Chronic kidney failure following lancehead bite envenoming: a clinical report from the Amazon region.

BACKGROUND: Snakebite envenoming can be a life-threatening condition, for which emergency care is essential. The Bothrops (lancehead) genus is responsible for most snakebite-related deaths and permanent loss of function in human victims in Latin America. Bothrops spp. venom is a complex mixture of different proteins that are known to cause local necrosis, coagulopathy, and acute kidney injury. However, the long-term effects of these viper envenomings have remained largely understudied. CASE PRESENTATION: Here, we present a case report of a 46-years old female patient from Las Claritas, Venezuela, who was envenomed by a snake from the Bothrops genus. The patient was followed for a 10-year period, during which she presented oliguric renal failure, culminating in kidney failure 60 months after the envenoming. CONCLUSION: In Latin America, especially in Brazil, where there is a high prevalence of Bothrops envenoming, it may be relevant to establish long-term outpatient programs. This would reduce late adverse events, such as chronic kidney disease, and optimize public financial resources by avoiding hemodialysis and consequently kidney transplantation.

Chronic kidney failure following lancehead bite envenoming: a clinical report from the Amazon region

Snakebite envenoming can be a life-threatening condition, for which emergency care is essential. The Bothrops (lancehead) genus is responsible for most snakebite-related deaths and permanent loss of function in human victims in Latin America. Bothrops spp. venom is a complex mixture of different proteins that are known to cause local necrosis, coagulopathy, and acute kidney injury. However, the long-term effects of these viper envenomings have remained largely understudied. Case presentation: Here, we present a case report of a 46-years old female patient from Las Claritas, Venezuela, who was envenomed by a snake from the Bothrops genus. The patient was followed for a 10-year period, during which she presented oliguric renal failure, culminating in kidney failure 60 months after the envenoming. Conclusion: In Latin America, especially in Brazil, where there is a high prevalence of Bothrops envenoming, it may be relevant to establish long-term outpatient programs. This would reduce late adverse events, such as chronic kidney disease, and optimize public financial resources by avoiding hemodialysis and consequently kidney transplantation.(AU)

Chemopreventive effects of the dietary histone deacetylase inhibitor tributyrin alone or in combination with vitamin A during the promotion phase of rat hepatocarcinogenesis.

The chemopreventive effects of tributyrin (TB) and vitamin A (VA), alone or in combination, were investigated during the promotion phase of rat hepatocarcinogenesis. Compared to diethylnitrosamine control rats, TB and TB+VA-treated rats, but not VA-treated rats, presented a lower incidence and mean number of hepatocyte nodules and a smaller size of persistent preneoplastic lesions (pPNLs). In addition, TB and TB+VA-treated rats exhibited a higher apoptotic body index in pPNL and remodeling PNL, whereas VA-treated rats presented only a higher apoptotic body index in remodeling PNL. None of the treatments inhibited cell proliferation in PNL. TB and TB+VA-treated rats, but not VA-treated rats, exhibited higher levels of H3K9 acetylation and p21 protein expression. TB and VA-treated rats exhibited increased hepatic concentrations of butyric acid and retinoids, respectively. Compared to normal rats, diethylnitrosamine control animals exhibited lower retinyl palmitate hepatic concentrations. All groups had similar expression levels and exhibited similar unmethylated CRBP-I promoter region in microdissected pPNL, indicating that epigenetic silencing of this gene was not involved in alteration of retinol metabolism in early hepatocarcinogenesis. Data support the effectiveness of TB as a dietary histone deacetylase inhibitor during the promotion phase of hepatocarcinogenesis, which should be considered for chemoprevention combination strategies.

Investigation of the acute effect of leptin on the inhibition of glycogen catabolism by insulin in rat liver perfused in situ.

Leptin, a cytokine secreted by adipose tissue, has been implicated in the insulin resistance associated with obesity. Here we examined the acute influence of leptin at physiological (10 ng/ml) and supraphysiological (50 ng/ml and 100 ng/ml) concentrations on the inhibition of glycogen catabolism promoted by insulin in rat liver perfusion experiments. Perfusion of the liver with insulin (20 microU/ml) decreased the activation of glucose production (p < 0.05) and glycogenolysis by cAMP (3 microM). However, the infusion of leptin, at concentrations similar to those found in non-obese (10 ng/ml), obese (50 ng/ml), and morbidly obese (100 ng/ml) individuals did not influence the acute inhibitory effect of insulin (20 microU/ml) on glucose production and glycogenolysis stimulated by cAMP (p > 0.05).We conclude that neither physiological nor supraphysiological concentrations of leptin directly influence the inhibition of glycogen catabolism promoted by insulin in rat liver perfused in situ.

Central role of cAMP in the inhibition of glycogen breakdown and gluconeogenesis promoted by leptin and insulin in perfused rat liver.

Leptin showed less prominent inhibiting effect on the activation of hepatic glycogen breakdown and gluconeogenesis promoted by cAMP. The role of cAMP in the inhibition of glycogen breakdown and gluconeogenesis induced by physiological levels of leptin (10 ng/ml) and insulin (20 microU/ml) in the perfused liver was investigated. Insulin but not leptin inhibited (p < 0.05) the activation of glycogen breakdown promoted by cAMP (3 microM). Contrary to cAMP, the activation of glycogen catabolism promoted by 8-Br-cAMP (0.3 microM), a cAMP analogue more resistant to hydrolysis by phosphodiesterase 3B (PD3B), was inhibited (p < 0.05) not only by insulin (20 microU/ml) but also by leptin (10 ng/ml). The effect of leptin, however, was less intense than that of insulin. To verify the participation of the intracellular levels of cAMP, the experiments were repeated with N(6)-monobutyryl-cAMP (N(6)-MB-cAMP), a cAMP analogue, which is not metabolized by PD3B. The activation of glycogen breakdown promoted by N(6)-MB-cAMP (0.3 microM) was not affected by leptin or insulin. In agreement with the results regarding glycogen catabolism, insulin and leptin at 50 ng/ml but not leptin at 10 ng/ml inhibited (p < 0.05) the activation of gluconeogenesis promoted by cAMP (7.5 microM). Taken together, these results led us to postulate that the convergent signaling pathways of these two hormones causing the inhibition of glycogen catabolism and gluconeogenesis involve a reduction of intracellular cAMP. Thus, cAMP levels may play an important role in the cross talk between both hormones and for the insulin-like effects of leptin.