Immunostimulatory effects of polar glycopeptidolipids of Mycobacterium chelonae for inactivated rabies vaccine.

Humoral and cellular immune responses were analyzed with Fuenzalida-Palacios rabies vaccine associated with pGPL-Mc, polar glycopeptidolipids extracted from Mycobacterium chelonae, aiming at its use as adjuvant. These results were compared to those obtained with BCG, a well-known immunostimulator, under the same conditions. Rabies vaccine plus pGPL-Mc (2.5 mg/kg) induced a significant increase in serum neutralizing activity, in vitro lymphocyte proliferation (spontaneous, specific and mitogen stimulation) and delayed type hypersensibility. In addition, pGPL-Mc, as well as BCG, enhanced the vaccine potency. Our results support further studies to encourage the use of pGPL-Mc as an immunostimulator of veterinary vaccines, before consideration for human vaccines.

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.

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 pregnancy. 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 at 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%) and 500 mg/kg (93.4%). A higher frequency of fetuses showing signs of delayed ossification (control: 17.4%; 125 mg/kg: 27.4% and 250 mg/kg: 62.8%; P < 0.05 vs control) indicated that fetal growth was retarded at doses > or = 125 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%; 125 mg/kg: 14.8%; 250 mg/kg: 45.7%; 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.

Study of the embryofoetotoxicity of alpha-terpinene in the rat.

alpha-Terpinene (1-isopropyl-4-methyl-1,3-cyclohexadiene) (TER) is a monoterpene found in the essential oils of a large variety of useful plants. Despite the widespread use of plants and essential oils containing TER in folk medicine potions and cosmetics, and as a flavouring food additive, toxicity studies of this monoterpene are scarce. The present study was undertaken to provide data on the embryofoetotoxic potential of TER in the rat. TER (30, 60, 125 and 250 mg/kg body weight) in corn oil was given by gavage to female Wistar rats from day 6 to 15 of pregnancy. Caesarean sections were performed on day 21 of pregnancy. The number of implantation sites, living and dead foetuses, resorptions and corpora lutea were recorded. All foetuses were weighed, examined for externally visible malformations, numbered with a marker pen and fixed in 5% formalin solution. One-third of the foetuses of each litter, chosen at random, were evaluated for visceral anomalies by a microsectioning technique. Heart, lungs, thymus, liver, spleen and kidneys of foetuses that were microdissected were also weighed. The remaining foetuses were examined for skeletal malformations after clearing with potassium hydroxide and staining with Alizarin Red S. A reduction in body weight minus uterine weight at term indicated that the two highest doses tested [125 and 250 mg TER/kg body weight orally] were maternally toxic. No increase in the ratio of resorptions/implantations was observed over the dose range tested. The highest dose of TER (250 mg/kg body weight) reduced the ratio of pregnant/treated female. A decrease in foetal body weight and an increase in foetal kidney weights were noted at 250 mg TER/kg body weight. Signs of delayed ossification (poorly ossified and not ossified bones as well as irregular spongy bones) and a higher incidence of minor skeletal malformations were observed at doses of 60 mg/kg body weight or more. These findings indicate that the no-observed-adverse-effect level for TER-induced embryofoetotoxicity can be set at 30 mg/kg body weight by the oral route.

Single dose toxicity study of beta-myrcene, a natural analgesic substance.

The present study was undertaken to provide data on acute toxicity of beta-myrcene, a peripheral analgesic substance found in the essential oils of several plants. Although myrcene has long been used in perfumes and as a food additive, there is almost no information on its toxicological hazards. The acute oral toxicity of myrcene was low in rodents, with approximate lethal doses (ALD) of 5.06 g/kg body weight for mice and greater than 11.39 g/kg body weight for rats. Necropsy data did not reveal any relevant alteration in rats but histopathology findings in mice suggested that the liver and stomach may be target organs for myrcene toxicity after oral administration. Myrcene is highly irritant to the peritoneum, and deaths after intraperitoneal injection of this monoterpene in rats (ALD 5.06 g/kg body weight) and in mice (ALD 2.25 g/kg body weight) were probably due to drug-induced chemical peritonitis.

Single dose toxicity study of beta-myrcene, a natural analgesic substance

The present study was undertaken to provide date on acute toxicity of ß-myrcene, a peripheral analgesic substance found in the essential oils of several plants. Although myrcene has long been used in perfumes and as a food additive, there is almost no information on its toxicological hazards. The acute oral toxicity of myrcene was low in rodents, with with approximate lethal doses (ALD) of 5.06g/Kg body weight for mice and greater than 11.39 g/Kg body weight for rats. Necropsy data did not reveal any relevant alteration in rats but histophatology findings in mice suggested that the liver and stomach may be target organs for myrcene toxicity after oral administration. Myrcene is highly irritant to the peritoneum, and deaths after intraperitoneal injection of this monoterpene in rats (ALD 5.06 g/Kg body weight) and in mice (ALD 2.25 g/Kg body weight) were probably due to drug-induced chemical peritonitis