Evaluation of immature platelet fraction as a marker of dengue fever progression.

OBJECTIVES: Progression of dengue is often associated with thrombocytopenia resulting from viral-induced bone marrow suppression and immune-mediated peripheral platelet consumption. Immature platelet fraction (IPF), which can be measured using a haematology analyser, is a precursor indicating platelet formation in the bone marrow. This study evaluated the trend of IPF as an early recovery indicator of platelets in dengue patients with thrombocytopenia, and its relationship with severe dengue in conjunction with reticulocyte count. METHODS: Hospitalized patients with dengue were enrolled and followed-up daily until discharge. Blood investigations included daily full blood counts and IPF measured using a haematology analyser. RESULTS: In total, 287 patients with confirmed dengue were enrolled in this study, 25 of whom had severe dengue. All patients had a decreasing trend in platelet count in the first week of illness, concomitant with an increasing trend in the percentage of immature platelets to total platelets (IPF%) for more than 3 days prior to platelet recovery. IPF% was significantly increased in patients with severe dengue compared with patients with non-severe dengue on days 3-5 after the onset of fever. Reticulocyte count increased significantly in patients with severe dengue on day 5. CONCLUSIONS: IPF can be utilized as an early recovery indicator of platelets in patients with dengue and thrombocytopenia.

Metformin reduces body weight gain and improves glucose intolerance in high-fat diet-fed C57BL/6J mice.

In an acute treatment experiment, metformin (150, 300 mg/kg, per os (p.o.)) markedly reduced the consumption of a high-fat diet (HFD) (45 kcal% fat-containing diet) for 2 h after the HFD was given to the fasted male C57BL/6J (B6) mice. In addition, metformin at a higher dose increased plasma active glucagon-like peptide-1 (GLP-1) levels at 1 h after the HFD was given. On the other hand, pioglitazone (12 mg/kg, p.o.) slightly increased the food intake but did not affect active GLP-1 levels when given at 6 and 12 mg/kg, p.o. In a long-team experiment for 9 weeks, metformin treatment (0.25, 0.5% in the HFD) resulted in reduction of body weight gain and HFD intake. When wet weights of various body fat pads of each mouse were measured at 9 weeks after treatment, metformin markedly decreased these weights. However, pioglitazone treatment (0.01, 0.02% in the HFD) did not have obvious effects on these parameters. Oral glucose tolerance test was carried out after 20-h fasting at 4 weeks post-treatment. Whereas metformin treatment (0.25, 0.5%) markedly improved glucose intolerance, pioglitazone treatment (0.02%) slightly improved this parameter. At 9 weeks, both metformin and pioglitazone markedly improved hyperglycemia and hyperinsulinemia. Metformin treatment also improved hyperleptinemia, whereas pioglitazone was ineffective. These results indicate that metformin reduces body weight gain and improves glucose intolerance in HFD-induced obese diabetic B6 mice.

Involvement of hyperglycemia in deposition of aggregated protein in glomeruli of diabetic mice.

The aim of this study was to clarify the influence of hyperglycemia on the deposition of aggregated protein in the glomeruli of diabetic mice. KK-A(y) mice injected with aggregated bovine serum albumin accumulated more of it in the glomeruli than did ICR mice. There were no histological alterations in the glomeruli of KK-A(y) mice. KK-A(y) mice given voglibose in mouse-chow for 2 weeks had significantly reduced blood glucose, glycated albumin, and hemoglobin A(1C) levels compared with control mice. The voglibose-treated KK-A(y) mice were injected with aggregated bovine serum albumin and accumulated significantly less albumin in the glomeruli than did the control mice. Pioglitazone decreased blood glucose levels compared with the control, and reduced the glomerular deposition of aggregated albumin. Glomerular aggregated bovine serum albumin levels and blood glucose levels were reduced significantly by the injection of insulin. Six times more advanced glycation endproducts were produced from aggregated bovine albumin than from non-aggregated bovine albumin on incubation with glucose and L-lysine in vitro. Glucose-loaded ICR mice generated more advanced glycation endproducts from aggregated albumin, and had more aggregated bovine albumin in the glomeruli. It was suggested that hyperglycemia contributes to an increase in the deposition of aggregated protein in glomeruli even early on in diabetes.

Pioglitazone improves obesity type diabetic nephropathy: relation to the mitigation of renal oxidative reaction.

Medications to treat hyperglycemia and hyperinsulinemia are expected to inhibit the accumulation of advanced glycation end-products in the diabetic kidney and improve renal function by inhibiting oxidative reactions. In this study, we examined the effect of pioglitazone, an insulin sensitizer, on diabetic nephropathy. Feed containing pioglitazone at 0.01 or 0.02% was given to Zucker-fatty rats for 27 weeks. Pioglitazone reduced plasma glucose, plasma insulin, and blood HbAlc levels. It also decreased plasma total cholesterol, triglyceride, phospholipid and cystatin C levels and inhibited the increase in urine of 8-hydroxydeoxyguanosine and in plasma of malondialdehyde. In the histopathological examinations, pioglitazone inhibited diffusive or nodular thickening of the mesangial matrix, atrophy of the proximal convoluted tubule, thickening of the basement membrane of the tubule, and mild cellular infiltration (mostly small lymphocytes) in the stroma. Furthermore, pioglitazone inhibited the mRNA expression of the receptor for advanced glycation end-products (RAGE) and that of transforming growth factor-beta. Long-term administration of pioglitazone improved hyperglycemia lipid profiles, hypercholesterolemia, and hyperinsulinemia and had a protective effect on diabetic nephropathy in Zucker-fatty rats.

Increase in the deposition of aggregated protein in the glomeruli of spontaneously diabetic mice.

The aim of this study was to investigate the disposal of aggregated protein in the glomeruli of spontaneously diabetic mice. Diabetic mice, KK-A(y) and db/db, and age-matched ICR mice were injected intravenously with aggregated bovine serum albumin (a-BSA) at 0.6 mg/g, and the glomeruli and the blood were obtained. Diabetic mice had larger amounts of a-BSA in their glomeruli than the ICR mice, threefold in KK-A(y) and twofold in db/db, at 3 h after the a-BSA injection. Additionally, the disappearance of a-BSA was retarded in the diabetic glomeruli. KK-A(y) displayed a-BSA in the glomeruli 24 h after the a-BSA injection and db/db did after 12 h, while the ICR did by 8 h. In spite of increases of insulin to similar degrees in both strains of diabetic mice after the a-BSA injection, blood glucose levels markedly decreased in KK-A(y) compared with db/db. There were no histopathological alterations in the glomeruli of the diabetic mice. Depositions of a-BSA were confirmed to be higher in the diabetic glomeruli by the immunofluorescence technique, and KK-A(y) displayed higher depositions of a-BSA than did db/db. The present study suggests that hyperglycemia is involved in the increased deposition of aggregated protein in the glomeruli and that the degradation of aggregated protein is retarded in diabetic glomeruli.

[Anti-allergic action effect of Pseudolarix amabilis Rehd. extract and its efficacy on atopic dermatitis].

Pseudolarix amabilis Rehd. extract was examined in vitro for antibacterial effects, anti-inflammatory effects, and inhibitory effects on histamine release. Pseudolarix amabilis Rehd. extract was also examined for efficacy on dermatitis in atopic dermatitis model mice (NC mice) and effects on keratinous moisture level and transepidermal water loss in miniature pigs. Pseudolarix amabilis Rehd. extract had antibacterial effects on Staphylococcus aureus, Candida albicans, and Streptococcus pyogenes; however this antibacterial effect varied with the temperature at which and conditions under which Pseudolarix amabilis Rehd. was extracted. Pseudolarix amabilis Rehd. extract at the final concentration of 2 mg/mL significantly inhibited the hyaluronidase activity; and at 0.005, 0.05, and 0.5 mg/mL, it also significantly inhibited the histamine release. In the mice in which atopic dermatitis had been induced, 28-day administration of Pseudolarix amabilis Rehd. extract at 4 and 400 mg/mL significantly inhibited aggravation of dermatitis without having effects on body weight. In the dorsal skin of miniature pigs, Pseudolarix amabilis Rehd. extract at 4 and 400 mg/mL significantly increased keratinous moisture level with the increase in the number of dosing days, and caused no changes in transepidermal water loss. From the above results, it is clear that Pseudolarix amabilis Rehd. extract inhibits both proliferation of bacteria and inflammation caused by antigens. Furthermore, it is suggested that Pseudolarix amabilis Rehd. extract will serve as a medicinal drug which effectively moistens the skin and prevents and heals dermatitis.

[Analysis of scratching behavior in a picryl chloride induced atopic dermatitis model in mice].

To elucidate the actual state of scratching behavior of NC mice noted when PiCl-induced dermatitis occurs, the circadian rhythm in scratching behavior of this mouse model was examined, and the time when scratching behavior, which is useful to evaluate the severity of itch, occurs was assessed. A steroid drug (Prednisolone ointment), which has been confirmed to inhibit dermatitis from worsening, was used to examine whether or not, or how it inhibits scratching behavior in this mouse model. It became clear that scratching behavior increased during a period from the evening to the night in the animals which had not been sensitized (normal animals); compared with the day time, scratching behavior occurred more often in the nighttime. It also became clear that scratching behavior increased in the animals with PiCl-induced dermatitis increase in the frequency of induction of dermatitis, and Prednisolone ointment significantly inhibited scratching behavior in the animals in which dermatitis had been induced with PiCl six times. From these results, it can be said that scratching behavior increases in PiCl-induced mouse atopic dermatitis models correlatively with the increase in the frequency of induction of dermatitis, and steroid drugs decrease the frequency of the scratching behavior. In conclusion, it is strongly suggested that this mouse model is useful for development of therapeutic methods and novel medicinal drugs for atopic dermatitis.