Brote de enfermedad aguda de Chagas adquirida oralmente en Sucre, 2019-2020 / Outbreak of orally acquired acute Chagas disease in Sucre, 2019-2020

Introducción: En las dos últimas décadas, varios países de América Latina han experimentado múltiples brotes de la enfermedad de Chagas oral. El estudio: Estudio retrospectivo que analiza un brote de enfermedad de Chagas oral aguda en Sucre, Colombia durante diciembre-enero de 2020. Los casos fueron confirmados por diferentes métodos diagnósticos. Hallazgos: Durante dos semanas se confirmaron 16 casos, donde la edad media fue de 14 años. Del total, 14 pacientes fueron hospitalizados y 2 fallecieron. Las manifestaciones clínicas incluyeron: fiebre, edema facial, hepatoesplenomegalia. En 13 de los pacientes se observaron tripomastigotes de Trypanosoma cruzi en los frotis fino y grueso. La transmisión oral se estableció como la vía más probable. Conclusiones: La enfermedad de Chagas aguda transmitida por vía oral puede poner en peligro la vida o incluso ser mortal, por tanto, es urgente mejorar las medidas de control epidemiológico a nivel nacional y en otros países de América Latina.

Background:In the last two decades, several Latin Americancountrieshaveexperiencedmultiple outbreaksoforalChagasdisease.Thestudy: Retrospective study analyzing an outbreak of acute oralChagasdiseaseinSucre,Colombiaduring December-January 2020. The cases were confirmed by different diagnostic methods. During two Finding:weeks, 16 cases were confirmed, where the mean age was 14 years and 12 were male. Of the total, 14 patientswerehospitalizedand2died.Clinical manifestationsinclude:fever,facialedema, hepatosplenomegaly,In13ofthepatients Trypanosoma cruzi trypomastigotes were observed in thethinandthicksmears.Oraltransmissionis established as the most likely route in 14 of the patients. Acute orally transmitted Conclusions: Chagas disease can be life-threatening or even fatal, therefore, it is urgent to improve epidemiological control measures at the national level and in other Latin American countries.

A central pacemaker that underlies the production of seasonal and sexually dimorphic social signals: functional aspects revealed by glutamate stimulation.

The cyclic enrichment of behavioral repertoires is a common event in seasonal breeders. Breeding males Brachyhypopomus gauderio produce electric organ discharge (EOD) rate modulations called chirps while females respond with interruptions. The electromotor system is commanded by a pacemaker nucleus (PN) which sets the basal rate and produces the rate modulations. We focused on identifying functional, seasonal and sexual differences in this nucleus in correlation to these differences in behavior. The in vivo response to glutamate injection in the PN was seasonal, sexually dimorphic and site specific. Non-breeding adults and breeding females injected in dorsal and ventral sites generated EOD rate increases and interruptions, respectively. Reproductive males added a conspicuous communication signal to this repertoire. They chirped repetitively when we injected glutamate in a very restricted area of the ventral-rostral nucleus, surprisingly one with a low number of relay cell somata. This study shows that the PN is functionally organized in regions in a caudal-rostral axis, besides the previously documented dorsal-ventral division. Functional regions are revealed by seasonal changes that annually provide this nucleus with the cellular mechanisms that allow the bursting activity underlying chirp production, only in males.

[Biology of aging]. / Biología del envejecimiento.

The study of biological aging has seen a spectacularly fast progress in the last decade. Besides a better understanding and comprehension of physiological aspects, an important advance has been the identification of at least a hundred different genes which control the process of aging. Their mechanism of action falls within the expectations from a handful of theories which attempt to provide a global explanation of the phenomenon of aging, including free radicals, cell senescence and loss of regenerative capacity through the activation of stem cells. In this review we will concentrate in these biological aspects, with a special emphasis on animal models used to study both the genetics and physiology of aging as well as experimental approaches to test the aforementioned theories. It should be emphasized that, while the emphasis is in purely biological aspects of the process, the fast pace of aging of the world's population, including Chile, needs a rapid advance also in our understanding o fits social and economic implications.

Biología del envejecimiento / Biology of aging

The study of biological aging has seen a spectacularly fast progress in the last decade. Besides a better understanding and comprehension of physiological aspects, an important advance has been the identification of at least a hundred different genes which control the process of aging. Their mechanism of action falls within the expectations from a handful of theories  which attempt to provide a global explanation of the phenomenon of aging, including free radicals, cell senescence and loss of regenerative capacity through the activation of stem cells. In this review we will concentrate in these biological aspects, with a special emphasis on animal models used to study both the genetics and physiology of aging as well as experimental approaches to test the aforementioned theories. It should be emphasized that, while the emphasis is in purely biological aspects of the process, the fast pace of aging of the world's population, including Chile, needs a rapid advance also in our understanding o fits social and economic implications.

Sexual and seasonal plasticity in the emission of social electric signals. Behavioral approach and neural bases.

Behavior in electric fish includes modulations of a stereotyped electric organ discharge (EOD) in addition to locomotor displays. Gymnotiformes can modulate the EOD rate to produce signals that participate in different behaviors. We studied the reproductive behavior of Brachyhypopomus pinnicaudatus both in the wild and laboratory settings. During the breeding season, fish produce sexually dimorphic social electric signals (SES): males emit three types of chirps (distinguished by their duration and internal structure), and accelerations, whereas females interrupt their EOD. Since these SES imply EOD frequency modulations, the pacemaker nucleus (PN) is involved in their generation and constitutes the main target organ to explore seasonal and sexual plasticity of the CNS. The PN has two types of neurons, pacemakers and relays, which receive modulatory inputs from pre-pacemaker structures. These neurons show an anisotropic rostro-caudal and dorso-ventral distribution that is paralleled by different field potential waveforms in distinct portions of the PN. In vivo glutamate injections in different areas of the PN provoke different kinds of EOD rate modulations. Ventral injections produce chirp-like responses in breeding males and EOD interruptions in breeding females, whereas dorsal injections provoke EOD frequency rises in both sexes. In the non-breeding season, males and females respond with interruptions when stimulated ventrally and frequency rises when injected dorsally. Our results show that changes of glutamate effects in the PN could explain the seasonal and sexual differences in the generation of SES. By means of behavioral recordings both in the wild and in laboratory settings, and by electrophysiological and pharmacological experiments, we have identified sexual and seasonal plasticity of the CNS and explored its underlying mechanisms.

The release of sympathetic neurotransmitters is impaired in aged rats after an inflammatory stimulus: a possible link between cytokine production and sympathetic transmission.

Aging results in a general decline in the response to external insults, including acute inflammatory challenges. In young animals, the inflammatory response requires activation of the sympathetic system, including neurotransmitters such as ATP, and catecholamines (epinephrine and norepinephrine). To test whether aging affects activation of this axis, and whether this in turn might affect cytokine release, we administered lipopolysaccharide (LPS) i.p. to adult, middle-aged and aged Fisher 344 rats (6-, 15- and 23-month old, respectively) and evaluated the early (0-12h) serum levels of Neuropeptide-Y (NP-Y), ATP and vanillyl mandelic acid (VMA, as an indirect measurement of catecholamine levels). In addition, we evaluated the association between these factors and serum levels of the cytokines tumor necrosis factor-alpha (TNFalpha) and interleukin-10 (IL-10). Induction of both ATP and NP-Y was markedly reduced in the serum of aged animals, when compared to their younger counterparts, while induction of VMA was not affected by age. In spite of these changes, serum levels of TNFalpha and IL-10 were strongly hyper induced and delayed in aged rats. The results suggest that during aging there is a dysregulation in sympathetic neurotransmitter regulatory mechanisms, and this might play a role in the impairment of the inflammatory response.

T-kininogen induces endothelial cell proliferation.

Basal proliferation of endothelial cells increases with age, and this might play a role in the etiology of age-related vascular diseases, as well as angiogenesis. Serum kininogen levels increase during aging in rats and humans, and T-kininogen (T-KG) can affect proliferative homeostasis in several cell models. Both kinins and kininogens have been shown previously to be angiogenic through activation of endothelial cell proliferation, and here we show that exposure of endothelial cells to T-KG results in vigorous cell proliferation, accompanied by ERK/AKT activation. In our experiments, the proliferative response requires B1 and B2 kinin receptors, even though kinins are not released from the precursor. We hypothesize that the age-related increase in T-KG could play a significant role in the age-related dysregulation of vascular physiology and function.

Serum from aged F344 rats conditions the activation of young macrophages.

There is considerable controversy about the molecular mechanisms responsible for the variations in innate immunity associated with age. While in vivo, aged animals and humans react to an inflammatory signal with an excessive production of pro-inflammatory cytokines, studies in vitro generally show that this response is attenuated in macrophages from old individuals. In an effort to examine possible extrinsic factors that might affect the response of macrophages to lipopolysaccharide (LPS), we have challenged peritoneal macrophages obtained from young rats with sera obtained from rats of different ages. Our results indicate that the serum from aged rats significantly impairs the capacity of young macrophages to induce tumor necrosis factor-alpha (TNF-alpha) production, while at the same time it increases the basal levels of interleukin-6 (IL-6). The effect of serum from aged donors on TNF-alpha secretion requires pre-incubation and is sensitive to heat inactivation. In contrast, the stimulating effect on IL-6 is resistant to heat, and thus should not be due to a protein factor. Therefore, our results indicate that the age-related changes in macrophage activity are not only the consequence of intrinsic changes, but there also appears to be a modulatory effect imparted by the external milieu.

T-kininogen, a cystatin-like molecule, inhibits ERK-dependent lymphocyte proliferation.

Plasma levels of kininogens increase with age in both rats and humans. Kininogens are inhibitors of cysteine proteinases, and filarial cysteine proteinase inhibitors (cystatins) reduce the proliferation of T cells. We evaluated whether T-kininogen (T-KG) might mimic this effect, and here we present data indicating that exposure of either rat splenocytes or Jurkat cells to purified T-KG results in inhibition of both ERK activation and [(3)H]-thymidine incorporation, both basal and in response to ConA or PHA. Interestingly, T-KG did not impair [(3)H]-thymidine incorporation in response to IL-2, which requires primarily the activation of the JNK and Jak/STAT pathways. These effects were neither the consequence of increased cell death, nor required the activity of kinin receptors. Furthermore, when T cell receptor proximal events were bypassed by the use of PMA plus Calcium ionophore, T-KG no longer inhibited ERK activation, suggesting that inhibition occurs upstream of these events, possibly at the level of membrane associated signal transduction molecules. We conclude that, like filarial cystatins, T-KG inhibits ERK-dependent T cell proliferation, and these observations suggest a possible role for T-KG in immunosenescence.

Sodium-dependent plateau potentials in electrocytes of the electric fish Gymnotus carapo.

The weakly electric fish Gymnotus carapo emits a triphasic electric organ discharge generated by muscle-derived electrocytes, which is modified by environmental and physiological factors. Two electrode current clamp recordings in an in vitro preparation showed that Gymnotus electrocytes fired repetitively and responded with plateau potentials when depolarized. This electrophysiological behavior has never been observed in electrocytes from related species. Two types of plateaus with different thresholds and amplitudes were evoked by depolarization when Na(+)-dependent currents were isolated in a K(+)- and Ca(2+)-free solution containing TEA and 4-AP. Two electrode voltage clamp recordings revealed a classical fast activating-inactivating Na+ current and two persistent Na(+)-dependent currents with voltage-dependencies consistent with the action potential (AP) and the two plateaus observed under current clamp, respectively. The three currents, the APs and the plateaus were reduced by TTX, and were absent in Na(+)-free solution. The different Na(+)-dependent currents in Gymnotus electrocytes may be targets for the modifications of the electric organ discharge mediated by environmental and physiological factors.

Estudio psicosocial en un grupo de pacientes hemofílicos adultos 18 años después de haber sido estudiados en su niñez / Psychosocial study of a group of adult hemophilic patients eighteen years after having been studied in their childhood

Se estudiaron las características de personalidad, el perfil psicopatológico, los aspectos psicosociales y el conocimiento sobre la enfermedad en 19 pacientes hemofílicos adultos que habían sido evaluados psicológicamente en su niñez. Se utilizó la prueba de los 16 factores de la personalidad, el Inventario Multifacético de la Personalidad de Minnesota, una entrevista psicosocial y una encuesta de conocimiento de la enfermedad. Los sujetos pueden describirse como reservados, emotivos y dependientes. El perfil psicopatológico de este grupo es característico de personas con depresión, tristeza, dificultad para expresar sus sentimientos, inseguridad y necesidad de afecto. El 21 por ciento presentó dificultades para su integración a actividades sociales. El 52 por ciento están casados. Todos tienen al menos 9no. grado. El 78 por ciento tiene vínculo laboral activo. Todos poseen buen dominio de los aspectos esenciales de la enfermedad. En este grupo se observó una situación psicosocial más favorable que la reportada en este tipo de pacientes décadas atrás.

T-kininogen inhibits kinin-mediated activation of ERK in endothelial cells.

Serum levels of T-kininogen increase dramatically as rats approach the end of their lifespan. Stable expression of the protein in Balb/c 3T3 fibroblasts leads to a dramatic inhibition of cell proliferation, as well as inhibition of the ERK signaling pathway. T-kininogen is a potent inhibitor of cysteine proteinases, and we have described that the inhibition of ERK activity occurs, at least in part, via stabilization of the MAP kinase phosphatase, MKP-1. Since fibroblasts are not a physiological target of T-kininogen, we have now purified the protein from rat serum, and used it to assess the effect of T-kininogen on endothelial cells. Adding purified T-kininogen to EAhy 926 hybridoma cells resulted in inhibition of basal ERK activity levels, as estimated using appropriate anti-phospho ERK antibodies. Furthermore, exogenously added T-kininogen inhibited the activation of the ERK pathway induced by either bradykinin or T-kinin. We conclude that the age-related increase in hepatic T-kininogen gene expression and serum levels of the protein could have dramatic consequences on endothelial cell physiology, both under steady state conditions, and after activation by cell-specific stimuli. Our results are consistent with T-kininogen being an important modulator of the senescent phenotype in vivo.

T-kininogen inhibits kinin-mediated activation of ERK in endothelial cells

Serum levels of T-kininogen increase dramatically as rats approach the end of their lifespan. Stable expression of the protein in Balb/c 3T3 fibroblasts leads to a dramatic inhibition of cell proliferation, as well as inhibition of the ERK signaling pathway. T-kininogen is a potent inhibitor of cysteine proteinases, and we have described that the inhibition of ERK activity occurs, at least in part, via stabilization of the MAP kinase phosphatase, MKP-1. Since fibroblasts are not a physiological target of T-kininogen, we have now purified the protein from rat serum, and used it to assess the effect of T-kininogen on endothelial cells. Adding purified T-kininogen to EAhy 926 hybridoma cells resulted in inhibition of basal ERK activity levels, as estimated using appropriate anti-phospho ERK antibodies. Furthermore, exogenously added T-kininogen inhibited the activation of the ERK pathway induced by either bradykinin or T-kinin. We conclude that the age-related increase in hepatic T-kininogen gene expression and serum levels of the protein could have dramatic consequences on endothelial cell physiology, both under steady state conditions, and after activation by cell-specific stimuli. Our results are consistent with T-kininogen being an important modulator of the senescent phenotype in vivo