Study of the effects of ß-myrcene on rat fertility and general reproductive performance

Beta-Myrcene (MYR) is a monoterpene found in the oils of a variety of aromatic plants including lemongrass, verbena, hop, bay, and others. MYR and essential oils containing this terpenoid compound are used in cosmetics, household products, and as flavoring food additives. This study was undertaken to investigate the effects of MYR on fertility and general reproductive performance in the rat. MYR (0, 100, 300 and 500 mg/kg) in peanut oil was given by gavage to male Wistar rats (15 per dose group) for 91 days prior to mating and during the mating period, as well ass to females (45 per dose group) continuously for 21 days before mating, during mating and pregnancy, and throughout the period of lactatiomn up to postnatal day 21. On day 21 of pregnancy one-third of the females of each group were submitted to cesarean section. Resorption, implantation, as well as dead and live fetuses were counted. All fetuses were examined for external malformation, weighed, and cleared and stained with Alizarin Red S for skeleton evaluation. The remaining dams were allowed to give birth to their offspring. The progeny was examined at birth and subsequently up to postnatal day 21. Mortality, weight gain and physical signs of postnatal development were evaluated. Except for an increase in liver and kidney weights, no other sign of toxicity was noted in male and female rats exposed to MYR. MYR did not affect the mating index (proportion of females impregnated by males) or the pregnancy index (ratio of pregnant to sperm-positive females). No sign of maternal toxicity and no increase in externally visible malformations were observed at any dose level. Only at the highest dose tested (500 mg/kg) did MYR induce an increase in the resorption rate and a higher frequency of fetal skeleton anomalies. No adverse effect of MYR on postnatal weight gain was noted but days of appearance of primary coat, incisor eruption and eye opening were slightly delayed in the exposed offspring. On the basis of the data presented in this paper the no-observed-adverse-effect level (NOAEL) for toxic effects on fertility and general reproductive performance can be set at 300 mg of Beta-myrcene/kg body weight by the oral route.

Ventilação não-invasiva no cardiopata grave / Noninvasive ventilation in the severe congestive heart failure patient

A insuficiência cardíaca congestiva leva a aumento na água extravascular pulmonar, redução do volume e da complacência pulmonar e aumento da resistência de vias aéreas, resultando em aumento do trabalho respiratório, aumento do consumo de oxigênio e aumento da sobrecarga ventricular esquerda. A utilização de pressão positiva contínua nesses pacientes melhora a oxigenação, diminui o trabalho respiratório, melhora a mecânica pulmonar, reduz a pressão transmural sobre o ventrículo esquerdo e diminui o retorno venoso, contribuindo para maior desempenho cardíaco. O uso de pressão positiva contínua diminui a necessidade de ventilação mecânica no edema agudo de pulmão e reduz o tempo de internação na unidade de terapia intensiva. A utilização de pressão positiva contínua noturna em cardiopatas crônicos demonstrou melhora significativa da fração de ejeção durante o dia, em associação com melhora da classe funcional, após o tratamento por um mês em pacientes com cardiomiopatia dilatada e apnéia obstrutiva do sono concomitante. O uso de pressão positiva contínua deve ser entendido não só como o primeiro suporte ventilatório no edema agudo dos pulmöes, como também um tratamento não-farmacológico que tem o potencial de melhorar a função cardíaca nos pacientes clinicamente estáveis, porém com insuficiência cardíaca grave.

Study of the embryofeto-toxicity of Crown-of-Thorns (Euphorbia milii) latex, a natural molluscicide

The crude latex of Crown-of-Thorns (Euphorbia milii var. Hislopii) is a potent plant molluscicide and a promising alternative to the synthetic molluscicides used in schistosomiasis control. The present study was undertaken to investigate the embryofeto-toxic potential of E. Milii latex. The study is part of a comprehensive safety evaluation of this plant molluscicide. Lyophilized latex (0, 125, 250 and 500 mg/kg body weight) in corn oil was given by gavage to Wistar rats (N = 100) from days 6 to 15 of pregnancy and cesarean sections were performed on day 21 of pegnancy. The numbers of implantation sites, living and dead fetuses, resorptions and corpora lutea were recorded. Fetuses were weighed, examined for external malformations, and fixed for visceral examination, or cleared and stained with Alizarin red S for skeleton evaluation. A reduction of body weight minus uterine weight al term indicated that E. Milii latex was maternally toxic over the dose range tested. No latex-induced embryolethality was noted at the lowest dose (125 mg/kg) but the resorption rate was markedly increased at 250 mg/kg (62.5 percent) and 500 mg/kg (93.4 percent). A higher frequency of fetuses showing signs of delayed ossification (control: 17.4 percent; 125 mg/kg: 27.4 percent and 250 mg/kg: 62.8 percent; P<0.05 vs control) indicated that fetal growth was retarded at doses ³125 mg latex/kg body weight. No increase in the proportion of fetuses with skeletal anomalies was observed at the lowest dose but the incidence of minor skeletal malformations was higher at 250 mg/kg body weight (control: 13.7 percent; 125 mg/kg: 14.8 percent; 250 mg/kg: 45.7 percent; P<0.05 vs control). Since a higher frequency of minor malformations was noted only at very high doses of latex which are embryolethal and maternally toxic, it is reasonable to conclude that this plant molluscicide poses no teratogenic hazard or, at least, that this possibility is of a considerably low order of magnitude.

Embryotoxic effects of misoprostol in the mouse

Misoprostol (MSP) is a synthetic prostaglandin E1 methyl analogue indicated for the prevention of gastric ulcers induced by nonsteroidal anti-inflammatory drugs (NSAIDs). Because of its abortifacient properties, MSP has been extensively missused for abortion induction in Brazil. Since abortion induction with MSP very often fails and pregnancy continues to term, there has been increasing concern regarding the potential teratogenicity of this PGE1 analogue in humans. The objective of the present study was to evaluate the embryotoxicity of MSP in mice. A single dose of MSP(20 or 30 mg/kg body weight) was administered to Han:NMRI mice (ca 60 days old) by gavage on day 10 of pregnancy. The number of treated mice was as follows: control, 19; MSP 20 mg/kg, 10; MSP 30 mg/kg, 28. Cesarean sections were performed on day 18 of pregnancy and the number of resorptions and implantation sites were recorded. Fetuses were weighed, examined for external malformations, fixed, cleared and stained with Alizarin Red S for skeleton evaluation. No evidence of embryotoxicity was found at the lower dose tested. A slight and reversible deficit in pregnancy weight gain ...

Embryotoxicity of methanol in well-nourished and malnourished rats

1. The objective of the present study was to investigate whether maternal protein-energy malnutrition alters methanol-induced embryotoxic effects in rats. 2. On day 0 of pregnancy, dams were assigned at random to one of the following treatment groups: well-nourished methanol (WNM), well-nourished control (WNC), malnourished methanol (MNM) and malnourished control (MNC). Malnourished animals received half of the well-nourished food intake (ca 12 g/day) throughout pregnancy. Methanol was adminsitered by gavage (2.5 g/kg body weight) from gestation day 6 to 15. 3. Rats were weighed on days 0,6 to 15, and 21 of pregnancy. On day 21 rats were submitted to cesarean section. The number of implantations, living and dead fetuses, resorptions and corpora lutea was recorded. All fetuses were weighed, examined for externally visible malformations, fixed, and examined for skeletal anomalies after clearing and staining with Alizarin Red S. 4. An increased proportion of fetuses with skeletal malformations, particularly cervical extra ribs, was found in the methanol-treated groups (fetuses with skeletal malformations: WNC = 5.6 percent WNM = 45.4 percent, MNC = 3.8 percent, and MNM = 38.8 percent). Malnutrition produced fetal growth retardation, but did not cause any increase in the occurrence of gross structural malformations. The methanol-induced increase in the proportion of fetuses with extra ribs was not altered by malnutrition, but methanol potentiated the malnutrition-induced increase in the proportion of fetuses with sings of delayed ossification (WNC = 18.6 percent, WNM = 25.4 percent, MNC = 39.7 percent, and MNM = 78.4 percent). 5. These findings suggest that methanol-induced gross structural malformations are not affected by maternal malnutrition, but the delay in ossification caused by malnutrition is aggravated by treatment with methanol

Comparison of five methods for the determination of lethal dose in acute toxicity studies

The aim of the prsent study was to compare the realibility of LD50 determination using the traditional Litchfield and Wilcoxon method with that obtained by forur alternative tests requiring smaller numbers of animals, for the purpose of classifyng chemicals according to their acute toxicity. Acute lethal dose determinations were carried out in mice for oral and intraperitoneal administration of hexachlorophene, lidocaine, methanol, phenobarbital and physostigmine. The Molinengo method proved not to be as reliable as suggested by its author. Determination of LD50 using the Thompson and Weil method or, alternatively, the maximal non-lethal dose and the approximate lethal dose permitted the classification of the chemicals in essentially the same order. The approximate lethal dose method, in particular, seems to be a very suitable alternative method to the classical LD50 test since it requires only about 6 animals, provides enough information to order chemicals according to their toxicities, and provides useful information for planning subsequent repeated-dose studies