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Biomedical subjects

M E Freeman

Publications and source records attributed to M E Freeman.

At least 91 records · Page 5Linked to original sources

Neurotransmitter turnover in rat striatum is correlated with morphine self-administration.

Drugs of abuse probably exert their reinforcing effects through 'reward' pathways in the central nervous system (CNS). Neuronal systems mediating opiate reinforcement have been investigated using pharmacological and electrolytic lesion procedures. Drugs that interfere with catecholaminergic and cholinergic neuronal activity decrease intravenous (i.v.) morphine self-administration in monkeys and rats. Electrolytic lesion procedures in rats have demonstrated that the medial forebrain bundle and caudate nucleus are important in maintaining i.v. morphine self-administration. We have now carried out a direct investigation of striatal (caudate nucleus, putamen and globus pallidus) neuronal systems. We show here that striatal catecholaminergic systems are important in mediating opiate reinforcement, and present direct evidence for the involvement of neurotransmitter systems in morphine reward.

Animals↗

Hypothalamic sites which control the surges of prolactin secretion induced by cervical stimulation.

Artificial stimulation of the uterine cervix (CS) of the rat institutes two daily surges of PRL. These surges in turn activate and maintain luteal progesterone secretion for a 13-day interval known as pseudopregnancy. Electrolytic lesions of the medial preoptic area (MPOA) or electrical stimulation of the dorsomedial-ventromedial areas (DMN-VMN) of the hypothalamus also induce pseudopregnancies. This study was designed to determine if these pseudopregnancies are also characterized by the biphasic pattern of PRL secretion. Bilateral electrolytic lesions were placed in the MPOA on the morning of either estrus or the 14th day after ovariectomy. Both experimental models had nocturnal (0500 h) but no diurnal (1900 h) surges of PRL on the second day after placement of the lesion. Sham-lesioned rats had neither surge. When both surges were initiated by CS on proestrus, placement of the lesion on estrus blocked the diurnal but not the nocturnal surge of PRL. These data suggest that the MPOA possesses neurons which are inhibitory to nocturnal surges and stimulatory to diurnal surges of PRL and that CS removes the inhibition over the former and stimulates the latter. Electrical stimulation of the DMN-VMN initiates both surges of PRL in intact or ovariectomized rats. Thus, CS may also act either directly or indirectly w;thin the DMN-VMN to induce both surges of PRL.

Animals↗

Hemagglutination-inhibiting antibodies in vaccinated children with renal disease.

One year after immunization with a single 0.5-mL dose of influenza virus vaccine, serum samples from 30 children with renal diseases were tested for serum hemagglutination-inhibiting (HI) antibody titers to A/New Jersey/76, A/Victoria/75, and A/USSR/77. Eleven unvaccinated children with renal diseases formed a comparison group. In contrast to the comparison group (0/11), 53% (16/30) of the vaccinated group had a protective level of serum HI titers (greater than or equal 1:40) against A/New Jersey. A protective level of serum HI titer against A/Victoria was noted in 83% (25/30) of the vaccinated group, while 54% (6/11) of the unvaccinated group had similar HI titers. None had a detectable HI titer against A/USSR. A minor common cold-like illness occurred in seven of the 30 vaccinated children; one of these had exacerbation of nephrotic syndrome. The data suggest a good protection against influenza one year after vaccination in children with renal disease.

Age Factors↗

Influenza virus immunization. Antibody response and adverse effects in children with renal disease.

Before and four weeks after immunization with a single 0.5-ml dose of influenza virus vaccine, sera from 36 children with renal diseases were tested for serum hemagglutinating-inhibiting antibody (HAI) titers to A/New Jersey/76, A/Victoria/75, and A/Port Chalmers/73. Before immunization, 1:40 HI antibodies to A/New Jersey were noted in one child only, to A/Victoria in ten children (27%), and to A/Port Chalmers in 25/34 children (68%). Serum HAI titers increased fourfold or more (P less than .01) in 31/36 children (86%) after immunization. Neither the type of the renal disease nor therapy with prednisone had any effect on the rise of serum HAI titers (P less than .05). Of the seven children with preimmunization proteinuria, four had a transient rise in protein levels following immunization. None required an increased prednisone dose for exacerbation of nephrotic syndrome. Children with chronic renal problems should be protected against influenza.

Adolescent↗

Effect of thyroid status on spontaneous and induced surges of luteinizing hormone.

This study was designed to describe the effects of thyroid status on the preovulatory surge of LH and to determine the site(s) at which these effects are exerted. The treatment of normal 4-day cycling rats with a hyperthyroid dose of thyroxine (T4, 20 mug/100 g BW/day) for 8 days resulted in surges of LH on proestrus which were depressed to 25% of control levels. In ovariectomized (OV) or ovariectomized-thyroidectomized (OV-Tx) rats maintained on a physiological regimen of T4 (2 mug/100 gBW/day), the amount of estrogen required to induce an LH surge was far greater than that required in OV-TX rats receiving no T4 replacement. These data suggest that T4 attenuates preovulatory surges of LH by acting at the hypothalamic-pituitary axis. However, the pituitary might be eliminated as a site of action since hyerthyroid proestrous rats responded to a challenge of LH-releasing hormone (500 ng) by secreting a quantity of LH equivalent to that in euthyroid animals. Similarly, there was no difference in the quantity of LH released by hyperthyroid and euthyroid proestrous rats in response to electrochemical stimulation (100 muA, 60 sec) of the medial preoptic area of the hypothalamus. On the other hand, hyperthyroid rats secreted significantly less LH in response to stimulation of the arcuate nucleus-median eminence area (ARN-ME) than did controls. Thus, T4, apparently modifies LH release by depressing the response of the ARN.

Animals↗

The control of progesterone secretion during the estrous cycle and early pseudopregnancy in the rat: prolactin, gonadotropin and steroid levels associated with rescue of the corpus luteum of pseudopregnancy.

The hormonal factors associated with converting a corpus luteum of estrous cycle into a corpus luteum of pseudopregnancy were studied by measuring LH and FSH prolactin, estradiol and progesterone levels in decapitated rats during the 4-day estrous cycle and a comparable time of pseudopregnancy (lights on 0600-0800 hr.). During the estrous cycle, prolactin, LH and FSH remained low and unchanging except on the afternoon of proestrus, when typical proestrous surges were observed. In contrast, estradiol levels began to increase on D-1, from baseline values of 7 pg/ml to approximately 15-20 pg/ml. These levels were maintained until the afternoon of D-2 when estradiol further increased to reach peak levels of 40-50 pg/ml by 0900 hr on proestrus. Estradiol then declined in relation to the increase in LH secreation and had returned to baseline by estrus. Progesterone secretion by the corpora lutea of the cycle also increased on the afternoon of D-1 and reached a maximum value of 25-30 ng/ml early on the morning of D-2. At this time, a precipitious fall in progesterone occurred, returning to baseline values of 5-1- ng/ml by 0700 on D-2 signifying the regression of the corpora lutea of the cycle. Progesterone remained low thereafter until the afternoon of proestrus when levels increased in response to the proestrus when levels increased in response to the proestrous surge of LH. Following cervical stimulation at 1900 hr on proestrus, no differences were noted, with respect to the estrous cycle, in LH, FSH or estradiol secreation through the afternoon of D-2. Surprisingly, progesterone levels did not differ in the cycle and pseudopregnancy until the early morning of D-29 instead of progesterone levels falling to baseline as they had during the cycle, the corpora lutea of pseudopregnancy were rescused, progesterone increasing dramatically to reach levels of 45-50 ng/ml by 1700 hr on that same day. The only difference in hormone secretion that was noted which could account for this marked divergence in progesterone secretion was the pattern of prolactin secretion following cervical stimulation. In contrast to the low levels seen during the estrous cycle, biphasio surges of prolactin secretion occured each day, one being nocturnal (0100-0900 hr) and the other diurnal (1500-2100 hr). The rescue of the corpus luteum occured in association with the nocturnal surge on D-2. These results suggest that nocturnal surge on D-2, PROLACTIN IS THE MAJOR Luteotropic stimulus which transforms and estrous cycle into pseudopregnancy by prolonging progesterone secretion from the corpus luteum. Moreover, if LH is important for progesterone secretion, no changes were observed in the pattern of LH secretion which can account for the rescue of the corpus luteum.

Animals↗

Thyroid hormone regulation of the pulsatile discharges of luteinizing hormone in ovariectomized rats.

The pulsatile discharges of luteinizing hormone (LH) were characterized in ovariectomized rats in the presence or absence of thyroid hormone. LH secretion in ovariectomized rats with intact thyroid glands and thyroidectomized-ovariectomized rats receiving daily physiological doses of thyroxine (2 mug/100 g BW/day for 8 days) showed equivalent periodic discharges with frequencies between 15 and 45 min. Though the frequency of the plasma LH rhythm in untreated athyroid-ovariectomized rats was normal, the maximum and minimum concentrations were 2- to 3-fold higher than those of euthyroid-ovariectomized animals. On the other hand, treatment of athyroid-ovariectomized rats with a daily hyperthyroid dose of thyroxine (20 mug/100 g BW) for 8 days, attenuated pulsatile discharges of LH. The LH measured in the sera of these animals each gave dose-response curves by radioimmunoassay which were identical to the authentic rat LH reference preparation. Furthermore, neither the molecular profile nor the metabolic clearance rate of LH was affected by alterations in thyroid status. These results suggest that altered thyroid status does not influence the synthesis and metabolism of LH but does exert a profound effect on the secretion of this hormone by presumably acting directly on the hypothalamo-pituitary axis.

Animals↗