Glutathione and glutathione peroxidase in type 1 diabetic patients.

OBJECTIVE: Diabetic (DM) patients are claimed to be under oxidative stress because of hyperglycemia. The influence of free radical production by this hyperglycemic induction may involve cardiovascular complications in diabetes. The present study aimed to compare the glutathione (GSH) level and glutathione peroxidase (GPx) activity in type 1 DM and a normal healthy group. MATERIAL AND METHOD: GSH level and GPx activity were determined in red cells of 20 subjects of type 1 DM containing fasting plasma glucose (FPG) > or = 140 mg/dL. Twenty healthy normal subjects with normal plasma glucose level (FPG < or = 110 mg/dL) and matched for gender and age served as the control group. These oxidative stress parameters of type 1 DM were compared to a control group by unpaired student's t-test. The association of these parameters with FPG was performed by Pearson product moment correlation. RESULTS: The level of red cell GSH was significantly lower in type 1 DM (p = 0.011) but red cell GPx activity was significantly increased (p = 0.003) when compared to age-matched normal control. The decrement of red cell GSH may be due to the higher rate of consumption of GSH, increasing GPx activity or a reduction of pentose phosphate pathway, stimulated by insulin, resulting in lowered GSH recycle. The correlation between FPG and GSH in type I diabetic patients compared with healthy normal subjects was also observed and it was found that there was a negative correlation, but not found between FPG and GPx activity. CONCLUSION: The present finding suggested that type 1 DM patients were susceptible to oxidative stress and higher blood glucose level had an association with free-radical-mediated lipid peroxidation. Therefore, any means that can reduce oxidative stress may be beneficial for slow progression of cardiovascular complication in type 1 diabetic patients.

Hypercalcemia of malignancy: a study of clinical features and relationships among circulating levels of calcium, parathyroid hormone and parathyroid hormone-related peptide.

OBJECTIVE: Examine the clinical and biochemical features including serum intact PTH (iPTH) and plasma PTH-related peptide (PTHrP) levels in patients with malignancy-associated hypercalcemia (MAHC). MATERIAL AND METHOD: Forty-eight patients with histopathological or cytological proven malignancies and MAHC who were admitted to Siriraj Hospital were studied. RESULTS: The malignancies that caused MAHC were squamous cell carcinoma (45.8%), non-squamous cell solid tumors (31.3 %), and hematological malignancies (22.9%). Most patients (93.8%) had advanced stage malignancies. Corrected serum total calcium (cTCa) levels were 10.8-19.1 mg/dL (13.6 +/- 2.4) and severe hypercalcemia was observed in 17 cases (40.5%). Serum iPTH levels were 0.95-17.1 pg/mL (3.9 +/- 3.6). Most patients had suppressed serum iPTH levels of < 10 pg/mL. Plasma PTHrP levels were 0.2-44.0 pmol/L (3.8 +/- 6.8). There were 27 cases (56.3%) that had humoral hypercalcemia of malignancy (HHM) with plasma PTHrP levels of > 1.5 pmol/L, and 22 cases had squamous cell carcinoma. There was no difference in serum cTCa, phosphorus, alkaline phosphatase, and iPTH levels between patients with HHM and non-HHM. In 48 MAHC patients, serum cTCa correlated to plasma PTHrP (r = 0.35, p = 0.029) and to serum iPTH (r = 0.49, p = 0.003). In 25 patients with HHM, a stronger correlation between serum cTCa and serum iPTH (r = 0.55, p = 0.005) but not between serum cTCa and plasma PTHrP levels (r = 0.41, p = 0.05) was observed. Stepwise multiple regression analyses showed that serum iPTH but not plasma PTHrP levels independently correlated to serum cTCa levels (r = 0.39, p = 0.04). CONCLUSION: The clinical manifestations of MAHC observed in the present study were similar to those previously reported. Serum calcium correlated to serum iPTH more strongly than to plasma PTHrP levels. The low but detectable serum iPTH level might play a role in the development of severe MAHC particularly in HHM.

Antioxidant status and lipid peroxidation end products in patients of type 1 diabetes mellitus.

BACKGROUND AND OBJECTIVE: In Type 1 diabetes mellitus (DM), hyperglycemia is considered a primary cause of diabetic vascular complications and is associated with oxidative stress. The role of antioxidants, particularly alpha tocopherol, in Type 1 DM and its contribution in the development of vascular complications is not clear. Therefore, the present study aims to investigate the relationship between antioxidant status (alpha tocopherol) and lipid peroxidation end products (malondialdehyde; MDA) in the plasma of 20 Type 1 DM and 20 nondiabetic healthy control subjects. MATERIAL AND METHOD: Lipid levels in all subjects were analyzed spectrophotometrically by enzymatic reagent kits. Plasma MDA was assessed by spectrofluorometry, whereas plasma alpha tocopherol was estimated by high performance liquid chromatography in Type 1 DM as well as in the control subjects of matched sex and ages. The results of Type 1 DM were compared with a control group using unpaired Student's t-test. The correlations between fasting plasma glucose and other laboratory parameters were assessed by Pearson rank correlation coefficient. RESULTS: The plasma MDA concentration was significantly higher in Type 1 diabetic patients as compared to controls, (p < 0.01). A significantly reduced plasma antioxidant status of Type 1 DM patients was found only in alpha tocopherol / total lipid as compared to controls (p < 0.05). However, no significant difference was observed in plasma a tocopherol and a tocopherol / total cholesterol (p > 0.05) as compared to the control subjects. The positive correlation between MDA and FPG was demonstrated in Type 1 diabetic compared with normal subjects. CONCLUSION: We conclude that antioxidant supplementation may be necessary for treatment to reduce oxidative stress for diabetic complication protection in Type 1 DM.

Plasma lipid peroxidation and antioxidiant nutrients in type 2 diabetic patients.

BACKGROUND AND OBJECTIVE: Observation shows diabetic patients to be more prone to oxidative stress because of hyperglycemia. The elevation of free radical production by this hyperglycemic production may exacerbate cardiovascular complication in diabetes. This study aims to investigate the oxidative stress related parameters in type 2 DM. Since the effects of glycemic control and cardiovascular complications in DM on these parameters has been not fully determined, the comparison between plasma MDA (malondialdehyde) and antioxidant nutrients with their age-matched normal healthy group may be used to determine the susceptibility of oxidative stress in this type of DM. MATERIAL AND METHOD: MDA and antioxidant nutrients (vitamin A, C, E and beta-carotene) were analyzed in plasma of 19 subjects with poorly controlled type 2 DM (fasting plasma glucose [FPG] > 180 mg/dl), 26 subjects with fairly controlled type 2 DM (FPG < or = 180 mg/dl), and 20 subjects with type 2 DM complicated coronary heart disease (CHD) who were matched for age and gender. Twenty healthy subjects with normal plasma glucose level (FPG < 110 mg/dl) and matched for age and gender served as a control group. In all groups of DM these oxidative stress parameters were compared to a normal group. RESULTS: The plasma MDA levels were significantly higher in all types of DM compared to age-matched normal control. Plasma antioxidant vitamin C and E significantly lower only in poorly controlled and CHD complicated type 2 DM, respectively. The mean of plasma vitamin E level was lowest in type 2 DM complicated with CHD. No significant differences in both plasma vitamin A and beta-carotene were noted between any types of DM and age-matched normal healthy group. The positive correlation between MDA and FPG was demonstrated in most group of patients with their normal subjects except in fairly controlled type 2 DM and negative correlation between vitamin E and FPG was also demonstrated in type 2 DM with CHD. CONCLUSION: These findings suggested that diabetic patients were susceptible to oxidative stress and higher plasma glucose level had an association with free radical-mediated lipid peroxidation. The lowest level of vitamin E in type 2 DM complicated with CHD indicated that oxidative stress played an important role in cardiovascular complication and vitamin E supplementation may be necessary for treatment and prevention in this group of diabetics.

Craniopharyngioma : A review of 14 cases at Siriraj Hospital.

Objective: 1) To characterize clinical presentations of craniophryngioma in the hypothalamic- pituitary region. 2) To examine both pre-treatment and post-treatment endocrine dysfunction of patients with craniopharyngioma. Methods: Medical records of patients with craniopharyngiomas from the Endocrine Division, Department of Medicine from 1997 to 2005 (9 years) were retrospectively reviewed. Data were expressed as mean+ SD (range) or percent as appropriate. Results: There were 14 cases (7 males and 7 females) with histological-proven diagnosis of craniopharyngioma. Their mean age was 32.3 + 13.0 years (15-56). The major distinguishing feature leading to diagnosis was visual field defects (85.7%), and a quarter of them were blind. Other distinguishing symptoms were headaches (78.6%), and menstrual disorders (28.6%). Pre-operative evaluations of their pituitary function revealed hypogonadotropic hypogonadism (55.6%), diabetes insipidus (DI) (42.9%), secondary adrenal insufficiency (18%) and elevated prolactin levels (36.4%) with a mean level of 36.1+39.2 ng/ml (12-138). All tumors were confirmed by pituitary CT or MRI. Mean tumor size was 3.83+1.3 cm. (2-6), and hydrocephalus was found in 54.5% of all patients. Craniotomy was performed in 13 cases with one transphenoidal surgery. Post-operative endocrine evaluations revealed more frequent hypogonadotropic hypogonadism (90%), both secondary adrenal insufficiency and diabetes insipidus (85.7%). 50% of DI cases were permanent DI. Secondary hypothyroidism was found post-operatively (78%). All cases of elevated serum prolactin levels became normal post-operatively and 44% of all patients had visual field improvement within a follow up period of 2.1+2.3 years (0-7). Conclusion: Craniopharyngioma is associated with high morbidity pre and post-operation. Visual field tests should be carefully evaluated in all patients with headaches to make early diagnosis in order to improve the treatment outcome.

Improved glycemic control among Thai children and young adults with type 1 diabetes participating in the diabetes camp.

Diabetes Education Program, Faculty of Medicine Siriraj Hospital has provided summer camps for Thai children with type 1 diabetes since 1990. The objective of this study was to evaluate the effectiveness of the diabetes camp in glycemic control. Twenty male and forty-two female patients participated in the 5-day diabetes camp held in Karnchanaburi, Thailand in 2003. The mean age was 14.1 +/- 4.3 years and the mean duration of disease was 4.5 +/- 3.5 years. Fifty out of sixty-two patients returned for a 3-month-postcamp visit. The glycemic control improved significantly. The mean precamp and postcamp HbA1c levels were 10.0 +/- 3.1% and 9.0 +/- 2.6% (p = 0.008) respectively. The diabetes camp is a valuable program for patients to learn diabetes-self management skills, especially in countries where the diabetes education programs are not always available.

Glutathione and glutathione peroxidase in type 2 diabetic patients.

Objectives: Hyperglycemia is claimed to cause oxidative stress in diabetic (DM) patients. The influence of free radical production by hyperglycemia may exacerbate the cardiovascular complications in diabetes. However, the effects of glycemic control and cardiovascular complications is diabetes on oxidative stress parameters have been not fully studied. This study compared the red cell glutathione (GSH) level and glutathione peroxidase (GPx) activity in fairly controlled typed 2DM(Fasting plasma glucose {EPG}-<180 mg/dl) poorly-controlled type 2 DM (FPG>180 mg/dl), and type 2 DM complicated with coronary heart disease (CHD) with that in a normal healthy group (FPG <110 mg/dl). Materials & Methods : GSH level and GPx activity were determined in the red cells of 19 subjects with poorly controlled type 2 DM, 26 subjects with fairly controlled type 2 DM, and 20 subjects with type 2 DM complicated CHD with that of 20 healthy subjects with normal plasma glucose level matched for age and gender who served as a control group. In all groups of DM these oxidative stress parameters were compared to a control group by one-way ANOVA test. The association between these parameters and FPG was to a control group by one-way ANOVA test. The association between these parameters and FPG was determined using the Pearson product moment correlation. Results : The red cell GSH levels were significantly lower in all types of diabetes compared with those of age-matched normal control subjects (p<0.05).Red cell GPx activity was significantly increased only in the poorly controlled type 2 DM and type 2DM with CHD (<0.05). The decrement of red cell GSH may be due to the higher consumption of GSH for the increasing of GPx activity or there is a reduction or the pentose phosphate pathway that stimulated by insulin resulting in lowered GSH recycling. The association between FPG and GSH or GPx activity in all subgroups of type 2 diabetic patients compared with normal healthy subjects showed no correlation. Conclusion : These findings suggested that type 2 DM patients were susceptible to oxidative stress and higher blood glucose level in poorly controlled type 2DM and type 2 DM complicated with CHD had an association with free radical-mediated lipid peroxidation. Therefore, any means that can reduce oxidative stress may be beneficial for the prevention or slowing of progression of cardiovascular complication in these types of diabetic patients.

Adrenal cortical carcinoma presenting as liver abscess: Report of a case.

A 60 year-old woman presented with clinical signs and symptoms of liver abscess. She had a cystic mass on the right lobe of the liver. Liver needle aspiration was performed and anchovy-paste like material was obtained. She recovered after treatment with oral metronidazole even though investigations for Entamoeba histolytica were negative. Two and a half years later, she returned with the same clinical signs and symptoms. Liver needle aspirations were performed many times and the same anchovy-paste like material was obtained but no definite diagnosis was made. Finally, laparotomy showed an extrahepatic retroperitoneal cystic mass of the right adrenal gland adjacent to the liver. Intravenous pyelography, adrenal CT scan and adrenal angiography were performed. The tumor was removed and the final histopathological diagnosis was adrenal cortical carcinoma.

Primary hyperparathyroidism due to parathyriod carcinoma: Report of a case and review of literature.

A 21-year-old male with a history of bone pain for four months is described. He lost 2 cm of his height and also had polyuria and weight loss. Physical examination revealed a cachectic and mildly pale man with a firm mass of 0.8 cm in diameter on the fight side of his neck, generalized muscle wasting and proximal muscle weakness. kyphoscliosis and deformed thoracic cage. Skeletal X-ray showed finding compatible with the changes found in primary hyperparathyroidism. Biochemical parameters revealed a serum corrected total calcium of 15 mg/dl (8.5-10.5 mg/dl), inorganic phosphate of 3.7 mg/dl (305-5.0 mg/dl) and alkaline phosphatase of 1,008 U/l (39-117 U/l). Primary hyperparathyroidism was confirmed by a serum parathyroid hormone level of 1,733 pmol/l (0.100 pmol/l), Ultrasonography and computerized tomography of the neck showed a right neck mass with a diameter of 2 x 2.2 x 3 cm cm which was visualized by 99mTc-sestamibi scan. The patient underwent an uneventful surgical exploration of the neck. Histopathological study of the excised neck mass showed findings consistent with parathyroid carcinoma.