Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0011570 (depression)
 172,036 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

One hundred ninety-four nonmelancholic depressed outpatients with features of atypical depression took part in a 6-week randomized trial of imipramine hydrochloride, phenelzine sulfate, and placebo. Their courses of illness were also rated for chronicity. Significantly more patients responded to phenelzine (71%) than to imipramine (48%), which benefited significantly more patients than placebo (26%). Both chronicity and DMS-III diagnosis predicted response on several outcome measures. For example, patients with dysthymic disorder responded better to treatment than did those with major depression, suggesting that dysthymic disorder can be treated with medication. Placebo response correlated inversely with chronicity, regardless of DMS-III diagnosis. Atypical depression and longitudinal course of illness may add to the usefulness of DMS-III depressive diagnosis as a predictor of antidepressant response.
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PMID:Relevance of DMS-III depressive subtype and chronicity of antidepressant efficacy in atypical depression. Differential response to phenelzine, imipramine, and placebo. 268 75

Knees of mature dogs were immobilized for 6 weeks by long-leg casts allowing 8 degrees-15 degrees of motion, a model studied by others, or with external fixators, a new, more severe model that kept the joints rigid. Some animals were allowed to recover for 1 week after the immobilization period. Articular cartilage was examined histologically and biochemically. After 6 weeks of immobilization, water increased 7% in both casted and fixator-immobilized joints compared with normal knee cartilage, while hexuronic acid was 23 and 28% lower, respectively. The limited motion permitted by the casts resulted in a smaller depression of proteoglycan synthesis and less proteoglycan loss during immobilization than occurred in the rigid external fixator group. The protective effect of limited motion was shown clearly during the recovery period: as measured by hexuronic acid content, cartilage from the casted joints had almost recovered within 1 week, whereas the external fixator group experienced little or no recovery during the week after treatment. In contrast to previous studies by others with casted joints, both newly synthesized [35S]sulfate-labeled and accumulated unlabeled proteoglycans from both casted and fixator-immobilized cartilages were able to form complexes with exogenous hyaluronic acid to the same extent as those from control cartilage. Thus, in immobilized cartilage, failure of the newly synthesized proteoglycan to bind to hyaluronate is not a mechanism of accelerated proteoglycan loss. The accelerated proteoglycan turnover appears to be caused by a combination of decreased synthesis and increased proteolysis of the secreted proteoglycans.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Biochemical changes in articular cartilage after joint immobilization by casting or external fixation. 270 26

Controlled release morphine sulfate (MS Contin) is a relatively new oral preparation for the relief of chronic severe (cancer) pain. We describe a patient with severe neuralgia who experienced respiratory depression after ingestion of one single dose of morphine sulfate (20 mg). Administration of nalorphine chloride resulted in instant normalisation of respiratory function. This case illustrates respiratory depression as an adverse effect of MS Contin.
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PMID:[Respiratory depression following controlled-release morphine sulfate tablets]. 271 Feb 34

A double-blind, double-dummy, crossover study compared oral controlled-release morphine sulfate (MS Contin tablets [MSC], Purdue Frederick, Norwalk, CT) every 12 hours, and immediate-release morphine sulfate (IRMS) tablets, every 4 hours, in 14 evaluable patients with chronic cancer pain. The test model described showed assay sensitivity for steady-state analgesia, requiring relatively few subjects to yield statistical significance in pharmacologic potency estimates. Initial doses were the calculated equivalents of about one third the previous opioid requirements or at least 30 mg MSC every 12 hours or 15 mg IRMS every 4 hours. This was generally subtherapeutic; hence, additional IRMS was available for break-through pain. Doses of MSC and IRMS were titrated upwards until the requirement for rescue IRMS was less than 20% of the total daily amount of morphine. In both study phases, the total dose of morphine increased significantly from the first day to the last, on which it was significantly (34%) higher for IRMS than MSC. Pain was significantly less intense and frequent in the last 24 hours of each treatment arm than in the first, and equally well controlled by both regimens. The two treatments were equipotent in a pharmacologic assay using dosages and pain scores. The requirement for rescue analgesia was similarly comparable for both treatments, decreasing significantly with upward dose titration. The few side effects experienced (one with MSC and three with IRMS) did not include serious reactions such as respiratory depression. It is concluded that MSC, 12-hourly, controls cancer pain as effectively and safely as IRMS on a 4-hour schedule. MS Contin exhibits a 12-hour duration of action as previously shown in other well-controlled trials. A problem of pain exacerbation at the start of each study phase was found to be associated with the design of this study. It may be resolved with a higher initial study dose and/or use of a patient-controlled analgesia device for parenteral rescue doses.
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PMID:Evaluation of a cancer pain model for the testing of long-acting analgesics. The effect of MS Contin in a double-blind, randomized crossover design. 272 May 81

A prospective double-blind study was undertaken to compare the effectiveness of the agonist-antagonist nalbuphine hydrochloride with morphine sulfate in relieving pain from burn debridement. The study consisted of two groups in which each was given a preprocedure dose of the study medication followed by administration of incremental doses up to one half the initial dose as requested. After reviewing the literature, we set the ratio of nalbuphine hydrochloride/morphine sulfate at 2:1 mg, respectively. Safety and efficacy were determined by measurements of vital signs, sedation, adverse effects, and patient evaluation of pain intensity and relief with the use of both an adjective and a visual analogue scale. Analysis showed no significant differences in the variables measured. Therefore in relieving burn debridement pain, we found nalbuphine hydrochloride to be as effective as morphine sulfate. We also found that respiratory depression was not a problem in either group.
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PMID:Effectiveness of nalbuphine for relief of burn debridement pain. 274

The ventilatory pharmacodynamics of morphine sulfate (MS) in the awake dog (n = 14) were investigated. Two routes of MS administration were employed: 1) 4 h continuous intravenous (iv) infusion (1 mg.kg-1 loading dose, 10 micrograms.kg-1.min-1 thereafter); and 2) fourth ventricle to cisterna magna perfusion (VCP) at increasing infusate morphine concentrations (0.1-100 micrograms.ml-1). The former was associated with a constant plasma and cisternal CSF (and presumably tissue) free morphine concentration. The latter produced, over 1 h at a constant infusate morphine delivery, a cisternal CSF free morphine concentration that leveled off by 30 min, little or no distribution of drug beyond superficial dorsal and superficial ventral brainstem tissue, and no detectable levels of morphine in plasma. When comparing the two routes of administration, ventilatory depression for a given cisternal free morphine level in the iv infusion studies was of a much greater magnitude than that seen in VCP experiments. Differences in the ventilatory patterns were also noted. Thus, iv delivery produced a decrease in tidal volume (VT) and no change or reduced respiratory frequency (f) with prolonged exposure. VCP delivery was also associated with reduction in VT but produced significant increases in f. An apparent maximal ventilatory depression with 1 h VCP administration was observed at morphine infusate levels of greater than 10 micrograms.ml-1, with higher infusate concentrations and extension of the perfusion period to 3 h producing no significant additional changes. Finally, VCP delivery of the mu-antagonist nalbuphine could only partially reverse the ventilatory depression accompanying iv morphine administration. These findings suggest that the ventilatory depression associated with iv morphine is a result of interactions with brain u-opiate receptors in superficial brainstem tissue and in deep brainstem and/or suprapontine tissue as well.
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PMID:Comparative ventilatory effects of intravenous versus fourth cerebroventricular infusions of morphine sulfate in the unanesthetized dog. 275 45

Comprehensive examinations of dermal morphology and function, carried out in 50 patients suffering from psoriasis, have revealed manifest hypoxia, depression of the intramitochondrial energy production, reduction of the cellular synthetic potency, increased protein catabolism, impaired transcapillary transport and vascular and tissue permeability, immediate and delayed type hypersensitivity local immune reactions. Basing on these findings, the authors have developed a new effective method for multiple modality treatment of psoriasis patients. The new scheme includes, besides the routine modalities (sedative and lipotropic drug, vitamins, UV irradiation, diets, ointments), subcutaneous injections of oxygen into the large foci (200 ml daily, 12-18 injections per course, alternating the injection sites) and oral intake of copper sulfate and reduced iron (3 times daily after meals for 20-30 days). The study has involved 112 patients with psoriasis (61 patients in the test group and 51 in the reference one). Clinical and morphologic examinations have demonstrated the advantages of the new method: clinical remission has occurred 1.8 times more often, the length of treatment has been cut by 7 days, an earlier and more complete recovery of the morphofunctional characteristics of the dermis has been achieved.
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PMID:[Validation and experience in the use of local oxygen therapy in the system of the combined treatment of psoriasis patients]. 276 7

Thirty-two patients (14 women and 18 men) whose age ranged between 15 and 76 were admitted on an emergency and anesthetized with propofol in view of various surgical interventions (9 appendectomies, 9 fractures, 5 wound healing, 6 abscess incisions, 2 corneal grafts and one complex trauma surgery) undergone 24 hours after their admission. Premedication included hydroxyzine 1.5 mg.kg-1, atropine sulfate 0.5 to 0.75 mg and pethidine 1 mg.kg-1 according to pain intensity and initial pathology. Narcosis was induced by 2.5 mg.kg-1 propofol injected intravenously. Propofol was then administered continuously at a dose of 9 mg.kg-1 in the first hour and of 4.5 mg.kg-1.h-1 in the following hours for 28 of the patients. Four patients undergoing short operations were given additional injections of one third of the initial dose. Analgesia and myorelaxation were obtained with fentanyl (0.16 +/- 0.06 mg) and vecuronium (9.3 +/- 4 mg). Narcosis proved to be very efficient. The side effects observed (13% myoclonia, 6% rash, 6% bradycardia, 0.3% pains at the time of injection) were similar to those quoted in the literature. Blood pressure stabilized after a short slight depression (13% to 18% of the standard values). Pulse remained regular. We can thus say that propofol is a good hypnotic drug for emergency anesthesia provided that its contra-indications especially shocks of cardiac or septic origin and hypovolemia, are carefully respected.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Propofol in emergency anesthesia]. 278 40

M13 coat protein is a small (50 amino acids) lipid-soluble protein that becomes an integral membrane protein during the infection stage of the life cycle of the M13 phage and is therefore used as a model membrane protein. To study side-chain dynamics in the protein, we have measured individual hydrogen-exchange rates for a primary amide in the side chain of glutamine-15 and for the indole amine of tryptophan-26. The protein was solubilized with the use of perdeuteriated sodium dodecyl sulfate (SDS), and hydrogen-exchange rates were measured by using 1H nuclear magnetic resonance spectroscopy. The glutamine-15 syn proton exchanged at a rate identical with that in glutamine model peptides except that the pH corresponding to minimum exchange was elevated by about 1.5 pH units. The tryptophan-26 indole amine proton exchange was biphasic, suggesting that two populations of tryptophan-26 exist. Approximately one-fourth of the tryptophan-26 resonance intensity exchanged at the same rate as a tryptophan model peptide, whereas three-fourths of the tryptophan-26 resonance intensity exchanged about 1000-fold more slowly. It is suggested that the two populations may reflect protein dimerization or aggregation in the SDS micelles. The pH values of minimum exchange for tryptophan-26 in both environments were also elevated by 1.3-1.9 pH units. This phenomenon is reproduced when small tryptophan- and glutamine-containing hydrophobic peptides are dissolved in the presence of SDS micelles. The electrostatic nature of this phenomenon is proven by showing that the minimum pH for exchange can be reduced by dissolving the hydrophobic peptides in the positively charged detergent micelle dodecyltrimethylammonium bromide. A small hydrophobic effect, which involves the depression of base catalysis to a significantly greater extent than acid catalysis, was observed for some of the peptides solubilized with the neutral detergent octyl glucoside.
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PMID:Side-chain dynamics of a detergent-solubilized membrane protein: measurement of tryptophan and glutamine hydrogen-exchange rates in M13 coat protein by 1H NMR spectroscopy. 279 27

Cysteine is required for the synthesis of cosubstrates for two pathways of acetaminophen metabolism: 3'-phosphoadenosine-5'-phosphosulfate (PAPS) for sulfation and glutathione (GSH) for detoxification of the reactive metabolite (N-acetyl-p-benzoquinoneimine, NAPQI). Dietary deficiency of cysteine may reduce hepatic production of PAPS and GSH and thereby reduce metabolism of the drug (by sulfation and detoxification of NAPQI) and hence lead to potentiation of acetaminophen liver injury. Conversely, limitation of sulfur-containing amino acids could result in depression of protein synthesis and hepatic cytochrome P450 levels, and hence in decreased reactive metabolite formation and decreased liver injury. To determine whether the potentiating effects exceed the protective effects, rats were fed isocaloric AIN-76 liquid diets containing various levels of methionine as the sole source of sulfur in the diet for 3 weeks prior to administration of acetaminophen. Sulfur deficiency was assessed by measuring urinary inorganic sulfate levels. Sulfur-deficient diets retarded growth but did not affect nitrogen balance. Sulfur-deficient animals had lower basal levels of hepatic GSH. Pharmacokinetic studies revealed that at low doses of acetaminophen (20 mg/kg), animals fed sulfur-deficient diets metabolized the drug more slowly due to a markedly reduced sulfation capacity, whereas at the high dose of acetaminophen (400 mg/kg), rats that were fed sulfur-deficient diets had a higher clearance of the drug than rats that were fed the complete diet. The increase in clearance was due largely to an enhanced glucuronidation capacity and an enhanced P450-dependent oxidation as indicated by mercapturate formation. Histologic studies revealed that rats fed sulfur-deficient diets showed increases in both incidence and severity of acetaminophen hepatic necrosis. Thus, the potentiating effects exceeded the protective effects. These observations raise the possibility that nutritional inadequacy of sulfur-containing amino acids which could occur during protein malnutrition may similarly enhance susceptibility to acetaminophen liver injury in humans.
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PMID:Effects of sulfur-amino acid-deficient diets on acetaminophen metabolism and hepatotoxicity in rats. 281 88


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