Biomedical subjects
Publications and source records attributed to J Candido.
The authors report three clinical cases of acute transverse myelitis in young patients with emphasis given to the seriousness of this kind of pathology, the need to exclude a potentially treatable cause and the controversial corticosteroid treatment.
Chronic treatment with an opioid antagonist, such as naltrexone, increases opioid receptor density and opioid agonist potency. Since stimulants such as d-amphetamine can increase opioid potency and opioid abusers may administer stimulants during naltrexone treatment, the effect of chronic d-amphetamine on naltrexone-induced opioid receptor upregulation and supersensitivity was examined in mice. Mice were implanted s.c. with a 15 mg naltrexone or placebo pellet for 8 days. Mice were injected daily with saline or d-amphetamine (7.5 or 5.0 mg/kg per day s.c.) for 7 days beginning 24 h following implantation. Naltrexone and placebo pellets were removed on the 8th day, and 24 h later mice were tested for morphine analgesia (tail-flick) or whole brain was removed and opioid receptor binding studies were conducted. Chronic naltrexone significantly enhanced the analgesic potency of morphine in saline-treated mice. However, naltrexone treatment did not increase morphine potency in mice treated with d-amphetamine. In binding studies, naltrexone increased [3H][D-Ala2,NMePhe4,Gly-ol5]enkephalin (DAGO) Bmax (+60-70%) without altering KD in both saline- and d-amphetamine-treated mice. Results from studies with 2 nM [3H][D-Pen2,D-Pen5]enkephalin (DPDPE) were similar. These studies indicate that daily d-amphetamine can limit naltrexone-induced supersensitivity but not receptor upregulation. Thus, upregulation can be dissociated from functional supersensitivity.
These studies examined the effect of cocaine on the analgesia produced by systemically and centrally administered opioid agonists. Cocaine (50 mg/kg, s.c.) increased the analgesic potency of systemic, ICV and IT morphine; and the ICV and IT analgesic effects of the delta selective peptide, [D-Pen2,D-Pen5]enkephalin (DPDPE). Cocaine also increased the analgesic potency of the mu selective ligand [D-Ala2,NMePhe4,Gly-ol5]enkephalin (DAGO) administered ICV. However, cocaine did not alter the ED50 for IT DAGO. GC-MS studies indicated that brain cocaine concentration was approximately 3.0 micrograms/g wet weight 45 min following s.c. administration. These results suggest that cocaine-induced increases in opioid analgesic potency are mediated at brain mu and delta receptors and spinal mu receptors. Furthermore, there might be functional differences between spinal and supraspinal sites at which DAGO produces analgesia.
The role of endocrine factors on opioid analgesia (antinociception) and opioid receptors was studied in male and female Swiss-Webster mice. Morphine was more potent in male than in female mice, although this difference appears to be due to greater availability of morphine to the brain in males. Saturation binding studies indicated that the density and affinity of brain mu- and delta-opioid binding sites were equivalent in males and females. Males and females were implanted SC with naltrexone (NTX) or placebo pellets for 8 days, and then the pellets were removed. This treatment increased the density of mu and delta binding sites in brain and increased the potency of morphine for both sexes, although the increase in antinociceptive effects for males was greater than for females. Adrenalectomy (ADX) in male mice increased the potency of morphine and methadone but did not alter the brain levels of either drug. ADX did not alter brain opioid binding of either mu or delta ligands. When male ADX and control mice were treated with NTX, the potency of morphine and brain opioid binding sites were increased equivalently in both groups. Gonadectomy (GDX) in male mice tended to decrease morphine potency, although this was not found to be a very reliable effect. When male GDX and control mice were implanted with NTX, brain opioid binding was increased similarly in both groups, although morphine potency was increased less in GDX mice. Overall, these studies show that sex differences and hormones of the adrenals and gonads in male mice do not alter brain opioid receptors.(ABSTRACT TRUNCATED AT 250 WORDS)
The authors have done a revision of 450 patients admitted during the last 3 years to the emergency service of the Hospital de S. José with the diagnosis of CVA. In this retrospective study were included the patients of greater than or equal to 3 degree of the RLS/85 coma scale, the diagnostic being confirmed by CAT, angiography and/or autopsy, and simultaneously evaluated by the Glasgow coma scale. The studied population was grouped into: SAH; ICH with or without ventricular drowning, cerebellar haematoma, brainstem haematoma, ischaemic CVA. The factors of vascular risk: diabetes and hypertension, the age of the patients and coma level were correlated with the degree of cerebral disability of discharge in all patients. The following factors are clearly related with bad prognosis: coma of degree greater than or equal to 4 in the RLS/85 scale; ischaemic aetiology; intraventricular haemorrhage.
The present study evaluates the effect of pertussis toxin (PTX) on morphine-induced analgesia and lethality. Mice were injected with 0.2 microgram PTX intracerebroventricularly (i.c.v.) and 0.2 micrograms PTX intrathecally (i.t.) or saline. Mice were tested for morphine-induced analgesia (tail flick) and lethality 16 days later; mice were also examined for pentobarbital-induced mortality. Morphine analgesic potency was decreased by approximately 4-fold in PTX-treated mice compared to controls. Conversely, the lethal potency of morphine was increased by 10-fold in PTX-treated mice compared to controls. PTX treatment did not alter the lethal potency of pentobarbital. Morphine-induced analgesia and lethality were dose-dependently antagonized by naloxone in both PTX and saline-treated groups. The results of this study suggest that morphine analgesia is mediated through PTX-sensitive G proteins. On the other hand, morphine-induced lethality appears to be limited by PTX-sensitive factor(s) since PTX treatment enhanced morphine's lethal potency. The increase in lethal potency of morphine may be due to unmasking of an excitatory opioid receptor mediated effect by PTX.
The mu opioid receptor ligand [D-Ala2, NMePhe4, Gly-ol5]enkephalin (DAGO) and delta opioid receptor ligand [D-Pen2,D-Pen5]enkephalin (DPDPE) show similar specificity in competition binding studies in whole brain homogenate in rat and mouse. However, in saturation studies, the density and affinity of DPDPE binding sites were substantially greater in the mouse. There was no difference between the mouse and rat in the density and affinity of DAGO sites. Results from dose-response studies for analgesia using the same ligands administered i.c.v. in both species paralleled the binding studies. DAGO was approximately 2 times more potent in the mouse compared to the rat; while DPDPE was more than 15 times more potent in the mouse. Thus, binding capacity and affinity differences appear to be related to the functional potency of the mu and delta ligands in the two species. These results suggest that the difference in potency of DPDPE between rat and mouse is related to the differences in brain delta opioid receptors.