cell proliferation was reversible. Conclusion We show that the tankyrase inhibitor G007-LK is well tolerated by the mice, although proliferation of the LGR5+ intestinal stem cells was inhibited. Our observations suggest the presence of a tankyrase inhibitor-resistant cell population in the duodenum, able to rescue tissue integrity in the presence of G007-LK-mediated inhibition of the WNT signalling dependent LGR5+ intestinal epithelial stem cells.

Suporte e participação social em indivíduos com hanseníase / Social Support and participation of individuals with leprosy

O contexto de isolamento social e de restrição dos relacionamentos sociais gerado pela hanseníase promove adiminuição na participação na comunidade, destacando a importância do suporte social. Desta forma, esse estudo tevecomo objetivo avaliar o grau de restrição de participação e o suporte social recebido pelos indivíduos em tratamentopara hanseníase em dois centros de referência para hanseníase no município de Juiz de Fora-MG, Brasil. Foram aplicadasas Escalas de Participação e de Avaliação do Suporte Social, no primeiro semestre de 2014, nos indivíduos inseridosnesses centros. Para análise estatística foram utilizados teste de Wilcoxon, correlação de Spearman e teste exato deFisher, com nível de significância de p<0,05. A partir dos resultados, observa-se que 60% dos sujeitos não apresentaramrestrição de participação, e altos valores de disponibilidade e de satisfação dos suportes oferecidos. Pode-se ressaltara família e os profissionais de saúde como fonte desse suporte. Destaca-se o suporte social tipo emocional, vistoque os indivíduos com hanseníase que apresentavam incapacidades e os que não tiveram restrição de participaçãoapontaram uma associação com a satisfação desse suporte. A partir deste estudo, conclui-se que o suporte social podeser apontado como um fator protetor, tornando-se essencial a escuta ao indivíduo, não perdendo de vista a noçãode que o cuidado não se remete apenas aos sinais visíveis da doença, mas antes a todo o contexto social ao qual oportador encontra-se inserido

The context of social isolation and restriction of social relationships created by leprosy promotes decreased participationin the community, highlighting the importance of social support. Thus, this study aimed to assess the degree ofparticipation restriction and social support received by individuals in treatment for leprosy in two reference centers forleprosy in the city of Juiz de Fora. The Participation and Evaluation of Social Support Scales were applied in the firsthalf of 2014 to individuals inserted in these centers. Statistical analyses were performed using Wilcoxon test, Spearmancorrelation and Fisher’s exact test, with a significance level of p<0.05. According to the results, 60% of the subjects didnot present participation restriction, and high values of availability and satisfaction of the support offered were observed.The family and health professionals can be highlighted as this source of support. The emotional type of social supportis noteworthy, as individuals with leprosy who had disabilities and those without participation restriction showed anassociation with the satisfaction of that support. It was concluded that social support can be seen as a protective factor,making it essential to listen to the individual, not losing sight of the notion that care does not refer only to the visiblesigns of the disease, but rather the whole social context to which the carrier is inserted

Influence of ultrafiltration membrane on ophiopogonins and homoisoflavonoids in Ophiopogon japonicus as measured by ultra-fast liquid chromatography coupled with ion trap time-of-flight mass spectrometry / 中国天然药物

Ultrafiltration is one of the most fascinating technologies, which makes it possible to improve the quality of traditional medicines for application in the pharmaceutical industry. However, researchers have paid little attention to the effect of ultrafiltration membrane on traditional medicines chemical constituents. In this work, Ophiopogon japonicus (L.f) Ker-Gawl. was used as an example to illuminate the influence of ultrafiltration with different material and molecular weight cut-off (MWCO) membrane on natural chemical constituents as measured by ultra-fast liquid chromatography coupled with ion trap time-of-flight mass spectrometry (UFLC-IT-TOF/MS). Our results indicated that ultrafiltration membrane significantly impacted homoisoflavonoids, especially homoisoflavonoids that were almost completely retained on the polyethersulfone (PES) membrane. We also found that the larger number of aglycone hydroxy and sugar moiety in steroid saponins, the higher the transmittance. Furthermore, the passage rate (%) of ophiogenin type saponins was higher than that of others. The possible adsorptive mechanisms were hydrogen bonding, hydrophobic interactions, and benzene ring interaction by π-π stacking. In conclusion, it is crucial to choose appropriate ultrafiltration membrane based on the characteristics of produce products for application of ultrafiltration technique.

Effect of polyunsaturated fatty acids ω-3 and ω-6 on angiogenesis formation in human gastric cancer / 中华胃肠外科杂志

<p><b>OBJECTIVE</b>To investigate the effects of polyunsaturated fatty acids (PUFA) ω-3 and ω-6, and their middle metabolites PGE2 and PGE3 on angiogenesis formation of gastric cancer, and to explore associated mechanism.</p><p><b>METHODS</b>The effects of ω-3, ω-6, PGE2, PGE3 on the proliferation and migration of human umbilical vein endothelial cell (HUVEC) were measured by proliferation and migration assay respectively. The angiogenesis assay in vivo was used to measure the effects of ω-3, ω-6, PGE2 and PGE3 on neovascularization. In all the assays, groups without ω-3, ω-6, PGE2 and PGE3 were designed as the control.</p><p><b>RESULTS</b>With the increased concentration of ω-6 from 1 μmol/L to 10 μmol/L, the proliferation ability of HUVECs enhanced, and the number of migration cells also increased from 28.2±3.0 to 32.8±2.1, which was higher than control group (21.2±3.2) respectively (both P<0.05). With the increased concentration of ω-3 from 1 μmol/L to 10 μmol/L, the proliferation ability of HUVECs was inhibited, and the number of migration cells decreased from 15.8±2.0 to 11.0±2.1, which was lower than control group (22.1±3.0) respectively (both P<0.05). In the angiogenesis assay, compared with control group (standard number: 43 721±4 654), the angiogenesis ability of HUVECs was significantly enhanced by ω-6 in concentration-dependent manner (1 μmol/L group: 63 238±4 795, 10 μmol/L group: 78 166±6 123, all P<0.01). Meanwhile, with the increased concentration of ω-3 from 1 μmol/L to 10 μmol/L, the angiogenesis ability was significantly decreased from 30 129±3 102 to 20 012±1 541(all P<0.01). The proliferation and migration ability of HUVECs were significantly promoted by ω-6 metabolites PGE2 (P<0.05) in a concentration-dependent manner. In contrast, ω-3 metabolites PGE3 significantly inhibited the proliferation and migration ability of HUVECs in a concentration-dependent manner (all P<0.05). After rofecoxib (a COX-2 specific inhibitor) inhibited the expression of COX-2, the expression level of PGE2 was significantly decreased in a dose-dependent manner. In co-culture system, whose gastric cancer cells expressed positive COX-2, ω-6 could increase angiogenesis of gastric cancer cells(P<0.01), but ω-3 could inhibit such angiogenesis(P<0.01). In co-culture system, whose gastric cancer cells did not express COX-2, ω-3 could inhibit the angiogenesis of gastric cancer cells (P<0.05), but ω-6 had no effect on angiogenesis.</p><p><b>CONCLUSIONS</b>The PUFA ω-6 can enhance the angiogenesis via the promotion of proliferation and migration of HUVECs, and COX-2 and PGE2 may play an important role in this process, whereas, the ω-3 can inhibit the angiogenesis through its middle metabolites PGE3 to inhibit the proliferation and migration of HUVECs. Results of this experiment may provide a new approach to inhibit and prevent the spread of gastric cancer.</p>

Fixed drug eruption by etoricoxib confirmed by patch test

Abstract: Non-steroidal, anti-inflammatory drugs, followed by antibiotics, are the main causes of fixed drug eruption. They provoke one or several round erythematous or bullous lesions that recur in the same place after taking the causative medication. A positive patch test on residual, lesional skin can replace satisfactorily oral reintroduction. We describe the case of a 74-year-old woman with numerous, rounded, erythematous lesions on the trunk and recurrent blistering on the fifth right-hand finger, which developed a few hours after taking etoricoxib. Lesional patch testing with etoricoxib was positive and reproduced the typical pattern of a fixed drug eruption upon histopathology. We emphasize the specific reactivity of the etoricoxib patch test, and the capacity to reproduce the histologic pattern of the reaction.

Propolis protective role against morphological, hormonal biochemical and histological alterations induced by sildenafil overdoses / Rol protector del propóleo contra las alteraciones morfológicas, hormonales, bioquímicas e histológicas inducidas por sobredosis de sildenafil

Sildenafil is widely used for the treatment of erectile dysfunction with few studies are available on the protective role of propolis against its reproductive toxicity. The present study aims to investigate the hormonal biochemical and histomorphometric alterations induced in the testicular tissues by sildenafil overdoses. Four groups of rabbits were exposed to sildenafil with or without propolis as follows: Group I received the formulated vehicle, Group II received sildenafil (3 mg/kg), Group III received propolis (50 mg/kg), Group IV received sildenafil plus propolis. Sildenafil lowered body weight gain, testosterone and follicular stimulating hormone concentration but increased testis index while luteinizing hormone was almost not affected. Moreover, sildenafil treated rabbits showed degenerative seminiferous tubules and disturbance of spermatogenesis together with spermatocytes sloughing and nuclear alterations. Exposure to sildenafil plus propolis ameliorated tubular alterations, spermatogenesis disturbances, hormonal levels changes and partially protected spermatocytes from morphological nuclear alterations but could not ameliorate the effect on the body weight gain and testis index. The findings of the present work may indicate that propolis can ameliorate partially the reproductive toxicity induced by sildenafil overdoses with more need for further studies on the adverse effect of these doses on the other vital organs.

El sildenafil es un medicamento ampliamente utilizado para el tratamiento de la disfunción eréctil y existen pocos estudios disponibles referente a la función protectora del propóleo contra su toxicidad reproductiva. El objetivo fue investigar las alteraciones hormonales, bioquímicas e histomorfométricas, inducidas en los tejidos testiculares por sobredosis de sildenafil. Cuatro grupos de conejos fueron expuestos a sildenafil con o sin propóleo de la siguiente manera: grupo I recibió el sildenafil formulado, grupo II recibió sildenafil (3 mg/kg), grupo III recibió propóleo (50 mg/kg) y el grupo IV recibió sildenafil más propóleo. El sildenafil redujo el peso corporal, la testosterona y la concentración de la hormona foliculoestimulante, sin embargo, se observó un aumento del índice testicular mientras que la hormona luteinizante casi no se vio afectada. Por otra parte, los conejos tratados con sildenafil mostraron degeneración de los túbulos seminíferos, trastornos de la espermatogénesis y alteraciones nucleares de los espermatocitos. Con el uso de sildenafil más propóleo fue posible disminuir las alteraciones de los túbulos seminíferos, los trastornos de la espermatogénesis y los niveles de cambios hormonales; los espermatocitos fueron protegidos parcialmente de alteraciones nucleares morfológicas, pero no pudo mejorar el efecto de aumento de peso corporal e índice testicular. Los resultados indican que el propóleo puede aliviar, en parte, la toxicidad en la reproducción inducida por sobredosis de sildenafil. No obstante, existe la necesidad de realizar más estudios sobre los efectos adversos de estas dosis en otros órganos vitales.

Effects of sildenafil on dental pulp: immunohistochemical and ultrastructural evaluation / Efectos de sildenafil en la pulpa dental: evaluación inmunohistoquímica y ultraestructural

Sildenafil is a strong peripheral vasodilator and is used to treat cardiovascular and neurosurgery. The purpose of this study was to investigate the immunohistochemical and ultrastructural effects of sildenafil on dental pulp of rats. The study was performed with adult female Wistar-Albino rats. Control group (n= 7) were fed on standard laboratory diet until surgery. The study group (n= 7) were administered sildenafil orally with orogastric tube 10 mg·kg-1 once a day for 30 days. Each rat was anesthetized and incisor teeth were removed. This study examined the immunohistochemical and ultrastructural effects of sildenafil on the dental pulp in rats. The relaxation from the vessel, endothelial cell hyperplasia, moderate degeneration of collagen fibers were observed to cause degenerative changes in odontoblast with sildenafil. In the pulp tissue long-term use sildenafil is thought to cause degeneration and new vessel formation.

El sildenafil es un vasodilatador periférico importante y se utiliza para tratar enfermedades cardiovasculares y en neurocirugía. El propósito de este estudio fue investigar los efectos inmunohistoquímicos y ultraestructurales del sildenafil sobre la pulpa dental de ratas. El estudio se realizó con ratas Wistar albinas, hembras adultas. El grupo de control (n= 7) fue alimentado con una dieta estándar de laboratorio hasta que se realizó la cirugía. El grupo de estudio (n= 7) fue tratado con sildenafil por vía oral y sonda orogástrica 10 mg·kg-1 una vez al día durante 30 días. Cada rata fue anestesiada y se extrajeron los dientes incisivos. Se examinaron los efectos inmunohistoquímicos y ultraestructurales del sildenafil sobre la pulpa dentaria. Con la administración de sildenafil se observó la relajación de los vasos, la hiperplasia de las células endoteliales y una degeneración moderada de fibras colágenas causando cambios degenerativos en los odontoblastos. En el tejido pulpar, el uso de sildenafil a largo plazo puede causar la degeneración y neoformación de vasos.

Gastric and renal effects of COX-2 selective and non-selective NSAIDs in rats receiving low-dose aspirin therapy

Abstract The consumption of low-dose aspirin (LDA) to prevent cardiovascular disease continues to increase worldwide. Consequently, the number of chronic LDA users seeking dental procedures that require complementary acute anti-inflammatory medication has also grown. Considering the lack of literature evaluating this interaction, we analyzed the gastric and renal effects caused by a selective COX-2 inhibitor (etoricoxib) and a non-selective COX-2 inhibitor (ibuprofen) nonsteroidal anti-inflammatory drug (NSAID) in rats receiving chronic LDA therapy. Male Wistar rats were divided into six experimental groups (carboxymethylcellulose (CMC) - vehicle; LDA; LDA + ibuprofen; ibuprofen; LDA + etoricoxib; and etoricoxib) and submitted to long-term LDA therapy with a subsequent NSAID administration for three days by gavage. After the experimental period, we analyzed gastric and renal tissues and quantified serum creatinine levels. The concomitant use of LDA with either NSAID induced the highest levels of gastric damage when compared to the CMC group (F = 20.26, p < 0.05). Treatment with either LDA or etoricoxib alone was not associated with gastric damage. No significant damage was observed on kidney morphology and function (F = 0.5418, p > 0.05). These results suggest that even the acute use of an NSAID (regardless of COX-2 selectivity) can induce gastric damage when combined with the long-term use of low-dose aspirin in an animal model. Additional studies, including clinical assessments, are thus needed to clarify this interaction, and clinicians should be careful of prescribing NSAIDs to patients using LDA.

Effects of vardenafil on the kidney of Wistar rats submitted to acute ischemia and reperfusion

PURPOSE: To investigate the effect of vardenafil in kidney of rats submitted to acute ischemia and reperfusion. METHODS: Twenty-eight rats were randomly distributed into two groups. Right nephrectomy was performed and the vardenafil group received vardenafil solution (at a concentration of 1 mg/ml in 10 mg/kg) while the control group received 0.9% saline solution (SS) one hour prior to the ligature of the left renal pedicle. After one hour of ischemia, animals were submitted to twenty-four hours of reperfusion, followed by left nephrectomy. The kidney's histological parameters evaluated on the study included vacuolar degeneration and tubular necrosis. Apoptosis was assessed by immunohistochemistry for cleaved caspase-3 using the point-counting and digital methods (Cytophotometry). Also, a biochemical analysis for creatinine was conducted. RESULTS: There were statistically significant differences between groups only with regards to the vacuolar degeneration parameter and to the cleaved caspase-3 digital method. CONCLUSION: Vardenafil showed a protective effect on the kidney of rats subjected to acute ischemia and reperfusion in this model .

Discussões em torno da reconstrução do significado da lepra no período pós-sulfônico, Minas Gerais, na década de 1950 / Discussions regarding the reconstruction of the significance of leprosy in the post-sulfone period, Minas Gerais, in the 1950s

Da perspectiva histórica, todos os elementos que envolvem uma doença, desde sua nomeação até a carga de significado que lhe é atribuída, resultam de "negociações" elaboradas por múltiplos atores sociais. No caso da lepra, a descoberta das sulfonas, em 1941, contribuiu de forma significativa para a transformação do entendimento dessa enfermidade, gerando um questionamento acerca das ações utilizadas para o seu controle/combate, sobretudo o isolamento compulsório dos doentes. Com base nesses pressupostos, este artigo analisa o debate que se constituiu acerca do processo de substituição das antigas práticas profiláticas para o controle da lepra, em um importante periódico de circulação nacional, Arquivos Mineiros de Leprologia, na década de 1950.

From a historical viewpoint, all the elements surrounding a disease, from its name to the weight of meaning attached to it, are the result of "negotiations" in which many sections of society are participants. In the case of leprosy, the discovery of sulfones in 1941 made a significant contribution towards transforming our understanding of this disease, leading to questions being raised as to the measures adopted for its prevention and control, particularly the compulsory isolation of sufferers. On the basis of these assumptions, this article examines the debate which took place regarding the process whereby the old prophylactic procedures for the control of leprosy were replaced, in an important national journal, Arquivos Mineiros de Leprologia, in the 1950s.

Euphorbia fischeriana extract reactivates latent HIV through nuclear factor-κB pathway / 南方医科大学学报

<p><b>OBJECTIVE</b>To investigate the effect of Euphorbia fischeriana extract on latent HIV reactivation and the pathway involved in this process and discuss the value of Euphorbia fischeriana extract in eliminating HIV.</p><p><b>METHODS</b>Fresh tissues of Euphorbia fischeriana root were crushed into powder after quick freezing with liquid nitrogen and extracted with acetone followed by a three-day vacuum freeze-drying for dehydration of the extract. The extract (EFE) was separated using RP-C18 column with high-performance liquid chromatography (HPLC) and identified with mass spectrometry (MS). The activity of reactivated latent HIV was analyzed by fluorescence-activated cell sorting in a J-Lat 10.6 cell model treated with EFE (50 µg/mL) for 24 h, using TNF-α (10 ng/mL) as the positive control. The effect of a NF-κB pathway inhibitor (Bay 11-7082) on EFE activity was tested. The changes in P65 expression in the cell nuclei within 2 h and HIV protein p24 expression within 24 h were analyzed by Western blotting in cells treated with EFE.</p><p><b>RESULTS</b>EFE was obtained by one-step acetone extraction, and the concentration of prostratin in the extract was around 0.53 mmol/L. About 50% of the cells showed HIV reactivation after treatment with 50 µg/mL EFE for 24 h accompanied by a significantly increased p24 expression. The activity of EFE in reactivating latent HIV was inhibited by Bay 11-7082 in a concentration-dependent manner, and p65 accumulation was detected in the cell nuclei within 2 h.</p><p><b>CONCLUSION</b>EFE we obtained contains the active compounds of prostratin and its analogues and shows a strong capacity to reactivate latent HIV through classical NF-κB pathway.</p>

The Trend of Leprosy Treatment / 나학회지

Since Mycobacterium Leprae was founded by Dr. Armauer Hansen in 1873, leprosy was proven to infectious disease by a germ not from hereditaty, from a cause, or from sin. For it has no definite method of treatment, made a conclusion at the 1st international leprosy association meeting at Berlin in 1897, isolation is the only way to prevent the disease. So all country started to built a leprosarium and isolated the leprosy patients. Various methods and drugs were used for leprosy treatment including potassium iodide, arsenic, antimony, copper, sera, vaccines and aniline dyes and then X-ray, radium, electric current till 1925. Chaulmoogra oil was introduced to western world in 1854 by Dr. FJ Mouat and used for the leprosy treatment drug. Dr RM Wilson in Kwangju Leprosy Hospital started to use Chaulmoogra oil since 1909 and reported the results of it at JAMA in 1923. But it was replaced to sulfones in 1940'. Mordern treatment started in 1937 when Parke-Davis co. synthesized promin But promin is expensive and have to injection. Then Dapsone delivered from promin and it could be used per oral. Dr. RM Wilson In Aeyang Hospsoital (former Kwangju leposy hospial) started to use Dapson in 1946 with his son Dr. J Wilson. And it was the first episode to use DDS in Korea. When Dr. Cochraine came and visited all the leprosy centers in Korea in 1955 he noticed that some hospital like Aeyangwon and St. Nazarus used DDS but not other hospital. DDS was adopted as main drug of choice in Carville, Loisiana but noticed dapsone resistant bacilli and then WHO recommended the MDT from 1981.

Entre o campo e o laboratório: a dinâmica de produção de conhecimento no Ambulatório de Menopausa do Caism/Unicamp / Between the country and the laboratory: the dynamics of the production of knowledge at the Menopause Outpatients Clinic at Caism, Unicamp

Este estudo investiga as práticas de produção de conhecimento sobre a menopausa no Caism/Unicamp, centro de referência para políticas públicas em saúde da mulher. Foram realizadas observações de consultas ginecológicas, entrevistas com mulheres e médicos e observação de reuniões de apoio psicológico, buscando identificar os discursos que circulam no lugar e o processo de alistamento de diferentes atores para que os conhecimentos ali produzidos alcancem credibilidade e “viajem” além dos limites do hospital-escola, tornando-se “universais”. A análise baseia-se nos “estudos localistas”, alinhados aos estudos sociais de ciência e tecnologia.

This study investigates the practices involved in the production of knowledge about menopause at Caism, Unicamp, a reference center for public policies for women’s health. Gynecological appointments and psychological support meetings were observed, and women and doctors were interviewed in order to identify what discourse circulates there and how different actors are brought in to ensure that the knowledge produced attains credibility and “travels” beyond the boundaries of the teaching hospital to become “universal”. The analysis is based on localized studies aligned with social studies of science and technology.

The effects of vardenafil and pentoxifylline administration in an animal model of ischemic colitis

OBJECTIVES: Vardenafil enhances dilatation of vascular smooth muscle and inhibits platelet aggregation. The purpose of this study was to evaluate the clinical effects of vardenafil and pentoxifylline administration in an experimental model of ischemic colitis. METHODS: Forty female Wistar albino rats weighing 250-300 g were randomized into five experimental groups (each with n = 8) as follows:1) a sham group subjected to a sham surgical procedure and administered only tap water; 2) a control group subjected to a standardized surgical procedure to induce ischemic colitis and administered only tap water; 3) and 4) treatment groups subjected to surgical induction of ischemic colitis followed by the postoperative administration of 5 mg/kg or 10 mg/kg vardenafil, respectively; and 5) a treatment group subjected to surgical induction of ischemic colitis followed by postoperative administration of pentoxifylline at 50 mg/kg/day per day as a single dose for a 3-day period. All animals were sacrificed at 72 h post-surgery and subjected to relaparotomy. We scored the macroscopically visible damage, measured the ischemic area and scored histopathology to determine the severity of ischemia. Tissue malondialdehyde levels were also quantified. RESULTS: The mean Gomella ischemic areas were 63.3 mm2 in the control group; 3.4 and 9.6 mm2 in the vardenafil 5 and vardenafil 10 groups, respectively; and 3.4 mm2 in the pentoxifylline group (p = 0.0001). The mean malondialdehyde values were 63.7 nmol/g in the control group; 25.3 and 25.6 nmol/g in the vardenafil 5 and vardenafil 10 groups, respectively; and 22.8 nmol/g in the pentoxifylline group (p = 0.0001). CONCLUSION: Our findings indicate that vardenafil and pentoxifylline are effective treatment options in an animal model of ischemic colitis. The positive clinical effects produced by these drugs are likely due to their influence on the hemodynamics associated ...

PDE5 Inhibitor Treatment Persistence and Adherence in Brazilian Men: Post-hoc Analyses from a 6-Month, Prospective, Observational Study

Purpose Characterize persistence and adherence to phosphodiesterase type - 5 inhibitor (PDE5I) on-demand therapy over 6 months among Brazilian men in an observational, non-interventional study of Latin American men naïve to PDE5Is with erectile dysfunction (ED). Materials and Methods Men were prescribed PDE5Is per routine clinical practice. Persistence was defined as using ≥ 1 dose during the previous 4 - weeks, and adherence as following dosing instructions for the most recent dose, assessed using the Persistence and Adherence Questionnaire. Other measures included the Self - Esteem and Relationship (SEAR) Questionnaire, and International Index of Erectile Function (IIEF). Multivariate logistic regression was used to identify factors associated with persistence/adherence. Results 104 Brazilian men were enrolled; mean age by treatment was 53 to 59 years, and most presented with moderate ED (61.7%). The prescribed PDE5I was sildenafil citrate for 50 (48.1%), tadalafil for 36 (34.6%), vardenafil for 15 (14.4%), and lodenafil for 3 patients (2.9%). Overall treatment persistence was 69.2% and adherence was 70.2%; both were numerically higher with tadalafil (75.0%) versus sildenafil or vardenafil (range 60.0% to 68.0%). Potential associations of persistence and/or adherence were observed with education level, ED etiology, employment status, and coronary artery disease. Improvements in all IIEF domain scores, and both SEAR domain scores were observed for all treatments. Study limitations included the observational design, brief duration, dependence on patient self - reporting, and limited sample size. Conclusion Approximately two-thirds of PDE5I-naive, Brazilian men with ED were treatment persistent and adherent after 6 months. Further study is warranted to improve long-term outcomes of ED treatment. .

Does sildenafil enhance the effect of tamsulosin in relieving acute urinary retention?

Objective To compare the safety and efficacy of combined therapy using sildenafil and tamsulosin for management of acute urinary retention (AUR) with tamsulosin alone in patients with benign prostate hyperplasia (BPH). Materials and Methods 101 patients were enrolled in a randomized placebo-controlled study from June 2009 to April 2012. Patients presenting with an initial episode of spontaneous AUR underwent urethral catheterization and then prospectively randomized to receive tamsulosin 0.4mg plus sildenafil 50mg in group A and tamsulosin 0.4mg plus placebo in group B for three days. Urethral catheter was removed three days after medical treatment and patient’s ability to void assessed at the day after catheter removal and seven days later. Patients who voided successfully were followed at least for three months. Results Mean age of patients was 59.64 ± 3.84 years in group A and 60.56 ± 4.12 years in group B (p value = 0.92). Mean prostate volume and mean residual urine were comparable between both groups (p value = 0.74 and 0.42, respectively). Fifteen patients in group A (success rate: 70%) and nineteen patients in group B (success rate: 62.7%) had failed trial without catheter (TWOC) at 7th day following AUR (p value = 0.3). No significant difference was noted between both groups regarding the rate of repeated AUR at one month and three month follow-up period (p = 0.07 and p = 0.45, respectively). Conclusion It seems that combination therapy by using 5-phosphodiesterase inhibitor and tamsulosin has no significant advantages to improve urinary retention versus tamsulosin alone. .