A case with fear of emitting body odour resulted in successful treatment with clomipramine.

A patient with fear of emitting body odour of about 20 years' duration is reported. The patient was improved with clomipramine, a tricyclic antidepressant. Generally in Japan, he would be classified as having anthropophobia. However, according to the criteria advocated by Munro and Chmara (1982), he could be classified as having monosymptomatic hypochondriasis (MH). There are some reports that antidepressants have been effective in patients with either anthropophobia or MH. Therefore, a subgroup of patients which respond to antidepressants may exist in these disorders.

Striatal N-methyl-D-aspartate receptors in haloperidol-induced catalepsy.

Bilateral ablation of the frontal cortex of rats markedly reduced the catalepsy induced by haloperidol (1 mg/kg i.p.). Similarly, the selective antagonist of N-methyl-D-aspartate (NMDA) receptors, D(-)-2-amino-5-phosphonopentanoic acid (10 micrograms/side), injected bilaterally into the rostral part of the caudate-putamen (CP) reduced haloperidol-induced catalepsy whereas its injection into the intermediate part of the CP was ineffective. The quisqualate receptor antagonist, L-glutamic acid diethyl ester (100 micrograms/side), did not affect haloperidol-induced catalepsy when injected into the rostral part of the CP. On the other hand, NMDA (1 micrograms/side) injected bilaterally into the rostral part of the CP was able to restore haloperidol-induced catalepsy in frontally decorticated rats without any notable cataleptic effect of its own. These findings suggest that a certain degree of tonic stimulatory effect of corticostriatal glutamatergic pathways on NMDA receptors within the rostral part of the CP is a prerequisite for the expression of the cataleptogenic action of haloperidol.

[Characteristics and regulation of 3H-haloperidol binding to rat brain sigma receptors].

Rat brain sigma receptors were labeled by 3H-haloperidol, and the effects of repeated administrations of pentazocine and haloperidol on these binding sites were investigated. On the basis of preliminary experiments, 30 nM spiperone was included in the assay medium in the frontal cortex (to block binding to D2 dopamine and S2 serotonin sites), but not in the hippocampus or cerebellum; the specific binding was defined by inhibition by 30 or 100 microM (+)3-(3-hydroxy)-N-(1-propyl)piperidine. In the brain regions from untreated animals, saturation studies for the specific binding revealed a single population of saturable binding sites; inhibition studies revealed a distinct sigma receptor pharmacology. Fourteen days successive administrations of 7.5 mg/kg of pentazocine induced a significant increase in Kd without affecting Bmax of the binding in the frontal cortex, but not in the cerebellum. Similar treatments with haloperidol (2 or 4 mg/kg) resulted in a significant decrease in Bmax without changes in Kd of the binding in the frontal cortex and hippocampus. However, no effects were observed in the cerebellum. These findings indicate rat brain sigma receptors respond differently to pentazocine and haloperidol, and there are regional differences in the regulatory mechanisms of sigma receptors.

Rat cortical sigma receptors differentially regulated by pentazocine and haloperidol.

Repeated administrations of 7.5 mg/kg of pentazocine (for 14 days) resulted in a significant decrease in the affinity of 3H-haloperidol binding to rat cortical sigma receptors without any changes in the maximal number of binding sites (Bmax). On the other hand, similar treatment with haloperidol (2 or 4 mg/kg) induced a dose dependent decrease in the Bmax values without affecting the affinity of the 3H-haloperidol binding. These findings indicate that rat cortical sigma receptors are differentially regulated by pentazocine and haloperidol.

The restorative action of coenzyme Q10 in 2,4-dinitrophenol-depressed electrical and contractile activities of guinea-pig heart.

With electrophysiological methods, mechanisms of the restorative action of coenzyme Q10 (CoQ10) in 2,4-dinitrophenol-depressed electrical and mechanical activities of isolated guinea-pig hearts were studied. Isoproterenol (3 X 10(-8) M)-induced action potential and contraction of the heart in 27 mM KCl Tyrode solution were abolished by 6 X 10(-6) M 2,4-dinitrophenol, while the additional application of CoQ10 (50 micrograms/ml) restored both these activities of the heart. This restorative action of CoQ10 was dose related (2 to 50 micrograms/ml) and was inhibited by 10 micrograms/ml 15-hydroperoxyarachidonic acid (15-HPAA) or pretreatment of the animals with indomethacin (5 mg/kg i.v.). When exogenously applied, 200 ng/ml prostacyclin also restored the 2,4-dinitrophenol-depressed electrical and contractile activities of the heart, but this restorative action of prostacyclin was affected neither by 15-HPAA nor by indomethacin pretreatment. These results suggest the possible participation of prostacyclin in the restorative action of CoQ10 in 2,4-dinitrophenol-depressed electrical and mechanical activities of the heart.

Modulation by alpha 2-adrenergic stimulation of IgE-mediated 14C-serotonin release from rat mast cells.

The formaldehyde method was used to examine the effects of clonidine and methoxamine on IgE-mediated 14C-serotonin release from rat mast cells in vitro. Clonidine (10(-11) -10(-8) M) caused dose-related enhancement of the mediator release 7 min after the antigen challenge; yohimbine (10(-6) M) blocked this enhancement by clonidine (10(-6) M), but prazosin (10(-6) M) did not. Methoxamine did not enhance this immunological release reaction at concentrations up to 10(-6) M. PGE1 (2 X 10(-8) -2 X 10(-5) M), isoproterenol (10(-10) -10(-8) M), dopamine (4 X 10(-8) -4 X 10(-8) M) and aminophylline (6 X 10(-6) -6 X 10(-4) M) caused dose-related inhibition of this mediator release 1 min after antigen challenge. Clonidine (10(-13) -10(-12) M), but not methoxamine (10(-8) -10(-6) M), reversed dose-dependently this inhibition of mast cells by PGE1 (2 X 10(-6) M), isoproterenol (10(-8) M), dopamine (4 X 10(-6) M); yohimbine (10(-8) M) antagonized this reversing action of clonidine (10(-12) M), but prazosin (10(-10) M) did not. Neither clonidine (10(-14) -10(-11) M) nor methoxamine (10(-8) -10(-6) M) reversed the inhibitory action of aminophylline (2 X 10(-4) M). These results suggests that clonidine enhances IgE-mediated 14C-serotonin release from rat mast cells and also antagonizes the inhibition of mast cells by PGE1, isoproterenol and dopamine, but not by aminophylline in this immunological reaction through alpha 2-adrenergic receptors, and that the inhibition of adenylate cyclase of mast cells is one of the biochemical actions of alpha 2-adrenergic mechanisms.

Interactions of morphine with PGE1, isoproterenol, dopamine and aminophylline in rat mast cells; their effect on IgE-mediated 14C-serotonin release.

The formaldehyde method was used to examine the interactions of morphine with PGE1, isoproterenol, dopamine and aminophylline in rat mast cells by their effects on IgE-mediated 14C-serotonin release. PGE1 (2 x 10(-8) -2 x 10(-5) M), isoproterenol (10(-10) -10(-8) M), dopamine (4 x 10(-8) -4 x 10(-6) M) and aminophylline (6 x 10(-6) -6 x 10(-4) M) caused dose-related inhibition of the mediator release 1 min after an antigen challenge, and propranolol (10(-7) M) blocked the inhibition by isoproterenol (10(-8) M) but not that by dopamine (4 x 10(-6) M), while haloperidol (4 x 10(-6) M) blocked that by dopamine (4 x 10(-6) M) but not that by isoproterenol (10(-8) M). Morphine (3 x 10(-7) -3 x 10(-5) M) reversed the inhibitory effects of PGE1 (2 x 10(-6) M), isoproterenol (10(-8) M) and dopamine (4 x 10(-6) M) dose-dependently and stereospecifically; naloxone (2 x 10(-4) M) antagonized these reversing actions of morphine (3 x 10(-5) M). Morphine (10(-6) -10(-4) M) did not reverse the inhibitory action of aminophylline (6 x 10(-4) M). These results suggest that the inhibitory responses of mast cells to PGE1, isoproterenol and dopamine but not to aminophylline in immunological mediator release were reversed by morphine through opioid receptors, and that the inhibition of adenylate cyclase in mast cells is one of the biochemical actions of morphine.

A possible mechanism of adriamycin cardiotoxicity. Inhibition of NADP-linked isocitrate dehydrogenase.

In heart muscle, NADP-linked isocitrate dehydrogenase activity is particularly high when compared with that of the other representative NADPH-generating enzyme, glucose-6-phosphate dehydrogenase. Approximately 80% of cardiac NADP-linked isocitrate dehydrogenase activity originates in the mitochondria. Adriamycin inhibited the activity of both mitochondrial and cytoplasmic NADP-linked isocitrate dehydrogenase dose dependently but had no effect on glucose-6-phosphate dehydrogenase. The inhibition was kinetically distinguished as noncompetitive. Preincubation of crude cardiac enzyme preparations with adriamycin enhanced the inhibition time dependently for 45 min. However, there was no evidence to suggest that the metabolites of adriamycin produced in this system were active as inhibitors. Adriamycin-binding protein was fractionated by affinity chromatography, but NADP-linked isocitrate dehydrogenase activity was not detected in this fraction.

IgE-mediated 14C-serotonin release from passively sensitized rat mast cells: comparative kinetic study with formaldehyde and ice-cold methods.

The kinetics of IgE-mediated release of serotonin from passively sensitized rat mast cells in vitro was studied by stopping 14C-serotonin release with the application of formaldehyde fixative or ice-cold mast cell medium (MCM). Antigen dose-release curves of 14C-serotonin and/or histamine were comparable when mediator release was terminated with either formaldehyde at a final concentration of 1% or ice-cold MCM 15 min after antigen challenge. However, the kinetic study of immunological mediator release stopped by formaldehyde showed that the addition of antigen resulted in a progressive increase of released 14C-serotonin for 7 min, the release curve being sigmoidal, whereas the application of ice-cold MCM artificially enhanced 14C-serotonin and histamine release in the first 2 min. The results suggest that stopping IgE-mediated release of 14C-serotonin with formaldehyde is a simple, rapid and accurate method of studying the kinetics of mediator release from mast cells.

IgE-mediated 14C-serotonin release from rat mast cells modulated by morphine and endorphins.

The formaldehyde method was used to examine the interaction of PGE1 with morphine, beta-endorphin and Met-enkephalin on rat mast cells by their effects on IgE-mediated 14C-serotonin release. PGE1 (2x10(-8) -2x10(-5) M) caused a dose-related inhibition of the mediator release 1 min after an antigen challenge, and morphine (3x10(-7) -3x10(-5) M) reversed this PGE1 effect dose-dependently and stereospecifically; naloxone (2x10(-4) M) antagonized this action of morphine. Beta-Endorphin (3x10(-7) -10(-5) M) and Met-enkephalin (3x10(-6) -10(-4) M) mimicked this morphine action dose-dependently and were antagonized by naloxone (2x10(-4) M). These results suggest that morphine and endorphins modulate immunological mediator release from rat mast cells through opioid receptors.

Cardiac hypertrophy: its characteristics as a growth process.

The causal relation between cardiac function and growth is analyzed in this review article. Three different levels of development are discussed: cytodifferentiation, embryogenesis and postnatal development. The earliest stage of cardiac morphogenesis, that is, the appearance of cell-specific proteins and of spontaneous contractions, appears to be independent of hemodynamic forces. Also, the first major morphologic transformation of the primitive heart, looping, is the intrinsic property of the heart itself. However, at any later stage of life, hemodynamic function in both health and disease is closely coupled to cardiac growth.

Studies on beta-pyridylcarbinol as a precursor of nicotinamide adenine dinucleotide.

The major part of orally administered beta-pyridylcarbinol was converted to nicotinic acid in the gastrointestinal tract, whereas that administered intraperitoneally was partially converted to nicotinic acid in the liver. The conversion of this compound to nicotinic acid in both the gastrointestinal tract and liver involved enzymatic processes. The converted nicotinic acid from beta-pyridylcarbinol may play a dominant role in the biological actions of beta-pyridylcarbinol and possibly involves in the synthesis of NAD via Preiss-Handler's pathway.

Effect of 4-hydroxypyrazolo[3,4-d]pyrimidine (allopurinol) administration of growth of Ehrlich tumor cells.

Effect of the administration of 4-hydroxypyrazolo([3,4-d]pyrimidine (allopurinol) on the growth of Ehrlich ascites tumor cells was investigated in an in vivo system. Oral administration of allopurinol (0.1% in diet) suppressed the growth of both ascites and solid types of the tumor after the implantation of Ehrlich tumor cells in mice. The inhibitory action depended on the dose but was lost repidly when the administration was interrupted. Possible mechanisms involved in the inhibitory effect of allopurinol on tumor growth were briefly discussed.

Effect of xanthine oxidase inhibitor on myocardial ischemia.

The xanthine oxidase inhibitor, 4-hydroxypyrazolo(3,4-d) pyrimidine (HPP), Allopurinol, caused augmentation of myocardial uptake of [3H] hypoxanthine, which was eventually completely incorporated into ATP. The decrease of [32P] orthophosphate incorporation into ATP induced by isoproterenol was restored by HPP administration.