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PubMed1994

Fluphenazine vs placebo supplementation for prodromal signs of relapse in schizophrenia.

BACKGROUND: We studied the effectiveness of treating patients with low doses of fluphenazine decanoate and supplementing them with oral fluphenazine when there was evidence of prodromal symptoms of psychotic exacerbations. METHODS: Eighty schizophrenic patients who were receiving 5 to 10 mg of fluphenazine decanoate every 2 weeks were monitored for prodromal symptoms using an idiosyncratic prodromal rating scale. When patients met our criteria for a prodromal episode, they were randomly assigned to a double-blind comparison of oral fluphenazine hydrochloride (5 mg twice daily) or a placebo for the current and future prodromal episodes. We compared rates of psychotic exacerbations in the two treatment groups. RESULTS: Thirty-six patients (45%) met the criteria for a prodrome at some point during the trial and were randomized to drug or placebo. Using survival analysis during the entire 2 years, we did not find a significant difference between fluphenazine and placebo in the likelihood that a prodrome would continue to an exacerbation. Survival analysis beginning at the start of the second year of treatment did indicate a significant reduction in exacerbation risk for patients receiving drug supplementation (P = .032). Similarly, there was no difference between the two groups in the proportion of time at risk spent in exacerbation during the first year, but patients receiving active drug supplementation spent less time in an exacerbated state in the second year (P = .05). CONCLUSIONS: Our treatment strategy appeared to be effective for some patients, particularly those who were able to remain in the study beyond the first year. Although the occurrence of a prodrome was a fairly good marker that a patient was at high risk of ultimate exacerbation with our low-dose maintenance protocol, prodromes were not highly sensitive indicators of imminent exacerbation.

Acute Disease↗
PubMed2000

Zuclopenthixol acetate in the treatment of acute schizophrenia and similar serious mental illnesses.

BACKGROUND: People with schizophrenia or other psychotic illnesses may have delusions or hallucinations that may lead them to be aggressive or violent to themselves or others. Medication that is used in this context require the properties of rapid onset of effect (tranquillisation or at least initial sedation in order to quell aggressive or disorganised behaviour, but also antipsychotic effect), low frequency of administration and low levels of side effects, such as cardiological or neurological side effects, or pain at the injection site. Zuclopenthixol is the cis(Z)-isomer of clopenthixol, a neuroleptic of the thioxanthene group, used for treating people with psychotic symptoms. There is one oral preparation and two depot forms: zuclopenthixol acetate and zuclopenthixol decanoate. The acetate version does not stay in the body for very long (a single dose persists for only 72 hours) and is said to have these properties. OBJECTIVES: To estimate the effectiveness of zuclopenthixol acetate for the acute treatment of serious mental illnesses in comparison to other neuroleptic drugs. SEARCH STRATEGY: Searches of the Cochrane Schizophrenia Group's Register of Trials, The Cochrane Library, MEDLINE, abstracts of congresses and trial reference lists were performed. Appeals for unpublished data to the research community and to the Medical Information Department of Lundbeck Limited were also made. Attempts were made to contact relevant authors. SELECTION CRITERIA: Two reviewers independently assessed citations or papers and selected all randomised trials that included people with serious mental illnesses and compared zuclopenthixol acetate with other drug regimes. DATA COLLECTION AND ANALYSIS: Data were extracted independently by two reviewers. Attempts were made to contact authors for additional or missing information. Odds-ratios (OR) and 95% confidence intervals (CI) were estimated for binary data. Where possible, OR were pooled using Peto method and intention-to-treat analysis undertaken. Mean differences were used for continuous variables. MAIN RESULTS: Pooled data shows no difference for the outcome 'no important improvement' in psychotic symptoms at the end of the follow-up period (OR 0.84 CI 0. 34-2.05). Sedation was evaluated using different instruments. Only one study presented data which suggested an earlier and more intense sedation in zuclopenthixol acetate users at 4 hours (OR 0.18 CI 0. 04-0.93). Use of additional antipsychotic medication was not avoided in the zuclopentixol acetate group (OR 2.18, CI 0.64-7.42) and data on total number of administrations was not obtainable. Side effect data were poorly reported but there is no evidence of a consistent difference between zuclopenthixol acetate and other 'standard drugs' for either the pattern of side effects or the wish to leave the study early. Hospital and service outcomes, number of aggressive incidents, satisfaction with care and economic outcomes were not addressed by any study. REVIEWER'S CONCLUSIONS: Recommendations on the use of zuclopenthixol acetate for the management of psychiatric emergencies in preference to 'standard' treatment have to be viewed with caution. Most trials present important methodological flaws and findings are poorly reported. This review did not find any suggestion that zuclopenthixol acetate is more effective in controlling aggressive/disorganised behaviour, acute psychotic symptoms, or preventing side effects. There were no data directly related to tranquillisation, but it may produce more earlier and intense sedation than oral haloperidol. Well conducted randomized controlled trials are needed to confirm claims related to the use of zuclopenthixol acetate in emergency psychiatry.

Acute Disease↗
PubMed2006

Thermal stabilization of human albumin by medium- and short-chain n-alkyl fatty acid anions.

A comprehensive study of the thermal stabilization of defatted human albumin monomer by n-alkyl fatty acid anions (FAAs), formate through n-decanoate, was carried out by differential scanning calorimetry (DSC). The concentration of each ligand affording maximum thermal stabilization was determined; n-nonanoate provides the greatest stabilization but is only marginally better than n-octanoate and n-decanoate. The use of reversible thermodynamics and a two-state denaturation model for albumin has been validated. Standard free energies of binding, calculated from increases in free energy of denaturation, for n-butanoate and longer FAAs, are linear with n-alkyl chain length whereas those for formate, acetate, and n-propionate deviate from linearity; those for acetate and n-propionate are even greater than that of n-butanoate, thereby suggesting, in addition to the common class of sites available to all such ligands, the presence of an additional class of lower affinity binding sites available only to these shortest ligands. Competition experiments involving acetate and n-octanoate and involving n-pentanoate and n-octanoate confirmed the binding of acetate to lower affinity sites unavailable to n-octanoate and n-pentanoate. Furthermore, an equation is provided, allowing computation of the transition temperature as a function of the free energy for any reversible process causing a change in thermal stability of a protein undergoing reversible, two-state denaturation. With this equation, modeling the competition experiments by using the binding parameters determined by DSC provides additional support for the class of lower affinity sites, which play a significant role in thermal stabilization of albumin at higher concentrations of these shortest FAAs.

Anions↗
PubMed2002

Simultaneous production of polyhydroxyalkanoates and rhamnolipids by Pseudomonas aeruginosa.

The feasibility of the simultaneous production of polyhydroxyalkanoates (PHAs) and rhamnolipids, as a novel approach to reduce their production costs, was demonstrated by the cultivation of Pseudomonas aeruginosa IFO3924. Fairly large amounts of PHAs and rhamnolipids were obtained from the bacterial cells and the culture supernatant, respectively. Decanoate was a more suitable carbon source than ethanol and glucose for the simultaneous production, although glucose was suitable for cell growth without an induction period under pH control. The kind of carbon source affected PHA monomer composition markedly and PHA molecular weight slightly. Monorhamnolipids and dirhamnolipids were included in the rhamnolipids extracted from the culture supernatant using decanoate, glucose, or ethanol as the carbon source. Both PHAs and rhamnolipids were synthesized after the growth phase. PHA content in the cell reached a maximum when the carbon source was exhausted. After exhaustion of the carbon source, PHA content decreased rapidly, but rhamnolipid synthesis, which followed PHA synthesis, continued. This resulted in a time lag for the attainment of maximum levels of PHAs and rhamnolipids. The reusability of the cells used in rhamnolipid production was evaluated in the repeated batch culture of P. aeruginosa IFO3924 for the simultaneous production of PHAs and rhamnolipids. High concentrations of rhamnolipids in the culture supernatant were attained at the end of both the first and second batch cultures. High PHA content was achieved in the resting cells that were finally harvested after the second batch. Simultaneous production of PHAs and rhamnolipids will enhance the availability of valuable biocatalysts of bacterial cells, and dispel the common belief that the production cost of PHAs accumulated intracellularly is almost impossible to become lower than that of cells themselves.

Alkanes↗
PubMed2002

The effect of age on the pharmacological management of ambulatory patients treated with depot neuroleptic medications for schizophrenia and related psychotic disorders.

BACKGROUND: Cross-sectional studies indicate that, in comparison to younger patients, older schizophrenic patients have a higher risk for neuroleptic-induced Parkinsonism and tardive dyskinesia (TD). It has been suggested, therefore, that older patients with schizophrenia could be maintained on reduced doses of conventional neuroleptics. METHOD: We examined the effect of age on psychopharmacological management in a naturalistic study of a group of 165 patients with a clinical diagnosis of schizophrenia or a related psychotic disorder (age range = 21-84 years; subjects > or = 1;45 years n = 86) treated with either haloperidol decanoate or fluphenazine decanoate. RESULTS: Increasing age was not correlated with total daily dose of neuroleptics or anticholinergic medication. However, a modest negative correlation of age with daily neuroleptic dose was found in patients aged 45 years and older. CONCLUSION: The results of this study highlight the need for prospective assessments of depot neuroleptic dose requirements in older patients suffering from primary psychotic disorders.

Adult↗
PubMed2003

Prolonged QTc intervals in medicated patients with schizophrenia.

Psychotropic drugs have been associated with sudden deaths and the lengthening of corrected-QT interval (QTc) on the electrocardiogram which may be a precursor of life-threatening arrhythmias as reported with some of these drugs. The objectives of this study were to measure the frequency of QTc lengthening in patients with schizophrenia receiving psychotropic drugs, and to assess whether QTc lengthening was associated with certain psychotropic drugs and other risk factors. One hundred and sixty three patients with schizophrenia (104 males and 59 females) were included in the study. Clinical and demographic data were collected from the case records. One hundred healthy volunteers were recruited to establish values for upper limits of normal for measurement of QTc interval and dispersion. Eleven (6.7%) of the patients had a prolonged QTc interval. The significant predictors obtained from a logistic regression modelling were chlorpromazine, flupenthixol decanoate and fluphenazine decanoate. Caution should be exercised and monitoring with ECG should be considered in patients prescribed chlorpromazine and depot antipsychotic medications even at recommended doses.

Aged↗
PubMed1981

Comparison of quantitation methods for L-1210 cell populations and evaluation of selected cytotoxic agents in leukemic mice.

A more rapid cell-counting technique using an electronic cell counter was developed as an improvement over the slower hemocytometer method. The electronic counting method produced cell counts that had a smaller standard deviation but were not significantly different from the hemocytometer method. The acetate, hexanoate, and decanoate esters of p-N,N-bis(2-chloroethyl)aminophenol were investigated for acute toxicity in mice, effects on survival times, and effects on L-1210 cell populations in L-1210 leukemic mice. The decanoate ester was the least toxic compound and was most effective in lengthening the lifespan of the mice. The acetate and hexanoate esters were more effective in reducing L-1210 cell populations.

Aniline Mustard↗
PubMed1982

Synthesis and bioevaluation of a series of fatty acid esters of p-[N,N-bis(2-chloroethyl)amino]phenol.

A series of even numbered fatty acid esters (C2-C18) of p-[N,N-bis(2-chloroethyl)amino]phenol were synthesized and evaluated as to acute toxicity as well as effectiveness against L-1210 mouse leukemia. The acetate through the decanoate derivatives demonstrated toxicity between 2 and 3 times that of phenol mustard in HA/ICR mice. The less soluble laurate, myristate, palmitate, and stearate derivatives were less toxic. Significant survival times in the leukemia studies (T/C% greater than or equal to 125) were observed for all compounds except the acetate and hexanoate derivatives. The myristate derivative produced the greatest significant increase in survival time, 162%. The palmitate and stearate derivatives produced significant survival at five and four dosage levels, respectively. The butyrate and laurate derivatives produced significant survival at three dosage levels and the octanoate, decanoate, and myristate at two dosage levels.

Aniline Mustard↗
PubMed1992

Determination of the acyl moieties of the antibiotic complex A40926 and their relation with the membrane lipids of the producer strain.

Structures of the fatty acid residues characterizing the various components of A40926 were determined by gas chromatography/mass spectrometry on the methyl esters obtained by methanolysis of the complex. The results confirm the residues previously assigned to Factor A (n-undecanoic acid) and B (10-methyl-undecanoic acid) and establish the residues of Factor A1 (9-methyl-decanoic acid), B1 (n-dodecanoic acid), RS1 (8-methyl-nonanoic acid), RS2 (n-decanoic acid), and RS3 (n-tridecanoic acid). As the Actinomadura species contain in their mycelia large quantities of C15-C17 fatty acid residues as membrane phospholipids, these mycelia were saponified and the fatty acids obtained were analyzed as above. There is a close correlation between the fatty acid content of A40926 complex and that of the longer homologues in the producer mycelia.

Anti-Bacterial Agents↗
PubMed1997

Anabolic-androgenic steroid effects on sexual receptivity in ovariectomized rats.

Anabolic-androgenic steroid (AAS) compounds are synthetic androgens taken by athletes to increase physical strength and endurance. Recent studies in our laboratory have demonstrated that AAS administration disrupts the estrous cycle of Long-Evans rats. The present experiments examined the effects of six commonly abused AAS compounds on sexual receptivity in ovariectomized rats. Adult female Long-Evans rats received estradiol benzoate (EB; 2.0 micrograms/day s.c.) for 6 consecutive days followed by 15 days of EB concurrent with daily s.c. injections of 7.5 mg/kg of one of the following AAS compounds: 17 alpha-methyltestosterone, methandrostenolone, nandrolone decanoate, stanozolol, oxymetholone, testosterone cypionate, or the oil vehicle. On Day 15, all female rats received progesterone (1.0 mg/rat) 4 h before testing. Tests for sexual receptivity were conducted on Days 3, 6, 14, and 15 of AAS treatment. Although the time course of AAS effects on sexual receptivity varied, some overall effects were clear. For example, 17 alpha-methyltestosterone, methandrostenolone, nandrolone decanoate, and stanozolol interfered with the display of sexual receptivity on Day 14, whereas oxymetholone and testosterone cypionate had no effect. Rats in all groups displayed high levels of sexual receptivity after receiving progesterone on Day 15. Our results show that AAS compounds vary in their degree of inhibition of female sexual behavior in ovariectomized rats.

Anabolic Agents↗
PubMed1992

Three-year calcitonin combination therapy for postmenopausal osteoporosis with crush fractures of the spine.

Forty-five postmenopausal osteoporotic women with at least one osteoporotic vertebral crush fracture were randomized into three treatment groups. Each patient was on calcitonin, 50 U, on alternate days for 2 weeks monthly (350 U/month), and 500 mg/day oral calcium supplementation. In group II, this therapy was supplemented with phosphate (750 mg/day), and in group III, norandrostenolone decanoate (50 mg/month) was added to the calcitonin+calcium therapy. Bone mineral content, by single photon absorptiometry, of the radius midshaft and distal site (3 cm), as well as the lumbar and metacarpal radiomorphometrical indices were estimated seminannually. The therapeutic trial lasted 36 months except in the phosphate supplementation group, where, due to unfavorable results, treatment was discontinued after 24 months. Calcitonin practically prevented further bone loss for 24 months even in this relatively small and intermittent dosage. Phosphate supplementation was without benefit; however, according to the majority of the examined parameters, combination of calcitonin with the anabolic steroid norandrostenolone decanoate extended efficacy up to 36 months. This latter combination seems to be a promising, relatively inexpensive therapeutic regimen in the treatment of established postmenopausal osteoporosis.

Aged↗
PubMed1983

Reduction of nigral glutamic acid decarboxylase in rats with neuroleptic-induced oral dyskinesia.

Following eight monthly haloperidol decanoate injections rats showed an increased rate of vacuous chewing movements (VCM's), which gradually disappeared within 4 drug-free months. Another single dose of non-decanoate haloperidol reinstated a second increase in VCM rate which was still significant after 2 months. The glutamic acid decarboxylase (GAD) activity in the substantia nigra of these chronically haloperidol-treated rats was lower than untreated controls. Furthermore, there was a significant negative correlation between individual VCM rates and nigral GAD activity. No corresponding changes occurred in other brain regions. The depression of nigral GAD may reflect a reduced tissue density of GABA-ergic axon terminals within the descending striato-nigral pathway.

Animals↗
PubMed1983

Variation in oro-facial tardive dyskinesia during depot antipsychotic drug treatment.

Oro-facial (tardive) dyskinesia, occurring in patients on long-term antipsychotic (dopamine antagonist) medication, can be suppressed temporarily by increasing the drug dose. Lowering the dose can exacerbate the condition. In patients receiving regular fluphenazine decanoate (FPZ) and flupenthixol decanoate (FPT) injections, characteristic profiles of the fluctuations in plasma level concentrations, occurring during the injection interval, have been demonstrated. The possible effects of these relatively predictable plasma level changes on the severity of oro-facial dyskinesia, and parkinsonism, were investigated. Regular assessment of oro-facial dyskinesia throughout the injection interval was carried out in six patients receiving FPZ and two patients receiving FPT. In both groups, changes were observed in the severity of oro-facial dyskinesia consistent with the expected effects of drug level fluctuations. The main implication of this finding is that, in investigations of tardive dyskinesia in patients receiving depot medication, ratings should be carried out at a standard time relative to injections.

Aged↗
PubMed1982

A depot neuroleptic withdrawal study. Plasma concentration of fluphenazine and flupenthixol and relapse frequency.

A double-blind withdrawal trial in 41 chronic schizophrenic outpatients was carried out during 6 months. Depot neuroleptics (fluphenazine decanoate or flupenthixol decanoate) were compared with placebo to evaluate clinical and neurological effects during continued therapy and during withdrawal. The drugs were significantly more effective than placebo in preventing relapse and rehospitalization. In the placebo group 62% relapsed compared to 27% in the drug group. There was a weak and nonsignificant tendency to a higher relapse frequency in the flupenthixol group compared to the fluphenazine group. After withdrawal for 6 months, plasma levels for fluphenazine were detectable. Plasma levels for flupenthixol were not detectable after 9 weeks of withdrawal. The differences in the plasma levels may possibly explain the difference in relapse rate between the two depot neuroleptics. Furthermore, it was found that the patients who relapsed during fluphenazine treatment had a significantly lower plasma level of the drug than patients who did not relapse during treatment. The results from this study provide some information on the therapeutic levels of fluphenazine and flupenthixol in schizophrenic patients.

Delayed-Action Preparations↗
PubMed1987

Local anesthetic action of carboxylic esters: evidence for the significance of molecular volume and for the number of sites involved.

The effects of the homologous series of carboxylic esters, methyl propionate to methyl decanoate, on the steady-state inactivation of the sodium current in squid axons have been studied. The esters moved the relationship between the inactivation parameter, h infinity, and the membrane potential in the hyperpolarizing direction, thus reducing the number of sodium channels available at the resting potential. The concentration dependence of the shift at the mid-point of the curve of h infinity against potential has been measured for all esters except decanoate, which was almost inactive. Two aspects of these concentration dependences suggest that molecular volume is an important determinant of the effectiveness of each ester. Firstly, there is a sharp decline in activity above methyl hexanoate. This cut-off in activity resembles that for hydrocarbons where it has been suggested [e.g., Haydon, D.A., Urban, B.W. 1983, J. Physiol. (London) 341:411-427] to a result from a decrease in uptake with increasing molecular volume. (Further data for the hydrocarbons n-butane to n-heptane are reported here.) Secondly, the smallest compounds, methyl propionate and methyl butyrate, are less effective than would be predicted if equal membrane concentrations of each ester produced the same shift. The aqueous concentration dependences for these esters indicate that below methyl hexanoate, as the series is descended, progressively higher membrane concentrations are required to produce a given shift. This would be expected if the volume of ester in the membrane, rather than the number of molecules, is important.(ABSTRACT TRUNCATED AT 250 WORDS)

Anesthetics, Local↗
PubMed1989

[Distribution and elimination of medium- and long-chain fatty acids of a fat emulsion in lipoproteins of severely injured patients following bolus injection].

A fat emulsion containing 20% fat as medium chain triglycerides (MCT) and long chain triglycerides (LCT) (1:1) was injected as a bolus in an amount of 0.2g fat per kg body weight to six patients, three to five days after a serious injury. Triglyceride concentrations increased within two min in lipoprotein fractions d less than 0.95 g/ml (Chylomicrons), d less than 1.006 g/ml (VLDL), d less than 1.063 g/ml (LDL) and d less than 1.21 g/ml (HDL). Sixty minutes after injection triglyceride concentrations had again reached preexperimental values in all lipoprotein fractions. Cholesterol values did not change. According to the composition of the fat emulsion, linoleic acid content increased in triglycerides of all lipoprotein fractions, whereas octanoic and decanoic acid did so only in triglyceride-rich lipoproteins (d less than 1.006). Half-life values of elimination of octanoic acid (3.3 min) and decanoic acid (3.9 min) in triglycerides of lipoprotein fraction d less than 1.006 were nearly half as short as that of long chain fatty acids (linoleic acid, 6.4 min; oleic acid, 6.5 min; palmitic acid, 7.5 min). Thus in contrast to LCT, MCT are only found in triglyceride-rich lipoproteins (d less than 1.006) and are also eliminated more rapidly.

Fat Emulsions, Intravenous↗
PubMed1980

Origins of the cholesterol in milk.

Studies were conducted to investigate the origin of milk cholesterol in the ruminant. In the first experiment, [1(-14)C]sodium acetate was infused into one side of the udder of a lactating goat via the test canal whereas in the second, (1,2-3H]cholesterol was injected intravenously and concurrently with a [14C]acetate intramammary infusion. In both experiments, blood and milk samples were collected at intervals for 6 days postinjection. Maximum unesterified cholesterol specific activity (sp act) in whole milk appeared at 78 hr after intravenous injections of 3H cholesterol and within 3-7 hr after infusion of [14C]acetate. Virtually all the tritium in milk was associated with unesterified cholesterol. The sp act of 14C-labeled cholesterol was only 20% of gland-synthesized decanoic acid. Decanoic acid is known to be completely synthesized in the mammary gland, and, like cholesterol, acetate is its precursor. The results indicate that, although some milk cholesterol is synthesized in the mammary gland, it is derived principally from serum cholesterol. The data show also that serum cholesterol equilibrates with membrane cholesterol of the lactating cell prior to its secretion in milk.

Acetates↗
PubMed2006

A 15-year open study on a cohort of West-African out-patients with a chronic psychosis.

BACKGROUND: We wanted to find out if the additional costs of depot neuroleptic in comparison to oral medication was justified by a decrease in admission days. METHODS: An open study on a cohort of chronic psychotic out-patients (n=45) consisting of a retrospective 10-year period on oral medication followed by a prospective 5-year period of treatment with haloperidol decanoate. After recording socio-demographic characteristics and a DSM-III-R diagnosis, patients were assessed before and after the administration of depot neuroleptic with the BPRS, the NOSIE, the SDRS and a list of side effects. A semi-structured interview was conducted with the patients and their families to ask about the change in social relationships with family members and other people after starting the depot treatment. Social intervention was limited to involvement of the family in the monthly depot medication outpatient clinic and to an explanation of the rationale of follow-up treatment and deinstitutionalisation of psychiatric care in the village of origin. RESULTS: The number of admission days decreased from an average of 100 days a year on oral medication to 5 days a year on depot neuroleptic. Patients report a sharp decrease in symptoms paralleled by an increase in social functioning over the first 3 months. After 6-9 months this pattern stabilised and was maintained over the period from 1 to 5 years whereas the dosage was further decreased to an average of 1 cc decanoate or 20 haldol equivalents monthly. CONCLUSIONS: This study suggests that depot neuroleptic in the context of a public mental health approach is a highly effective and feasible treatment for West African patients suffering from a chronic functional psychosis.

Adolescent↗