El Virus del Nilo Occidental: Revisión / West Nile Virus: Review

El virus del Nilo Occidental (VNO) es un arbovirus perteneciente a la familia Flaviviridae, filogenéticamente relacionado con el complejo de la encefalitis japonesa y aislado por primera vez en el año 1937 a partir del suero de una paciente febril, nativa del Nilo Occidental en Uganda-África. Al igual que muchos otros arbovirus, el VNO, presenta dos ciclos de transmisión: un ciclo enzoótico primario o ciclo de amplificación que envuelve un grupo de vectores (mosquitos y hospedadores aviares), y un ciclo secundario que involucra diferentes artrópodos, con la correspondiente transmisión del virus a hospedadores como humanos y caballos, entre otros. La infección por el VNO causa un espectro de manifestaciones clínicas que van desde la infección subclínica hasta la muerte. Su amplia distribución geográfica, la transmisión por mosquitos, la relación con aves silvestres como hospedadores en zoóticos y algunas infecciones humanas fueron bien documentadas en los años sesenta. El VNO no había sido considerado como un patógeno humano de importancia porque muchas infecciones resultaban asintomáticas o febriles, sin ninguna complicación. Es a partir del año 1996 cuando se reportan importantes epidemias, en donde un gran porcentaje de pacientes después de algunos días de fiebre, progresaron al síndrome de meningoencefalitis. La emergencia del virus del Nilo Occidental (VNO) en el Este de Estados Unidos en 1999 representó un evento muy importante en la arbovirología moderna, no sólo por el impacto de la enfermedad o por la amenaza potencial que representó, sumado a esto, alertó al mundo que los patógenos podrían emerger en cualquier lugar y momento. En este artículo se hace una revisión bibliográfica relacionada con la emergencia del virus del Nilo Occidental en las Américas, ecología, epidemiología, clínica, diagnóstico, manejo clínico y prevención de la enfermedad.

The West Nile Virus (WNV), an arthropod borne virus belonging to the family Flaviviridae, is phylogenetically related to the Japanese Encephalitis group, and it was firts isolated in 1937 from the blood of a woman with fever in the West Nile province of Uganda-Africa. Like others arboviruses, the West Nile Virus has two transmission cycles: one primary enzootic cycle or amplifying cycle that involves a group of mosquitoes vectors and birds as the main amplifying hosts and a second cycle that comprises differents virus-carring arthropod with virus transmission to susceptibles humans and horses, among others. WNV infection in humans causes a spectrum of manifestations from subclinical infection to death. WNV broad geographic distribution, its transmission by mosquitoes and its circulation in cycles of transmission between wild birds as enzootic hosts and some human infections were well documented in the 1960's years. WNV had not been considered important as a human pathogen due to cases with no symptoms or mild clinical symptoms in cases without severity. Since 1996 have been reported important outbreaks with an important progression to cases of meningoencephalitis. The emergence of WNV in eastern North America in 1999 was a major event in modern arbovirology, not only because of the disease impact or the potential threat it represented, but because it alerted the world that pathogens may turn up anywhere at anytime. This article briefly reviews the emergence of West Nile Virus in the Americas, its ecology and epidemiology, clinic, diagnosis and treatment and prevention of West Nile Virus illness.

Expression of Sox8, Sox9 and Sox10 in the developing valves and autonomic nerves of the embryonic heart.

We describe the expression pattern of Sox8, Sox9 and Sox10 during the development of the chick embryo heart. These Sox genes constitute the group E of the large Sox family of transcription factors. We show that the expression of Sox8, Sox9 and Sox10 in the developing heart correlates with heart septation and with the differentiation of the connective tissue of the valve leaflets. Sox10 appears also as a specific marker of developing heart nerves. These findings fit with the occurrence of morphological and functional anomalies of the heart reported in humans deficient for Sox9 and Sox10.

Blood glucose, insulin, and free fatty acid levels during oral glucose tolerance tests in 158 obese children.

In 158 obese children, aged from three months to 15 years, blood glucose, immunoreactive insulin, and free fatty acid levels were measured during a standard oral glucose tolerance test carried out prior to treatment. The results were analyzed for the total sample as well as for three age groups: 0-5 years, 6-10 years, and 11-15 years and compared with those of 70 normal-weight children matched for age and sex. Glucose tolerance is normal in the obese children. It is different from the controls only two hours after glucose loading, when a slight but significant elevation is found. The glucose levels at one and two hours are significantly higher in the obese children of group III than in the younger ones. Fasting F.F.A. levels are similar in normal and obese children, but the F.F.A. decrease following glucose absorption is significantly diminished in the obese. The F.F.A. levels of the youngest obese are significantly higher than those of the older ones. A constant and important hyperinsulinism, fasting and postabsorptive, is demonstrated in obese children of all ages, even before five years and at the beginning of obesity. Age- and sex-related differences in insulin secretion are much more marked in the obese than in normal children. The degree of hyperinsulinemia is related to the degree of obesity, but not to its duration. The results suggest that hyperinsulinism is associated with obesity from its onset rather than being a long-term consequence of overweight. However, the origin of hyperinsulinism in obesity and the mechanism of insulin resistance still remain obscure.

Insulin secretion by human pancreas cultured for one year.

The pancreas of a child with intractable neonatal hypoglycemia was explanted in tissue culture on plasma clot and in monolayer culture after enzymatic dissociation. 1. Cytological and immunoenzymatic studies of pancreas before explantation showed a very altered structure, suggesting a polyendocrine tumor composed mainly of B cells. Endocrine cells were present in the epithelium of duct-like structures. Large islets were often in continuity with these structures, suggesting islet budding from ducts, and supporting the hypothesis of the persistence of embryonic characteristics. 2. In vitro, the pancreatic endocrine cells survived and proliferated; they were maintained for 362 days. During this time, they maintained their secretory capacity, as shown by radioimmunoassays of the culture media: the cells released insulin in rapidly decreasing amounts, then continued excreting low levels (5 to 60 muU/flask/day), in alternative periods of secretion and absence of secretion. 3. Cytological study by light and electron microscopy of the cells in tissue and in monolayer cultures shows that they can undergo morphological changes, and may become epithelioid, fibroblastoid or round, while retaining their secreting activity. 4. In long-term culture, the cells did not contain typical mature secretion granules. The hormone might be released into the medium by a clasmatosis mechanism. On the other hand, hormone excretion by vesicles originating from the rough endoplasmic reticulum is possible.

In vitro secretion of gastrin, insulin, and glucagon in tissue cultures of pancreas from a child with neonatal intractable hypoglycemia.

Small pieces of pancreatic tissue were obtained at surgery from a subtotal pancreatectomy performed in a 45-day-old child suffering from intractable neonatal hyperinsulinic hypoglycemia. Histological examination was performed using aldehyde fuchsin, Grimelius', and Hellerström-Hellman's stainings, and immunoperoxidase labeling of insulin and gastrin. The pancreatic tissue before explantation showed numerous and sometimes hyperplastic islets, together with isolated insulin-, glucagon-, and gastrin-containing cells scattered among the exocrine tissue, in aspects similar to "B cell nesidioblastosis." These features could be interpreted as an acinoinsular transformation and/or an embryonic malformation. Extralobular endocrine islet formation by budding from ductular structures was evoked, suggesting the persistency of embryonic properties. The pieces were cultivated on rooster plasma coagulum covered with culture medium. In vitro, endocrine cells survived for 43 days, with outgrowth from the explant and with retention of their secretory abilities. After each medium renewal, radioimmunoassays were performed on the culture medium; they showed that insulin and glucagon secretions decreased with time. On the contrary, secretion of immunoreactive gastrin progressively increased, and kept up to 43 days, with subcultures. Some explants developed in a peculiar way, outgrowing as epithelial layers rich in gastrin-secreting cells as indicated by radioimmunoassays performed after they were reexplanted.

Insulin and free fatty acid levels during oral glucose tolerance tests and their relation to age in 70 healthy children.

In 70 healthy children aged from three months to 15 years, blood glucose, immunoreactive insulin, and free fatty acids were measured during a three-hour glucose tolerance test. The results are presented for the whole group as well as for three age groups: three months-five years, six-10 years, and 11-15 years. It is demonstrated that (1) glucose levels are significantly lower in young children (younger than five years); (2) there are no significant age-related changes in free fatty acid concentration; (3) insulin levels are increasing constantly and significantly with age, the most strikingly at the age of onset of puberty; the absence of notable changes in glucose tolerance results in a rise of the I/G ratio as well. The causes for the increase of insulin secretion with age, whether of peripheral or pancreatic order, are still speculative.

[Blood insulin levels during oral glucose tolerance tests in the obese child. Influence of age, sex, degree and duration of obesity]. / L'insulinémie au cours de l'hyperglycémie provoquée par voie orale chez l'enfant obese. Influence de l'âge du sexe, du degré et de la durée de l'obesite

A significant increase in basic and post-stimulation insulin secretion was observed in 173 obese children undergoing oral glucose tolerance tests. The hyperinsulinism, which was not related to hyperclycemia, was more important in older and heavier children. It was also observed however in younger children since the onset of obesity. It may therefore play a role in the maintenance of the obesity but also in its development. Various hypothesis to explain the origin of this hyperinsulinism and the adaptation of the system to it are discussed.