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At least 919 records · Page 51Linked to original sources
PubMed1993

Trial of maintenance neuroleptic dose reduction in schizophrenic outpatients: two-year outcome.

BACKGROUND: An open trial was undertaken to assess the feasibility of reducing maintenance doses in a public clinical setting and to identify eventual predictors of outcome after dose reduction in schizophrenia. METHOD: Forty-one remitted and chronically psychotic schizophrenic outpatients were assigned, on the basis of their previously clinically determined maintenance dosages, to one of two reduced fluphenazine decanoate regimens: 35 mg/4 wk (19 patients) or 10 mg/4 wk (22 patients). Subsequently, patients were assessed, for a 2-year period, by means of the Brief Psychiatric Rating Scale, the Scale for the Assessment of Positive Symptoms, the Scale for the Assessment of Negative Symptoms, the Simpson-Angus Scale, and the Abnormal Involuntary Movement Scale. RESULTS: Chronically psychotic patients, who represented 74% of the high-dose group and only 14% of the low-dose group, had a significantly higher cumulative relapse rate (81%) than remitted patients (38%). For most remitted patients a dose of 10 mg of fluphenazine decanoate, injected every 4 weeks, was satisfactory. Both remitted and chronically psychotic patients displayed reductions in the severity of neuroleptic side effects. CONCLUSION: Maintenance dose reductions may be beneficial for many schizophrenic outpatients. Chronically psychotic and remitted patients maintained on lowered dosages differ significantly in the stability of their course of illness.

Adolescent↗
PubMed1996

Utilization of depot neuroleptic medication in psychiatric inpatients.

This report describes the extent and pattern of use of depot neuroleptics within the 21 adult civil psychiatric hospitals operated by the New York State Office of Mental Health (OMH). All inpatients receiving depot or oral neuroleptics in calendar year 1994 were identified. In addition to descriptive data on admission and drug orders, a logistic regression was fit using gender, age, race, and facility for the probability of receiving depot. Depot utilization ranged from 12 percent to 39 percent of all patients receiving neuroleptics (N = 18,543). Differences among facilities were statistically significant (p < .05). Gender was not found to be a statistically significant factor, but blacks and Hispanic/others were found to be more likely than whites to receive depot (p < .05), and those 65 years or older were found to be less likely to receive depot (p < .05). For patients admitted in 1994, depot neuroleptics were typically started within a month or two of admission and continued for 2 to 3 months, with 86 percent of these patients discharged by December 31, 1995. Except for milligram dose and frequency of injection, haloperidol decanoate and fluphenazine decanoate did not differ in terms of extent and pattern of use.

Adult↗
PubMed1997

Absorption and metabolism of the absorption enhancer didecanoylphosphatidylcholine in rabbit nasal epithelium in vivo.

The absorption enhancer, didecanoylphosphatidylcholine (DDPC), improves the nasal absorption of human growth hormone in rabbits. We elucidated the uptake and the metabolism of 1,2-di[1-14C]decanoyl-L-3-phosphatidylcholine and 1,2-didecanoyl-L-3-phosphatidyl[N-methyl-3H]choline in rabbit nasal mucosa in vivo. One minute after nasal application of DDPC, 4.4-7.5% of the applied dose was found absorbed into the mucosa. The retained radioactivity left the tissue in <2 hr. The lipophilic tissue extract revealed that, at t = 1 min, only 1.1-1.4% of the applied dose was found as intact DDPC in the nasal mucosa. The other labeled compounds were decanoic acid, DDPC reacylated with endogenous fatty acids, a neutral lipid, and very small amounts of lyso-DDPC and phosphatidylethanolamine. The water-soluble metabolites revealed formation of phosphorylcholine, glycerophosphorylcholine, cytidinediphosphatecholine, and a slight amount of choline. The detection of these metabolites suggests that DDPC was rapidly cleared from the nasal mucosa, partly by degradation by phospholipases. In addition, data illustrated reutilization of DDPC metabolites in the formation of cytidinediphosphatecholine and phosphatidylethanolamine, together with DDPC being reacylated with endogenous fatty acids. The rapid formation of decanoic acid raises the possibility that this acid may contribute significantly to the drug-enhancing properties of DDPC.

Administration, Intranasal↗
PubMed1979

Inhibitors of oxidative degradation of protein: gerontological implications.

Compounds were studied that inhibit the oxidative degradation of human serum albumin by peroxidase and the enzyme model, iron hydroxide. Differences between the two oxidants gave clues for the mechanism of inhibition. The inhibitors studied were inorganic anions, phosphate, sulfate, carbonate and molybdate; organic anions, decanoate and glycocholate; and the nonionic species, glycogen. Such inhibitors might be considered as adjuvants in senescence: by decreasing the rate of enzymic oxidation of essential body proteins, they would, in the course of aging, reduce some of the physiological changes occurring as a result of accumulation of degraded protein.

Aging↗
PubMed1983

Severe anemia as a manifestation of metastatic jugular paraganglioma.

A young woman who had a right glomus jugulare paraganglioma had diffuse pulmonary metastases three years after surgical excision of the paraganglioma. Associated with these developments were profound anemia and an extraordinarily rapid ESR. These findings have been previously noted in patients with metastatic paraganglioma and have not as yet, to our knowledge, had a satisfactory explanation. Noteworthy in our patient was a diminished serum erythropoietin level, which may indicate that metastatic paragangliomas inhibit production of or interfere with maintenance of serum erythropoietin. Symptomatic palliation of the severe anemia was attained in this patient by injections of nandrolone decanoate. Follow-up examinations of patients with paragangliomas should include surveillance of the CBCs and ESR, both of which may reflect tumor activity.

Adult↗
PubMed1985

Gas chromatographic/mass spectrometric analysis of 19-nortestosterone urinary metabolites in man.

A sensitive and highly specific method based on capillary column gas chromatography/mass spectrometry has been developed for the detection of 19-nortestosterone (17 beta-hydroxy-4-estren-3-one) metabolites in urine. After intramuscular administration of 19-nortestosterone decanoate to man, urine samples were collected during several days and treated with Helix pomatia digestive juice. The free steroids were extracted and converted into O-methyl-oxime-trimethylsilyl or the trimethylsilyl ether derivatives and analysed by capillary column gas chromatography/mass spectrometry (GC/MS). Three isomeric metabolites were detected and identified as 3 alpha-hydroxy-5 alpha-extran-17-one (19-norandrosterone), 3 alpha-hydroxy-5 beta-estran-17-one (19-noretiocholanolone) and 3 beta-hydroxy-5 alpha-estran-17-one (19-norepiandrosterone). Packed column GC/MS was also employed in the selected ion monitoring mode for the specific detection of 19-norandrosterone, the most abundant urinary metabolite of 19-nortestosterone. These gas chromatographic/mass spectrometric methods are highly specific tests which can be used on a routine basis for the confirmation of 19-nortestosterone administration to athletes as well as for therapeutic monitoring following administration of the drug.

Estranes↗
PubMed1996

Toxicant-induced alterations in two-dimensional electrophoretic patterns of hepatic and renal stress proteins.

Recent studies in this laboratory and by others suggest that two-dimensional polyacrylamide gel electrophoresis of proteins (2-DE) possesses significant utility in the detection of chemical toxicity and in providing information regarding toxic mechanism. After having identified a set of specific heat-shock and glucose-regulated proteins whose expression in rodent liver and kidney is highly conserved and constitutive, we compared the effect of in vivo exposure to perfluoro-n-octanoic acid and perfluoro-n-decanoic acid on their expression. The following stress proteins were identified, their x, y coordinate positions mapped, and abundance statistically analyzed and compared: hsp32, hsp60, hsc70, hsp70, hsp90, grp75, grp94, protein disulfide isomerase (PDI), and ER60. We report here that the stress response to perfluorocarboxylic acids is tissue-, toxicant-, and stress protein class-specific and dose-related. Furthermore, because nearly all of the proteins studied were constitutively expressed at detectable levels in both liver and kidney, the 2-DE stress protein pattern may be suitable to future toxicologic screening applications.

Animals↗
PubMed1998

Expression of recombinant psoriasis-associated fatty acid binding protein in Escherichia coli: gel electrophoretic characterization, analysis of binding properties and comparison with human serum albumin.

The psoriasis-associated fatty acid binding protein (PA-FABP, also known as FABP5) is a novel keratinocyte protein that is highly up-regulated in psoriatic plaques (P. Madsen, H. H. Rasmussen, H. Leffers, B. Honoré and J. E. Celis, J. Invest. Dermatol. 1992, 99, 299-305). Here we have expressed PA-FABP in Escherichia coli as a fusion protein containing an NH2-terminal hexa-His tag followed by a factor Xa cleavage site. The recombinant protein was expressed at a level of about 30% of the soluble proteins and was purified to homogeneity using a simple two-step protocol consisting of affinity chromatography on Ni2+-nitrilotriacetic acid agarose followed by gel filtration. The recombinant protein was then digested with factor Xa and characterized by two-dimensional gel electrophoresis. The ability of PA-FABP to bind saturated fatty acids ranging from 6 to 16 carbons was determined directly by dialysis and compared to human serum albumin (HSA). The results showed that PA-FABP binds multiple molecules of the fatty acids hexanoate (C6:0), octanoate (C8:0), decanoate (C10:0) and laurate (C12:0), all with a K1 of about 10(4) M(-l), and myristate (C14:0) with a K1 of 4.4 X 10(5) M(-l). Palmitate (C16:0) also bound strongly with multiple molecules. Due to the very low solubility of palmitate its affinity to PA-FABP was measured relatively to HSA and found to be 8.1 times lower. At ligand/protein ratios below 1, all fatty acids bound to PA-FABP with about one to three orders of magnitude lower affinity than to HSA. The difference in the fatty acid binding properties of the two proteins may reflect differences in their three-dimensional structures, which in the case of PA-FABP consists mainly of beta-sheets while HSA contains predominantly alpha-helices.

Albumins↗
PubMed1992

Myotrophic effects of an anabolic steroid in rabbit limb muscles.

There has been no reliable evidence that the actions of anabolic steroids extend to limb muscles. In this study, female rabbits were treated with anabolic steroid (nandrolone decanoate) or arachis oil placebo for 4 weeks or 12 weeks. After 12 weeks, tibialis anterior muscles of treated animals showed highly significant increases in wet weight (38%), twitch tension (66%), maximum isometric tetanic tension (48%), maximum cross-sectional area (27%), and specific tension (17%). Fiber type composition showed a significant trend toward a less oxidative metabolic character. The experiments provided clear physiological and morphological evidence of a steroid-induced hypertrophy that was not attributable to fluid retention or changes in body weight. Of the muscles examined, the myotrophic effect was confined to the tibialis anterior muscle; extensor digitorum longus, plantaris, and soleus muscles showed no significant response. The work establishes an experimental model for the responses of limb muscles to anabolic compounds.

Anabolic Agents↗
PubMed1984

Alterations in the biophysical properties of the human endothelial cell plasma membrane induced by a chemotactic tripeptide: correlation with enhanced adherence of granulocytes.

Human umbilical vein endothelial cells in monolayer culture were used to study the effects of the chemotactic tripeptide, N-formylmethionylleucylphenylalanine (FMLP), on structure and function of the endothelium. Endothelial cell morphology was unaffected by concentrations of 10(-8)-10(-4)M. No effect on endothelial cell proliferative capacity, as measured by the DNA content of cultures, was seen at the FMLP concentrations studied (10(-8)-10(-6)M). Using fluorescent molecular probes to investigate FMLP-induced alterations in membrane structure, it was shown using the monomer-excimer method with pyrene decanoic acid that FMLP caused a marked restructuring of the plasma membrane. This took the form of a restriction of the surface available to the lipophile reporter molecules, probably caused by a molecular reorganization of the membrane protein component. Experiments with diphenylhexatriene indicated that FMLP did not make the plasma membrane of the endothelial cell more fluid. Concomitant with these changes in the physical properties of the membrane, an FMLP-induced increase in granulocyte adherence to the endothelial cells was observed. A theoretical model is presented correlating granulocyte adherence with the lateral mobility of lipids in the endothelial cell membrane. The significance of the FMLP-induced increase in granulocyte adherence to endothelial cells for the pathogenesis of sepsis is discussed.

Cell Adhesion↗
PubMed1994

Modification of hepatic immunoglobulin heavy chain binding protein (BiP/Grp78) following exposure to structurally diverse peroxisome proliferators.

This investigation was conducted to determine the comparative effect of structurally diverse peroxisome proliferators (PP) on the two-dimensional protein pattern of rat liver whole homogenates. Perfluoro-n-decanoic acid (PFDA), perfluoro-n-octanoic acid (PFOA), clofibrate, and di(2-ethylhexyl)phthalate (DEHP) are all known to cause the proliferation of hepatic peroxisomes and the induction of peroxisomal beta-oxidative and microsomal omega-oxidative enzymes. To clarify the mechanistic differences between these compounds with regard to the liver, we examined the unique patterns of protein alteration produced by in vivo exposure to them. Following exposure to various doses, whole liver homogenates were prepared and separated by two-dimensional gel electrophoresis (2DE) using the ISO-DALT system. Stained gels were digitized and protein patterns analyzed using the Kepler 2D gel analysis system. Immunoglobulin heavy chain binding protein (BiP), also known as 78-kDa glucose-regulated protein (Grp78), was identified immunologically and by comigration of recombinant Grp78. BiP is a luminal endoplasmic reticular protein that functions in the assembly and folding of nascent proteins as they enter the ER. The present results suggest a selective posttranslational modification of BiP following PFDA exposure. Single-dose exposure to PFDA was associated with a notable charge modification of BiP that persists up to 30 days. PFOA, clofibrate, and DEHP had less effect in this regard. The identity of BiP/Grp78 as the halothane hepatitis-associated trifluoroacetylated protein was also demonstrated. The nature of this PFDA-associated protein modification (reactive metabolite conjugation, abnormal ribosylation, or phosphorylation) is currently under investigation.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1994

Decrease in androgen binding and effect of androgen treatment in a case of X-linked bulbospinal neuronopathy.

X-linked recessive bulbospinal neuronopathy is a motoneuron disorder to be distinguished from amyotrophic lateral sclerosis, Effective treatment is not known. Patients with X-linked recessive bulbospinal neuronopathy may show gynecomastia and testicular atrophy, and a mutation in the androgen receptor gene has been found associated with the disease. Intermediate steps leading from the androgen receptor abnormality to the clinical syndrome have not yet been elucidated. Therefore, binding of androgen ([3H]dihydrotestosterone) to its specific receptor by genital skin fibroblasts cultured from a patient with X-linked recessive bulbospinal neuronopathy and confirmed androgen receptor mutation was studied. Markedly decreased binding capacity was found. We treated the patient for 6 months with nandrolone-decanoate. No effect on his neuromuscular status was observed during 2 years of follow-up.

Anabolic Agents↗
PubMed1987

Chain length and pressure dependence of lipid translational diffusion.

The translational diffusion of pyrene, pyrene butyric acid and pyrene decanoic acid has been determined in phosphatidylcholine bilayers of different chain length and under pressure up to 200 bars. In the liquid crystalline phase and at a given temperature the diffusion decreases with increasing chain length. At a constant reduced temperature, Tred (about 10 K above the transition temperature), long chain lipids exhibit the fastest diffusion which is in disagreement with hydrodynamic models but favours free volume models for diffusion in lipid bilayers. The volume of activation, Vact, calculated from the decrease of the diffusion coefficient with pressure, delta lnD/delta P, depends on lipid chain length. Vact decreases with decreasing lipid chain length at a given temperature, T = 65 degrees C, and increases at the reduced temperature. These results are again in agreement with the dependence of the diffusion on lipid chain length and therefore with the free volume model.

Chemical Phenomena↗
PubMed1992

Isoprenoid quinones and fatty acids of Zoogloea.

Nine Zoogloea strains including the type strain of Z. ramigera (IAM 12136 = ATCC 19544 = N.C. Dondero 106) and newly isolated strains were investigated for isoprenoid quinone composition and whole-cell fatty acid profiles. Seven of the tested strains, having phenotypic properties typical of Zoogloea, were characterized by their production of both ubiquinone-8 and rhodoquinone-8 as major quinones, whereas the remaining two strains, Z. ramigera IAM 12669 (= K. Crabtree I-16-M) and IAM 12670 (= P.R. Dugan 115), formed ubiquinone-10 and ubiquinone-8, respectively, as the sole quinone. All rhodoquinone-producing strains contained palmitoleic acid and 3-hydroxy-decanoic acid as the major components of nonpolar and hydroxylated fatty acids, respectively. Marked differences were noted in the fatty acid composition between the strains with and without rhodoquinones. The chemotaxonomic data suggested that the rhodoquinone-lacking strains should be excluded from the genus Zoogloea. Since there have been no reliable taxonomic tools for Zoogloea, rhodoquinone analysis may provide a new criterion of great promise for identifying Zoogloea strains.

Chromatography, High Pressure Liquid↗
PubMed1988

Reversibility of the haemodynamic effects of anabolic steroids in rats.

The haemodynamic effects of 6 weeks nandrolone decanoate treatment (total dose 30 mg.kg-1) (SG I, n = 12) and their reversibility were studied in anaesthetised, open-chest male rats exposed to 5 min isoproterenol (2.5 micrograms.kg-1) and CaCl2 (25.0 mg.kg-1) loads. In SG I, the heart weight and its ratio to body weight were greater than in the untreated rats (CG I, n = 13) (p less than 0.05 and p less than 0.01 respectively). The initial heart rate and the inotropic and chronotropic responses to isoproterenol were lower in SG I than in CG I (p less than 0.05 in all cases). Peripheral resistance decreased during both infusions in SG I but remained unaltered in CG I (p less than 0.05). 6 weeks after finishing anabolic steroid treatment (SG II, n = 11), in the CaCl2-test the ejection fraction (p less than 0.05) and stroke index were smaller than in control rats of the same age (CG II, n = 12). Mean aortic pressure was lower in SG II than in CG II. In the CaCl2-test peripheral resistance was initially higher, but decreased during the infusion in SG II while it increased in CG II (p less than 0.05 in both cases). In conclusion, anabolic steroid treatment reversibly reduces the left ventricular response to isoproterenol. It decreases peripheral vascular tone during inotropic loads. Six weeks after the cessation of treatment, the pumping efficiency of the heart is reduced.

Anabolic Agents↗
PubMed1979

On two-dimensional passive random walk in lipid bilayers and fluid pathways in biomembranes.

The lateral mobility of pyrene, pyrene decanoic acid, and 1-palmitoyl-2-pyrene decanoyl-phosphatidyl choline (pyrene lecithin) in lipid bilayers is determined by the excimer formation technique. This method is applied to vesicles of lecithins differing in chain length and in the degree of saturation of the hydrocarbon chains. These values are compared with results in cephalins of different chain length and in dipalmitoyl phosphatidic acid at variable pH. The influence of cholesterol is investigated. The results are analyzed in terms of the Montroll model of two-dimensional random walk. The jump frequency of the probe molecule within the lipid lattice is obtained. The advantage of this measure of transport in lipid layers is that it does not involve lipid lattice parameters. The main results of the present work are: (i) The lateral mobility of a given solute molecule in lamellae of saturated lecithins is independent of hydrocarbon chain length and rather a universal function of temperature. (ii) In unsaturated dioleyl lecithin the amphiphatic molecules have lateral mobilities of the same size as in saturated lipids. The jump frequency of pyrene, however, is by a factor of two larger in the unsaturated lecithin. (iii) The jump frequencies in phosphatidyl ethanolamines are about equal to those in lecithins. (iv) In phosphatidic acid layers the hopping frequencies depend on the charges of the head groups of both the lipids and the probes. (v) Cholesterol strongly reduces the jump frequency in fluid layers. (vi) The lateral mobility in biological membranes is comparable to that in artificial lipid bilayers. The experimental results are discussed in terms of the free volume model of diffusion in fluids. Good agreement with the predictions made from this model is found. A striking result is the observation of a tilt in dioleyl-lecithin bilayer membranes from the hopping frequencies of pyrene and pyrene lecithin. A tilt angle of phi = 17 degrees is estimated.

Cholesterol↗
PubMed1994

Fatty acid and positional selectivities of gastric lipase from premature human infants: in vitro studies.

Gastric lipase activity in aspirates from premature human infants was tested for fatty acid and positional selectivity using racemic diacid triacylglycerols (TG) as substrates. The resulting free fatty acids and monoacylglycerols (MG) were recovered and analyzed. Octanoic acid (8:0) and decanoic acid (10:0) were hydrolyzed with a preference of 61.5:1 and 2.4:1 compared to palmitic acid (16:0) from rac-16:0-8:0-8:0 and rac-16:0-10:0-10:0, respectively. The ratio of lauric acid (12:0) to oleic acid (18:1) hydrolyzed from rac-18:1-12:0-12:0 was 13:1. Myristic acid (14:0), 18:1 and linoleic acid (18:2) were released at similar rates. These data and the composition of the MG suggest that, in vitro, the lipase is selective for shorter chain fatty acids and for fatty acids on the primary positions of the TG backbone.

Caprylates↗
PubMed1990

Fatty acid hydroxylase system in the Japanese harvest mouse, Micromys minutus.

Liver microsomes of the Japanese harvest mouse (Micromys minutus), which is the smallest known mammal among rodents, catalyze the hydroxylation of various fatty acids (C8 to C18) to the corresponding omega-hydroxy and (omega-1)-hydroxy derivatives. Although laurate is most effectively hydroxylated among saturated fatty acids by liver microsomes of other species, harvest mouse liver microsomes most effectively catalyze the hydroxylation of decanoate. From inhibitor and cofactor studies, and from the substrate specificity for hydroxylation, it was concluded that omega- and (omega-1)-hydroxylation of fatty acids are catalyzed by different cytochrome P-450 species in the liver microsomes of the harvest mouse.

Animals↗