Anti-Proliferative Effects of Rutin on OLETF Rat Vascular Smooth Muscle Cells Stimulated by Glucose Variability

PURPOSE: Proliferation of vascular smooth muscle cells (VSMCs) plays a crucial role in atherosclerosis. Rutin is a major representative of the flavonol subclass of flavonoids and has various pharmacological activities. Currently, data are lacking regarding its effects on VSMC proliferation induced by intermittent hyperglycemia. Here, we demonstrate the effects of rutin on VSMC proliferation and migration according to fluctuating glucose levels. MATERIALS AND METHODS: Primary cultures of male Otsuka Long-Evans Tokushima Fatty (OLETF) rat VSMCs were obtained from enzymatically dissociated rat thoracic aortas. VSMCs were incubated for 72 h with alternating normal (5.5 mmol/L) and high (25.0 mmol/L) glucose media every 12 h. Proliferation and migration of VSMCs, the proliferative molecular pathway [including p44/42 mitogen-activated protein kinases (MAPK), mitogen-activated protein kinase kinase 1/2 (MEK1/2), p38 MAPK, phosphoinositide 3-kinase (PI3K), c-Jun N-terminal protein kinase (JNK), nuclear factor kappa B (NF-kappaB), and Akt], the migratory pathway (big MAPK 1, BMK1), reactive oxygen species (ROS), and apoptotic pathway were analyzed. RESULTS: We found enhanced proliferation and migration of VSMCs when cells were incubated in intermittent high glucose conditions, compared to normal glucose. These effects were lowered upon rutin treatment. Intermittent treatment with high glucose for 72 h increased the expression of phospho-p44/42 MAPK (extracellular signal regulated kinase 1/2, ERK1/2), phospho-MEK1/2, phospho-PI3K, phospho-NF-kappaB, phospho-BMK1, and ROS, compared to treatment with normal glucose. These effects were suppressed by rutin. Phospho-p38 MAPK, phospho-Akt, JNK, and apoptotic pathways [B-cell lymphoma (Bcl)-xL, Bcl-2, phospho-Bad, and caspase-3] were not affected by fluctuations in glucose levels. CONCLUSION: Fluctuating glucose levels increased proliferation and migration of OLETF rat VSMCs via MAPK (ERK1/2), BMK1, PI3K, and NF-kappaB pathways. These effects were inhibited by the antioxidant rutin.

Case of Acute Methemoglobinemia Caused by Nitrobenzene Ingestion / 대한내과학회지

Nitrobenzene is a poisonous agent, not commonly encountered in clinical practice, which belongs to the aniline dyes. Ingestion of nitrobenzene may cause methemoglobinemia, a condition in which the iron in hemoglobin is oxidized from the ferrous state to the ferric state, resulting in the inability to transport oxygen. A 41-year-old man presented with the clinical features of methemoglobinemia after drinking nitrobenzene. The patient was treated conservatively with intravenous methylene blue. We report a case of acute methemoglobinemia due to ingestion of nitrobenzene.

Pheochromocytoma in pregnancy: A case report / 대한내과학회지

Pheochromocytoma during pregnancy is very rarely discovered, and this condition is life threatening to both mother and fetus. Maternal and fetal survival depend a lot on an early diagnosis, a correct medical therapy and a correct timing of delivery and surgery. We describe a case of pheochromocytoma during pregnancy. A patient was transferred to our hospital during gestational week 24 with severe hypertension, generalized edema. Pheochromocytoma caused by a left adrenal mass was diagnosed. The patient was treated with titrated dose of phenoxybenzamine, propranolol, and intravenous nicardipine, but intermittent severe hypertension was developed. At 33 weeks gestation, fetal distress was developed, and emergent cesarean section was done. Two weeks after delivery, she underwent a successful left adrenalectomy. Two months after surgery, all antihypertensive medications were discontinued and her blood pressure have remained normal range.

The Expression of L-type Calcium Channel mRNA by the Concentrations of Glucose on the Cell Proliferation in Cultured OLETF Rat Aortic Vascular Smooth Muscle Cells

BACKGROUND: The proliferation of vascular smooth muscle cell(VSMC) is a part of the major pathogenic mechanism for atheroscle- rosis. It has been reported that L-type calcium channel plays a role in the VSMC proliferation in diabetic rats. But there is a little study results about the association between L-type calcium channel and VSMC proliferation by glucose concentrations in culture media. So we examined the association between voltage-dependent L-type calcium channel of VSMCs and the proliferative activity of vascular smooth muscle cells. METHODS: Rat aortic VSMCs were isolated from the aorta of OLETF rat by enzyme method. VSMCs were cultured in various concentrations of glucose(5.5, 25 mM). The VSMCs(1x104 cells in 24-well plates) were incubated in the presence of Bay K 8644 (10-6M) with/without verapamil(10-6M) for 48 hours. Then the proliferation was assessed by MTT(methylthiazole tetrazolium) assay and expression of L-type calcium channel mRNA was measured by RT-PCR. RESULTS: The proliferative ability and the expression of L-type calcium channel of cultured VSMCs were increased dose-dependently by the glucose concentrations(p<0.05). Bay K 8644 enhanced the proliferation of VSMC and verapamil blocked the incremental effects induced by Bay K 8644. CONCLUSION: These results suggest that L-type calcium channel may play a role in VSMC proliferation of OLETF rat.

Relationship between Metabolic Syndrome and Coronary Heart Disease in Elderly

BACKGROUND: Metabolic syndrome, a concurrence of disturbed glucose and insulin metabolism, over- weight and abdominal fat distribution, dyslipidemia and hypertension, is associated with subsequent de- velopment of type 2 diabetes mellitus and cardiovascular disease, especially coronary heart disease. The aim of the study is to assess the relationship between metabolic syndrome and coronary heart disease in elderly greater than 65 years old. METHODS: Eighty two elderly patients greater than 65 years old who underwent coronary angiography were divided into two groups with metabolic syndrome or without metabolic syndrome, and assessed the association with coronary angiographic finding. The metabolic syndrome factors and cardiovascular risk factors of JNC 7 were investigated to assess the relationship with coronary heart disease in elderly. Coronary heart disease was defined as 50% or greater diameter in stenosis of coronary artery in coronary angiography. RESULTS: In elderly patients with metabolic syndrome, coronary angiographically abnormal findings(p<0.05) and multi vessel disease findings(p<0.05) were presented significantly higher than non metabolic syndrome patients. In elderly patients with 3 and more cardiovascular risk factors of JNC 7, coronary angiographically abnormal findings(p<0.05) and multi vessel disease findings(p=0.059) were presented more than the other patients. Diabetes mellitus was related significantly with coronary heart disease(p value 0.044). CONCLUSION: In elderly patients, metabolic syndrome was significantly related with coronary heart disease and diabetes mellitus had strong relationship with coronary heart disease. Metabolic syndrome and cardiovascular risk factors of JNC 7 should be further evaluated to assess the relationship with coronary heart disease in the future.

Human adjuvant disease manifesting as SLE / 대한내과학회지

Human adjuvant disease means the autoimmune disease or autoimmune disease like syndrome developed after plastic surgery using foreign body implantation. After first report of HAD by Miyoshi at 1964, a number of cases have been reported especially from Japan. Silicone has been known as biologically inert material, but a couple of side reaction and experimental data argue against such conventional idea. It is impossible to identify the exact role of implanted substance in the occurrence of autoimmune disease, but there are a few indirect evidences for adjuvant effect of silicone. The spectrum of HAD are as follows: unclassifiable connective disease like syndrome, rheumatoid arthritis, SLE, polymyositis, adult Still's disease, ITP, Hashimoto's thyroiditis, etc. We experienced two cases of HAD manifesting as SLE who had been injected with silicone fluid with for augmentation mammoplasty and report this with a review of the literature.

Assessment of Autonomic Disturbance by 24-hour Heart Rate Variability in Patients with Liver Cirrhosis / 대한내과학회지

OBJECTIVE: Heart rate variability(HRV) is helpful to diagnosis autonomic disturbance and sympathetic-parasympathetic imbalance in patients with myocardial infarction and diabetes mellitus. Patients with liver cirrhosis demonstrate reduced blood pressure despite increased heart rate and increased cardiac output, indicating a fall in peripheral vascular resistance. Autonomic disturbance may contribute to this phenomenon. The aim of the present study is to evaluate the degree of autonomic disturbance and the circadian rhythm of autonomic nervous system by estimating HRV with 24 hour-Holter recorder, METHODS: 24 hour-HRV with Del Mar Avionics 563 Holter recorder and cardiovascular reflex tests were carried out on 32 patients with liver cirrhosis and 20 control subjects. We evaluated the presence of autonomic disturbance, and assessed quantitatively the autonomic disturbance. RESULTS: 1) Among cardiovascular reflex tests, Valsalva test, standing test and deep breathing test were showed a significantly decreased response in liver cirrhosis compared with control groups. 2) The standard deviation of 24hours average R-R intervals were showed a significantly decrease in liver cirrhosis than control groups(P<0.0001). The HRV of low frequency(LF. P<.D.001), high frequency(HF, P<0.0001) and total power spectral density (P<0.0001) in liver cirrhosis were statistically lower than control. 3) The LF/HF ratio of patients with liver cirrhosis was showed higher than control at night CONCLUSION: Non-invasive assessment of 24 hour-HRV has a few advantages in the diagnosis and degree of autonomic disturbance, evaluation of diurnal variation of autonomic tone.

Renal potassium wasting and hypocalciuria ameliorated with magnesium repletion in Gitelman's syndrome

A woman aged 45 years was presented with hypokalemic metabolic alkalosis and hypomagnesemia associated with renal potassium and magnesium wasting. Her 24-hour urinary calcium excretion was strikingly low despite normocalcemia and normal creatinine clearance, which is one of characteristic findings of Gitelman's syndrome (GS). She was evaluated for the responses following Mg supplementation for 10 days, which showed marked increments in serum potassium and magnesium as well as improvements of the degree of renal potassium wasting and hypocalciuria. This amelioration of abnormal biochemical pictures in this patient after Mg supplementation proposes that the hypokalemia with renal potassium wasting and hypocalciuria may be caused by abnormal Mg metabolism.

Utility of Serum Fructosamine as a Measure of Glycemia in Elderly Diabetic Patients

BACKGROUND: Glycemic profile has traditionally been with the use of HbAlc over a 2 to 4 month period. Recently, serum fructosamine is highly sensitive to acute metabolic deterioration(period 2 to 3 weeks), and is suitable for automation, allowing multiple assays with minimal effort. In some report, despite evidence suggesting a reduction in serum albumin level with increasing age, serum fructosamine was strongly correlated with HbAlc in elderly diabetic patients. This study was conducted to define the correlation between fructosamine and other parameters in elderly diabetic patients. METHODS: The study group consisted of 56 elderly patients(age range : 66-85 years, group A) and 58 adult patients(age range: 18-64 years, group B), who were stable over recent 2 months in fasting glucose values and serum albumin levels. Fructosamine was measured in 114 diabetic patients. The measured levels were related to HbAlc and fructosamine/albumin index(FAI). RESULTS: 1) There was significant correlation between HbAlc and fructosamine in all diabetic patients(r=0.705, p=0.0001). The correlation between HbAlc and fructosamine was stronger in group A than in group B [group A: r=0.831, group B: r=0.367, p=0.0001](p<0.05). 2) The correlation between HbAlc and FAI was significantly stronger compared to that between HbAlc and fructosamine in elderly diabetic patients(p<0.05). 3) Glycation ratio provides a vector-like insight into the recent trend of glycemia, and Glycation ratio was stable in all diabetic patients. CONCLUSIONS: Our study suggests that correlation between HbAlc and fructosamine in elderly daibetic patients was significantly lower in adult diabetic patients. Further studies are needed to determine the ultimate values of this test in the clinical management of elderly patient with diabetes.

A Case of Xanthogranulomatous Cholecystitis / 대한내과학회지

Xanthogranulomatous cholecystitis is an extremely rare benign inflammatory disease of the gall bladder characterized by yellowish focal nodular appearance with tissue necrosis and lipid-containing histiocyte (xanthomacell). Recently, we experienced a case of xanthogranulomatous cholecystitis. A 71-year old woman was admitted with the complaints of RUQ pain for 1 month. On abdominal ultrasound examination, there were diffuse gallbladder wall thickening, echogenic nodule with acoustic shadow, the calculous cholecystiti and the gall badder cancer were strongly suspected and the operation was performed. At operation the gall bladder was marked enlarged and wall thickening with two brownish, oval shaped, smooth surfaced stones. The specimen was revealed a xanthogranulomatous cholecystitis by the pathology.

Thiazide-induced Electrolyte Disturbance with Altered Mental Status / 대한신장학회잡지

We report a severe case of hyponatremic encephalopathy in a 38 year old schizophrenic patient with polydipsia that was very likely precipitated by hydrochlorothiazide given for the accompanied hypertension in this patient. On admission via emergency room, this patient's electrolyte imbalances include not only hyponatremia but also hypokalemia, hypomagnesemia and metabolic alkalosis, which have been well known as the complications of thiazide diuretics. Fortunately, this patient recovered from comatose condition with the treatment of hyponatremia at the correction rate of about 0.5mEq/L/hr in addition to potassium and volume replacements. However, this case gives us the warning that the presence of hyponatremic condition such as polydipsia should be ruled out before thiazide diuretics prescribed for patients with schizophrenia, and other electrolytes imbalance in addition to hyponatremia as the complications of thiazide diuretics should be looked for the simultaneous treatment for them.

A Case of Sarcoidosis with Bone Involvemnt / 결핵

Sarcoidosis is a chronic multisystemic disorder of unknown cause characterized by presence of noncaseating Epithelioid granuloma in affected organ. It was first reported in 1887 by Hutchinson and is relatively common in western countries. But it is not commonly seen in East Asia including Korea. All parts of the body can be affected, but the lung is the most frequently affected organ. Other common site of involvement include lymph node, eye, skin, etc. It is known that 3~9% of all cases of sarcoidos is associated with bone involvement. Bone involvement usually cause no symptom and frequently affect bones in hands an feet. In many cases, it is known to be associated with skin involvement. We recently experienced one case of sarcoidosis which typically showed X-ray finding of sarcoidosis with associated skin lesion(lupus pernio) and report it with review of the literature.