Anti-Oxidative Therapy with Oral Dapsone Improved HCV Antibody Positive Annular Elastolytic Giant Cell Granuloma

A 72-year-old fisherman who was positive for the HCV antibody developed an annular, erythematous, infiltrated lesions on sun-exposed areas. The lesions were diagnosed as annular elastolytic giant cell granuloma both clinically and histologically. Topical corticosteroid and cryotherapy with liquid nitrogen for several months failed to improve the lesions. We then started dapsone, a known anti-oxidant, at 50 mg/day. A month later, the margins of the erythematous lesions faded, and the infiltration gradually decreased. No recurrence has been observed for one year after the start of the therapy. Anti-oxidative therapy appears to be effective for annular elastolytic giant cell granuloma and could be an alternate therapy for refractory granulomatous disease.     

Granular cell tumors of the breast: A report of two cases

Granular cell tumors (GCT) are rare neoplasms, and only 173 cases of benign GCT of the breast have been documented. We report herein the cases of two patients with this tumor and discuss the methods of diagnosis and treatment. The first patient was a 60-year-old woman who presented with a firm ill-defined mass in her left breast. Mammography showed a dense shadow with spicula and skin thickness, and ultrasonography revealed a hypoechoic mass with an irregular border. Radical mastectomy was performed under the wrong preoperative diagnosis of breast cancer. The second patient was a 31-year-old woman who presented with an elastic-hard mass in her left breast. Mammography showed a well-demarcated dense mass, and ultrasonography revealed a well-defined hypoechoic mass with a large depth-width ratio. Fine-needle aspiration cytology (FNAC) showed a large number of histiocytic cells with abundant granular cytoplasm. An excisional biopsy was performed, and histological examination confirmed a diagnosis of GCT. GCT is benign, but often misdiagnosed as breast cancer both clinically and radiologically. Therefore, histological examination is essential for making a correct diagnosis, while FNAC is also useful. Local resection is still the treatment of choice, and surgeons should do their utmost to avoid performing needless radical mastectomy.     

Glycogen synthase kinase-3beta is involved in the process of myocardial hypertrophy stimulated by insulin-like growth factor-1.

BACKGROUND: Glycogen synthase kinase-3 beta (GSK-3beta) is involved in many cellular processes, such as metabolism, apoptosis, differentiation and proliferation. Insulin-like growth factor-1 (IGF-1), which is well known to have a hypertrophic effect on cardiomyocytes, inactivates (phosphorylates) GSK-3beta in some cell types. The role of GSK-3beta in cardiomyocytes as a negative regulator of cardiac hypertrophy has been recently reported and the present study investigated the role of GSK-3beta in the cardiac hypertrophy of cultivated neonatal rat cardiomyocytes induced by IGF-1. METHODS AND RESULTS: First, the IGF-1 induced signal transduction leading to GSK-3beta in neonatal rat cardiomyocytes was examined. The phosphatidylinositol (PI) 3-kinase/Akt/GSK-3 beta signaling induced by IGF-1 was investigated using inhibitors of PI 3-kinase and Ad AktAA, a dominant negative form of Akt. Furthermore, using Ad MEK DN, a dominant negative form of MEK, it was found that MEK negatively regulates Akt phosphorylation upon IGF-1 stimulation. Next, it was examined whether GSK-3beta acts as a negative regulator in the cardiac hypertrophy induced by IGF-1. Sustained stimulation by IGF-1 caused cardiac hypertrophy in protein synthesis and cellular morphology, and overexpression of unphosphorylatable GSK-3beta (Ad GSK-3beta S9A) repressed these hypertrophic effects of IGF-1. CONCLUSIONS: GSK-3beta may play an important role as a negative regulator of cardiac hypertrophy induced by IGF-1.     

Migration of keratinocytes is impaired on glycated collagen I

Advanced glycation end products are the chemical modification of proteins induced by sugars in a hyperglycemic condition. Extracellular matrix proteins are prominent targets of nonenzymatic glycation because of their slow turnover rates. The aim of this study was to investigate the influence of nonenzymatic glycation of type I collagen on the migration of keratinocytes. The migration of keratinocytes was dramatically promoted on native type I collagen-coated dishes compared with that on uncoated dishes. When type I collagen was glycated with glycolaldehyde, large amounts of advanced glycation end products were produced; the glycated collagen I-coated dishes did not promote the migration of keratinocytes. Glycated collagen I did not affect the proliferative capacity of keratinocytes. However, the adhesion of keratinocytes to glycated collagen I was profoundly diminished in a glycation intensity-dependent manner. alpha2beta1 integrin is responsible for the migration and adhesion of keratinocytes to type I collagen. Pretreatment with glycated collagen I did not affect the expression level or functional activity of alpha2beta1 integrin on keratinocytes. These findings suggest that in the presence of glycated collagen I, keratinocytes lose their adhesive and migratory abilities. As the glycation did not modify the alpha2beta1 integrin on keratinocytes, it is suggested that glycation may diminish the binding capacity of type I collagen.     

Amlodipine-induced reduction of oxidative stress in the brain is associated with sympatho-inhibitory effects in stroke-prone spontaneously hypertensive rats.

Amlodipine is a dihydropyridine calcium channel blocker that is widely used for the treatment of hypertensive patients and has an antioxidant effect on vessels in vitro. The aim of the present study was to examine whether treatment with amlodipine reduced oxidative stress in the brains of stroke-prone spontaneously hypertensive rats (SHRSP). The animals received amlodipine, nicardipine or hydralazine for 30 days in their drinking water. Levels of thiobarbituric acid-reactive substances (TBARS) in the brain (cortex, cerebellum, hypothalamus, and brainstem) were measured before and after each treatment. Systolic blood pressure decreased to similar levels in the amlodipine-, nicardipine-, and hydralazine-treated groups. Urinary norepinephrine excretion was significantly reduced in SHRSP after treatment with amlodipine, but not with nicardipine or hydralazine. Levels of TBARS in the cortex, cerebellum, hypothalamus, and brainstem were significantly higher in SHRSP than in Wistar-Kyoto rats (WKY), and were reduced in amlodipine-treated, but not in nicardipine- or hydralazine-treated, SHRSP. Electron spin resonance spectroscopy revealed increased levels of reactive oxygen species in the brains of SHRSP, which were reduced by treatment with amlodipine. Intracisternal infusion of amlodipine also reduced systolic blood pressure, urinary norepinephrine excretion, and the levels of TBARS in the brain. These results suggested that oxidative stress in the brain was enhanced in SHRSP compared with WKY rats. In addition, antihypertensive treatment with amlodipine reduced oxidative stress in all areas of the brain examined and decreased blood pressure without a reflex increase in sympathetic nerve activity in SHRSP.     

Validity and reliability of the Japanese version of the Neuropsychiatric Inventory Caregiver Distress Scale (NPI D) and the Neuropsychiatric Inventory Brief Questionnaire Form (NPI-Q)]

OBJECTIVE: Neuropsychiatric disturbances are common and burdensome symptoms of dementia. Assessment and measurement of neuropsychiatric disturbances are indispensable to the management of patients with dementia. Neuropsychiatric Inventory (NPI) is a comprehensive assessment tool that evaluates psychiatric symptoms in dementia. We translated the NPI-Caregiver Distress Scale part of NPI (NPI-D) and NPI-Brief Questionnaire Form (NPI-Q) into Japanese and examined their validity and reliability. SUBJECTS AND METHODS: The subjects were 152 demented patients and the caregivers who lived with them. These patients consisted of 76 women and 76 men; their mean age was 73.9 +/- 7.8 (S.D.; range: 49 to 93) years. Their caregivers consisted of 46 men and 106 women; their mean age was 65.0 +/- 11.4 (S.D.; range: 35 to 90) years. The Mini-Mental State Examination (MMSE) was conducted with all patients and NPI-Q, NPI, NPI-D, and the Zarit caregiver burden interview (ZBI) were conducted with all caregivers. We examined validity of NPI-D by comparing its score with the MMSE and ZBI scores, and the validity of NPI-Q by comparing its score with the NPI and NPI-D scores. In order to evaluate test-retest reliability, NPI-D was re-adopted to 30 randomly selected caregivers by a different examiner one month later and NPI-Q was re-executed by 27 randomly selected caregivers one day later. RESULTS: Total NPI-D score was significantly correlated with ZBI (rs = 0.59, p < 0.01). Test-retest reliability of NPI-D was adequate (ri = 0.47, p < 0.01). Total NPI-Q severity score and distress score were strongly correlated with NPI (r = 0.77, p < 0.01) and NPI-D (r = 0.80, p < 0.01) scores, respectively. Test-retest reliability of the scores of NPI-Q was acceptably high (the severity score; ri = 0.81, p < 0.01, the distress score; ri = 0.80, p < 0.01). CONCLUSION: The Japanese version of NPI-D and NPI-Q demonstrated sufficient validity and reliability as well as the original version of them. These are useful tools for evaluating psychiatric symptoms in demented patients and their caregivers' distress attributable to these symptoms.     

Extended total arch replacement for type B aortic dissection with ascending aneurysm following healed aortic dissection

We describe a case of type B aortic dissection with large ascending aortic aneurysm occurring 12.8 years after aortic root replacement (Cabrol procedure) in a non-Marfan patient with cystic medial necrosis of the aorta. We have successfully performed an extended total aortic arch replacement using a four-branched graft through the “L-indsion” approach (a combination of a left anterior thoracotomy and upper half median sternotomy). Of note, a histological specimen from the aneurysmal ascending aortic wall revealed “healed aortic dissection” with fibrous tissue replacing the media and intima in addition to multiple foci of cystic medial necrosis.     

Effects of adrenergic drugs on isolated and perfused hearts of streptozotocin-induced diabetic rats

To examine the myocardial contractile response of the diabetic heart, effects of isoproterenol (ISO) and norepinephrine (NE) on perfused hearts isolated from streptozotocin (STZ)-induced diabetic rats and insulin-treated diabetic rats were evaluated. Male Sprague-Dawley rats, weighing 200-260 g, were divided into the control (C)-group, diabetes mellitus (DM)-group and diabetes mellitus treated with insulin (DMI)-group. The C group was injected with buffered vehicle. DM and DMI groups were injected intravenously with 60 mg/kg STZ on the first day. Three days after STZ injection, the DMI group was subsequently treated with 4 U of Lente insulin subcutaneously every day. At 45 days after injection of STZ, experiments were performed using a Langendorff perfused heart preparation. The heart was paced at 300 beats/min, and myocardial developed tension (T) was measured isometrically. Plasma glucose values (mg/dl) were 142.4 +/- 8.7 in C, 499.3 +/- 15.6 in DM and 370.6 +/- 27.6 in DMI group. The order of percent increase in T induced by ISO (3 X 10(-9) - 3 X 10(-8) g) was C = DMI much greater than DM, and that by NE (10(-7) - 10(-6) g) was C greater than DMI greater than DM. On the other hand, the percent increase in T induced by CaCl2 (1.1 X 10(-4) - 2.2 X 10(-3) g) and aminophylline (AMI, 0.31 X 10(-3) - 5.00 X 10(-3) g) was not significantly different among three groups. These results indicate that adrenergic receptor-mediated contractile response was significantly depressed in the diabetic heart.