Effects of ascorbic acid on the mouse embryo and on cyclophosphamide-induced cephalic DNA strand breaks in vivo.

Pregnant C3H mice were exposed to 3.34 and 6.68 g ascorbic acid/kg body weight on the 11th day post-copulation, and to co-administration of a teratogenic dose of cyclophosphamide (CP, 15 mg/kg body weight). The effects on embryonal cephalic DNA strand breaks were assessed 16 h after drug administration. In order to establish whether vitamin C was embryotoxic or altered CP-induced toxicity, mice were sacrificed on day 18 after copulation to record fetal weights, gross morphological abnormalities, and fetal mortality. Administration of 3.34 g ascorbate/kg was not associated with demonstrable toxic effects but with 6.68 g ascorbic acid/kg there was a 46% incidence of fetal mortality. In embryos exposed to CP, 15 mg/kg, there was a decrease in fetal weight (median fetal weight 678 mg compared with 967 mg in controls), all fetuses were morphologically abnormal and 59% of cephalic DNA was double stranded compared with 81% for controls (p less than 0.001). When vitamin C, 3.34 g/kg, was co-administered with CP the incidence of DNA strand breaks remained unchanged. However, all fetuses were morphologically normal and there was no reduction in fetal weight. These findings demonstrate that administration of 6.68 g vitamin C/kg is toxic to the mouse embryo, but a lower dose of 3.34 g/kg is not, and has a protective effect against the toxic manifestations of CP. This protection is not associated with prevention of cephalic DNA strand breaks.

[Use of buprenorphine as a cornerstone in narcosis and as analgesic in the postoperative period in gynecologic surgery]. / Impiego della buprenorfina come agente cardine della narcosi e come analgesico nel post-operatorio in chirurgia ginecologica.

In a clinical trial buprenorphine (0.3 mg i.v.) was administered, 20-45 minutes before the surgical operation, to 220 women undergoing gynecological surgery. If necessary buprenorphine (0.2-0.3 mg i.m.) was administered also in the post-operative period. By the pre-operatory administration of buprenorphine, a great stability of life parameters was observed during the surgical operation. In the post-operative period most of the patients showed absence of pain or mild pain.

Cyclophosphamide induced DNA strand breaks in mouse embryo cephalic tissue in vivo.

Pregnant C3H mice were exposed to teratogenic doses of cyclophosphamide (CPA), on the 11th day after copulation. The effects of this agent on embryonal cephalic DNA strand breaks were assessed between 3 and 40 h after drug administration. Administration of 15, 30 and 60 mg CPA/kg body weight resulted in conversion of 23, 30 and 44% of the DNA to the single-stranded form, respectively. No detectable DNA damage was evident 3 h after drug administration, but after 6 h significant DNA damage had occurred, reaching a maximum after 9 h. However, no evidence of DNA strand breaks was present at 22, 30 and 40 h after CPA treatment, suggesting that these lesions had been repaired. These findings demonstrate that cephalic DNA damage induced by CPA in the developing mouse embryo occurs in a time and concentration dependent manner, and provide some insight into the kinetics of formation and removal of DNA strand breaks caused by CPA in vivo.

The effects of in vivo administration of teratogenic doses of vitamin A during the preimplantation period in the mouse.

To examine the effects of vitamin A administered during the preimplantation period, pregnant C3H mice were exposed to teratogenic doses of the vitamin 60 h after copulation. Fetuses were examined for gross abnormalities on the 18th day of gestation and viability, cell number, mitotic index, and chromosome structure were assessed in 81-h blastocysts to determine whether embryotoxic effects were apparent in the preimplantation embryo. There was a reduction in the fetal weight of 18-day fetuses treated in this manner with 15,000 and 30,000 IU vitamin A (p less than 0.0003 in each case), and doses of 10,000 IU and greater were associated with a significantly higher incidence of gross abnormalities. Malformations included exophthalmos, anophthalmia, microphthalmia, exencephaly, exomphalos, and limb defects. Administration of 30,000 IU vitamin A resulted in resorption and intrauterine death in 70% of cases. There was no indication that vitamin A adversely affected 81-h blastocyst viability, cell number, mitotic index, and chromosome structure. The findings suggest that the teratogenic effects that were noted later in fetal life were the result of an action on the developing fetus of the vitamin at a stage later than 81-h and are consistent with the relative resistance of the preimplantation embryo to toxic injury. Persistence of vitamin A, either in the mother or the embryo, is the most likely explanation for the later expression of toxic injury, which is characteristic of the effects that are noted as a result of exposure to the teratogen during the period of organogenesis.

Immunological features of nonhealing midline granuloma.

A 60-year-old man affected by nonhealing midline granuloma (NHmG) is described. The histopathological features, the clinical course and the radiosensitivity of the lesion clearly differentiate this pathological condition from malignant lymphomas and from Wegener's granulomatosis (WG). The presence of antinuclear antibodies with an antinucleolar pattern in a subject bearing HLA-B8 suggests the involvement of autoimmune phenomena and a close relation between NHmG and WG.