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Biomedical subjects

M W Adler

Publications and source records attributed to M W Adler.

At least 19 recordsLinked to original sources
PubMed1992

Effect of mu-, kappa-, and delta-selective opioid agonists on thermoregulation in the rat.

The effect of selective mu-, kappa-, and delta-agonists on brain surface temperature (Tb), oxygen consumption (Vo2), and heat exchange (Q) was studied in unrestrained, male Sprague-Dawley rats using whole-body calorimetry. Hyperthermia, produced by PL-017 (1.86 nM) given ICV, resulted from increased Vo2 and reduced Q during the first 15-45 min postinjection. Tb returned to control levels due to a combination of increased Q and reduced Vo2. PL-017-induced hyperthermia was abolished by the mu-selective antagonist CTAP (0.75 nM). Dynorphin A1-17 (4.65 nM), a kappa-selective agonist, reduced both Vo2 and Q, resulting in hypothermia that was blocked by the kappa-selective antagonist nor-binaltorphimine (25 nM). The delta-selective agonist DPDPE (4.64 nM) caused no significant changes in Tb, Vo2, or Q. The data indicate that central stimulation of the mu- and kappa-opioid receptors affects both oxidative metabolism and heat exchange, which result in a change in Tb. These alterations can be prevented with selective opioid antagonist pretreatment.

Amino Acid Sequence↗
PubMed1992

The effect of arginine vasopressin on the autologous mixed lymphocyte reaction.

Arginine vasopressin (AVP) is a nonapeptide that has been shown to be released from the supraoptic and paraventricular nuclei of the hypothalamus during stress. Although noted primarily for its hemodynamic as well as homeostatic properties, AVP also appears to have an effect on the immune system. It may modulate cellular immunity via its enhancement of the autologous mixed lymphocyte response (AMLR), an effect which we have demonstrated to occur over a wide dose range with a maximum at 10(-7) M. The increase in proliferation following a single addition of AVP in a 6-day culture appears to be augmented when the peptide is added daily throughout the same culture period. Enhanced proliferation appears to be a specific response that is influenced by arginine residues in position 8 of this nonapeptide. Having provided evidence for the existence of receptors with moderate affinity for AVP, we suggest a potential modulatory role for AVP in support of the concept of a communication between the neuroendocrine and immune systems. Since various autoimmune conditions may be aggravated by stress, stress-induced release of neuropeptides such as AVP may play an important role in modulating immune regulation of these disease states.

Amino Acid Sequence↗
PubMed1992

Differential effects of morphine and naltrexone on the antibody response in various mouse strains.

Morphine treatment has been shown to suppress several immunologic parameters. In this study, we examined the effects of morphine pellet implantation in vivo on the primary antibody response measured in vitro in various mouse strains. Effects of mouse strain and sex on morphine-induced suppression of the plaque-forming cell response, as well as spleen weight and mortality were determined. Morphine suppressed the primary antibody response in C3HeB/FeJ, C3H/HeJ and C57Bl/6 mice, while Balb/cByJ and the mu-receptor-deficient strain CxBk/ByJ mice were not affected. There was no difference in the response to morphine between male and female C3HeB/FeJ mice. Naltrexone reversed the morphine-induced suppression in the C3H strains, but not in C57Bl/6 mice. In addition, naltrexone caused significant mortality in Balb/cByJ mice. Spleen weight was decreased by morphine treatment in all the strains, but only the C3H strains were sensitive to the lethal effects of morphine. Thus, immune suppression did not correlate with splenic atrophy or mortality. The strain differences in response to chronic morphine and naltrexone treatment suggest that morphine may be acting through both opioid and non-classical opioid (e.g., not blocked by naltrexone) mechanisms.

Animals↗
PubMed1991

Immunomodulatory activity of mu- and kappa-selective opioid agonists.

Opioids and opioid peptides have been shown by numerous laboratories to modulate various parameters of the immune response, but little attention has been given to the type of opioid receptor that might be involved. This study focuses on the in vitro influences of morphine and DAMGE (Tyr-D-Ala-Gly-N-Me-Phe-Gly-ol), mu-selective agonists, and U50,488H and U69,593, kappa-selective agonists, on the generation of antibody to sheep erythrocytes in vitro. It was found that the mu and kappa opioid agonists were able to inhibit the capacity of murine lymphoid cells to generate antibody at concentrations as low as 10(-10) M. The effects were almost completely blocked by pretreatment with naloxone or naltrexone, opioid-specific antagonists. Only the kappa-agonist activity was abrogated by pretreatment with norbinaltorphimine, a kappa-specific antagonist. The stereospecificity of the kappa effect was demonstrated using isomers of U50,488H, with the (-) form possessing significantly greater immunomodulatory activity. Additional studies, using a mu receptor-deficient mouse strain, demonstrated that only the kappa agonists were capable of suppressing antibody responses, whereas mu- and kappa-selective agonists suppressed the parent mu-responsive strain. Our results clearly indicate that mu and kappa opioid receptors are involved in regulation of lymphoid cell production of antibodies.

3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cycloh↗
PubMed1991

Production of hypothermia in the guinea pig by a kappa-agonist opioid alone and in combination with chlorpromazine.

In rats, kappa opioids decrease body temperature and the combination of a selective kappa agonist with chlorpromazine induces a profound hypothermia. Because of the greater density of kappa-opioid receptors and increased ratio of kappa to mu in the guinea pig, the actions of these drugs on body temperature were compared in this species. Groups of young adult, male Hartley guinea pigs were injected SC with trans-3,4-dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneace tamide methanesulfonate, hydrate (U50, 488H; 20-80 mg/kg) and chlorpromazine (2.5-5 mg/kg), either alone or in combination. Rectal temperatures were measured over a 5-h period. U50, 488H produced a dose-related decrease in temperature, with a mean maximum drop of approximately 7 degrees C. The maximum decrease with chlorpromazine was approximately 1.6 degrees C. When doses at the lower end of the range for each drug were given together, the combined effect was greater than that expected from the individual drugs. Both the peak effect and the duration of the hypothermia appeared to be potentiated. At the highest dose combination only an additive effect was seen. Compared to the rat, the hypothermic effect of the kappa agonist alone is much greater in the guinea pig. The potentiation between the two drugs, however, is greater in the rat.

3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cycloh↗
PubMed1991

Prevalence of HIV, hepatitis B and associated risk behaviours in clients of a needle-exchange in central London.

In order to determine the prevalence of risk behaviour for, and antibodies to HIV and hepatitis B in clients of a needle-exchange scheme in central London we employed an anonymous, self-administered questionnaire along with salivary antibody testing by immunoglobulin (Ig) G antibody capture immunoassay. Two hundred and thirty-two subjects (193 men, 39 women; median age 32) participated; a response rate of 89%. Clients were long-term, frequent injectors. Lending used equipment at any time was reported by 55%, and borrowing by 52%. Of those who had shared needles and syringes during the last year, the majority had lent to, or borrowed from, one person only (53 and 55%, respectively). Younger clients (less than 29 years of age) reported more recent sharing than older clients (greater than 30 years of age). Five out of 211 (2.4%) samples tested for anti-HIV were positive. One hundred and eleven out of 199 (56%) samples were positive for anti-hepatitis B core (HBc). In this population of needle-exchange attenders there is no evidence of further spread of HIV, and a low prevalence of HIV infection appears to have been sustained. However, the high prevalence of anti-HBc provides evidence of previous risk behaviour and so constant vigilance is necessary if further viral spread is to be avoided. This study has established an acceptable method for the anonymous surveillance of current risk behaviour and salivary antibodies to HIV and hepatitis B virus (HBV) in a drug-using population.

Adolescent↗
PubMed1991

HIV, confidentiality and 'a delicate balance': a reply to Leone Ridsdale.

The passing on of information to GPs by genito-urinary doctors is to be encouraged but is not always possible and ultimately the patient's wishes and confidentiality must be respected if sexually transmitted diseases and HIV infection are to be controlled. Infected health-care workers should seek counselling and medical support and clear guidelines from professional organisations which are in existence. However, they will only do so if strict confidentiality is maintained and assurance about future employment can be given.

Confidentiality↗
PubMed1990

Morphine-induced pupillary fluctuation: physiological evidence against selective action on the Edinger-Westphal nucleus.

In the rat, the predominant pupillary effect of morphine sulfate (30 mg/kg, i.p.) is mydriasis, interrupted periodically by miotic excursions. Using infrared video pupillometry, respirometry and EEG recording, we had previously reported that miotic excursions are always correlated with the onset of EEG bursting, while mydriatic excursions are preceded by respiratory slowing and correlated with EEG burst cessation. In the current study, we found that during morphine-induced EEG bursting and related miosis, delivery of an alerting stimulus to the rat caused an immediate conversion sequence composed of respiratory slowing, burst cessation and mydriatic excursion. We also simulated morphine-induced EEG bursting through non-opioid means by delivering kindling electrical stimuli to the amygdala. When the stimulus was given during morphine-induced mydriasis, the stimulus-induced bursting resulted in a miotic excursion identical to spontaneous morphine-induced miotic excursions. These results indicate 1) that the reticular activating system is involved in morphine-induced mydriatic excursions and 2) that EEG bursting is not simply correlated with morphine-induced miotic excursions, but causes them. Collectively, these results strengthen our hypothesis that the Edinger-Westphal nucleus is not the site in which the selective, receptor-mediated pupillary effects of morphine are initiated.

Amygdala↗
PubMed1990

Immunomodulatory activity of kappa-, mu-, and delta-selective opioid compounds.

1. Morphine, DAMGE and U50,488H each inhibit the in vitro proliferative response of murine splenocytes to the mitogenic agents PMA or SEB. The kappa agonist U50,488H is much more potent than either of the mu-receptor agonists. The immunosuppressive activity of U50,488H is reversed by the opioid antagonists naloxone or norBNI. On the other hand, the immunomodulatory activity of morphine is reversed only by naloxone. 2. The mu-receptor agonists morphine and DAMGE also inhibit the development of an antibody response in vitro. Much more potent inhibitory activity was also observed for the kappa agonists U50,488H and U69,593. The delta agonist DPDPE failed to exert measurable immunomodulatory activity under these experimental conditions. 3. The immunosuppressive activity of the kappa agonists was reversed by both naloxone and norBNI. In addition, the activity of these opioid compounds exhibited stereospecificity. 4. Strain analysis has revealed the existence of two groups of mouse strains. The relatively sensitive mouse strains appear to include the BALB/c, C57BL/6 and B10.A(5R) strains. Four relatively less sensitive strains have also been identified. 5. Immunomodulatory activity has been detected for the kappa-selective agonists in the mu receptor-deficient strain CxBK/ByJ. Both mu and delta agonists fail to exert immunosuppressive activity in this mouse strain.

Adjuvants, Immunologic↗
PubMed1990

Differential release of substance P and somatostatin in the rat spinal cord in response to noxious cold and heat; effect of dynorphin A(1-17).

Dynorphin A(1-17), the proposed endogenous ligand for the kappa receptor, has been reported to demonstrate no antinociceptive activity when tested in analgesic assays involving noxious (heat (e.g., tail-flick and hot-plate assays). By using a rat tail-flick analgesic assay that utilizes extreme cold as its noxious stimulus (an ethylene glycol-water mixture maintained at -10 degrees C), we have recently reported a dose-related and naloxone-reversible antinociceptive effect for i.c.v. administered dynorphin A(1-17). To elucidate the biochemical mechanism of this antinociception, we designed a push-pull perfusion system which would allow us to measure changes in neuropeptide release in the spinal cord during exposure to noxious heat or cold. Male Sprague-Dawley rats were implanted surgically with two lengths of PE-10 tubing inserted into the spinal subarachnoid space via the cisterna magna, with the push cannula at the level of T-1, and the pull cannula at the rostral edge of the lumbar enlargement. At the time of testing, samples of cerebrospinal fluid were collected both in the presence and absence of a noxious stimulus. Substance P (SP) and somatostatin (SST) levels were measured by radioimmunoassay. Exposing the animal's tail to the noxious cold (30 sec/min for 20 min) resulted in a significant elevation in SP release (69% above base-line levels), but no change in the level of SST release. Conversely, exposure to noxious heat (50 degrees C, 20 sec/min for 20 min) produced a significant increase in SST release (56% above base line), but no change in the level of SP release.(ABSTRACT TRUNCATED AT 250 WORDS)

3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cycloh↗
PubMed1990

The epidemiology of sexually transmitted diseases in the West.

Sexually transmitted diseases (STDs) continue to increase in number throughout the world, as do the number of agents that are spread by the sexual route; the most recent new agent is the human immunodeficiency virus. Most countries do not have adequate control programs for STDs or training programs for physicians and nurses designated to look after patients. The diseases are associated with considerable morbidity and recently, with the advent of the acquired immunodeficiency syndrome, with considerable mortality.

Europe↗