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Biomedical subjects

L J Forman

Publications and source records attributed to L J Forman.

At least 37 records · Page 2Linked to original sources
PubMed1992

Determination of free valproic acid: evaluation of the Centrifree system and comparison between high-performance liquid chromatography and enzyme immunoassay.

Valproic Acid (VPA) is an important drug for the treatment of several types of seizures because it has a wide spectrum of activity. Since VPA has an unusual nonlinear binding characteristic and a wide interindividual variation, monitoring of its free concentration can be helpful in patient management. The determination of unbound VPA is more difficult because an extra sample preparation step is needed and the concentration of free VPA is low. Free drug monitoring can assume a more important role if there is a refinement in the technology. A high-performance liquid chromatography (HPLC) method with isocratic elution has been established for the analysis of the 4-bromomethyl-7-methoxycoumarin (BrMMC) derivative of free VPA. This method has a better sensitivity, linearity, and precision than enzyme immunoassay (EIA). Ultrafiltration with the Centrifree system was evaluated for the sample preparation. The influence of centrifuge times, relative centrifugal forces, and the starting sample amounts on the final results of the ultrafiltration were investigated. There was a satisfactory correlation between the free VPA levels determined by the HPLC method and the concentrations obtained by EIA. The total and free VPA were determined on 100 samples from 36 patients. The total VPA levels were in a range of 25 to 208 micrograms/ml, free VPA concentrations ranged from 1.92 to 55.75 micrograms/ml with the free fractions from 7 to 37%.

Anticonvulsants↗
PubMed1991

Possible opiate action in the anxiolytic and antinociceptive actions of alprazolam.

Chronic treatment with alprazolam reversed the effect of acute stress on the concentration of immunoreactive beta-endorphin (IR-BE) in the anterior pituitary (AP) and increased the amount of beta-endorphin (BE) relative to beta-lipotropin (B-LPH). In chronically stressed animals, administration of alprazolam did not alter the effect of a single stressful episode on the concentration of IR-BE in the AP, the NIL or the plasma, however, the amount of BE relative to B-LPH was increased in the AP and the plasma. Administration of alprazolam resulted in a significant decrease in the perception of pain. A low dose of alprazolam produced the most consistent decrease in nociception over time. The present findings suggest that alprazolam may modify the effects of acute and chronic stress on BE release from the pituitary. Moreover, alprazolam appears to have an antinociceptive effect in addition to its affect as an anxiolytic.

Alprazolam↗
PubMed1990

Beta-endorphin in the male rat pituitary: testosterone influences the effect of cocaine.

In order to determine if the effect of cocaine on the concentration of immunoreactive beta-endorphin (IR-BE) in the anterior pituitary (AP), neurointermediate lobe of the pituitary (NIL) and hypothalamus was modulated by gonadal steroid, the following groups of animals were studied: a) castrated male rats treated with vehicle, b) castrated male rats treated chronically with cocaine (daily for 10 days), c) castrated male rats treated with testosterone propionate (TP) and d) castrated male rats treated with TP and chronically administered cocaine. Only in castrated rats given TP did cocaine induce a significant increase in the concentration of IR-BE in the AP. The concentration of IR-BE in the NIL was increased by cocaine and was not influenced by the presence or absence of TP. Hypothalamic IR-BE remained unchanged in response to cocaine and was decreased by TP. Column chromatography revealed that TP and cocaine interacted to modulate the amount of beta-endorphin relative to beta-lipotropin in the AP. These findings suggest that in the male rat, the effect of cocaine on the concentration of IR-BE in the AP is modulated by the gonadal steroid environment. By contrast, gonadal does not appear to play a role in the effect of cocaine on the concentration of IR-BE in the NIL.

Animals↗
PubMed1989

The response to analgesia testing is affected by gonadal steroids in the rat.

The effect of gonadal steroids on the response to analgesia testing was determined in castrated male and female rats and castrated male and female rats treated with testosterone propionate (TP) and estradiol benzoate (EB), respectively. The time to respond to a noxious somatic stimulus in the form of heat was assessed using the tail withdrawal test (tail withdrawal from hot water) and hot plate test (the time to paw lick or jump). In male rats, castration resulted in a significant reduction of the reaction time for tail withdrawal. This effect was reversed by treatment with TP. The time to paw lick or jump in male rats was also diminished by castration. Treatment with TP resulted in a partial reversal of the effect of castration on this response. In castrated female rats, the time required for tail withdrawal was decreased by castration and increased by treatment with EB. The reaction time to the hot plate in female rats was diminished by castration and further reduced by EB administration. These data indicate that gonadal steroids influence the response to a noxious heat stimulus in male and female rats and that the effect may vary according to sex and the way in which the stimulus is applied.

Analgesia↗
PubMed1989

Localization of beta-endorphin in the rat heart and modulation by testosterone.

Chromatographic analysis and radioimmunoassay were used to identify and quantitate beta-endorphin (BE) and beta-lipotropin (B-LPH) in the hearts (devoid of major blood vessels and atria) from intact male rats, castrated male rats, and castrated male rats treated with testosterone propionate (TP). BE and B-LPH in the plasma of these animals were also identified and measured. In comparison to intact animals, castration resulted in a significant elevation in the content of BE in the heart which was reversed by the administration of TP. The content of B-LPH in the heart was not affected by castration or castration in combination with TP. The ratio of BE to B-LPH in the heart of castrated animals was significantly elevated as compared with intact controls. Treatment of castrates with TP returned the ratio of BE to B-LPH to that observed in intact animals. The concentration of BE in the plasma was greater in castrated rats and castrated rats given TP than in intact males, whereas the concentration of B-LPH was diminished in castrated animals given TP. The ratio of BE to B-LPH was greater in castrated animals treated with TP than in castrated and intact animals. The content of BE and B-LPH, as well as the ratios of the two peptides, varied independently in the cardiac tissue and plasma. The present findings indicated that (i) BE and B-LPH are present in cardiac tissue, (ii) the amount of BE and B-LPH in the heart and the ratio of BE to B-LPH appear to be modulated by TP, and (iii) BE and B-LPH detected in the heart was not simply a reflection of the presence of these peptides in the plasma.

Animals↗
PubMed1988

Cocaine influences beta-endorphin levels and release.

Immunoreactive beta-endorphin (IR-BE) was measured in the plasma, anterior pituitary (AP), neurointermediate lobe of the pituitary (NIL) and hypothalamus of male rats treated chronically (once daily for ten days) with cocaine. Cocaine produced a consistent elevation in the concentration of IR-BE in the plasma, the AP and the NIL at doses of 2.5 - 20 mg/kg/ip. The release of IR-BE from the AP and the NIL was determined in vitro and was found to be increased by treatment with cocaine. Chronic administration of cocaine did not affect the concentration of IR-BE in the hypothalamus. Chromatographic analysis revealed that cocaine produced a slight decrease in the amount of beta-endorphin relative to beta-lipotropin in the AP. Beta-endorphin was the major form of IR-BE released by the AP and the sole constituent and secretory product of the NIL. These data indicate that chronic administration of cocaine stimulates the endogenous opiate system, elevating the levels of IR-BE in the pituitary and promoting beta-endorphin release.

Animals↗
PubMed1988

The effects of immobilization stress on beta-endorphin levels are modulated by testosterone.

Immunoreactive beta-endorphin (IR-BE) levels were determined in the anterior pituitary (AP), neurointermediate lobe of the pituitary (NIL) and the hypothalamus of castrated male rats and castrated male rats treated with testosterone proprionate (TP), subsequent to exposure to acute (once for 45 min) or chronic (45 min each day for 15 consecutive days) immobilization stress. Acute stress resulted in a reduction in the concentration of IR-BE in the AP of castrated male rats, which was potentiated by TP. The concentration of IR-BE in the NIL was elevated by acute stress in castrated male rats and was not affected by acute stress in castrated male rats administered TP. Exposure to chronic immobilization stress elevated the concentration of IR-BE in the AP of castrated animals and not animals treated with TP. The concentration of IR-BE in the NIL of castrated animals was not altered by chronic immobilization. Chronic stress did result in a significant rise in the level of IR-BE in the NIL of castrated male rats given TP. Hypothlamic IR-BE levels in castrated male rats were reduced by TP and were not influenced by acute or chronic stress. Chromatographic analysis indicated that acute and chronic stress promoted the accumulation of beta-lipotropin rather than beta-endorphin in the AP. This effect was attenuated by TP. Beta-endorphin was the only form of immunoreactivity detected in the NIL and hypothalamus.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1988

Eight weeks of streptozotocin-induced diabetes influences the effects of cold stress on immunoreactive beta-endorphin levels in female rats.

Cold stress produced a significant reduction in the concentration of immunoreactive beta-endorphin (IR-BE) in the anterior pituitary of diabetic female rats. IR-BE levels in the anterior pituitary of non-diabetic female rats were not affected by exposure to the cold. The effects of cold stress on IR-BE levels in the neurointermediate lobe of the pituitary and the hypothalamus were attenuated in diabetic as compared to control animals. These data suggest that in female rats, eight weeks of diabetes produced alterations in the neuroendocrine mechanisms which modulate IR-BE levels in the pituitary and hypothalamus in response to cold stress.

Animals↗
PubMed1988

Estrogen influences the effect of immobilization stress on immunoreactive beta-endorphin levels in the female rat pituitary.

Immunoreactive beta-endorphin (IR-BE) levels in the plasma, anterior pituitary (AP), the neurointermediate lobe of the pituitary (NIL), and the hypothalamus were determined in castrated female rats and castrated female rats treated with estradiol benzoate (estrogen), after exposure to acute (once for 45 min) or chronic (45 min each day for 15 consecutive days) immobilization stress. Acute and chronic stress increased plasma levels of IR-BE to the same extent in castrated female rats and castrated female rats treated with estrogen. In castrated female rats, acute stress produced an increase in the concentration of IR-BE in the AP, which was attenuated by the administration of estrogen. Although IR-BE in the NIL was not influenced by acute stress in castrated animals, exposure to acute stress resulted in an elevation in IR-BE levels in the NIL of rats given estrogen. Chronic stress did not affect the concentration of IR-BE in the AP of castrated females or castrated females treated with estrogen. Chronic stress did, however, increase the concentration of IR-BE in the NIL of castrated animals. This affect of stress on IR-BE levels in the NIL was potentiated by estrogen administration. IR-BE levels in the hypothalamus were reduced by estrogen and were not affected by acute or chronic stress, regardless of the gonadal steroid environment. As determined by column chromatography, administration of estrogen, as well as subjection to chronic stress, promoted the processing of the proopiomelanocortin precursor to form beta-lipotropin rather than beta-endorphin in the AP. By these methods, the only immunoreactivity detected in the NIL and the hypothalamus was beta-endorphin. These data indicate that IR-BE levels in the plasma, the AP, and the NIL of female rats are affected by immobilization stress and that estrogen modulates the effects of acute immobilization stress on IR-BE levels in the AP and the NIL and the effects of chronic immobilization stress on the levels of IR-BE in the NIL.

Acute Disease↗
PubMed1987

Administration of gonadal steroids to neonatal rats affects beta-endorphin levels in the adult.

Administration of gonadal steroids to neonatal rats has a profound effect on the function of the neuroendocrine system in the adult animal. Considering that gonadal steroids modulate hypothalamic and pituitary levels of beta-endorphin (BE) in adult male and female rats, the effects of neonatal gonadal steroid treatment on BE levels in the adult animal were investigated. Neonatal male rats were administered testosterone and neonatal female rats were treated with estrogen. Matched control littermates received vehicle. All animals were sacrificed at 90 days of age. Neonatal gonadal steroid treatment did not affect the level of immunoreactive beta-endorphin (IR-BE) in the anterior pituitary (AP) of male rats but did result in a significant increase in IR-BE in the AP of female rats. Neonatal administration of gonadal steroids produced a significant decrease in IR-BE in the neurointermediate lobe of the pituitary (NIL) of both male and female rats, with the magnitude of the decrease being greater in the NIL of the female rats. IR-BE levels in the hypothalamus of male or female rats were not altered by the treatments. Column chromatography indicated that the increase in IR-BE in the AP represented a proportional increase in BE and beta-lipotropin, while the reduction in IR-BE in the NIL of the treated rats represented a reduction in BE. These findings suggest that gonadal steroids may influence the development of the neurotransmitter systems which regulate BE levels in the adult pituitary, the development of the biosynthetic mechanisms of the adult pituitary, or both.

Animals↗
PubMed1987

Plasma levels of beta-endorphin in young and aged human males during the morning hours.

Age-related alterations in plasma levels of beta-endorphin (BE) were investigated in young and aged human males. This was accomplished by obtaining repeated measurements of BE levels in the plasma of young and aged human male subjects during the morning hours, when a diurnal elevation of BE in the plasma is reported to occur. BE was extracted from the plasma and measured by radioimmunoassay. No differences were found in plasma levels of BE between young and elderly males at any time during the time period studied. In addition, the mean level of BE in the plasma during the entire sampling period did not differ between the two age groups. These data suggest that in human males, the levels of BE in the plasma during the morning hours are not modified by aging.

Adolescent↗
PubMed1986

Effect of CNS-active drugs on TRH-induced prolactin release.

The effects of several central acting drugs upon thyrotropin-releasing hormone (TRH)-induced increases in prolactin (PRL) release were compared in estrogen-primed male rats. Administration of the serotonin antagonist, p-chlorophenylalanine, or the opiate antagonist, naltrexone, did not alter TRH-induced release of PRL. Pre-treatment with either the dopamine agonist, piribedil, or the cholinergic agonist, pilocarpine, resulted in significantly reduced TRH-induced PRL release. Pilocarpine did not inhibit the TRH-induced increase in PRL release when rats were first pre-treated with the dopamine receptor blocker, haloperidol. These results indicate that the dopaminergic and cholinergic systems can modify TRH-induced release of PRL in vivo.

Animals↗
PubMed1986

Streptozocin diabetes alters immunoreactive beta-endorphin levels and pain perception after 8 wk in female rats.

Plasma, pituitary, and hypothalamic levels of the endogenous opioid peptide beta-endorphin were measured by radioimmunoassay and column chromatography in female rats 8 wk after the induction of diabetes with streptozocin (STZ) and in control female rats. In addition, pain perception was determined by measuring the latency to paw lick or jump after being placed on a hot plate. Plasma levels of immunoreactive beta-endorphin (IR-BE) were significantly reduced in STZ-induced diabetic female rats, as were the content and concentration of IR-BE in the neurointermediate lobe of the pituitary (NIL) and the content of IR-BE in the hypothalamus. The concentration but not the content of IR-BE in the anterior pituitary (AP) of the STZ-induced diabetic rats was increased significantly. Streptozocin-induced diabetes also resulted in a significant reduction in the total protein content of the AP, NIL, and hypothalamus. Column chromatography indicated that the decrease in IR-BE in the plasma, NIL, and hypothalamus represented a decrease in beta-endorphin, whereas the increase in IR-BE in the AP represented an increase in both beta-endorphin and beta-lipotropin. Diabetic animals consistently showed decreased latencies to paw lick or jump when subjected to hot-plate testing after 7 wk. These findings suggest that in female rats, central and peripheral endogenous opiate levels and tolerance to nociceptive thermal stimulation were diminished by 8 wk of chemically induced diabetes.

Animals↗
PubMed1985

Release of immunoreactive beta-endorphin in vitro from pituitaries of young and old male rats.

The release of immunoreactive beta-endorphin (IR-BE) in vitro from the anterior pituitary (AP) and the neurointermediate lobe of the pituitary (NIL) from old male rats was significantly greater than from the AP and NIL from young male rats. In addition, the content and concentration of IR-BE in the AP and NIL was significantly greater in old than in young male rats, as was the concentration of IR-BE in the plasma. Chromatographic analysis revealed that in old male rats, the increase in IR-BE contained in and released by the AP and NIL, and found in the plasma, represented an increase in a peptide which coeluted with beta-endorphin rather than beta-lipotropin. These data suggest that both the AP and the NIL contribute to the elevation in plasma levels of IR-BE observed in old male rats, and that the increase in pituitary and plasma IR-BE in old male rats represents an increase in beta-endorphin.

Aging↗
PubMed1985

Diabetes induced by streptozocin results in a decrease in immunoreactive beta-endorphin levels in the pituitary and hypothalamus of female rats.

Immunoreactive beta-endorphin (IR-BE) was measured by radioimmunoassay in the anterior pituitary (AP), neurointermediate lobe of the pituitary (NIL), and hypothalamus of female rats 4 wk after being made diabetic by a single injection of streptozocin (STZ). STZ-induced diabetes resulted in a significant reduction in the content and concentration of IR-BE in the AP and the content of IR-BE in the hypothalamus. Total hypothalamic protein was also significantly diminished. IR-BE levels in the NIL were unchanged. Column chromatography indicated that the reduction in IR-BE in the AP of the diabetic female rats represented a decrease in peptides that co-eluted with beta-endorphin and beta-lipotropin. In the hypothalamus, the reduction in IR-BE was represented solely by a decrease in a peptide co-eluting with beta-endorphin. Beta-lipotropin was not detectable in the hypothalami of control or diabetic female rats. These results suggest that, in the rat, diabetes may produce alterations in the mechanism(s) that regulate endogenous opiate levels in the pituitary and hypothalamus.

Animals↗
PubMed1985

The effect of chronic estrogen treatment on immunoreactive beta-endorphin levels in intact female rats.

Intact female rats were treated chronically with estradiol benzoate (EB) until a state of constant estrus (CE) was achieved and maintained. When compared to female rats on the day of estrus, estrogen-treated rats in constant estrus demonstrated a 33% decrease in the concentration of immunoreactive beta-endorphin (IR-BE) in the plasma, and a 45-50% decrease in the content and concentration of IR-BE in the anterior pituitary and hypothalamus. The content and concentration of IR-BE in the neurointermediate lobe of the pituitary were similar in each group. Column chromatography revealed that the reduction in IR-BE in the plasma and anterior pituitary of EB-treated CE female rats appeared to be due to a reduction in peptides coeluting with beta-endorphin and beta-lipotropin, whereas the reduction in IR-BE in the hypothalamus represented a decrease in a peptide which coeluted with beta-endorphin. These data suggest that constant estrus, induced by prolonged treatment of intact female rats with estrogen, resulted in a reduction in central and peripheral levels of IR-BE in these animals as compared to female rats on the day of estrus.

Animals↗
PubMed1984

Decreased ability of old male rats to secrete luteinizing hormone (LH) is not due to alterations in pituitary LH-releasing hormone receptors.

The present study was undertaken to determine if the diminished release of LH in male rats with age in response to castration or LHRH injection is due to alternations in the number or affinity of LHRH receptors in the pituitary. Young (3-4 months old) and old (18-20 months) male Sprague-Dawley rats were killed 0, 2, 4, and 8 days after castration. Serum was collected for determination of LH concentrations, and anterior pituitaries were removed for analysis of LHRH receptors. The numbers and affinity constants of receptors were determined by Scatchard analysis using iodinated des-Gly10-[D-Ala6]LHRH ethylamide (LHRH-a) as ligand. Plasma LH in young rats increased from 54 ng/ml in intact animals to 319 ng/ml 8 days after castration, but in old animals, LH increased only from 47 to 119 ng/ml during the same period (P less than 0.01). However, there were no age-related differences in LHRH receptors in intact animals, and both young and old animals showed similar increases in pituitary LHRH receptors after castration when expressed either as receptors per pituitary (young, 132 +/- 27 to 262 +/- 43 fmol/pituitary; old, 175 +/- 27 to 299 +/- 19 fmol/pituitary) or as receptors per mg protein (young, 420 +/- 48 to 847 +/- 172 fmol/mg protein; old, 432 +/- 38 to 866 +/- 62 fmol/mg protein). Receptor affinity was not statistically different in intact young or old animals (4.51 +/- 0.41 X 10(9) and 4.51 +/- 1.23 X 10(9) M1, respectively), and receptor affinity increased in both groups in response to castration. The capacity of young and old male rats to produce LHRH receptors in response to exogenous LHRH was tested in a second experiment. Animals were castrated and given daily injections of testosterone propionate (500 micrograms/kg, im) for 13 days. Beginning on day 9, LHRH-a (250 micrograms/kg, sc) was injected for 5 days. The rises in serum LH after a single injection of LHRH-a were similar in young and old animals on the first and fifth days of LHRH-a treatment. LHRH receptors at the cessation of hormone therapy also increased similarly in both young and old animals in response to LHRH-a (715 +/- 135 and 811 +/- 203 fmol/mg protein, respectively). Receptor affinity was not statistically different in young (6.27 +/- 0.40 X 10(9) M-1) or old (6.67 +/- 0.79 X 10(9) M-1) animals. In a third experiment, male rats were castrated and given injections of LHRH (166 ng/kg) at 30-min intervals for 4.5 h.(ABSTRACT TRUNCATED AT 400 WORDS)

Aging↗