Urinary metabolites of benzbromarone in man

Benzbromarone [3,5-dibromo-4-hydroxyphenyl)-(2-ethyl-3-benzofuranyl)-ketone) is a widely used uricosuric drug which was reported to be metabolized by successive debromination. Recently, however, it was reported that benzbromarone is not debrominated but hydroxylated at the ethyl side chain. The presented paper describes further studies on the metabolism of the drug in man. The metabolites were identified in urine samples from two different patients intoxicated suicidally with high doses of benzbromarone after cleavage of conjugates, extraction and derivatization by acetylation using gas chromatography-mass spectrometry. The following five metabolites could be identified besides the unchanged benzbromarone (BB): hydroxy-alkyl-BB, oxo-BB, two isomers of hydroxyaryl-BB and hydroxy-methoxy-aryl-BB. Therefore, the following two phase I metabolic pathways can be postulated: successive oxidation of the ethyl side chain and one- and twofold hydroxylation of the benzofuran ring followed by methylation of one of the hydroxy groups. Benzbromarone and its metabolites are excreted in urine partly in a conjugated form. Debrominated metabolites could not be detected, although the concentrations of benzbromarone and its metabolites were very high in the urine samples studied.     

Bioequivalence of sodium monofluorophosphate with sodium fluoride and compatibility with calcium

The study was conducted in a triple cross-over on 12 healthy Caucasian volunteers (4 males and 8 females) of an age between 23 and 44 years. The following products were given in a single oral dose in fasting state. 1. Solution of 29.18 mg of sodium fluoride in 80 ml of water (reference NaF solution). 2. Solution of 100 mg sodium monofluorophosphate (CAS 10163-15-2) in 80 ml of water (Na2FPO3 solution). 3. Tablets with 100 mg sodium monofluorophosphate and 1250 mg calcium carbonate (Na2FPO3 + Ca tablets). The three products were equivalent in fluorine content (13.2 mg). The bioavailability of fluorine was evaluated on the basis of the plasma levels and of the urinary excretion of fluoride. After administration of the products, fluoride appeared in blood with a lag time smaller than 0.05 h and invaded the blood with a t1/2 from 0.07 to 0.12 h. The Cmax of fluoride in plasma was 412-466 ng/ml at a tmax of 0.5-0.7 h. The AUCs of fluoride after Na2FPO3 solution and after Na2FPO3 tablets were within the 0.80-1.20 bioequivalence limits with regard to the AUC after NaF solution. The three products can therefore be considered bioequivalent according to the Westlake criteria. In the 24 h following the administration, the urinary excretion of fluoride accounted for 51 +/- 10%, 46 +/- 6% and 47 +/- 8% of the administered dose, respectively for NaF solution, Na2FPO3 solution and Na2FPO3 + Ca tablets. The difference between the three products was statistically not significant and confirms their bioequivalence.(ABSTRACT TRUNCATED AT 250 WORDS)     

Intrastriatal infusions of ascorbate antagonize the behavioral response to amphetamine

Compared to saline, bilateral infusions of ascorbate (AA) into the neostriatum of freely moving rats attenuated rearing, head bobbing, and sniffing at various times after systemic amphetamine administration. Comparable AA infusions into overlying cerebral cortex failed to alter the amphetamine behavioral response. Intrastriatal AA also enhanced the ability of haloperidol to antagonize amphetamine-induced forepaw shuffling and locomotion. Voltammetric measurements in separate animals revealed a linear increase in neostriatal AA that remained within reasonable physiological limits over the course of the AA infusion. Thus, endogenous AA may modulate behavior via mechanisms intrinsic to the neostriatum.     

三七细胞大量培养物中主要药用成分皂甙的分离和鉴定

植物细胞大量培养技术工业化生产次级代谢产物,与栽培植物比较,具有不占用良田、不受地区、季节、气候的影响,无农药残留,不影响出口及药用,很少受市场波动的影响,有利于提高生产率降低成本,提高有效成分含量和获得新的有用物质等优点。三七Panax notoginseng(Burk)F.H.Chen为云南特产的名贵中药,但它在栽培中却存在着生产周     

Receptors for peanut agglutinin (Arachus hypogea) in childhood acute lymphoblastic leukemia: possible clinical significance

The presence of lymphocyte receptors for peanut agglutinin in significant numbers (greater than 15%) was identified on leukemic cells from T-cell acute lymphoblastic leukemia (T-ALL) (3/4), B-cell ALL (B- ALL) (2/4), null cell ALL (8/17), and on normal fetal thymic lymphocytes but not on normal human peripheral blood lymphocytes. Peanut agglutinin (PNA) binding was blocked specifically on leukemia lymphoblasts and thymic lymphocytes by the addition of galactose to the medium. When all immunologic subgroups of ALL are combined, preliminary data suggest that of the 13 ALL patients having greater than 15% PNA- positive lymphoblasts, 8 had relapsed, whereas none of the 12 ALL patients with less than 15% PNA-positive cells have recurrent disease at this time. It is likely that analysis of PNA receptors on ALL lymphoblasts may be a useful adjunct to the existing clinical and immunologic prognostic indicators.     

Soft tissue sarcoma of the head and neck in childhood: nonorbital and nonparameningeal sites. A report of the Intergroup Rhabdomyosarcoma Study (IRS)-I

Seventy-two patients with soft tissue sarcoma arising in the oral cavity, oropharynx, larynx, parotid region, cheek, scalp, and neck, were entered on the Intergroup Rhabdomyosarcoma Study (IRS)-I, and could be analyzed for survival. Sixty-three (88%) attained complete remission (CR), of whom 13 subsequently relapsed (78% actuarial 5-year retained CR rate). The patients with primary tumor arising in sites other than the neck had a retained CR rate exceeding 90%. In contrast, 11 relapses occurred in the 26 patients with neck primaries (54% retained CR rate). Females, and infants younger than age 24 months were more likely to relapse. Prognostic factors with little or no influence on relapse included tumor size, histology, regional lymph node status, clinical group, and treatment arm. Five of the 6 patients with failure at the primary site had either no radiotherapy (2 patients) or an insufficient dose (less than 3000 rad). No patient required major organ sacrifice such as laryngectomy or pharyngectomy. Isolated failure in regional nodes did not occur. Children with nonorbital, nonparameningeal head and neck soft tissue sarcoma treated in accordance with the IRS protocol have an excellent rate of local control and survival. Primary tumors arising in the neck are more likely to relapse locally or distantly.     

Histopathology of childhood sarcomas, Intergroup Rhabdomyosarcoma Studies I and II: clinicopathologic correlation

Histopathologic material from 1,782 patients registered in the Intergroup Rhabdomyosarcoma Study Committee (IRS)-I and -II were reviewed by the IRS Pathology Committee in order to provide a uniform approach to classification and correlate patient survival with tumor type. Categories considered eligible were the four types of rhabdomyosarcoma (RMS) (criteria of Horn and Enterline), extraosseous Ewing's tumor (EOE), and a group of somewhat variable undifferentiated sarcomas designated small round cell sarcoma, type indeterminate (STI). Tumors that were clearly sarcomas but were unclassifiable also were included (NOS). The committee diagnoses were embryonal (Emb) RMS in 877 (54%), alveolar (Alv) RMS in 343 (21%), botryoid (Botr) RMS in 88 (5%), pleomorphic (Pleo) RMS in 11 (1%), STI in 135 (8%), and EOE in 84 (5%). One in nine were mixtures of types, eg, Emb and Alv. Five percent of the sarcomas could not be classified because of inadequate material. In general, there was close agreement (94%) between the review committee and institutional pathologists in the diagnosis of RMS, but not in the specific types, particularly Alv RMS (41%) and STI (36%). This observation is important, since patients with Alv RMS and STI tumors had decreased survival compared with the other histologies. The prognosis varied by histology, with Botr having the best, Alv RMS and STI the worst, and Emb RMS and EOE an intermediate prognosis.     

Schizophrenie und Depression

BACKGROUND: Comparison of symptom-related and social role development between patients with schizophrenia, major depression and healthy controls provided insights into the untreated early course of the two disorders. SAMPLES AND METHODS: Symptoms, functional impairment and social disability were assessed and compared using the IRAOS and several other cross-sectional instruments in three samples. RESULTS: At the early illness stages there was considerable overlap in the symptom patterns and impairments presented by persons with schizophrenia and severe depression.The two disorders did not diverge until later in the early illness course with the onset of psychotic symptoms. Depressive symptoms showed a maximum in the first psychotic episode and relapse episodes and decreased with the remitting episode. Due to differences in cognitive appraisal depressed patients reported more functional impairment and social disability than patients with schizophrenia did. CONCLUSION: The early course of symptoms and social impairment in schizophrenia and depression seems to offer an opportunity to distinguish these disorders from variants of normal development fairly early. However, early diagnostic distinction and prediction of psychosis versus depression risk at the pre-psychotic prodromal stage do not seem promising due to the broad overlap in symptoms and impairment.     

Reduced structural integrity of the uncinate fasciculus in incarcerated women scoring high on psychopathy

Brain Imaging and Behavior - Both men and women scoring high on psychopathy exhibit similar structural and functional neural abnormalities, including reduced volume of the orbitofrontal cortex...     

Lithium-induced enhancement of mitochondrial oxidative phosphorylation in human brain tissue

Objectives:  Extensive preclinical and clinical evidence suggests mitochondrial dysfunction in bipolar disorder. Studies of brain energy metabolism in bipolar disorder suggest an impairment of energy generation by mitochondrial oxidative phosphorylation. Lithium is an effective drug widely used in treating bipolar disorder, but its mechanism of action has remained uncertain. The aim of this study was to clarify the effect of lithium on mitochondrial oxidative phosphorylation.
Methods:  We spectrophotometrically determined the activities of the respiratory chain complexes I + III [antimycin A-sensitive nicotinamide adenine dinucleotide (NADH) cytochrome c oxidorductase], complexes II + III (succinate cytochrome c oxidoreductase), succinate dehydrogenase, and complex IV [cytochrome c oxidase (COX)], and of the mitochondrial matrix enzyme citrate synthase in postmortem human brain cortex homogenates following exposure to lithium (up to 10 mM).
Results:  Activities of complexes I + III and of complexes II + III were dose-dependently increased by lithium with maximum values at 1 mM (165%, p = 0.03, and 146%, p = 0.00002, of controls). Activity of succinate dehydrogenase remained unchanged up to 2 mM, but was raised at higher drug concentrations (maximum 220%, p = 0.01, of controls). In contrast, activity of COX was not significantly affected by the drug (decrease of 12% at 1 mM, p = 0.4).
Conclusions:  Our study suggests that lithium stimulates mitochondrial respiratory chain enzyme activities at clinically relevant concentrations. Lithium's effect on the mitochondrial respiratory chain presents further evidence of the pathophysiological significance of mitochondrial dysfunction in bipolar disorder. The effect may be relevant to the therapeutic efficacy of the drug by potentially reversing a disease-related alteration.