Is cell salvage cost-effective in posterior arthrodesis for adolescent idiopathic scoliosis in the public health system?

BACKGROUND: To evaluate the efficacy and cost-effectiveness of cell salvage (CS) in reducing allogeneic transfusion in patients undergoing surgery for idiopathic scoliosis. METHODS: A case-control study with 42 patients with adolescent idiopathic scoliosis (AIS), submitted to posterior arthrodesis with instrumentation from 8/2008 to 12/2014 at the General Hospital of Fortaleza, Brazil. CS was used in 27 patients and not used in 15. The data was processed using the SPSS 20.0. The confidence level was 0.05. RESULTS: There were no significant differences between the groups for the variables of age, sex, preoperative weight, postoperative blood drainage, and surgical time. There was a significant reduction in the intra-operative allogeneic transfusion in the case group compared to the control; there was no significant difference in the postoperative period. Adding the two periods together there was a significant difference with less allogeneic red blood cells (RBC) transfused in the CS group. The total cost of allogeneic RBC between the intra and postoperative groups was higher in the control group (P=0.01). Due to this difference ($350.00-$136.93) the cost was $213.07. The net savings were $213.07. Multiplying this by the 27 subjects, allogeneic RBC transfusion led to a cost reduction of $5,752.89 for the State. CONCLUSIONS: The CS was effective in reducing allogeneic transfusion during surgery and in the total period that AIS patients underwent surgery it was also cost-effective.

Indicadores de sa?de bucal da aten??o b?sica: a compreens?o e a informa??o registrada pelos cirurgi?es-dentistas / Oral health indicators in primary health care: the understanding andthe information recorded by dentist-surgeons

Objective: This study aimed to know the understanding of Oral health indicators recommended by the Ministry of Health by dentists in the family health strategy of the state of Cear? in 2008. Methods: It is a descriptive, cross-sectional study in which it was used a questionnaire to obtain the data concerning the way information on oral health actions performed in Family Health Care Units and other social spaces are registered, as well as investigate their knowledge about oral health indicators. The calculation of the sample of dentist-surgeons adopted an absolute sampling error of 6.8% and a significance level of 5%, resulting in an initial sample of 175 dentists; however, only 159 participated in this study according to the inclusion criteria. For instance, they should have been working in the service in the period from 2001 to 2007. In all, 32 cities participated in the research, distributed in 18 Regional Health Cells selected by drawing lots. The data were processed in the program SPSS version 17.0 and considered statistically significant the inferential analyses with p < 0.05.Results: it was observed that there are differences between the interpretation of the indicators objectives and the data relating to oral health actions recorded by dentist-surgeons from the Family Health Strategy. They also differ from the guidelines of the Ministry of Health.Conclusion: The pregnant present some knowledge about oral health that can be improved by means of educational, preventive and healing programs. This group exert big it influences in the family ambit, could act as agents multipliers and avoiding the child's precocious contamination.

Objetivo: Conhecer o entendimento e informa??es fornecidas pelos cirurgi?es-dentistas atuantes na Estrat?gia Sa?de da Fam?lia do Estado do Cear? no ano de 2008 acerca dos indicadores de Sa?de Bucal preconizados pelo Minist?rio da Sa?de. M?todos: Para isso, utilizou-se um instrumento (question?rio) que foi aplicado aos cirurgi?es-dentistas atuantes na Estrat?gia Sa?de da Fam?lia do Estado, onde se indagou a respeito do conhecimento deles sobre os indicadores de Sa?de Bucal e como costumavam informar as a??es de Sa?de Bucal que realizavam diariamente nas Unidades B?sicas de Sa?de da Fam?lia e nos demais espa?os sociais em que atuavam. Resultados: Observou-se que h? diverg?ncias entre a interpreta??o dos objetivos dos indicadores e o registro dos dados relativos ?s a??es de Sa?de Bucal pelos cirurgi?es-dentistas atuantes na Estrat?gia Sa?de da Fam?lia. Conclus?o: H? a necessidade de serem implementadas medidas de capacita??o permanente para esclarecer aspectos relacionados aos indicadores deSa?de Bucal.

Heparin modulates the endopeptidase activity of Leishmania mexicana cysteine protease cathepsin L-Like rCPB2.8.

BACKGROUND: Cysteine protease B is considered crucial for the survival and infectivity of the Leishmania in its human host. Several microorganism pathogens bind to the heparin-like glycosaminoglycans chains of proteoglycans at host-cell surface to promote their attachment and internalization. Here, we have investigated the influence of heparin upon Leishmania mexicana cysteine protease rCPB2.8 activity. METHODOLOGY/PRINCIPAL FINDINGS: THE DATA ANALYSIS REVEALED THAT THE PRESENCE OF HEPARIN AFFECTS ALL STEPS OF THE ENZYME REACTION: (i) it decreases 3.5-fold the k 1 and 4.0-fold the k -1, (ii) it affects the acyl-enzyme accumulation with pronounced decrease in k 2 (2.7-fold), and also decrease in k 3 (3.5-fold). The large values of ΔG  =  12 kJ/mol for the association and dissociation steps indicate substantial structural strains linked to the formation/dissociation of the ES complex in the presence of heparin, which underscore a conformational change that prevents the diffusion of substrate in the rCPB2.8 active site. Binding to heparin also significantly decreases the α-helix content of the rCPB2.8 and perturbs the intrinsic fluorescence emission of the enzyme. The data strongly suggest that heparin is altering the ionization of catalytic (Cys(25))-S(-)/(His(163))-Im(+) H ion pair of the rCPB2.8. Moreover, the interaction of heparin with the N-terminal pro-region of rCPB2.8 significantly decreased its inhibitory activity against the mature enzyme. CONCLUSIONS/SIGNIFICANCE: Taken together, depending on their concentration, heparin-like glycosaminoglycans can either stimulate or antagonize the activity of cysteine protease B enzymes during parasite infection, suggesting that this glycoconjugate can anchor parasite cysteine protease at host cell surface.

The maternal self-efficacy scale for preventing early childhood diarrhea: validity and reliability.

OBJECTIVE: This study aimed to develop and validate a psychometric scale for preventing early childhood diarrhea in endemic areas. DESIGN AND SAMPLE: Before applying to the field, the scale was subjected to content validity by a panel of experts and piloting. The final version was applied to 448 mothers of children 0- to 5-year-olds, living in Fortaleza, northeast Brazil. Structured interviews were conducted to identify diarrheal episodes in the study children. RESULTS: Significant negative correlations were found between higher maternal self-efficacy scores and previous childhood diarrhea (p = .001). In addition, positive correlations were found with maternal age (p = .018). The frequency of children (6-36 months old) with diarrhea was significantly lower when scale scores were higher (p = .015). The predictive validity revealed that high levels of maternal self-efficacy were a protective factor against childhood diarrhea. Cronbachs alpha was .84. CONCLUSIONS: The scale was found reliable. Cultural adjustments may be needed to extrapolate the scale to other endemic areas worldwide.

Prevalence of soft tissue oral lesion in elderly and its relations with deleterious habits.

INTRODUCTION: With ageing, the oral mucosa becomes more susceptible to external stimuli. OBJECTIVE: To investigate the prevalence of soft tissue oral lesion in elderly and its relations with deleterious habits. MATERIALS AND METHODS: It was a quantitative research conducted at the dental clinic of UNIFOR, Fortaleza-CE, in the period from 1998 to 2006. The sample consisted of all 756 records of the elderly, and the data were processed by SPSS 15.0 (SPSS, Inc., Chicago, IL, USA). RESULTS: The majority (63.0) were women, age 60-92, mean age 67 ± 6. The most significant proportions were married (48.4%), retired (42.3%) and incomplete primary school (31.5%). It was found a prevalence of 18.3% of oral lesions, with the risk being 1.6 times higher (p = 0.030) among youngest (up to 65 years) and 1.7 times higher among smokers (p = 0.048). Although this risk is 1.6 times higher among those who drank alcohol, it was not statistically significant (p = 0.122). CONCLUSION: The elderly showed a high prevalence of oral lesion, being the youngest, the smokers and the alcohol consumers those most vulnerable to the emergence of these diseases. Dental services need to implement programs of elderly care and health education, essential to clarify the risks and their associations with oral diseases, aiming to promote health.

Mechanism of heparin acceleration of tissue inhibitor of metalloproteases-1 (TIMP-1) degradation by the human neutrophil elastase.

Heparin has been shown to regulate human neutrophil elastase (HNE) activity. We have assessed the regulatory effect of heparin on Tissue Inhibitor of Metalloproteases-1 [TIMP-1] hydrolysis by HNE employing the recombinant form of TIMP-1 and correlated FRET-peptides comprising the TIMP-1 cleavage site. Heparin accelerates 2.5-fold TIMP-1 hydrolysis by HNE. The kinetic parameters of this reaction were monitored with the aid of a FRET-peptide substrate that mimics the TIMP-1 cleavage site in pre-steady-state conditionsby using a stopped-flow fluorescence system. The hydrolysis of the FRET-peptide substrate by HNE exhibits a pre-steady-state burst phase followed by a linear, steady-state pseudo-first-order reaction. The HNE acylation step (k2 = 21±1 s⁻¹) was much higher than the HNE deacylation step (k3 = 0.57±0.05 s⁻¹). The presence of heparin induces a dramatic effect in the pre-steady-state behavior of HNE. Heparin induces transient lag phase kinetics in HNE cleavage of the FRET-peptide substrate. The pre-steady-state analysis revealed that heparin affects all steps of the reaction through enhancing the ES complex concentration, increasing k1 2.4-fold and reducing k₋1 3.1-fold. Heparin also promotes a 7.8-fold decrease in the k2 value, whereas the k3 value in the presence of heparin was increased 58-fold. These results clearly show that heparin binding accelerates deacylation and slows down acylation. Heparin shifts the HNE pH activity profile to the right, allowing HNE to be active at alkaline pH. Molecular docking and kinetic analysis suggest that heparin induces conformational changes in HNE structure. Here, we are showing for the first time that heparin is able to accelerate the hydrolysis of TIMP-1 by HNE. The degradation of TIMP-1is associated to important physiopathological states involving excessive activation of MMPs.

The association between blood pressure in adolescents and the consumption of fruits, vegetables and fruit juice--an exploratory study.

OBJECTIVE: The objective of this study was to correlate blood pressure levels with the consumption of fruit, vegetables and pulses and fruit juice among Brazilian adolescents. BACKGROUND: Scientific evidence has shown a relationship between the regular consumption of vegetables and the prevention of cardiovascular disturbances, such as arterial hypertension, cerebrovascular disease and dyslipidemia. DESIGN: A cross-sectional and correlational study was designed involving a random sample of 794 adolescents from 12 private schools located in a metropolitan area in the north-east of Brazil. METHOD: The subjects responded to a questionnaire structured so as to investigate their regular consumption of fruits, vegetables, pulses and juice. Blood pressure was measured three times, with an interval of one minute between each measurement. The average of the last two measurements was used for the study. The chi-square test, Kruskal-Wallis test and Spearman's rank correlation were used to investigate the association between blood pressure and the consumption of fruit, vegetables, pulses and juice. RESULTS: Lower values of systolic and diastolic blood pressure were identified in adolescents with a consumption of fruit ≥twice daily (p<0·001). In the case of vegetables and pulses, systolic blood pressure was lower among adolescents who consumed more of this type of food (p=0·021). CONCLUSIONS: This study concluded that adolescents who consume more fruit have lower systolic and diastolic blood pressure, while those who regularly consume vegetables and pulses also had lower levels of systolic pressure. RELEVANCE TO CLINICAL PRACTICE: The results of this study suggest that nurses can develop health education activities in schools to encourage the consumption of fruits, vegetables, pulses and fruit juices, especially among those adolescents who are more likely to develop arterial hypertension.

Comparative study of the concentration of salivary and blood glucose in type 2 diabetic patients.

The objective of the present study was to comparatively evaluate the concentrations of blood and salivary glucose as well as salivary flow and xerostomia in type 2 diabetic and non-diabetic patients. The mean salivary glucose level in diabetic patients was 14.03 +/-16.76 mg/dl and 6.35 +/- 6.02 mg/dl (P = 0.036) in the control group. The mean capillary blood glucose level in diabetic patients was 213 +/- 88 mg/dl, while that in non-diabetic patients was 99 +/- 14 mg/dl (P = 0.000). The mean value for resting salivary flow was 0.21 +/- 0.16 ml/min in diabetic patients and 0.33 +/- 0.20 ml/min in the control group (P = 0.002). The stimulated salivary flow was lower in the group of diabetic patients, with a mean of 0.63 +/- 0.43 ml/min, whereas the control group showed a mean of 1.20 +/- 0.70 ml/min (P = 0.000). Of the diabetic patients, 45% exhibited hyposalivation, in contrast to 2.5% of the non-diabetic patients (P = 0.000). Xerostomia was reported in 12.5% of diabetic patients and 5% of non-diabetic patients (P = 0.23). We can conclude that salivary glucose concentration was significantly higher in the experimental group and that there was no correlation between salivary and blood glucose concentrations in diabetic patients. The total salivary flow was significantly reduced in diabetic patients and there was no significant difference as to the presence of xerostomia in both groups.

Psychometric assessment of the Brazilian version of the Breastfeeding Self-Efficacy Scale.

OBJECTIVES: The purpose of this study was to translate and psychometrically assess the Breastfeeding Self-Efficacy Scale (BSES) among women living in Fortaleza, CE, Brazil, and examine the relationship between breastfeeding self-efficacy (BSE) and maternal demographic variables. DESIGN AND SAMPLE: This methodological study is the first translation of BSES conducted in South America. The psychometric assessment of the original study was replicated. This methodological study enrolled a group (sample of judgment) of 117 pregnant women. MEASURES: BSES and maternal sociodemographic variables were studied. RESULTS: The Cronbach's alpha coefficient for the translated BSES was .88. Significant differences in BSES scores were found among mothers with a previous satisfactory breastfeeding experience (M = 145.81; SD = + or - 6.82, p = .0001). Significant relationships were found among prenatal BSE and maternal age (r = .228; p = .01), educational level (r = .234; p = .01), and marital status (r = .183; p = .04). No relationship was found among BSE and maternal occupation, family income, or number of pregnancies. CONCLUSIONS: Altogether, our findings suggest that BSES translated into Portuguese may be a reliable and valid measure to assess maternal BSE in Brazilian culture. Minor changes may be needed to use it in other Portuguese-speaking countries, such as Portugal and Mozambique.

Prevalência de sintomas de rinite em adolescentes de 13 e 14 anos avaliada pelo método ISAAC, na cidade de Fortaleza / Prevalence of rhinitis symptoms in 13 to 14-year old adolescents assessed by the method ISAAC, in the city of Fortaleza

Objetivo: Avaliar a prevalência de sintomas de rinite em escolares de 13 e 14 anos de Fortaleza. Métodos: Aplicou-se o questionário ISAAC (International Study of Asthma and Allergies in Childhood), módulo rinite, em estudo de desenho transversal de base populacional, com amostragem probabilística de 3.015 escolares, de escolas públicas e privadas, no período de 2006 a 2007. Resultados: A prevalência cumulativa de rinite, rinite ativa, rinoconjuntivite alérgica e rinite diagnosticada foi 56,7%, 43,2%, 18,7% e 20,2%, respectivamente. Sintomas de rinite e rinite diagnosticada predominaram de forma significativa no gênero feminino (RP = 1,29, IC95%: 1,20-1,38, p<0,001; RP = 1,27, IC95%: 1,19 - 1,35, P<0,001; RP=1,26, IC95%: 1,18 -1,36, p<0,001 e RP=1,14, IC95%: 1,05 - 1,22, p=0,001, respectivamente) e entre os adolescentes das escolas privadas (RP = 1,62, IC95%:1,43-1,87, p<0,001; RP = 1,71, IC95%: 1,52-1,92 , p<0,001; RP=1,59, IC95%: 1,41-1,80, p<0,001 e RP=1,97, IC95%: 1,76-2,20, p<0,001, respectivamente). Interferência dos sintomas com as atividades diárias foi relatada por 24% dos pesquisados, e 4,7% relataram ser moderada ou intensamente afetados, com predomínio no gênero feminino (RP:1,22, IC95%: 1,08 - 1,38, p=0,005). Conclusões: a prevalência de sintomas de rinite e da morbidade associada, entre adolescentes de 13 e 14 anos de Fortaleza, mostrou-se acima da média nacional, com predomínio no gênero feminino e no grupo das escolas privadas. A prevalência de sintomas de rinoconjuntivite alérgica foi semelhante à média nacional. Observou-se também que rinite é subdiagnosticada entre os adolescentes de Fortaleza.

Aim: To evaluate the prevalence of rhinitis symptoms among 13 to 14-year old schoolchidren from Fortaleza, Brazil. Methods: The cross-sectional study used the self-applied International Study of Asthma and Allergies in Childhood questionnaire. The sample included 3.015 students from public and private schools, from 2006 to 2007. Results: The prevalence of cumulative rhinitis, current rhinitis, rhinoconjunctivitis and diagnosed rhinitis was 56.7%, 43.2%, 18.7% and 20.2%, respectively. Rhinitis symptoms and diagnosed rhinitis were significantly more prevalent among females (PR = 1.29, CI95%: 1.20-1.38, p<0.001; PR = 1.27, CI95%: 1.19 - 1.35, p<0.001; PR=1.26, CI95%: 1.18--1.36, P<0.001 and PR=1.14, CI95%: 1.05 - 1.22, p=0.001, respectively), and private school students (PR = 1.62, CI95%: 1.43-1.87, p<0.001; PR = 1.71, CI95%: 1.52-1.92 , p<0.001; PR=1.59, CI95%: 1.41-1.80, p<0.001 e PR=1.97, CI95%: 1. 76-2.20, P<0.001, respectively). Interference with daily activities was reported by 24%, and 4.7% claimed to be moderately or severely affected, with females predominating over males (PR=1.22, CI95%: 1.08-1.38, p=0.005). Conclusions: The prevalence of rhinitis symptoms and associated morbidity among 13 to 14-year old schoolchidren from Fortaleza was above the Brazilian average, with predominance among females and private school students. The prevalence of allergic rhinoconjunctivitis symptoms was similar to the national average. It was observed that rhinitis was under diagnosed this population.

Fatores de risco para queimaduras e choque elétrico em crianças no ambiente domiciliar / Risk factor for burns and electric shock in children in the domestic setting / Factores de riesgo para las quemaduras y choques eléctricos en niños en el ambiente domiciliario

INTRODUÇÃO: Queimaduras e choque elétrico são acidentes graves que podem causar seqüelas irreversíveis ou a morte. OBJETIVO: Identificar a presença de fatores de riscos para queimaduras e choque elétrico, na opinião das mães e do pesquisador, em crianças da primeira infância, e verificar a associação com os dados sociodemográficos das mães. MÉTODO: Estudo descritivo e abordagem quantitativa. Foram realizadas visitas domiciliares a 87 famílias de crianças de entre 1 e 6 anos que freqüentavam creche, em Fortaleza-CE, no período de 2004-2006, utilizando um formulário sobre o tema. RESULTADOS: O fator de risco mais citado para queimaduras, observado pelas mães (34) e pelo pesquisador (64), foi: panelas ao alcance das crianças, observado pelas mães (34) e pelo pesquisador (64); para choque, o fator de risco mais observado pelas mães (33) e pelo pesquisador (53) foi tomada elétrica não protegida e ao alcance das crianças, observado pelas mães (33) e pelo pesquisador (53). CONCLUSÃO: A enfermagem deve orientar familiares na prevenção de acidentes, minimizando os riscos de acidentes na infância.

INTRODUCTION: Burns and electric shock are severe accidents that can cause irreversible results and death. OBJECTIVE: This study intended to identify mothers' opinions about risk factors in the household associated with burns and shock to which children are exposed. We also verified the correlation between demographic variables and risk factors for burns and shock. METHOD: This is a descriptive study, using a quantitative approach. We conducted household visits, involving 87 families with children aged 1 to 6 years old, who had attended the nursery care center, in Fortaleza, state of Ceará, Brazil, during 2004 to 2006, talking to them and filling out a thematic form. RESULTS: Saucepans within the reach of children were the most significant burn risk factor referred by mothers (34) and by the researcher (64). For electric shock, exposed electric outlets were said to be the most important risk factor by mothers (33) and by the researcher (53). CONCLUSION: Nurses should inform family members how to prevent accidents, therefore reducing accidents in childhood.

INTRODUCCIÓN: Las quemaduras y choques eléctricos son accidentes graves que pueden tener consecuencias irreversibles e incluso llevar a la muerte. OBJETIVO: Identificar la presencia de factores de riesgo para quemaduras y choques eléctricos, según las madres y el investigador, en niños de primera infancia y analizar si tales riesgos están vinculados a los datos sociodemográficos. MÉTODO: se trata de un estudio descriptivo con enfoque cuantitativo. Se visitaron 87 familias en sus domicilios con niños entre uno y seis años que iban a una guardería en Fortaleza, Estado de Ceará. El estudio se realizó entre los años 2004 y 2006 con un formulario que trataba del asunto. RESULTADOS: el factor de riesgo más mencionado, tanto por las madres como por el investigador, fue para quemaduras las ollas y para choques eléctricos las tomas eléctricas o enchufes no protegidos al alcance de los niños. CONCLUSIÓN: enfermería debe orientar a los familiares cómo prevenir accidentes, minimizando los riesgos de accidentes en la infancia.

Conhecimento das mães sobre o aleitamento materno: estudo descritivo / Mother's knowledge about breastfeeding: a descriptive study

Aims: Characterize the demographic profile of mothers who breastfeed exclusively or not, to verify the type of feeding offered to the infants and to inquire the mother's knowledge about important points concerning breastfeeding. Methods: Quantitative, descriptive study involving 102 mothers followed at the Center for Family Development whom were selected randomly, by adopting the following criteria: mothers of suckling infants up to 2 years of life, exclusively breastfed or not. The research was conducted using individual interviews; collected data were processed using the Software Package for the Social Sciences (SPSS 13.0). Results: 93 (91.2%) families had income between 1 to 3 minimum salaries; 70.6% of the mothers had ages between 18 and 30 years; 76.5% of the infants were breastfed and 31.4% were exclusively breastfed. In relation to the maternal knowledge on breastfeeding, it was observed that the previous breastfeeding experience and duration were significantly associated with the right answers on breastfeeding free demand (p=0.018), and water presence in the composition of maternal milk (p=0.031), as indicated correctly by 92 (90.1%) and 79 (77.5%) of the mothers, respectively. Conclusions: The study found that the mothers demonstrated a good knowledge level about breastfeeding issues; however, this finding is not indicative of awareness or self-confidence in the context of child health promotion, therefore mothers have not breastfed their children in the expected manner yet.

Objetivos: caracterizar o perfil sociodemográfico das mães que amamentaram exclusivamente ou não, verificar o tipo de alimentação oferecida aos lactentes e averiguar o conhecimento das mães sobre pontos importantes do aleitamento materno. Métodos: Estudo quantitativo, descritivo envolvendo 102 mães de lactentes acompanhados no Centro de Desenvolvimento Familiar selecionadas aleatoriamente, adotando os seguintes critérios: mães de lactentes até o segundo ano de vida e que amamentaram ou que ainda continuavam amamentando seus filhos exclusivamente ou não. A pesquisa foi realizada a partir de entrevistas individuais e os dados foram processados no Software Package for the Social Sciences (SPSS 13.0). Resultados: 93 (91,2%), famílias tinham renda de 1 a 3 salários mínimos; 70,6% das mães tinham idades entre 18 e 30 anos; 76,5% das mães estavam amamentando sendo que 31,4% o faziam exclusivamente. Em relação ao conhecimento materno sobre o amamentação, observou-se que a experiência e duração do aleitamento materno anterior apresentou associação estatística significante em relação às assertivas sobre a amamentação em livre demanda (p=0,018), e presença de água na composição do leite materno (p=0,031), apontadas como corretas por 92 (90,1%) e 79 (77,5%) mães respectivamente. Conclusões: O estudo evidenciou que as mães têm demonstrado bom nível de conhecimento sobre aleitamento, contudo essa sinalização não é indicativa de tranqüilidade ou de vitória no contexto da promoção à saúde infantil, pois as mães ainda não têm amamentado seus filhos do modo esperado.

Calcium modulates endopeptidase 24.15 (EC 3.4.24.15) membrane association, secondary structure and substrate specificity.

The metalloendopeptidase 24.15 (EP24.15) is ubiquitously present in the extracellular environment as a secreted protein. Outside the cell, this enzyme degrades several neuropeptides containing from 5 to 17 amino acids (e.g. gonadotropin releasing hormone, bradykinin, opioids and neurotensin). The constitutive secretion of EP24.15 from glioma C6 cells was demonstrated to be stimulated linearly by reduced concentrations of extracellular calcium. In the present report we demonstrate that extracellular calcium concentration has no effect on the total amount of the extracellular (cell associated + medium) enzyme. Indeed, immuno-cytochemical analyses by confocal and electron microscopy suggested that the absence of calcium favors the enzyme shedding from the plasma membrane into the medium. Two putative calcium-binding sites on EP24.15 (D93 and D159) were altered by site-directed mutagenesis to investigate their possible contribution to binding of the enzyme at the cell surface. These mutated recombinant proteins behave similarly to the wild-type enzyme regarding enzymatic activity, secondary structure, calcium sensitivity and immunoreactivity. However, immunocytochemical analyses by confocal microscopy consistently show a reduced ability of the D93A mutant to associate with the plasma membrane of glioma C6 cells when compared with the wild-type enzyme. These data and the model of the enzyme's structure as determined by X-ray diffraction suggest that D93 is located at the enzyme surface and is consistent with membrane association of EP24.15. Moreover, calcium was also observed to induce a major change in the EP24.15 cleavage site on distinctive fluorogenic substrates. These data suggest that calcium may be an important modulator of ep24.15 cell function.

Tellurium-based cysteine protease inhibitors: evaluation of novel organotellurium(IV) compounds as inhibitors of human cathepsin B.

New organotellurium(IV) compounds with specific cysteine protease inhibitory activity were synthesized. Serine and aspartic protease activity were not affected by any of these compounds. All Te(IV) compounds tested exhibited high specific second-order constant for cathepsin B inactivation. Tellurium(IV) compound 6 was the best inhibitor of the series, showing a second-order constant of 36,000 M(-1)s(-1). This value is about 100-fold higher than the second-order rate for cysteine protease inactivation shown by the historic Te(IV) compound AS 101 (1). The inhibition was irreversible and time and concentration dependent; no saturation kinetics were observed, suggesting a direct bimolecular reaction. The results described in this paper show that the new organotellurium(IV) compounds are powerful inhibitors of cathepsin B, constituting promising potential anti-metastatic agents.

Novel natural peptide substrates for endopeptidase 24.15, neurolysin, and angiotensin-converting enzyme.

Endopeptidase 24.15 (EC; ep24.15), neurolysin (EC; ep24.16), and angiotensin-converting enzyme (EC; ACE) are metallopeptidases involved in neuropeptide metabolism in vertebrates. Using catalytically inactive forms of ep24.15 and ep24.16, we have identified new peptide substrates for these enzymes. The enzymatic activity of ep24.15 and ep24.16 was inactivated by site-directed mutagenesis of amino acid residues within their conserved HEXXH motifs, without disturbing their secondary structure or peptide binding ability, as shown by circular dichroism and binding assays. Fifteen of the peptides isolated were sequenced by electrospray ionization tandem mass spectrometry and shared homology with fragments of intracellular proteins such as hemoglobin. Three of these peptides (PVNFKFLSH, VVYPWTQRY, and LVVYPWTQRY) were synthesized and shown to interact with ep24.15, ep24.16, and ACE, with K(i) values ranging from 1.86 to 27.76 microm. The hemoglobin alpha-chain fragment PVNFKFLSH, which we have named hemopressin, produced dose-dependent hypotension in anesthetized rats, starting at 0.001 microg/kg. The hypotensive effect of the peptide was potentiated by enalapril only at the lowest peptide dose. These results suggest a role for hemopressin as a vasoactive substance in vivo. The identification of these putative intracellular substrates for ep24.15 and ep24.16 is an important step toward the elucidation of the role of these enzymes within cells.

Heparan sulfate modulates kinin release by Trypanosoma cruzi through the activity of cruzipain.

Trypanosoma cruzi activates the kinin pathway through the activity of its major cysteine proteinase, cruzipain. Because kininogen molecules may be displayed on cell surfaces by binding to glycosaminoglycans, we examined whether the ability of cruzipain to release kinins from high molecular weight kininogen (HK) is modulated by heparan sulfate (HS). Kinetic assays show that HS reduces the cysteine proteinase inhibitory activity (K(i app)) of HK about 10-fold. Conversely, the catalytic efficiency of cruzipain on kinin-related synthetic fluorogenic substrates is enhanced up to 6-fold in the presence of HS. Analysis of the HK breakdown products generated by cruzipain indicated that HS changes the pattern of HK cleavage products. Direct measurements of bradykinin demonstrated an up to 35-fold increase in cruzipain-mediated kinin liberation in the presence of HS. Similarly, kinin release by living trypomastigotes increased up to 10-fold in the presence of HS. These studies suggest that the efficiency of T. cruzi to initiate kinin release is potently enhanced by the mutual interactions between cruzipain, HK, and heparan sulfate proteoglycans.

Comprometimento pulmonar em trauma eletrico: relato de caso / Pulmonary lesion in eletric injury: case report

Trauma eletricos severos constituem cerca de 5 por cento das admissoes em Unidades de Queimados. O acometimento visceral pela corrente eletrica apresenta grande morbidade e mortalidade. A presenca de lesoes viscerais sem continuidade com lesao de partes moles e pouco referida, porem de extrema gravidade, principalmente pela dificuldade diagnostica que apresenta. Lesoes cardiacas tem sido mais frequentemente relatadas, ocorrendo em 10 a 25 por cento dos pacientes, consistinto basicamente em arritmias e disturbios de conducao, consequentes a espasmos coronarios ou lesao muscular difusa pela corrente...

Utilizaçäo da imuno-histoquímica na detecçäo da sede primária em neoplasias metastáticas / Use of the immunohistochemistry in the detection of the primary site in neoplasm metastasis

O objetivo deste trabalho é demonstrar a utilizaçäo de marcadores teciduais, tendo como base amostra selecionada de tumores metastáticos em linfonodos de diversas origens para avaliar sua aplicabilidade, sensibilidade e especificidade na determinaçäo dos sítios primários. Para tanto foram selecionados 19 casos de metástases de neoplasias primárias dos seguintes órgäos: mama (6) , estômago (4), reto (1), cólon (1), tiróide (3), próstata (1), pâncreas (1), ovário (1) e melanoma cutâneo (1). Cortes histológicos desse material foram processados pelo método da imunoperoxidase utilizando-se dois anticorpos policlonais antitiroglobulina e antiantígeno específico de próstata e os anticorpos monoclonais: BRST-1, BRST-2, CAR-3, BD-5 E HMB-45, sendo os dois primeiros marcadores de mama, os outros dois de neoplasias gastrointestinais e o último marcador de melanoma. BRST-1 e BRST-2 coraram três das seis metástases de mama. BRST-1 foi também positivo para as metástases de melanoma e próstata. Os anticorpos monoclonais CAR-3 e BD-5 resultaram positivos em cinco das seis metástases gastrointestinais. Quatro das seis metástases de mama e as da tiróide foram positivas para CAR-3, assim como as metástases de próstata, ovário, pâncreas e melanoma. O anticorpo BD-5 corou também a metástase de próstata. Tiroglobulina e antígeno específico de próstata resultaram positivos nas metástases de tiróide e próstata, respectivamente. Em conclusäo, os anticorpos monoclonais e as técnicas imuno-histoquímicas têm se revelado ferramentas úteis na detecçäo da sede primária de neoplasias de origem desconhecida. Em alguns campos os resultados obtidos já säo satisfatórios, embora na maioria das áreas, estudos adicionais ainda sejam necessários

Hiperandrogenismo decorrente de hipertecose ovariana associada à menopausa: avaliaçäo diagnóstica / Hyperandrogenism following ovarian hyperthecosis associated with menopause: diagnosis evaluation

Uma mulher de 62 anos com síndrome virilizante de longa duraçäo é descrita. As gonadotrofinas plasmáticas estavam em níveis de pós-menopausa (LH:64,7mUl/ml e FSH:78,8mUI/ml) e os níveis plasmáticos de testosterona estavam elevados (T: 2,6lng/ml). Estudos pré-operatórios, com supressäo dos elevados níveis de testosterona plasmática durante administraçäo de estrógeno e posterior elevaçäo durante administraçäo de gonadotrofina coriônica humana, sugerem uma fonte ovariana para o excesso do andrógeno. As concentraçöes venosas ovarianas de testosterona (11,7ng/ml e 24,37ng/ml) foram nove e 18 vezes maiores que as periféricas. Os ovários foram removidos, com normalizaçäo dos níveis plasmáticos de testosterona