ABSTRACT Objective: Abnormalities involving the TGFB1 gene and its receptors are common in several types of cancer and often related to tumor progression. We investigated the role of single nucleotide polymorphisms (SNP) in the susceptibility to cancer, their impact on its features, as well as the role of mRNA expression of these genes in thyroid malignancy. Materials and methods: We genotyped TGFB1, TGFBR1, and TGFBR2 SNPs in 157 papillary thyroid cancer (PTC) patients and 200 healthy controls. Further, we investigated RNA samples of 47 PTC and 80 benign nodules, searching for differential mRNA expression. Results: SNPs rs1800472 and rs1800469 were associated with characteristics of PTC aggressiveness. Effect predictor software analysis of nonsynonymous SNP rs1800472 indicated increasing protein stability and post-translational changes. TGFB1 mRNA expression was upregulated in PTC and downregulated in benign samples, differentiating malignant from benign nodules (p<0.0001); PTC from goiter (p<0.0001); and PTC from FA (p<0.0001). TGFBR1 mRNA expression was upregulated in goiter and PTC, but downregulated in FA, distinguishing PTC from goiter (p=0.0049); PTC from FA (p<0.0001); and goiter from FA (p=0.0267). On the other hand, TGFBR2 was downregulated in all histological types analyzed and was not able to differentiate thyroid nodules. Conclusion: TGFB1 polymorphism rs1800472 may confer greater activity to TGF-β1 in the tumor microenvironment, favoring PTC aggressiveness. Evaluation of TGFB1 and TGFBR1 mRNA levels may be useful to identify malignancy in thyroid nodules.

A contaminação ambiental por geohelmintos representa um problema mundial de saúde pública e tem sido bem documentada por diversos autores. No entanto, poucos trabalhos descrevem a presença de contaminação em solos salinos de praias litorâneas. Este estudo foi realizado nas praias do município de Santos no período entre maio de 2004 a abril de 2005 com o objetivo de determinar o grau de contaminação, e possíveis correlações entre sazonalidade e características ambientais. Das 2.520 amostras analisadas, 18,2% (458) estavam contaminadas, 32,3% (148) das quais foram localizadas em areas de lazer das crianças(playgrounds). O perfil parasitário encontrado nas amostras analisadas indicaram a presença de vários parasitos com potencial zoonótico: larvas de Ancylostoma (82,5%), ovos de Toxocara sp (59,4%), ovos semelhantes aos de Ancilostomídeos (37,1%), oocistos de coccídeos (13,5%), ovos de Trichostrongylus sp., ovos de Ascaris lumbricoides, (11,6%), cistos de Entamoeba sp. (10,0%), Strongyloides sp. (4,8%), vários nematóides de vida livre e algumas estruturas parasitárias não identificadas que podem corresponder a um parasita (3,3%). Foi estabelecido que a maior frequência de estruturas parasitárias ocorreu nos meses entre maio e outubro de 2004, e de fevereiro a março de 2005. Um aumento na diversidade de formas parasitárias foi documentado nos meses entre fevereiro a dezembro de 2004 e de janeiro a abril de 2005, esses períodos com a maior pluviosidade.

The environmental contamination by geohelminths represents a world public health problem and has been well documented by several authors. However, few papers describe the presence of such contamination in saline soils of coastal beaches. A study was performed on the beaches of the municipality of Santos in the period between May 2004 to April 2005 with the aim of determining the degree of contamination, and the correlation between contamination level and seasonal conditions and characteristics of the environment. Of the 2,520 samples analyzed, 18.2% (458) were contaminated, 32.3% (148) of which were localized in children's recreational areas (playgrounds). The parasite profile found in the analyzed samples indicated the presence of several zoonotic parasites: Ancylostoma larvae (82.5%), Toxocara sp. eggs (59.4%), Ancylostomidae-like eggs (37.1%), coccid oocysts (13.5%), Trichostrongylus sp. eggs and larvae, Ascaris lumbricoides eggs, (11.6%), Entamoeba sp. cysts (10.0%), Strongyloides sp. (4.8%), several free nematoids and some non-identified parasitic structures (3.3%). It was established that the highest frequency of parasitic structures occurred in the months between May and October 2004, and from February to March 2005. An increase in the diversity of parasitic forms was documented in the months between February to December 2004 and from January to April 2005, these periods having the highest rainfall.

Recently, we described the improved immunogenicity of new malaria vaccine candidates based on the expression of fusion proteins containing immunodominant epitopes of merozoites and Salmonella enterica serovar Typhimurium flagellin (FliC) protein as an innate immune agonist. Here, we tested whether a similar strategy, based on an immunodominant B-cell epitope from malaria sporozoites, could also generate immunogenic fusion polypeptides. A recombinant His6-tagged FliC protein containing the C-terminal repeat regions of the VK210 variant of Plasmodium vivax circumsporozoite (CS) protein was constructed. This recombinant protein was successfully expressed in Escherichia coli as soluble protein and was purified by affinity to Ni-agarose beads followed by ion exchange chromatography. A monoclonal antibody specific for the CS protein of P. vivax sporozoites (VK210) was able to recognise the purified protein. C57BL/6 mice subcutaneously immunised with the recombinant fusion protein in the absence of any conventional adjuvant developed protein-specific systemic antibody responses. However, in mice genetically deficient in expression of TLR5, this immune response was extremely low. These results extend our previous observations concerning the immunogenicity of these recombinant fusion proteins and provide evidence that the main mechanism responsible for this immune activation involves interactions with TLR5, which has not previously been demonstrated for any recombinant FliC fusion protein.

Acanthamoeba and Naegleria species are free-living amoebae (FLA) found in a large variety of natural habitats. The prevalence of such amoebae was determined from dust samples taken from public non-hospital internal environments with good standards of cleanliness from two campuses of the same University in the city of Santos (SP), Brazil, and where young and apparently healthy people circulate. The frequency of free-living amoebae in both campuseswas 39% and 17% respectively, with predominance of the genus Acanthamoeba. On the campus with a much larger number of circulating individuals, the observed frequency of free-living amoebae was 2.29 times larger (P< 0.00005). Two trophozoite forms of Naegleria fowleri, are the only species of this genus known to cause primary amoebian meningoencephalitis, a rare and non-opportunistic infection. We assume that the high frequency of these organisms in different internal locations represents some kind of public health risk.

JUSTIFICATIVA E OBJETIVOS: A sedação de dependentes de álcool e drogas em Unidades de Terapia Intensiva (UTI) é um desafio pela elevada incidência de tolerância às drogas sedativas e da elevada freqüência de síndromes de abstinência. O objetivo deste relato é mostrar um caso de paciente jovem admitido na UTI que desenvolveu síndrome de abstinência alcoólica e tolerância às drogas sedativas, solucionadas somente após o uso de clonidina. RELATO DO CASO: Paciente do sexo masculino, 18 anos, dependente de álcool, tabaco, cocaína e maconha, vítima de acidente por arma de fogo, foi admitido na UTI no 1º dia de pós-operatório de enterectomia, após aspiração de conteúdo gástrico durante reintubação traqueal. Evolução clínica: drogas vasoativas até o 4º dia de internação e broncopneumonia bilateral com derrame pleural e necessidade de ventilação artificial até o 15º dia. O esquema de sedação inicial utilizado foi a associação de midazolam e fentanil. A partir do 4º dia, o paciente apresentou vários episódios de agitação psicomotora, mesmo com a associação de lorazepam no 6° dia. No 9° dia, o paciente recebeu as maiores doses dos fármacos, mas permanecia agitado. Optou-se pela associação de dexmedetomidina, que reduziu as doses das outras drogas em 35% e diminuiu a agitação. No 12° dia, o midazolam e a dexmedetomidina foram substituídos pela infusão de propofol, com piora do quadro. No 13° dia, foi associada clonidina ao esquema de sedação, com resolução do quadro de agitação. No 14° dia, o propofol foi suspenso, sendo mantida a infusão de fentanil e reintroduzida a infusão de midazolam, com doses respectivamente 75% e 65% menores em relação ao pico de uso destas drogas. No 15° dia, o paciente foi extubado e teve alta da UTI. CONCLUSÕES: A droga de escolha para o tratamento da síndrome de abstinência alcoólica é o benzodiazepínico. Entretanto, no presente relato, somente o uso adjuvante de clonidina conseguiu proporcionar tratamento adequado ao paciente.

BACKGROUND AND OBJECTIVES: Sedation of patients with past history of alcohol and drug abuse in Intensive Care Units (ICU) is a challenge due to the high incidence of sedative drugs tolerance and withdrawal syndromes. This report aimed at describing a case of a young patient admitted to the ICU who developed alcohol withdrawal syndrome and tolerance to sedatives, resolved only after clonidine administration. CASE REPORT: Male patient, 18 years old, alcohol, tobacco, cocaine and marijuana abuser, victim of firearm accident, who was admitted to the ICU in the first post-enterectomy day, after gastric content aspiration during tracheal re-intubation. Clinical evolution was: vasoactive drugs up to the 4th day; bilateral bronchopneumonia with pleural effusion and need for artificial ventilation up to the 15th day. Initial sedation scheme was the association of midazolam and fentanyl. As from the 4th day, patient presented with several psychomotor agitation episodes, even after the association of lorazepam in the 6th day. In the 9th day, patient received the largest doses but remained agitated. Dexmedetomidine was associated, which has decreased other drug doses in 35% and has improved agitation. In the 12th day, midazolam and dexmedetomidine were replaced by propofol infusion with worsening of agitation. In the 13th day, clonidine was associated to the sedation scheme with total resolution of agitation. Propofol was withdrawn in the 14th day, fentanyl was maintained and midazolam infusion was restarted, with doses 75% and 65% lower as compared to peak doses of such drugs. Patient was extubated in the 15th day and was discharged from ICU. CONCLUSIONS: Benzodiazepines should remain the drugs of choice for the treatment of acute alcohol withdrawal syndrome. However in this report, only adjuvant clonidine was able to adequately treat the patient.

JUSTIFICATIVA Y OBJETIVOS: La sedación de dependientes de alcohol y drogas en Unidades de Terapia Intensiva (UTI) es un desafío por la elevada incidencia de tolerancia a las drogas sedativas y de la elevada frecuencia de síndromes de abstinencia. El objetivo de este relato es mostrar un caso de un paciente joven admitido en la UTI que desarrolló síndrome de abstinencia alcohólica y tolerancia a las drogas sedativas, solucionadas solamente después del uso de clonidina. RELATO DEL CASO: Paciente del sexo masculino, 18 años, dependiente de alcohol, tabaco, cocaína y mariguana, víctima de accidente por arma de fuego, fue admitido en la UTI en el 1º día de post-operatorio de enterectomía, después de aspiración de contenido gástrico durante reintubación traqueal. Evolución clínica: drogas vasoactivas hasta el 4º día de internación y broncopneumonia bilateral con derrame pleural y necesidad de ventilación artificial hasta el 15º día. El esquema de sedación inicial utilizado fue la asociación de midazolan y fentanil. A partir del 4º día, el paciente presentó varios episodios de agitación psicomotora, mismo con la asociación de loracepam en el 6° día. En el 9° día, el paciente recibió las mayores dosis de los fármacos, más permanecía agitado. Se optó por la asociación de dexmedetomidina, que redujo las dosis de las otras drogas en 35% y diminuyó la agitación. En el 12° día, el midazolan y la dexmedetomidina fueron substituidos por la infusión de propofol, con empeoramiento del cuadro. En el 13° día, fue asociada clonidina al esquema de sedación, con resolución del cuadro de agitación. En el 14° día, el propofol fue suspenso, siendo mantenida la infusión de fentanil y reintroducida la infusión de midazolan, con dosis respectivamente 75% y 65% menores en relación al pico de uso de estas drogas. En el 15° día, el paciente fue extubado y tuvo alta de la UTI. CONCLUSIONES: La droga escogida para el tratamiento del síndrome de abstinencia alcohólico es el benzodiazepínico. No obstante, en el presente relato, solamente el uso coadyuvante de clonidina consiguió proporcionar tratamiento adecuado al paciente.