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PubMed2006

Novel depots of buprenorphine prodrugs have a long-acting antinociceptive effect.

An analgesic with a prolonged duration may be desirable in patients with long-lasting pain. In this study, we evaluated the antinociceptive effects and durations of action of three novel depots of buprenorphine esters buprenorphine propionate, enanthate, and decanoate given by IM injection, in rats. The pharmacokinetic profiles of buprenorphine in blood after IM injection of these depots were also evaluated. Antinociception was evaluated using the plantar test. Buprenorphine concentrations in blood were assayed using high-performance liquid chromatography. We found that the traditional form of buprenorphine HCl (in saline) produced a dose-related antinociceptive effect. A dose of 0.6 micromol/kg buprenorphine HCl (in saline) produced a significant antinociceptive effect lasting 5 h. The same dose of buprenorphine base, propionate, enanthate, and decanoate (in oil) also produced a significant antinociceptive effect with longer durations of action of 26, 28, 52, and 70 h, respectively. The pharmacokinetic studies demonstrated that all the buprenorphine esters were prodrugs of buprenorphine. We conclude that the novel depots of buprenorphine prodrugs: buprenorphine propionate, enanthate, and decanoate produced a long-acting antinociceptive effect after IM injection in rats.

Analgesics, Opioid↗
PubMed1998

Studies of drug delivery systems for a therapeutic agent used in osteoporosis. II. Enhanced absorption of elcatonin from nasal mucosa in rabbits.

In this study, the effects of a protease inhibitor, endocytosis inhibitors and an absorption-enhancing agent on the absorption of ((Asu1,7)-eel calcitonin, ECT) from the nasal mucous membrane in rabbits were examined, and the results were compared with those obtained following the rectal absorption of ECT reported in our previous paper. ECT was efficiently absorbed from the nasal mucous membrane and effectively decreased serum calcium (Ca) concentrations. The increase in the area under the percent decrease in serum Ca concentration (deltaCa%)-time curve (deltaCa%-AUC) value, assumed to be an index of the pharmacodynamics (hypocalcemic effect) of ECT, depended on the dose of ECT administered intranasally. When nafamostat mesilate, a protease inhibitor, was coadministered with ECT, the deltaCa%-AUC markedly increased. It is presumed that the influence (enzymatic barrier function) of protease on the nasal absorption of ECT is significant. However, no significant difference in the deltaCa%-AUC value was observed when an endocytosis inhibitor (cytochalasin B or monensin) was coadministered with ECT. ECT administration in combination with sodium decanoate, the sodium salt of a medium-chain fatty acid, effectively increased the deltaCa%-AUC value due to the enhancing effect of sodium decanoate on the nasal absorption of ECT. We conclude that the nasal application offers a promising approach for the administration of pharmaceutical preparations containing ECT with additives such as nafamostat mesilate and sodium decanoate.

Absorption↗
PubMed2005

Exploring the flexibility of ribosome recycling factor using molecular dynamics.

Ribosome recycling factor is proposed to be flexible, and that flexibility is believed to be important to its function. Here we use molecular dynamics to test the flexibility of Escherichia coli RRF (ecRRF) with and without decanoic acid bound to a hydrophobic pocket between domains 1 and 2, and Thermus thermophilus RRF (ttRRF) with and without a mutation in the hinge between domains 1 and 2. Our simulations show that the structure of ecRRF rapidly goes from having an interdomain angle of 124 degrees to an angle of 98 degrees independently of the presence of decanoic acid. The simulations also show that the presence or absence of decanoic acid leads to changes in ecRRF flexibility. Simulations of wild-type and mutant ttRRF (R32G) show that mutating Arg-32 to glycine decreases RRF flexibility. This was unexpected because the range of dihedral angles for arginine is limited relative to glycine. Furthermore, the interdomain angle of wild-type T. thermophilus goes from 81 degrees to 118 degrees whereas the R32G mutant remains very close to the crystallographic angle of 78 degrees . We propose that this difference accounts for the fact that mutant ttRRF complements an RRF deficient strain of E. coli whereas wild-type ttRRF does not. When the ensemble of RRF structures is modeled into the ribosomal crystal structure, a series of overlaps is found that corresponds with regions where conformational changes have been found in the cryoelectron microscopic structure of the RRF/ribosome complex, and in the crystal structure of a cocomplex of RRF with the 50S subunit. There are also overlaps with the P-site, suggesting that RRF flexibility plays a role in removing the deacylated P-site tRNA during termination of translation.

Binding Sites↗
PubMed2003

Structure-function relationships affecting the insecticidal and miticidal activity of sugar esters.

Synthetic sugar esters are a relatively new class of insecticidal compounds that are produced by reacting sugars with fatty acids. The objective of this research was to determine how systematic alterations in sugar or fatty acid components of sugar ester compounds influenced their insecticidal properties. Sucrose octanoate, sorbitol octanoate, sorbitol decanoate, sorbitol caproate, xylitol octanoate, xylitol decanoate and xylitol dodecanoate were synthesized and evaluated against a range of arthropod pests. Dosage-mortality studies were conducted on pear psylla (Cacopsylla pyricola Foerster) on pear, tobacco aphid (Myzus nicotianae) Blackman and tobacco hornworm (Manduca sexta [Johannson]) on tobacco, and twospotted spider mite (Tetranychus urticae Koch) on apple in laboratory bioassays. These sugar esters were compared with insecticidal soap (M-Pede, Dow AgroSciences L.L.C., San Diego, CA), to determine how toxicologically similar these materials were against the arthropod pests. Substitutions in either the sugar or fatty acid component led to significant changes in the physical properties and insecticidal activity of these compounds. The sugar esters varied in their solubility in water and in emulsion stability, yet, droplet spread upon pear leaves occurred at low concentrations of 80-160 ppm and was strongly correlated with psylla mortalities (R2 = 0.73). Sequentially altering the sugar or fatty acid components from lower to higher numbers of carbon chains, or whether the sugar was a monosaccharide or disaccharide did not follow a predictable relationship to insecticidal activity. Intuitively, changing the hydrophile from sorbitol (C6) to xylitol (C5) would require a decrease in lipophile chain length to maintain hydrophilic-lipophilic balance (HLB) relationships, yet an increase in lipophile chain length was unexpectedly needed for increasing insecticidal activity. Thus, the HLB of these materials did not correlate with pear psylla mortalities. Initial insect bioassays and dosage-mortality data found significant differences among sugar ester compounds' toxicity to the range of arthropod species. Sucrose octanoate high in monoester content had the highest activity against the range of arthropod pests at low concentrations of 1200-2400 ppm. No single chemical structure for the xylitol or sorbitol esters were optimally effective against the range of arthropods we tested and sorbitol octanoate and xylitol decanoate had the highest insecticidal activity of this group. All of the sugar ester materials produced high T. urticae mortalities on apple at very low concentrations of 400 ppm. Overall, most of the sugar esters that were examined had superior insecticidal activity compared with insecticidal soap. Sugar ester chemistry offers a unique opportunity to design an insecticide or miticide specific to certain arthropod pests which would be valuable in crop integrated pest management (IPM) programs. Sucrose esters are currently used as additives in the food industry which makes them especially attractive as safe and effective insecticides.

Animals↗
PubMed1998

Risperidone. A pharmacoeconomic review of its use in schizophrenia.

UNLABELLED: The availability of new atypical antipsychotics, such as risperidone, that have higher acquisition costs than conventional treatments has promoted pharmacoeconomic evaluation of their costs and benefits. Risperidone is reported to have superior efficacy to haloperidol and similar efficacy to other atypical antipsychotics. At dosages < or = 8 mg/day, risperidone is generally associated with a lower risk of extrapyramidal symptoms than conventional antipsychotics and may have a more favourable effect on cognitive function and quality of life. Overall treatment costs during the first year of risperidone treatment were lower than in the previous year in a number of studies in patients with schizophrenia, reflecting a reduction in hospitalisation, although costs slightly increased after risperidone initiation in 2 studies. Total treatment costs were not significantly different with risperidone or conventional antipsychotics in a large, prospective naturalistic study. The use of risperidone in preference to conventional antipsychotics in patients with chronic schizophrenia has been supported by several modelled studies, including a cost-effectiveness analysis that compared risperidone and haloperidol in chronic schizophrenia and a cost-utility study that compared the drug with oral haloperidol, depot haloperidol decanoate and depot fluphenazine decanoate for 1 year's treatment of an initially hospitalised chronic schizophrenic patient with moderate symptoms. In another study, the cost-utility ratio for risperidone versus haloperidol was 24,250 Canadian dollars per quality-adjusted life year (year of costing not stated), but only drug costs were considered. Risperidone had favourable cost-benefit ratios relative to conventional antipsychotic treatment in a study that investigated a scenario in which all patients hospitalised with newly diagnosed schizophrenia received conventional antipsychotic therapy for 6 months, and then those who did not respond received a 6-month trial of risperidone or clozapine. The results of 2 limited decision-analytical models did not favour risperidone. One study compared risperidone with oral haloperidol or depot haloperidol decanoate for the outpatient treatment of a schizophrenic patient with a history of relapse and rehospitalisation. The other compared risperidone, olanzapine and oral haloperidol for the treatment of schizophrenia. CONCLUSIONS: Despite its high acquisition cost, risperidone does not increase, and may even reduce, overall treatment costs of schizophrenia by reducing hospitalisation compared with standard treatment regimens. While further pharmacoeconomic evaluation of risperidone as a first-line agent is required, pharmacoeconomic data overall support its use in patients with chronic schizophrenia.

Antipsychotic Agents↗
PubMed2002

Effects of adjuvant androgen on anemia and nutritional parameters in chronic hemodialysis patients using low-dose recombinant human erythropoietin.

BACKGROUND: Recombiant human erythropoietin (epoetin) has greatly contributed to improvement of the anemia of chronic renal failure patients on hemodialysis. However, the reduced erythropoietic effect to epoetin and its high cost have induced lots of supplementary treatments. Therefore, we performed a prospective study to evaluate the effects of adjuvant low-dose androgen therapy in patients using a lower-dose of epoetin than the commonly recommended dose on anemia and the nutritional parameters. METHODS: 17 patients of hemoglobin (Hgb) less than 9 g/dL even after being treated with 1,000 U epoetin subcutaneously (s.c.) 3 times per week on a stable status for more than 6 months, who were on hemodialysis at our institution were examined. They were injected with the same dose of epoetin s.c. and nandrolone decanoate 100 mg intramuscularly (i.m.) weekly for another 6 months. Blood test was performed every month before therapy for 6 months and after therapy for 6 months and the mean values were reviewed for comparison. RESULTS: Hgb (7.75 +/- 0.9 vs 8.99 +/- 1.39 g/dL, p < 0.01) and hematocrit (Hct) (23.68 +/- 2.85 vs 26.66 +/- 3.91%, p < 0.01) were apparently changed before and after adjuvant therapy. Hgb and Hct, weekly dose of epoetin were not statistically different in 9 male patients before and after adjuvant therapy. The weekly dose of epoetin was not statistically different in 8 female patients, but Hgb and Hct (8.02 +/- 0.6 vs 9.72 +/- 1.31 g/dL, 24.54 +/- 1.7 vs 28.74 +/- 3.06%, p < 0.01) were statistically different before and after adjuvant therapy. In comparison between male and female groups, weekly doses of epoetin and nandrolone decanoate were significantly greater in the female group than the male group (epoetin: 50.66 +/- 6.23 vs 61.18 +/- 8.76 U/kg/week, nandrolone decanoate: 1.69 +/- 0.2 vs 2.04 +/- 0.29 mg/kg/week, p < 0.05). CONCLUSION: Our data show that the adjuvant androgen therapy is effective for the anemia of hemodialysis patients who did not recover from anemia even after being continuously treated with low-dose epoetin.

Adult↗
PubMed2004

Successful treatment of refractory anemia with a combination regimen containing recombinant human erythropoietin, low-dose methylprednisolone and nandrolone.

Myelodysplastic syndromes (MDS) are a heterogenous group of hematological clonal malignancies. Patients belonging to the refractory anemia (RA) subtype are usually treated with recombinant human erythropoietin (EPO). Not all patients respond to EPO administration and they are strictly dependent on supportive therapy with red cell blood (RBC) transfusions. The aim of this study was to investigate the efficacy of an alternative combination regimen containing EPO, low-dose methylprednisolone and nandrolone decanoate, in patients with RA unresponsive to EPO administration alone. Ten patients, 4 women and 6 men, median age: 70 years (range: 55-78 years) with refractory anemia unresponsive to EPO administration and RBC transfusion-dependent were included in the study. Median hematological data at baseline were Hb: 8.7 g/dl, (range 6.2-9.8), WBC: 3.35x10(9)/l (range 2.1-4), PLT: 82.5x10(9)/l (range 59-110). EPO 150 U/Kg three times/week subcutaneously, low-dose methylprednisolone 8 mg/day orally and nandrolone decanoate (Decadurabolin) 50 mg two-times/week intramuscularly were administered. As complete response (CR) to treatment was considered the normalization of the peripheral blood and bone marrow smears and biopsy. As partial response (PR) was considered increase in Hb level > or = 2 g/dl, or up to 10 g/dl and discontinuation of RBC transfusions. The response to therapy was evaluated on the 4th week after the initiation of the combination treatment. Bone marrow smear evaluation was carried out at baseline and every six months afterwards. After a 4-week treatment all patients achieved PR and discontinued RBC transfusions. Median and range hematological values on the 4th week after treatment initiation were Hb: 11.2 g/dl, (range: 9.8-12.8), WBC: 4.4x10(9)/l (3.5-6.6), PLT: 130x10(9)/l (95-160). The increase observed in hematological values was significant (p = 0.0001, 0.0004 and < 0.0001, respectively, for Hb, WBC and PLT counts). Treatment was well tolerated. Furthermore, two women, on treatment with the combination regimen, achieved CR one after six months and the second after 12 months. They are alive after 5 years from initiation of the combination treatment. After a median period of 18 months (range 12 to 20 months) in PR three men developed acute leukemia; they received intensive antileukemic chemotherapy without any response and died during the phase of pancytopenia. Three other men achieved CR, one after 6 and two after 12 months of therapy and they are on regular follow-up. Two women after 10 and 14 months in PR developed acute leukemia and died. In conclusion, combination therapy with EPO, nandrolone decanoate and low-dose methylprednisolone may be effective as an alternative treatment for RBC transfusion-dependent patients with RA unresponsive to EPO administration alone.

Aged↗
PubMedDate not supplied

[Study of residual levels of delayed-action neuroleptics].

Pharmacokinetics of the depot antipsychotics are unclear and mainly depend on releasing from the depot site (according to a "flip-flop" model). Few data are available on residual plasma concentrations of those drugs. We have practiced 38 blood determinations among 15 patients treated by long-acting neuroleptics (10 by fluphenazine decanoate, 4 by flupentixol decanoate and 1 by pipotiazine palmitate). Radio Receptor Assay method was used (based on competition for dopamine receptors binding), with results expressed as chlorpromazine equivalents. They showed; a wide interindividual variability; considering each subject, intraindividual variability is attenuated; blood measurements are mainly higher than therapeutic ranges (especially for patients on fluphenazine decanoate). Those results might involve that some patients are overdosed, but other studies are needed in this way.

Adult↗
PubMed1985

Chemotherapy with neuroleptics. Clinical and pharmacokinetic aspects with a particular view to depot preparations.

Attempting to improve long-term neuroleptic treatment of schizophrenic patients several injectable depot neuroleptics have been developed. Moreover pharmacokinetic data increasingly have been clinically applied. On this background the purpose of the present paper has been to make an updated review of the clinical and pharmacokinetic knowledge of depot neuroleptic treatment. First, general aspects of antipsychotics have been summarized, and an outline of methodological questions relevant to clinical-pharmacological trials are given. Subsequently general aspects including pros & cons of depot administration are examined. Finally the available data of the various depot preparations have been scrutinized. It is concluded that our present pharmacokinetic knowledge of the particular preparations is incomplete. Thus more information of clinical relevant aspects are needed, e.g., the existence of a therapeutic range, maximum/minimum concentration ratio, and the significance of active metabolites. Comparing the various depot neuroleptics, no significant differences are seen regarding the clinical effects. However, the decanoate esters seem clinical superior to the corresponding enanthate esters explained by the more flat concentration curve of the decanoates. Apart from that, a comparison of the pharmacokinetic data is difficult because of the heterogenecy of the available data. Haloperidol, clopenthixol and perphenazine decanoates are among the best examined preparations in pharmacokinetic respects. A controlled double-blind comparative study of these preparations would be of interest.

Administration, Oral↗
PubMed1987

[Heat-stable hemolysin of Pseudomonas aeruginosa].

Pseudomonas aeruginosa produces at least two distinct hemolysins: heat-labile hemolysin, which is known as phospholipase C, and heat-stable hemolysin, which is considered to be a glycolipid but its true nature is not found yet. Cellophane agar plate method was applied to hasten and enhance the hemolysin production by Pseudomonas aeruginosa, and the hemolysin obtained by this method was examined biochemically. This heat-stable hemolysin consisted of two major acidic glycolipids. One was considered to be the same glycolipid as that obtained by the same method of Jarvis and Johnson's from the peptone-glycerol culture filtrate of the same organism, which is composed of two moles of rhamnose and two moles of beta-hydroxy decanoic acid, and the other one being a glycolipid composed of one mole of rhamnose and two moles of beta-hydroxy decanoic acid. By this method, the rhamnolipid with one mole of rhamnose was produced more than the rhamnolipid with two moles of rhamnose, and they were produced in the same ratio from the first to fifth culture day. From the examinations of hemolytic activities of the hydrolyzed products of these glycolipids, the hemolysis producing moiety of the hemolysin was considered to be the dimer of beta-hydroxy decanoic acid contained in the glycolipid molecule. Hemolytic activities of these glycolipids are regarded as their detergent like effects. Since these activities are interfered by small amount of serum protein, their pathogenic role would not be important in vitro. However, their interaction with other toxic substances produced by this organism would be subject to be solved.

Bacteriological Techniques↗
PubMed1986

Depot neuroleptics and manic depressive psychosis.

Twelve patients (eight men and four women) suffering from manic depressive disorder who were receiving both lithium and antipsychotic medication had their antipsychotic changed to depot haloperidol decanoate, with their lithium medication remaining unchanged. Successful transfer to haloperidol decanoate was achieved with a reduced incidence of extrapyramidal side effects, and 100% compliance in eight patients who all remained free of hypomanic relapse, including four patients with rapid-cycling disorder. By comparison, in the three years before switching to haloperidol decanoate these four patients had required sixteen admissions for hypomanic relapses resulting in thirty-four months in-patient treatment.

Adolescent↗
PubMed1986

Effects of sex, gonadectomy and several steroids on the development of insulin-dependent diabetes mellitus in the BB rat.

The spontaneous development of the putative autoimmune insulin-dependent diabetes mellitus (IDDM) in BB rats was not affected by the following factors: (a) sex, (b) gonadectomy, (c) administration of testosterone decanoate, 11 alpha-hydroxynandrolone decanoate, ethinyloestradiol or Org OD14 (tibolone). Treatment with nandrolone decanoate lead to a statistically significant decrease in the incidence of diabetes in male rats in one experiment, but failed to do so in the second. These results and various data from the literature suggest that the influence of sex and steroids on the development of diabetes mellitus in the BB rat is different to that of autoimmune disorders in other animal models (New Zealand Black/White, New Zealand Black mice, Obese Strain chickens) and in man.

Age Factors↗
PubMed1979

Radiometric measurement of differential metabolism of fatty acids by Mycobacterium lepraemurium.

An assay system has been developed based on automated radiometric quantification of 14CO2 produced through oxidation of (1--14C) fatty acids by mycobacteria. With this system, the Hawaiian strain of M. lepraemurium was studied using the K-36 buffer as a suspending solution for the organisms along with 5.0 muCi of one of the following fatty acids: acetate, butyric, hexanoic, octanoic, decanoic, lauric, myristic, palmitic, stearic, oleic, linoleic, linolenic, and malonic. The 14CO2 production by this organism was greatest with lauric, decanoic, myristic, octanoic, stearic, oleic, linoleic, linolenic, and malonic. The 14CO2 production by this organism was greatest with lauric, decanoic, myristic, octanoic, and stearic acids, in decreasing order. Assimilation studies and radiochromatograms confirmed that most of the oxidized substrates were converted into by-products with no change in those from which no oxidation was found. These data suggest that the radiometric measurement of differential fatty acid metabolism may provide a basis of radiometric identification of M. lepraemurium and assessment of the growth requirements of this organism.

Carbon Dioxide↗
PubMedDate not supplied

Eleven years of experience with depot neuroleptics.

The authors prescribe depot neuroleptics almost exclusively to chronic schizophrenics; the minimum duration of treatment is 6 months; 63% of long-acting neuroleptics are fluphenazine decanoate or flupentixol decanoate (main indication: inactive schizophrenics), 37% are clopentixol decanoate (main indication: productive and agitated schizophrenics). Safety, compliance and pharmacokinetics are much better with long-acting neuroleptics (LANs) than with oral medications, but the authors question the reality of a dose reduction as compared to oral neuroleptics since the latter are taken irregularly. The lowest possible dose and an increase of intervals between injections are advocated, because of less cumulative effects and less tardive dyskinesias. LANs bring about a quantitative reduction of symptomatology, but not a cure of the schizophrenic process: most patients relapse upon discontinuation.

Antipsychotic Agents↗
PubMed1982

Radiometric measurement of differential metabolism of fatty acid by mycobacteria.

An assay system has been developed based on automated radiometric quantification of 14CO2 produced through oxidation of [1-14C] fatty acids by mycobacteria. Two stains of M. tuberculosis (H37Rv and Erdman) and one of M. bovis (BCG) in 7H9 medium (ADC) with 1.0 microCi of one of the fatty acids (butyric, hexanoic, octanoic, decanoic, lauric, myristic, palmitic, stearic, oleic, linoleic and linolenic) were studied. Results previously published on M. lepraemurium (Hawaiian) were also included for comparison. Both strains of M. tuberculosis had maximum 14CO2 production from hexanoic acid. Oxidation of butyric and avid oxidation of lauric acids were also found with the H37Rv strain but not with Erdman. In contrast, 14CO2 production by M. bovis was greatest from lauric and somewhat less from decanoic acid. M. lepraemurium showed increasing oxidation rates from myristic, decanoic and lauric acids. Assimilation studies of M. tuberculosis H37Rv confirmed that most of the oxidized substrates were converted into by-products with no change in those from which no oxidation was found. These data suggest that the radiometric measurement of differential fatty acid metabolism may provide a basis of strain identification of the genus Mycobacterium.

Carbon Dioxide↗
PubMed1980

behavior of rats and mice administered active metabolites of fluphenazine, 7-hydroxy-fluphenazine and fluphenazine-sulfoxide.

We investigated the effects of 7-hydroxy-fluphenazine and fluphenazine-sulfoxide, main metabolites of fluphenazine (FZ), on behavior of mice and rats. These metabolites inhibited open-field behavior and methamphetamine-induced hyperactivity, lowered body temperature, and elicited catalepsy in mice, as did FZ-2HCl, FZ-enanthate and FZ-decanoate. After intramuscular administration, the onset of action of FZ-enanthae, FZ-decanoate and their metabolites was somewhat delayed compared to findings with FZ-2HCl, and the duration of FZ-enanthate and FZ-decanoate lasted longer than that of FZ-2HCl and metabolites. FZ-metabolites decreased stereotypy induced by a high dose (4 mg/kg, i.p.) of apomorphine and yawning elicitedby a low dose (0.25 mg/kg i.p.) of apomorphine in rats. The results suggest that 7-hydroxy-FZ and FZ-sulfoxide exert their psychotropic actions by blocking pre- and postsynaptic dopamine receptors and that formation of active metabolite may affect theprolonged therapeutic action of depot-type preparations of FZ.

Animals↗
PubMed2000

Role of Yersinia intermedia and Pseudomonas putida in the development of a fruity off-flavour in pasteurized milk.

Analysis by gas chromatography-mass spectrometry of pasteurized milk with a fruity (pineapple like) off odour and a sour, rancid and soapy taste indicated the presence of concentrations at microg/ml levels of ethyl butanoate, ethyl hexanoate, ethyl octanoate, ethyl decanoate, octanoic acid, decanoic acid and dodecanoic acid. The off-odour and taste were attributed to the presence of these compounds in the milk. Microbiological examination confirmed that the milk was also contaminated with a series of psychrotrophic bacteria including Yersinia intermedia, Pseudomonas putida and Rahnella aquatilis. Growth of isolates of these bacteria in UHT milk at 23 degrees C for 7 d showed that Yer. intermedia produced significant quantities of the C4-C12 alkanoic acids; Ps. putida produced only small quantities of these acids and Rah. aquatilis produced none. In addition, Yer. intermedia and Ps. putida also produced small but significant quantities of the corresponding ethyl esters. In milk inoculated with both Yer. intermedia and Ps. patida, the quantity of ethyl esters produced was greater than that found in cultures containing only one of the isolates. These studies indicated that Yer. intermedia was the principal source of the alkanoic acids in the tainted milk and that the major producer of the corresponding ethyl esters was Ps. patida. This is the first report that Yer. intermedia and Ps. putida can cause an off-odour or taste in dairy products.

Animals↗
PubMed1975

The long-acting phenothiazines.

Injected intramuscularly, the enanthane and decanoate esters of the phenothiazine fluphenazine are an effective treatment of the disordered behavior and thinking of schizophrenia. The decanoate preparation is not only slightly longer-acting but also has a smaller incidence of side-effects that the enanthate. The major adverse effect of these medications is the high frequency of extrapyramidal system disturbance. Since the 50% rate of failure of schizophrenic outpatients to take prescribed oral medications decreases treatment failure to about 20% with the use of long-acting injectable phenothiazines, this route of administration offers an advantage in patient management particularly applicable to community mental health systems. Moreover, parenteral administration of long-acting fluphenazine may be useful for patients who do not attain effective serum levels with medication taken orally because of metabolic or absorption difficulties.

Antiparkinson Agents↗