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Biomedical subjects

G Torres

Publications and source records attributed to G Torres.

At least 55 records · Page 3Linked to original sources

Optimizing PCP therapy.

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AIDS-Related Opportunistic Infections↗

Cocaethylene stimulates the secretion of ACTH and corticosterone and the transcriptional activation of hypothalamic NGFI-B.

Cocaethylene is an active cocaine metabolite formed by hepatic carboxylesterases in the presence of alcohol. The effects of cocaethylene on the hypothalamic-pituitary-adrenal (HPA) axis were investigated in vivo using adrenocorticotropic hormone (ACTH) and corticosterone secretion as indices of peripheral stimulation. To ascertain the central effects of cocaethylene on discrete neurons of the paraventricular nucleus (PVN) of the hypothalamus, a specific cRNA probe was used to follow changes in the transcriptional activation of nerve growth factor I-B (NGFI-B), a member of the family of immediate-early genes. Intravenous (i.v.) injection of cocaethylene (16 mumol/kg) to rats produced a marked but transient increase in plasma levels of ACTH and corticosterone within 10 min of drug exposure. Secretion of these hormones was accompanied by elevated levels of NGFI-B mRNA detected 30 min after i.v. or intraperitoneal (i.p., 60 mumol/kg) cocaethylene administration. The transcriptional stimulation of this immediate-early gene within parvocellular secretory neurons was relatively brief in duration, returning to basal levels by 180 min after drug exposure. As expected both routes of cocaethylene administration produced an increase in locomotor activity compared to saline-vehicle rats, with no differences between i.v. or i.p. routes with respect to duration of behavioral activation. Taken together, these findings indicate that cocaethylene has neuroendocrine properties on its own, targeting a critical region of the brain that regulates stressful events in the body. This, combined with other neurochemical properties, points to the possibility of cocaethylene augmenting the effects of a drug-dependent state.

Adrenocorticotropic Hormone↗

Combined effects of ethanol and cocaine on FOS-like protein and cocaethylene biosynthesis in the rat.

To study the simultaneous effects of ethanol and cocaine on striatal FOS-like protein, rats were exposed to an (8.7%) ethanol solution for 15 days followed by single or daily cocaine injections (20 mg/kg; IP). Ethanol consumption reduced the induction of the nuclear protein under both temporal regimens of cocaine administration. In contrast, sucrose pair-fed or ad libitum control groups exhibited a robust induction of FOS-like protein throughout the striatum, particularly in dorsal-central quadrants of the caudate putamen. This pattern of combined drug use produced blood ethanol concentrations in the range of 22-370 mg/dl, corresponding with those associated with mild intoxication in humans. Under both cocaine regimens, the presence of ethanol led to the transesterification of cocaine into the active metabolite, cocaethylene (31-121 ng/ml). Plasma levels of this metabolite did not exceed those of cocaine (17-1024 ng/ml), suggesting that under this drug regimen at least, cocaethylene formation is relatively low and perhaps dependent upon specific levels of ethanol and cocaine in hepatic microsomes. In addition, systemic administration of cocaethylene to rats (60 mumol/kg; molar equivalent of 20 mg/kg cocaine) induced widespread FOS-like protein in the caudate putamen. Induction of the transcription factor protein by cocaethylene was similar in magnitude and anatomic distribution to that of cocaine, suggesting that these two drug congeners share common molecular mechanisms of gene expression.

Animals↗

Neuropeptide Y inhibits 3[H]noradrenaline release in the rat vas deferens independently of cAMP levels.

The purpose of the present investigation was to ascertain the functional significance of the reduction in cyclic AMP (cAMP) levels in the inhibitory action of neuropeptide Y (NPY) on [3H]noradrenaline ([3H]NA) release, as well as to further characterize the subtype(s) of NPY receptors involved in the peptide's actions in the rat vas deferens. We studied the effects of NPY, carboxyterminal fragments of this peptide and the NPY analog (Leu31,Pro34)-NPY on three functional responses, namely, the release of [3H]NA and the associated muscle contractions evoked by electrical stimulation, and the accumulation of cAMP stimulated by forskolin. NPY, a known inhibitor of the electrically-evoked [3H]NA release and neurogenic contractions is also a potent inhibitor of the forskolin-stimulated cAMP synthesis in the prostatic portion of the rat vas deferens. However, the ability of NPY to inhibit cAMP accumulation is lost upon tissue denervation, suggesting that this is likely to be a prejunctional effect. Elevation of cAMP levels by the use of the cell permeant analog of cAMP, 8-(p-chlorophenylthio)-cAMP (8pCPTcAMP) increases the electrically-evoked release of [3H]NA. However, the inhibition of [3H]NA release by NPY is not prevented by 8pCPTcAMP. Structure-activity relationship studies reveal that NPY and related peptides inhibit the release of [3H]NA, the muscle contractions and the synthesis of cAMP with a similar pharmacological profile. NPY is the most potent inhibitory agent, whereas [Leu31,Pro34]-NPY and NPY13-36, the respective Y1 and Y2 selective agonists, display similar potencies to inhibit the three responses. It is concluded that NPY inhibits neurotransmission in the rat vas deferens through the activation of a peptide receptor different from the known NPY-Y1 or NPY-Y2 receptor subtypes. NPY receptor activation in the vas deferens is negatively coupled to adenylyl cyclase activity. This intracellular signalling pathway is, however, not likely to mediate the peptide effects on the prejunctional regulation of noradrenaline release.

Adenylyl Cyclases↗

Individual and combined effects of ethanol and cocaine on intracellular signals and gene expression.

1. Ethanol and cocaine are drugs of abuse that can produce long-lived changes in behavior, including dependence. 2. A common set of neural pathways appears to mediate the addictive actions of ethanol and cocaine. 3. Many prominent aspects of drug dependence may be the result of alterations in intracellular signals as well as specific patterns of gene expression. 4. For instance, changes in G proteins and cAMP, phosphorylation of proteins and induction of c-fos and zif/268 in specific drug-sensitive brain regions may represent adaptive changes in response to a drug-dependent state. 5. The concurrent use of ethanol and cocaine is the most prevalent pattern of drug abuse in humans. However, the number of studies investigating the behavioral and molecular effects of this combination are few. 6. Emerging evidence indicates a possible antagonistic effect of ethanol and cocaine action on transcription factor function. In addition, cocaethylene (a psychoactive metabolite derived from combined ethanol and cocaine exposure) has significant effects on gene expression as well.

Animals↗

Antiviral roundup.

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CD4 Lymphocyte Count↗

Fenfluramine-induced c-fos in the striatum and hypothalamus: a tract-tracing study.

Systemic administration of DL-fenfluramine (20 mg kg-1), an indirect serotonergic agonist, induced widespread FOS-like protein in the rat caudate putamen (CPu), paraventricular nucleus (PVn) of the hypothalamus and several intralaminar thalamic nuclei. To ascertain whether the dopaminergic nigrostriatal system coordinated transcriptional effects on the CPu, discrete microinjections of dextran into the substantia nigra (cell group A9) were evaluated for retrograde axonal transport. The protein product was induced preferentially in medium-sized spiny nerve cells of the CPu. Dextran microinjections into the PVn demonstrated that perikarya bearing FOS-like protein projected their extensions directly to thalamic nuclei and indirectly to immunopositive neurons of the striatum. The significance of these latter results is discussed in terms of a possible dopaminergic mechanism.

Animals↗

Bone pain palliation with strontium-89 in breast cancer patients with bone metastases and refractory bone pain.

Fifteen patients with breast cancer and skeletal metastases who had bone pain refractory to opioid analgesics and who were not eligible for or had not responded to local field radiotherapy, were treated with strontium-89. All patients had received previous treatment with chemotherapy and radiotherapy for bone metastases. Severity of bone pain, sleeping pattern, mobility and dependency on analgesics were evaluated before and 4, 8 and 12 weeks after 89Sr administration. Patients received 2 MBq/kg (118-148 MBq) of 89Sr by i.v. injection. Pain relief and a reduction in analgesic requirements were observed in 7 of the 15 (47%) patients, with a reduction in the severity score from 34% to 71%. Duration of the response varied from 3 to 7 months. A decrease in peripheral blood cell count was observed in 11 patients: a 15%-66% reduction in white cell count and a 14%-75% reduction in platelet count were detected at 12 weeks after treatment in these patients. We conclude that 89Sr is effective (47% response rate) for bone pain palliation in patients with bone metastases from breast cancer. Dependency on opioid analgesics may be reduced in patients with refractory bone pain.

Aged↗

Comparison of outcomes and complications for open and laparoscopic cholecystectomy in Mexico.

A retrospective analysis of the outcome and surgical complications of two groups of patients undergoing cholecystectomy was performed. Group I consisted of 253 patients who underwent laparoscopic cholecystectomy between 1991 and 1994, and group II was formed by 292 patients who met the same preoperative criteria than patients of group I and underwent open cholecystectomy between 1986 and 1990, prior to the introduction of laparoscopic cholecystectomy in our hospital. General characteristics and associated clinical conditions were similar for both groups. Intraoperative cholangiography was used more frequently in group II whereas preoperative ERCP was performed more frequently in group I patients. There was no operative mortality in any of the groups. There were no statistically significant differences between both groups in terms of type and number of complications.

Cholangiopancreatography, Endoscopic Retrograde↗

111In-octreotide and 99mTc(V)-dimercaptosuccinic acid studies in the imaging of recurrent medullary thyroid carcinoma.

Detection of recurrence from medullary thyroid carcinoma (MTC) remains a diagnostic problem, especially when increased serum tumour marker levels suggest recurrence and conventional imaging techniques are non-diagnostic. In this study, we performed 111In-octreotide and 99mTc(V)-dimercaptosuccinic acid (DMSA) scans in a series of eleven patients with MTC presenting with elevated serum tumour markers after surgery. 111In-octreotide whole body studies detected tumour in six of the eleven patients studied and detected nine tumoral localizations. 99mTc(V)-DMSA whole body studies detected tumour in five of the eleven patients studied and eight tumoral localizations. 111In-octreotide and 99mTc(V)-DMSA studies detected recurrence in all four patients with basal calcitonin levels above 1000 ng/l. We conclude that 111In-octreotide and 99mTc(V)-DMSA studies have limited sensitivity to detect recurrence in patients with MTC, although their sensitivity may improve with high serum calcitonin levels. These radionuclide imaging techniques should be employed when conventional imaging techniques are negative or inconclusive or, in the case of 111In-octreotide studies, should be employed when we went to investigate the presence of somatostatin receptors that provide the basis for treatment with somatostatin analogues.

Adult↗