Os estudos de bioequivalência: Relevância para a medicina veterinária

Os estudos de Bioequivalência (BE) são utilizados para a comparação de diferentes produtos farmacêuticos que contêm o mesmo princípio ativo, de diferentes lotes de um mesmo produto ou, ainda e de uma maneira ampla, de diferentes vias de administração de um mesmo medicamento. No Brasil dos dias de hoje, encontramos legislações sobre medicamentos genéricos e bioequivalência apenas na área de Medicina Humana. No campo da Medicina Veterinária, os testes de BE têm sido considerados, em muitos países, como requerimentos necessários para o registro de produtos destinados aos animais visto que eles asseguram, ao mesmo tempo, a eficácia do produto, a saúde dos animais tratados e a qualidade dos alimentos provenientes desses animais. O presente trabalho faz uma revisão crítica sobre BE. Para tanto, o assunto foi dividido em três grandes partes: 1- Entendendo a bioequivalência: importância de estudos de BE para a saúde animal e humana; 2- tipos de estudos de BE; 3- considerações gerais sobre delineamentos experimentais que envolvam estudos de bioequivalênciaBioequivalence (BE) studies are scientific methods that allow comparison of different medicinal products containing the same active substance, or different batches of the same medicinal products or, in a broad sense, different routes of administration of the same product.Actually, legislation on generic drugs and bioequivalence only exist in Brazil for drugs intended for human purposes. In the field of Veterinary Medicine, BE is being used in many countries as part of the necessary requirements for registration of animal health products, i.e., to provide efficacy and safety animal data and to allow consumers safety; indeed, they also assure the quality of the food derived from treated animals. The present manuscript was designed to review and discuss BE; for that, it was divided into three major parts: 1- understanding bioequivalence: importance of BE studies for animal and human health; 2- type of BE studies included; 3- general consideration on experimental design involved o BE studie

Effect of cyhalothrin on Ehrlich tumor growth and macrophage activity in mice

Cyhalothrin, a pyrethroid insecticide, induces stress-like symptoms, increases c-fos immunoreactivity in the paraventricular nucleus of the hypothalamus, and decreases innate immune responses in laboratory animals. Macrophages are key elements in cellular immune responses and operate at the tumor-host interface. This study investigated the relationship among cyhalothrin effects on Ehrlich tumor growth, serum corticosterone levels and peritoneal macrophage activity in mice. Three experiments were done with 10 experimental (single gavage administration of 3.0 mg/kg cyhalothrin daily for 7 days) and 10 control (single gavage administration of 1.0 mL/kg vehicle of cyhalothrin preparation daily for 7 days) isogenic BALB/c mice in each experiment. Cyhalothrin i) increased Ehrlich ascitic tumor growth after ip administration of 5.0 x 106 tumor cells, i.e., ascitic fluid volume (control = 1.97 ± 0.39 mL and experimental = 2.71 ± 0.92 mL; P < 0.05), concentration of tumor cells/mL in the ascitic fluid (control = 111.95 ± 16.73 x 106 and experimental = 144.60 ± 33.18 x 106; P < 0.05), and total number of tumor cells in the ascitic fluid (control = 226.91 ± 43.22 x 106 and experimental = 349.40 ± 106.38 x 106; P < 0.05); ii) increased serum corticosterone levels (control = 200.0 ± 48.3 ng/mL and experimental = 420.0 ± 75.5 ng/mL; P < 0.05), and iii) decreased the intensity of macrophage phagocytosis (control = 132.3 ± 19.7 and experimental = 116.2 ± 4.6; P < 0.05) and oxidative burst (control = 173.7 ± 40.8 and experimental= 99.58 ± 41.7; P < 0.05) in vitro in the presence of Staphylococcus aureus. These data provide evidence that cyhalothrin simultaneously alters host resistance to Ehrlich tumor growth, hypothalamic-pituitary-adrenocortical (HPA) axis function, and peritoneal macrophage activity. The results are discussed in terms of data suggesting a link between stress, HPA axis activation and resistance to tumor growth.FAPESPCNP

Efeitos do praguicida amitraz no comportamento agressivo induzido pelo isolamento social em camundongos

Estudaram-se os efeitos do amitraz, um derivado formamidínico, no comportamento agressivo induzido pelo isolamento social em camundongos. Os resultados mostraram que o amitraz aumentou a latência para o primeiro ataque e diminuiu não somente a duração de briga como as freqüências de ataques entre esses animais. Estes resultados sugeriram que os efeitos do praguicida sobre o comportamento agressivo dos camundongos foram conseqüência de um efeito inibitório do mesmo sobre a atividade da enzima monoamina oxidase no Sistema Nervoso Central, e, conseqüentemente, de um aumento dos níveis cerebrais de serotonina.The effects of amitraz, a formamidine derivative on isolation-induced aggression were studied in mice. Results show that amitraz increased the latency to the first attack and increased not only the fight duration but also the frequencies of attacks and tail flickings. These results suggested that pesticide effects on aggressive behavior could be a consequence of it’s inhibitory effects on monoamine oxidase activity within the Central Nervous System, most probably through the increments it produces on serotonin levels

Dose-response effects of systemic anandamide administration in mice sequentially submitted to the open field and elevated plus-maze tests

The endocannabinoid system is involved in the control of many physiological functions, including the control of emotional states. In rodents, previous exposure to an open field increases the anxiety-like behavior in the elevated plus-maze. Anxiolytic-like effects of pharmacological compounds that increase endocannabinoid levels have been well documented. However, these effects are more evident in animals with high anxiety levels. Several studies have described characteristic inverted U-shaped dose-response effects of drugs that modulate the endocannabinoid levels. However, there are no studies showing the effects of different doses of exogenous anandamide, an endocannabinoid, in animal models of anxiety. Thus, in the present study, we determined the dose-response effects of exogenous anandamide at doses of 0.01, 0.1, and 1.0 mg/kg in C57BL/6 mice (N = 10/group) sequentially submitted to the open field and elevated plus-maze. Anandamide was diluted in 0.9% saline, ethyl alcohol, Emulphor® (18:1:1) and administered ip (0.1 mL/10 g body weight); control animals received the same volume of anandamide vehicle. Anandamide at the dose of 0.1 mg/kg (but not of 0.01 or 1 mg/kg) increased (P < 0.05) the time spent and the distance covered in the central zone of the open field, as well as the exploration of the open arms of the elevated plus-maze. Thus, exogenous anandamide, like pharmacological compounds that increase endocannabinoid levels, promoted a characteristic inverted U-shaped dose-response effect in animal models of anxiety. Furthermore, anandamide (0.1 mg/kg) induced an anxiolytic-like effect in the elevated plus-maze (P < 0.05) after exposing the animals to the open field test.FAPESPCNP

Alterações morfológicas em ratas induzidas pelo tratamento prolongado com o bromopride

There were morphoIogicaIy examined the ovaries, uterus, fallopian tubes and mammary glands of adult female rats, that were long-term treated with bromopride. Large corpus luteum, uterus in a secretory stage and hipertrophiated mammary gland were observed in treated animals. These marked morphological changes were correlated to the neuroendocrinal effects of the drug, considering what it is able to block tuberoinfundibuIar dopamine (DA) receptors leading to an increase in prolactin levels.Foram examinados ovários, úteros, trompas de falópio e glândulas mamárias, provenientes de ratas tratadas prolongadamente com o bromopride. Foram observados corpos lúteos muito desenvolvidos, úteros em fase secretória e glândulas mamárias hipertrofiadas. Estas alterações morfológicas marcantes estão correlacionadas com os- efeitos neuroendócrinos da droga, pois esta é capaz de bloquear os dopaninoceptores do sistema tuberoinfundibular, aumentando, assim, os níveis séricos de prolactin

THE ROAD TO 2024 OLYMPIC GOLD MEDAL: A CASE REPORT OF THREE ELITE BEACH VOLLEYBALL PLAYERS

The anthropometrics, limbs maximum isometric force and jump performance in beach-volleyball players were described. Three female elite beach volleyball players selected to participate in the 2022 World Championships Circuit were recruited to participate in the study. Body composition, squat, supine, and rowing isometric maximal force, and power test, squat, and countermovement jumps were measured. Body fat percentage varied between 13 and 24.2%. Squat, supine and rowing isometric force (N) presented median (M) and interquartile ranges (IQR) of 145 (128, 186.6), 40 (33, 66.75) and 65.2 (57.6, 76,6). The height (cm), absolute (W) and relative power (W/kg) M and IQR range values were 32.55 (27.32, 35.10), 32.69 (31.50, 34.69) and 44.18 (40.65, 46.30). Findings can guide morphological and physical training for elite players

Behavioral and biochemical effects of xylazine: possible interactions between central noradrenergic-dopaminergic systems

Alguns efeitos comportamentais e bioquímicos da xilazina foram estudados em ratos e camundongos. Os resultados mostraram que a xilazina: a) diminuiu a atividade geral de ratos e camundongos observados em campo-aberto; b) foi incapaz de produzir catatonia e suprimiu este comportamento induzido pelo haloperidol em camundongos; c) potencializou o comportamento estereotipado induzido pela apomorfina em ratos; d) aumentou os níveis cerebrais de noradrenalina, porem não alterou aqueles de dopamina. Estes resultados foram discutidos considerando-se ação da xilazina em sislemas noradrenérgicos centrais e da interação entre sistemas noradrenérgicos e dopaminérgicos centrais.Behavioral and biochemical effects of xylazine were studied both in rats and mice. The results showed that xylazine: a) decreased the general activity of rats and mice observed in an open field; b) was unable to produce catatonia and suppressed haloperidol-induced catatonia in mice; c) increased apomorphine-induced stereotyped behavior in rats; and d) increased brain noradrenaline without effect on brain dopamine levels. These results were discussed in the light of a possible interference of xylazine with brain noradrenergic system and, thus, with the dynamic interaction between noradrenergic-dopaminergic neurons within the Central Nervous System

A Documentação Arqueológica sobre as Figuras Zoomorfas de Cerâmica do Sítio Brazabrantes I no Centro Oeste Brasileiro

This article seeks to highlight small zoomorphic ceramic pieces found in the state of Goias- Goiania 30 km from the capital near the town of Brazabrantes in Brazabrantes Site I, within the North-South Railway Project. Excavation methods began with artificial levels of 0.10 m throughout the rescue, even when it started to dig the trench and its expansions resulting from the large amount of material found. Hopefully that the deepening of the research material in Brazabrantes Site I and analysis laboratory of all material rescued can bring further clarification of the pieces found there.O presente artigo pretende destacar pequenas peças zoomorfas em cerâmica encontradas no Estado de Goiás a 30 km da capital Goiânia próximo à cidade de Brazabrantes no Sítio Brazabrantes I, dentro do Projeto da Ferrovia Norte-Sul, Extensão Sul. Os métodos de escavação utilizados iniciaram-se com níveis artificiais de 0,10 m durante todo o resgate, até quando se começou a escavação da trincheira e suas ampliações decorrentes da grande quantidade de material encontrado. Espera-se que o aprofundamento das pesquisas no Sítio Brazabrantes I e a análise laboratorial de todo material resgatado possa trazer mais esclarecimentos sobre as peças ali encontradas

A method for the quantitative analysis of the dog’s lacrimal secretion

Descrevem os autores, um método quantitativo para avaliar o fluxo da secreção lacrimal de cães, obtida durante a estimulação elétrica contínua do nervo lacrimal de animais anestesiados. Os autores sugerem que o efeito da secreção lacrimal pela estimulação elétrica é máximo quando as características do estímulo empregado são: supramáximo, 2 milissegundos; 15 Hz, durante 5 minutos por 5 minutos de intervalo.A new method is described for the quantitative analysis of the dog’s lacrimal secretion obtained during continuous electrical stimulation of the lacrimal nerve in anesthetized animals. The nature of the secretory fibres conveyed by the lacrimal gland is discussed. The authors suggest that the effects of lacrimal nerve stimulation on lacrimal secretion are maximal when electrical stimulation with the following characteristics is used: supramaximum, 2 miliseconds duration, 15 Hz, during 5 min with a 5 min-interval

Efeitos comportamentais e bioquímicos da xilazina: possíveis interações entre os sistemas noradrenérgico e dopaminérgico centrais

Alguns efeitos comportamentais e bioquímicos da xilazina foram estudados em ratos e camundongos. Os resultados mostraram que a xilazina: a) diminuiu a atividade geral de ratos e camundongos observados em campo-aberto; b) foi incapaz de produzir catatonia e suprimiu este comportamento induzido pelo haloperidol em camundongos; c) potencializou o comportamento estereotipado induzido pela apomorfina em ratos; d) aumentou os níveis cerebrais de noradrenalina, porem não alterou aqueles de dopamina. Estes resultados foram discutidos considerando-se ação da xilazina em sislemas noradrenérgicos centrais e da interação entre sistemas noradrenérgicos e dopaminérgicos centrais