Acute hemorrhagic gastropathy with multiple shallow ulcers and duodenitis caused by a laboratory infection of Helicobacter pylori.
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Adult↗
Biomedical subjects
M Okada
Publications and source records attributed to M Okada.
High prebeta1-HDL levels in hypercholesterolemia are maintained by probucol but reduced by a low-cholesterol diet.
Previous study has shown that prebeta1-HDL levels increase in hypercholesterolemia, or high cholesteryl ester transfer protein (CETP) activity. To determine how prebeta1-HDL levels change after treatment with probucol or by following a low-cholesterol diet, we randomly assigned 24 hypercholesterolemic patients to either the probucol (P), or low-cholesterol diet group (D), and measured prebeta1-HDL levels before and after treatments using native two-dimensional gel electrophoresis. We also examined 12 subjects with normolipidemia (N). At baseline, prebeta1-HDL levels were higher in P (P < 0.05) and D (P < 0.05) than in N (9.2 +/- 4.3, 10.4 +/- 5.5, and 5.9 +/- 2.3 mg/dl apo A-I). After a 4-week treatment, prebeta1-HDL levels were still high in P (10.5 +/- 4.2 mg/dl apo A-I, N.S.), but reduced in D (7.7 +/- 3.0 mg/dl apo A-I, P < 0.001). Delta prebeta1-HDL (Y) was positively correlated with deltaCETP mass (X) in P (y = 7.83x - 1.93; r = 0.584, P < 0.05). In summary, high prebeta1-HDL levels in hypercholesterolemia are maintained by probucol but reduced by a low-cholesterol diet. These findings suggest that prebeta1-HDL levels may be regulated by cholesterol and CETP levels.
Aged↗
Low-density lipoprotein cholesterol can be chemically measured: a new superior method.
The association between elevated levels of low-density lipoprotein (LDL) cholesterol and an increased risk of premature coronary heart disease (CHD) is well documented. Most clinical laboratories estimate LDL cholesterol concentrations according to the Friedewald formula. It provides a relatively reliable estimate of LDL cholesterol concentration, provided the triglyceride concentration is <200 mg/dL. However, the reliability is considerably decreased if the triglyceride concentration is > or =400 mg/dL. The interactions between lipoproteins and surfactants, divalent cations, sugars, and lectins were investigated, and we developed a new assay protocol to chemically measure the LDL cholesterol level in serum that does not require immunoseparation or centrifugation. The assay protocol was evaluated by measuring serum samples obtained from 88 patients and 20 healthy volunteers. The triglyceride levels of the patient samples ranged from 66 to 2199 mg/dL, and the samples were classified as <200 mg/dL (n=36) and > or =400 mg/dL (n=52; 23, 3, and 26 patients had type IIb, type III, and type IV hyperlipoproteinemia, respectively) for comparative studies. The accuracy and precision of our assay protocol fulfilled the criteria of the NCEP Lipid Standardization Panel, and no matrix effect influenced the measurements. The assay protocol is less sensitive to LDL-I than to LDL-II and LDL-III. LDL cholesterol measurements correlated well with those obtained by the ultracentrifugal assay of normotriglyceridemic and hypertriglyceridemic samples. This evidence shows that the results obtained with our assay protocol are superior to those obtained with the Friedewald formula.
Blood Chemical Analysis↗
Arterio-venous extracorporeal membrane oxygenation of fetal goat incubated in artificial amniotic fluid (artificial placenta): influence on lung growth and maturation.
PURPOSE: The authors attempted to achieve extrauterine support of goat fetuses using arteriovenous extracorporeal membrane oxygenation (A-V ECMO) via umbilical vessels, incubated in a warm bath. They hypothesized that this extrauterine support system affected both the lung growth and maturation of goat fetuses. METHODS: Four goat fetuses at about 125 days' gestation (term, 150 days) were placed in this fetal ECMO system. Their four twin fetuses with similar body weights were harvested and examined for baseline data before ECMO (pre-ECMO data). The mean duration of A-V ECMO was 138.8+/-66.9 hours (range, 87 to 237 hours). Tracheal ligation was performed on all four fetuses to prevent the efflux of fetal tracheal fluid and to collect a sample of tracheal fluid daily. The surfactant and electrolytes of the tracheal fluid were analyzed in pre-ECMO (twin fetuses) and during ECMO. The surfactant of lung tissue, and lung weight were analyzed in pre-ECMO (twin fetuses) and after ECMO. Plasma cortisol and T3 levels were also assayed as hormonal factors that affected lung maturation in pre-ECMO and during ECMO. RESULTS: The phospholipid, phosphatidylcholine, and lecithin-sphingomyelin ratio of the tracheal fluid on day 5 during ECMO (15.0+/-7.1 mg/dL, 53.4+/-26.5%, and 6.2+/-7.1) were elevated above pre-ECMO (10.0+/-4.6 mg/dL, 43.0+/-0.6%, and 4.0+/-2.9), but there were no significant differences. The phosphatidylcholine and disaturated phosphatidylcholine of the lung tissue after ECMO were 72.3+/-15.4 mg/g and 19.2+/-8.2 mg/g, which were significantly higher than pre-ECMO (53.7+/-13.9 mg/g and 11.6+/-4.1 mg/g). The Cl- and K+ of the tracheal fluid were 123.5+/-6.2 mEq/L and 3.7+/-0.7 mEq/L on day 1 during ECMO, which were significantly lower than pre-ECMO (141.8+/-2.9 mEq/L and 6.8+/-1.1 mEq/L), but they then recovered to pre-ECMO levels. The wet and dry lung weights after ECMO were 87.8+/-18.0 g and 6.3+/-1.9 g, which were significantly higher than pre-ECMO (49.3+/-5.9 g and 4.2+/-1.3 g). Plasma cortisol levels and T3 levels during ECMO were significantly higher than pre-ECMO. Electron microscopy demonstrated a higher increase of mature type 11 cells in the lungs after ECMO than pre-ECMO. CONCLUSION: This fetal A-V ECMO system in the bath showed a production of surfactant, the maintenance of ion transport by the pulmonary epithelium, an increase in lung weight, and an increase in mature type II cells, resulting in lung growth and maturation.
Amniotic Fluid↗
Proposal for reasonable mediastinal lymphadenectomy in bronchogenic carcinomas: role of subcarinal nodes in selective dissection.
OBJECTIVE: The aims of this study were to reveal the characteristics of skipping N2 lung cancer and to develop a more reasonable approach for dissecting mediastinal lymph nodes. METHODS: Of consecutive 956 patients who were operated on for primary lung cancer from 1986 through 1996, 760 (79.5%) had a diagnosis of non-small cell carcinoma and were subjected to complete resection of the tumor together with hilar and mediastinal lymphadenectomy. RESULTS: Of 141 patients with N2 disease, 53 (37.6%) had skipping metastases. Among 78 patients with N2 cancer of the upper lobe, 37 (47.4%) had skipping metastases affecting upper or aortic mediastinal nodes whereas none of them had skipping metastases affecting lower mediastinal nodes. Among 47 patients with N2 cancer of the lower lobe, 13 (27.7%) had skipping metastases affecting mediastinal nodes. Of these 13 patients, 11 (84.6%) had skipping metastases affecting the subcarinal node. The remaining 2 patients had a huge primary tumor. CONCLUSIONS: Dissection of the upper part of the mediastinum including the aortic regions should be performed regardless of the operative appearance when cancer is located in the upper lobe, but it is not required for lower lobe tumors with negative hilar and subcarinal nodes. Dissection of the subcarinal node in patients with an upper lobe tumor is not routinely needed when the nodes in both the hilum and upper mediastinum are intact. We consider that the subcarinal node is of significance and skipping metastases should be defined as metastases that skip the subcarinal node in addition to N1 nodes.
Adenocarcinoma↗
A canine model of dilated cardiomyopathy induced by repetitive intracoronary doxorubicin administration.
OBJECTIVE: A simple and reproducible large animal model of dilated cardiomyopathy has yet to be developed. This study was performed to establish a canine model of dilated cardiomyopathy. METHODS: Six closed-chest pure-bred beagles weighing 8 to 12 kg (10 +/- 1.9 kg) underwent intracoronary infusion of doxorubicin (Adriamycin). Low-dose (0.7 mg/kg) doxorubicin was infused into the left main coronary artery through a 5F Judkins catheter. Infusions were repeated weekly for 5 weeks. We evaluated the effects on cardiac hemodynamics, chamber size, the neuroendocrine system, and cardiac ultrastructure before and 1 and 3 months after five intracoronary infusions of doxorubicin. RESULTS: Three months after treatment, fractional shortening (mean +/- standard error of the mean) had decreased from 36.5% +/- 0.8% to 21.7% +/- 1.4% (p = 0.0003), and left ventricular ejection fraction had decreased from 71.0% +/- 3.3% to 36.3% +/- 5.5% (p = 0.001). The left ventricular diastolic dimension had increased from 27.8 +/- 0.9 to 35.5 +/- 0.6 mm (p = 0.003), and the left ventricular end-diastolic volume had increased from 27.5 +/- 1.8 to 38.3 +/- 1.9 ml (p = 0.015). Left ventricular end-diastolic pressure had increased from 8.5 +/- 0.9 to 14.5 +/- 1.1 mm Hg (p = 0.01), and the stroke volume had decreased from 16.7 +/- 0.9 to 11.5 +/- 0.4 ml (p = 0.001). During the same period, the plasma norepinephrine concentration also increased from 114 +/- 27.4 to 423 +/- 88.9 pg/ml (p = 0.024), and plasma atrial natriuretic peptide levels increased from 33.8 +/- 7.0 to 76.5 +/- 14.8 pg/ml (p = 0.012). Histologic changes such as myofiber atrophy and cytoplasmic vacuolation, accompanied with interstitial fibrosis, were found predominantly in the left ventricle. CONCLUSION: Repeated intracoronary infusions of doxorubicin represent a simple and reliable technique to produce dilated cardiomyopathy in the dog. This model can be used to evaluate the effects of new therapies, especially surgical treatments such as dynamic cardiomyoplasty and reduction ventriculoplasty, on dilated cardiomyopathy.
Animals↗
Operative approach for multiple primary lung carcinomas.
Of 908 patients who underwent operation for primary lung cancer between January 1985 and June 1996, we considered 57 (6.3%) to have a second primary lung cancer, which was synchronous in 28 cases (3.1%) and metachronous in 29 cases (3.2%). Five-year survival for patients with synchronous and metachronous disease from initial treatment of cancer was 70.3% and 66.0%, respectively. Survival after the development of a metachronous lesion was 32.9% at 5 years. Sixteen of the synchronous second tumors (57%) were detected on preoperative radiography or bronchoscopy and 11 (39%) at the time of operation. Survival of patients at stage I or II from treatment of a synchronous lesion (p = 0.002) and of a metachronous second lesion (p = 0.028) was significantly better compared with those at stage III or IV. Therefore it is important to carefully examine a synchronous lesion before and during the operation of a primary lung cancer and to perform close follow-up surveillance for early detection of a metachronous lesion. In treating multiple lung carcinomas consideration should always be given to performing precise staging, aggressive operative approach for early stage, and oncologically sound parenchymal sparing procedures.
Actuarial Analysis↗
A new artificial placenta with a centrifugal pump: long-term total extrauterine support of goat fetuses.
PURPOSE: We tried long-term total extrauterine support of goat fetuses at high pump flow, which was pulsatile and synchronized with the cardiac cycle and at low oxygen tension in the umbilical artery and vein by use of the new artificial placenta. METHOD: This system consisted of an arteriovenous extracorporeal membrane oxygenation using umbilical artery and vein and a thermoregulated water bath. Five goat fetuses (125 +/- 0.7 days of gestation, 2.0 +/- 0.9 kg) were incubated in lactated Ringer's solution. Mean pump flow rate ranged from 113 +/- 16 to 193 +/- 13 ml/min/kg, and umbilical arterial oxygen tension was maintained at 20 +/- 3 to 23 +/- 5 mm Hg for five fetuses. RESULT: Blood gas analysis echocardiogram showed that fetal circulation and sufficient oxygen consumption could be maintained, and fetal extrauterine support conditions were made as similar as possible to physiologic circulatory conditions. We achieved long-term extrauterine support of goat fetuses up to 237 hours (mean 137 +/- 58 hours). CONCLUSION: We believe that this system can be used for experimental models of the fetus and will come into clinical application for fetal extrauterine support systems and backup systems for fetal operations.
Animals↗
Chitin-graft-poly(2-methyl-2-oxazoline) enhanced solubility and activity of catalase in organic solvent.
Catalase from bovine liver was lyophilized from an aqueous solution containing chitin-graft-poly(2-methyl-2-oxazoline) (3), which was synthesized by the reaction of 52% deacetylated chitin (1) with living poly(2-methyl-2-oxazoline) (2). The rate of consumption of H2O2 in chloroform catalyzed by the lyophilized catalase with 3 was enhanced more than 10 times that by catalase without 3. The dispersibility and solubility of lyophilized catalase with 3 in chloroform were improved in comparison with catalase itself.
Animals↗
Glutamate receptors: brain function and signal transduction.
Glutamate receptors are important in neural plasticity, neural development and neurodegeneration. N-methyl-d-aspartate (NMDA) receptors and alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA)/kainate receptors act as glutamate-gated cation channels, whereas metabotropic receptors (mGluRs) modulate the production of second messengers via G proteins. Molecular studies from our and other laboratories indicated that NMDA receptors and mGluRs exist as multiple subunits (NMDAR1 and NMDAR2A-2D) and multiple subtypes (mGluR1-mGluR8). In light of the molecular diversity of glutamate receptors, we explored the function and intracellular signaling mechanisms of different members of glutamate receptors. In the visual system, retinal bipolar cells receive glutamate transmission from photoreceptors and contribute to segregating visual signals into ON and OFF pathways. The molecularly cloned mGluR6 is restrictedly expressed at the postsynaptic site of ON-bipolar cells in both rod and cone systems. Gene targeting of mGluR6 results in a loss of ON responses without changing OFF responses and severely impairs detecting visual contrasts. Since AMPA receptors mediate OFF responses in OFF-bipolar cells, two distinct types of glutamate receptors effectively operate for ON and OFF responses. mGluR1 and mGluR5 are both coupled to inositol triphosphate (IP3)/calcium signal transduction with an identical agonist selectivity. Single-cell intracellular calcium ([Ca2+]i) recordings indicated that glutamate evokes a non-oscillatory and oscillatory [Ca2+]i response in mGluR1-expressing and mGluR5-expressing cells, respectively. This difference results from a single amino acid substitution, aspartate of mGluR1 or threonine of mGluR5, at the G protein-interacting carboxy-terminal domains. Protein kinase C phosphorylation of the threonine of mGluR5 is responsible for inducing [Ca2+]i oscillations in mGluR5-expressing cells and cultured glial cells. Thus, the two closely related mGluR subtypes mediate diverging intracellular signaling in glutamate transmission.
Animals↗
Characterization of cyclothiazide-enhanced kainate excitotoxicity in rat hippocampal cultures.
Cyclothiazide has been shown to block desensitization of alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA)-preferring receptors and to enhance quisqualate-, AMPA- and kainate-induced neurotoxicity. The pharmacology behind this cyclothiazide-enhanced kainate-induced excitotoxicity was characterized in embryonic rat hippocampal cell cultures. Treatment of cell cultures with a combination of cyclothiazide and kainate for 24 h resulted in excessive neuronal death as measured by the release of lactate dehydrogenase into the culture media. Cyclothiazide produced a leftward shift of the kainate dose-response curve and enhanced the maximum response of kainate excitotoxicity. AMPA-preferring receptor antagonists, 2,3-dihydroxy-6-nitro-7-sulphamoyl-benzo(F)quinoxaline(NBQX) and 1-(4-amino-phenyl)-4-methyl-7,8-methylenedioxy-5H-2,3-benzodiazepine (GYKI 52466) blocked cyclothiazide-enhanced kainate toxicity completely, and cyclothiazide increased the IC50S for NBQX and GYKI 52466 against kainate toxicity. The N-methyl-D-aspartate (NMDA) antagonist, (+)-5-methyl-10,11-dihydro-5H-dibenzo[a,d] cyclohepten-5,10-imine (MK801) also blocked cyclothiazide-enhanced kainate toxicity, but only partially. Cyclothiazide also increased the IC50 for MK801 against kainate toxicity. These data suggest that cyclothiazide enhances both AMPA-preferring receptor- and NMDA receptor-mediated toxicity in kainate-induced toxicity in embryonic rat hippocampal cultures.
Animals↗
Foot venous pressure measurement for evaluation of lower limb venous insufficiency.
PURPOSE: Foot venous pressure measurement is considered to be useful for assessing lower limb venous insufficiency, because venous hypertension is the main factor predisposing to venous insufficiency. In this study, we investigated the utility of foot venous pressure measurement in the evaluation of venous insufficiency. METHODS: A total of 148 limbs of 101 patients with venous insufficiency associated with varicose veins and treated over 5 years were studied. The measurements assessed were percentage decrease in foot venous pressure with manual calf compression (%drop), rate of increase in foot venous pressure during a 4-second period after release of compression (4SR%), and time to 50% recovery of foot venous pressure (RT50). RESULTS: A higher incidence of skin changes (clinical, etiologic, anatomic, and pathophysiologic classification classes 4 to 6) caused by venous insufficiency was associated with %drop, 4SR%, and RT50 values. Skin changes were found in more than 50% of the limbs with a %drop less than 50%, 4SR% more than 50%, or RT50 less than 4 seconds. After tourniquets were applied to occlude the superficial veins, limbs with severe below-knee deep venous reflux (%drop 60.3 +/- 14.6, 4SR% 36.7 +/- 30.2, RT50 13.9 +/- 14.7) showed significantly worse values than those with no reflux (%drop 79.9 +/- 3.2, 4SR% 8.1 +/- 3.1, RT50 48.9 +/- 17.9) or with mild above-knee reflux (%drop 77.0 +/- 5.0, 4SR% 7.1 +/- 3.2, RT50 46.9 +/- 26.7). After sclerotherapy or surgical treatment, including deep venous reconstruction for severe below-knee reflux, all limbs showed significant improvement in clinical manifestations and foot venous pressure values (%drop 68.1 +/- 7.5 to 76.5 +/- 5.8, 4SR% 33.1 +/- 12.9 to 12.7 +/- 7.6, RT50 7.5 +/- 4.2 to 20.1 +/- 6.5). CONCLUSION: Foot venous pressure measurements showed a good correlation with clinical severity and degree of venous reflux and were very useful for evaluating the outcome of therapy for venous insufficiency.
Adult↗
Surgical treatment for transvenous tumor extension into the heart: four cases.
From 1984 to 1996, four patients with transvenous intracardiac tumor extension underwent operations in the Kobe University Hospital. The primary tumors of two were intravenous leiomyomatoses originating from the uterus; a third patient had invasive thymoma, and the fourth patient had clear cell sarcoma of the kidney. In 1985, one patient had a curative, staged resection. One-stage operations were carried out in three patients, and all intracardiac tumors were successfully resected en bloc with the primary tumors under conditions of electrical ventricular fibrillation and mild hypothermia. Combined venous reconstructions were necessary for en bloc resection in three cases. Two patients with malignancy received postoperative chemoradiotherapy, and all four patients were discharged uneventfully from our hospital. We consider radical resection with curative intent only for patients with tumors extending into the heart. In these cases, a one-stage operation is preferable, and electrical ventricular fibrillation with mild hypothermia is a recommended method of circulatory assist because of its simplicity.
Adult↗
Effects of carbamazepine on hippocampal serotonergic system.
To establish the mechanism of action of the antiepileptic and psychotropic effects of carbamazepine (CBZ), its effects on serotonin (5-HT) transmission, metabolism and re-uptake activity in the rat hippocampus were studied. After acute and chronic administrations of 25 mg/kg CBZ, the plasma concentration of CBZ was found to be within the therapeutic range, whereas both acute and chronic administrations of 50 and 100 mg/kg CBZ resulted in a supratherapeutic plasma concentration. Acute administration of the therapeutic dose of CBZ resulted in an increase in the hippocampal extracellular and total level of 5-HT, its metabolite, 5-hydroxydoleacetic acid (5-HIAA) and its precursor, 5-hydroxytryptophan (5-HTP). The acute administration of 50 mg/kg CBZ resulted in an increase in the hippocampal levels of extracellular 5-HT and 5-HIAA as well as in the total levels of 5-HTP, whereas hippocampal levels of extracellular 5-HTP, total 5-HT and 5-HIAA remained unaffected. CBZ at a dose of 100 mg/kg decreased the levels of all of these substances. After chronic administration, 25 mg/kg/day CBZ increased hippocampal total levels of 5-HT, 5-HTP and 5-HIAA, whereas 100 mg/kg/day CBZ decreased all of these total levels. CBZ at a dose of 50 mg/kg/day decreased total levels of 5-HT, however neither total levels of 5-HIAA nor 5-HTP were affected. Both therapeutic and supratherapeutic plasma concentrations of CBZ inhibited 5-HTP accumulation, and did not affect 5-HT re-uptake activity in vitro. These results suggest that a therapeutic concentration of CBZ enhances 5-HT turnover and transmission, whereas a supratherapeutic concentration of CBZ inhibits 5-HT turnover and transmission without affecting 5-HT re-uptake activity. These effects of CBZ on serotonergic systems may be, at least partially, involved in the mechanisms of action of CBZ.
5-Hydroxytryptophan↗
Recombinant human erythropoietin for late-onset anemia after allogeneic bone marrow transplantation.
Recombinant human erythropoietin (rHu EPO) has been reported to accelerate early erythroid reconstitution after bone marrow transplantation (BMT). We conducted a pilot study on rHu EPO for late-onset anemia in 9 patients after allogeneic BMT. The patients achieved initial erythropoietic recovery (hemoglobin (Hb) range 9.1-13.4, mean 10.8 g/dl), but then developed transplant-related anemia (Hb range 6.3-9.7, mean 8.2 g/dl) more than 50 days after BMT. This type of anemia was related to graft-versus-host disease (GVHD), cytomegalovirus infection, and/or impaired EPO secretion. The patients received 3,000 or 12,000 U of rHu EPO subcutaneously three or seven times weekly. Hb levels increased by more than 2 g/dl in 6 of the 9 patients, but were unchanged in the 3 patients with severe GVHD. These findings suggest that in some cases rHu EPO is effective for the treatment of late-onset anemia after BMT.
Adult↗
Myelodysplastic syndrome with B cell clonality in a patient five years after renal transplantation.
A female patient received a renal transplantation from an unrelated cadaver donor, and five years later developed myelodysplastic syndrome (MDS) with immunological abnormalities. Chromosomal analysis showed trisomy 8 in bone marrow cells. FISH analysis indicated that trisomy 8 was present in 4% of CD19 + cells, suggesting that the MDS clone involved B lymphocytes. Polymerase chain reaction of the human androgen receptor gene indicated B cell clonality (54%) and granulocyte clonality (63%). There have been no previous reports of secondary MDS following renal transplantation in which the MDS clone involved the B cell lineage. The abnormal MDS B cell clone may have caused the immunological abnormalities.
B-Lymphocytes↗
Three-month effects of candesartan cilexetil, an angiotensin II type 1 (AT1) receptor antagonist, on left ventricular mass and hemodynamics in patients with essential hypertension.
Using cine magnetic resonance imaging (MRI) and echocardiography, we investigated the effects of candesartan cilexetil, a specific angiotensin II type 1 (AT1) receptor antagonist, on left ventricular (LV) mass and hemodynamics in patients with essential hypertension. Ten patients (four men and six women) with essential hypertension received candesartan cilexetil 2-8 mg/day orally for 8-12 weeks. After drug administration, systolic blood pressure (BP) decreased from 178.9 +/- 17.2 mmHg (mean +/- SD) to 150.2 +/- 14.3 mmHg (P < 0.0001) and diastolic BP from 101.4 +/- 6.5 mmHg to 87.8 +/- 11.9 mmHg (P = 0.0021). Both MRI and echocardiography revealed a significant decrease in LV mass index (LVMI) after candesartan cilexetil. MRI indicated that LVMI decreased from 111.3 +/- 31.3 g/m2 to 102.6 +/- 32.1 g/m2 (P = 0.0484) and echocardiography that LVMI decreased from 123.9 +/- 31.1 g/m2 to 115.8 +/- 31.4 g/m2 (P = 0.0316). Total systemic vascular resistance decreased significantly during treatment with candesartan cilexetil in both MRI and echocardiography assessment, from 1847.2 +/- 636.3 dynes.s.cm-5 to 1540.4 +/- 432.0 dynes.s.cm-5 (P = 0.0034) on MRI and from 1820.4 +/- 318.8 dynes.s.cm-5 to 1659.0 +/- 317.7 dynes.s.cm-5 (P = 0.0060) on echocardiography. These findings suggest that candesartan cilexetil 2-8 mg/day orally for 8-12 weeks is beneficial in the regression of cardiac hypertrophy in patients with essential hypertension.
Adult↗
Effects of Ca2+ channel antagonists on striatal dopamine and DOPA release, studied by in vivo microdialysis.
1. To elucidate the mechanisms regulating the release of striatal dopamine and its precursor, 3,4-dihydroxyphenylalanine (DOPA), we determined the effects of various Ca2+ channel antagonists, an N-type Ca2+ channel antagonist, omega-conotoxin GVIA, a P-type Ca2+ channel antagonist, omega-agatoxin IVA, and a Q-type Ca2+ channel antagonist, omega-conotoxin MVIIC, on the basal and Ca2+- and K+-evoked release of striatal dopamine and DOPA, by use of in vivo microdialysis. 2. Omega-conotoxin GVIA strongly inhibited striatal basal dopamine release (IC50 = 0.48 nM), whereas this toxin only weakly modulated basal striatal DOPA release (IC50 = 9.55 nM). Neither omega-agatoxin IVA nor omega-conotoxin MVIIC affected the basal striatal release of dopamine and DOPA. 3. Omega-conotoxin GVIA strongly inhibited Ca2+-evoked striatal dopamine release (IC50 = 0.40 nM), whereas Ca2+-evoked striatal DOPA release only was weakly modulated (IC50 = 10.51 nM). Neither omega-agatoxin IVA nor omega-conotoxin MVIIC affected the Ca2+-evoked release of striatal dopamine and DOPA. 4. Both omega-agatoxin IVA and omega-conotoxin MVIIC inhibited the K+-evoked release of striatal dopamine (IC50 of omega-agatoxin IVA = 2.65 nM; IC50 of omega-conotoxin MVIIC = 12.54 nM) and DOPA (IC50 of omega-agatoxin IVA = 0.15 nM; IC50 of omega-conotoxin MVIIC = 3.05 nM), whereas omega-conotoxin GVIA had no effect on the K+-evoked release of striatal dopamine and DOPA. 5. An increase in the extracellular Ca2+ and K+ concentrations (Ca2+- and K+-evoked stimulation) did not affect tyrosine hydroxylase activity in vivo. 6. These findings suggest that striatal DOPA release is neurotransmitter-like and that, unlike the mechanisms of striatal dopaminergic transmission, this striatal DOPA transmission is at least partly regulated by voltage-sensitive Ca2+ channels.
Animals↗