The ghrelin gene products and exendin-4 promote survival of human pancreatic islet endothelial cells in hyperglycaemic conditions, through phosphoinositide 3-kinase/Akt, extracellular signal-related kinase (ERK)1/2 and cAMP/protein kinase A (PKA) signalling pathways.

AIMS/HYPOTHESIS: Pancreatic islet microendothelium exhibits unique features in interdependent relationship with beta cells. Gastrointestinal products of the ghrelin gene, acylated ghrelin (AG), unacylated ghrelin (UAG) and obestatin (Ob), and the incretin, glucagon-like peptide-1 (GLP-1), prevent apoptosis of pancreatic beta cells. We investigated whether the ghrelin gene products and the GLP-1 receptor agonist exendin-4 (Ex-4) display survival effects in human pancreatic islet microendothelial cells (MECs) exposed to chronic hyperglycaemia. METHODS: Islet MECs were cultured in high glucose concentration and treated with AG, UAG, Ob or Ex-4. Apoptosis was assessed by DNA fragmentation, Hoechst staining of the nuclei and caspase-3 activity. Western blot analyses and pharmacological inhibition of protein kinase B (Akt) and extracellular signal-related kinase (ERK)1/2 pathways, detection of intracellular cAMP levels and blockade of adenylyl cyclase (AC)/cAMP/protein kinase A (PKA) signalling were performed. Levels of NO, IL-1ß and vascular endothelial growth factor (VEGF)-A in cell culture supernatant fractions were measured. RESULTS: Islet MECs express the ghrelin receptor GHS-R1A as well as GLP-1R. Treatment with AG, UAG, Ob and Ex-4 promoted cell survival and significantly inhibited glucose-induced apoptosis, through activation of PI3K/Akt, ERK1/2 phosphorylation and intracellular cAMP increase. Moreover, peptides upregulated B cell lymphoma 2 (BCL-2) and downregulated BCL-2-associated X protein (BAX) and CD40 ligand (CD40L) production, and significantly reduced the secretion of NO, IL-1ß and VEGF-A. CONCLUSIONS/INTERPRETATION: The ghrelin gene-derived peptides and Ex-4 exert cytoprotective effects in islet MECs. The anti-apoptotic effects involve phosphoinositide 3-kinase (PI3K)/Akt, ERK1/2 and cAMP/PKA pathways. These peptides could therefore represent a potential tool to improve islet vascularisation and, indirectly, islet cell function.

Evolución de la coqueluche en la Argentina a finales del siglo XX / Pertussis: its evolution in Argentina at the end of the twentieth century

The objective of this study was to analize data of pertussis morbidity and mortality in Argentina and vaccination coverage with combined pertussis vaccine (DwPT), which was available from 1969 until 2000 inclusive, and to investigate their interrelation. A retrospective study was performed based on National Registers. Notification and mortality annual mean variation rates and geometric mean rates, by periods, were analyzed, and correlation coefficients between each one of them and with vaccination coverage were calculated. Notification annual mean variation rates for 1969-2000 were -14.34 and for 1980-2000 -17.26; mortality annual mean variation rates for 1980-2000 was -10.41. Vaccination coverage in infants up to one year of age (3 doses) was 44.4% in 1980; less than 60% until 1982 and higher than 80% after 1990. A highly significant inverse correlation was observed, between (a) vaccine implementation, increase in its coverage, introduction of a fifth vaccine dose, and (b) notification and mortality rates. It was observed during the study, that in our country there is a relatively little knowledge about disease occurrence in adults, and an apparent absence of population-based studies performed on the efficacy of erythromycin chemo prophylaxis in epidemics outbreaks. Based on these data, strategies for a better surveillance and control of pertussis, are exposed.

Se analizaron los datos de morbilidad y mortalidad por coqueluche y su relación con la cobertura de vacunación con vacuna triple bacteriana (DPT), entre los años 1969 y 2000 inclusive, con base en la información disponible en los registros nacionales. Se calcularon el porcentaje de variación anual promedioy las medias geométricas de las tasas de notificación y mortalidad, por períodos, y los coeficientes de correlaciónentre las mismas y entre cada una de ellas y la cobertura de vacunación. La variación anual promedio, de la tasa de notificación para el período 1969-2000 fue –14.34 y para 1980-2000 –17.26 y la correspondiente a la tasa de mortalidad para 1980-2000 fue –10.41. Las coberturas de vacunación del niño menor de un año (3 dosis), fueron del 44.4% en 1980; inferiores al 60% hasta 1982 y mayores al 80% a partir de 1990. Se observó una correlación inversa altamente significativa entre (a) la implementación de la vacunación, el aumento de su cobertura, la introducción de la quinta dosis a los 6 años de edad, y (b) las tasas de incidencia y mortalidad. Se observó además que en nuestro país existe poco conocimiento sobre la ocurrencia de la enfermedad enel adulto y que no se cuenta con estudios poblacionales sobre la eficacia de la quimioprofilaxis con eritromicina,durante brotes epidémicos. Se proponen estrategias para la mejor vigilancia y control de esta enfermedad.

Surveillance for rotavirus in Argentina.

Group A rotaviruses are the major cause of severe gastroenteritis in young children worldwide. Because rotavirus vaccination appeared imminent, a nationwide surveillance program was organized between October 1996 and October 1998 in the largest Argentine cities. Surveillance for disease burden, rotavirus detection, and rotavirus typing was undertaken at nine locations. Results showed rotavirus to be associated with 42% of diarrhea admissions. Although the prevalent G types changed from year to year, common G types were found in 96% of the cases and were usually associated with common P types. Uncommon G types, G9 and G5, were found at low prevalence and uncommon G/P combinations occurred at almost every study site. These data suggest that a rotavirus vaccine could substantially decrease the rotavirus disease burden in Argentina, but that introduction of a vaccine should be accompanied by a concurrent surveillance system.

Multicentered study of viral acute lower respiratory infections in children from four cities of Argentina, 1993-1994.

This study describes the first multicentered study of acute lower respiratory infection viral etiology in young children from four different geographical areas of Argentina. A total of 1,278 children under 5 years of age, hospitalized in primary care centers from Buenos Aires, Córdoba, Santa Fé and Mar del Plata cities during a 2-year period were studied (1993-1994). Nasopharyngeal aspirates were investigated for respiratory syncytial virus (RSV), adenovirus, parainfluenza, and influenza A and B viruses by indirect immunofluorescence. Out of the patients studied, 946 (74%) were under 1 year of age. Viruses were detected in 399 patients (32%). RSV was observed in 25.3% of the samples, representing 78.2% of all viral positive cases. Adenoviruses were detected in 2.5% of the cases, parainfluenza in 2.2%, influenza A in 2.1%, and influenza B in 0.2%. Compared with other viruses, the higher RSV frequency was statistically significant (P < 0.000). Most RSV cases were detected between May and September with a significant peak in July (P < 0.000). Pneumonia was observed in 46% of the patients, bronchiolitis in 41% and other entities in 13%. The case fatality rate observed during the 2 year study was 0.73%. Most of the above respiratory viruses were detected in the four cities, however, the frequency of RSV and influenza were different in the southern city.

[Rotavirus laboratory network: results after one year of observation]. / Red de laboratorios de Rotavirus: resultados del primer año de vigilancia.

Rotavirus is the most common cause of severe diarrhea in children and it has been estimated that in Argentina Rotavirus is responsible for 21,000 hospitalizations, 85,000 medical attentions and an annual medical cost of US$ 27 millions. Given that a Rotavirus vaccine is about to be approved, a laboratory network based surveillance system was organized. Herein, we present the results after one year of study. Severe diarrhea was responsible for 9% of pediatric hospitalizations and rotavirus was detected in 42.1% of the diarrhea cases. We estimated that Rotavirus causes 3.8% of pediatric hospitalizations. The number of diarrhea and Rotavirus diarrhea hospitalizations was greater during the first year of life (62% and 71.3%, respectively). The number of diarrhea hospitalizations during the December-May semester was significantly higher than the rest of the year. A Rotavirus diarrhea peak was detected between April and June. These results indicate that Rotavirus is the most important etiological agent of severe diarrhea in Argentine children and show the importance of performing Rotavirus diagnosis in every pediatric hospital. The additional costs will be compensated by many benefits such as better use of antibiotics, improved nosocomial spread control, better handling of hospital beds and of laboratory resources and of the hospitalized patient.

Red de laboratorios de Rotavirus: resultados del primer año de vigilancia / Rotavirus laboratory network: results after one year experience

Rotavirus es el principal agente productor de diarrea infantil y se ha estimado que provoca en Argentina 21.000 hospitalizaciones, 85.000 atenciones ambulatorias, y un costo mayor a los 27 millones de dolares anuales. Ante la inminente aprobación de una vacuna contra este patógeno se organizó un Sistema de Vigilancia Epidemiológica en base a una Red de laboratorios. Se presentan los resultados obtenidos luego del primer año de funcionamiento de esta Red. Se encontró que el 9 por ciento de la internación pediátrica es debido a diarrea aguda, y rotavirus se halló en el 42,1 por ciento de los casos estudiados. Se estimó que rotavirus provoca el 3,8 por ciento de las internaciones pediátricas. La internación por diarrea y la internación asociada a diarrea por rotavirus fue mayor en el primer año de vida (62 por ciento y 71,3 por ciento respectivamente). En el semestre de diciembre a mayo el número de internaciones por diarrea fue significativamente mayor que en el semestre restante. Se detectó un pico de diarreas por rotavirus entre abril y junio en las distintas Unidades centinelas. Estos resultados señalan a los rotavirus como el principal agente etiológico de la gastroenteritis infantil aguda en nuestro país y avalan la necesidad de incorporar su diagnóstico en todos los hospitales pediátricos. Los costos adicionales serán ampliamente superados por los beneficios relacionados con elmejor manejo de las camas hospitalarias, los recursos del laboratorio, y el paciente internado por diarrea, el uso correcto de antibióticos, y el control de la diseminación intrahospitalaria de rotavirus

Factors that make difficult the implementation of an integrated leprosy control programme in health zone II, Santa Fe Province, Argentina.

With the help of a pre-tested, structured questionnaire and participatory observation, effects of several variables that have a bearing on the process of integration were studied in Zone II of the Santa Fe Province of Argentina. Patient's knowledge and the presence of an NGO were identified as factors facilitating integration. The presence of a vertical programme staff and insufficient commitment towards integration were identified as factors hindering integration.

[Usefulness of the enzyme immunoassay in the diagnosis of tuberculosis]. / Utilidad del enzimoinmunoensayo en el diagnóstico de la tuberculosis.

To assess the usefulness of enzyme immunoassay as a rapid method of diagnosing tuberculosis, a study was conducted of 687 serum samples from 271 children and 416 adults. With 55 sera from nontuberculous children as controls, the specificity was 0.98, and with 137 controls from the adult population, 0.93. Prior vaccination with BCG did not influence the level of detectable anti-PPD antibody. The results were similar in healthy PPD-positive and negative adults. The test differentiated mycoses and nontuberculous mycobacterioses from tuberculosis. The sensitivity rates in 49 children and 200 adults diagnosed with bacteriologically confirmed pulmonary and extrapulmonary tuberculosis were calculated at 0.51 and 0.69, respectively. In those tuberculosis cases not bacteriologically confirmed or at other sites, the test was positive in 28.1% of 114 children and in 48.6% of 35 adults. The cost, speed, and availability of reagents for this test were comparable to those for direct microscopic examination. Both methods were positive for 49% of the tuberculosis cases confirmed by culture, and a total of 84% of those cases were found positive using one method or the other. It is concluded that enzyme immunoassay can be especially useful in the rapid diagnosis of nonbacilliferous pulmonary, extrapulmonary, and childhood tuberculosis.

Detection of circulating antibodies to purified protein derivative by enzyme-linked immunosorbent assay: its potential for the rapid diagnosis of tuberculosis.

An enzyme-linked immunosorbent assay for detecting antibodies to purified protein derivative was evaluated as a rapid method for serodiagnosis of childhood tuberculosis. Its specificity for IgG antibodies was 0.98 as determined in 55 sera from nontuberculous children who showed no significant effect of previous Bacillus Calmette-Guérin vaccination on the production of specific antibodies. Results were negative in 29 of 33 (87.9%) tuberculin-positive children and in 18 of 20 (90.0%) contacts, none of whom had evidence of tuberculosis. The sensitivity of this test was 0.51 as determined in 49 sera from bacteriologically confirmed cases; 17 of 27 smear positive cases and 8 of 22 children with positive cultures were detected. Results were positive in 32 of 114 (28.1%) patients with a diagnosis of tuberculosis not confirmed by microbiology. Consequently whereas a negative result does not rule out tuberculosis, a positive result is a strong indication of the disease. The IgM antibody determination yielded much less discriminative results.

Evaluation of the effectiveness of BCG vaccination using the case-control method in Buenos Aires, Argentina.

A retrospective case-control study was conducted in Argentina to determine the protection conferred by BCG vaccination against tuberculosis in children under six years of age, in an area where coverage is about 55%. A total of 175 tuberculosis patients were included. Five controls selected from patients treated at the same hospital as those under study for reasons other than tuberculosis were matched to each case on the basis of age, socioeconomic origin, nutritional status and place of residence. Information on BCG vaccination status was collected by an independent examiner. Tuberculosis localizations were as follows: 152 pulmonary, pleural and/or miliary; 18 meningitis; 2 lymphadenitis; 2 osteoarticular; and 1 otic. The diagnosis was based on bacteriological and histopathological tests, computerized tomography, radiology, clinical examination, endoscopy, and proved source of infection. The protective effect of BCG among those who were vaccinated was 73.0% with 95% confidence limits of 82% and 62%. According to these results BCG vaccination given early in life is very effective in preventing tuberculosis.