An open-label prospective cross-over trial was performed to compare the efficacy and safety of once daily low-dose gliclazide (20 mg/day) with that of nateglinide at the usual dosage (270 mg/day, 90 mg t.i.d.) in Japanese type 2 diabetics with relatively good glycemic control (HbA₁c<7.0%). Eight patients received 20 mg/day of gliclazide and 16 received 270 mg/day of nateglinide. After at least 12 weeks of gliclazide or nateglinide therapy, the drugs were switched and treatment was continued for another 12 weeks. The final HbA₁c value was modestly, but significantly, lower after gliclazide treatment than after nateglinide treatment (6.2% vs. 6.4%). However, symptoms related to hypoglycemia were significantly more common with gliclazide treatment than nateglinide treatment (7 vs. 0 cases), although there were no severe hypoglycemic events. While gliclazide acts as a free radical scavenger, there was no effect on parameters of oxidative stress such as malondialdehyde-modified low density lipoprotein and thiobarbituric acid-reactive substances at the low dosage tested. In conclusion, both drugs are reasonable options for early type 2 diabetes. Compared with the regular dose of nateglinide, 20 mg/day of gliclazide achieved modestly better glycemic control with an increased frequency of hypoglycemia in diabetic patients with relatively good glycemic control.

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In order to clarify the role of apoptosis and the expression of Bcl-2 family proteins in the pathology of Graves' disease (GD), we evaluated the apoptosis by in situ end-labeling of fragmented DNA and the expression of Bcl-2, Bax and Bak by immunohistochemistry in thyroid tissues from 20 patients with GD and in normal thyroid tissues from 6 patients with follicular adenoma (N). Apoptotic nuclei were found in thyrocytes and in germinal center of lymphoid follicles. Bcl-2 was strongly expressed in both GD and N thyrocytes. Bax was not expressed in either GD or N thyrocytes. Bak was expressed in thyrocytes from 5 of 20 patients with GD, while it was detected in all N thyrocytes. In lymphoid follicles Bcl-2 was expressed in the mantle zone, while Bax and Bak were both expressed in the germinal center. The percentage of apoptotic nuclei in GD thyrocytes was low (0~3.6%), and negatively correlated with the weight of the thyroid glands resected (rs = –0.43, P<0.05). It was greater in Bak-positive GD thyrocytes than in Bak-negative ones (mean ± SD; 1.7 ± 0.7% vs. 0.7 ± 0.9%, P<0.05). These findings suggest that the differential expression of Bcl-2 family proteins in both thyrocytes and lymphoid follicles may be involved in the pathology of GD.

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To examine the short- and long-term influences of the Marmara earthquake, which occurred on August 17, 1999 in Turkey, on glycemic control and quality of life (QOL), HbA_1c, insulin requirement and QOL of 88 people with type 1 diabetes living in the quake zone were evaluated one year before (PreE), 3 months after (PostE) and one year after (FE) the earthquake. HbA_1c levels and daily insulin requirements increased significantly at PostE (HbA_1c from 7.4 ± 1.3% to 8.5 ± 1.8%, p<0.05; insulin from 0.58 ± 0.2 IU/kg/day to 0.77 ± 0.2 IU/kg/day, p<0.05). Mean total QOL scores at PostE were significantly lower than the scores obtained at PreE (62.7 ± 17.3 vs 74.2 ± 13.4, p<0.001). There were no significant differences between HbA_1c levels and total QOL scores at PreE and FE. People with type 1 diabetes living in the same house after the earthquake and not having enough food supply were reported to have lower QOL than people moving to another house and having enough food supply after the earthquake (p = 0.014, p<0.0001, respectively). The Marmara Earthquake had a negative impact on the glycemic control and QOL of the subjects with type 1 diabetes for the short term but prequake scores might be achieved after a long period.

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Leptin receptors are distributed throughout the body and leptin has been shown to have various effects. As we have recently demonstrated a positive correlation between serum leptin levels and TSH in euthyroid subjects, we investigated the effect of leptin on the thyroids. It was observed that serum leptin levels were negatively correlated with free thyroxine/TSH ratios in the serum of euthyroid female subjects. This suggests that leptin may modulate TSH effects. RT-PCR for leptin receptor expression revealed that FRTL-5 cells possess the gene transcript to the long cytoplasmic form of the receptor. Leptin actually appeared to induce an increase in c-fos mRNA expression. However, it inhibited iodide uptake typically induced by both TSH and dibutyryl cAMP, while leptin did not inhibit TSH-induced cAMP production or TSH-stimulated DNA synthesis in 4H medium (in the absence of insulin and TSH). Leptin also was observed to inhibit TSH- and dibutyryl cAMP-induced Na⁺/I^– symporter and thyroglobulin mRNA expression. Lastly, leptin was seen to inhibit TSH-stimulated thymidine incorporation in 5H medium. Taken together, these results suggest that leptin suppresses TSH-induced thyroid function. Therefore, we hypothesized that leptin may be one of the regulators of thyroid function in obese patients.

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Many athletes use drugs, especially anabolic androgenic steroids (AAS), but there are few reports on the endocrinological and pathological changes in AAS abusers. In this study we reported the results of endocrinological examinations in rats administered AAS and also physical changes. We separated 37 male Wistar rats (7 weeks old) into 3 groups: Group A was medicated with nandrolone decanoate, metenolone acetate, and dromostanolone; Group B with nandrolone decanoate and saline; and Group C was given only saline. They were given subcutaneous injections of the medications or the control vehicle once a week for 6 weeks. Medications were stopped for 4 weeks, and then resumed for another 6 weeks. After that, rats were sacrificed. Serum testosterone level in Group A was significantly higher than that in Group C. Serum dihydrotestosterone in Group A was significantly higher than that in both Groups B and C. Serum estradiol-17β levels in Groups A and B were significantly higher than that in Group C. In pathological evaluation, heart, testis, and adrenal gland were severely damaged. These findings indicate that there is a high degree of risk related to the use of AAS.

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We demonstrated severe hyponatremia in a 68 year-old man who had pituitary tumor. He had poor appetite and was disoriented. Tests revealed hyponatremia of 110 mmol/l, and he was admitted to Jichi Medical School Omiya Medical Center to undergo further tests. Physical findings revealed disturbance of consciousness with Japan Coma Scale I-2. There was neither dehydration nor edema. Laboratory data showed a serum sodium level of 112 mmol/l; plasma osmolality, 219 mmol/kg; and urinary osmolality, 555 mmol/kg. Plasma arginine vasopressin (AVP) level was 1.6 pmol/l despite the marked hypoosmolality. Anterior pituitary function was normal. Brain magnetic resonance imaging showed a pituitary tumor of 20 × 18 × 20 mm in size, which pushed the pituitary stalk upward. After the adenomectomy, serum sodium level was kept normal without any treatment. Histology showed basophilic adenoma. These findings indicate that local pituitary tumor may cause exaggerated secretion of AVP, resulting in the syndrome of inappropriate secretion of antidiuretic hormone (SIADH).

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Two acute leukemia cases who presented autoimmune thyroid diseases after bone marrow transplantation (BMT) are described with reference to the pathogenesis of their autoimmune clones. A 37-year old Japanese woman developed Graves' hyperthyroidism 39 months after allogeneic BMT for acute myeloid leukemia (AML) donated from her sister. Although both donor and recipient were euthyroid and negative for thyroid autoimmunity before BMT, the donor was positive for anti-nuclear and anti-single strand DNA autoantibodies. Studies on polymorphism for variable number of tandem repeat region of T-cell receptor gene suggested that the lymphocytes responsible for the hyperthyroidism were of donor origin. The second case was a 12-year-old Japanese schoolboy who presented nongoitrous hypothyroidism 2 years after autologous BMT for acute lymphoblastic leukemia (ALL). He had been clinically euthyroid before transplantation. Family history revealed that his mother and sister had a history of Graves' disease. His serum was positive for thyroid-stimulation blocking antibody. It is highly likely that the autoimmune process was activated after transient immune suppression during peri-BMT period in this patient. Pathogenesis, incidence, and observed time lag between BMT and development of autoimmune thyroid diseases were discussed.

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Metastasis from prostate to thyroid gland is very uncommon. Here we report a 77-year-old man who was admitted to the hospital because of a nodular goiter. A fine-needle aspiration biopsy of the nodule showed metastatic prostatic adenocarcinoma. This is the second case of a metastatic prostate carcinoma to the thyroid gland.

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