Radioimmunoassay of relaxin throughout pregnancy and during parturition in the rat.

Relaxin immunoactivaity concentrations in the peripheral sera been measured during pregnancy and parturition in rats with a homologous rat relaxin RIA. Relaxin was not detected until day 10 of pregnancy (day 10). Relaxin levels increased markedly over the next 4 days and generally ranged between 50-100 ng/ml from days 14-20. A prepartum surge in relaxin levels, which appeared to be associated with the photoperiod, occurred on day 21 in unanesthetized rats bled via indwelling jugular cannulas. Mean relaxin levels in these animals increased sharply from less than 80 ng/ml on day 20 to approximately 140 ng/ml at 1400 h on day 21 and declined to less than 60 ng/ml during the 12-24 h preceding parturition. The prepartum surge in relaxin immunoactivity may be associated with luteolysis, since there was an accelerated decline in progesterone concentrations concurrent with the prepartum relaxin surg. Rats also experienced a surge in relaxin concentrations during parturition. The mean maximal level of relaxin during parturition was approximately 180 ng/ml. The rate of decline of rat relaxin immunoactivity levels after bilateral ovariectomy on day 21 demonstrated characteristics of a multiexponential curve. The mean clearance t 1/2 from 0-30 min was 22 +/- 3 min (+/- SEM), and the mean t 1/2 from 30-180 min was 56 +/- 7 min (+/0 SEM).

Second primary lung cancer.

We reviewed our experience with second primary lung cancer (SPLC) at the Little Rock Veterans Affairs Medical Center from 1966 to 1993. Fifty-four patients were found to have 65 such lesions after 1,572 "curative" resections for lung cancer (4.1%). Eleven patients had at least a third primary tumor (3 having more). Metachronous SPLCs comprised 60% (39/65) and synchronous 40% (26/65). The mean interval between first and second tumors was 54.63 +/- 8 (standard error) months (range, 5 to 218 months), and that between second and third was 26.1 +/- 7.4 (standard error) (range, 5.5 to 51 months). Squamous cell carcinoma comprised 58.4% (38/65), adenocarcinoma 30.8% (20/65), and small cell carcinoma 10.8% (7/65). Histology of the SPLC was the same as that of the first tumor in 50.7% (33/65). Stage I primary tumors comprised 76% (41/54) of index tumors, 61.1% (33/54) of SPLCs, and 72.2% (8/11) of third primary tumors. Second primary lung cancer followed minimal resection in 44% (24/54), lobectomy in 37% (20/54), and pneumonectomy in 13% (7/54) of cases. There was no evidence that minimal resection for the first primary tumor predisposed to SPLC. After 1983 the majority of SPLCs were diagnosed with computed tomographic scanning. After resection of SPLCs, survival rates at 3 and 5 years were 26% and 18%, metachronous 39% and 23.4%, and synchronous 12.25% and 12.25%.

Effects of dimethyl sulfoxide (DMSO) on pulmonary fibrosis in rats and mice.

Dimethyl sulfoxide (DMSO), a putative anti-inflammatory agent and free radical scavenger, was shown to protect against acute bleomycin-induced pulmonary fibrosis in the rat (Pepin and Langner, Biochem. Pharmacol., 34 (1985) 2386). We examined the effect of DMSO on bleomycin-induced pulmonary toxicity in Swiss outbred mice and Sprague-Dawley rats, and on butylated hydroxytoluene (BHT)-induced pulmonary toxicity in Swiss outbred mice. Bleomycin (BL)-induced mortality in mice (20% at 0.1 units BL) and rats (50% at 1.5 units BL) was increased to 100% by daily DMSO (5 g/kg 50% in saline). Similar DMSO treatment after lower doses of bleomycin (1 unit BL in rats and 0.075 or 0.050 units in mice) increased lung hydroxyproline content in the rat but had no effect in the mouse. Lung hydroxyproline content in mice 14 days after 400 mg/kg BHT in corn oil was also slightly increased by daily DMSO at 5 g/kg, but not at 1 or 2 g/kg. Daily DMSO (5 g/kg) did not alter cellular proliferation [( 14C]thymidine incorporation into pulmonary DNA) in the lung at 2 or 5 days after BHT. Thus, we found that DMSO potentiated the lethality of bleomycin, and potentiated or had no effect on bleomycin or BHT-induced pulmonary fibrosis in the rat and mouse.

Functional development of the hypothalamic-adenohypophyseal-testicular (HAT) axis in the chick embryo.

Plasma testosterone concentrations in intact and surgically partially decapitated (hypothalamo-hypophyseoprivic) chick embryos were determined by radioimmunoassay for the incubation interval, Days 7.5-17.5. "Hypophysectomy" of male chick embryos at 33-38 hr of incubation resulted in plasma testosterone levels which were significantly lower than those of intact embryos on Days 13.5, 15.5, and 17.5. The addition of luteinizing hormone (LH) to the chorioallantoic membrane (CAM) of decapitated embryos increased plasma testosterone concentrations to normal levels by Day 13.5, while LH and pituitary transplants to the CAM elevated plasma testosterone to above normal values by Day 15.5. These observations, together with other findings, are interpreted as demonstrating that in the chick embryo the adenohypophyseal-testicular axis is functional by Day 13.5 of incubation. There are also indications that the hypothalamic-adenohypophyseal-testicular complex is functional at this same embryonic time.

Effect of relaxin on parturition and frequency of live births in pigs.

Gilts on Day 105 of gestation were sham ovariectomized (Group C, N = 5); ovariectomized and given i.m. injections of 100 mg progesterone twice daily from Day 105 to 112 (Group OP, N = 5); or ovariectomized and given progesterone and i.m. injections of 1 mg highly purified porcine relaxin 4 times/day from Day 105 until the end of parturition (Group OPR, N = 5). Concentrations of progesterone in peripheral plasma of gilts in Group OP were similar to those in Group C. Relaxin was undetectable in peripheral plasma of gilts in Group OP which also showed prolonged parturition (P less than 0.001) and impaired frequency of live births (P less than 0.001), although onset of lactation was not affected. In Group OPR the duration of parturition and frequency of live births were similar to those observed for gilts in Group C. These results indicate that the ovarian hormone relaxin is necessary for normal duration of parturition and frequency of live births and that the onset of lactation is not prevented by an absence of relaxin.

Release of relaxin by a nonluteolytic dose of prostaglandin F2 alpha in pregnant swine.

Ten gilts were infused intravenously for 5 min on Days 105 and 108 of gestation with 50 micrograms prostaglandin F2 alpha (PGF2 alpha) in 10 ml of saline or saline alone. Plasma concentrations of relaxin and progesterone were determined in samples taken 1) immediately before and after infusion, 2) at 10-min intervals throughout the first h postinfusion, 3) at 30-min intervals throughout the next 5 h, and 4) at 12-h intervals from Day 103 of gestation through Day 1 postpartum. Plasma concentrations of relaxin were increased immediately after infusion with PGF2 alpha and peaked within 10 min postinfusion. The peak was followed by a rapid decline in plasma relaxin throughout the remainder of the first hour following infusion. Progesterone values did not change from preinfusion levels for either treatment during this time period and did not differ between treatments for the remainder of the gestation period. When compared to controls, PGF2 alpha-treated animals were not significantly different with respect to length of gestation, duration of parturition or frequency of live births. These results indicate that exogenous PGF2 alpha can stimulate relaxin release from the corpus luteum without inducing luteolysis.