[A case of jejunal adenocarcinoma with anxiety disorder].
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Adenocarcinoma↗
Biomedical subjects
Y Kiuchi
Publications and source records attributed to Y Kiuchi.
Exercise intensity determines the magnitude of IOP decrease after running.
The effects of the intensity, duration and quantity (intensity x duration) of exercise on the reduction of intraocular pressure (IOP) in healthy and physically fit individuals were studied. Five minutes after 15 minutes of exercise at 70%, 55% and 40% of maximum exercise load (%HRmax) the IOP decreased 4.3 +/- 0.7 mmHg, 2.2 +/- 0.7 mmHg and 0.6 +/- 0.5 mmHg, respectively. The magnitude of IOP reduction increased with exercise load. Running for 7.5 minutes at 70%HRmax decreased IOP comparable to 15 minutes of running at the same exercise load (4.4 +/- 0.6 mmHg). Twenty-five minutes of running at 40%HRmax is almost the same quantity of exercise as 15 minutes of running at 70%HRmax. However, the former did not result in IOP reductions to equal the latter (2.3 +/- 0.5 vs 4.4 +/- 0.6 mmHg). The amount of IOP reduction after short-term exercise seems to depend on the intensity of exercise, not on the duration of exercise or the quantity of exercise.
Adult↗
[Antidepressant and antimanic drugs--pharmacological mechanisms and pharmacokinetics].
In Japan, fifteen drugs, including tricyclic and non-tricyclic antidepressants or an MAO inhibitor, are clinically available for treatment of depression. However, the pharmacological mechanism(s) of their antidepressive effect remain uncertain. "Receptor hypothesis" that functional changes of monoamine receptors after chronic treatment, such as down-regulation of beta-adrenoceptor or 5-HT2 receptor, bring about a therapeutic effect, seems to be unsatisfactory. Recent studies focus on interaction between antidepressants and intracellular signal transduction pathways. For effective and safe uses of antidepressants, especially in aged patients or those with hepatic and renal diseases, pharmacokinetics such as distribution, protein binding and metabolism must be well understood. In this paper, pharmacokinetic characteristics of antidepressants are also reviewed.
Antidepressive Agents↗
Role of calcium ions in dopamine release induced by sodium cyanide perfusion in rat striatum.
We have previously reported a transient and remarkable increase in dopamine (DA) release in the rat striatum during application of 2 mM sodium cyanide (NaCN) through a brain microdialysis membrane. In the present study we examined the involvement of extracellular Ca2+ in this response. Rats were divided into 4 groups. In the NaCN group a microdialysis probe inserted into the striatum was perfused with Ringer's solution containing 2 mM NaCN for 60 min. The Ca2+ free + NaCN group was subjected to perfusion with NaCN dissolved in Ca2+ free Ringer's solution, and the CdCl2 + NaCN group with the same plus 0.3 mM CdCl2 (a non-specific Ca2+ channel blocker). In the NaCN and Ca2+ free + NaCN groups DA levels in the dialysates increased to 36- and 44-fold of the control level, respectively, while this was suppressed to only a 16-fold increase in the CdCl2 + NaCN group. In response to a 100 mM KCl perfusion given 3 hr later DA levels were increased (22-fold) in the control group. On the other hand this response was inhibited in the NaCN group (3-fold), but not in the other two groups. An in vitro study with striatal slices showed a gradual increase in intracellular Ca2+ during incubation with 2 mM NaCN. These results suggest that excessive influx of extracellular Ca2+ during NaCN perfusion may contribute partly to the increase in the extracellular DA level in the striatum, and also to the suppression of a DA increase in response to high K+ stimulation observed 3 hr later.
Animals↗
Sustained increase in adrenergic activity in gerbil striatum following transient ischemia.
We investigated the changes in striatal monoaminergic functions, focusing on the release and metabolism, in a cerebral ischemic model induced by a 5-min bilateral occlusion of the carotid arteries (BOCA) and reperfusion in anesthetized gerbils. In the microdialysis study, the striatal extracellular level of dopamine (DA) markedly increased (144-fold) immediately after BOCA. Although norepinephrine (NE) and 5-hydroxytryptamine (5-HT) could not be detected in the dialysates throughout the baseline period, they increased to detectable levels after BOCA. On the contrary, the tissue contents of NE and 5-HT decreased or tended to decrease up to 4 hr following reperfusion. Striatal DA contents did not show any changes in the early period after ischemia-reperfusion and slightly increased at 4 hr or later. Tissue contents of 3-methoxytyramine (3-MT), a metabolite of DA by catechol-O-methyltransferase (COMT), increased 0 and 5 min after reperfusion. Normethanephrine (NMN), which is a metabolite of NE by COMT, also increased not only 5 min after but also up to 4 hr after ischemia-reperfusion, indicating a sustained increase in NE release. These results suggested that the neuronal activity of NE, which is supposed to exert a protective effect on ischemic damage, was enhanced for a longer period than that of DA after transient ischemia.
Animals↗
Effects of the contents of dietary crude protein on growth rate and NK activity.
The relationship between body weight gain and food intake was examined using 3 strains of mice, C3H/He, C57BL/6 and A/J mice, that were fed 4 kinds of diets differing in crude protein contents. Body weight gain of the mice fed the diet containing 3% protein was extremely small, while that of the mice fed the diet containing 40% protein was smaller than that of the mice fed the diet containing 10% or 20% protein. Mice were shown to possess a characteristic ability to intake an almost constant amount of calories irrespective of crude protein contents in diets, with some exceptions. These experimental results indicate that crude protein intake plays an important role for body weight gain. It was also assumed that energy consumption in C57BL/6 mice fed the 40% protein diet was accelerated because of excessive protein intake. Normal NK activity and antibody responses to SRBC were maintained at the age of 12 weeks in all the strains of mice fed the different diets.
Animal Nutritional Physiological Phenomena↗
Melatonin does not increase IOP significantly in rabbits.
New Zealand white rabbits have a circadian rhythm of intraocular pressure; pressure is higher during the dark than during the light. We explored the possibility that the dark phase increase of serum and/or ocular melatonin plays a role in regulating the rhythm of intraocular pressure. Exogenous melatonin was delivered by four routes: topical application (0.1 and 10 micrograms), intravenous injection (1 microgram), intravitreal injection (9 micrograms) and intra-arterial infusion (50 ng and 1 microgram). Melatonin delivered by these routes did not increase intraocular pressure. We also measured the concentration of melatonin in the aqueous after unilateral intra-arterial infusion to confirm that melatonin delivered by this route reached the eye. The concentration was 419 +/- 99 and 109 +/- 17 pg/ml (n = 8, p < 0.025) in the ipsilateral and contralateral eyes, respectively. The concentration of melatonin in the aqueous after intra-arterial infusion of saline was less than the sensitivity of the assay (< 16 pg/ml, n = 6). The results of these experiments indicate that melatonin does not increase IOP significantly under the experimental conditions employed in this study.
Administration, Topical↗
Binding of antiglaucomatous drugs to synthetic melanin and their hypotensive effects on pigmented and nonpigmented rabbit eyes.
The binding of ocular hypotensive drugs to synthetic melanin was studied spectrophotometrically in vitro. The ocular hypotensive effects of the drugs, namely, timolol, befunolol, carteolol, pilocarpine, epinephrine, prostaglandin A2, F2 alpha and E2, also were compared in vivo on eyes of pigmented and albino rabbits. At an initial concentration of 10(-4) M, each of the three beta-blockers exhibited a binding rate of 80-85% as compared to only 40% for pilocarpine and 50% for epinephrine. Almost none of the prostaglandins were found to bind to synthetic melanin. Topically applied, 0.5% timolol and 3% pilocarpine significantly lowered the intraocular pressure in albino but not in pigmented rabbits. Epinephrine (1%) caused a significant reduction in the intraocular pressure both in albino and pigmented rabbits; however, the maximum reduction was greater in albino than in pigmented rabbits. Intraocular pressure was reduced to the same extent and with a similar time-course in both albino and pigmented rabbits by 0.02% prostaglandin A2, F2 alpha and E2. These findings show that several ocular hypotensive drugs bind to melanin and suggest that this process can modify the extent of their pharmacological effects when tested in a single dose, or the time-course of their effects when used to treat chronic conditions.
Adrenergic beta-Antagonists↗
Ophthalmic diseases in bedridden patients with severe dementia.
Ophthalmologic examinations were performed on the 176 eyes of 88 bedridden patients with severe dementia. There were some pathologic changes in the external and anterior segments of 93 eyes. We observed infectious external and anterior segment eye diseases in 80 of these 93 eyes (86.0%). Fundus diseases were found in 34 eyes, but treatment was not necessary. Infectious eye diseases appeared to be the most prevalent ocular problem in these patients. Cultures of conjunctival swabs commonly demonstrated Staphylococcus aureus. No differences were noted in tear secretion rate or lysozyme concentrations in tears between eyes with and without infection. The blinking frequency was significantly reduced in infected eyes compared to normal eyes. Failure of the lacrimal drainage system was observed more often in infected eyes than in normal eyes. This study demonstrated that bedridden patients with severe dementia develop infectious eye diseases easily, to which stasis of tear flow seems to predispose. In caring for bedridden patients with severe dementia, ophthalmologists must be concerned with controlling infectious eye diseases.
Adult↗
Effect of local cyanide perfusion on rat striatal extracellular dopamine and its metabolites as studied by in vivo brain microdialysis.
To investigate in vivo effects of energy failure on functions of dopaminergic neurons, we administered 0 (control), 0.2, 1 or 2 mM sodium cyanide (NaCN) dissolved in Ringer's solution for 60 min into the rat striatum through a brain microdialysis membrane. During NaCN perfusion, a transient and concentration-dependent increase in dopamine (DA) levels in the dialysate was observed. The maximum DA level during 2 mM NaCN perfusion was found to be 63-fold higher than the control levels. Leves of 3,4-dihydroxyphenylacetic acid and homovanillic acid were continuously lowered during and after NaCN perfusion. These data suggest that suppression of ATP production by NaCN induces an abrupt and remarkable increase in dopamine release from the nerve terminal in the striatum.
3,4-Dihydroxyphenylacetic Acid↗
WHT/Ht mouse contains plasma cells in the thymus.
Numerous plasma cells and B cells were present in the thymuses of aged WHT/Ht mice. Plasma cells containing IgG and the follicle-like structure were present in the cortex and medulla, respectively. In these respects, WHT/Ht strain of mice is unique and interesting for studies on lymphocyte development.
Animals↗
Rabbits have a circadian rhythm of aqueous humor cyclic AMP.
Rabbits have circadian rhythms of intraocular pressure (IOP) and aqueous flow. The dark phase increases of IOP and flow are associated with increased aqueous cyclic AMP. If the daily rhythm of aqueous cyclic AMP reflects changes of tissue levels of cyclic AMP which mediate one of the mechanisms which control the rhythms of IOP and aqueous flow, then it must be a circadian rhythm as are the rhythms of IOP and flow. A recent report showed no change in aqueous cyclic AMP from 2 hrs before to 2 hrs after the beginning of subjective dark in animals housed in constant dark. Because the increase of intraocular pressure at the same times did persist in constant dark, the authors concluded that a significant portion of the circadian rhythm of IOP is unrelated to cyclic AMP mediated ocular mechanisms. However, if an inhibitor of cyclic nucleotide phosphodiesterase is added to aqueous samples after harvesting by paracentesis, it is possible to show that most of the increase of aqueous cyclic AMP from mid-light phase to mid-dark phase persists in constant dark and is therefore likely to reflect a circadian rhythm of tissue cyclic AMP.
1-Methyl-3-isobutylxanthine↗
Do alpha-adrenergic receptors participate in control of the circadian rhythm of IOP?
The alpha 2-adrenergic antagonists, yohimbine and rauwolscine, and the alpha 1-adrenergic antagonist, bunazosin, were used to explore the role of alpha-adrenergic receptors in the regulation of the circadian rhythms of intraocular pressure and aqueous flow in New Zealand white rabbits. Blockade of alpha 2-adrenergic receptors with yohimbine or rauwolscine produced small decreases in intraocular pressure during both light and dark phases. Rauwolscine had no effect on aqueous flow during the light or dark, but it increased the concentration of norepinephrine in the aqueous during both light and dark. These observations are difficult to reconcile with earlier suggestions that increased sympathetic input to the eye increases intraocular pressure and aqueous flow during the dark. The role of alpha 2-adrenergic receptors in the control of the circadian rhythm of intraocular pressure is unclear. Blockade of alpha 1-adrenergic receptors with bunazosin produced a dose-dependent reduction of IOP during the dark phase of the circadian cycle, a smaller reduction during the light phase, and no reduction during either light or dark in rabbits after superior cervical ganglionectomy or preganglionic section of the cervical sympathetic trunk (decentralization). Bunazosin decreased pupil diameter during the dark phase but had no effect on aqueous flow. Because it is unlikely that alpha 1-adrenergic blockade increased outflow facility or uveoscleral outflow, the mechanism for the role of alpha 1-adrenergic receptors in the control of the circadian rhythm of intraocular pressure in rabbits remains to be identified.
Adrenergic alpha-Antagonists↗
Primary orbital malignant lymphoma: a clinicopathology study of 17 cases.
We investigated the clinicopathologic characteristics of 17 patients (13 men and 4 women) with primary orbital malignant lymphoma using the Working Formulation. Most of the cases belonged to the low-grade malignancy group, and more women than men were in the histologically high-grade malignancy group. The phenotype of the tumor cells was investigated immunohistochemically. All cases showed the monoclonal feature of a B-cell lineage. All patients received chemotherapy with or without radiotherapy. Of 16 subjects, 15 achieved a complete remission; none of these patients has had a recurrence since the completion of the initial therapy (range of follow-up from 16 months to 10 years). One patient died.
Adult↗
Morphological analysis of neovascularization at early stages of rat splenic autografts in comparison with tumor angiogenesis.
This study was undertaken to reveal the neovascularization at early stages of splenic autografts three-dimensionally, to illustrate the differences between it and tumor angiogenesis, and to establish its origin. Early vascular formation after transplantation of the rat spleen or Walker tumor into the major omentum was examined by using a video macroscope, vascular casting methods and the organ culture technique. A complex vascular network layer (vascular cortex) was first formed beneath the capsule of an autograft; later, vascular buds grew from this network toward the necrotic center. They anastomosed and changed into a form resembling withered twigs (vascular medulla). Tumor angiogenesis did not present such morphological features and was characterized by capillary loop formation with a columnar vertex resembling an "inverted V". This fundamental structure did not change throughout angiogenesis except for dilation and irregularity of vascular diameter. The organ culture technique demonstrated that the preliminary vasculature was formed in splenic autografts by regeneration of preexisting vessels in the graft and not by invading capillaries. Transmission electron microscopy showed that the cells present had characteristics of sinus endothelial cells. These results suggest that preexisting sinus endothelial cells rearrange themselves after devascularization and reconstruct a new vasculature that anastomoses with the penetrating capillaries. This mechanism establishes vascular circulation at an early stage, and accelerates regeneration of the splenic autograft before complete necrosis.
Animals↗
Guanosine 5'-triphosphate converts some populations of propylbenzilylcholine mustard-sensitive muscarinic cholinoceptor sites to sites resistant to the drug in intestinal smooth muscle.
From functional studies with propylbenzilylcholine mustard (PrBCM), we reported that there coexist PrBCM-sensitive and PrBCM-resistant muscarinic cholinoceptor mechanisms in guinea pig taenia caecum. We investigated the interrelationship between these two cholinoceptor mechanisms using an in vitro receptor binding assay with [3H]quinuclidinyl benzilate (QNB) and [3H]PrBCM. Pretreatment of the muscle strips with 300 nM PrBCM (in vivo alkylation) for 10-50 min resulted in progressive decreases of the number of the maximum [3H]QNB binding sites. However, a prolongation of the period of in vivo alkylation up to 90 min was accompanied with no further loss in the binding sites. Under these conditions, there is no significant change in the affinity of [3H]QNB for the binding sites. The concentration of carbachol required to displace 50% of the bound [3H]QNB was larger in membranes obtained from the tissues that had been alkylated in vivo with PrBCM for 50 min than that from control strips, but was not altered when the pretreatment with the drug was carried out after homogenization (in vitro alkylation). When GTP was added during in vitro alkylation, the affinity of carbachol was lower than that in control membranes, as observed when in vivo alkylation was carried out. In the presence of guanine nucleotide, PrBCM thus appears to recognize two distinct populations or states of muscarinic receptors.
Alkylation↗
The response to acoustic stimulation and the changes in brain amine levels after repeated administration of beta-phenylethylamine in rats.
Reverse tolerance to stereotyped behavior was induced after repeated administration of beta-phenylethylamine (PEA) (50 mg/kg, i.p., daily for 10 days) in rats. The reverse tolerance was maintained for at least 4 weeks after the last administration. We studied the effects of acoustic stimulation on locomotor activity 2 days and 4 weeks after withdrawal from PEA and measured the changes in brain monoamine levels 4 weeks after the withdrawal. Locomotor activity during acoustic stimulation was increased in the saline treated group, and this response was unaffected after repeated PEA treatment. Four weeks after withdrawal, significant increases in noradrenaline levels in the cerebral cortex and decreases in 5-hydroxytryptamine levels in the hypothalamus were found. The effects of acoustic stimulation on locomotor activity and the changes in brain monoamine levels were different from those of methamphetamine treatment obtained in our previous study. In conclusion, it may be suggested that the response to acoustic stimulation after repeated PEA administration in rats cannot be a model for abnormal responsiveness to environmental stimulation that is observed in chronic paranoid schizophrenics.
Acoustic Stimulation↗
Antinucleolar autoantibody induced in mice by mercuric chloride. A genetic study.
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Animals↗