Prevention of incipient diabetic cardiomyopathy by high-dose thiamine

Diabetic cardiomyopathy can progress toward overt heart failure with increased mortality. The hexosamine biosynthesis pathway has been implicated in signaling for fibrosis by the kidney. Thiamine (vitamin B(1)) is an indispensable coenzyme and required at intracellular glucose metabolism. In this study, we assessed if decrease of flux through the hexosamine biosynthesis pathway induced by high-dose thiamine therapy counteracts diabetes-induced cardiac fibrosis. The diabetes model used was the streptozotocin-induced diabetic rat. Normal control and diabetic rats were studied for 2 weeks with and without thiamine, and followings were analyzed; plasma biochemicals (total cholesterol and triglycerides), morphological changes, mRNA abundance relevant to cardiac failure (brain natriuretic peptide) and fibrosis (transforming growth factor-beta1, thrombospondine, fibronectin, plasminogen activator-I and connective tissue growth factor) as well as and matrix metalloproteinase activity were investigated. Thiamine repletion prevented diabetes-induced cardiac fibrosis without changes in plasma glucose concentration. This was achieved by prevention of thiamine depletion, increased pro-fibrotic mRNA abundance and decreased metalloproteinase activity in the heart of diabetic rats. O-glycosylated protein was significantly higher in the left ventricular of diabetic rats compared to control rats, which was decreased by thiamine administration. Thiamine repletion prevented diabetes-induced cardiac fibrosis in experimental diabetes, probably by suppression of hexosamine biosynthesis pathway.     

Formation of dentin-like particles in dentin defects above exposed pulp by controlled release of fibroblast growth factor 2 from gelatin hydrogels

The induction of dentin formation on exposed dental pulp is a major challenge in research on the regeneration of the dentin-pulp complex. We examined the effects of fibroblast growth factor 2 (FGF2), which was delivered in either a collagen sponge (noncontrolled release) or incorporated into gelatin hydrogels (controlled release), on the formation of dentin in exposed rat molar pulps. During the early phase of pulp wound healing, pulp cell proliferation and invasion of vessels into dentin defects above exposed pulp were induced in both groups. In the late phase, the induction of dentin formation was distinctly different between the 2 types of FGF2 release. The noncontrolled release of free FGF2 from collagen sponge induced excessive reparative dentin formation in the residual dental pulp, although dentin defects were not noted. In contrast, controlled release of FGF2 from gelatin hydrogels induced the formation of dentin-like particles with dentin defects above exposed pulp. These results suggest the possibility of a novel therapeutic approach for dentin-pulp complex by controlled release of bioactive FGF2.     

A New Bleaching Protocol for Hyperpigmented Skin Lesions with a High Concentration of All-trans Retinoic Acid Aqueous Gel

A new bleaching protocol for skin hyperpigmentation with a higher concentration of all-trans retinoic acid (atRA) aqueous gel than those commercially available is introduced. AtRA aqueous gel (0.1%) was applied topically twice a day along with 4% hydroquinone, 7% lactic acid ointment to oriental patients with hyperpigmented lesions such as senile lentigines, melasma, and postinflammatory hyperpigmentation. The clinical results of 39 patients treated with 0.1% atRA aqueous gel were compared to those of 22 patients treated with 0.1% atRA hydrophilic ointment. Better clinical results and subjective satisfaction were obtained through a significantly shorter period of treatment with 0.1% atRA aqueous gel than with 0.1% atRA hydrophilic ointment, although side effects such as erythema and irritation were seen at a higher frequency. It is suggested that our bleaching protocol with a high concentration of atRA aqueous gel in combination with hydroquinone and lactic acid has a strong bleaching ability and a potential as a standard therapy for various kinds of skin lesions with hyperpigmentation.     

Catalepsy induced by calcium channel blockers in mice

It is known that calcium channel blockers induce Parkinsonism. In this study, amlodipine-, diltiazem-, and verapamil-induced catalepsy was investigated in mice. All of these three calcium channel blockers induced catalepsy. Dopamine D₁, D₂, and mACh receptor occupancies were estimated under the same conditions, and the affinities of these drugs for each receptor were also estimated in vitro. Intensity of catalepsy was predicted by dopamine D₁, D₂, and mACh receptor occupancies with the dynamic model which had already been constructed and was compared with the observed values. The predicted and the observed values were comparable (r = 0.98, p <0.001). In conclusion, the dynamic model considering D₁, and D₂, and mACh receptor occupancy may be useful for quantitative prediction of drug-induced catalepsy. © 1998 John Wiley & Sons, Ltd.     

Uptake of Colchicine,a Microtubular System Disrupting Agent,by Isolated Rat Hepatocytes

The possible mechanism of hepatic uptake of colchicine (CLC), a microtubule system disrupting agent, was examined using isolated rat hepatocytes. The existence of a carrier-mediated active transport system for CLC was demonstrated. This transport system is saturable, is affected by metabolic inhibitors (dinitrophenol, KCN) and a SH-group blocker (p-hydroxymercuribenzoic acid but not N-ethylmaleimide), and is sensitive to temperature. Ouabain, an inhibitor of Na⁺, K⁺-ATPase, does not affect the transport system of CLC.     

Takotsubo cardiomyopathy

Takotsubo cardiomyopathy (TC) is characterized by transient left ventricular apical wall motion abnormalities, chest pain with electrocardiographic changes, and modest myocardial enzymatic release mimicking acute coronary syndrome, but without significant coronary artery disease. TC is an increasingly recognized type of acquired cardiomyopathy occurring commonly after a recent stressful event, in particular emotional stress, and is relatively common in middle-aged and older women. The pathogenetic mechanism remains unknown. Catecholamine surge related to emotional distress seems to play a major role in the pathogenesis of this cardiomyopathy, rendering TC a type of neurocardiological disorder that manifests as acute but reversible heart failure. Clinicians should consider this syndrome in the differential diagnosis of patients presenting with clinical findings suggestive of acute coronary syndrome, especially in postmenopausal women with a recent history of acute emotional or physical stress.     

Cerebellar peduncle injury predicts motor impairments in preterm infants: A quantitative tractography study at term-equivalent age

Purpose

Cerebellar injury is well established as an important finding in preterm infants with cerebral palsy (CP). In this study, we investigated associations between injury to the cerebellar peduncles and motor impairments in preterm infants using quantitative tractography at term-equivalent age, which represents an early phase before the onset of motor impairments.

Massive Pericardial Effusion in a Case of Acute Pericarditis with Slight ST-Segment Elevation of Short Duration

We present the case of a 77-year-old woman who suffered from chest pain. Her white blood cell count was 10,200/μL and C-reactive protein level was 5.5 mg/dL. There was no electrocardiogram abnormality up to 5 hours after admission. At 15 hours, slight ST-segment elevation occurred, but this disappeared on day 4. Imaging revealed slight pericardial effusion. Nonsteroidal anti-inflammatory drugs and antibiotics were administered. However, the pericardial effusion, inflammatory response, and bilateral heart failure worsened. Pericardiotomy on day 6 released 350 mL of fluid, and symptoms improved. Viral pericarditis was assumed. Massive pericardial effusion is rare in cases of acute viral pericarditis, as is slight, short-duration ST-segment elevation.     

Data mining reveals complex interactions of risk factors and clinical feature profiling associated with the staging of non‐hepatitis B virus/non‐hepatitis C virus‐related hepatocellular carcinoma

Aim: Non‐hepatitis B virus/non‐hepatitis C virus‐related hepatocellular carcinoma (NBNC‐HCC) is often detected at an advanced stage, and the pathology associated with the staging of NBNC‐HCC remains unclear. Data mining is a set of statistical techniques which uncovers interactions and meaningful patterns of factors from a large data collection. The aims of this study were to reveal complex interactions of the risk factors and clinical feature profiling associated with the staging of NBNC‐HCC using data mining techniques. Methods: A database was created from 663 patients with NBNC‐HCC at 20 institutions. The Milan criteria were used as staging of HCC. Complex associations of variables and clinical feature profiling with the Milan criteria were analyzed by graphical modeling and decision tree algorithm methods, respectively. Results: Graphical modeling identified six factors independently associated with the Milan criteria: diagnostic year of HCC; diagnosis of liver cirrhosis; serum aspartate aminotransferase (AST); alanine aminotransferase (ALT); α‐fetoprotein (AFP); and des‐γ‐carboxy prothrombin (DCP) levels. The decision trees were created with five variables to classify six groups of patients. Sixty‐nine percent of the patients were within the Milan criteria, when patients showed an AFP level of 200 ng/mL or less, diagnosis of liver cirrhosis and an AST level of less than 93 IU/mL. On the other hand, 18% of the patients were within the Milan criteria, when patients showed an AFP level of more than 200 ng/mL and ALT level of 20 IU/mL or more. Conclusion: Data mining disclosed complex interactions of the risk factors and clinical feature profiling associated with the staging of NBNC‐HCC.     

Measurement of area of surplus X-ray radiation by dose-area product meter at image intensifier in angiography X-ray units

The aim of this study was to assess the area of surplus X-ray radiation (surplus area) of three image intensifiers (I.I.) of two angiography X-ray units. Surplus area refers to an area surrounded with a circular collimator and effective field of view (FOV). Dose-area product (DAP) was used to measure surplus X-rays. A ratio of surplus area when based on each FOV showed an 8% to 39.3% increase with expansion of FOV, surplus area showed an 18 cm(2) to 95 cm(2) decrease with FOV. When the circular collimator was narrowed to a degree that could be confirmed partially in effective FOV, the rate of surplus area was decreased almost as much as the rate of scattered radiation. Surface dose was almost unchanged. The radiation exposure of the physician as well as that of the patient was reduced by the reduction of surplus area. The DAP meter, while a tool for patient radiation exposure management, is also highly useful for machinery management such as the measurement of surplus area at the I.I. system.