Association of IL-9, IL-10, and IL-17 Cytokines With Hepatic Fibrosis in Human Schistosoma mansoni Infection.

This is a case series study to evaluate immunological markers associated with schistosomiasis advanced fibrosis, including 69 patients from an endemic area from the State of Sergipe and from the Hepatology Service of the University Hospital in Sergipe, Brazil. Hepatic fibrosis was classified based on Niamey protocol for ultrasonography (US). Immune response to Schistosoma mansoni antigens was evaluated by stimulating peripheral blood mononuclear cells (PBMCs) from these patients with either adult worm (SWAP-10 µg/ml) or egg (SEA-10 µg/ml) antigens or purified protein derivative of turberculin (PPD-10 µg/ml) or phytohemagglutinin (PHA-1 µg/ml) for 72 h. The levels of IFN-γ, TNF-α, IL-5, IL-10, and IL-17 were measured in these supernatants by ELISA and IL-9 by Luminex. Single nucleotide polymorphisms in IL-17, IL10, and CD209 genes were genotyped using TaqMan probe by qPCR. Higher levels of IL-9, IL-10, and IL-17 were found in PBMC supernatants of patients with advanced hepatic fibrosis. Direct correlations were detected between IL-9 and IL-17 levels with US spleen sizes, portal vein diameters, and periportal thickening. The CD209 rs2287886 AG polymorphism patients produce higher IL-17 levels. Together, these data suggest a role of these cytokines in the immunopathogenesis of advanced fibrosis in human schistosomiasis.

Trends in prostate cancer incidence and mortality to monitor control policies in a northeastern Brazilian state.

Prostate cancer differently affects different regions of the world, displaying higher rates in more developed areas. After the implementation of prostate-specific antigen (PSA) testing, several studies described rising rates globally, but it is possible that indolent lesions are being detected given the lack of changes in mortality data. The Brazilian government recommends against PSA screening in the male population regardless of age, but the Urology Society issued a report recommending that screening should start at 50 years old for certain men and for those aged ≥75 years with a life expectancy exceeding 10 years. In this study, we examined the incidence and mortality rates of invasive prostate cancer over time in the Sergipe state of Brazil. The databases of the Aracaju Cancer Registry and Mortality Information System were used to calculate age-standardized rates for all prostate tumors (International Classification of Diseases 10th edition: C61 and D07.5) in the following age ranges: 20-44, 45-54, and ≥65 years. We identified 3595 cases of cancer, 30 glandular intraepithelial high-grade lesions, and 3269 deaths. Using the Joinpoint Regression Program, we found that the incidence of prostate cancer dramatically increased over time until the mid-2000s for all age groups, after which the rates declined. Prostate cancer mortality rates increased until 2005, followed by a non-significant annual percent change of 22.0 in 2001-2005 and a stable rate thereafter. We noticed that the increases and decreases of the incidence rates of prostate cancer were associated with the screening recommendations. Meanwhile, the increased mortality rates did not appear to be associated with decreased PSA testing; instead, they were linked to the effects of age and improvements in identification of the cause of death. Thus, we do not believe a PSA screening program would benefit the population of this study.

Temporal trend of cancer mortality in a Brazilian state with a medium Human Development Index (1980-2018).

Emerging economy countries in epidemiological transition have been especially challenged in the fight against cancer. This was an ecological study that aimed to describe the temporal trend of cancer mortality in a Brazilian northeastern state with a medium Human Development Index using official Brazilian mortality data from 1980 to 2018. We calculated the mortality crude rate (CR) and age-standardized rate (ASR) based on official population counts and estimates. The Joinpoint Regression Program, National Cancer Institute, USA, was used to calculate time trends of cancer mortality. There were 34,214 deaths from cancer, excluding nonmelanoma skin cancer, in Sergipe. The overall cancer mortality ASR was 70.1 and 57.9 per 100,000 men and women, respectively. For the last five years, the leading causes of cancer deaths were prostate (21.3), trachea, bronchus and lung (11.7), stomach (6.5), oral cavity (5.4) and liver and intrahepatic bile ducts (5.1) in males and breast (13.8), trachea, bronchus and lung (6.6), cervix (6.4), colon/rectum (5.8) and central nervous system (3.6) in females. In addition, there was a significant reduction in deaths from ill-defined causes in the series. Our results show that although there has been an increase in cancer mortality rates associated with Western lifestyles, such as prostate, breast and colon/rectum, high rates of cancer related to poverty and infections, such as stomach and cervix, still persist in Sergipe.

Trends in cervical cancer and its precursor forms to evaluate screening policies in a mid-sized Northeastern Brazilian city.

Cervical cancer is a health issue that disproportionately affects developing countries, where the Papanicolaou test (Pap smear) remains an important screening tool. Brazilian government recommendations have focused screening on the female population aged from 25 to 64 years old. In this study, we examined the incidence and mortality rates of invasive cervical cancer lesions and the incidence rates of in situ precancerous cervical lesions, aiming to calculate their respective statistics over time in a mid-sized Brazilian city, Aracaju. The 1996-2015 database from the Aracaju Cancer Registry and Mortality Information System was used to calculate age standardized rates for all invasive cervical tumors (International code of diseases, ICD-10: C53) and preinvasive cervical lesions (ICD-10: D06) in the following patient age ranges; ≤ 24, 25-34, 35-44, 45-54, 55-64 and ≥ 65 years old. We identified 1,030 cancer cases, 1,871 in situ lesions and 334 deaths. Using the Joinpoint Regression Program, we calculated the annual percentage incidence changes and our analyses show that cervical cancer incidence decreased up to 2008, increased up to 2012 and decreased again thereafter, a significant trend in all age groups from 25 years. The incidence of precursor lesions increased from 1996 to 2005 and has since decreased, a result significant in all age groups until 64 years. Cervical cancer mortality has decreased by 3.8% annually and trend analysis indicates that Pap smears have been effective in decreasing cancer incidence and mortality. However, recent trends shown here show a decreasing incidence of in situ lesions and may indicate either a real decrease or incomplete catchment. Thus, we suggest health policies should be re-considered and include sufficient screening and HPV vaccination strategies to avoid cervical cancer resurgence in the population.

Phenotypic high-throughput screening platform identifies novel chemotypes for necroptosis inhibition.

Regulated necrosis or necroptosis, mediated by receptor-interacting kinase 1 (RIPK1), RIPK3 and pseudokinase mixed lineage kinase domain-like protein (MLKL), contributes to the pathogenesis of inflammatory, infectious and degenerative diseases. Recently identified necroptosis inhibitors display moderate specificity, suboptimal pharmacokinetics, off-target effects and toxicity, preventing these molecules from reaching the clinic. Here, we developed a cell-based high-throughput screening (HTS) cascade for the identification of small-molecule inhibitors of necroptosis. From the initial library of over 250,000 compounds, the primary screening phase identified 356 compounds that strongly inhibited TNF-α-induced necroptosis, but not apoptosis, in human and murine cell systems, with EC50 < 6.7 µM. From these, 251 compounds were tested for RIPK1 and/or RIPK3 kinase inhibitory activity; some were active and several have novel mechanisms of action. Based on specific chemical descriptors, 110 compounds proceeded into the secondary screening cascade, which then identified seven compounds with maximum ability to reduce MLKL activation, IC50 >100 µM, EC50 2.5-11.5 µM under long-term necroptosis execution in murine fibroblast L929 cells, and full protection from ATP depletion and membrane leakage in human and murine cells. As a proof of concept, compound SN-6109, with binding mode to RIPK1 similar to that of necrostatin-1, confirmed RIPK1 inhibitory activity and appropriate pharmacokinetic properties. SN-6109 was further tested in mice, showing efficacy against TNF-α-induced systemic inflammatory response syndrome. In conclusion, a phenotypic-driven HTS cascade promptly identified robust necroptosis inhibitors with in vivo activity, currently undergoing further medicinal chemistry optimization. Notably, the novel hits highlight the opportunity to identify new molecular mechanisms of action in necroptosis.

Assessing trends of breast cancer and carcinoma in situ to monitor screening policies in developing settings.

There have been arguments about the role of breast cancer screening at the population level, and some points of controversy have arisen, such the establishment of organized screening policies and the age at which to begin screening. The real benefit of screening has been questioned because the results of this practice may increase the diagnosis of indolent lesions without decreasing mortality due to breast cancer. The authors have proposed a study of incidence and mortality trends for breast cancer in a developing setting in Brazil to monitor the effectiveness of the official recommendations that prioritize the age group from 50 to 69 years. The database of the Cancer Registry and the Mortality Information System was used to calculate age-standardized and age-specific rates, which were then used to calculate incidence and mortality trends using the Joinpoint Regression Program. The results showed stability in trends across all ages and age-specific groups in both incidence and mortality. In conclusion, we found that incidence and mortality rates are compatible with those in regions with similar human development indexes, and trends have demonstrated stabilization. Thus, we do not endorse changes in the official recommendations to conduct screening for ages other than 50 to 69 years, nor should policy makers implement organized screening strategies.

Combining 1,3-Ditriazolylbenzene and Quinoline to Discover a New G-Quadruplex-Interactive Small Molecule Active against Cancer Stem-Like Cells.

Quadruplex nucleic acids are promising targets for cancer therapy. In this study we used a fragment-based approach to create new flexible G-quadruplex (G4) DNA-interactive small molecules with good calculated oral drug-like properties, based on quinoline and triazole heterocycles. G4 melting temperature and polymerase chain reaction (PCR)-stop assays showed that two of these compounds are selective G4 ligands, as they were able to induce and stabilize G4s in a dose- and DNA sequence-dependent manner. Molecular docking studies have suggested plausible quadruplex binding to both the G-quartet and groove, with the quinoline module playing the major role. Compounds were screened for cytotoxicity against four cancer cell lines, where 4,4'-(4,4'-(1,3-phenylene)bis(1H-1,2,3-triazole-4,1-diyl))bis(1-methylquinolin-1-ium) (1 d) showed the greater activity. Importantly, dose-response curves show that 1 d is cytotoxic in the human colon cancer HT-29 cell line enriched in cancer stem-like cells, a subpopulation of cells implicated in chemoresistance. Overall, this study identified a new small molecule as a promising lead for the development of drugs targeting G4 in cancer stem cells.

Pólipos de glândulas fúndicas: a histologia pode ser utilizada para prever uso de inibidores de bomba de próton? / Gastric fundic gland polyps: can histology be useful to predict proton pump inhibitors use?

ABSTRACT BACKGROUND: Fundic gland polyps allegedly increased in frequency in recent decades, and had attracted great attention due to possible association with prolonged proton pump inhibitor therapy. Prolonged use of this drug could cause parietal cell hyperplasia, obstruction of glandular lumen and cystic dilation of the gland. OBJECTIVE: This study aims to analyze clinical and pathological features of fundic gland polyps in patients with and without proton pump inhibitor therapy in a selected population from Brazil. METHODS: It was selected a sample of 101 Brazilian patients (78 females and 23 males), from a five years retrospective search of the files from a private pathology laboratory. The patients had an average age of 57 years and we included patients with a histological diagnosis of fundic gland polyp. The clinical data were obtained from their files and all histological slides were reviewed and examined with hematoxylin and eosin (HE) and Giemsa. RESULTS: Information about the use or non-use of proton pump inhibitors (PPI) was obtained in 84 patient files. In 17 cases we could not determine if PPI were used or not. Among those in which the information was available, a positive history of anti-acid therapy was observed in 63 (75.0%) patients. Parietal cell hypertrophy/hyperplasia and parietal cell protrusions were detected in most slides. Histological findings were identical in PPI users and PPI negative patients. Helicobacter pylori infection was detected in just two samples. Epithelial dysplasia or adenocarcinoma were not observed in our cases. Histopathological analysis of fundic gland polyps could not distinguish between PPI and non-PPI related cases. Parietal cell cytoplasmic protrusions, an alleged marker of prolonged acid suppression therapy, was detected in both groups. CONCLUSION: Histological features could not discriminate anti-acid therapy related fundic glands polyps in our patients.

RESUMO CONTEXTO: Os pólipos das glândulas fúndicas do estômago supostamente aumentaram em frequência nas últimas décadas e atraíram grande atenção devido à possível associação com a terapia prolongada com inibidores da bomba de prótons. O uso prolongado deste fármaco pode causar hiperplasia das células parietais, obstrução do lúmen glandular e dilatação cística da glândula. OBJETIVO: Este estudo tem como objetivo analisar os aspectos clínicos e patológicos dos pólipos das glândulas fúndicas em pacientes com e sem terapia com inibidores da bomba de prótons em uma população selecionada do Brasil. MÉTODOS: Foi selecionada uma amostra de 101 pacientes brasileiros (78 do sexo feminino e 23 do sexo masculino), a partir de uma pesquisa retrospectiva de cinco anos dos arquivos de um laboratório privado de patologia. Os pacientes tinham uma idade média de 57 anos e foram incluídos pacientes com diagnóstico histológico de pólipo das glândulas fúndicas. Os dados clínicos foram obtidos a partir de seus prontuários e todas as lâminas histológicas foram revisadas e examinadas com hematoxilina e eosina (HE) e Giemsa. RESULTADOS: Informações sobre o uso ou não uso de inibidores da bomba de próton (IBP) foram obtidas em 84 prontuários de pacientes. Em 17 casos, não foi possível determinar se o IBP foi usado ou não. Entre aqueles em que a informação estava disponível, observou-se uma história positiva de terapia com IBP em 63 (75,0%) pacientes. A hipertrofia das células parietais/hiperplasia e protrusões das células parietais foram detectadas na maioria das lâminas. Os achados histológicos foram idênticos em usuários de IBP e pacientes não usuários. A infecção por Helicobacter pylori foi detectada em apenas duas amostras. A displasia epitelial ou o adenocarcinoma não foram observados em nossos casos. A análise histopatológica dos pólipos das glândulas fúndicas não pôde distinguir entre os casos IBP e não relacionados ao IBP. As protuberâncias citoplasmáticas das células parietais, um suposto marcador de terapia prolongada de supressão de ácido, foram detectadas em ambos os grupos. CONCLUSÃO: Características histológicas não podem discriminar os pólipos das glândulas fúndicas relacionados à terapia anti-secretora em nossos pacientes.

Phenotypic screening identifies a new oxazolone inhibitor of necroptosis and neuroinflammation.

Necroptosis is a regulated form of necrosis, which may be critical in the pathogenesis of neurodegenerative diseases. Neuroinflammation, characterized by the activation of glial cells such as microglia, is closely linked with neurodegenerative pathways and constitutes a major mechanism of neural damage and disease progression. Importantly, inhibition of necroptosis results in disease improvement, unveiling an alternative approach for therapeutic intervention. In the present study, we screened a small library of new molecules, potentially inhibitors of necroptosis, using two cellular models of necroptosis. A new oxazolone, Oxa12, reduced tumour necrosis factor α (TNF-α)-induced necroptosis in mouse L929 fibrosarcoma cells. Notably, Oxa12 strongly inhibited zVAD-fmk-induced necroptosis in murine BV2 microglial cells. Moreover, Oxa12 blocked phosphorylation of mixed-lineage kinase domain-like protein (MLKL), and interfered with necrosome complex formation, indicating that Oxa12 targets components upstream of MLKL. In fact, in silico molecular docking studies revealed that Oxa12 is occupying a region similar to the 1-aminoisoquinoline type II kinase inhibitor inside the receptor-interacting protein 1 (RIP1) kinase domain. Finally, in microglial cells, Oxa12 attenuated zVAD-fmk- and lipopolysaccharide (LPS)-induced inflammatory processes, as revealed by a marked decrease of TNF-α and/or IL-1ß expression. More specifically, Oxa12 negatively targeted c-Jun N-terminal kinase (JNK) and p38 mitogen-activated protein kinase (MAPK) pathways, as well as NF-κB activation. Overall, we identified a strong lead inhibitor of necroptosis that is also effective at reducing inflammation-associated events. Oxa12 is a promising candidate molecule for further development to target disease states dependent on RIP kinase activity.

GASTRIC FUNDIC GLAND POLYPS: CAN HISTOLOGY BE USEFUL TO PREDICT PROTON PUMP INHIBITORS USE?

BACKGROUND: Fundic gland polyps allegedly increased in frequency in recent decades, and had attracted great attention due to possible association with prolonged proton pump inhibitor therapy. Prolonged use of this drug could cause parietal cell hyperplasia, obstruction of glandular lumen and cystic dilation of the gland. OBJECTIVE: This study aims to analyze clinical and pathological features of fundic gland polyps in patients with and without proton pump inhibitor therapy in a selected population from Brazil. METHODS: It was selected a sample of 101 Brazilian patients (78 females and 23 males), from a five years retrospective search of the files from a private pathology laboratory. The patients had an average age of 57 years and we included patients with a histological diagnosis of fundic gland polyp. The clinical data were obtained from their files and all histological slides were reviewed and examined with hematoxylin and eosin (HE) and Giemsa. RESULTS: Information about the use or non-use of proton pump inhibitors (PPI) was obtained in 84 patient files. In 17 cases we could not determine if PPI were used or not. Among those in which the information was available, a positive history of anti-acid therapy was observed in 63 (75.0%) patients. Parietal cell hypertrophy/hyperplasia and parietal cell protrusions were detected in most slides. Histological findings were identical in PPI users and PPI negative patients. Helicobacter pylori infection was detected in just two samples. Epithelial dysplasia or adenocarcinoma were not observed in our cases. Histopathological analysis of fundic gland polyps could not distinguish between PPI and non-PPI related cases. Parietal cell cytoplasmic protrusions, an alleged marker of prolonged acid suppression therapy, was detected in both groups. CONCLUSION: Histological features could not discriminate anti-acid therapy related fundic glands polyps in our patients.

ADVANCED LIVER INJURY IN PATIENTS WITH CHRONIC HEPATITIS B AND VIRAL LOAD BELOW 2,000 IU/mL.

INTRODUCTION:: According to the guidelines, the viral load of 2,000 IU/mL is considered the level to differentiate between inactive carriers and HBeAg(-) chronic hepatitis B patients. Even so, liver damage may be present in patients with lower viral load levels, mainly related to regional variations. This study aims to verify the presence of liver injury in patients with viral load below 2,000 IU/mL. METHODS:: Patients presenting HBsAg(+) for more than six months, Anti-HBe(+)/HBeAg(-), viral load below 2,000 IU/mL and serum ALT levels less than twice the upper limit of normality underwent liver biopsy. Clinical and laboratory characteristics were evaluated in relation to the degree of histologic alteration. Liver injury was considered advanced when F ≥ 2 and/or A ≥ 2 by the METAVIR classification. RESULTS:: 11/27 (40.7%) patients had advanced liver injury, with a mean viral load of 701.0 (± 653.7) IU/mL versus 482.8 (± 580.0) IU/mL in patients with mild injury. The comparison between the mean values of the two groups did not find a statistical difference (p = 0.37). The average of serum aminotransferases was not able to differentiate light liver injury from advanced injury. CONCLUSIONS:: In this study, one evaluation of viral load did not exclude the presence of advanced liver damage. Pathologic assessment is an important tool to diagnose advanced liver damage and should be performed in patients with a low viral load to indicate early antiviral treatment.

Targeting KRAS Oncogene in Colon Cancer Cells with 7-Carboxylate Indolo[3,2-b]quinoline Tri-Alkylamine Derivatives.

BACKGROUND: A guanine-rich strand within the promoter of the KRAS gene can fold into an intra-molecular G-quadruplex structure (G4), which has an important role in the regulation of KRAS transcription. We have previously identified indolo[3,2-b]quinolines with a 7-carboxylate group and three alkylamine side chains (IQ3A) as effective G4 stabilizers and promising selective anticancer leads. Herein we investigated the anticancer mechanism of action of these compounds, which we hypothesized due to stabilization of the G4 sequence in the KRAS promoter and subsequent down-regulation of gene expression. METHODOLOGY/PRINCIPAL FINDINGS: IQ3A compounds showed greater stabilization of G4 compared to duplex DNA structures and reduced KRAS promoter activity in a dual luciferase reporter assay. Moreover, IQ3A compounds showed high anti-proliferative activity in HCT116 and SW620 colon cancer cells (IC50 < 2.69 µM), without eliciting cell death in non-malignant HEK293T human embryonic kidney, and human colon fibroblasts CCD18co. IQ3A compounds significantly reduced KRAS mRNA and protein steady-state levels at IC50 concentrations, and increased p53 protein steady-state levels and cell death by apoptosis in HCT116 cells (mut KRAS, wt p53). Furthermore, KRAS silencing in HCT116 p53 wild-type (p53(+/+)) and null (p53(-/-)) isogenic cell lines induced a higher level of cell death, and a higher IQ3A-induced cell death in HCT116 p53(+/+) compared to HCT116 p53(-/-). CONCLUSIONS: Herein we provide evidence that G4 ligands such as IQ3A compounds can target G4 motifs present in KRAS promoter, down-regulate the expression of the mutant KRAS gene through inhibition of transcription and translation, and induce cell death by apoptosis in colon cancer cell lines. Thus, targeting KRAS at the genomic level with G4 ligands may be a new anticancer therapy strategy for colon cancer.

KRAS oncogene repression in colon cancer cell lines by G-quadruplex binding indolo[3,2-c]quinolines.

KRAS is one of the most frequently mutated oncogenes in human cancer, yet remaining undruggable. To explore a new therapeutic strategy, a library of 5-methyl-indolo[3,2-c]quinoline derivatives (IQc) with a range of alkyldiamine side chains was designed to target DNA and RNA G-quadruplexes (G4) in the promoter and 5'-UTR mRNA of the KRAS gene. Biophysical experiments showed that di-substituted IQc compounds are potent and selective KRAS G4 stabilizers. They preferentially inhibit the proliferation of KRAS mutant cancer cell lines (0.22 < IC50 < 4.80 µM), down-regulate KRAS promoter activity in a luciferase reporter assay, and reduce both KRAS mRNA and p21(KRAS) steady-state levels in mutant KRAS colon cancer cell lines. Additionally, IQcs induce cancer cell death by apoptosis, explained in part by their capacity to repress KRAS expression. Overall, the results suggest that targeting mutant KRAS at the gene level with G4 binding small molecules is a promising anticancer strategy.

[Endocervical schistosomiasis: case report]. / Esquistossomose endocervical: relato de caso.

Schistosomiasis mansoni is found in different endemic areas of Brazil. It is a serious public health problem in Brazil and worldwide. Ectopic forms of the disease may affect the female reproductive system, representing a rare type of Schistosoma mansoni infection. A 26-year-old patient complained of vaginal discharge, dyspareunia and pain on palpation of the hypogastrium. Gynecological examination revealed an endocervical polyp. A biopsy was performed. Under microscopy, several granulomas surrounding degenerate and viable eggs of Schistosoma mansoni were seen. Treated with praziquantel, she was asymptomatic after four weeks of treatment. Vaginal discharge and dyspareunia may be secondary causes of cervicitis caused by Schistosoma mansoni. The search for eggs in routine vaginal smear or histological examination should be part of the gynecologic evaluation of patients from endemic areas, with the purpose of tracking ectopic schistosomiasis of the female genital tract.

Esquistossomose endocervical: relato de caso / Endocervical schistosomiasis: case report

A esquistossomose mansoni, endemia encontrada em diferentes áreas do território brasileiro, constitui um grave problema de saúde pública no Brasil e no mundo. Formas ectópicas da doença podem acometer o sistema reprodutor feminino, constituindo um tipo raro de infecção pelo S. mansoni. Paciente com 26 anos queixava-se de corrimento vaginal, dispareunia e dor à palpação do hipogástrio. No exame ginecológico foi observado pólipo endocervical, que foi biopsiado. O exame histológico evidenciou vários granulomas envolvendo ovos degenerados e viáveis de Schistosoma mansoni. Tratada com praziquantel, retornou assintomática após quatro semanas do tratamento. Corrimento vaginal e dispareunia podem ser causas secundárias de cervicite por Schistosoma mansoni. Pesquisa de ovos em esfregaço vaginal de rotina ou exame histológico devem fazer parte da avaliação ginecológica de pacientes de área endêmica, com o objetivo de rastrear forma ectópica da esquistossomose do trato genital feminino.

Schistosomiasis mansoni is found in different endemic areas of Brazil. It is a serious public health problem in Brazil and worldwide. Ectopic forms of the disease may affect the female reproductive system, representing a rare type of Schistosoma mansoni infection. A 26-year-old patient complained of vaginal discharge, dyspareunia and pain on palpation of the hypogastrium. Gynecological examination revealed an endocervical polyp. A biopsy was performed. Under microscopy, several granulomas surrounding degenerate and viable eggs of Schistosoma mansoni were seen. Treated with praziquantel, she was asymptomatic after four weeks of treatment. Vaginal discharge and dyspareunia may be secondary causes of cervicitis caused by Schistosoma mansoni. The search for eggs in routine vaginal smear or histological examination should be part of the gynecologic evaluation of patients from endemic areas, with the purpose of tracking ectopic schistosomiasis of the female genital tract.

Biomonitoreo de la contaminación atmosférica en La Habana durante la campaña 2004-2005 / Biomonitoring of the atmospheric pollution in Havana during 2004-2005 survey

RESUMEN Para evaluar la calidad del aire en La Habana se utilizó como bioindicador una especie de liquen epífi to (physcia alba sp.) que crece sobre Palma real (Roystonea regia). Se colectó un total de 225 muestras de líquenes en 181 sitios seleccionados de acuerdo con las condiciones de contaminación por tráfi co y actividades industriales. Se determinaron las concentraciones de 15 elementos (Na, Mg, Al, Ca, V, Cr, Mn, Fe, Co, Ni, Cu, Zn, Sr, Cd and Pb), empleando espectrofotometría de absorción atómica, fluorescencia de rayos X por refl exión total y voltametría de redisolución anódica. Se aplicaron métodos estadísticos (componentes principales) a los resultados analíticos y se obtuvieron y seleccionaron varios factores. Por último se presentan mapas con los perfiles de distribución elementales y de factores y su posible correlación con distintas fuentes de contaminación.

ABSTRACT An epiphytic lichen (physcia alba sp.) grown over Royal Palm (Roystonea regia) tree was used as bioindicator of air quality in Havana City. A total of 225 lichen samples were collected in 181 selected sites according to traffic and industrial conditions. The concentrations of 15 elements (Na, Mg, Al, Ca, V, Cr, Mn, Fe, Co, Ni, Cu, Zn, Sr, Cd and Pb) were determined by Atomic Absorption Spectrophotometry, Total Reflection X-Ray Fluorescence and Anodic Stripping Voltammetry. Principal Component Analysis was applied to analytical results and some factors were obtained. Finally, maps with lichen elemental contents and factors’ patterns are presented. Several possible pollution sources were identified.

Polymyositis associated with nephrotic syndrome.

Polymyositis (PM) is a systemic disease of the idiopathic inflammatory myopathy group, clinically characterized by symmetric and proximal muscle weakness. There are reports in literature of PM associated with malignancies, autoimmune diseases, and viral infections. However, the association between PM and nephropathy is not common. We describe a case report of a patient with polymyositis who developed nephrotic syndrome due to mesangial glomerulonephritis.

Polimiosite associada à síndrome nefrótica / Polymyositis associated with nephrotic syndrome

A polimiosite (PM) é uma doença sistêmica do grupo das miopatias inflamatórias idiopáticas, clinicamente caracterizada por fraqueza muscular proximal e simétrica. Há relatos na literatura de PM associada a neoplasias, doenças autoimunes e infecções virais. Entretanto, a associação entre PM e nefropatia não é frequente. Descrevemos o caso de um paciente com polimiosite que evoluiu com síndrome nefrótica devido à presença de glomerulonefrite mesangial.

Polymyositis (PM) is a systemic disease of the idiopathic inflammatory myopathy group, clinically characterized by symmetric and proximal muscle weakness. There are reports in literature of PM associated with malignancies, autoimmune diseases, and viral infections. However, the association between PM and nephropathy is not common. We describe a case report of a patient with polymyositis who developed nephrotic syndrome due to mesangial glomerulonephritis.

Uso do tamoxifeno no tratamento de quelóides e cicatrizes hipertróficas / Tamoxifen as treatment to keloids and hypertrophic scars

Introdução: Existe pouco entendimento a respeito dos mecanismos que levam à formação dos quelóides e cicatrizes hipertróficas (CHT), assim como não há um tratamento padrão-ouro para essas lesões. Experiências recentes demonstraram que as alterações na formação dessas cicatrizes envolvem concentrações desequilibradas de fatores de crescimento locais, em particular o fator de crescimento transformador (TGF) β1. O tamoxifeno, ao inibir a produção desta citocina, pode ser uma nova opção na conduta terapêutica destas lesões. Método: Dezoito pacientes portadores de quelóides e CHT foram selecionados para a avaliação do uso do citrato de tamoxifeno 0,1% por um período de seis meses. Durante essa evolução, foi realizado registro fotográfico, mensuração e análise histopatológica das lesões e questionários relativos a aspectos da lesão foram aplicados aos pacientes. Resultados: Houve redução significativa da altura(p < 0,0001), da largura (p = 0,009) e do comprimento (p = 0,009) das lesões. Os critérios de textura, altura e prurido foram os que obtiveram as maiores variações entre os períodos pré e pós-tratamento. As alterações histológicas sugerem uma ação de remodelamento do colágeno nessas cicatrizes. Conclusões: O citrato de tamoxifeno apresentou uma resposta favorável na maioria dos critérios analisados, mínimos efeitos colaterais e baixo custo, constituindo uma opção de tratamento segura e cômoda, principalmente nas CHT. São necessários novos estudos com maior amostragem para obtenção de conclusões mais abrangentes.

Background: Keloids and hypertrophic scars (HScs) are poorly understood cicatricial lesions without a gold-standard treatment. Recent experiments demonstrated that cytokines imbalance has an action in scar pathogenesis, mainly due to transforming growth factor (TGF) β1 over expression. Tamoxifen, an antioestrogenic drug, can inhibit TGF-β1 release and consequently fibroblastic proliferation. This indicates a possible role of Tamoxifen as a therapeutic option in keloids and HScs. Method: Eighteen patients were selected for the evaluation of tamoxifen citrate 0.1% for six months. During that evolution, photographic registration, dimensional evaluation and hystopathologic analisis of the lesions were accomplished and questionnaires about aspects of the lesion were applied to patients. Results: There was a significant reduction of the lesion height (p < 0.0001), width (p = 0.009) and length (p = 0.009). Texture criteria, height and itch were the ones that obtained the largest variations among the periods before and after treatment. Histological changes suggested remodelling action of the collagen in those scars. Conclusions: Tamoxifen citrate presented positive results in most of the analyzed criteria, minima side effects and low cost, constituting a safe and comfortable treatment option, mainlyin HScs. There will be necessary more research with larger sampling for greater conclusions.

É o exame anatomopatológico de rotina indispensável em cirurgias orificiais / Is the histopathologic examination essential in orificial sugeries

Introdução: O exame anatomopatológico é feito rotineiramente em cirurgias orificiais e é importante para diagnosticar doenças anais concomitantes, lesões malignas e doenças sexualmente transmissíveis não previstas anteriormente no exame clínico. O gasto com estes exames é bastante significativo para o serviço público o que evidencia a necessidade de avaliar o custo/benefício da sua utilização rotineira. Objetivos: Avaliar o tempo decorrido entre a entrega do material e a emissão do laudo, o nível de concordância entre a impressão diagnóstica e a conclusão do anatomopatológico, a importância clínica das patologias diagnosticadas secundariamente, o custo de realização dos exames e a relação custo/benefício dos mesmos. Metodologia: Estudo descritivo e retrospectivo de 173 exames anatomopatológicos de pacientes do Hospital Universitário de Aracaju realizados de 2005 a 2007, que foram submetidos à cirurgias orificiais. Resultados: O nível de concordância entre a impressão diagnóstica e a conclusão do anatomopatológico foi elevada e, dos laudos discordantes, poucos apresentaram relevância clínica, havendo somente um caso de neoplasia anorretal. Houve um atraso significativo na emissão dos laudos, sugerindo sobrecarga do serviço e o custo/benefício para realização dos exames foi desfavorável. Conclusão: Sugerimos triagem para um uso racional e criterioso do exame anatomopatológico em cirurgias orificiais baseada na história clínica e fatores de risco do paciente.

Introduction: The histopathologic examination is repeatedly done in orificial surgeries and it's important to diagnose anal diseases associated, malign lesions and sexually transmitted diseases that weren't previously predicted on the clinic examination. The cost of the histopathologic examinations is very significant to the public health service, which shows the need to do a cost-benefit analysis of their routine use. Objectives: Evaluate the time between the surgical specimen's delivery and the emission of the histopathologic examination's report, the concordance level between the clinic impression and the histopathologic examination's report, the clinical relevance of the diseases secondarily diagnosed, the cost of the histopathologic examinations and the cost-benefit analysis of them. Methods: Descriptive and retrospective study of 173 histopathologic examinations from patients of the Hospital Universitário de Aracaju made from 2005 to 2007, that were submitted to orificial surgeries. Results: High concordance level between the clinic impression and the histopathologic examination's report; from the discordants reports, a few had clinical relevance and was only one case of anal cancer. There was a significant delay on the reports' emission, which suggests that the pathology service is overloaded; and the cost-benefit analysis was unfavorable. Conclusions: We suggest screening to a rational and judicious use of the histopathologic examination in orificial surgeries based on the patient's clinical history and risk factors.