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1.
Rev Sci Instrum ; 93(5): 053502, 2022 May 01.
Article in English | MEDLINE | ID: mdl-35649751

ABSTRACT

We developed a steady-state high-density plasma source by applying a hollow cathode to a cascade arc discharge device. The hollow cathode is made of a thermionic material (LaB6) to facilitate plasma production inside it. The cascade arc discharge device with the hollow cathode produced a stationary plasma with an electron density of about 1016 cm-3. It was found that the plasma source produces a strong pressure gradient between the gas feed and the vacuum chamber. The plasma source separated the atmospheric pressure (100 kPa) and a vacuum (100 Pa) when the discharge was performed with an argon gas flow rate of 5.0 l/min and a discharge current of 40 A. An analysis of the pressure gradient along the plasma source showed that the pressure difference between the gas feed and the vacuum chamber can be well described by the Hagen-Poiseuille flow equation, indicating that the viscosity of the neutral gas is the dominant factor for producing this pressure gradient. A potential profile analysis suggested that the plasma was mainly heated within cylindrical channels whose inner diameter was 3 mm. This feature and the results of the pressure ratio analysis indicated that the temperature, and, thus, viscosity, of the neutral gas increased with the increasing number of intermediate electrodes. The discharge characteristics and shape of the hollow cathode are suitable for plasma window applications.

2.
JDR Clin Trans Res ; 2(2): 187-197, 2017 Apr.
Article in English | MEDLINE | ID: mdl-30931780

ABSTRACT

There has been a growing interest in the association between the number of teeth and dietary intake in older populations. However, people around the age of 80 y have frequently lost most of their teeth, and dental prostheses replacing the missing teeth play an important role in masticatory function. Therefore, masticatory function cannot be evaluated by the number of teeth alone. The occlusal force of the complete dental arches is an index of masticatory function, reflecting not only the number of teeth, but the effect of removable dentures. The purpose of this cross-sectional study was to determine the relative importance of the number of teeth and occlusal force in association with dietary intake in 80-y-old Japanese people. This study included 760 community-dwelling Japanese people aged 79 y to 81 y. The authors measured bilateral maximal occlusal force in the intercuspal position using pressure-sensitive sheets. Removable denture wearers kept their dentures in place during the measurements. Energy-adjusted food groups and nutrient intake during the preceding month were assessed by a brief self-administered diet history questionnaire. The authors assessed linear trends in food and nutrient intake in relation to the number of teeth and occlusal force after adjusting for gender and socioeconomic status (education level, financial status, family structure, resident area and BMI). P values of < 0.05 were considered to be statistically significant. The authors found that the number of teeth was not associated with the energy-adjusted intake of any food group examined. In contrast, a decline in occlusal force was significantly associated with a lower intake of vegetables, fish and shellfish, protein, polyunsaturated fatty acids, dietary fiber and most vitamins and minerals ( P for trend < 0.05). We conclude that food and nutrient intake was more closely associated with occlusal force than the number of teeth in community-dwelling Japanese people aged 79 y to 81 y. Knowledge Transfer Statement: This cross-sectional study of older Japanese people showed that, after controlling for considerable covariates, occlusal force rather than the number of teeth is positively associated with energy-adjusted intake of vegetables, fish and shellfish, protein, polyunsaturated fatty acids, dietary fiber and most of vitamins and minerals. This means that reduced occlusal force may unconsciously lead older people toward a habitual unhealthy dietary intake. Older people have frequently lost most of their teeth and require prosthetics to restore masticatory function. Bilateral occlusal force is therefore a better measure of masticatory function than the number of remaining teeth. Our findings suggest that prosthetic rehabilitation is a significant factor in the prevention and management of chronic diseases and frailty through better dietary intake in older populations.

3.
J Oral Rehabil ; 44(1): 22-29, 2017 Jan.
Article in English | MEDLINE | ID: mdl-27748531

ABSTRACT

The sense of taste plays a pivotal role for personal assessment of the nutritional value, safety and quality of foods. Although it is commonly recognised that taste sensitivity decreases with age, alterations in that sensitivity over time in an old-old population have not been previously reported. Furthermore, no known studies utilised comprehensive variables regarding taste changes and related factors for assessments. Here, we report novel findings from a 3-year longitudinal study model aimed to elucidate taste sensitivity decline and its related factors in old-old individuals. We utilised 621 subjects aged 79-81 years who participated in the Septuagenarians, Octogenarians, Nonagenarians Investigation with Centenarians Study for baseline assessments performed in 2011 and 2012, and then conducted follow-up assessments 3 years later in 328 of those. Assessment of general health, an oral examination and determination of taste sensitivity were performed for each. We also evaluated cognitive function using Montreal Cognitive Assessment findings, then excluded from analysis those with a score lower than 20 in order to secure the validity and reliability of the subjects' answers. Contributing variables were selected using univariate analysis, then analysed with multivariate logistic regression analysis. We found that males showed significantly greater declines in taste sensitivity for sweet and sour tastes than females. Additionally, subjects with lower cognitive scores showed a significantly greater taste decrease for salty in multivariate analysis. In conclusion, our longitudinal study revealed that gender and cognitive status are major factors affecting taste sensitivity in geriatric individuals.


Subject(s)
Cognitive Dysfunction/physiopathology , Feeding Behavior/physiology , Geriatric Assessment , Taste Perception/physiology , Taste/physiology , Aged , Aged, 80 and over , Diet , Female , Follow-Up Studies , Food Preferences , Frail Elderly , Humans , Japan/epidemiology , Longitudinal Studies , Male , Nutrition Assessment , Reproducibility of Results
4.
J Oral Rehabil ; 42(11): 828-32, 2015 Nov.
Article in English | MEDLINE | ID: mdl-26059645

ABSTRACT

Although the shortened dental arch (SDA) concept has been known to all over the world, acceptance of the SDA concept as an oral health standard can be questionable from the patients' point of view, even if it is biologically reasonable. Furthermore, because the health insurance system covers removable partial dentures (RPDs) for all citizens in Japan, SDA patients seem to prefer to receive prosthetic treatment to replace the missing teeth. However, there were few field surveys to investigate the usage rate of RPDs in Japan. The purpose of this study was to determine the usage rate of RPDs in older Japanese subjects and to investigate the factors related to the usage of RPDs. Partially edentate participants (n = 390) were included in this study. Oral examinations were conducted to record several indices. The Cochran-Armitage trend test was used to evaluate the relationship between the number of missing teeth and the usage rate of RPDs. Chi-squared tests and logistic regression analysis were conducted to evaluate the factors related to the usage rate of RPDs. Usage of RPDs had a significantly positive association with the number of missing distal extension teeth and bilaterally missing teeth. The usage rate of RPDs increased as the number of missing distal extension teeth increased (P for trend < 0·001). The conclusion of this study was that participants with missing distal extension teeth had higher usage rates of RPDs than other participants, and the usage rate increased as the number of missing distal extension teeth increased.


Subject(s)
Dental Arch/physiology , Denture, Partial, Removable/statistics & numerical data , Jaw, Edentulous, Partially/rehabilitation , Aged , Female , Humans , Japan , Logistic Models , Male , Middle Aged , Risk Factors
5.
Int J Geriatr Psychiatry ; 28(3): 233-41, 2013 Mar.
Article in English | MEDLINE | ID: mdl-22535710

ABSTRACT

OBJECTS: Identification of biomarkers for Alzheimer's disease (AD) is important for its early diagnosis and prevention and a key in advancing our understanding of its pathophysiology. The aim of this study was to determine whether systemic inflammatory interleukin-1ß (IL-1ß) and interleukin-6 (IL-6) as well as hypertension (HT), diabetes mellitus (DM), and body mass index (BMI) are predictors of AD. METHODS: We performed a 10-year follow-up study on 133 elderly who were institutionalized in a nursing home. The associations of IL-1ß and IL-6 at both rest and agitation, as well as HT, DM, and BMI at baseline, were analyzed with the incidences of vascular dementia (VD) and AD during a 10-year follow-up period. RESULTS: The Kaplan-Meier method with log-rank test and Cox regression analyses for the total of 133 subjects showed significantly higher incidences of both VD and AD in subjects with DM or HT at baseline. Resting IL-1ß or IL-6 value, or agitation score, was not significantly associated with the subsequent development of VD or AD. The analyses of 40 subjects who had shown agitation at least once in the previous 3 months demonstrated that IL-1ß and IL-6 values at the agitation stage were significantly associated with AD, but not with VD. CONCLUSION: Our results indicate that systemic inflammatory IL-1ß and IL-6 at the agitation stage are risk factors for the development of AD, but not VD. Inflammatory mechanisms for AD seem to be causal and specific to the development of AD.


Subject(s)
Alzheimer Disease/blood , Dementia, Vascular/blood , Interleukin-1beta/blood , Interleukin-6/blood , Psychomotor Agitation/blood , Aged , Aged, 80 and over , Alzheimer Disease/epidemiology , Biomarkers/blood , Body Mass Index , Dementia, Vascular/epidemiology , Diabetes Mellitus/epidemiology , Female , Humans , Hypertension/epidemiology , Incidence , Japan/epidemiology , Male , Predictive Value of Tests , Psychomotor Agitation/epidemiology
6.
Mod Rheumatol ; 22(3): 394-404, 2012 Jun.
Article in English | MEDLINE | ID: mdl-21928092

ABSTRACT

We (JMAAV [Japanese patients with MPO-ANCA-associated vasculitis] Study Group) performed a prospective, open-label, multi-center trial to evaluate the usefulness of severity-based treatment in Japanese patients with myeloperoxidase-anti-neutrophil cytoplasmic antibodies (MPO-ANCA)-associated vasculitis. Patients with MPO-ANCA-associated vasculitis received a severity-based regimen according to the appropriate protocol: low-dose corticosteroid and, if necessary, cyclophosphamide or azathioprine in patients with mild form; high-dose corticosteroid and cyclophosphamide in those with severe form; and the severe-form regimen plus plasmapheresis in those with the most severe form. We followed up the patients for 18 months. The primary end points were the induction of remission, death, and end-stage renal disease (ESRD). Fifty-two patients were registered, and 48 patients were enrolled in this study (mild form, n = 23; severe form, n = 23; most severe form, n = 2). Among the 47 patients who received the predefined therapies, 42 achieved remission within 6 months, 5 died, and 1 developed ESRD. Disease flared up in 8 of the 42 patients with remission during the 18-month follow-up period. The JMAAV trial is the first prospective trial for MPO-ANCA-associated vasculitis to be performed in Japan. The remission and death rates were comparable to those in several previous clinical trials performed in western counties. The regimen employed in this trial was tailor-made based on patients' disease severity and disease type, and it seems that standardization can be consistent with treatment choices made according to severity.


Subject(s)
Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis/drug therapy , Antibodies, Antineutrophil Cytoplasmic/immunology , Peroxidase/immunology , Aged , Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis/immunology , Asian People , Cyclophosphamide/therapeutic use , Female , Glucocorticoids/therapeutic use , Humans , Immunosuppressive Agents/therapeutic use , Japan , Male , Middle Aged , Prednisolone/therapeutic use , Remission Induction , Severity of Illness Index , Treatment Outcome
7.
Placenta ; 31(8): 731-7, 2010 Aug.
Article in English | MEDLINE | ID: mdl-20580083

ABSTRACT

OBJECTIVES: To determine if fetal-placental hypoxia is a primary outcome of defective spiral artery remodeling. STUDY DESIGN: Pregnancies in Rag2(-/-)Il2rg(-/-) double knock-out mice, which fail to undergo normal physiological spiral arterial remodeling, were compared to syngeneic BALB/c control pregnancies. Mice at gestation day (gd)6, 8, 10, 12 and 18 were infused with Hypoxyprobe-1 before euthanasia to enable detection of cellular hypoxia by immunohistochemistry. RESULTS: In implantation sites of both phenotypes, trophoblast cells were reactive to Hypoxyprobe-1. No major differences were observed between the phenotypes in decidua or placenta at any gd or in gd18 fetal brain, lung, heart, liver or intestine or in maternal heart, brain, liver or spleen. Maternal kidneys from BALB/c were significantly hypoxic to Rag2(-/-)Il2rg(-/-) kidneys. CONCLUSIONS: In mice, lack of pregnancy-associated spiral artery remodeling does not impair oxygen delivery to the conceptus, challenging the concept that deficient spiral arterial remodeling leads to fetal hypoxia in human gestational complications such as preeclampsia and fetal growth restriction. The isolated hypoxic response of normal kidney has revealed that renal lymphocytes may have unique, tissue-specific regulatory actions on vasoconstriction that are pregnancy independent.


Subject(s)
Embryo Implantation , Fetal Diseases/metabolism , Hypoxia/metabolism , Oxygen/metabolism , Placenta/metabolism , Uterine Artery/physiology , Animals , Female , Kidney Tubules/metabolism , Mice , Mice, Inbred BALB C , Mice, Knockout , Pregnancy
8.
Placenta ; 31(4): 327-33, 2010 Apr.
Article in English | MEDLINE | ID: mdl-20149452

ABSTRACT

OBJECTIVE: Wingless-type mouse mammary tumor virus integration site family, member 5A (WNT5A), is expressed in mouse decidua and is thought to play an important role in decidualization. We examined expression of the receptor for WNT5A, receptor tyrosine kinase-like orphan receptor 2 (ROR2), in the uteri of cycling and pregnant mice. STUDY DESIGN: Reverse transcription (RT)-PCR and immunohistochemistry were performed. RESULTS: RT-PCR revealed that transcripts for Ror2, Wnt3a, Wnt5a and inhibitor of WNT signaling, Dickkopf homolog 1 (Dkk1), were present in the pregnant uterus. Immunohistochemistry revealed that in the virgin uterus, ROR2 is expressed in stromal cells and on the basal side of uterine gland and endometrial epithelial cells. During pregnancy, both the luminal and basal side of uterine gland epithelial cells expressed ROR2, stromal cell expression of ROR2 became more frequent and ROR2 expressing uterine Natural Killer (NK) cells and cells lining the maternal vascular space emerged. Immunofluorescence imaging and flow cytometry revealed that although uterine NK cells expressed ROR2, NK cells of the spleen were ROR2 negative. CONCLUSION: The expression of ROR2 by endometrial epithelial cells may suggest WNT signaling has roles in uterine epithelial cell polarity or implantation. Expression of ROR2 by uterine NK cells may suggest WNT signaling regulates uterine NK cell functions such angiogenesis and regulation of trophoblast migration. In summary, our results show that ROR2 expression by maternal uterine cells is influenced by pregnancy.


Subject(s)
Receptor Tyrosine Kinase-like Orphan Receptors/biosynthesis , Uterus/metabolism , Animals , Female , Intercellular Signaling Peptides and Proteins/genetics , Killer Cells, Natural/metabolism , Mice , Pregnancy , Receptor Tyrosine Kinase-like Orphan Receptors/genetics , Wnt Proteins/genetics , Wnt-5a Protein , Wnt3 Protein , Wnt3A Protein
9.
Int J Geriatr Psychiatry ; 25(6): 604-11, 2010 Jun.
Article in English | MEDLINE | ID: mdl-19728317

ABSTRACT

OBJECTIVE: Alzheimer's disease (AD) is a neurodegenerative disorder that is the most common cause of dementia in the elderly and is frequently accompanied by emotional disorder, including agitation. Although evidence of neuroendocrine immune and inflammatory functions during emotional changes has been accumulated, the pathogenic mechanisms in the development of agitation accompanied by AD remain to be elucidated. METHODS: To clarify the involvement of neuroendocrine and immune and inflammatory systems in agitation in AD, we examined agitation levels, circadian rhythms of behavior, cortisol, interleukin-1beta (IL-1beta), and natural killer cell activity (NKCA) in controls without dementia and 16 AD patients who were recognized to be easily agitated in their nursing homes. These behavioral and blood indicators were assessed according to the progress of the stage of agitation in 16 AD patients (stable, pre-agitation, and agitation stages). RESULTS: Elevations in night behavior and blood cortisol, IL-1beta and an reduced blood NKCA level in the evening were observed not only in the agitation stage, but also when stable in AD patients as compared to the control. Increased IL-1beta and decreased NKCA occurred in both the morning and evening in pre-agitation and agitation stages in AD. CONCLUSIONS: The increased IL-1beta and decreased NKCA with the progress of agitation in AD suggest that inflammation produces agitation and aggravates AD.


Subject(s)
Alzheimer Disease/immunology , Interleukin-1beta/blood , Killer Cells, Natural/immunology , Psychomotor Agitation/immunology , Aged , Alzheimer Disease/blood , Alzheimer Disease/complications , Analysis of Variance , Biomarkers/blood , Circadian Rhythm , Enzyme-Linked Immunosorbent Assay , Female , Humans , Hydrocortisone/blood , Male , Neuropsychological Tests , Psychomotor Agitation/blood , Psychomotor Agitation/etiology
10.
Placenta ; 30(6): 501-6, 2009 Jun.
Article in English | MEDLINE | ID: mdl-19427693

ABSTRACT

Viable human CD56+ CD16- peripheral blood Natural Killer (NK) cells show specific in vitro binding under shear forces to ligands expressed by endothelial cells in cryostat sections of gestation day (gd)7 mouse decidua basalis. In serial assays, numbers of cells adhering to gd7 tissue are constant for men but have cyclical variation for fertile women, suggesting a brief gain in functional decidual homing potential of this NK cell subset during the menstrual cycle. Regardless of gender, numbers of adhering cells from an individual donor, increase dramatically when the substrate is decidua basalis from a later gestational timepoint. Here, we report that human blood CD56+ CD16- NK cells which adhere as single cells over gd7 decidua basalis, adhere as large clusters over gd8 and gd9 tissues, suggestive of antigen recognition and lymphocyte activation. We asked which cells within mouse decidua basalis trigger this response in CD56+ CD16- cells. Using decidua from mice transgenic for myeloid dendritic cell (mDC) expression of enhanced yellow fluorescent protein (eYFP), we found cluster formation was independent of mDC contact. Use of decidua from alymphoid mice showed clustering behavior required substrate lymphocytes. By use of decidua containing NK cells but lacking T and B cells, decidual T and/or B lymphocytes were identified as the cells altered after gd7 in a manner that activates CD56+ CD16- cell clustering. This timepoint is just prior to mouse spiral arterial modification and its detection by these indicator cells implicates adaptive, decidual immune responses in the regulation of NK cell function.


Subject(s)
Adaptation, Physiological/immunology , Decidua/immunology , Immunity, Cellular/physiology , Killer Cells, Natural/physiology , Adult , Animals , Cells, Cultured , DNA-Binding Proteins/genetics , Female , Gestational Age , Humans , Interleukin Receptor Common gamma Subunit/genetics , Killer Cells, Natural/immunology , Male , Mice , Mice, Inbred BALB C , Mice, Inbred C57BL , Mice, Knockout , Pregnancy , Time Factors
12.
Clin Exp Rheumatol ; 26(1): 13-7, 2008.
Article in English | MEDLINE | ID: mdl-18328141

ABSTRACT

BACKGROUND: Familial Mediterranean fever (FMF) is an autosomal recessive disease characterized by recurrent attacks of fever with serosal inflammation. FMF gene (MEFV) mutations have been identified primarily in patients from Mediterranean populations. Although several clinical cases have been reported in Japan, there have been few reports to date on mutation analysis. We studied FMF patients and their relatives to examine the clinical and genetic features of this disease in the Japanese population. METHODS: Twelve Japanese FMF patients who met the Tel Hashomer criteria and a total of 17 relatives from 5 of 10 families underwent molecular genetic studies to detect MEFV mutations. The characteristics of these Japanese FMF patients and geno-phenotypical correlations were examined. RESULTS: Almost all of our patients had been suffering for a long time from fever of unknown origin and one patient also had systemic amyloidosis. In our 12 FMF patients, we detected the substitutions E84K, L110P, E148Q, R761H and M694I. We also newly diagnosed 2 relatives as having FMF based on clinical symptoms and the existence of FMF mutations. One patient was homozygous for E148Q, the patient with systemic amyloidosis was a homozygote for M694I and 4 patients from 3 families were compound heterozygotes for E148Q and M694I. Three patients in one family were compound heterozygotes for E148Q, L110P and M694I. There were 3 patients who were heterozygous for E84K, L110P-E148Q or M694I and had no other nucleotide changes in the exons of MEFV. On the other hand, 2 relatives who had never experienced symptoms of FMF were homozygous for L110P-E148Q as well as compound heterozygous for E148Q/E148Q-R761H. E148Q and M694I were the most frequently detected substitutions in our study. CONCLUSIONS: MEFV mutations occur in Japanese FMF patients though FMF is rare in Japan. The identification of MEFV mutations could be a reliable diagnostic test for FMF. The results of genetic analyses on 14 Japanese FMF patients in this study revealed that E148Q and M694I are frequent alleles.


Subject(s)
Cytoskeletal Proteins/genetics , Familial Mediterranean Fever/genetics , Mutation , Adolescent , Adult , Amyloidosis, Familial/genetics , Female , Heterozygote , Homozygote , Humans , Japan , Male , Middle Aged , Phenotype , Pyrin
13.
Int Angiol ; 22(3): 243-9, 2003 Sep.
Article in English | MEDLINE | ID: mdl-14612851

ABSTRACT

AIM: Cold water-immersion induces vasoconstriction with an elevation of blood endothelin-1, which is a potent vasoconstrictor peptide, in patients with primary Raynaud's phenomenon (PRP). However, physiological involvement of endothelin-1 in cold-induced vasodilation (CIVD) remains to be elucidated. METHODS: We monitored changes of finger blood flow during cold water (10 degrees C) immersion and assayed blood endothelin-1 in 7 PRP patients and 7 workers with vibration-induced white finger (VWF) and in the respective control subjects. RESULTS: While significant reductions in finger blood flow at 2 min after the immersion were observed in PRP patients and VWF workers, its elevation at 4 min, which was considered to reflect CIVD, was recognized only in PRP patients. In healthy controls, blood endothelin-1 increased at 4 min and returned to the basal level immediately after the immersion. The increase in blood endothelin-1 at 4 min in PRP patients was greater than that in controls, and continued even after the immersion. Conversely, the increase neither at 4 min nor after immersion was seen in VWF workers. Local vascular changes produced by repetitive vibration may be responsible for the attenuated CIVD and unchanged blood endothelin-1 during cold water-immersion in VWF workers. CONCLUSION: Our results showing elevated blood endothelin-1 during and after immersion in PRP contrast with that in VWF suggesting that endothelin-1 is related to sympathetic hyperactivity which is more involved in PRP rather than VWF. It seems unlikely that endothelin-1 is functionally or directly associated with CIVD.


Subject(s)
Endothelin-1/blood , Hypothermia, Induced/methods , Occupational Diseases/physiopathology , Peripheral Vascular Diseases/physiopathology , Raynaud Disease/physiopathology , Vasodilation/physiology , Adult , Female , Fingers/blood supply , Humans , Immersion , Male , Middle Aged , Occupational Diseases/blood , Occupational Diseases/etiology , Peripheral Vascular Diseases/blood , Peripheral Vascular Diseases/etiology , Raynaud Disease/blood , Vibration/adverse effects
14.
Nephron ; 89(4): 408-15, 2001 Dec.
Article in English | MEDLINE | ID: mdl-11721158

ABSTRACT

Rapid amelioration of hypercholesterolemia by LDL apheresis (LDL-A) was performed for long-standing nephrotic syndrome (NS) with hyperlipidemia due to focal segmental glomerulosclerosis (FGS) and the clinical data and prognosis were compared between LDL-A-treated and nontreated groups. Seventeen steroid-resistant NS patients treated with LDL-A (LDL-A group) and 10 NS patients treated with steroids only (steroid-monotherapy (SM) group) were compared. Serum cholesterol and phospholipid levels were significantly lowered only in the LDL-A group (p < 0.01, respectively). The LDL-A group showed a significant decrease of urinary protein (UP, p < 0.01) and increase of serum albumin (p < 0.05). Average time needed to achieve a decrease of UP to less than nephrotic range (< 3.5 g/day) was significantly shorter in the LDL-A group than in the SM group (p < 0.01). Although this is not a prospective study, it is highly expected that a rapid improvement of hypercholesterolemia by LDL-A in steroid-resistant NS will provide more rapid relief from NS than steroid therapy alone.


Subject(s)
Anti-Inflammatory Agents/therapeutic use , Blood Component Removal , Cholesterol, LDL/blood , Glomerulosclerosis, Focal Segmental/drug therapy , Nephrotic Syndrome/drug therapy , Prednisolone/therapeutic use , Adolescent , Adult , Aged , Blood Proteins/analysis , Blood Urea Nitrogen , Creatinine/blood , Drug Resistance , Female , Humans , Hyperlipidemias/therapy , Kidney Function Tests , Male , Middle Aged , Proteinuria/therapy , Retrospective Studies , Treatment Outcome
15.
J Clin Psychopharmacol ; 21(3): 257-61, 2001 Jun.
Article in English | MEDLINE | ID: mdl-11386487

ABSTRACT

Although intravenous haloperidol (HAL) is an effective medication that is often prescribed to treat agitation, several instances of torsade de pointes or prolonged QT interval have been reported. To investigate the association between intravenous HAL and QT prolongation and between intravenous HAL and ventricular tachyarrhythmia, a cross-sectional cohort study was performed that included measuring corrected QT intervals (QTc) on an emergency basis before intravenous HAL and continuously monitoring electrocardiographic (ECG) findings after intravenous HAL. During a 2-month period, 47 patients received intravenous injections to control psychotic disruptive behavior. According to clinical practice, patients were divided as follows. The FZ-alone group was treated with intravenous flunitrazepam (FZ), and the FZ-plus-HAL group received intravenous FZ followed by intravenous HAL. Although the difference in the mean QTc immediately after intravenous FZ between the two groups was not significant, the mean QTc after 8 hours in the FZ-plus-HAL group was longer than that in the FZ-alone group (p < 0.001). Four patients in the FZ-plus-HAL group had a QTc of more than 500 msec after 8 hours. The change in QTc during 8 hours significantly differed between the two groups (t = 2.64, p > 0.05). Furthermore, the change in QTc was moderately correlated with the dose of intravenous HAL, as evidenced by a coefficient of correlation of 0.48 (p < 0.001). However, ventricular tachyarrhythmia was not detected among 307 patients within a 1-year period, although the ECG was continuously monitored for at least 8 hours after intravenous HAL. The modest nature of QTc prolongation and the apparent absence of ventricular tachyarrhythmia under continuous ECG monitoring indicate that QTc prolongation associated with intravenous HAL is not necessarily dangerous. However, in an emergency situation, clinicians cannot exclude patients predisposed to torsade de pointes, such as those with inherited ion channel disorders. Therefore, clinicians should be aware of the association between intravenous HAL and QT prolongation.


Subject(s)
Antipsychotic Agents/therapeutic use , Haloperidol/therapeutic use , Long QT Syndrome/chemically induced , Adult , Anti-Anxiety Agents/therapeutic use , Cohort Studies , Confidence Intervals , Cross-Sectional Studies , Dose-Response Relationship, Drug , Drug Therapy, Combination , Electrocardiography , Female , Flunitrazepam/therapeutic use , Humans , Injections, Intravenous , Linear Models , Long QT Syndrome/physiopathology , Male , Middle Aged , Monitoring, Physiologic/methods , Psychomotor Agitation/drug therapy , Psychomotor Agitation/psychology , Statistics, Nonparametric , Tachycardia, Ventricular/chemically induced , Tachycardia, Ventricular/physiopathology
16.
Brain Behav Immun ; 15(1): 43-53, 2001 Mar.
Article in English | MEDLINE | ID: mdl-11259079

ABSTRACT

To clarify whether corticotropin releasing hormone (CRH) and beta-endorphin (betaEP) system mediate maternal immunosuppression in pregnant rats exposed to heat through central or placental pathway, we examined the effects of intravenous (iv) (100 or 500 microg) or intracerebroventricular (icv) (5 microg) administration of CRH receptor antagonist alpha-helical CRH (9-41) on splenic natural killer cell activity (NKCA) as well as betaEP in blood, pituitary lobes, and placenta in pregnant rats at 15 to 16 days gestation. Two-way ANOVA revealed that heat reduced NKCA and elevated blood and pituitary betaEP but did not change placental betaEP. Iv administered 500 microg and icv administered alpha-helical CRH reversed the reduced NKCA and the elevated pituitary betaEP, while iv administration of 100 microg alpha-helical CRH did not. The increased blood betaEP was reversed by iv 100 and 500 microg alpha-helical CRH and icv administration. Both iv and icv administrations reduced placental betaEP independent of heat exposure. Thus, the response of placental betaEP to iv administration of alpha-helical CRH seemed to be stronger than that of pituitary betaEP. These results indicate that alpha-helical CRH which acts on pituitary betaEP antagonizes heat-induced immunosuppression during pregnancy, suggesting that immunosuppression produced by heat stress during pregnancy is mediated by the central CRH system. The placental CRH-betaEP system seems unlikely to be involved in the immunosuppression. Physiologic roles of placental CRH and opioid system should be clarified by future in vitro experiments using placenta specimen including placental immunocyte.


Subject(s)
Corticotropin-Releasing Hormone/immunology , Heat Stress Disorders/immunology , Pituitary Gland/immunology , Placenta/immunology , Pregnancy, Animal/immunology , Animals , Corticotropin-Releasing Hormone/metabolism , Corticotropin-Releasing Hormone/pharmacology , Female , Heat Stress Disorders/metabolism , Hormone Antagonists/pharmacology , Injections, Intraventricular , Killer Cells, Natural/immunology , Killer Cells, Natural/metabolism , Male , Neuroimmunomodulation/drug effects , Neuroimmunomodulation/immunology , Opioid Peptides/metabolism , Pituitary Gland/metabolism , Placenta/metabolism , Pregnancy , Pregnancy, Animal/metabolism , Rats , Rats, Wistar , beta-Endorphin/blood , beta-Endorphin/immunology
17.
Neuroscience ; 103(2): 561-79, 2001.
Article in English | MEDLINE | ID: mdl-11246169

ABSTRACT

In vivo recordings from Mauthner cells in adult zebrafish (Danio rerio) and goldfish (Carassius auratus) preparations with potassium chloride filled electrodes revealed a new class of long-lasting synaptic events in these cells. Their decay time constant ranged from 20 to 80ms, which is about 20 times longer than that of previously identified fast glycinergic inhibitory postsynaptic potentials in this neuron. The average time to peak of these slow events ranged from 1 to 6ms. We demonstrated that they are also inhibitory since (i) they were resistant to antagonists of the excitatory glutamatergic receptors; (ii) their amplitude was increased following chloride loading of the Mauthner cell; (iii) their reversal potential was the same as that of fast, glycinergic inhibitory postsynaptic potentials; and (iv) they produced an inhibitory shunt of the cell's membrane resistance. Furthermore, as with the fast inhibitory postsynaptic potentials, the decay time of the slow events is voltage dependent, increasing when the Mauthner cell is depolarized. However, these inhibitory postsynaptic potentials had a different pharmacological profile to the fast glycinergic ones. That is, they persisted in the presence of strychnine at doses that abolished the fast ones and they were more sensitive to bicuculline. These data are compatible with the notion that these inhibitory postsynaptic potentials are mediated by activation of a different inhibitory receptor type, and may be GABAergic. In addition, the decay time constant of the fast inhibitory postsynaptic current was shorter than the first of the two components that contribute to the bi-exponential decay reported previously for miniature inhibitory postsynaptic currents in Mauthner cells of larval zebrafish. This suggests developmental modifications and/or a switch in the assembly of glycine receptor subtypes. While amplitude distributions of the fast miniature inhibitory postsynaptic potentials recorded in the presence of tetrodotoxin generally could fit with a single Gaussian function, the amplitude histograms of slow miniature events were skewed, often with multiple nearly equally spaced peaks, consistent with the synchronous release of several quantal units. These previously undescribed slow unitary inhibitory postsynaptic potentials contribute to inhibitory synaptic noise recorded in the Mauthner cells. Specifically, autocorrelation analysis revealed gamma-like rhythms (30-80Hz) in each of two phases, characterized as "noisy" and "quiet", and dominated by the fast and slow inhibitory postsynaptic potentials, respectively. The major frequencies of these two states were significantly different (i.e. around 90 and 40Hz, respectively), suggesting that the fast and slow inhibitory postsynaptic potentials are derived from different inhibitory networks. Chloride-filled Mauthner cells gradually hyperpolarized in the presence of tetrodotoxin, reflecting the effect of ongoing activity in the interneurons that produce the slow events. We conclude that this new class of inhibitory postsynaptic potentials contributes to the tonic inhibition which controls the Mauthner cell's excitability. In physiological conditions, this regulatory influence is expressed as a continuous shunt of this neuron's input resistance and responsiveness to sensory inputs.


Subject(s)
Escape Reaction/physiology , Motor Neurons/physiology , Neural Inhibition/physiology , 2-Amino-5-phosphonovalerate/pharmacology , 6-Cyano-7-nitroquinoxaline-2,3-dione/pharmacology , Action Potentials/drug effects , Action Potentials/physiology , Animals , Bicuculline/pharmacology , Chlorides/metabolism , Excitatory Amino Acid Antagonists/pharmacology , GABA Antagonists/pharmacology , Glycine/metabolism , Glycine Agents/pharmacology , Goldfish , Interneurons/physiology , Neural Inhibition/drug effects , Patch-Clamp Techniques , Reaction Time/physiology , Strychnine/pharmacology , Tetrodotoxin/pharmacology , Zebrafish , gamma-Aminobutyric Acid/metabolism
19.
Placenta ; 21(5-6): 510-5, 2000.
Article in English | MEDLINE | ID: mdl-10940201

ABSTRACT

There is some evidence showing an existence of corticotropin releasing hormone (CRH) and opioid peptides, including beta-endorphin (betaEP), in human placenta, whereas physiological roles of the placental peptides in response to stress remain to be elucidated. To clarify the involvement of CRH and opioid system in the uteroplacental circulation in the pregnant rats exposed to heat, we examined the effects of heat and intravenous administration of CRH receptor antagonist alpha-helical CRH (9-41) on the uteroplacental blood flow, as well as blood CRH, and blood and placental betaEP in pregnant rats. Heat did not change uterine blood flow in virgin rats, but reduced uteroplacental blood flow in pregnant rats. The reduced uteroplacental blood flow induced by heat in pregnant rats was reversed by the administration of alpha-helical CRH. Independent of the status of pregnancy, heat increased blood CRH, which was not reversed by alpha-helical CRH. Although heat did not change placental betaEP, alpha-helical CRH reduced blood and placenta betaEP in pregnant rats. These results suggest that the uteroplacental circulatory disturbance caused by heat is mediated by CRH, possibly through the involvement of CRH receptor in rat placenta. The placental opioid system seems unlikely to be involved in the mediation of uteroplacental circulation.


Subject(s)
Corticotropin-Releasing Hormone/physiology , Hot Temperature , Placental Circulation/physiology , Pregnancy, Animal/physiology , Animals , Body Temperature , Corticotropin-Releasing Hormone/antagonists & inhibitors , Corticotropin-Releasing Hormone/blood , Corticotropin-Releasing Hormone/pharmacology , Female , Hormone Antagonists/pharmacology , Injections, Intravenous , Male , Microwaves , Placenta/drug effects , Placenta/metabolism , Placental Circulation/drug effects , Pregnancy , Rats , Rats, Wistar , beta-Endorphin/blood
20.
Psychiatry Res ; 94(3): 279-85, 2000 Jul 17.
Article in English | MEDLINE | ID: mdl-10889294

ABSTRACT

Some recent clinical studies indicate that hypokalemia is characteristic for acute psychotic patients at the time of emergency admission. As hypokalemia is one of the major causes for prolonged QT interval, it was hypothesized that acute psychotic patients could show prolonged QT interval. Sixty-seven drug-free, acute psychotic patients were evaluated for corrected QT (QTc) interval, as well as demographic and clinical characteristics at the time of emergency admission. The mean QTc interval of psychiatric emergency patients was prolonged, and the mean QTc interval of psychiatric emergency patients was longer than that of psychiatric outpatients (t=5.20, P<0.0001). Age- or gender-related difference, circadian fluctuation of QT interval, medication, concomitant disease, obesity, and serum electrolytes except potassium were not major causes. There was a significant negative correlation as evidenced by a coefficient of correlation of -0.28 (P<0.05). As psychiatric emergency patients often receive parenteral antipsychotics, which may have adverse effects on prolonged QT interval, paying attention to QT interval might have some clinical significance on emergency admission.


Subject(s)
Long QT Syndrome/etiology , Psychotic Disorders/psychology , Acute Disease , Adult , Antipsychotic Agents/adverse effects , Circadian Rhythm/physiology , Emergency Medical Services , Female , Humans , Hypokalemia/complications , Hypokalemia/diagnosis , Long QT Syndrome/diagnosis , Male , Patient Admission , Psychotic Disorders/diagnosis , Psychotic Disorders/drug therapy
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