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PubMed2000

Fluphenazine levels during maintenance treatment of recent-onset schizophrenia: relation to side effects, psychosocial function and depression.

RATIONALE: The utility of fluphenazine levels during maintenance treatment of schizophrenia is still unclear. OBJECTIVES: This study investigated the relationship between fluphenazine levels and a variety of clinical measures during maintenance treatment of schizophrenia. METHODS: Fluphenazine levels, side effects, depression and psychosocial outcome were measured at five time points over approximately 1 year in 59 recent onset schizophrenic patients treated with a maintenance dose of injectable fluphenazine decanoate. Negative symptoms were evaluated at the 1-year endpoint. RESULTS: Fluphenazine levels showed marked intraindividual variability even when measurements were restricted to the second 6 months of treatment, by which time steady state levels should have been achieved. No consistent relationship was found between fluphenazine levels and any of the outcome measures. CONCLUSIONS: The results of this study suggest that fluphenazine plasma levels do not routinely add relevant clinical information beyond that of dose in evaluating potential side effects or negative consequences during maintenance treatment with the decanoate form of the medication.

Adult↗
PubMed1988

Dual action of 2-decynoyl coenzyme A: inhibitor of hepatic mitochondrial trans-2-enoyl coenzyme A reductase and peroxisomal bifunctional protein and substrate for the mitochondrial beta-oxidation system.

The present study was designed to determine the action of the 2-acetylenic acid thioester on mitochondrial fatty acid chain elongation and beta-oxidation. Addition of 2-decynoyl CoA to a rat liver mitochondrial suspension resulted in a significant stimulation of the rate of oxidation of NADPH and NADH. This enhanced oxidation rate was not due to the mitochondrial trans-2-enoyl CoA reductase-catalyzed conversion of the 2-acetylenic acid thioester to the saturated product, decanoate, as measured by gas-liquid chromatography. On the contrary, the mitochondrial trans-2-enoyl CoA reductase activity was markedly inhibited by the 2-acetylenic acid derivative, as evidenced by the decrease in the reduction of trans-2-decenoyl CoA to decanoic acid. Incubation of the mitochondrial fraction with either NADPH or NADH and 2-decynol CoA resulted in the gas chromatographic identification of three products: beta-ketodecanoate, beta-hydroxydecanoate, and trans-2-decenoate. In the absence of reduced pyridine nucleotide, a single product was formed and identified as beta-ketodecanoate. Confirmation of the identity of this product was obtained by the observation of the formation of the Mg2+-enolate complex (303-nm absorbance peak). These results suggest that, although the 2-decynoyl CoA is an inhibitor of mitochondrial trans-2-enoyl CoA reductase activity, it is a substrate for the mitochondrial trans-2-enoyl CoA hydratase (crotonase). This was confirmed by incubation of 2-decynoyl CoA with commercially purified liver mitochondrial crotonase. The beta-ketodecanoate is formed in a two-step process: hydration of the 2-decynoyl CoA to an unstable enol intermediate which undergoes rearrangement to the beta-ketodecanoyl CoA. Interestingly, although the mitochondrial crotonase can utilize the 2-acetylenic acid thioesters, this was not the case for the peroxisomal bifunctional hydratase which was markedly inhibited by varying concentrations of 2-decynoyl CoA.

3-Hydroxyacyl CoA Dehydrogenases↗
PubMed1986

Chronic treatment with five different neuroleptics elicits behavioral supersensitivity to opiate infusion into the nucleus accumbens.

It has previously been demonstrated that direct opiate infusion into nucleus accumbens elicits psychomotor activation in rats. In the present study, the effects of chronic treatment with five different neuroleptics on this behavioral response were investigated. All neuroleptics tested (haloperidol, sulpiride, flupentixol decanoate, perphenazine enanthate, fluphenazine decanoate, palmitic ester of pipotiazine) induced a marked behavioral supersensitivity to intraaccumbens opiate infusion. A similarly enhanced sensitivity was observed in chronic reserpine-treated rats. The maximum sensitivity to opiates appeared 2-3 weeks after the beginning of neuroleptic treatment and was present up to 1 month after the end of treatment. Naloxone blocked the neuroleptic-induced enhanced response to opiates. It is concluded that chronic blockade of dopaminergic transmission results in considerable functional alterations of the endogenous opiate systems. The results are discussed in terms of possible underlying neuronal mechanisms, and important clinical implications are noted.

Animals↗
PubMed1992

Chronic neuroleptic administration decreases extracellular GABA in the nucleus accumbens but not in the caudate-putamen of rats.

The extracellular levels of gamma-aminobutyric acid (GABA) in the caudate-putamen and the nucleus accumbens of rats following administration of haloperidol decanoate, fluphenazine decanoate, or vehicle for 8 months were assessed using intracranial microdialysis. Basal levels of extracellular GABA were significantly decreased in the nucleus accumbens of both neuroleptic-treated groups while levels of GABA in the caudate-putamen were not significantly different between groups. These results provide evidence for selective chronic neuroleptic-induced effects on in vivo GABA function in different terminal regions containing dopamine receptors.

Animals↗
PubMed1995

High-performance liquid chromatographic determination of the rhamnolipids produced by Pseudomonas aeruginosa.

The bacterial biosurfactants 3-[3'-(L-rhamnopyranosyloxy)decanoyloxy]decanoic acid (RL-1) and 3-[3'-(2"-O-alpha-L-rhamnopyranosyl-alpha-L-rhamnopyranosyloxy) decanoyloxy]decanoic acid (RL-2) were isolated from Pseudomonas aeruginosa DSM 2659 cultures. An HPLC method was developed for the p-bromophenacyl esters of the rhamnolipids. Separation was obtained within 25 min on a RP C18 column using a linear gradient of water-acetonitrile (30:70 to 0:100) and UV detection (265 and 320 nm). Linearity of response existed for 1.2-25 microg of the RL-1 and 1.8-25 microg of the RL-2-p-bromophenacyl ester (0.9-19.2 microg RL-1 and 1.3-18.0 microg RL-2). The reproducibility of the entire analytical method (extraction, derivatisation) was tested.

Carbohydrate Sequence↗
PubMed1993

Behavioral effects of long-term administration of an anabolic steroid in intact and castrated male Wistar rats.

Once a week, intact and castrated male Wistar rats were intramuscularly injected with a 0.2 ml suspension of either 0, 10, or 50 mg nandrolone decanoate in cottonseed oil, for 8 consecutive weeks. After the sixth injection, locomotor activity was measured in an open-field and the acquisition of lever press behavior was assessed in an autoshaping procedure. Subsequently, all subjects were exposed to four sessions of continuous reinforcement prior to one session in which the effects of steroid administration on extinction were assessed. Locomotor activity decreased for all groups of rats with continued exposure to the open-field, differences between groups were not observed. Rats treated with the highest dose of nandrolone decanoate spent more time in the margin of the open-field. There were no significant differences between groups on any of the learning measures. Long-term, high-dose steroid administration in conjunction with mild food deprivation inhibited growth in intact and castrated rats, while low dose administration affected body weight in intact rats only. Steroid administration resulted in heavier and enlarged kidneys and lighter testes as well. These results suggest that the administration of anabolic steroids not only produces observable physiological changes, but that it may also affect spontaneous behavior. The failure to find differences in learning indices may have been a function of the particular paradigms used in the present experiment.

Anabolic Agents↗
PubMed1983

Correlation of fluphenazine plasma levels versus clinical response in patients: a pilot study.

Five schizophrenic patients (diagnosed using Research Diagnostic Criteria) under treatment with intramuscular fluphenazine decanoate or oral fluphenazine dihydrochloride had serial plasma fluphenazine and plasma prolactin levels determined by a direct radioimmunoassay method. Clinical state was assessed utilizing the Global Assessment Scale and the Extrapyramidal Symptoms-Neurological Rating Scale. There was no correlation between clinical state and plasma fluphenazine or prolactin levels. All patients under treatment with the depot preparation remained clinically stable with serum fluphenazine levels between 1 and 3 ng/ml. In one patient, who received an intramuscular dose of fluphenazine decanoate, plasma levels were determined using direct radioimmunoassay, extraction followed by radioimmunoassay and gas liquid chromatography-mass spectrometry. There were good correlation between the three methods.

Administration, Oral↗
PubMed1989

Pharmacokinetics of three different injectable zuclopenthixol preparations.

1. The zuclopenthixol concentrations in serum has been investigated in man and dog after injection of three different zuclopenthixol preparations. These were zuclopenthixol dihydrochloride in aqueous solution, zuclopenthixol acetate in oil and zuclopenthixol decanoate in oil. 2. The pharmacokinetic profiles of the three injectable zuclopenthixol preparations are very different. Maximum serum levels are obtained after about 1 hour for zuclopenthixol dihydrochloride, after 36 hours for zuclopenthixol acetate and after one week for zuclopenthixol decanoate. 3. The different pharmacokinetics of the three injectable zuclopenthixol preparations are reflected in their clinical properties.

Adult↗
PubMed1991

Comparative aspects of microsomal cytochrome P-450-dependent monooxygenase activities in musk shrew (Suncus murinus), Mongolian gerbil (Meriones unguiculatus), harvest mouse (Micromys minutus) and rat.

1. The cytochrome P-450 content (0.75 +/- 0.13 nmol/mg microsomal protein) in musk shrew (suncus, Suncus murinus) liver microsomes was lower than that (1.30 +/- 0.26) in rat liver microsomes, but it is approximately the same level as in the Mongolian gerbil (Meriones unguiculatus, 1.18 +/- 0.14), harvest mouse (Micromys minutus, 1.11 +/- 0.02) and rat. 2. The hydroxylation activity (based on cytochrome P-450) of medium-chain fatty acids (otanoic, decanoic, lauric and tridecanoic acids) is much higher in suncus, Mongolian gerbil and harvest mouse than in rat, with the exception of the activity of decanoic and tridecanoic acids in Mongolian gerbil. 3. This suggests that cytochrome P-450 species catalyzing the hydroxylation of medium-chain fatty acids are present in these laboratory animals in higher concentrations. 4. The aminopyrine N-demethylation activity based on microsomal protein or cytochrome P-450 in suncus is significantly lower than that in rat, but the N-demethylation activity in Mongolian gerbil and harvest mouse is approximately 1.7-2.0-fold greater than that in rat.

Aminopyrine↗
PubMedDate not supplied

Regional differences in chronic neuroleptic effects on extracellular dopamine activity.

The extracellular levels of dopamine (DA) and DA metabolites in the caudate-putamen (CPu) and the nucleus accumbens (NA) of rats following administration of haloperidol (HAL) decanoate and fluphenazine (FLU) decanoate for 8 months were assessed using intracranial microdialysis 1 month after final injection. Both HAL- and FLU-treated animals showed persisting plasma neuroleptic levels at time of sacrifice. Extracellular basal levels of homovanillic acid (HVA) in the CPu were significantly elevated in the FLU-treated animals, while basal levels of 3,4-dihydroxyphenylacetic acid (DOPAC) in the CPu were significantly elevated in the HAL-treated animals. Basal levels of DA and the serotonin metabolite, 5-hydroxyindoleacetic acid (5HIAA) in the CPu were not significantly different between groups. No significant between-group differences were found for basal levels of any of the analytes in the NA. Neuroleptic-treated animals showed an enhanced response to direct infusion through the dialysis probe of amphetamine (1 microM) and nomifensine (10 microM) in the CPu but not the NA. These results suggest that chronic neuroleptic treatment produces enhanced extracellular DA activity in nigrostriatal, but not mesolimbic DA pathways.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1992

Immunocytochemical survey of haloperidol-induced immunoreactive changes of [Met]enkephalin-Arg6-Gly7-Leu8 in the rat forebrain.

It has already been demonstrated that chronic treatment with the dopamine receptor blocker, haloperidol, results in an increase of proenkephalin-A-derived peptides in the caudate-putamen (CP). To examine this phenomenon at the cellular level, we used immunocytochemistry to investigate the effects of haloperidol on [Met]enkephalin-Arg6-Gly7-Leu8 (MEAGL) immunoreactivity in the rat forebrain. After daily haloperidol (5 mg/kg, IP, for 6 days) or haloperidol decanoate (70 mg/kg, IM, given once or twice) treatment, immunoreactive neurons appeared diffusely in the whole CP and in the core part of the nucleus accumbens (Acb) and less frequently in the outer shell part of the Acb and the cell-dense layer of the tuberculum olfactorium (TuO). Increase of MEAGL-immunoreactive fibers in the CP, Acb, and TuO was also detected after these treatments, a particularly prominent increase being found in the striopallidal terminals in the globus pallidus and ventral pallidum. Haloperidol or haloperidol decanoate had no effect on MEAGL immunoreactivity in the cerebral cortex, amygdala, or hypothalamus. Reserpine treatment (5 mg/kg, IP, for 6 days) caused similar effects on the dorsal and ventral striopallidal system, and the direct injection of 6-hydroxydopamine (10 micrograms/5 microliters) into the CP led to the appearance of MEAGL-immunoreactive neurons in accordance with the depleted dopaminergic terminal area. These findings suggest that haloperidol influences enkephalinergic neurons region specifically and that in the dorsal and ventral striopallidal enkephalinergic system haloperidol increases MEAGL immunoreactivity in cell bodies, fibers, and terminals by blocking intrastriatal dopaminergic neurotransmission.

Animals↗
PubMed2005

Mechanistic analysis of wheat chlorophyllase.

Chlorophyllase catalyzes the initial step in the degradation of chlorophyll and plays a key role in leaf senescence and fruit ripening. Here, we report the cloning of chlorophyllase from Triticum aestivum (wheat) and provide a detailed mechanistic analysis of the enzyme. Purification of recombinant chlorophyllase from an Escherichia coli expression system indicates that the enzyme functions as a dimeric protein. Wheat chlorophyllase hydrolyzed the phytol moiety from chlorophyll (k(cat) = 566 min(-1); K(m) = 63 microM) and was active over a broad temperature range (10-75 degrees C). In addition, the enzyme displays carboxylesterase activity toward p-nitrophenyl (PNP)-butyrate, PNP-decanoate, and PNP-palmitate. The pH-dependence of the reaction showed the involvement of an active site residue with a pK(a) of approximately 6.5 for both k(cat) and k(cat)/K(m) with chlorophyll, PNP-butyrate, and PNP-decanoate. Using these substrates, solvent kinetic isotope effects ranging from 1.5 to 1.9 and from 1.4 to 1.9 on k(cat) and k(cat)/K(m), respectively, were observed. Proton inventory experiments suggest the transfer of a single proton in the rate-limiting step. Our analysis of wheat chlorophyllase indicates that the enzyme uses a charge-relay mechanism similar to other carboxylesterases for catalysis. Understanding the activity and mechanism of chlorophyllase provides insight on the biological and chemical control of senescence in plants and lays the groundwork for biotechnological improvement of this enzyme.

Amino Acid Sequence↗
PubMed2006

Characterisation of membrane mimetics on a dual polarisation interferometer.

Dual polarisation interferometry (DPI) has been used to characterise the formation of hybrid bilayer membranes (HBM) on a silicon-oxynitride surface. This technique allows the simultaneous determination of multiple physical properties of an HBM, as the HBM is being formed in a single experiment: mass, thickness in the z-direction (normal to the surface), tilt angle of the first layer and refractive index. Decanoic acid was covalently attached to an amine modified silicon-oxynitride sensor chip surface via 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide hydrochloride condensation reaction. The decanoic acid layer was 0.92+/-0.12 nm thick, indicating a tilt angle of 57 degrees from surface normal, and possessed a mass of 1.05+/-0.10 ng mm(-2) and a refractive index (RI) of 1.450+/-0.020. Phospholipid vesicles made from 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) or 1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC) were injected over the fatty acid surface to form an HBM. The DPPC HBM was 4.32+/-0.68 nm thick, with a total mass of 3.18+/-0.60 ng mm(-2) and a RI of 1.404+/-0.007. The DMPC HBM was 2.12+/-0.34 nm thick, with a total mass of 2.25+/-0.51 ng mm(-2), and a RI of 1.435+/-0.007. DPI thus provides an insight into HBM formation and differences between the structural organisation of HBMs of different composition.

Biomimetic Materials↗
PubMed2005

Application of purge and trap extraction and gas chromatography for determination of minor esters in cider.

The validation of a method based on the purge and trap technique combined with gas chromatography-mass spectrometry-flame ionization detection has been carried out in order to apply it to the analysis of ciders. Although 49 compounds were identified, our work was focused on the study of nine minor esters, obtaining recoveries ranging between 93% for ethyl decanoate and 117% for ethyl 3-methylbutyrate, and a precision (RSDs) ranging between 2.2% for hexyl acetate and ethyl decanoate and 10.9% for isopentyl acetate. To demonstrate the feasibility of the procedure, the method was applied to the analysis of commercial ciders.

Beverages↗
PubMed2007

Headspace-solid phase microextraction-gas chromatography as a tool to define an index that establishes the retention capacity of the wine polymeric fraction towards ethyl esters.

A headspace-solid phase microextraction followed by gas chromatographic analysis (HS-SPME-GC) was developed to be applied in the study of the interactions between the wine polymeric fraction and the ethyl esters: ethyl hexanoate, ethyl octanoate, and ethyl decanoate. Wine models (WM) were prepared with 10% (v/v) aqueous ethanol at pH 3.5 with distinct wine polymeric concentrations prepared from white wine of Vitis vinifera L. var. Fernão-Pires: 1.0 g L(-1) (PWM1), with a polymeric concentration approaching the real one in wine; 10.0 g L(-1) (PWM10); and 30.0 g L(-1) (PWM30), saturated with polymeric fraction. A reference wine model (RWM) was prepared without polymeric fraction. Each volatile compound (4.0 mg L(-1)) was added separately to the RWM and to the WM with the three levels of polymeric material (PWM). From the retention index (RI) calculated for each compound using the formula: [RI = 1 - (C(RWM) - C(PWM))/C(RWM)], where C(RWM) is the concentration of the compound in the RWM and C(PWM) is the concentration of the compound in the given PWM, the retention capacity of each wine polymeric fraction towards the three esters was established. The higher retention indexes were observed for ethyl decanoate, the more hydrophobic compound, and for the PWM with higher concentration. Furthermore, this study also suggested that the retained compounds are dosed to the headspace, which may promote the perception of their aroma for a longer period of time.

Adsorption↗
PubMed2004

Effects of protein-rich supplementation and nandrolone in lean elderly women with femoral neck fractures.

AIM: To evaluate the effects of a protein-rich liquid supplementation, alone or in combination with the anabolic steroid nandrolone decanoate, on body composition, activities of daily living (ADL) status and the health-related quality of life (HRQoL) after a femoral neck fracture. METHODS: Sixty women, aged 83 +/- 5 years (mean +/- SD), BMI < 24 kg/m2 (20.4 +/- 2 kg/m2 ) and capable of co-operating, with a femoral neck fracture treated with internal fixation, were randomised to open treatment during 6 months with a protein-rich liquid formula alone (PR, Fortimel, 200 ml/day, 20 g protein/day) or in combination with nandrolone decanoate (PR/N, Deca-Durabol 25 mg i.m./3 weeks) or to a control group (C). The patients were re-examined after 6 and 12 months regarding body weight (BW), lean body mass (LBM, DXA), ADL status according to Katz, HRQoL according to EQ 5-D and fracture healing. RESULTS: LBM decreased in the C (-1.2 +/- 2 kg) and PR groups (-1.2 +/- 1 kg) but remained the same in the PR/N group (0.3 +/- 1 kg) (P < 0.05 between groups). ADL remained at a high level in the two intervention groups but declined significantly in the C group (P < 0.005 between groups). The decline in HRQoL was least pronounced in the PR/N group at 6 months (P < 0.05 between groups). Patients with fracture healing complications lost more BW (P < 0.05) and LBM (P < 0.01) than patients with uneventful fracture healing. CONCLUSION: Protein-rich liquid supplementation in combination with nandrolone given for 6 months to lean elderly women after a femoral neck fracture may positively affect LBM, ADL and HRQoL.

Activities of Daily Living↗
PubMed2003

Differential effects of antipsychotics on haloperidol-induced vacuous chewing movements and subcortical gene expression in the rat.

The behavioral and neurochemical effects of switching from typical to atypical medications have not been evaluated in the rodent models of tardive dyskinesia. Thus, we treated rats with haloperidol-decanoate for 12 weeks, and assessed the effects of additional treatment with olanzapine, haloperidol, clozapine, or vehicle on vacuous chewing movements and expression of transcripts for dopamine receptors, tyrosine hydroxylase, delta-opioid receptor, prodynorphin, preproenkephalin, glutamic acid decarboxylase-65 (glutamic acid decarboxylase (GAD)-65) and GAD-67 and N-methyl-D-aspartate (NMDA) receptor subunits in the striatum and its efferent pathways. Haloperidol-decanoate induced vacuous chewing movements extinguished following an additional 4 weeks of treatment with vehicle, olanzapine or haloperidol, but not clozapine. Post-treatment, vacuous chewing movements in the clozapine group were significantly higher than the vehicle, olanzapine and haloperidol groups. GAD-67 mRNA expression in the globus pallidus was decreased following additional treatment with olanzapine or haloperidol, but not clozapine. Changes in expression of other transcripts were not detected. These findings demonstrate important differences in the effects of typical and atypical antipsychotics on chronic vacuous chewing movements.

Animals↗
PubMed2006

Degradation of vitamin D3 in a stressed formulation: the identification of esters of vitamin D3 formed by a transesterification with triglycerides.

Four unknown degradants in the LC-UV profile of a stressed experimental tablet formulation that contains vitamin D3 have been identified by a combination of Ag+-cationization electrospray ionization (ESI) LC/MS and atmospheric pressure chemical ionization (APCI) LC/MS/MS. The peaks elute in the method chromatography in two pairs of two peaks. The first pair of peaks has m/z 511 while the second pair has m/z 539. The major, first peak of each set of peaks corresponds to the octanoate and decanoate ester of vitamin D3, respectively. These are formed by a transesterification with the two major fatty acid components (octanoate and decanoate) of the triglycerides present in the formulation. The formation of two degradation products with each fatty acid is due to the presence of both vitamin D3 (major component) and the isomeric pre-vitamin D3 (minor component) in the stressed formulation.

Chemistry, Pharmaceutical↗