Two Novel Nanosized Radiolabeled Analogues of Somatostatin for Neuroendocrine Tumor Imaging.

The somatostatin receptors (SR), which are overexpressed in a majority of neuroendocrine tumors, are targets for radiopeptide-based imaging using for example the 99mTc-Tyr3-Octreotide peptide. Dendrimers are hyperbranched polymeric structures. The nanoscopic size and near-monodisperse nature properties give polyamidoamine (PAMAM) dendrimers an edge over linear polymers in the context of drug delivery. Gold nanoparticles (AuNPs) conjugated to peptides produces stable multimeric systems with target-specific molecular recognition. The aim of this research was to prepare two nanosized multimeric systems for neuroendocrine tumor imaging, 99mTc-PAMAM-Tyr3-Octreotide and 99mTc-AuNP-Tyr-Octreotide, and to compare their in vitro uptake in SR-positive AR42J cancer cells as well as their biodistribution profile in athymic mice bearing AR42J tumors. [Tyr3, Lys(Boc)5]-Octreotide was conjugated to the carboxylate groups of the PAMAM dendrimer (G3.5) with further Boc deprotection using TFA. 99mTc labeling was carried out by a direct method. 99mTc-Tyr3-Octreotide was conjugated to AuNPs (20 nm) by spontaneous reaction with the thiol group of cysteine. Radiochemical purity (RP) was determined by size-exclusion HPLC and ITLC-SG analyses. In vitro binding studies were carried out in AR42J cancer cells. Biodistribution studies were accomplished in athymic mice with AR42J-induced tumors with blocked and unblocked receptors. Elemental analysis demonstrated that 26 Tyr3-Octreotide molecules were successfully conjugated to one molecule of PAMAM. RP for both nanosized conjugates was > 94% and showed recognition for SR in AR42J cells. The tissue distribution of radioactivity 2 h after 99mTc-PAMAM-Tyr3-Octreotide administration in mice showed specific tumor uptake (4.12 ± 0.57% of injected dose/g) and high accumulation in the pancreas (15.08 ± 3.11% of injected dose/g) which expresses SR. No significant difference in the tumor uptake was found between 99mTc-PAMAM-Tyr3-Octreotide and 99mTc-AuNP-Tyr3-Octreotide. However, the dendrimer-peptide conjugate showed a significant renal excretion. Both radiopharmaceuticals demonstrated properties suitable for use as target-specific agents for molecular imaging of tumors that overexpressed SR.

Serology for hepatitis B and C, HIV and syphilis in the initial evaluation of diabetes patients referred for an external nephrology consultation.

INTRODUCTION: Information is available regarding the prevalence and incidence of positive microbiological serology results both in the general population and in patients on haemodialysis in Spain. Nevertheless, little information is known regarding patients with diabetes attended in external nephrology consultations. OBJECTIVE: To evaluate the percentage of patients with positive serology results for hepatitis B and C, Human Immunodeficiency Virus (HIV), and syphilis in the initial assessment of patients referred to diabetic nephropathy external consultations. PATIENTS AND METHOD: Retrospective study of 500 patients assessed over the course of 5 years with the diagnosis of diabetic nephropathy originating in external consultations and for which hepatitis B, C, HIV, and syphilis serology had been requested. RESULTS: With regard to hepatitis B virus, 0.4% of patients had chronic hepatitis B, 10.2% had overcome the hepatitis and were in recovery, and 4.2% had received the hepatitis B vaccine. As for hepatitis C, 2.4% of the patients studied had antibodies against hepatitis C. With regard to syphilis, 0.8% of patients had positive serological results. No patients had positive HIV serology results. CONCLUSIONS: Despite major methodological limitations, this would be the first study to evaluate the microbiological serology of diabetic nephropathy patients treated in external consultations.

Conhecimento sobre DST/AIDS, hepatites e conduta sexual de universitários de São José do Rio Preto, SP / Self-awareness in relation to STD/AIDS, hepatitis and sexual behavior of university students in São José do Rio Preto, SP

Introdução: apesar de se conhecer, atualmente, a dimensão da epidemia da aids, há um relativo desconhecimento sobre a doença entre universitários. Objetivo: levantar o nível de informação sobre as DST/aids, hepatites B e C, assim como analisar a conduta sexual de jovens universitários de um município do interior do estado de São Paulo e obter subsídios para nortear estratégias de prevenção em relação a essa população. Métodos: aplicação de questionário anônimo entre alunos de três Instituições Educacionais de Ensino Superior (IES) da cidade estudada, com metodologia baseada em um plano de amostragem probabilística estratificada e proporcional. Resultados: dos 888 questionários respondidos, 25 foram descartados em função de inconsistências no preenchimento; deste total, 75,3% são do sexo feminino e 77,8% têm até 24 anos de idade; predomina, entre esses alunos, a orientação heterossexual e 81% deles declararam já ter iniciado sua vida sexual; as principais doenças sexualmente transmissíveis são lembradas por mais de 90% da amostra e as hepatites B e C foram mencionadas por 70 a 89% dos pesquisados. Conclusão: encontrou-se um predomínio de mulheres na amostra de universitários pesquisada, sendo que a maioria desses estudantes apresentaram vida sexual ativa, demonstraram conhecimento adequado sobre os métodos contraceptivos, DST/aids, e fizeram referência ao uso do preservativo como a melhor forma de prevenção de DST/aids. Esses alunos iniciaram sua vida sexual com cerca de 17 anos, para os homens, e 18 anos, para as mulheres; e, embora 70% destes jovens tenham relatado uso de preservativo na primeira relação sexual, este número cai para 46,1% na prática atual.

Introduction: nowadays the dimension of the AIDS epidemy is well-known, but the prevention conducts among university students is a subject not widely studied. Objective: collect information about young university students concerning their level of awareness in relation to STD/AIDS, Hepatitis B and C. Methods: an anonymous questionnaire was filled in by students from three universities in the city observed. A methodology based on a plan of stratified-random probabilistic sampling was used. Results: Eight hundred and eighty-eight questionnaires were answered and 25 were excluded due to inconsistent answers; thetotal number, 75,3% are females and are 24 years old; there is a predominance among these students of heterosexuals, and 81% of them stated that they had already started their sexual life; the most important STDs were mentioned by more than 90% of the sampling, and hepatitis B and C were mentioned by 70 to 89% of the students. Conclusion: a predominance of women in the sampling of university students researched was found, most of these students have an active sexual life; they have adequate knowledge on contraceptive methods, STD/AIDS, and they also stated that condom is the best prevention method for STD/ AIDS; these students started their sexual life around 17 years old, in case of men, and 18 years old in case of women; although 70% of these young students said that they had used condom in their first sexual experience, these figures decreased to 46,1% when it was asked about their present conduct.

Mortalidad materna: Hospital Dr. Prince Lara 2001-2004 / Maternal mortality: Hospital Dr. Prince Lara 2001-2004

Conocer la incidencia de la mortalidad materna en nuestro hospital. Estudio descriptivo retrospectivo epidemiológico analítico de las muertes maternas sucedidas durante el período de 2001-2004. Se analizaron 11 historias de las cuales 6 fueron por causas directas y 2 indirectas y 3 muertes tardías con 11.753 nacidos vivos. Departamentos de Obstetricia y Ginecología, "Dr. Adolfo Prince Lara", Puerto Cabello, Estado Carabobo. La razón promedio de la mortalidad materna directa fue 51,05 por 100000. Las principales causas de muerte: toxemia, hemorragia y sepsis con 33,33 por ciento de las dos primeras y 16,66 por ciento la última. Predominaron procedentes del Estado Carabobo (83,33 por ciento). Antecedente familiar determinante la hipertensión (33,33 por ciento), personales no se reportaron, edad materna entre 20-34 años (50 por ciento); sin control prenatal (33,33 por ciento). Destacaron I gestas (50 por ciento), embarazos a término (83,33 por ciento). Todas las muertes ocurrieron poscesárea. La razón muestra cifras altas con moderadas oscilaciones, predominio de causas hemorrágicas y toxemias, lo que orienta hacia una eficiente actividad preventiva

PP1/PP2A phosphatases inhibitors okadaic acid and calyculin A block ERK5 activation by growth factors and oxidative stress.

Okadaic acid is an inhibitor of the protein Ser/Thr phosphatases PP1 and PP2A, which blocks the activation of extracellular signal-regulated protein kinase 5 (ERK5), a member of the MAP kinase family activated by growth factors and several types of stressors. The blocking of ERK5 activation by okadaic acid was observed in HeLa cells exposed to epidermal growth factor and H(2)O(2) as well as in PC12 cells stimulated by nerve growth factor and H(2)O(2). Calyculin A, another PP1 and PP2A inhibitor, behaved similarly although these compounds are not structurally related. This suggests that either PP1 or PP2A or both are necessary for ERK5 activation. Protein kinase C (PKC) acts as a negative regulator of the ERK5 activation pathway, however our data suggest that the effects of PKC and the phosphatase are unrelated.