Safety Evaluation of Goat Milk Added with the Prebiotic Inulin Fermented with the Potentially Probiotic Native Culture Limosilactobacillus mucosae CNPC007 in Co-culture with Streptococcus thermophilus QGE: Analysis of Acute and Repeated Dose Oral Toxicity.

Despite functional goat milk products having emerged due to their importance for human nutrition and health, few studies have assessed the safety of consumption of goat dairy products containing potentially probiotic autochthonous lactic acid bacteria supplemented with prebiotic carbohydrates. Aiming this field, this study evaluated the safety of goat's milk fermented with Streptococcus thermophilus QGE, the autochthonous Limosilactobacillus mucosae CNPC007 culture, and the prebiotic inulin, through single- and repeated-dose oral toxicity tests (SDT and RDT, respectively) in animals. Ten female Swiss Webster mice were used for SDT evaluation - 2 groups, SDTc (20 mL/kg of filtered water) and SDTt (20 mL/kg of fermented milk) - and 40 Wistar rats for RDT - RDT3, RDT6, and RDT12 (treated with fermented milk at doses of 3 mL/kg, 6 mL/kg, and 12 mL/kg, respectively) and also RDTc (12 mL/kg of filtered water). For SDT, no signs of mortality or toxicity were observed, and the animals maintained the expected weight gain and feed intake. The RDT trials did not show mortality or signs of toxicity, as well as no change in body weight and organs, in the hematological and biochemical parameters, and also in relation to morphology and histology. Since the fermented milk did not cause any toxic effect in the conditions evaluated, it can be said that its no-adverse effect level (NOAEL) was considered to be higher than 20 mL/kg/day. Thus, the fermented milk with L. mucosae CNPC007 and inulin was considered to be of low toxicity, safe for use in rodents, and allowed for use in further studies.

Non-clinical repeated dose 28-day oral toxicity, reproductive toxicity and cytotoxicity studies of the polar fraction of Parkinsonia aculeata aerial parts extract.

This study was aimed to evaluate toxicity in repeated doses for 28 days, reproductive toxicity and cytotoxicity of a polar fraction obtained from the hydroethanolic extract of Parkinsonia aculeata (PfrHEPA) in experimental models. To perform the toxicity test in repeated doses for 28 days, male and female Wistar rats were treated via orogastric for 28 days with PfrHEPA (35, 70 or 140 mg/kg) according to the guidelines established by the Organisation for Economic Co-operation and Development (OECD) number 407 (1995). For assessment, the impact of PfrHEPA on the reproductive output various parameters were measured, including maternal weight, no. of pregnant females, female fertility index (%), gestation lengthtime, implantation sites, litter size and placental index of test animals. The cytotoxicity of PfrHEPA was performed on the tumor lines NCI-H292 (human lung carcinoma), HL-60 (human promyelocytic leukemia) and HCT-116 (colorectal cancer). In the repeated dose toxicity test for 28 days, no mortality was observed in the male and female rats treated with PfrHEPA as well as morphological changes and biochemical and hematological parameters. In the reproductive toxicity test, no abnormalities were observed related to the toxicological parameters in both mothers and offspring. Regarding the cytotoxicity assay, the PfrHEPA fraction did not demonstrate significant cytotoxic effect on the cell lines analyzed. The present results suggest the use of PfrHEPA is safe and well tolerated in rats. Further studies are planned to identify and purify the active compounds for subsequent in vivo evaluation.

Evaluation of acute oral toxicity, embryotoxicity and cytotoxicity of the polar fraction of Parkinsonia aculeata aerial parts extract.

Ethnopharmacobotanical information reports that Parkinsonia aculeata infusion is used to control diabetes-related complications and dyslipidemia. However, few studies are reported on the safe use of this species. The aim of this study is to evaluate the acute toxicity, embryotoxicity and cytotoxicity of a polar fraction obtained from hydroethanolic extract of P. aculeata (PfrHEPA). For the acute toxicity test, we considered the Up and Down method which the guidelines are described by the Organization for Economic Cooperation and Development (OECD N°425). The animals were treated with PfrHEPA (2000 mg/kg) or with distilled water (10 ml/kg) by gavage and observed from Day 1 to14. For embryotoxicity assay, zebrafish embryos were exposed to PfrHEPA (100 mg/L) and toxicity parameters were observed during four consecutive days. The cytotoxicity of PfrHEPA (5, 10, 25, 50, 75 and 100 µg/ml, respectively) was performed on normal cell lines (mesenchymal stem cells, African green monkey renal cells and mouse pre-adipocytes 3 T3-L1 using the MTT salt reduction assay. In the acute toxicity test, no mortality was observed in mice treated with PfrHEPA (2000 mg/kg), as well as behavioral changes, histopathological abnormalities and hematological and biochemical variables. In the embryotoxicity test, no abnormal changes related to the toxicological parameters were observed in the period of 96 h. Regarding the cytotoxicity assay, PfrHEPA showed no cytotoxic effect on the normal cell lines tested, with an IC50 value > 100 µg/ml. These results suggest the safe use of P. aculeata, however, more trials are needed for PfrHEPA to be presented as new safe therapeutic proposal for the control of metabolic disorders.

Proximal femoral epiphysis: manual morphometry versus digital morphometry / Epífisis femoral proximal: morfometría manual versus morfometría digital

It is important and necessary to know the morphometric characteristics of the proximal femur in order to reduce the risk of complications associated with surgical procedures performed in the area due to vascular, metabolic or trauma causes, and to achieve an alignment of prosthesis to be implanted. The morphometric analysis has proved possible to be used, and can be a valid help to obtain certain parameters that may contribute to scientific research in several areas. For this, a good understanding of evaluation techniques and principles that can be applied to obtain reliable and valid results is needed. To measure the proximal femoral epiphysis by manual morphometry, with the aid of the caliper, and digital morphometry, with the aid of software and compare them. Twenty nine femurs were used to measure the following parameters: diameter of the femoral head in the cranio caudal axis (DFH­CC) and sagittal axis (DFH­S), diameter of the femoral neck cranio caudal axis (DFN­CC) and sagittal axis (DFN­S), length of the femoral neck (LFN) and length of the intertrochanteric line (LIL). After the measurements, the mean values were compared between the two morphometric techniques. The manual morphometry obtained the following average values: DFH­CC 4.42±0.44, DFH­S 4.38±0.47; DFN­CC 3.10±0.35; DFN­S 2.50±0.37; LFN 2.55±0.42; LIL 4.79±0.62. While the values obtained by digital morphometry were: DFH­CC 3.09±0.41, DFH­S 3.35±0.40; DFN­CC 1.79±0.26; DFN­S 2.26±0.23; LFN 1.42±0.33; LIL 3.33±0.54. All parameters measured from the manual technique showed values significantly higher (p<0.05) than values obtained by digital morphometry. This study showed that there is no morphometry gold standard. Different morphometric methods can effectively reproduce, the values of morphometric anatomical structures, depending on the purpose of the study, the anatomical structures and experience of the researcher.

Es importante y necesario conocer las características morfométricas del fémur proximal con el fin de reducir el riesgo de complicaciones asociadas con los procedimientos quirúrgicos realizados en la zona debido a causas vasculares, metabólicas o traumáticas y para lograr una alineación de prótesis para ser implantada. El análisis morfométrico ha demostrado que es posible utilizar, y puede ser una ayuda válida para obtener ciertos parámetros que pueden contribuir a la investigación científica en diversas áreas. Para ello, se necesita un buen conocimiento de las técnicas de evaluación y los principios que se pueden aplicar para obtener resultos fiables y válidos. El objetivo fue medir la epífisis femoral proximal mediante morfometría manual mediante la ayuda de pinza y compararla con la morfometría digital mediante software . Veintinueve fémures fueron utilizados para medir los siguientes parámetros: diámetro de la cabeza femoral en el eje cráneo-caudal (DFH­CC) y eje sagital (DFH-S), diámetro del eje cráneo-caudal del cuello femoral (DFN­CC) y eje sagital (DFN­S), longitud del cuello femoral (LFN) y la longitud de la línea intertrocantérica (LIL). Después de las mediciones, los valores medios se compararon entre las dos técnicas morfométricas. La morfometría manual obtuvo los siguientes valores medios: DFH­CC 4,42±0,44, DFH­S 4,38±0,47; DFN­CC 3.10±0.35; DFN­S 2,50±0,37; LFN­2,55±0,42; LIL 4,79±0,62. Mientras que los valores obtenidos por la morfometría digitales fueron: DFH­CC 3,09±0,41, DFH­S 3,35±0,40; DFN­CC 1,79±0,26; DFN­S 2,26±0,23; LFN 1,42±0,33; LIL 3,33±0,54. Todos los parámetros medidos de la técnica manual mostraron valores significativamente mayores (p<0,05) que los valores obtenidos por morfometría digital. Este estudio mostró que no existe un estándar en morfometría. Diferentes métodos morfométricos pueden reproducir de manera efectiva los valores de las estructuras anatómicas morfométricas, dependiendo del propósito del estudio, de las estructuras anatómicas y la experiencia del investigador.