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Biomedical subjects

M Takashima

Publications and source records attributed to M Takashima.

At least 127 records · Page 7Linked to original sources

Chronic dietary treatment with antidepressants decrease brain Met-enkephalin-like immunoreactivity in the rat.

This report describes the effect of chronic dietary treatment with antidepressants or antimanic drugs on brain Met-enkephalin-like immunoreactivity in the rat. The chronic treatment was administered through food containing 250-1000 mg desipramine, imipramine or clomipramine, 200-800 mg amoxapine or mianserin, 750-1500 mg lithium chloride, or 50 mg haloperidol per 1 kg food for 40 days. In the striatum, each antidepressant decreased the enkephalin content, while lithium or haloperidol, having an antimanic effect, increased the enkephalin content. Following the chronic administration of each antidepressant tested, the concentration of the peptide was reduced in the nucleus accumbens, hypothalamus and thalamus. We further examined the acute effect of the antidepressant (10 or 20 mg/kg) on the striatal enkephalin content at 60 min after a single intraperitoneal injection. The striatal content was decreased after the acute treatment with each antidepressant tested. These results indicate that the antidepressants had an effect on the neuronal activity of Met-enkephalin not only after chronic treatment, but also after acute treatment. The reduction in Met-enkephalin-like immunoreactivity after prolonged treatment with the antidepressant may possible contribute to the mechanism of antidepressive action.

Animals↗

Circadian fluctuations in pain responsiveness and brain Met-enkephalin-like immunoreactivity in the rat.

The 24-hour patterns of pain responsiveness and brain Met-enkephalin-like immunoreactivity (MLI) were determined in male Wistar rats housed under a 12-hour light and dark cycle (lights on from 0700 hr to 1900 hr). A circadian rhythm was observed in latencies to hot plate test (55 degrees C), showing the peak level near the onset of the dark phase (2000 hr). Pretreatment with naloxone (5 mg/kg, subcutaneously) decreased the highest latency (2000 hr), but did not change the lowest latency (1100 hr). In the mesolimbic area and the striatum, MLI had a negative correlation with the circadian fluctuation in pain sensitivity. MLI at 2000 hr was reduced significantly compared to that at 1100 hr in the basal ganglia, the frontal cortex and the substantia nigra. These results suggest that the circadian variation in hot plate latencies follows a circadian change in the activity of the endogenous opioid peptides system, and that Met-enkephalin may participate in the enhancement of the opioid system in the brain.

Animals↗

Neurotransmitters, receptors and neuropeptides in post-mortem brains of chronic schizophrenic patients.

In the analysis of post-mortem brains of 14 chronic schizophrenic patients and 10 controls, biochemical evidence of a hyperdopaminergic state was found in the basal ganglia of schizophrenics; tyrosine hydroxylase activity was increased with a concomitant increase of homovanillic acid. Unusually high tyrosine hydroxylase activity was noted in 2 schizophrenic cases. The Bmax value of 3H-spiperone binding for schizophrenics was higher than the controls. We also found increased specific binding of 3H-kainic acid to the prefrontal cortex in schizophrenics. A negative correlation existed between 3H-kainic acid binding in the medial frontal cortex, and glutamic acid content in various brain areas. Increased immunoreactivity of substance P was found in more than ten brain areas. Methionine-enkephalin was also increased in three areas of the prefrontal cortex of schizophrenics. These results suggest that the hyperdopaminergic state co-existed with glutamatergic hypofunction and increased neuropeptides in various brain areas of chronic schizophrenic patients.

Adult↗

Effects of chronic treatment with trihexyphenidyl and carbamazepine alone or in combination with haloperidol on substance P content in rat brain: a possible implication of substance P in affective disorders.

To assess the roles of substance P in neurologic or psychiatric illnesses, effects of acute or chronic (40- or 80-day dietary) treatment with trihexyphenidyl and carbamazepine alone or in combination with haloperidol on substance P content were investigated in the rat brain. Either acute or chronic trihexyphenidyl administration did not alter substance P content when administered alone and did not prevent the haloperidol-induced substance P decrease in the striatum and substantia nigra when coadministered with haloperidol. Chronic dietary carbamazepine administration dose-dependently increased substance P content in the striatum and substantia nigra, but not in the raphe area, in a haloperidol-reversible manner. Carbamazepine also dose-dependently increased gamma-aminobutyric acid levels in the substantia nigra without altering the striatal dopamine turnover rate. The lack of effect of trihexyphenidyl, an anticholinergic drug used to treat antipsychotic drug-induced extrapyramidal (Parkinson) syndromes, suggests that antipsychotic drug-induced reduction in substance P content is not involved in the extrapyramidal side effects. Since the effects of carbamazepine on substance P content are identical with previously described effects of lithium, an alteration in substance P neurotransmission may be one of the neurochemical bases of common clinical and behavioral effects of carbamazepine and lithium on affective disorders.

Animals↗

[The effect of prolactin on the early embryogenesis of mice in vitro].

It is said the prolactin (PRL) is correlated with fetal lung maturation during late pregnancy. However, there are few reports about PRL during early pregnancy and the period of peri-implantation. Recently, transient hyperprolactinemia at the preovulatory phase or after follicle aspiration for in vitro fertilization has been reported. Nonetheless, the effect of high PRL on the folliculogenesis and the early embryogenesis is still controversial. Moreover, some researchers reported that human fetal umbilical cord sera was good for the development of ova fertilized in vitro. Therefore, we studied the effect of graded concentrations of PRL (10, 30, 100 ng/ml) on the development of embryos fertilized in vivo or in vitro using ddY mice. We concluded that higher PRL levels caused a smaller number of developed embryos, in statistical significance, into blastocysts and hatched blastocysts. In general, embryos fertilized in vivo developed better than those fertilized in vitro.

Animals↗

[A pre- and post-operative clinical study in three patients with benign prostatic hypertrophy and implicated chronic renal failure].

We present three cases of benign prostatic hypertrophy associated with chronic renal failure for three years from 1982 to 1984. Endogenous 24-hour creatinine clearance (Ccr) on admission ranged from 8.7 to 29.4 ml/min. Temporary hemodialysis treatment was required in one patient at the beginning of hospitalization. Indwelling intraurethral catheterization for 3 months or more improved the renal function in one patient, but brought troublesome complications of gross hematuria, intractable urethral pain or recurrent pyelonephritis in the other patients. These complications might arise from strong uninhibited detrusor contractions triggered or accelerated by stimuli and/or urinary tract infection induced by urethra-indwelt catheters. Intermittent self catheterization reduced these complications in one patient. In two patients, Ccr increased beyond 30 ml/min as a desirable standard level for safe operations. Suprapubic prostatectomy was successfully performed in all the patients. However, severe gastric ulcer or fatal duodenal ulcer occurred in two patients. Hypoproteinemia and/or urinary tract infection was thought to be highly related to ulceration. In conclusion, we would like to emphasize that a Ccr of more than 30 ml/min is needed for safe operations concerning renal function in patients with benign prostatic hypertrophy associated with chronic renal failure.

Aged↗

[A clinical observation on aged patients subjected to urological surgery].

A clinical analysis was made on 44 inpatients over 80 years old at our department from 1980 to 1984. Forty-three urological surgeries were performed on 36 out of the 44 patients, accounting for 3.4% of all the inpatients. Benign prostatic hypertrophy, which was the most popular disease in our study, was seen in 20 patients. Preoperative examinations revealed one or more complications besides urological disorders in 35 patients (97.5%), 11 patients of which needed some prophylactic treatments prior to urological surgery. Although major postoperative complications consisted of heart disease in 4 patients, gastrointestinal tract disease in 3 patients, and pulmonary disease in 2 patients, there was no operative death. Postoperative laboratory test results revealed hypoproteinemia in 16 patients (44.4%). Postoperative urological complications such as wound dehiscence, urinary fistula, or acute epididymitis occurred in 9 patients, all of whom had urinary tract infections. These results suggest that aged patients have fewer problems if extensive preoperative examinations and active treatments for any abnormality are made and careful attention is paid to postoperative complications.

Aged↗

Haloperidol in large doses reduces the cataleptic response and increases noradrenaline metabolism in the brain of the rat.

The neurochemical basis for the clinical observation that some patients receiving a large dose of haloperidol exhibit no extrapyramidal side effects was investigated in rats. Haloperidol at doses of 1, 2.5, 5, 7.5 and 10 mg/kg (i.p.) caused a dose-dependent decrease in the duration of catalepsy. Haloperidol at a dose of 10 mg/kg induced catalepsy lasting for only 20% of that obtained with 1 mg/kg. Haloperidol decreased the content of noradrenaline in the frontal cortex and thalamus in a dose-dependent manner, while the content of 3-methoxy-4-hydroxyphenylglycol (MHPG) showed a dose-dependent increase in the same areas of the brain. Thus, there was an inverse relationship between the duration of catalepsy and the ratio of 3-methoxy-4-hydroxyphenylglycol to noradrenaline in the frontal cortex or thalamus. The concomitant administration of 20 mg/kg of phenoxybenzamine with 10 mg/kg of haloperidol induced a long-lasting catalepsy. The result may indicate that the increased metabolism of noradrenaline by large doses of haloperidol was not secondary to the blocking of dopaminergic receptors. In contrast, haloperidol caused a dose-dependent decrease in the content of homovanillic acid and 3,4-dihydroxyphenylacetic acid in the striatum and mesolimbic area. These results indicate that noradrenergic hyperfunction in the frontal cortex or thalamus induced by large doses of haloperidol may reduce the cataleptogenic effect of the drug via indirect stimulation of a dopaminoceptive neuron in the striatum or mesolimbic area.

Animals↗

Primary hypomagnesemia with secondary hypocalcemia. Report of a case and review of the world literature.

Primary hypomagnesemia with secondary hypocalcemia (PHSH) is a rare type of hypocalcemic disorder which occurs in early infancy and is clinically characterized by recurrent tetany and/or convulsion. In this paper, a male infant with PHSH who had frequent seizures at the age of 9 days is described. Besides PHSH, several illnesses in infancy are manifested by hypomagnesemia and hypocalcemia, i.e. transient neonatal hypomagnesemic hypocalcemia, congenital renal or hepatic insufficiencies, magnesium-losing nephropathy, combined impairments of intestinal absorption and renal reabsorption of magnesium. PHSH is to be differentiated from these illnesses by the demonstration of a combination of the following findings; hypocalcemia refractory to calcium but responsive to magnesium, continuous requirement for magnesium supplementation to maintain normocalcemia, lack of hypermagnesiuria and/or impaired intestinal absorption of magnesium. Twenty cases from the literature were found to exhibit these characteristics. The clinical, biochemical, and endocrine features of PHSH are summarized on the basis of a review of the data of these and the present case. No associated illness was known in the afflicted infants or mothers. Both male and female infants were afflicted at a male to female ratio of 15:6. Some siblings were afflicted but none of the parents or relatives. The onset of tetany and/or convulsion was between the 9th day and 4th month, which is later than that of other neonatal hypocalcemic illnesses. Hypocalcemia was more pronounced than other infantile hypocalcemic illnesses. The role of the parathyroid hormone in the pathogenesis of hypocalcemia has been studied in several studies but no unifying concepts have yet been established.

Calcium↗

[Effect of etidronate disodium (EHDP) on calcium oxalate renal stones induced by synthetic 1 alpha(OH) vitamin D3 and ethylene glycol in rats].

Combination of 1 alpha(OH) D3(vit D) and ethylene glycol induced renal or ureteral stones or both consisting of calcium oxalate in male Wistar rats. This study investigates the effect of EHDP on calcium oxalate stone using the rat model. EHDP reduced the frequency of renal stone and calcium content in the kidney, and reduced the size of the stones in the renal pelvis and ureter. EHDP biochemically ameliorated renal injury induced by vit D and ethylene glycol. EHDP suppressed urinary excretion of calcium even though serum calcium slightly increased. EHDP had a phosphaturic action. EHDP elevated urinary excretion of magnesium. However, the severity of hypermagnesuria decreased in the rat which was not given EHDP concomitantly. Although EHDP slightly elevated urinary excretion of oxalate in the control rat, it did not affect the high level of urinary oxalate in the vit D/ethylene glycol rat. EHDP did not produce any histological change in the kidney or femoral bone. These data indicate that EHDP can suppress renal stone formation in the vit D/ethylene glycol rat. It is speculated that firstly, EHDP may physicochemically inhibit stone formation in the process of nidus, aggregation and crystal growth of calcium oxalate, under the supersaturated condition of calcium oxalate in the urine, and secondly, EHDP may endocrinologically inhibit production of 1,25 (OH)2 vit D in the kidney or inhibit 1, 25 (OH)2 vit D-mediated intestinal calcium absorption. It is suggested that in order to prevent stone recurrence, EHDP may be clinically applied not only to calcium phosphate stones but also to calcium oxalate stones and hypercalciuria mediated by an active form of vitamin D.

Animals↗

Increased brain serotonin metabolism during rebound sleep in sleep-deprived rats.

Adult male Wistar rats were almost totally deprived of sleep by handling for 24 hr. 5-Hydroxyindolacetic acid concentrations in the dorsal raphe nucleus area and thalamus increased by 140-180%, immediately after sleep deprivation and when the rats had a 3- or 30-min rebound sleep. The higher levels of 5-hydroxyindolacetic acid were still observed after the rats were awakening from a 4-hr sleep. The concentrations of 5-hydroxytryptamine (serotonin) decreased after sleep deprivation and increased during and after sleep, but the differences were not significant. Tryptophan accumulated in the dorsal raphe area and thalamus after sleep deprivation, and an elevated level did not return to baseline concentrations until the rats were awakening. Tryptophan hydroxylase activity did not change in the dorsal raphe area during and after sleep deprivation. These results suggest that the release and synthesis of 5-hydroxytryptamine in the dorsal raphe area and thalamus increased when the rats had a sleep pressure or a rebound sleep after total sleep deprivation. An increased transport of tryptophan into the brain may be closely involved in sleep-inducing mechanisms.

Animals↗

Increased muscarinic cholinergic receptors in prefrontal cortices of medicated schizophrenics.

Alterations in 3H-quinuclidinyl benzilate binding sites associated with muscarinic cholinergic receptors were investigated in orbito-frontal and medial frontal cortices from 12 schizophrenics, 6 on-drug and 6 off-drug cases, and from 10 controls. Significantly lower affinities of the sites were found in both areas of schizophrenics than controls. An increase in receptor number was shown only in the orbito-frontal cortex from schizophrenics. On-drug group of schizophrenics did, however, show a significant increase in receptor number and a significant decrease in affinity in both areas, while there were no significant differences in any binding parameters of off-drug schizophrenics from controls. Also in the caudate the similar results were obtained. It is, thus, concluded that alterations in muscarinic cholinergic receptors of schizophrenic patients result from long-term medication with antimuscarinic actions.

Adult↗

Increased [3H]kainic acid binding in the prefrontal cortex in schizophrenia.

[3H]Kainic acid binding sites were measured post mortem in the putamen and prefrontal cortex areas from 10 control subjects and 12 schizophrenic patients. A 25-50% increase in [3H]kainic acid binding was observed in the medial frontal (Brodmann areas 9, 10 and 46) and eye-movement areas (8), but not in the other regions of schizophrenic brains. No significant correlation between the binding and either age at death, storage of the brains, duration of illness or neuroleptics-free period was observed. These findings suggest that a dysfunction of cortical excitatory amino acidergic transmission may be involved in schizophrenia.

Aged↗