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Non steroidal anti-inflammatory drugs （ NSAIDS） are widely used in athletes. Poultice are also widely used in athletes. One of them has side effect of photosensitive. It can be avoided if athlete knows its side effects. So in general， athletes should know medicinal of NSAIDS of their own use. Risk of injury occasion in athletes is high. Injured fingers or elbow of athletes should be rightly receiving cure of them. So they would not have hangover from them in future.

Mortality, macroangiopathic events and end-stage renal disease (ESRD) in the elderly under long-term, intensive multifactorial diabetes control were prospectively investigated. Three hundred and eighty-eight elderly patients (> or =65 years) with type 2 diabetes (the mean age 72.9 years, men/women ratio 176/212) were followed-up for 6 years with HbA1c 7.0%, BP 145/80 mmHg and total cholesterol

OBJECTIVES: To examine retinopathy and nephropathy in elderly patients with diabetes mellitus (DM) under intensive multifactorial DM control. DESIGN: Six-year interventional observation study. SETTING: Multicenter study including four hospitals. PARTICIPANTS: Four hundred thirteen elderly (≥65) patients with type 2 DM attending each hospital for 1 year or longer; those receiving hemodialysis or with uncured malignancy were excluded. MEASUREMENTS: Development, worsening, and improvement of retinopathy and nephropathy and respective risk factors. RESULTS: The mean baseline hemoglobin (HbA1c), blood pressure (BP), and total cholesterol were 6.8%, 137/74 mmHg, and 5.13 mmol/L, respectively. Retinopathy developed in 45 of 168 (27%) patients and, of 63 with nonproliferative retinopathy, worsened and improved in 11 (17%) and 23 (37%), respectively. Nephropathy developed in 53 of 227 (23%) patients and improved in 13 of 51 (25%) having it baseline. The mean change in glomerular filtration rate (ΔGFR, baseline GFR–GFR at the end of the study period) in those with nephropathy at baseline was 21.5 mL/min. HbA1c was related to development of retinopathy (P=.001, odds ratio (OR)=1.91), and serum creatinine (P=.03, OR=1.02), systolic BP (SBP) (P=.03, OR=1.22), and prior stroke (P=.005, OR=3.21) were related to development of nephropathy. In patients with nephropathy at baseline, SBP (P=.03, Spearman's rho (ρ)=0.310), total cholesterol (P=.01, ρ=0.361), and low-density lipoprotein cholesterol (P=.03, ρ=0.322) were correlated with ΔGFR. CONCLUSION: In elderly patients under intensive control for DM, the outcome of microangiopathy is favorable. Modifiable risk factors were hyperglycemia for development of retinopathy and hypertension and hypercholesterolemia for development or worsening of nephropathy; prior stroke was an unmodifiable risk factor for development of nephropathy.

A 68-year-old man was admitted because of tonic–clonic convulsion. He had been receiving 200 mg itraconazole for 10 days. He had hypokalaemia (2.2 mEq/l), hypercalcaemia (Ca corr 11.0 mg/dl) and elevated serum parathyroid hormone (PTH, 95 pg/ml). Ultrasound examination of the neck revealed a low echoic tumour. Cessation of itraconazole and fluid supplementation eradicated clinical symptoms and profound hypokalaemia, but serum potassium remained low normal (3.4 mEq/l) and the mild hypercalcaemia and elevated PTH were unchanged. To conclude, a small amount of itraconazole (200 mg) precipitated profound hypokalaemia and seizure in a patient with mild hyperparathyroidism and low normal serum potassium.

An 87-year-old man was admitted with fatigue, anorexia, vomiting, urinary incontinence, and a depressive state. His consciousness was evaluated as a 13 on the Glasgow Coma Scale (E4V3M6), and he had a body temperature of 36.4°C, a blood pressure of 91/60 mmHg, and a heart rate of 88 beats/min. General laboratory data were unremarkable except for a mildly elevated serum creatinine level. The plasma levels of growth hormone, luteinizing hormone, and follicle stimulating hormone were depressed. On the other hand, the prolactin level was elevated, and the corticotropin, cortisol, and thyrotropin levels were within the reference ranges. Cranial magnetic resonance imaging (MRI) revealed the marked swelling of the pituitary gland and the infundibular stalk, and the serum immunoglobulin G4 (IgG4) level was elevated (2.85 g/L; reference range, 0.048-1.05 g/L). Accordingly, a diagnosis of IgG4-related autoimmune hypophysitis (AH) was made. The patient responded well to glucocorticoid therapy, but the presence of diabetes insipidus was revealed and was subsequently controlled using desamino-D-arginine vasopressin (DDAVP). To our surprise, an empty sella was apparent on an MRI examination performed on Day 12. The patient's serum IgG4 level had decreased in a log-linear manner with a half-life of 30 days, which was comparable to the half-life of IgG4 in control subjects (21 days). At a 16-month follow-up examination, no substantial changes in the morphology or function of the pituitary gland were noted. In conclusion, an empty sella developed within 12 days after the clinical onset of AH in the present case, suggesting that an empty sella may be the direct outcome of AH. The conversion of AH to an empty sella was associated with an immediate shutdown of IgG4 overproduction.

In late years, there are many reports about increasing of virus infections. It is necessary to be careful not to become lacking in fatigue and sleeping for viral infections such as herpesvirus, coxsackievirus and enterovirus (case 1,5). Even if merely insect is said to stick by outdoor activity (insect bite), the quick treatment is expected in the case of a face without having a scar, and knowledge about a rare disorder to need appropriate judgment is demanded (case 2,3). As for the cervical adenitis (case 4) with pyrexia, many causes are thought about, but it is necessary for infectious mononucleosis to know that it is causal one with a young woman.

OBJECTIVE— The goal of this study was to know the fate of albuminuria in Japanese patients with type 2 diabetes under tight blood pressure and glycemic control. RESEARCH DESIGN AND METHODS— Patients having normoalbuminuria (urinary albumin excretion RESULTS— Development occurred in 27 (15%) of the normoalbuminuric patients and progression and regression in 16 (17%) and 20 (21%), respectively, of the microalbuminuric patients. Significant independent relationships existed between development and higher achieved mean systolic blood pressure (SBP) and regression and lower achieved mean SBP. In the patients with achieved mean SBP CONCLUSIONS— Development and progression were low and regression was high with SBP of 120 mmHg, provided A1C was maintained at 6.5%.

The purposes of this study were to develop the scale of self-efficacy for health behavior, and to examine the relationship between self-efficacy for health behvior and self-rated health. Six hundred and three women's university students participated in this study. In first analysis, the scale of self-efficacy for health behavior was developed and examined its reliability and validity. The results indicated that the scale of self-efficacy for health behavior had acceptable reliability and validity. A second analysis explored the relationship between self-rated health and self-efficacy for health behavior. Structural equation modeling indicated that the self-efficacy for health behavior had a significant positive relationship with the self-rated health. These results suggest that the self-efficacy for health behavior is an important factor in enhancement of the self-rated health.

The familial variant of cardiac myxomas is an autosomally dominant disease. Here, we report a case of recurrent multiple cardiac myxomas wherein the patient, a 36-year-old woman who was referred for palpitations and nocturnal dyspnea, had a relevant familial history. Her mother had undergone extirpation of cardiac myxoma when she was about 50 years old. Echocardiography showed the presence of multiple cardiac myxomas. One of the cardiac myxomas nearly obstructed the left ventricular inflow; therefore, we extirpated the myxomas under cardiopulmonary bypass and cardioplegic arrest. The operation was uneventful and the postoperative clinical course was good. Pathological examination confirmed that the extirpated mass was a myxoma. Approximately 3 years after the first cardiac operation, we found a recurrent cardiac myxoma in the same patient. She then underwent a second operation and was discharged without any complications. Pathological examination also confirmed that the cardiac mass was a myxoma and that there was no malignancy. Learning objective: This familial multiple cardiac case is a rare case because of its multiplicity, location (especially, the myxoma in right atrium is rare) and recurrence at the same position. And we may suggest the pitfall or prevention for recurrence of cardiac myxoma.>

Because vascular endothelial cell growth factor (VEGF) and transforming growth factor-beta (TGF-beta) are both involved in cellular growth and differentiation, we examined whether VEGF modifies TGF-beta signaling cascade in human umbilical cord vein endothelial cells (HUVEC). Production of plasminogen activator inhibitor-1 (PAI-1), which is under the specific control of TGF-beta, was strongly enhanced (3.5-fold) by TGF-beta treatment. Remarkably, physiological concentration of VEGF (30 nm) profoundly (by 60%) attenuated the TGF-beta stimulation of PAI-1 production without an effect on the basal PAI-1 production. In HUVECs transiently transfected with an expression construct containing a PAI-1 promoter fused to luciferase reporter gene, TGF-beta-stimulation of transcription of PAI-1 was clearly (by 60%) inhibited by VEGF. TGF-beta phosphorylation of Smad2/3, an obligatory step of intracellular TGF-beta signaling, was also suppressed by VEGF. VEGF attenuation of TGF-beta action was also demonstrated in two other endothelial cell lines. In conclusion, VEGF attenuates TGF-beta action in the human endothelial cell, specifically at the level of transcription of PAI-1 gene and Smad2/3 phosphorylation.

To elucidate the hierarchy in the evolution of glucose intolerance in the general population, the relationship between plasma glucose (PG), beta-cell function (insulinogenic index [II] = DeltaIRI(0-30)/DeltaPG(0-30) on 75 g oral glucose tolerance test [OGTT], where IRI is immunoreactive insulin), insulin sensitivity (Si; determined by quantitative insulin sensitivity check index [QUICKI]), age, and body mass index (BMI) were analyzed in 504 Japanese health examinees (men/women: 347/157). The mean (+/-SD) age was 53 (+/-11) years, BMI 23.6 (+/-3.2) kg/m2, fasting PG (FPG) 5.61 (+/-0.97) mmol/L, 2-hour PG 7.42 (+/-3.1) mmol/L, II 74.2 (+/-169.3) [pmol/L]. [mmol/l](-1), and QUICKI 0.385 (+/-0.057) [log (microU/mL) + log (mg/100 mL)](-1). Higher FPG and 2-hour PG, respectively, were independently correlated with lower II, lower QUICKI, higher age, and higher BMI; the standardized correlation coefficient was largest for the correlation between PG and II. Based on the multiple linear regression, FPG = 8.565 - 1.201. log [II] - 5.374. QUICKI + 0.007. age + 0.030. BMI (r2 = 0.442), and 2-hour PG = 14.239 - 4.206. log [II] - 0.141. QUICKI + 0.034 - age + 0.141. BMI (r2 = 0.493). Thus, elevation of PG correlated most prominently with beta-cell dysfunction and less prominently with decreased Si, higher age, and BMI (especially so in the case of 2-hour PG). In conclusion, the primacy of beta-cell dysfunction in the process of developing glucose intolerance was strongly suggested in the Japanese general population.

It is important for us as doctors or trainers to keep writing papers on rare cases. We experience three rare cases of respiratory disease. First is a 44-year-old male with allergic broncho pulmonary aspergillosis (ABPA) whose complain is chest pain. He is improved by the treatment of prednisolone. Second is a severe case of 20-year-old female with mycoplasma pneumonia accompanied with encephalopaty. She is also improved by the treatment of MINO and RKM. Third is a 69-year-old female with liver cirrhosis accompanied with hypoxemia (hepatopulmonary syndrome). Liver cirrhosis can the cause of right to left shunt. Hepatopulmonary syndrome will be well treated by liver transplantation.

Although "polar triiodothyronine (T(3)) syndrome" in chronic dwellers/workers in Antarctica has been established, alteration of the pituitary thyroid-axis upon accidental hypothermia is not well recognized. We report here a rare case of elevation of thyrotropin (TSH) upon accidental hypothermia.A 75-year-old man was admitted because of consciousness disturbance.The mean outside temperature was approximately -2.0°C (28.4°F) but his house was inadequately heated. His rectal temperature was 29.5°C (85.1°F). Goiter was not palpable and pitting edema, not myxedema, was present. Serum TSH was elevated (28.3 mU/L, reference range 0.27-4.2), and free T(3) (FT(3)) and free thyroxine (FT(4)) lowered (FT(3), 3.25 pmol/L with a reference range of 4.00-7.85, and FT(4), 9.18 pmol/L with a reference range of 12.87-23.179), but thyroid-related autoantibodies were all negative. By the next morning, body temperature had risen to36°C (96.8°F) and there was no further recurrence of hypothermia. Serum TSH decreased exponentially and the patient's condition had become normal by day 22. FT(3) and FT(4) were found to be slightly lowered and elevated, respectively, during the same period, in the subnormal range. At the end of the observation period, the patient settled into the state known as "nonthyroidal illness syndrome."Elevation of TSH in an elderly patient with accidental hypothermia was normalized after restoration of normal body temperature. Elevation of TSH upon accidental hypothermia was probably an adaptive response.In patients with accidental hypothermia, the possibility of an adaptive elevation of TSH should be borne in mind. This clearly warrants further studies of the adaptation of the pituitary-thyroid axis in patients with accidental hypothermia.

Whole pancreas or β-cell transplantation has opened the way for the treatment of advanced stage of diabetes mellitus. However, it is always limited by the scarcity of transplantation materials. The amniotic membrane is part of the fetal membrane and is composed of amniotic epithelium (HAE) and mesenchymal (HAM) cells that are derived from the inner cell mass in the blastocyst. Thus, HAE and HAM cells may have the potential to differentiate into various organs. The aim of our study was to assess the possibility of HAE cells differentiating into insulin-producing cells. In vitro, HAE cells stimulated with nicotinamide induced insulin mRNA in the culture cells. In vivo, HAE cells were capable of normalizing the blood glucose level of diabetic mice after several weeks of implantation into streptozotocin-induced diabetic mice. The distribution of human cells and human insulin secretion in mouse tissue studied by immunohistochemistry for anti-human-specific β-2-microglobulin and anti-human-specific insulin shows the same location in mouse tissue. These studies suggest that HAE cells have the potential to differentiate into β-cells in vivo, and hence that HAE cells have therapeutic potential for the treatment of type I diabetes mellitus.

Mycoplasma pneumonia is a well-known cause of community-acquired pneumonia, and has a variety of appearances on radiographs of the chest. A 31-year-old man with a solitary mass on chest radiograph with dry cough visited our hospital. Transbronchial lung biopsy from the upper lung showed type II pneumocyte hyperplasia. We treated him with clarithromycin given the low probability of Mycoplasma pneumonia, resulting in improvement. Mycoplasma pneumonia can appear as solitary mass on chest radiographs.

OBJECTIVE—To clarify mortality and morbidity of intensively managed elderly diabetic individuals and to explore factors predicting mortality and diabetes-related end points. RESEARCH DESIGN AND METHODS—A total of 390 elderly (≥65 years of age) outpatients with type 2 diabetes ( 173 men and 217 women, mean age 73.0 years) were analyzed. The mean HbA1c upon entry was 6.8% (332 receiving oral hypoglycemics and/or insulin) and blood pressure upon entry was 136/74 mmHg (219 receiving antihypertensive drugs). The patients have been followed-up for 3 years with HbA1c RESULTS—The mortality rate, 2.9% per year, was comparable to that of the age- and sex-matched general population. Stroke was a leading cause of mortality after malignancy. By the univariate Cox proportional hazards model, only high serum creatinine and prior stroke were highly significant and strong risks for both end points. In those without prior stroke and receiving antihypertensive agents, the incidence of the diabetes-related end point based on their systolic blood pressure (SBP) quartile was U-shaped, with the nadir at the 3rd (SBP, 137–147 mmHg) and the peak at the 1st (SBP ≤ 125 mmHg) quartile. CONCLUSIONS—In well-controlled elderly diabetic subjects, there was no excessive mortality compared to the age- and sex-matched general population. Renal dysfunction and prior stroke were independent risks for mortality and morbidity. In those without prior stroke, a risk of too much lowering of blood pressure was suggested.

The potential role of protein acylation in the control of biphasic insulin secretion has been studied in isolated rat pancreatic islets. The protein acylation inhibitor cerulenin inhibited both phases of glucose-stimulated insulin secretion. However, it did not affect the secretory response to a depolarizing concentration of KCl in either the absence or presence of diazoxide. Therefore, cerulenin has no deleterious effect on the l-type Ca2+ channels or subsequent events in Ca2+ stimulus–secretion coupling. Advantage was taken of this to study the effect of cerulenin on the KATP channel–independent pathway of glucose signaling. In the presence of KCl and diazoxide, cerulenin powerfully inhibited the augmentation of insulin release by glucose and palmitate. Similar inhibition of the augmentation of release by glucose and palmitate was seen under Ca2+-free conditions in the presence of 12-O-tetradecanoylphorbol-13-acetate and forskolin. As neither glucose oxidation nor the effect of glucose to inhibit fatty acid oxidation is affected by cerulenin, these data suggest that protein acylation is involved in the KATP channel–independent pathway of glucose signaling.

Nutrient augmentation of Ca(2+)-triggered insulin release occurs in an ATP-sensitive K(+) (K(ATP)) channel--independent manner. Here, using rat islets, we explored the possibility of the K(ATP) channel-independent nutrient triggering of insulin release. In the presence of 250 micromol/l diazoxide, simultaneous application of forskolin and 16.7 mmol/l glucose strongly stimulated insulin release: fourfold and eightfold increases with 1 and 30 micromol/l forskolin, respectively. alpha-Ketoisocaproate (KIC) and 3-isobutylmethylxanthine (IBMX) could be used in place of glucose and forskolin, respectively, to trigger insulin release in the presence of diazoxide. Triggering of insulin release by a combination of nutrients and forskolin was not attenuated by 10 micromol/l nifedipine (a blocker of voltage-dependent Ca(2+) channels) and 2 micromol/l thapsigargin (an inhibitor of intracellular Ca(2+)-ATPase), ascertaining independence of this phenomenon from Ca(2+) entry and from intracellular Ca(2+) liberation. As anticipated, the action of glucose and KIC was greatly (>80%) suppressed by inhibition of mitochondrial metabolism by 2 mmol/l sodium azide (NaN(3)). A combination of palmitate and dimethyl glutamate (a cell-permeable glutamate donor), but not either one alone, weakly but unequivocally triggered insulin release when applied simultaneously with forskolin. In this case, however, mitochondrial poisoning by azide was without effect. The finding suggests that a combination of induced palmitoylation and cytosolic glutamate accumulation partially reconstituted signaling beyond mitochondrial metabolism in the beta-cell upon glucose stimulation. In conclusion, a combination of cAMP signal and nutrients potently triggers insulin release under full activation of the K(ATP) channel, indicating the multiplicity of driving force for insulin exocytosis.

Acute experimental iron loading causes iron to accumulate in the renal tissue. The accumulation of iron may play a role in enhancing oxidant-induced tubular injury by producing increased amounts of reactive oxygen species. From findings in cells from heme oxygenase-1 (HO-1)-deficient mice, HO-1 is postulated to prevent abnormal intracellular iron accumulation. Recently, it has been reported that HO-1 is induced in the renal tubular epithelial cells, in which iron is deposited after iron loading, and that this HO-1 induction may be involved in ameliorating iron-induced renal toxicity. We previously showed that chronic administration of angiotensin II to rats induces HO-1 expression in the tubular epithelial cells. These observations led us to investigate whether there is a link between iron deposition and HO-1 induction in renal tubular cells in rats undergoing angiotensin II infusion. In the present study, rats were given angiotensin II for continuously 7 days. Prussian blue staining revealed the distinct deposits of iron in the proximal tubular epithelial cells after angiotensin II administration. Electron microscopy demonstrated that iron particles were present in the lysosomes of these cells. Histologic and immunohistochemical analyses showed that stainable iron and immunoreactive ferritin and HO-1 were colocalized in the tubular epithelial cells. Treatment of angiotensin II-infused rats with an iron chelator, deferoxamine, blocked the abnormal iron deposition in kidneys and also the induced expression of HO-1 and ferritin expression. Furthermore, deferoxamine treatment suppressed the angiotensin II-induced increase in the urinary excretion of protein and N-acetyl-beta-D-glucosaminidase, a marker of tubular injury; however, deferoxamine did not affect the angiotensin II-induced decrease in glomerular filtration rate. These results suggest that angiotensin II causes renal injury, in part, by inducing the deposition of iron in the kidney.

Various renal insults result in induction of heat shock protein (HSP) expression within the kidney. Some of the HSPs induced in that manner are postulated to have renoprotective effects via either chaperoning actions or antioxidative properties. We have previously reported that long-term angiotensin (Ang) II administration induces the expression of renal HSP32, also known as heme oxygenase-1 (HO-1). Here, we investigated the regulation of expression and localization of other HSPs, including HSP70, HSP25, and αB-crystallin, in the kidney of rats undergoing long-term administration of Ang II (0.7 mg · kg −1 · d −1 ). Immunoblot analysis demonstrated that Ang II increased renal expression of HSP70 and HSP25, as well as HO-1, but that expression of αB-crystallin was unaffected by this treatment. The Ang II–induced increase in renal HSP70 and HSP25 was dependent on the angiotensin type 1 receptor activation but not on hypertension per se. Immunohistochemistry revealed that HSP70 and HSP25 were expressed in the medullar regions and in the renal arterial wall in the kidney of control rats. After Ang II infusion, signals for HSP70, HSP25, and HO-1 proteins increased in intensity in the endothelium and medial smooth muscle of the renal artery. In addition, all of these HSPs were induced in proximal renal tubular epithelial cells from the same segments, suggesting that similar mechanisms are responsible for upregulating these HSPs. Our data show that Ang II infusion induces renal HSP70 and HSP25, as well as HO-1, and that Ang II can induce expression of these HSPs in renal cells in a pressor-independent manner.

We appreciate the comments by Dr Kawada [1] on our recent article [2] that confirmed 1-h plasma glucose value on an oral glucose tolerance test as a better predictor of the development of Type 2 diabetes than fasting or 2-h plasma glucose values. His letter contained three comments regarding our article that we address here. This article is protected by copyright. All rights reserved.

Effects of growth hormone (GH), insulin-like growth factor I (IGF-I), and endothelin-1 (ET-1) on endothelial cell migration and the underlying molecular mechanisms were explored using a human umbilical cord endothelial cell line, ECV304 cells, in vitro. Treatment of the cells with IGF-I or ET-1, but not GH, stimulated the cell migration. Interestingly, however, ET-1-induced, but not IGF-I-induced, migration of the cells was inhibited by GH. Both ET-1 and IGF-I caused activation of mitogen-activated protein kinase (MAPK) in the cells, and GH eliminated the MAPK activation produced by ET-1 but not that produced by IGF-I. On the other hand, migration of the cells was stimulated by protein kinase C (PKC) agonist, phorbol 12-myristate 13-acetate. ET-1 promoted PKC activity, and a PKC inhibitor, GF-109203X, blocked ET-1-induced cell migration. Although GH inhibited ET-1-induced cell migration and MAPK activity, it did not block ET-1-induced PKC activation. Thus ET-1 stimulation of endothelial cell migration appears to be mediated by PKC/MAPK pathway, and GH may inhibit the MAPK activation by ET-1 at the downstream of PKC.

Insulinotropic action of glucose can be categorized as 1) triggering of release, 2) augmentation of exocytosis elicited by Ca2+, and 3) time-dependent potentiation (TDP) of the exocytotic machinery. Glucose-induced closure of ATP-sensitive K+ (K+ATP) channel is required for the first but not for the latter two. We examined the legitimacy of a novel hypothesis that glutamate is a conveyer of the K+ATP channel-independent glucose action, using intact rat pancreatic islets. To this end, we compared glucose and cell permeable glutamate donors such as dimethylglutamate and glutamine for their potency of augmentation and TDP in the presence of diazoxide (250 micromol/l), a K+ATP channel opener. One millimolar leucine was employed as an activator of glutamate dehydrogenase (GDH) as needed. A high concentration (16.7 mmol/l) of glucose applied simultaneously with a depolarizing concentration (50 mmol/l) of K+ augmented (5.80 fold) insulin release elicited by the latter. Pretreatment of the islets with 16.7 mmol/l glucose caused TDP so that insulin release subsequently elicited by 50 mmol/l K+ alone was enhanced (4.70 fold). The augmentation and TDP caused by dimethylglutamate and glutamine (10 mmol/l each), respectively, were very weak (12% of the glucose effect utmost), and dramatically enhanced upon activation of GDH by leucine. Insulinotropic effect of the glutamate donors, but not that of 50 mmol/l K+, was eliminated by 2 mmol/l NaN3, a mitochondrial poison. Glutamate per se serves as a weakly metabolizable mitochondrial fuel, but not a direct conveyer of the K+ATP channel-independent glucose action in the islet beta cell.

A 62-year-old man, receiving chronic haemodialysis and suffering from alcoholic liver cirrhosis and chronic pancreatitis, presented with hypoglycaemic coma. Plasma cortisol was undetectable (< 5.5 nmol/L) with suppressed adrenocorticotropic hormone (ACTH), which established a diagnosis of adrenal failure due to ACTH deficiency. Twenty-five milligrams of oral hydrocortisone eradicated hypoglycaemia. Presentation of adrenal failure in this patient was atypical because he was hypertensive, serum electrolytes including sodium were normal and anaemia was unremarkable, which were all due to end-stage renal disease and its treatment with haemodialysis. As far as we are aware, this is the first case report of hypoglycaemic coma due to adrenal failure in a chronic haemodialysis patient.

Heme oxygenase (HO) is a heme-catabolizing enzyme that converts heme into biliverdin, iron, and carbon monoxide. HO-1, an inducible form of HO, is thought to act as an endogenous antioxidant defense mechanism. To determine whether chronic administration of angiotensin II affects HO-1 expression in the heart, expression and localization of HO-1 were investigated in the heart of rats receiving angiotensin II infusion (0.7 mg · kg−1· day−1) via osmotic minipump for up to 7 days. Angiotensin II induced formation of granulation tissue, characterized by myofibroblast proliferation, fibrous deposition, and inflammatory cell migration. Angiotensin II also upregulated cardiac HO-1 expression. Immunohistochemistry revealed that HO-1 was intensively expressed in the granulation tissue. The selective AT1-receptor antagonist, losartan, completely, but hydralazine only partially, suppressed angiotensin II-induced granulation tissue formation and HO-1 upregulation. Chronic norepinephrine infusion (2.8 mg · kg−1· day−1) did not induce granulation tissue formation or HO-1 upregulation. Our data suggest that angiotensin II upregulates cardiac HO-1 expression in the newly formed inflammatory lesion, which may represent an adaptive response to angiotensin II-induced cardiac damage.

Parathyroid hormone-related protein (PTHrP) is frequently produced in pancreatic endocrine tumors. PTHrP is synthesized as the precursor pro-PTHrP and undergoes a series of posttranslational processing reactions, among which cleavage of a 12 amino acid sequence from its precursor is crucial for the biological activation of PTHrP. This cleavage is catalyzed by furin, a proprotein-processing endoprotease that cleaves the consensus sequence-Arg-X-(Lys/Arg)-Arg ↓ X-. We previously reported that furin is highly expressed in rat pancreatic islets during the perinatal stage and that the expression of furin in pancreatic β cells induces faster cell growth. From this, we postulated that furin may be co-expressed with PTHrP in insulinomas. We immunostained insulin, PTHrP, and furin in 21 human pancreatic endocrine tumors: 10 insulinomas, 5 VIPomas, 4 gastrinomas, and 2 somatostatinomas. Of these 21 endocrine tumors, furin was positively stained in all 10 insulinomas. Likewise, PTHrP was detected in the same insulinomas. We found one VIPoma and one gastrinoma contained a few insulin-positive cells scatteringly, which were also positive for furin and PTHrP. But other non-insulinoma endocrine tumors did not display furin and PTHrP positivity. We conclude that furin and its substrate pro-PTHrP are co-expressed specifically in insulinomas.

Background: There are few reports on long-term convalescence with regard to cardiac injury caused by blunt chest trauma. Nuclear medicine study of the heart (NMSH) in the early stages of injury is reportedly superior to detect the correlation between injury and fatal arrhythmia. Therefore, we prospectively performed NMSH and Holter electrocardiogram (ECG) in the early and chronic stages for a cardiac injury patient, and we longitudinally examined the recovery process and the occurrence of fatal arrhythmia. Methods and Results: A total of 202 patients with blunt chest trauma were admitted to our hospital between April 2006 and January 2007. Of 65 patients who were diagnosed with cardiac injury by ECG, a myocardial enzyme, or cardiac ultrasonography, 11 were enrolled in this study because they agreed to outpatient visiting for regular examinations for 1 year. NMSH showed positive findings in 6 of the 11 patients in the acute period of < 1 month. Twelve months later, five patients improved but still exhibited protracted cardiac damage without complete recovery. Among the six patients in whom NMSH showed positive findings, Holter ECG indicated an abnormal finding in two patients in the acute period and in four patients in the chronic period, and detected one patient with a nonsustained ventricular tachycardia in the chronic period. Conclusion: Cardiac injuries may exacerbate cardiac functions and lead to fatal arrhythmia during the chronic period. Therefore, evaluating recovery for at least 12 months after myocardial damage is necessary to prevent sudden cardiac death.

Gastroesophageal reflux（GER）with sliding hernia can cause chronic cough or bronchial asthma. In late years，these reports of pulmonary disease with GERD（gastroesophageal reflux disease）are increasing in Asia. We experienced older aged woman with bronchial athma complicated with GERD. However increasing reports of asthma with GERD，the cause of brobchoconstriction complicated with sliding hernia is stil unclear. Previous researchers found a significantly higher incidence rate for GERD in those with a previous diagnosis of asthma than in controls，indicating that patients with asthma were 1.8 times more likely to evelop GERD than those without asthma. In this study，we reviewed the association between gastro-esophageal reflux disease and sthma.

Glucose metabolism in glycolysis and in mitochondria is pivotal to glucose-induced insulin secretion from pancreatic β cells. One or more factors derived from glycolysis other than pyruvate appear to be required for the generation of mitochondrial signals that lead to insulin secretion. The electrons of the glycolysis-derived reduced form of nicotinamide adenine dinucleotide (NADH) are transferred to mitochondria through the NADH shuttle system. By abolishing the NADH shuttle function, glucose-induced increases in NADH autofluorescence, mitochondrial membrane potential, and adenosine triphosphate content were reduced and glucose-induced insulin secretion was abrogated. The NADH shuttle evidently couples glycolysis with activation of mitochondrial energy metabolism to trigger insulin secretion.

Recent studies revealed favorable para- and/or autocrine effects of IGF-1 in the pathogenesis of diabetic complications. On the other hand, hyperglycemia is a risk factor for the development of diabetic vascular complications. In this study we examined the effects of high glucose and/or IGF-1 on cell migration and angiogenesis (tubular formation) by using human endothelial cells (EC) in vitro. First we examined cell migration by the two-chamber method. Chronic treatment with a high concentration of D-glucose strongly stimulated the cell migration, which was mimicked by PMA, a protein kinase C (PKC) agonist. The cell migration was also induced by IGF-1. The glucose-induced cell migration was blocked by PKC inhibitor, H7. IGF-1-induced cell migration was not blocked by PD98059, MAPK/ERK kinase (MEK) inhibitor or wortmannin, a phosphatidylinositol (PI) 3-kinase inhibitor. Next we examined the effects of high glucose and/or IGF-1 on the tubular formation of EC. The tubular formation was induced only when the cells were exposed to a combination of high glucose and IGF-1. The tubular formation was blocked by MEK inhibitor and PI 3-kinase inhibitor but not by PKC inhibitor. These results indicate that hyperglycemia and IGF-1, respectively, stimulate the EC migration, and tubular formation is induced by a combination of IGF-1 and hyperglycemia.

Graves' disease is an autoimmune disorder characterized by the presence of antibodies against thyrotropin receptor (TRAb). Stem cell factor (SCF), derived from bone marrow, is known to promote lymphohematopoiesis. To investigate the relation between the alteration in plasma levels of SCF, thyroid hormone status, and TRAb measured by thyrotropin binding inhibition (TBI), 13 untreated, 21 treated, and 4 relapsed hyperthyroid Graves' disease patients, 21 patients with Hashimoto's thyroiditis, 6 patients with subacute thyroiditis, and 11 control subjects were examined. In untreated hyperthyroid Graves' disease patients, serum levels of thyroxine (T4) and triiodothyronine decreased rapidly by methimazole treatment, and TBI decreased progressively, but variably. Simultaneously, the elevated plasma levels of SCF decreased gradually and progressively. The plasma levels of SCF correlated curvilinearly with the serum levels of T4. In 4 patients with relapsed hyperthyroid Graves' disease, TBI was marginally positive in 3 patients and negative in 1, but plasma levels of SCF were elevated significantly in all 4 patients. In patients with subacute thyroiditis and Hashimoto's thyroiditis with or without T4 replacement, plasma levels of SCF did not differ from that of controls. These findings indicate that the elevation of plasma levels of SCF relates to the longstanding thyrotoxic state and that short-term thyrotoxicosis does not significantly affect plasma levels of SCF. It remains to be determined whether the elevation in plasma levels of SCF is induced by excess thyroid hormone, reflecting the hypermetabolic state, or whether the elevation of plasma levels of SCF contributes to stimulation of lymphocytes producing TRAb.

Analysis of patients with persistent hypothyroidism due to Hashimoto's thyroiditis suggested that metabolism of thyroxine (T4), including deiodination to triiodothyronine (T3), was reduced in the elderly. The increase in the serum levels of T4 after oral administration of T4 was augmented in the elderly, whereas increase in the serum T3 level was not. Possibly due to the reduction in the pituitary deiodinase, suppression by T4 administration of serum thyrotropin (TSH) level was the same in elderly as in younger subjects despite a larger increase in the serum levels of T4 in the elderly. Consequently, the amount of T4 required to maintain a normal serum TSH level did not differ between elderly and younger subjects. Other characteristics of elderly patients with Hashimoto's thyroiditis were that goiter size was smaller, that hypothyroidism was more frequent, and that Graves' disease was less frequent.

This study was designed to delineate the nature of beta-cell dysfunction in a model of genetically determined nonobese diabetes, the Goto-Kakizaki (GK) rat. Pancreatic beta-cell function was analyzed immediately after weaning and 5 weeks thereafter, comparing animals with or without insulin treatment during the interval. In 3.5-week-old GK rats, fasting plasma glucose was mildly elevated with normoinsulinemia, and the islet insulin content was reduced by 33%. When incubated with 3-30 mM glucose in vitro, the GK rat islets showed reduced glucose sensitivity, i.e. the EC50 values were 19.5 and 15.9 mM, and the Hill constants for the positive cooperativity 2.1 and 4.2 in the islets of GK and the control rats, respectively. On the other hand, the maximum response to glucose was not attenuated when reduced islet insulin content was considered. In 8.5-week-old GK rats hyperglycemia worsened and glucose-stimulated insulin release by the islets more severely impaired. A daily insulin injection from the 3.5-8.5 weeks of age significantly lowered plasma glucose in the GK rat, accompanied by a marked suppression of both basal (with 3 mM glucose) and glucose (6-30 mM)-stimulated insulin release by the islets. In the GK rat, beta-cell dysfunction develops by the age of 3.5 weeks, and insulin treatment during the subsequent 5 weeks accelerates its progression.

The role of the renin-aldosterone system and the ability of renal sodium reabsorption to facilitate pressure natriuresis were analyzed by using a sufficient number of Japanese patients with essential hypertension.We studied 3222 normal Japanese subjects (610 in Kashiwa City Hospital and 2612 in Shinshu University Hospital), 741 Japanese patients with essential hypertension (256 in Kashiwa City Hospital and 485 in Shinshu University Hospital), 20 patients with aldosterone-producing adenomas and 11 patients with idiopathic hyperaldosteronism to determine the possible roles of sodium, renal function, and plasma aldosterone concentration (PAC) on blood pressure elevation. Inappropriate elevation of aldosterone levels [elevation of the aldosterone:plasma renin activity (PRA) ratio] was used to assess aldosterone action.The peak of the serum sodium distribution curve was approximately 2 mmol/l higher in the patients with essential hypertension than it was in controls. The prevalence of higher serum sodium concentrations (or = 147 mmol/l) also was increased significantly hypertensive patients. Age-related deterioration of renal function did not explain the hypertension and abnormal sodium metabolism in the hypertensive patients. In stepwise regression analysis, the serum sodium concentration was related inversely to the PRA and positively to the PAC:PRA ratio. Although there was an inverse relationship between urinary sodium excretion (representing sodium intake) and the PRA, urinary sodium excretion proved not to be significant as a source of variation in the PAC or in the PAC:PRA ratio in the hypertensive patients. Although the PAC was within the normal range in patients with serum sodium concentrations of 147 mmol/l or more and an elevated PAC:PRA ratio, it was inappropriately high for the stimulus applied, as indicated by the PRA; this is similar to the situation with aldosterone-producing adenomas or idiopathic hyperaldosteronism.Serum sodium distribution patterns differed between normal subjects and patients with essential hypertension in this Japanese population. The deterioration of renal function and increased sodium intake did not explain this abnormal sodium metabolism. A higher serum sodium concentration is related to an elevated blood pressure, and, in some patients, an inappropriate elevation of plasma aldosterone levels. Of the Japanese hypertensive patients, 10-14% exhibited serum sodium concentrations of 147 mmol/l or more and inappropriate elevations of aldosterone level (suppressed PRA and normal aldosterone level). The defect in these patients presumably lies in the inappropriately high secretion of aldosterone.

It is reported that viral infections have been increasing recent years. An epidemic parotitis is an acute systemic mumps viral infection that occurs most commonly in children, and clinically characterized by non-suppurative parotitis. Parotitis, meningitis, orchitis, and pancreatitis are clinical manifestations of mumps. The differential diagnosis of parotitis includes infections caused by other virus or bacteria. We experience two cases of parotitis. First is an 18-year-old female with bacterial parotitis, and second is a case of 33-year-old male orchitis with epidemic parotitis. Although sterility caused by orchitis is an uncommon complication, it is important for adults to make new viral preventive strategy against such as Mumps.

The risk factors for impaired fasting glucose (IFG) and impaired glucose tolerance (IGT) have yet to be established. Our aim was to elucidate the predisposing factors for IFG and IGT in Japanese subjects with normal glucose tolerance (NGT). Using a 75 g oral glucose tolerance test (OGTT), we analyzed 604 adults with the ADA-defined NGT. Follow-up glucose tolerance status was determined by 75 g OGTT performed 3.7 yrs later. Glucose-stimulated insulin secretion (GSIS), whole body insulin sensitivity (SI) and beta cell function (BCF) were estimated by Stumvoll indices, ISI(Matsuda), and a product of Stumvoll 1(st) and ISI(Matsuda), respectively, and hepatic SI by quantitative insulin sensitivity check index. Logistic regression analysis revealed that attenuated BCF due to low GSIS was an independent risk factor for IFG. Low whole body SI was an additional risk for IGT. Male gender and high BMI were independently related to the progression to both IFG and IGT, whereas a positive diabetes family history was independently related to IGT. The worsening of glucose tolerance at large was predicted with 66% sensitivity by risk engine with GSIS, whole body SI, gender, BMI and glucose. This finding may help when implementing early intervention strategies for diabetes.

To evaluate the switching from an angiotensin receptor blocker (ARB) to a drug combination containing an ARB and a diuretic drug in terms of effects on hypertension, cardiac load, and cardiac function.In a study conducted on 82 patients with a history of heart failure and hypertension who had been treated with an ARB but failed to reach the target blood pressure, ongoing oral ARB treatment was switched to a drug combination of losartan and hydrochlorothiazide (HCTZ). Using ambulatory blood pressure monitoring (ABPM), the variations in blood pressure and the effects on cardiac load and cardiac function were evaluated before and after treatment.Comparison of the ABPM findings before and after switching treatment showed significant improvements in mean systolic and diastolic blood pressure, improvements in systolic and diastolic blood pressure 1 hour before getting out of bed, and improvements in the plasma levels of human brain natriuretic peptide as an indicator of cardiac load.The drug combination of losartan and hydrochlorothiazide showed a stronger antihypertensive effect than that of the conventional ARB and improved heart function.

Aims To investigate whether the elevation of liver enzymes is associated with the progression from normal to impaired glucose tolerance. Methods A historical cohort study was conducted in 594 male workers at public schools, who had normal glucose tolerance at baseline. The progression to impaired glucose tolerance and impaired fasting glycaemia during a mean follow-up of 3.1 years was measured using an oral glucose tolerance test. Results Overall, 141 (23.7%) subjects developed impaired glucose tolerance and 68 (11.4%) subjects developed impaired fasting glycaemia, 23 of whom had combined impaired fasting glycaemia/impaired glucose tolerance. The incidence of impaired glucose tolerance increased significantly with increasing quartiles of serum aspartate aminotransferase, alanine aminotransferase and γ-glutamyltransferase (P for trend

1. This study examines whether the supplementation of isoflavones (ISO) exerts beneficial effects on the bone mineral density (BMD) measured by dual energy X-ray absorptiometry (DEXA). 2. Eighty-one healthy Japanese pre- and postmenopausal women were randomly assigned to the following two groups taking either ISO (100 mg) tablets (ISO group) or placebo tablets (P group) containing vitamins C (25 mg) and E (5 mg) daily for 24 weeks in a double-blind placebo controlled parallel design. 3. Seventy women completed the intervention study (34 on ISO, 36 on P), only ISO group was proven to increase significantly BMD (P < 0.05 vs before) and to significantly decrease body fat measured by the DEXA (P < 0.0001 vs before and P < 0.05 vs P group), while BMI was maintained in ISO group despite significant BMI increase in P group. Thus, percent changes in BMI were significantly different between ISO and P groups (P < 0.05) 24 weeks after the intervention. 4. This prospective DEXA study confirmed a long-term ISO supplementation, 100 mg/day could not only prevent menopausal bone resorption but also increase BMD and decrease body fat concomitantly with BMI reduction. Enough ISO supplementation may contribute to the risk reduction of osteoporosis and obesity and, thus to overall health promotion in menopausal women.

This is the first report as to the effects of thapsigargin (Tg), an inhibitor of intracellular Ca2+ pumps, on insulin release by pancreatic B-cells. Tg does not alter basal insulin release by the isolated islets, with 3 mM glucose. However, it potentiates high glucose-induced insulin release: potentiation of the first phase response is dose-related in a concentration range of 1.3-40 microM. In isolated B-cells, Tg causes a minimal rise in basal cytosolic free calcium concentration ([Ca2+]i) and eliminates high glucose-induced initial lowering of [Ca2+]i. Tg does not alter glucose oxidation by the islets and the islet insulin content. An elimination of glucose-induced sequestration of Ca2+ into Tg-sensitive intracellular pool(s) is considered to be the cause of Tg potentiation of glucose effect on insulin release.

A 52-year-old woman presenting with shortness of breath and having no related past medical history was diagnosed with takotsubo cardiomyopathy. However, she revealed respiratory failure atypical with takotsubo cardiomyopathy.We diagnosed myasthenia gravis with myasthenic crisis by acetylcholine receptor-binding antibody titer with mediastinal tumor.Physical or emotional stress is well known to trigger the onset of takotsubo cardiomyopathy. Similarly, myasthenia crisis is also triggered by stress. Here, we report a case of simultaneous occurrence of takotsubo cardiomyopathy and myasthenia crisis.

In fulminant type 1 diabetes (FT1D), irreversible destruction of pancreatic beta-cells occurs abruptly, leading to sudden diabetic ketoacidosis (DKA) in the absence of diabetes-related autoantibodies. This is the first case report of FT1D in which beta-cell was rescued with the commencement of insulin therapy during the evolution of FT1D.

Aim To identify predictors of coronary heart disease (CHD) in Japanese patients with type 2 diabetes (T2DM). Methods A matched case-control study was performed using 800 patients with T2DM admitted for treatment of hyperglycemia from January 2002 to June 2010. Cases comprised 16 patients who had developed acute myocardial infarction and/or received a coronary artery bypass by June 2010, and controls comprised 48 age- and sex-matched patients without CHD events. The mean age, glycated hemoglobin (HbA1c), and body mass index (BMI) were 61.5 yrs, 9.7% and 24.4 kg/m(2), respectively. The relationship of baseline variables, including lipid values, HbA1c, BMI, blood pressure, fasting blood sugar, 2h-post-breakfast blood sugar, delta blood sugar(0-2h), urinary albumin excretion, estimated glomerular filtration rate and treatment modalities (insulin/sulfonylurea/biguanide), to CHD development was analyzed by conditional logistic regression analysis. Results Total cholesterol (TC) (OR 2.35, 95%CI 1.11-4.98, p=0.03), non-HDL-cholesterol (OR 3.07, 95%CI 1.33-7.10, p=0.009), LDL-cholesterol (OR 2.84, 95%CI 1.24-6.51, p=0.01), non-HDL-cholesterol/HDL-cholesterol (OR 2.07, 95%CI 1.10-3.90, p=0.02) and LDL-cholesterol/ HDL-cholesterol (OR 2.74, 95%CI 1.22-6.15, p=0.01) were significantly related to CHD. Fold risk increment per 1-SD increase in basal TC, non-HDL-cholesterol, LDL-cholesterol, non-HDL-cholesterol/HDL-cholesterol and LDL-cholesterol/HDL-cholesterol was 2.33, 2.89, 2.52, 2.37 and 2.60, respectively. Only non-HDL-cholesterol was an independent risk factor. From the receiver operating characteristic curve, 3.89 mmol/L non-HDL-C was the best cutoff value. None of the non-lipid variables were significantly related to CHD. Conclusion Non-HDL-cholesterol was the most dominant predictor of the development of CHD in Japanese patients with T2DM.

Aim of this study was to formulate an index for glucose effectiveness (Sg), SgIo, based on 3-point (0, 30 and 120 min) 75 g oral glucose tolerance test (OGTT). The equation for SgIO was developed in the Chikuma cohort (n = 502). Firstly, post-loading plasma glucose without insulin action and Sg (PPG-without insulin and Sg) was calculated as follows: fasting plasma glucose (mg/dl) + [0.75 × 75,000]/[0.19 × BW(kg) × 10]. Secondly, ‘PPG-without insulin/with Sg’ was obtained from inverse correlation between log10DIO and 2-h post-glucose plasma glucose at OGTT (2hPG) in each glucose tolerance category: DIO denotes oral disposition index, a product of the Matsuda Index and δIRI0–30/δPG0–30. Thirdly, expected 2hPG (2hPGE) of a given subject was obtained from the regression, and the ratio of 2hPG to 2hPGE (2hPG/2hPGE) was determined as an adjustment factor. Lastly, SgIO ([mg/dl]/min) was calculated as \( \frac{{[{\text{PPG}} \hbox{-} {\text{without}}\;{\text{insulin}}\;{\text{and}}\;{\text{Sg}}] - [{\text{PPG}} \hbox{-} {\text{without}}\;{\text{insulin}}/{\text{with}}\;{\text{Sg}}] \times [(2{\text{hPG}})/(2{\text{hPG}}_{\text{E}})]}}{120} \). SgIO was validated against Sg obtained by frequently sampled intravenous glucose tolerance test in the Jichi cohort (n = 205). Also, the accuracy of prediction of Sg by SgIo was tested by the Bland–Altman plot. SgIO was 3.61 ± 0.73, 3.17 ± 0.74 and 2.15 ± 0.60 in subjects with normal glucose tolerance (NGT), non-diabetic hyperglycemia and diabetes, respectively, in the Chikuma cohort. In the Jichi cohort, SgIO was significantly correlated with Sg in the entire group (r = 0.322, P < 0.001) and in subjects with NGT (r = 0.286, P < 0.001), and SgIo accurately predicted Sg. In conclusion, SgIO could be a simple, quantitative index for Sg.

A 78-yr-old man was admitted in emergency with fatigue, anorexia, vomiting, hypothermia (35.1 °C on a hot August day), hypotension (89/56 mmHg) and hyponatraemia (126 mEq/l). Plasma corticotropin and cortisol were severely depressed: 0.84 pmol/L and 33.1 nmol/L respectively (reference range, 1.5-13.9 pmol/L and 110-505 nmol/L, respectively). Thyroid stimulating hormone was low-normal and free-triiodothyronine and free-thyroxine were subnormal. Magnetic resonance imaging revealed swelling of the pituitary gland and the stalk. The patient recovered after glucocorticoid replacement (200 mg/day intravenous hydrocortisone on Day 1 followed by tapering). Central diabetes insipidus which had become apparent had been treated with 1-desamino-8-D-arginine vasopressin. A surge of corticotropin and cortisol, 19.4 pmol/L and 712.1 nmol/L respectively, was found on Day 5 when luteinizing hormone, follicle stimulating hormone, and testosterone were subnormal and prolactin was slightly elevated. Subsequently, corticotropin and cortisol levels normalized together with normalization of luteinizing hormone, follicle stimulating hormone, anti-diuretic hormone, thyroid stimulating hormone, prolactin, testosterone and thyroid hormone levels. Shrinkage of the pituitary gland occurred after one month. Serum immunoglobulin G4 was elevated (3.21 and 6.02 g/l at 1- and 3-month follow-ups respectively). In conclusion, a paradoxical surge of corticotropin after glucocorticoid replacement was observed in a patient with central adrenal insufficiency due to immunoglobulin G4-related hypophysitis. Surge of ACTH in central adrenal insufficiency after glucocorticoid replacement has rarely been reported, and this is the second such case report.