Charles A. Hodson

Effects of Abdominal Vagotomy on the Estrous Cycle of the Rat and the Induction of Pseudopregnancy

Abdominal vagotomy of estrus or proestrus rats resulted in disruptions of the estrous cycle which was characterized by prolonged periods of diestrus (10-12 days in length). In contrast, vagotomy on metestrus or diestrus did not disrupt the estrous cycle. The induction of pseudopregnancy, in response to cervical stimulation on the morning of estrus, was also interrupted by abdominal vagotomy. The nocturnal and diurnal prolactin surges and elevations in serum progesterone, characteristic of pseudopregnancy, were prevented by vagotomy. Vagotomy, also, largely prevented the formation of deciduoma in response to traumatization of the uterus in cervically stimulated rats.

Effects of peripheral nerve lesions during pregnancy on parturition in rats

SummaryBilateral section of either the sensory or motor branch of the pelvic nerve or pudendal nerve was performed in rats on days 8–10 of pregnancy, and the effects on delivery were observed. Bilateral resection of the sensory branch of the pelvic nerve reduced the number of live pups per litter, and increased the number of stillbirths and the number of fetuses retained in utero per litter at day 24. Sectioning motor components of the pelvic nerve, or both motor and sensory components of the pudendal nerve, had no effects on delivery in rats. We conclude that of the peripheral nerves evaluated in this study, only the sensory branch of the pelvic nerve is required for normal vaginal delivery in this species.

Chronic hyperprolactinemia depletes hypothalamic dopamine concentrations in male rats

The tuberoinfundibular dopamine (TIDA) system appears to tonically inhibit pituitary prolactin secretion while moderate elevations in serum prolactin levels, in turn, augment the turnover rate of dopamine (DA) without affecting the steady state concentrations of DA in the TIDA neurons (1-5). The present study demonstrates that chronic elevations in serum prolactin, to greater than 2,000 ng/ml, induced by the prolactin secreting MtTW15 tumor, decreased DA concentrations by 47% in the median eminence-arcuate nucleus (ME-ARC) region, by 43% in the medial basal hypothalamus (MBH) and 14% in the preoptic area-anterior hypothalamic region (POA-AH) without influencing the norepinephrine levels in these regions. Thus, chronic stimulation of hypothalamic DA neurons by prolactin may lead to depletion of DA concentrations and this may be an important factor in the reduced DA levels observed in hyperprolactinemia of senescent rats or that produced by chronic estrogen treatment.

Endometrial carcinoma in vitro chemosensitivity testing of single and combination chemotherapy regimens using the novel microculture kinetic apoptosis assay: implications for endometrial cancer treatment

OBJECTIVE The in vitro microculture kinetic (MiCK) apoptosis assay has been used to predict single or combination chemotherapy response in leukemia patients. This feasibility study addressed MiCK in endometrial cancer specimens. METHODS Endometrial cancer specimens from total abdominal hysterectomies were processed at a central laboratory. Single cell suspensions of viable endometrial cancer cells were plated in individual wells. Single and combination regimens were tested: combinations of doxorubicin, cisplatin, and paclitaxel and carboplatin and paclitaxel (Gynecologic Oncology Group [GOG] 209 endometrial cancer phase III trial arms) as well as single agent testing with paclitaxel, carboplatin, doxorubicin, cisplatin, ifosfamide, and vincristine (active agents in GOG trials). Apoptosis was measured continuously over 48 hours. RESULTS Fifteen of nineteen patients had successful assays. The highest mean chemo sensitivity was noted in the combination of cisplatin, doxorubicin, and paclitaxel with lower mean chemosensitivity for carboplatin and paclitaxel. Combination chemotherapy had higher chemosensitivity than single drug chemotherapy. However, in 25% of patients a single drug had higher chemosensitivity than combination chemotherapy. As single agents, ifosfamide, cisplatin, and paclitaxel had the highest kinetic unit values. CONCLUSION Using a panel of agents simulating clinical dose regimens, the MiCK assay was feasible in evaluating in vitro chemosensitivity of endometrial cancer. MiCK assay results correlated with GOG clinical trial results. However, 25% of patients might be best treated with single agent chemotherapy selected by MiCK. Ifosfamide, cisplatin, and paclitaxel appear to have high activity as single agents. MiCK may be useful in future new drug testing and individualizing endometrial cancer patients chemotherapy management.

Effect of cyclosporin treatment on luteinizing hormone and prolactin

The effect of cyclosporin A (CsA) treatment on LH and prolactin was investigated. Chronic daily administration of an immunosuppressive dose of CsA (1.5 mg/100g bw) increased serum LH concentrations and pituitary gland LH content. CsA treatment also resulted in increased serum testosterone. Immunosuppressive doses of CsA had no effect on serum prolactin or pituitary gland prolactin content. Acute administration of low doses of 0.12, 1.2, 12 and 120ug CsA/100g bw had no effect on serum LH or prolactin. These results suggest that administration of immunosuppressive doses of CsA alters serum and pituitary LH and serum testosterone but not prolactin.

Effect of Abdominal Vagotomy at Proestrus on Ovarian Weight, Ovarian Antral Follicles, and Serum Levels of Gonadotropins, Estradiol, and Testosterone in the Rat

The effects of abdominal vagotomy at proestrus on ovarian weight and antral follicles greater than 150 microns diameter and on serum levels of gonadotropins and testosterone were assessed 24 and 48 h and 4 and 8 days after surgery. Serum levels of estradiol were assessed at 4 and 8 days. Vagotomy increased ovarian weight at 48 h, decreased ovarian weight at 4 days, but had no effect by day 8. Vagotomy increased healthy antral follicles 151-394 microns diameter at 24 and 48 h and increased atresia in this size range at 4 and 8 days. Vagotomy decreased healthy follicles 151-384 microns at day 8. Vagotomy decreased healthy follicles 395-570 microns at 24 h and decreased atretic follicles at 48 h. Vagotomy decreased the largest (over 570 micron diameter) healthy follicles at 24 h and 8 days. Vagotomy decreased basal serum LH levels at 48 h and 8 days. (In contrast, vagotomy increased FSH at 24 h). There was no effect on blood levels of estradiol and testosterone. These findings are discussed in relation to the hypothesis that the vagus nerve is a component of the hypothalamo-hypophyseal-ovarian axis.

Comparison of pharyngeal aspirate and amniotic fluid surfactant composition

Amniotic fluid and oropharyngeal aspirate lung maturity profiles obtained simultaneously at delivery in 16 patients are compared. The lecithin/sphingomyelin ratio was greater in oropharyngeal aspirates than in amniotic fluid (p less than 0.02). The percent phosphatidylinositol was greater in oropharyngeal aspirates than in amniotic fluid (p less than 0.03). The mean differences between percent phosphatidylglycerol were not significant. These findings were uninfluenced by the time interval between amniotic fluid and oropharyngeal sampling, gestational age, or neonatal weight. These data could explain the lack of sensitivity of the amniotic fluid lung maturity profile.

Effect of prior nicotine treatment on drug induced changes in serum LH concentrations in rats

The effect of daily injections of nicotine on drug induced changes in LH secretion was investigated in male rats. Daily administration of nicotine for 7 days resulted in decreased basal serum LH concentrations. Nicotine treatment blocked naloxone induced LH release and reduced LHRH induced increases in serum LH. Clonidine induced increases in serum LH were not altered by nicotine treatment and haloperidol treatment did not alter nicotine induced decreases in serum LH. In an acute study nicotine blocked LH secretion induced by the long acting opioid antagonist naltrexone. Collectively these results indicate that opioidergic neurons are involved in the reduction in serum LH that occurs following nicotine. They also indicate that chronic nicotine treatment can reduce the pituitary gland response to LHRH.

Naltrexone treatment attenuates the inhibitory effect of nicotine treatment on serum LH in rats.

The hypothesis that endogenous opioids might have a role in mediating the suppressive effects of nicotine on serum LH concentrations in rats was investigated. Naltrexone treatment prevented the inhibitory effect of high doses of nicotine on serum LH concentrations. Nicotine treatment also prevented the stimulatory effect of naltrexone on serum LH concentrations. These results suggest that the inhibitory effects of nicotine on serum LH concentrations involve an opioidergic component.

Effect of Vagotomy on Postcastration Gonadotropin Secretion in Male Rats

Abstract The postcastration increase in gonadotropins was studied in intact and vagotomized male rats. Rats underwent vagotomy or sham surgery immediately prior to castration. In the first experiment, rats were bled before castration and at 1,2, 4, and 7 days after castration. Serum LH and FSH were significantly lower in vagotomized rats 1 day after castration. On Days 2, 4, and 7 postcastration, serum gonadotropin levels were generally not different among experimental groups. In a second experiment, rats were decapitated at 12 or 24 hr after surgery and castration. Trunk blood was collected for assay of LH. Vagotomy had no effect on LH levels at 12 hr postcastration, but, at 24 hr postcastration, vagotomized rats had significantly lower serum LH than did sham-operated rats. These experiments indicate that vagotomy has a transient suppressive effect on gonadotropin release following castration. Such observations support the hypothesis that the vagus nerve may play a modulatory role in gonadotropin secretion.