Safety evaluation of the venom from scorpion Rhopalurus junceus: Assessment of oral short term, subchronic toxicity and teratogenic effect.

Rhopalurus junceus is the most common scorpion in Cuba and the venom is often used as a natural product for anti-cancer therapy. Despite this, no study has been published concerning its toxicological profile. The aim of the study was characterizing the short-term, subchronic toxicity and the teratogenic potential of Rhopalurus junceus scorpion venom by oral route in mice. Short-term oral toxicity was test in both sexes NMRI mice that received 100 mg/kg/day of scorpion venom extract for 28 days. For the subchronic study, mice were administered with three doses (0.1, 10, and 100 mg/kg) by oral route for 90 days. Teratogenic potential was tested in pregnant mice administered from day 6-15 post conception. Significant differences were observed in body weight and food intake of animal treated for short-term and subchronic assays. Variations in serum urea and cholesterol were observed after 90 days oral treatment. Spontaneous findings not related to the treatment were reveal in histology evaluation. Exposure in pregnant mice did not produce maternal toxicity. Signs of embryo-fetal toxicity were not observed. The current study provides evidence that exposure to low or moderate dose of Rhopalurus junceus scorpion venom by oral route did not affect health of animals and has low impact on reproductive physiology.

Prenatal effects of natural calcium supplement on Wistar rats during organogenesis period of pregnancy.

The potential of oral exposure to calcium and magnesium citrate, a natural product obtained from dolomite, to initiate teratogenesis was analyzed in Wistar rats. Animals received calcium and magnesium citrate oral doses of 250, 500 and 1000 mg/kg during the period of gestation from day 6 to 17 post conception. Maternal, embryo and fetal toxicity was evaluated. Calcium and magnesium citrate exposure did not produce maternal toxicity assessed by clinical observations, body weight gain, food intake, hematology, biochemical parameters and necropsy finding. Signs of embryo-fetal toxicity were not observed. Skeletal and visceral malformations were seen occasionally in all drug-treated and control groups. Skeletal and visceral variations were similar in control and drug-treated groups except for incomplete ossification rib. These finding was spontaneous and unrelated to the drug. In conclusion, in this study we found that the oral exposure to rats of up to 1000 mg/kg of calcium and magnesium citrate during organogenesis did not induce significant maternal and embryo-fetal toxicity. The experimentally derived NOAEL for developmental toxicity was 1000 mg/kg.

Short-term intra-nasal erythropoietin administration with low sialic acid content is without toxicity or erythropoietic effects.

The objective of this investigation was to assess the toxicological potential of nasal formulation of erythropoietin with low sialic acid content (Neuro EPO) after 28 days of intra-nasal dosing in rats besides to evaluate the immunogenicity and erythropoietic effect of the test substance. Healthy Wistar rats of both sexes were used for 28 days subacute toxicity and immunogenicity assays. Doses evaluated were 3450, 4830 and 6900 UI/kg/day. The toxicological endpoints examined included animal body weight, food consumption, hematological and biochemical patterns, antibodies determination, selected tissue weights and histopathological examination. Reversibility of toxic effects was evaluated at high dose 14 days after treatment period. Female B6D2F1 mice were used for evaluated erythropoietic effect of the nasal formulation. Hematological endpoints were examined every week during 28 days of intra-nasal dosing of 6900 UI/kg/day. Variations of hematological patterns were not observed after 28 days of intranasal dosing. A slight increase in glucose level of treated animals within the normal range was observed. This effect was not dose related and was reversible. Antibody formation was not observed in any of the test doses. Histopathological examination of organs and tissues did not reveal treatment induced changes. The administration of Neuro EPO in normocythaemic mice did not produce erythropoietic effect. These results suggest that Neuro EPO could be used as a neuroprotective agent, without significant systemic haematological side effects.

Eficacia de la intervención enfermera para cuidadores con cansancio del rol del cuidador / Effectiveness of nurse intervention in the case of carers wearing of its role

Introducción: El cuidado familiar de personas con enfermedad crónica ha emergido durante los últimos años como un importante problema social, generando cambios en las familias, donde se destaca la figura del cuidador principal quien es la persona familiar o cercana que se ocupa de brindar de forma prioritaria apoyo tanto físico como emocional a otro de manera permanente y comprometida el cual se convierte en un enfermo secundario ya que se ve expuesto a una elevada carga física y psíquica. Objetivo: determinar la eficacia de la intervención de enfermería apoyo al cuidador principal en cuidadores de enfermos crónicos con diagnóstico de enfermería cansancio del rol del cuidador. Métodos: Se realizó un ensayo clínico controlado, aleatorio, doblemente enmascarado. La población objeto fueron cuidadores principales de personas con enfermedades crónicas que recibieron atención en el Hospital Universitario de Santander; el tamaño de la muestra fue de 30 personas, los cuales fueron asignados aleatoriamente por bloques, y de los cuales 10 cuidadores fueron para el grupo intervenido y 20 para el grupo no intervenido, el análisis de datos se realizó por medio del análisis de covarianza y el número necesario para tratar. Resultados: se encontró un efecto de 0.5, estadísticamente significativo, en la etiqueta de resultado bienestar del cuidador al comparar el grupo control con el grupo intervenido y a favor de este último. Conclusiones: la intervención de enfermería realizada es eficaz para el diagnóstico de enfermería cansancio del rol del cuidador y tienen un importante impacto, demostrando que se obtienen resultados positivos cuando se aplican en un solo individuo(AU)

Introduction: The family care of persons presenting with a chronic disease appeared over past years as an important social problem leading to changes in families, where the role of the main carers is notable who is a family member or a relative offering in a priority way a permanent and involved a physical or emotional support to another person who became a secondary patient since is exposed to a high physical and psychic burden. Objective: To determine the effectiveness of nursing intervention related to the support to the main patient's carers wearing of its role. Methods: A double-blind, randomized, controlled and clinical trial of persons presenting with chronic diseases treated and cared in the University Hospital of Santander, Spain; sample included 30 persons who were random allocated to by blocks where 10 carers were in the intervention group and 20 for the non-intervention group; data analysis was made by covariance method and the number necessary to be treated. Results: There was an statistically significant effect of 0,5 in the result of carer wellbeing label comparing the control group with the intervention group one favoring this latter. Conclusions: The disease intervention carried out is effective for nursing diagnosis related to the role of a tired carer with an important impact, demonstrating that it is possible to achieve positive results when it is applied in an only subject(AU)

Acute and subchronic oral toxicities of Calendula officinalis extract in Wistar rats.

We have studied the acute and subchronic oral toxicities of Calendula officinalis extract in male and female Wistar rats. A single acute C. officinalis extract dose of 2000 mg/kg dissolved in distilled water was administered by oral gavage for acute toxicity. Subchronic doses of 50, 250 and 1000 mg/kg/day were administered in drinking water. The major toxicological endpoints examined included animal body weight, water and food intake, selected tissue weights, and histopathological examinations. In addition, we examined blood elements: hematocrit, hemoglobin concentration, erythrocyte count, total and differential leukocyte count and blood clotting time and blood chemistry: glucose, total cholesterol, urea, total proteins, alkaline phosphatase, alanine aminotransferase (ALT) and aspartate aminotransferase (AST). In the acute study, there were no mortality and signs of toxicity. In the subchronic study, several of the blood elements were significantly affected in males and females after 90 days; hemoglobin, erythrocytes, leukocytes and blood clotting time. For blood chemistry parameters, ALT, AST and alkaline phosphatase were affected. Histopathological examination of tissues showed slight abnormalities in hepatic parenchyma that were consistent with biochemical variations observed. These studies indicate that the acute and subchronic toxicities of C. officinalis extract are low.

Absence of hematological side effects in acute and subacute nasal dosing of erythropoietin with a low content of sialic acid.

The use of human recombinant erythropoietin (EPO) as a neuroprotective agent is limited due to its hematological side effects. An erythropoietin along with a low content of sialic acid (rhEPOb), similar to that produced in the brain during hypoxia, may be used as a neuroprotective agent without risk of thrombotic events. The objective of this investigation was to assess the toxicological potential of a nasal formulation with rhEPOb in acute, subacute and nasal irritation assays in rats. Healthy Wistar rats (Cenp:Wistar) were used for the assays. In an irritation test, animals received 15 µl of rhEPOb into the right nostril. Rats were sacrificed after 24 h and slides of the nasal mucosa tissues were examined. Control and treated groups showed signs of a minimal irritation consisting of week edema and vascular congestion in all animals. In the acute toxicity test, the dose of 47,143 UI/kg was administered by nasal route. Hematological patterns, body weight, relative organ weight, and organ integrity were not affected by single dosing with rhEPOb. In the subacute toxicity test, Wistar rats of both sexes received 6,600 UI/kg/day for 14 days. The toxicological endpoints examined included animal body weight, food consumption, hematological and biochemical patterns, selected tissue weights, and histopathological examinations. An increase of lymphocytes was observed in males that was considered to reflect an immune response to treatment. Histopathological examination of organs and tissues did not reveal treatment-induced changes. The administration of rhEPOb at daily doses of 6,600 UI/kg during 14 days did not produce hematological side effects. These results suggest that rhEPOb could offer the same neuroprotection as EPO, without hematological side effects.