Alba Vargas - Academia.edu (original) (raw)
Papers by Alba Vargas
Immunopharmacology and Immunotoxicology, 2008
protein fractions from D. marsupialis sera which were able to defend mice from the lethal effects... more protein fractions from D. marsupialis sera which were able to defend mice from the lethal effects of P.l. hutmanni venom. The fractions separated were homogeneous by conventional electrophoresis using SDS-PAGE. The protein bands obtained contained molecular weights of ˜ 6 to 220 kDa. These results revealed the presence of proteases inhibitors in the opossum sera fractions and the inhibition of venom activity by opossum sera suggesting a reciprocal adaptation at the molecular level.
Bothrops colombiensis is one of the poisonous snakes of great medical importance in Venezuela, wh... more Bothrops colombiensis is one of the poisonous snakes of great medical importance in Venezuela, which is considered responsible for a clinical picture that involves the development of edema, necrosis, coagulopathies and hemorrhages. The severity of this accident promoted the biochemical and biological characterization of its venom; however its toxic potential on essential target organs has not been studied. This work evaluated serum alterations in injury markers, such as creatine phosphokinase (CK), aspartate aminotransferase (AST), alanine aminotransferase (ALT), urea and creatinine, after 1, 3, 6, 15, 24, 48, 72, 96, 120, 144 y 168 hour (h) of the treatment of mice, with 40 μg of venom from B. colombiensis (Paracotos, Miranda State), intramuscular route. The controls included a group of mice treated with 0.85% NaCl solution and another group without treatment. The results obtained showed an increase in CK activity, between 3 and 15 h after treatment, with a maximum value of 4001 ± ...
Scientific Reports
Statins are prescribed to treat hypercholesterolemia and to reduce the risk of cardiovascular dis... more Statins are prescribed to treat hypercholesterolemia and to reduce the risk of cardiovascular disease. However, statin users frequently report myalgia, which can discourage physical activity or cause patients to discontinue statin use, negating the potential benefit of the treatment. Although a proposed mechanism responsible for Statin-Associated Myopathy (SAM) suggests a correlation with impairment of mitochondrial function, the relationship is still poorly understood. Here, we provide evidence that long-term treatment of hypercholesterolemic patients with Simvastatin at a therapeutic dose significantly display increased mitochondrial respiration in peripheral blood mononuclear cells (PBMCs), and platelets compared to untreated controls. Furthermore, the amount of superoxide is higher in mitochondria in PBMCs, and platelets from Simvastatin-treated patients than in untreated controls, and the abundance of mitochondrial superoxide, but not mitochondrial respiration trends with patie...
Revista De La Facultad De Farmacia, Jun 3, 2014
English Language Teaching, 2015
Acta Scientiae Veterinari
Background: Porthidium lansbergii hutmanni species occurs at Tropical level (800 meters altitude)... more Background: Porthidium lansbergii hutmanni species occurs at Tropical level (800 meters altitude) in Margarita Island, Venezuela. It seems to be constrained to this island. Two different species; Porthidium lansbergii rozei and P. lansbergii lansbergii live in the mountains surrounding the Cordillera de La Costa in mainland Venezuela. The principal damage and the main complication in fatal cases of Viperidae snakebites in Venezuela is acute renal failure (ARF) secondary to acute tubular necrosis. Kidney alterations in Porthidium snakebite human victims have concerned inconspicuous considerations. There is not literature description of Porthidium venom activity on the renal structure. The purpose of this study was to determine how intraperitoneal Porthidium lansbergii hutmanni venom injection into mice could lead to severe renal injury. Materials, Methods & Results: Lethal dose fifty (2.5 mg/kg body weight) in mice and polyacrylamide gel electrophoresis were carried out. Observing renal tissue under the electron microscope 3 h after CvPlh injection, proximal convoluted tubule showed widening and loss of interdigitations with normal mitochondria. Multiform and pleomorphic mitochondria were seen. Loss of the cytoarchitecture and empty vacuoles was noticed. After 6 h of CvPlh injection, panoramic view of apical and basal regions of distal convoluted tubule showed swollen mitochondria cristae; Golgi apparatus swollen elements and different wideness of interdigitations were seen. High enlarging of the basal membrane, alteration of the interdigitations with the formation of myelin-like figures were observed. An altered capillary with loss of the wall integrity was visualized. Swollen mitochondria and swollen rough endoplasmic reticulum were observed. After 24 h of CvPlh injection, in the glomeruli, rupture of the capillary endothelia, with podocytes of different widened were detected: they were irregulars and of different sizes. Basal membrane widened in some areas; vacuoles in the endothelial cells were also seen. CvPlh SDS-PAGE profile under native conditions showed approximately 14 bands distributed from 7.6 to 215.0 kDa. Discussion: The largest renal lesions observed in the experimental mice were tubular degeneration and necrosis. The alterations were typically restricted to proximal tubules. Mitochondria modifications were intense. The renal damage caused by CvPlh appeared to be due to both systemic effects (mainly renal ischemia) and direct tubulotoxic effects of the venom. It was also found visceral epithelial changes that included podocyte alterations, which could be associated with glomerular dysfunction. The condition usually causes edema, and nephrotic syndrome and it may progress leading to a renal failure. All renal structures can be involved. Tubular necrosis is the important pathological counterpart of acute renal failure. As far as we known this is the first time that after intramuscular administration of P. l .hutmanni venom glomerular and tubular kidney changes have been observed. It seems likely that mesangiolysis, mitochondria and microvascular damages are a consequence of the high proteolytic and PLA 2 activities of this venom. Studies are being designed to identify the fraction (s) venom responsible (s) for such ultrastructural changes.
RESUMEN Bothrops atrox es reconocida por la Organización Mundial de la Salud (OMS) como una de la... more RESUMEN Bothrops atrox es reconocida por la Organización Mundial de la Salud (OMS) como una de las serpientes suramericanas, que comúnmente causa incapacidad física o muerte. En Vene-zuela, esta especie se localiza en los estados Amazonas, Bolí-var y Delta Amacuro siendo responsable de un cuadro fisiopa-tológico caracterizado por edema, hemorragia, necrosis, incoa-gulabilidad sanguínea y hemólisis. Para el tratamiento del en-venenamiento por esta especie, en Venezuela se produce un antiveneno polivalente desde hace más de 30 años, sin em-bargo, no se ha estudiado su capacidad neutralizante contra las actividades letal, hemorrágica, edematizante, desfibrinante, coagulante y hemolítica indirecta inducidas por esta especie como recomienda la OMS. Este estudio planteó la caracteriza-ción de las actividades tóxicas del veneno total de B. atrox (Puerto Ayacucho-Edo. Amazonas) y la valoración del poten-cial neutralizante del antiveneno venezolano sobre estas acti-vidades, empleando pruebas...
Bothrops colombiensis es una de las serpientes venenosas predominantes en Venezuela, abarca todo ... more Bothrops colombiensis es una de las serpientes venenosas predominantes en Venezuela, abarca todo el oriente, centro, occidente y algunas regiones del sur del país, al norte del río Orinoco, desde el nivel del mar hasta unos 2.500 metros de altura. Esta amplia distribución geográfica en los ofidios venenosos ha sido asociada a variabilidad en la composición de sus venenos, característica que influye en la fisiopatología observada en las víctimas y en la capacidad neutralizante de los antivenenos, esto implica la necesidad de caracterizar toxinologicamente los venenos de importancia médica, para colectar datos experimentales que permitan mejorar el manejo clínico y seleccionar venenos representativos para la producción de antivenenos. Este estudio planteó la caracterización toxinológica del veneno de Bothrops colombiensis de Paracotos (Edo. Miranda), región geográfica no evaluada, estimando sus actividades letal, hemorrágica, edematizante, coagulante, defibrinante y necrosante, así co...
Deprivation of external calcium causes sudden potentiation of the twitch response of single muscl... more Deprivation of external calcium causes sudden potentiation of the twitch response of single muscle fibers. The potentiation was 64 4-8 %. Potentiation is simultaneous with membrane depolarization occurring after Ca +÷ removal. This depolarization amounted to 9 4-2 my. Ca ++ removal also alters the action potential. 3 rain after calcium withdrawal, action potential amplitude fell by 36 4-3 my; maximum rates of rise and fall of the spike decreased by 55 4-5 and 63 4-5 % respectively. Changes in shape of the A. P. differ from those seen with other potentiators of the twitch response, such as Zn ++. After short exposure to calcium-free media, potassium-induced contractures show potentiation of peak tension. The S-shaped curve relating potassium contracture tension to log [K]o shifts to the left after such treatment. Calcium deprivation also increased the rate of relaxation of the contractures. This effect depends on the duration of calcium deprivation, and is probably related to the effect of calcium lack on the membrane. The change in relaxation occurred immediately after calcium deprivation, and was reversed by sudden readmission of calcium. Relaxation of twitch and tetanus responses also were affected by Ca lack, but not as rapidly as potassium contractures. The results suggest that external calcium is not directly involved in the process responsible for tension development, supporting the view that this process is mediated by translocation of intracellular calcium. The relaxation process, however, appears to be rapidly affected by deprivation of external calcium. Normally the contractile response of muscle fibers is triggered by the lowering of the fiber m e m b r a n e potential to a threshold value at which the excitationcontraction coupling (ECC) process begins to be effective (1-4). T h e hypothesis which postulated t h a t calcium ions entering the fibers from the extracellular space upon depolarization of the m e m b r a n e activated the contractile material (5, 6) appears to be inadequate on the basis of theoretically calculated diffusion delays (4, 7, 8). However, the presence in the interior of the fiber of the system of transverse tubules which open out directly into the external space could reduce such delays (9, 10). a~77
Investigación Clínica, Jan 1, 2004
Envenoming by Tityus discrepans (TD) scorpions in northcentral Venezuela mainly causes pancreatic... more Envenoming by Tityus discrepans (TD) scorpions in northcentral Venezuela mainly causes pancreatic and gastrointestinal complications whereas the sting by Tityus zulianus (TZ) (western Venezuela) often produces respiratory arrest and death by pulmonary oedema. Since TZ pancreatic toxicity may have been overlooked, a study was carried out to evaluate TZ venom effect on mice pancreas. BALB/c mice were injected intraperitoneally with 0.5 mg protein/kg of either TD or TZ venoms. A significant increase in serum-amylase activity (IU/mL) was obtained after 3 h (20.6 +/- 3.0, p < 0.05) and 6 h (60.4 +/- 3.0, p < 0.001) of TZ venom injection compared to saline-inoculated mice. Increased amylase levels were also elicited by TD venom, although these were significantly lower than those induced by TZ. Light microscopy of pancreas from TZ-envenomed mice revealed interstitial oedema and vacuolization of acinar cells as soon as 1 h after injection. Differences in the time course of the pancreatic oedema (wet pancreas weight/body weight ratio) elicited by TD and TZ venoms suggest the existence of species-specific mechanisms for oedema formation. Taken together, these data suggest that the TZ venom contains components highly toxic to the mammalian pancreas, which may play a role in developing TZ-related pulmonary complications.
Immunopharmacology and Immunotoxicology, 2008
protein fractions from D. marsupialis sera which were able to defend mice from the lethal effects... more protein fractions from D. marsupialis sera which were able to defend mice from the lethal effects of P.l. hutmanni venom. The fractions separated were homogeneous by conventional electrophoresis using SDS-PAGE. The protein bands obtained contained molecular weights of ˜ 6 to 220 kDa. These results revealed the presence of proteases inhibitors in the opossum sera fractions and the inhibition of venom activity by opossum sera suggesting a reciprocal adaptation at the molecular level.
Bothrops colombiensis is one of the poisonous snakes of great medical importance in Venezuela, wh... more Bothrops colombiensis is one of the poisonous snakes of great medical importance in Venezuela, which is considered responsible for a clinical picture that involves the development of edema, necrosis, coagulopathies and hemorrhages. The severity of this accident promoted the biochemical and biological characterization of its venom; however its toxic potential on essential target organs has not been studied. This work evaluated serum alterations in injury markers, such as creatine phosphokinase (CK), aspartate aminotransferase (AST), alanine aminotransferase (ALT), urea and creatinine, after 1, 3, 6, 15, 24, 48, 72, 96, 120, 144 y 168 hour (h) of the treatment of mice, with 40 μg of venom from B. colombiensis (Paracotos, Miranda State), intramuscular route. The controls included a group of mice treated with 0.85% NaCl solution and another group without treatment. The results obtained showed an increase in CK activity, between 3 and 15 h after treatment, with a maximum value of 4001 ± ...
Scientific Reports
Statins are prescribed to treat hypercholesterolemia and to reduce the risk of cardiovascular dis... more Statins are prescribed to treat hypercholesterolemia and to reduce the risk of cardiovascular disease. However, statin users frequently report myalgia, which can discourage physical activity or cause patients to discontinue statin use, negating the potential benefit of the treatment. Although a proposed mechanism responsible for Statin-Associated Myopathy (SAM) suggests a correlation with impairment of mitochondrial function, the relationship is still poorly understood. Here, we provide evidence that long-term treatment of hypercholesterolemic patients with Simvastatin at a therapeutic dose significantly display increased mitochondrial respiration in peripheral blood mononuclear cells (PBMCs), and platelets compared to untreated controls. Furthermore, the amount of superoxide is higher in mitochondria in PBMCs, and platelets from Simvastatin-treated patients than in untreated controls, and the abundance of mitochondrial superoxide, but not mitochondrial respiration trends with patie...
Revista De La Facultad De Farmacia, Jun 3, 2014
English Language Teaching, 2015
Acta Scientiae Veterinari
Background: Porthidium lansbergii hutmanni species occurs at Tropical level (800 meters altitude)... more Background: Porthidium lansbergii hutmanni species occurs at Tropical level (800 meters altitude) in Margarita Island, Venezuela. It seems to be constrained to this island. Two different species; Porthidium lansbergii rozei and P. lansbergii lansbergii live in the mountains surrounding the Cordillera de La Costa in mainland Venezuela. The principal damage and the main complication in fatal cases of Viperidae snakebites in Venezuela is acute renal failure (ARF) secondary to acute tubular necrosis. Kidney alterations in Porthidium snakebite human victims have concerned inconspicuous considerations. There is not literature description of Porthidium venom activity on the renal structure. The purpose of this study was to determine how intraperitoneal Porthidium lansbergii hutmanni venom injection into mice could lead to severe renal injury. Materials, Methods & Results: Lethal dose fifty (2.5 mg/kg body weight) in mice and polyacrylamide gel electrophoresis were carried out. Observing renal tissue under the electron microscope 3 h after CvPlh injection, proximal convoluted tubule showed widening and loss of interdigitations with normal mitochondria. Multiform and pleomorphic mitochondria were seen. Loss of the cytoarchitecture and empty vacuoles was noticed. After 6 h of CvPlh injection, panoramic view of apical and basal regions of distal convoluted tubule showed swollen mitochondria cristae; Golgi apparatus swollen elements and different wideness of interdigitations were seen. High enlarging of the basal membrane, alteration of the interdigitations with the formation of myelin-like figures were observed. An altered capillary with loss of the wall integrity was visualized. Swollen mitochondria and swollen rough endoplasmic reticulum were observed. After 24 h of CvPlh injection, in the glomeruli, rupture of the capillary endothelia, with podocytes of different widened were detected: they were irregulars and of different sizes. Basal membrane widened in some areas; vacuoles in the endothelial cells were also seen. CvPlh SDS-PAGE profile under native conditions showed approximately 14 bands distributed from 7.6 to 215.0 kDa. Discussion: The largest renal lesions observed in the experimental mice were tubular degeneration and necrosis. The alterations were typically restricted to proximal tubules. Mitochondria modifications were intense. The renal damage caused by CvPlh appeared to be due to both systemic effects (mainly renal ischemia) and direct tubulotoxic effects of the venom. It was also found visceral epithelial changes that included podocyte alterations, which could be associated with glomerular dysfunction. The condition usually causes edema, and nephrotic syndrome and it may progress leading to a renal failure. All renal structures can be involved. Tubular necrosis is the important pathological counterpart of acute renal failure. As far as we known this is the first time that after intramuscular administration of P. l .hutmanni venom glomerular and tubular kidney changes have been observed. It seems likely that mesangiolysis, mitochondria and microvascular damages are a consequence of the high proteolytic and PLA 2 activities of this venom. Studies are being designed to identify the fraction (s) venom responsible (s) for such ultrastructural changes.
RESUMEN Bothrops atrox es reconocida por la Organización Mundial de la Salud (OMS) como una de la... more RESUMEN Bothrops atrox es reconocida por la Organización Mundial de la Salud (OMS) como una de las serpientes suramericanas, que comúnmente causa incapacidad física o muerte. En Vene-zuela, esta especie se localiza en los estados Amazonas, Bolí-var y Delta Amacuro siendo responsable de un cuadro fisiopa-tológico caracterizado por edema, hemorragia, necrosis, incoa-gulabilidad sanguínea y hemólisis. Para el tratamiento del en-venenamiento por esta especie, en Venezuela se produce un antiveneno polivalente desde hace más de 30 años, sin em-bargo, no se ha estudiado su capacidad neutralizante contra las actividades letal, hemorrágica, edematizante, desfibrinante, coagulante y hemolítica indirecta inducidas por esta especie como recomienda la OMS. Este estudio planteó la caracteriza-ción de las actividades tóxicas del veneno total de B. atrox (Puerto Ayacucho-Edo. Amazonas) y la valoración del poten-cial neutralizante del antiveneno venezolano sobre estas acti-vidades, empleando pruebas...
Bothrops colombiensis es una de las serpientes venenosas predominantes en Venezuela, abarca todo ... more Bothrops colombiensis es una de las serpientes venenosas predominantes en Venezuela, abarca todo el oriente, centro, occidente y algunas regiones del sur del país, al norte del río Orinoco, desde el nivel del mar hasta unos 2.500 metros de altura. Esta amplia distribución geográfica en los ofidios venenosos ha sido asociada a variabilidad en la composición de sus venenos, característica que influye en la fisiopatología observada en las víctimas y en la capacidad neutralizante de los antivenenos, esto implica la necesidad de caracterizar toxinologicamente los venenos de importancia médica, para colectar datos experimentales que permitan mejorar el manejo clínico y seleccionar venenos representativos para la producción de antivenenos. Este estudio planteó la caracterización toxinológica del veneno de Bothrops colombiensis de Paracotos (Edo. Miranda), región geográfica no evaluada, estimando sus actividades letal, hemorrágica, edematizante, coagulante, defibrinante y necrosante, así co...
Deprivation of external calcium causes sudden potentiation of the twitch response of single muscl... more Deprivation of external calcium causes sudden potentiation of the twitch response of single muscle fibers. The potentiation was 64 4-8 %. Potentiation is simultaneous with membrane depolarization occurring after Ca +÷ removal. This depolarization amounted to 9 4-2 my. Ca ++ removal also alters the action potential. 3 rain after calcium withdrawal, action potential amplitude fell by 36 4-3 my; maximum rates of rise and fall of the spike decreased by 55 4-5 and 63 4-5 % respectively. Changes in shape of the A. P. differ from those seen with other potentiators of the twitch response, such as Zn ++. After short exposure to calcium-free media, potassium-induced contractures show potentiation of peak tension. The S-shaped curve relating potassium contracture tension to log [K]o shifts to the left after such treatment. Calcium deprivation also increased the rate of relaxation of the contractures. This effect depends on the duration of calcium deprivation, and is probably related to the effect of calcium lack on the membrane. The change in relaxation occurred immediately after calcium deprivation, and was reversed by sudden readmission of calcium. Relaxation of twitch and tetanus responses also were affected by Ca lack, but not as rapidly as potassium contractures. The results suggest that external calcium is not directly involved in the process responsible for tension development, supporting the view that this process is mediated by translocation of intracellular calcium. The relaxation process, however, appears to be rapidly affected by deprivation of external calcium. Normally the contractile response of muscle fibers is triggered by the lowering of the fiber m e m b r a n e potential to a threshold value at which the excitationcontraction coupling (ECC) process begins to be effective (1-4). T h e hypothesis which postulated t h a t calcium ions entering the fibers from the extracellular space upon depolarization of the m e m b r a n e activated the contractile material (5, 6) appears to be inadequate on the basis of theoretically calculated diffusion delays (4, 7, 8). However, the presence in the interior of the fiber of the system of transverse tubules which open out directly into the external space could reduce such delays (9, 10). a~77
Investigación Clínica, Jan 1, 2004
Envenoming by Tityus discrepans (TD) scorpions in northcentral Venezuela mainly causes pancreatic... more Envenoming by Tityus discrepans (TD) scorpions in northcentral Venezuela mainly causes pancreatic and gastrointestinal complications whereas the sting by Tityus zulianus (TZ) (western Venezuela) often produces respiratory arrest and death by pulmonary oedema. Since TZ pancreatic toxicity may have been overlooked, a study was carried out to evaluate TZ venom effect on mice pancreas. BALB/c mice were injected intraperitoneally with 0.5 mg protein/kg of either TD or TZ venoms. A significant increase in serum-amylase activity (IU/mL) was obtained after 3 h (20.6 +/- 3.0, p < 0.05) and 6 h (60.4 +/- 3.0, p < 0.001) of TZ venom injection compared to saline-inoculated mice. Increased amylase levels were also elicited by TD venom, although these were significantly lower than those induced by TZ. Light microscopy of pancreas from TZ-envenomed mice revealed interstitial oedema and vacuolization of acinar cells as soon as 1 h after injection. Differences in the time course of the pancreatic oedema (wet pancreas weight/body weight ratio) elicited by TD and TZ venoms suggest the existence of species-specific mechanisms for oedema formation. Taken together, these data suggest that the TZ venom contains components highly toxic to the mammalian pancreas, which may play a role in developing TZ-related pulmonary complications.