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1.
Int J Circumpolar Health ; 80(1): 1886704, 2021 12.
Article in English | MEDLINE | ID: mdl-33617415

ABSTRACT

An Antarctic wintering-over station is a unique environment, as a small isolated society facing extreme survival margins. Psychological surveys have been done over ten years, including the Baum test, the Positive and Negative Affect Schedule (PANAS), the Coping Orientation to Problems Experienced (COPE), Subjective Health Complaints Inventory (SHC), the Two-Sided Personality Scale (TSPS) and medical consultations in Syowa Station, a Japanese Antarctic station to reveal the mental status of team members. Team members experienced fewer physical health risks in Antarctica than in Japan. Wintering-over team members reinterpreted situations positively and accepted their environment, sought instrumental social support, planned ahead, and used active coping skills and humour to overcome difficulties. They did not act out emotionally or deny problems. Individuals exhibited two types of coping, either stability through maintaining a previous lifestyle or flexible adjustment to a new way of life. Positive affect remained constant during the wintering-over period. In living through a harsh reality, team members drew support from the subjective feelings of an "internal relationship" with home or family in their minds. Thus, an Antarctic wintering-over station is an ideal isolated environment for psychological surveys, which can help understand future space travel and group managements in everyday societies.


Subject(s)
Adaptation, Physiological , Adaptation, Psychological , Antarctic Regions , Humans , Seasons , Surveys and Questionnaires
2.
Fujita Med J ; 7(1): 1-7, 2021.
Article in English | MEDLINE | ID: mdl-35111536

ABSTRACT

OBJECTIVES: It is common to treat type 2 diabetes by regular injections of insulin. We compared the efficacy and safety of twice-daily administration of short-acting, premixed, and long-acting insulins. METHODS: This was a multi-center, randomized, open-label, 52-week study. Patients were randomized to administer twice daily short-acting analog insulin (Aspart) plus a sulfonylurea (SU), premixed 70/30 analog insulin (Mix), or long-acting insulin (Detemir) plus a glinide derivative. RESULTS: Twelve (mean baseline HbA1c 9.86±1.71%), eight (9.24±1.14%), and eight (11.26±1.81%) patients were treated with Aspart, Mix, or Detemir, respectively, for 52 weeks. After 12 weeks, the reductions in HbA1c were similar in the groups. A further significant reduction in HbA1c occurred between weeks 12 and 52 in the Detemir, but not the Aspart or Mix groups. After 52 weeks, the target of an HbA1c <7.4% was achieved in 16.7% of the Aspart group, 37.5% of the Mix group, and 12.5% of the Detemir group (no significant differences among the three groups by χ2 analysis). The mean changes from baseline in blood glucose concentration measured after breakfast, and before and after dinner, were also similar in each group. CONCLUSIONS: Early and meaningful reductions in HbA1c were achieved by twice-daily administration of a premix, aspart plus an SU, and detemir plus a glinide, without severe hypoglycemia or an increase in body mass. However, the target HbA1c was achieved in relatively few participants, perhaps due to an insufficient dose of insulin or the small study size.

3.
J Physiol Sci ; 70(1): 21, 2020 Mar 30.
Article in English | MEDLINE | ID: mdl-32228438

ABSTRACT

Blood pressure response to head-up tilt (HUT) in 7 healthy subjects and 9 patients before and after coronary artery bypass grafting (CABG) was measured during supine and 15-min 60° HUT. Stroke volume (SV) and ejection fraction (EF) were assessed by echocardiography. Baseline mean arterial pressure (MAP) and heart rate (HR) in patients before CABG were similar to healthy subjects. MAP in patients decreased by 6 (4-9) mmHg [median (1st-3rd quartiles)] during 7-12 mmHg of HUT with decreased cardiac output (CO = SV × HR) while HR remained unchanged. MAP in healthy subjects remained unchanged during HUT with increased HR. Body weight decreased by 3.5 (2.5-3.7) kg and MAP decreased by 6 (2-13) mmHg during the last 3-min HUT while HR increased after CABG. Decreases in SV and CO during HUT disappeared after CABG. Blood pressure decreased during HUT in patients before and after CABG regardless of HR response.


Subject(s)
Cardiac Output/physiology , Coronary Artery Bypass/methods , Coronary Artery Disease/physiopathology , Heart Rate/physiology , Posture/physiology , Stroke Volume/physiology , Aged , Blood Pressure , Case-Control Studies , Cross-Sectional Studies , Echocardiography/methods , Female , Humans , Male , Middle Aged , Tilt-Table Test
4.
Hypertens Res ; 39(12): 863-867, 2016 Dec.
Article in English | MEDLINE | ID: mdl-27439493

ABSTRACT

The pupil is a suitable end organ for studying autonomic function because both sympathetic and parasympathetic nerve activity can be evaluated independently using a light stimulus. Sympathetic response elicited by physical stress is augmented in hypertensive patients compared with normotensive subjects, which increases the risk of cardiovascular events. We used pupillometry to evaluate the effects of the calcium channel blockers azelnidipine (AZ) and amlodipine (AM) on changes in autonomic nervous activity induced by isometric exercise in patients with hypertension. Twenty patients with essential hypertension who were administered AM and 21 who were administered AZ underwent a pupillary function test and blood pressure (BP) and pulse rate (PR) measurements before and after isometric handgrip exercise (IHG). Maximal velocities of pupil constriction (VC) and re-dilation (VD) obtained with light stimulation for 1 s were used as indices of parasympathetic and sympathetic nerve activity, respectively. Increases in systolic BP and PR elicited by IHG were significantly smaller in the AZ group than in the AM group. After IHG, both VC and VD significantly increased in the AM group but not in the AZ group. The low-to-high frequency ratio obtained from analysis of PR variability, another measure of sympathetic activity, also increased in only the AM group. Thus AZ inhibited autonomic activation and suppressed cardiovascular responses to IHG more effectively than AM. The sympathoinhibitory effect of AZ may therefore be beneficial for patients with essential hypertension. In addition, pupillometry was shown to be a useful tool for assessing autonomic function in hypertensive patients.


Subject(s)
Amlodipine/pharmacology , Antihypertensive Agents/pharmacology , Autonomic Nervous System/drug effects , Azetidinecarboxylic Acid/analogs & derivatives , Calcium Channel Blockers/pharmacology , Dihydropyridines/pharmacology , Exercise/physiology , Hypertension/drug therapy , Pupil/drug effects , Amlodipine/therapeutic use , Antihypertensive Agents/therapeutic use , Azetidinecarboxylic Acid/pharmacology , Azetidinecarboxylic Acid/therapeutic use , Blood Pressure/drug effects , Blood Pressure/physiology , Calcium Channel Blockers/therapeutic use , Dihydropyridines/therapeutic use , Essential Hypertension , Female , Humans , Male , Middle Aged , Pupil/physiology
5.
Clin Exp Hypertens ; 38(2): 209-17, 2016.
Article in English | MEDLINE | ID: mdl-26818039

ABSTRACT

We hypothesized that blockade of angiotensin II type 2 receptors (AT2Rs) in the rostral ventrolateral medullary pressor area (RVLM) may elicit sympathoexcitatory responses which are smaller in hypertensive rats compared to normotensive rats. This hypothesis was tested in urethane-anesthetized, artificially ventilated male 14-week-old spontaneously hypertensive rats (SHR). Age-matched male Wistar-Kyoto rats (WKY) and Wistar rats were used as controls. PD123319 (AT2R antagonist) was microinjected into the RVLM and mean arterial pressure (MAP), heart rate (HR) and greater splanchnic nerve activity (GSNA) were recorded. Increases in MAP, HR and GSNA elicited by unilateral microinjections of PD123319 into the RVLM were significantly smaller in SHR when compared with those in WKY and Wistar rats. Unilateral microinjections of l-glutamate (l-Glu) into the RVLM elicited greater increases in MAP and GSNA in SHR compared to those in WKY. AT2R immunoreactivity was demonstrated in the RVLM neurons which were retrogradely labeled from the intermediolateral cell column (IML) of the spinal cord. These results indicate that AT2Rs are present on the RVLM neurons projecting to the IML and their blockade results in sympathoexcitatory responses. Activation of AT2Rs has an inhibitory influence in the RVLM and these receptors are tonically active. Attenuation of the function of AT2Rs in the RVLM may play a role in genesis and/or maintenance of hypertension in SHR.


Subject(s)
Angiotensin II Type 2 Receptor Blockers/pharmacology , Arterial Pressure/drug effects , Glutamic Acid/pharmacology , Heart Rate/drug effects , Imidazoles/pharmacology , Medulla Oblongata/drug effects , Pyridines/pharmacology , Splanchnic Nerves/drug effects , Animals , Blood Pressure/drug effects , Hypertension , Immunohistochemistry , Male , Medulla Oblongata/metabolism , Microinjections , Neurons/metabolism , Rats , Rats, Inbred SHR , Rats, Inbred WKY , Rats, Wistar , Receptor, Angiotensin, Type 2/metabolism , Spinal Cord Lateral Horn/metabolism
6.
Case Rep Orthop ; 2015: 242078, 2015.
Article in English | MEDLINE | ID: mdl-26688765

ABSTRACT

Pachydermodactyly (PDD) is a rare and benign acquired form of digital fibromatosis, characterized by asymptomatic fusiform soft tissue hypertrophy of the lateral aspect of the proximal interphalangeal (PIP) joints of the fingers. The etiology of PDD remains unknown, but it usually affects healthy males around the age of puberty. It can be misdiagnosed as inflammatory rheumatic diseases, especially as juvenile chronic arthritis. Here, we report a case of PDD in an 18-year-old man who had progressive fusiform swelling of the PIP joint on his left middle finger. Although he had no pain or functional limitation of movement, he chose to undergo surgical resection of the lesion to obtain a conclusive diagnosis and to rectify the deformity's appearance. Histologically, the lesion was characterized by coarse fibrosis in the adipose tissue, peripheral nerve fibers, and eccrine glands; this is compatible with a diagnosis of PDD.

7.
Clin Exp Hypertens ; 37(7): 531-5, 2015.
Article in English | MEDLINE | ID: mdl-25977982

ABSTRACT

Pupillometry was used to evaluate the effects of the calcium channel blockers cilnidipine (CL) and amlodipine (AM) on changes in autonomic nervous activity induced by isometric exercise in patients with hypertension. After handgrip exercise, the velocity of miosis increased in both the CL and AM groups. However, the velocity of mydriasis increased in only the AM group. Velocity slopes of miosis and mydriasis were smaller in the CL group than in the AM group. The low-to-high frequency ratio obtained from pulse wave analysis increased in only the AM group. Sympathetic activation elicited by isometric exercise was suppressed more effectively by CL than by AM.


Subject(s)
Amlodipine/pharmacology , Autonomic Nervous System/drug effects , Dihydropyridines/pharmacology , Hypertension , Miosis/physiopathology , Mydriasis/physiopathology , Pupil , Aged , Calcium Channel Blockers/pharmacology , Exercise/physiology , Female , Hand Strength/physiology , Humans , Hypertension/drug therapy , Hypertension/physiopathology , Male , Middle Aged , Miosis/diagnosis , Mydriasis/diagnosis , Pupil/drug effects , Pupil/physiology , Reproducibility of Results
8.
Clin Exp Hypertens ; 37(3): 197-206, 2015.
Article in English | MEDLINE | ID: mdl-25051156

ABSTRACT

Stimulation of µ1-opioid receptors (M1ORs) in the medial nucleus solitarius (mNTS) by endomorphin-2 (EM2) elicits decreases in mean arterial pressure (MAP), heart rate (HR) and greater splanchnic nerve activity (GSNA) in Wistar rats. We tested the hypothesis that EM2-induced responses in the mNTS may be attenuated in the spontaneously hypertensive rat (SHR). Experiments were carried out in urethane-anesthetized, artificially ventilated, adult male SHR and Wistar-Kyoto rats (WKY). Alterations in responses to chemical stimulation of the hypothalamic arcuate nucleus (ARCN) after bilateral blockade of M1ORs in the mNTS were also studied. In SHR, microinjections of EM2 into the mNTS elicited smaller decreases in MAP, HR and GSNA compared to those elicited in WKY; smaller cardiovascular responses in SHR can be explained by lower expression of M1OR mRNA in the NTS of SHR compared to WKY. Decreases in MAP and GSNA and increases in HR were elicited by microinjections of N-methyl-D-aspartic acid (NMDA) into the ARCN of WKY. Bilateral blockade of M1ORs in the mNTS attenuated the decreases in MAP and GSNA and exaggerated the increases in HR elicited by the ARCN stimulation in WKY but not in SHR. Tonic inhibitory activity of neuropeptide Y/gamma-aminobutyric acid (NPY/GABA) neurons in the ARCN is attenuated in SHR; this observation may explain increases in MAP, GSNA and HR elicited by microinjections of NMDA into the ARCN of SHR. These results demonstrate that attenuation of EM2-induced responses in the mNTS of SHR may contribute to the excitatory responses elicited by ARCN stimulation in SHR.


Subject(s)
Cardiovascular System , Hypertension , Oligopeptides , Receptors, Opioid, mu , Solitary Nucleus , Splanchnic Nerves , Analgesics, Opioid/administration & dosage , Analgesics, Opioid/metabolism , Analgesics, Opioid/pharmacokinetics , Animals , Arcuate Nucleus of Hypothalamus/metabolism , Arcuate Nucleus of Hypothalamus/physiopathology , Cardiovascular System/metabolism , Cardiovascular System/physiopathology , Hypertension/genetics , Hypertension/physiopathology , Male , Microinjections , Oligopeptides/administration & dosage , Oligopeptides/metabolism , Oligopeptides/pharmacokinetics , Rats , Rats, Inbred SHR , Rats, Inbred WKY , Receptors, Opioid, mu/antagonists & inhibitors , Receptors, Opioid, mu/genetics , Solitary Nucleus/metabolism , Solitary Nucleus/physiopathology , Splanchnic Nerves/metabolism , Splanchnic Nerves/physiopathology
9.
Am J Physiol Heart Circ Physiol ; 306(3): H438-49, 2014 Feb.
Article in English | MEDLINE | ID: mdl-24285114

ABSTRACT

Angiotensin (ANG)-(1-12) excites neurons via ANG II type 1 receptors (AT1Rs), which are present in the caudal ventrolateral medullary depressor area (CVLM). We hypothesized that microinjections of ANG-(1-12) into the CVLM may elicit decreases in mean arterial pressure (MAP), heart rate (HR), and sympathetic nerve activity. This hypothesis was tested in urethane-anesthetized adult male Wistar rats. Microinjections of ANG-(1-12) into the CVLM elicited decreases in MAP, HR, and greater splanchnic nerve activity (GSNA). ANG-(1-12)-induced responses consisted of initial (first 1-8 min) and delayed (8-24 min) phases. Prior microinjections of losartan, A-779, and captopril into the CVLM blocked initial, delayed, and both phases of ANG-(1-12) responses, respectively. Blockade of GABA receptors in the rostral ventrolateral medullary pressor area (RVLM) attenuated cardiovascular responses elicited by microinjections of ANG-(1-12) into the ipsilateral CVLM. Microinjections of ANG-(1-12) into the CVLM potentiated the reflex decreases and attenuated the reflex increases in GSNA elicited by intravenous injections of phenylephrine and sodium nitroprusside, respectively. These results indicate that microinjections of ANG-(1-12) into the CVLM elicit decreases in MAP, HR, and GSNA. Initial and delayed phases of these responses are mediated via ANG II and ANG-(1-7), respectively; the effects of ANG II and ANG-(1-7) are mediated via AT1Rs and Mas receptors, respectively. Captopril blocked both phases of ANG-(1-12) responses, indicating that angiotensin-converting enzyme is important in mediating these responses. GABA receptors in the RVLM partly mediate the cardiovascular responses to microinjections of ANG-(1-12) into the CVLM. Microinjections of ANG-(1-12) into the CVLM modulate baroreflex responses.


Subject(s)
Adrenergic alpha-1 Receptor Agonists/pharmacology , Angiotensinogen/pharmacology , Baroreflex , Medulla Oblongata/physiology , Peptide Fragments/pharmacology , Angiotensin II/analogs & derivatives , Angiotensin II/pharmacology , Animals , Antihypertensive Agents/pharmacology , Blood Pressure , Captopril/pharmacology , Heart Rate , Losartan/pharmacology , Male , Medulla Oblongata/drug effects , Nitroprusside/pharmacology , Phenylephrine/pharmacology , Rats , Rats, Wistar , Vasomotor System/drug effects , Vasomotor System/physiology
10.
Hypertension ; 62(2): 281-7, 2013 Aug.
Article in English | MEDLINE | ID: mdl-23774228

ABSTRACT

We tested the hypothesis that tonic γ-aminobutyric acid-ergic activity in the hypothalamic arcuate nucleus (ARCN) modulates blood pressure control and attenuation of this inhibitory activity contributes to hypertension in the spontaneously hypertensive rats (SHR). Mean arterial pressure (MAP), heart rate (HR), and greater splanchnic nerve activity (GSNA) were recorded in urethane-anesthetized, artificially ventilated, adult male SHR and Wistar-Kyoto rats (WKY). Microinjections of gabazine into the ARCN elicited significantly smaller increases in MAP, HR, and GSNA in baroreceptor-intact SHR compared with baroreceptor-intact WKY. Attenuation of the responses to gabazine in SHR persisted, despite lowering of their baseline MAP to levels of WKY or barodenervation. Microinjections of N-methyl-d-aspartic acid (NMDA) into the ARCN elicited decreases in MAP and GSNA and increases in HR in baroreceptor-intact WKY. However, after microinjections of gabazine into the ARCN, microinjections of NMDA into the same nucleus elicited pressor responses in baroreceptor-intact WKY. In barodenervated WKY, increases in MAP and GSNA were elicited by ARCN stimulation by NMDA and the increases in HR were exaggerated. In baroreceptor-intact SHR, ARCN stimulation by NMDA elicited increases in MAP, GSNA, and HR which persisted, despite lowering of baseline MAP or barodenervation. Increases in MAP and GSNA elicited by ARCN stimulation by NMDA in barodenervated SHR were significantly greater than corresponding increases in barodenervated WKY. These results indicated that attenuated γ-aminobutyric acid-ergic activity in the ARCN and impaired baroreflex function may contribute to increases in blood pressure and sympathetic nerve activity after ARCN stimulation by NMDA and elevation of baseline blood pressure in SHR.


Subject(s)
Arcuate Nucleus of Hypothalamus/physiopathology , Hypertension/physiopathology , gamma-Aminobutyric Acid/physiology , Animals , Arterial Pressure/drug effects , Baroreflex , Denervation , Dose-Response Relationship, Drug , Heart Rate/drug effects , Male , N-Methylaspartate/pharmacology , Neuropeptide Y/physiology , Pyridazines/pharmacology , Rats , Rats, Inbred SHR , Rats, Inbred WKY
11.
PLoS One ; 7(9): e45180, 2012.
Article in English | MEDLINE | ID: mdl-23028831

ABSTRACT

The mechanism of cardiovascular responses to chemical stimulation of the hypothalamic arcuate nucleus (ARCN) was studied in urethane-anesthetized adult male Wistar rats. At the baseline mean arterial pressure (BLMAP) close to normal, ARCN stimulation elicited decreases in MAP and sympathetic nerve activity (SNA). The decreases in MAP elicited by ARCN stimulation were attenuated by either gamma-aminobutyric acid (GABA), neuropeptide Y (NPY), or beta-endorphin receptor blockade in the ipsilateral hypothalamic paraventricular nucleus (PVN). Combined blockade of GABA-A, NPY1 and opioid receptors in the ipsilateral PVN converted the decreases in MAP and SNA to increases in these variables. Conversion of inhibitory effects on the MAP and SNA to excitatory effects following ARCN stimulation was also observed when the BLMAP was decreased to below normal levels by an infusion of sodium nitroprusside. The pressor and tachycardic responses to ARCN stimulation at below normal BLMAP were attenuated by blockade of melanocortin 3/4 (MC3/4) receptors in the ipsilateral PVN. Unilateral blockade of GABA-A receptors in the ARCN increased the BLMAP and heart rate (HR) revealing tonic inhibition of the excitatory neurons in the ARCN. ARCN stimulation elicited tachycardia regardless of the level of BLMAP. ARCN neurons projecting to the PVN were immunoreactive for glutamic acid decarboxylase 67 (GAD67), NPY, and beta-endorphin. These results indicated that: 1) at normal BLMAP, decreases in MAP and SNA induced by ARCN stimulation were mediated via GABA-A, NPY1 and opioid receptors in the PVN, 2) lowering of BLMAP converted decreases in MAP following ARCN stimulation to increases in MAP, and 3) at below normal BLMAP, increases in MAP and HR induced by ARCN stimulation were mediated via MC3/4 receptors in the PVN. These results provide a base for future studies to explore the role of ARCN in cardiovascular diseases.


Subject(s)
Arcuate Nucleus of Hypothalamus/drug effects , Cardiovascular System/drug effects , Paraventricular Hypothalamic Nucleus/drug effects , Sympathetic Nervous System/drug effects , Animals , Arcuate Nucleus of Hypothalamus/metabolism , Arterial Pressure/drug effects , Arterial Pressure/physiology , Cardiovascular System/metabolism , Glutamate Decarboxylase/metabolism , Heart Rate/drug effects , Injections, Intraventricular , Male , N-Methylaspartate/pharmacology , Narcotic Antagonists , Neuropeptide Y/pharmacology , Nitroprusside/pharmacology , Paraventricular Hypothalamic Nucleus/metabolism , Rats , Rats, Wistar , Receptor, Melanocortin, Type 3 , Receptor, Melanocortin, Type 4/antagonists & inhibitors , Receptor, Melanocortin, Type 4/metabolism , Receptors, GABA-A/metabolism , Receptors, Melanocortin/antagonists & inhibitors , Receptors, Melanocortin/metabolism , Receptors, Neuropeptide Y/agonists , Receptors, Neuropeptide Y/antagonists & inhibitors , Receptors, Neuropeptide Y/metabolism , Receptors, Opioid/agonists , Receptors, Opioid/metabolism , Stimulation, Chemical , Sympathetic Nervous System/metabolism , beta-Endorphin/pharmacology
12.
PLoS One ; 7(12): e53111, 2012.
Article in English | MEDLINE | ID: mdl-23300873

ABSTRACT

We have previously reported that chemical stimulation of the hypothalamic arcuate nucleus (ARCN) in the rat elicited increases as well as decreases in blood pressure (BP) and sympathetic nerve activity (SNA). The type of response elicited from the ARCN (i.e., increase or decrease in BP and SNA) depended on the level of baroreceptor activity which, in turn, was determined by baseline BP in rats with intact baroreceptors. Based on this information, it was hypothesized that baroreceptor unloading may play a role in the type of response elicited from the ARCN. Therefore, the effect of barodenervation on the ARCN-induced cardiovascular and sympathetic responses and the neurotransmitters in the hypothalamic paraventricular nucleus (PVN) mediating the excitatory responses elicited from the ARCN were investigated in urethane-anesthetized adult male Wistar rats. Bilateral barodenervation converted decreases in mean arterial pressure (MAP) and greater splanchnic nerve activity (GSNA) elicited by chemical stimulation of the ARCN with microinjections of N-methyl-D-aspartic acid to increases in MAP and GSNA and exaggerated the increases in heart rate (HR). Combined microinjections of NBQX and D-AP7 (ionotropic glutamate receptor antagonists) into the PVN in barodenervated rats converted increases in MAP and GSNA elicited by the ARCN stimulation to decreases in MAP and GSNA and attenuated increases in HR. Microinjections of SHU9119 (a melanocortin 3/4 receptor antagonist) into the PVN in barodenervated rats attenuated increases in MAP, GSNA and HR elicited by the ARCN stimulation. ARCN neurons projecting to the PVN were immunoreactive for proopiomelanocortin, alpha-melanocyte stimulating hormone (alpha-MSH) and adrenocorticotropic hormone (ACTH). It was concluded that increases in MAP and GSNA and exaggeration of tachycardia elicited by the ARCN stimulation in barodenervated rats may be mediated via release of alpha-MSH and/or ACTH and glutamate from the ARCN neurons projecting to the PVN.


Subject(s)
Arcuate Nucleus of Hypothalamus/physiopathology , Blood Pressure/physiology , Cardiovascular System/innervation , Heart Rate/physiology , Pressoreceptors/physiopathology , Splanchnic Nerves/physiopathology , 2-Amino-5-phosphonovalerate/analogs & derivatives , 2-Amino-5-phosphonovalerate/pharmacology , Adrenocorticotropic Hormone/metabolism , Animals , Arcuate Nucleus of Hypothalamus/drug effects , Arcuate Nucleus of Hypothalamus/metabolism , Blood Pressure/drug effects , Cardiovascular System/drug effects , Denervation , Excitatory Amino Acid Antagonists/pharmacology , Heart Rate/drug effects , Male , Melanocyte-Stimulating Hormones/pharmacology , Paraventricular Hypothalamic Nucleus/metabolism , Pro-Opiomelanocortin/metabolism , Quinoxalines/pharmacology , Rats , Rats, Wistar , Receptors, Corticotropin/antagonists & inhibitors , Splanchnic Nerves/drug effects , Sympathetic Nervous System/drug effects , Sympathetic Nervous System/metabolism , Sympathetic Nervous System/physiopathology , alpha-MSH
13.
Int J Radiat Oncol Biol Phys ; 82(2): 626-34, 2012 Feb 01.
Article in English | MEDLINE | ID: mdl-21277117

ABSTRACT

PURPOSE: The purpose of this study was to elucidate the efficacy and optimal method of radiotherapy in the management of solitary extramedullary plasmacytoma occurring in the head and neck regions (EMPHN). METHODS AND MATERIALS: Sixty-seven patients (43 male and 24 female) diagnosed with EMPHN between 1983 and 2008 at 23 Japanese institutions were reviewed. The median patient age was 64 years (range, 12-83). The median dose administered was 50 Gy (range, 30-64 Gy). Survival data were calculated by the Kaplan-Meier method. RESULTS: The median follow-up duration was 63 months. Major tumor sites were nasal or paranasal cavities in 36 (54%) patients, oropharynx or nasopharynx in 16 (23%) patients, orbita in 6 (9%) patients, and larynx in 3 (5%) patients. The 5- and 10-year local control rates were 95% and 87%, whereas the 5- and 10-year disease-free survival rates were 56% and 54%, respectively. There were 5 (7.5%), 12 (18%), and 8 (12%) patients who experienced local failure, distant metastasis, and progression to multiple myeloma, respectively. In total, 18 patients died, including 10 (15%) patients who died due to complications from EMPHN. The 5- and 10-year overall survival (OS) rates were 73% and 56%, respectively. Radiotherapy combined with surgery was identified as the lone significant prognostic factor for OS (p = 0.04), whereas age, gender, radiation dose, tumor size, and chemotherapy were not predictive. No patient experienced any severe acute morbidity. CONCLUSIONS: Radiotherapy was quite effective and safe for patients with EMPHN. Radiotherapy combined with surgery produced a better outcome according to survival rates. These findings require confirmation by further studies with larger numbers of patients with EMPHN.


Subject(s)
Head and Neck Neoplasms/radiotherapy , Plasmacytoma/radiotherapy , Adolescent , Adult , Aged , Aged, 80 and over , Child , Combined Modality Therapy/methods , Combined Modality Therapy/mortality , Disease Progression , Disease-Free Survival , Female , Head and Neck Neoplasms/mortality , Head and Neck Neoplasms/surgery , Humans , Magnetic Resonance Imaging , Male , Middle Aged , Multiple Myeloma/pathology , Plasmacytoma/mortality , Plasmacytoma/surgery , Prognosis , Radiotherapy Dosage , Radiotherapy, Conformal , Survival Rate , Young Adult
14.
Arch Gynecol Obstet ; 284(4): 1007-14, 2011 Oct.
Article in English | MEDLINE | ID: mdl-21116639

ABSTRACT

PURPOSE: To examine the preliminary survival outcomes and treatment-related toxicity for elderly patients with cervical cancer treated with radiotherapy (RT). METHODS: Forty patients ≥75 years old with cervical cancer who were treated with RT were evaluated. Of these 40 patients, 25 were classified as FIGO stage I or II and 15 as stage III or IVA. Thirty-five patients were treated with radical RT (RRT), and five were treated with surgery plus adjuvant RT (S + ART). External beam radiotherapy combined with high-dose-rate intracavitary brachytherapy was performed on 31 patients who were treated with RRT and on 2 patients who were treated with S + ART because of positive vaginal surgical margins. The patients' median age was 78 years (range 75-89 years). Concurrent chemotherapy (CCT) was performed on five patients (RRT: 3, S + ART: 2). RESULTS: The median follow-up period was 20 months (range 1-85 months). Only one patient could not complete RT. The 3-year overall and disease-specific survival (OS and DSS) rates for all patients were 58 and 80%, respectively. Five patients experienced Grade 3 acute toxicity; two were treated with RRT (2/35), and three were treated with S + ART (3/5, 2 of them with CCT). Two patients experienced Grade 3 late toxicity; one was treated with RRT (1/35, with CCT) and the other was treated with S + ART (1/5). No Grade 4 or higher toxicity was experienced. CONCLUSIONS: RRT for elderly patients with cervical cancer is generally effective and safe, but severe toxicity may occur with more aggressive treatment modalities.


Subject(s)
Gastrointestinal Diseases/epidemiology , Neoplasm Recurrence, Local/radiotherapy , Radiotherapy/statistics & numerical data , Uterine Cervical Neoplasms/radiotherapy , Adenocarcinoma/mortality , Adenocarcinoma/pathology , Adenocarcinoma/radiotherapy , Aged , Aged, 80 and over , Brachytherapy/adverse effects , Brachytherapy/statistics & numerical data , Carcinoma, Squamous Cell/mortality , Carcinoma, Squamous Cell/pathology , Carcinoma, Squamous Cell/radiotherapy , Combined Modality Therapy , Disease-Free Survival , Female , Gastrointestinal Diseases/chemically induced , Health Services for the Aged , Humans , Japan/epidemiology , Neoplasm Recurrence, Local/mortality , Neoplasm Recurrence, Local/pathology , Neoplasm Staging , Radiotherapy/adverse effects , Radiotherapy, Adjuvant , Retrospective Studies , Treatment Outcome , Uterine Cervical Neoplasms/mortality , Uterine Cervical Neoplasms/pathology
15.
Heart Vessels ; 26(3): 321-37, 2011 May.
Article in English | MEDLINE | ID: mdl-21127886

ABSTRACT

We investigated cardiac and vascular gene profiles in response to immobilization stress (IMO) in rats, an animal model of emotional stress-induced takotsubo cardiomyopathy using microarray analysis, followed by re-confirmation with real-time reverse transcription-polymerase chain reaction. Expression levels of the identified genes were further estimated by pretreatment with an α1-adrenoceptor blocker and/or a ß1-adrenoceptor blocker. In response to IMO, expression of 46 genes was significantly altered in the heart and that of 49 genes was significantly altered in the aorta. Pathway analysis with DAVID Bioinformatics Resources indicated that regulation of transcription and response to endogenous stimulation were the top two scoring pathways. Altered expression of cardiac genes was blunted by pretreatment with a ß1-adrenoceptor blocker or α1 + ß1-adrenoceptor blockers. In contrast, that of aortic genes was blunted by pretreatment with an α1-adrenoceptor blocker or α1 + ß1-adrenoceptor blockers. Activation of α1-adrenoceptor in the blood vessels or activation of ß1-adrenoceptors in the heart were mainly responsible for emotional stress-induced alteration of cardiac and vascular gene profiles.


Subject(s)
Aorta/metabolism , Gene Expression Profiling , Myocardium/metabolism , Stress, Psychological/complications , Takotsubo Cardiomyopathy/genetics , Adrenergic alpha-1 Receptor Antagonists/pharmacology , Adrenergic beta-1 Receptor Antagonists/pharmacology , Analysis of Variance , Animals , Aorta/drug effects , Computational Biology , Disease Models, Animal , Emotions , Gene Expression Profiling/methods , Gene Expression Regulation , Male , Oligonucleotide Array Sequence Analysis , Rats , Rats, Wistar , Restraint, Physical/psychology , Reverse Transcriptase Polymerase Chain Reaction , Stress, Psychological/genetics , Takotsubo Cardiomyopathy/psychology , Time Factors , Transcription, Genetic
16.
Kobe J Med Sci ; 56(2): E38-49, 2010 Sep 28.
Article in English | MEDLINE | ID: mdl-21063145

ABSTRACT

A strategy to overcome radioresistance in cancer treatment has been expected. To evaluate the strategy, appropriate experimental models are needed. Radioresistant tumour models were originally established from human colon cancer cells, and we evaluated their molecular basis. Next, the growth inhibitory effects of newly synthesized vitamin K2 (VK2)-related compounds were tested. Here, we showed that these novel compounds have growth inhibitory effects not only on cancer cells of various origins, but also on radioresistant cells, through the generation of reactive oxygen species (ROS). Human colon, lung, and breast cancer cell lines were used for testing the growth inhibitory activities of several chemical compounds. Radioresistant tumour models were established by fractionated radiation exposure. Irradiated cells were selected by a single cell cloning method, and their sensitivity to ionizing radiation was evaluated by a colony-forming assay. The VK2 derivatives (named MQ-1, MQ-2, and MQ-3) were chemically synthesized. To evaluate the generation of ROS, flow cytometer analyses were performed. A radioresistant tumour model was established from the HCT116 human colon cancer cell line. The radioresistant cells from HCT116 also showed resistance to cisplatin. In the radioresistant cells, NF-κB was highly activated. MQ-1, MQ-2, and MQ-3 showed greater growth inhibitory activities than VK2 not only in various cancer cells but also in radioresistant cells through the generation of ROS. In conclusion, a radioresistant tumour model was originally established from colon cancer cell lines through NF-κB activation, and it could be a useful tool for evaluating anti-tumour agents. Newly synthesized VK2 derivatives (MQ-1, MQ-2 and MQ-3) seemed to be potential anti-tumour agents in various cancers and radioresistant cancers. The efficacy of those compounds was related to the generation of ROS. These findings together might pave the way for the treatment of radioresistant or recurrent cancers.


Subject(s)
Neoplasms/drug therapy , Neoplasms/radiotherapy , Radiation-Sensitizing Agents/pharmacology , Vitamin K 2/analogs & derivatives , Cell Line, Tumor , Cell Proliferation/drug effects , Cell Proliferation/radiation effects , Female , HCT116 Cells , Humans , NF-kappa B/metabolism , Neoplasms/metabolism , Neoplasms/pathology , Radiation Tolerance , Radiation-Sensitizing Agents/chemistry , Reactive Oxygen Species/metabolism , Tumor Stem Cell Assay , Vitamin K 2/chemistry , Vitamin K 2/pharmacology
17.
Head Neck ; 32(5): 646-55, 2010 May.
Article in English | MEDLINE | ID: mdl-19885926

ABSTRACT

BACKGROUND: The aim of this study was to evaluate the significance of nuclear factor-kappa B (NF-kappaB) expression as a marker of radioresistance in early-stage laryngeal cancer. METHODS: Thirty-five patients with local recurrence and 70 case-matched patients without local recurrence were entered in this study. NF-kappaB expression was compared with Bcl-2 and epidermal growth factor (EGF) receptor expression by immunohistochemistry, using pretreatment biopsy specimens. The prognostic value of NF-kappaB was also evaluated. Twenty-nine recurrent tumors were compared with pretreatment tumors. RESULTS: NF-kappaB expression in pretreatment tumors significantly correlated with local tumor control (p = .01), but bcl-2 and EGF receptor expression did not. Only NF-kappaB expression showed prognostic significance for local tumor control in both univariate and multivariate analyses (p = .008 and .04, respectively). NF-kappaB expression was markedly enhanced in 23 of 29 (80%) recurrent tumors. CONCLUSION: NF-kappaB expression may be a novel marker of radioresistance in early-stage laryngeal cancer.


Subject(s)
Carcinoma, Squamous Cell/radiotherapy , Laryngeal Neoplasms/radiotherapy , NF-kappa B/metabolism , Radiation Tolerance , Biomarkers, Tumor/metabolism , Carcinoma, Squamous Cell/pathology , Case-Control Studies , ErbB Receptors/metabolism , Female , Humans , Immunohistochemistry , Laryngeal Neoplasms/pathology , Male , Middle Aged , Neoplasm Recurrence, Local/metabolism , Prognosis , Proto-Oncogene Proteins c-bcl-2/metabolism
18.
Circ J ; 73(6): 1141-6, 2009 Jun.
Article in English | MEDLINE | ID: mdl-19372624

ABSTRACT

BACKGROUND: Disturbance of the coronary microcirculation and catecholamine intoxication, which may be responsible for the pathogenesis of takotsubo cardiomyopathy, could trigger an oxidative stress response in the heart. METHODS AND RESULTS: Expression and localization of inducible heme oxygenase-1 (HO-1), which is an oxidative stress-related factor in the heart of immobilization stressed (IMO) rats, an animal model of takotsubo cardiomyopathy, were investigated by real-time reverse transcriptase-polymerase chain reaction and in situ hybridization histochemistry and immunohistochemistry. In response to IMO, the levels of HO-1 mRNA in the heart and in the aorta were slightly increased at 90 min, and increased 3-fold at 3 h compared with control levels. The signals for HO-1 mRNA were expressed on scatted cells in the myocardium and aortic adventitia. Double fluorescence immunohistochemistry showed that HO-1 immunoreactive cells were also ED1 and ED2 positive, indicating that they were macrophages. The numbers of ED1 and ED2 positive cells were constant, whereas the number of HO-1 positive cells was increased 5-fold at 6 h compared with control levels. Blocking of alpha- and beta-adrenoceptors attenuated IMO-induced upregulation of HO-1 mRNA levels in the heart. CONCLUSIONS: Emotional stress and a surge of catecholamine upregulate HO-1 in the cardiac and aortic macrophages.


Subject(s)
Heme Oxygenase-1/metabolism , Takotsubo Cardiomyopathy/enzymology , Takotsubo Cardiomyopathy/pathology , Up-Regulation/physiology , Animals , Aorta/enzymology , Aorta/pathology , Catecholamines/metabolism , Disease Models, Animal , Heme Oxygenase-1/genetics , Macrophages/enzymology , Macrophages/pathology , Male , Myocardium/enzymology , Myocardium/pathology , Oxidative Stress/physiology , RNA, Messenger/metabolism , Rats , Rats, Wistar , Restraint, Physical/adverse effects , Stress, Psychological/enzymology , Stress, Psychological/etiology , Stress, Psychological/pathology , Time Factors
19.
Brain Res ; 1248: 115-26, 2009 Jan 12.
Article in English | MEDLINE | ID: mdl-19022229

ABSTRACT

This study was designed to examine the mechanism of heart rate (HR) responses elicited by the stimulation of hypothalamic paraventricular nucleus (PVN). Experiments were done in urethane-anesthetized, barodenervated, adult, male Wistar rats. Chemical stimulation of the PVN by unilateral microinjections of N-methyl-d-aspartic acid (NMDA) elicited increases in HR which were attenuated by bilateral vagotomy. PVN-induced tachycardia was also attenuated by the blockade of the spinal ionotropic glutamate receptors (iGLURs) which was accomplished by intrathecal injections at T9-T10 or direct application at T1-T4 of iGLUR antagonists. The blockade of spinal iGLURs combined with bilateral vagotomy completely blocked PVN-induced tachycardia. Blockade of GABA receptors in the medial nucleus tractus solitarius (mNTS) also attenuated the PVN-induced tachycardia. Complete blockade of PVN-induced tachycardia was also observed after the blockade of iGLURs in both the spinal cord and mNTS. Combination of the blockade of mNTS GABA receptors and spinal iGLURs also abolished PVN-induced tachycardia. PVN-induced tachycardia was not altered by the blockade of spinal vasopressin or oxytocin receptors at T1-T4. These results suggested that in barodenervated rats: 1) tachycardia elicited by the chemical stimulation of the PVN was mediated via both inhibition of vagal and activation of sympathetic outflows to the heart, 2) the vagal inhibition contributing to the PVN-induced tachycardia was mediated by the iGLURs and GABARs in the mNTS, 3) sympathetic activation contributing to the PVN-induced tachycardia was mediated via spinal iGLURs, and 4) spinal vasopressin and oxytocin receptors were not involved in the mediation of PVN-induced tachycardia.


Subject(s)
Heart Rate/physiology , Paraventricular Hypothalamic Nucleus/physiology , Animals , Antidiuretic Hormone Receptor Antagonists , Autonomic Denervation , Excitatory Amino Acid Antagonists/pharmacology , GABA Antagonists/pharmacology , Heart/innervation , Male , Microinjections , N-Methylaspartate/pharmacology , Rats , Rats, Wistar , Receptors, GABA/metabolism , Receptors, Glutamate/metabolism , Receptors, Vasopressin/metabolism , Solitary Nucleus/physiology , Spinal Cord/physiology , Spinal Nerves/physiology , Stimulation, Chemical , Sympathetic Nervous System/physiology , Vagotomy
20.
Clin Exp Hypertens ; 29(6): 403-18, 2007 Aug.
Article in English | MEDLINE | ID: mdl-17729057

ABSTRACT

Exposure of experimental animals to noxious somatic stimulations sometimes induces sustained hypertension. Information regarding the medullary projections of somatic afferents and the neurotransmitters involved in them is incomplete. The present investigation in urethane-anesthetized, artificially ventilated, adult male Wistar rats was undertaken to clarify some of these issues. It was observed that the inhibition of contralateral, ipsilateral, or bilateral rostral ventrolateral medullary pressor area (RVLM) with muscimol attenuated the pressor and tachycardic responses to sciatic nerve stimulation. Similar inhibition of the medial subnucleus of the solitary tract (mNTS) exaggerated the cardiovascular responses to sciatic nerve stimulation. Interruption of the baroreflex by microinjections of ionotropic glutamate receptor antagonists into the mNTS or barodenervation also exaggerated the responses to sciatic nerve stimulation. Unilateral stimulation of the aortic nerve blocked the cardiovascular responses to the sciatic nerve stimulation. These results indicated that in the rat, the ascending afferents in the sciatic nerve project bilaterally to the RVLM as well as mNTS; an excitatory amino acid, probably glutamate, is released in the mNTS in response to the sciatic nerve stimulation; and barodenervation or blockade of baroreflex in the mNTS exaggerates, while baroreceptor stimulation inhibits, cardiovascular responses to somatosensory stimulation.


Subject(s)
Baroreflex/physiology , Cardiovascular System , Sympathetic Nervous System , Afferent Pathways/anatomy & histology , Afferent Pathways/physiology , Animals , Blood Pressure/physiology , Cardiovascular Physiological Phenomena , Cardiovascular System/innervation , Cardiovascular System/metabolism , Excitatory Amino Acid Antagonists/administration & dosage , Excitatory Amino Acid Antagonists/metabolism , Glutamic Acid/administration & dosage , Glutamic Acid/metabolism , Heart Rate/physiology , Male , Medulla Oblongata/anatomy & histology , Medulla Oblongata/physiology , Microinjections , Rats , Rats, Wistar , Reflex/physiology , Sciatic Nerve/physiology , Solitary Nucleus/anatomy & histology , Solitary Nucleus/drug effects , Solitary Nucleus/physiology , Sympathetic Nervous System/anatomy & histology , Sympathetic Nervous System/physiology
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