SHORT CHAIN FATTY ACIDS UPREGULATE ADIPOKINE PRODUCTION IN TYPE 2 DIABETES-DERIVED HUMAN ADIPOCYTES.

PURPOSE: Short chain fatty acids (SCFAs) play a major regulatory role in adipocyte function and metabolism. The aim of this study was to investigate the effects of SCFAs on adiponectin and leptin expression in adipocytes, and also to determine whether the effects of SCFA treatment in visceral adipocytes obtained from healthy subjects are different relative to the effects in adipocytes from patients with type 2 diabetes. MATERIALS AND METHODS: Human pericardiac preadipocytes and human pericardiac preadipocytes type 2 diabetes were differentiated into adipocytes for 21 days in 48-well plates. After differentiation, two kinds of mature adipocytes, human pericardiac adipocytes (HPAd) and human pericardiac adipocytes-type 2 diabetes (HPAd-T2D) were incubated with or without 1 mM of acetic acid (AA), butyrate acid (BA), and propionic acid (PA). After 48 hours of incubation, intracellular lipid accumulation was measured using oil red staining. In addition, mRNA levels of adiponectin, leptin and Peroxisome Proliferator-Activated Receptor γ (PPARγ) were determined by Real-Time PCR system. RESULTS: In HPAd, SCFA supplementation did not inhibit lipid accumulation. By contrast, both AA (p<0.01) and PA (p<0.01) significantly inhibited lipid accumulation in HPAd-T2D. Regarding mRNA levels of adiponectin, no significant changes were found in HPAd, while all three types of SCFAs significantly increased (p<0.05) adiponectin expression in HPAd-T2D. Leptin mRNA expression levels were significantly increased by treatment with all three types of SCFAs in both HPAd (p<0.05) and HPAd-T2D (p<0.05). CONCLUSION: SCFAs inhibited lipid droplet accumulation and increased mRNA expression of adiponectin and leptin in T2D-derived adipocytes.

Effects of fat-enriched diet and methionine on insulin sensitivity in lactating cows.

The hyperinsulinemic-euglycemic clamp (EGC) technique was used to investigate the effects of calcium salts of long-chain fatty acids (LCFA-Ca) and rumen-protected Met (RPM) on insulin sensitivity in the peripheral tissues of lactating cows. Six multiparous Holstein cows were used in a 3 × 3 Latin square experiment in each 14-d period. Dietary treatments were 0 (RPM0), 20 (RPM20), and 60 (RPM60) g/d of RPM, supplemented with a diet containing 1.5% of LCFA-Ca equal to 110% of the cows' ME requirement. And as a control for the 3 LCFA-Ca-containing diets, a dietary treatment without LCFA-Ca (Con) was also included. After a 10-d adaptation period, milk samples were collected for 4 d, and EGC experiments were performed on d 14 of each treatment period. Insulin solution was infused through a jugular vein catheter at a rate of 0.1, 0.2, 0.3, and 0.4 milliunits·kg BW-1·min-1 for 30 min and then at a rate of 0.5 milliunits·kg BW-1·min-1 for 60 min. Glucose solution was variably infused to maintain plasma glucose at steady state through the same catheter. Blood samples for measurements were taken using the contralateral catheter. Plasma total cholesterol, cholesterol ester, free cholesterol, and phospholipid concentrations in RPM0 and RPM20 were higher than those in Con, whereas the concentrations in RPM60 were low at the same degree of those in RPM0 (P < 0.05). Plasma Met concentration was greatest in RPM60 (P < 0.05). In the EGC experiment, the glucose infusion rate was greater in RPM60 than in RPM0 and RPM20 and an effective concentration of insulin resulting in 50% maximal glucose infusion rate was lower in RPM60 compared with RPM0 (P < 0.05), indicating that insulin sensitivity was intensified in RPM60. Although the insulin sensitivity evaluated from the EGC data in RPM0, RPM20, and RPM60 was not different from Con, a slight decline was observed in RPM0 and insulin sensitivity in RPM60 was higher than Con. Our results from the EGC experiment demonstrated that the feeding RPM lead to increased insulin sensitivity, which suggests that dietary Met affects lipid metabolism via insulin action in lactating dairy cows fed a LCFA-Ca-containing diet.

Ingestion of medium chain fatty acids by lactating dairy cows increases concentrations of plasma ghrelin.

The purpose of this study was to elucidate the effects of medium-chain fatty acids (MCFAs) on plasma ghrelin concentration in lactating dairy cows. Five early-lactating Holstein cows were randomly assigned to 2 dietary treatments in a crossover design with 2-wk periods. Treatments consisted of diets supplemented or not (control) with calcium salts of MCFAs (MCFA-Ca; 1.5% dry matter). Plasma hormone and metabolite concentrations in blood samples taken from the jugular vein were measured on the morning of feeding on day 14 of each period. Dry matter intake, milk protein, and lactose content of cows fed the MCFA-Ca diet were decreased compared with controls, but with no change in milk yield. Plasma ghrelin concentrations were higher in cows fed the MCFA-Ca diet; however, no significant effect was found on glucagon-like peptide-1 concentrations in plasma. Plasma insulin concentrations decreased, but plasma glucagon concentrations remained unchanged in cows fed the MCFA-Ca diet. The concentrations of nonesterified FAs, total cholesterol, and ß-hydroxybutyrate in plasma increased in these cows. In conclusion, dietary MCFAs increase the plasma ghrelin concentrations in lactating dairy cows.

Partial response of angiosarcoma of the scalp to sorafenib: association with decreased expression of vascular endothelial growth factors and their receptors.

The prognosis of angiosarcoma remains very poor, even with combined, multimodal therapy. We report a case with partial response of angiosarcoma of the scalp to sorafenib, which is a new oral, molecular, targeted, multiple-kinase inhibitor. In addition, we confirmed, using immunohistochemistry, that sorafenib suppressed the expression of vascular endothelial growth factors and their receptors on the angiosarcoma tumour cells, and decreased cell numbers by inhibiting cellular proliferation.

Polyphenols from Parabarium huaitingii and their positive inotropic and anti-myocardial infarction effects in rats.

Eight phenolic compounds, including (-)-epicatechin (1) and seven proanthocyanidins (2-8), were obtained from the butanol extract of Parabarium huaitingii (PHB). Their chemical structures were identified based on analyses of mass spectra (MS), NMR, CD spectra, and partial acid catalyzed thiolytic degradation. The observation made by laser scanning confocal microscope found a significant increase of the concentration of intracellular Ca²+ ([Ca²+](i)) in single myocytes when the PHB was added, while compounds 1 and 3 had the same physiological effect. Further investigations showed PHB had a dose-dependent positive inotropic effect on isolated right atria and papillary muscle of left ventricle of the rat, while having no significant influence on the spontaneous beating rate of the isolated right atria. The inotropic effect of PHB could be greatly abolished by pretreating the myocardium in Ca²+-free solution. These findings indicated that PHB could significantly increase [Ca²+](i) in myocytes, which was greatly dependent on the influx of extracellular Ca²+. Compounds 1 and 3 might be the effective ingredients of the inotropic effect of PHB. In addition, PHB could also significantly decrease the infarct size of the heart on acute myocardial infarction (AMI) model rats, which suggested its myocardial protective effect on ischemic myocardium. The positive inotropic effect of PHB, together with its myocardial protective effect on AMI, suggested that PHB had a promising potential for the prevention and treatment of heart failure, especially the one that was caused by AMI.

The antioxidant effect of green tea catechin ameliorates experimental liver injury.

PURPOSE: Several studies have reported green tea catechin to have both antifibrotic and anti-oxidative effects. The goal of this study was to evaluate the effect of green tea cathechin therapy in hepatic tissue injury using cholestatic rats with bile duct ligation. MATERIALS AND METHODS: We performed bile duct ligation on cholestatic seven-week-old male Wistar rats and classified them into three groups according to the method of treatment. The groups comprised the SHAM group, the NT-group (no-treatment-group), and the T-group (treatment-group). The rats were orally administered green tea catechin at a dose of 50mg/kg/day and were sacrificed on the 17th postoperative day. We subsequently investigated the levels of fibrosis and antioxidant activity associated with various clinical markers. We evaluated the serum AST and ALT levels and performed immunohistochemical analyses for 4-hydroxynonenal (4-HNE), 8-oxo-2'deoxyguanosine (8-OHdG) and transforming growth factor-beta1 (TGF-beta1). We also evaluated the levels of activator protein-1 m-RNA (AP-1 m-RNA) and tissue inhibitor metalloproteinase-1 m-RNA (TIMP-1 m-RNA) by Real Time PCR. Finally, we performed Azan staining and immunohistochemical staining of alpha-smooth muscle actin (alpha-SMA) to evaluate the degree of fibrosis. RESULTS: The values of serum AST, serum ALT, AP-1 m-RNA, alpha-SMA, TGF-beta1, 4-HNE, and 8-OHdG in the T-Group were significantly lower than those in NT-Group. Therefore, the administration of green tea catechin might have suppressed the oxidative stress, controlled the stellate cell activation and consequently reduced the fibrosis. CONCLUSION: Green tea catechin may reduce hepatic fibrosis by suppressing oxidative stress and controlling the transcription factor expression involved in stellate cell activation.

Galantamine improves apomorphine-induced deficits in prepulse inhibition via muscarinic ACh receptors in mice.

BACKGROUND AND PURPOSE: Galantamine, a weak acetylcholine esterase (AChE) inhibitor and allosteric potentiator of nicotinic ACh receptors (nAChRs), improves apomorphine-induced deficits in prepulse inhibition (PPI), sensory information-processing deficits, via a nAChR-independent mechanism. The present study examined the role of muscarinic ACh receptors (mAChRs) in the effect of galantamine, and studied the mechanism of galantamine-induced increases in prefrontal ACh levels in mice. EXPERIMENTAL APPROACH: Apomorphine (1 mg kg(-1)) was administered to male ddY mice (9-10 weeks old) to create a PPI deficit model. Extracellular ACh concentrations in the prefrontal cortex were measured by in vivo microdialysis. KEY RESULTS: Galantamine- and donepezil-mediated improvements in apomorphine-induced PPI deficits were blocked by the preferential M(1) mAChR antagonist telenzepine. The mAChR agonist oxotremorine also improved apomorphine-induced PPI deficits. Galantamine, like donepezil, increased extracellular ACh concentrations in the prefrontal cortex. Galantamine-induced increases in prefrontal ACh levels were partially blocked by the dopamine D(1) receptor antagonist SCH23390, but not by antagonists of mAChRs (telenzepine) and nAChRs (mecamylamine). Galantamine increased dopamine, but not 5-HT, release in the prefrontal cortex. CONCLUSIONS AND IMPLICATIONS: Galantamine improves apomorphine-induced PPI deficits by stimulating mAChRs through increasing brain ACh levels via a dopamine D(1) receptor-dependent mechanism and AChE inhibition.

Intrabullous blood injection for lung volume reduction.

Bronchoscopic treatment for emphysematous lung diseases has attracted clinical attention, and several different approaches are being investigated. We present a case of emphysematous bullae that was effectively treated with a newly developed bronchoscopic intervention, autologous blood injection. A 59-year-old man was referred to our institution with exertional dyspnoea. Chest CT showed emphysema and bullae with a diameter of 12 cm in the right upper lobe. Bronchoscopic treatment was introduced as an alternative to surgery. Autologous blood and fibrinogen solution were infused into bullae via the transbronchial catheter, under fluoroscopic guidance. Post-treatment CT showed marked contraction of bullae to a diameter of 3 cm, corresponding to a volume reduction of 800 ml on body plethysmography. A significant reduction in dyspnoea was also noted. This therapeutic approach is less invasive and may represent a good option for reducing lung volume.

A ceramic prosthesis for the treatment of tumours of the distal radius.

Despite extensive experience with prosthetic replacement for the reconstruction of limbs following juxta-articular resection of tumours, there are few reports of prosthetic replacement of the distal radius. We present two cases of massive bone defects of the distal radius in which alumina ceramic prosthetic replacements were used. We evaluated the patients more than ten years after the procedure. Both patients had degenerative changes to the wrist. This, however, was not associated with pain or decreased function, and both had returned to their previous occupation after surgery. When a patient has a massive defect of the distal radius, reconstruction using a ceramic prosthesis is a reasonable alternative to using autograft. This method of treatment results in little pain, a moderate range of movement and satisfactory function.

A novel heterozygous missense mutation in the vasopressin moiety is identified in a Japanese person with neurohypophyseal diabetes insipidus.

The autosomal dominant familial neurohypophyseal diabetes insipidus (adFNDI) is caused by diverse mutations in one allele of the gene that encodes the arginine vasopressin (AVP) precursor protein, AVP-neurophysin II (AVP-NP II). Most of the mutations identified so far are located in either the signal peptide or NP II moiety. Two recently published mutations in the AVP gene identified in kindreds with adFNDI predict a substitution of histidine for tyrosine at position 2 and a deletion of phenylalanine at position 3 in AVP. They are unique among adFNDI mutations in that they are the only adFNDI mutations that affect amino acid residues in the AVP moiety of the pro-hormone. Here, we report a novel heterozygous missense mutation in the AVP moiety of the AVP-NP II gene in a Japanese person with neurohypophyseal diabetes insipidus (DI). This mutation occurs at position 2 in AVP and predicts a substitution of serine for tyrosine (Y21S). It is expected to interfere with normal binding of AVP with NP II, and thus result in misfolding of the precursor proteins. The data of this study support the notion that mutations affecting the AVP moiety can result in the initiation of the pathological processes.

The role of nuclear factor-kappa B in bacterial translocation in cholestatic rats.

Xanthinoxidase (XO) derived radical species are involved in bacterial translocation (BT) in cholestatic rats. The mechanism by which XO influences remains unclear. It has been shown recently that nuclear factor-kappa B (NF-kappaB), a ubiquitous transcription factor, can be activated by oxidative stress and thereby promote the process of BT. We investigated the effects of NF-kappaB inactivation on the incidence of BT in cholestatic rats. Sprague-Dawley rats were randomly assigned to one of eight groups: groups 1-4 were sham laparotomized rats either untreated (S1) or treated for 5 days with thalidomide (S2), curcumin (S3), or Inchin-ko (ICK; S4); groups 5-8 underwent common bile duct ligation (CBDL) for 5 days and were either untreated (C1) or treated with thalidomide (C2), curcumin (C3), or ICK (C4). After 5 days bacteriological cultures were performed from portal blood and V. cava, from the central mesenteric lymph node complex (MLN), spleen, and liver. The intensity of the activated NF-kappaB-subunit p65/p50 in the ileum mucosa was estimated by light microscopy and a scoring system from 1 to 20. Malondialdehyde (MDA) and myeloperoxidase activity (MPO) in the ileum were evaluated and expressed as U/g dry weight. Thalidomide and ICK reduced in CBDL-rats significantly the BT rate (63% vs. 18%, 63% vs. 30%, P<0.01). Enzyme estimations (MDA, MPO, and GSH) in sham operated animals showed no significant changes in the untreated groups compared with the treated groups. CBDL-rats pre-treatment with all three compounds caused a significant increase of MDA levels if groups were compared with the untreated C1-group (C1 31.6+/-7.7, C2 54.5+/-12.2, C3 53.3+/-11.2, and C4 47.2+/-9.4). GSH was reduced after the pre-treatment by all compounds but only significantly after curcumin pre-treatment (C1 vs. C3: 13.9+/-1.8 vs. 7.1+/-1.8; P<0.05). MPO estimations were significantly higher in the untreated C1-group if compared with groups C2, C3, and C4 (C1 1036.4+/-340.9, C2 709.9+/-125.9, C3 545.2+/-136.6, and C4 556.7+/-247.4; P<0.05). Thalidomide inhibited significantly the activation of NF-kappaB (C2 vs. C1: 6.0+/-4.5 vs. 12.7+/-5.3; P<0.01). Likewise, Curcumin and ICK suppressed NF-kappaB activation, but this did not reach significance in this experiment. NF-kappaB is involved in the process of BT in cholestatic rats and may be activated by XO derived ROS. We assume that the activated NF-kappaB initiates transcription of target genes inducing cytokine production, which in turn disrupts the tight junctions leading to BT from the intestinal lumen to the MLNs and circulation.

National hospital infection surveillance on methicillin-resistant Staphylococcus aureus.

Surveillance of methicillin-resistant Staphylococcus aureus (MRSA) infections in Japan was performed in 1995 and 1996. Hospital infection rates of MRSA appear to have remained stable in recent years, and this study was undertaken to test this hypothesis. In national surveillance, the incidence of MRSA hospital infections per 100 admissions remained stable at between 0.7 and 0.8 from 1999 to 2003, with a tendency towards a slight decline. This study shows that precautions against MRSA infection in Japan may prove to be an effective preventive measure.

Comparative clinical study of cefcapene pivoxil and cefteram pivoxil in chronic respiratory tract infections by a double-blind method.

In a double-blind study, the efficacy and safety of the novel cephem antibiotic cefcapene pivoxil (CFPN-PI; 450 mg/day) was compared with cefteram pivoxil (CFTM-PI; 600 mg/day) in 171 patients with chronic respiratory tract infections. There was no significant difference between the clinical efficacy of the two drugs (80.2% for CFPN-PI versus 78.9% for CFTM-PI). There was no significant difference in the rate of elimination of the causative bacteria (60.5% for CFPN-PI versus 65.9% for CFTM-PI). Side-effects were observed in 6.0% of patients treated with CFPN-PI compared with 6.4% of patients treated with CFTM-PI. There were no significant differences in incidence of abnormal laboratory findings following treatment with the two drugs (13.9% for each), and none of the side-effects was severe. We conclude that CFPN-PI (450 mg/day) was as effective and as well tolerated as CFTM-PI (600 mg/day) in the treatment of chronic respiratory tract infections.

A study on the spatial distribution of nitrogen and phosphorus balance, and regional nitrogen flow through crop production.

The spatial distribution patterns of the nitrogen and phosphorus input/intake amounts in crop production within two small basins are examined, based upon a cropping unit distribution map that is obtained from remote sensing data analysis. Firstly, we examine the availability and suitability of approaches to the spatial distribution analysis of cultivation patterns classified from material flow characteristics of crop production using seasonal remote-sensing data. Secondly, material flow units in crop production are grouped according to the cultivation patterns obtained from the remote-sensing data analysis. Consequently, the spatial patterns of the amounts of both nitrogen and phosphorus inputs/intakes through crop production on farmland are examined and their spatial distribution maps are prepared according to the material flow units. In addition, we developed a nitrogen flow and runoff model and the model is simulated based on the examination of the results of spatial distribution patterns of the material flow units. The annual nitrogen runoff from small catchments, where various crops are cultivated, varies from 2.7 kg ha(-1) year(-1) to 108 kg ha(-1) year(-1) and the annual balanced losses of nitrogen in small catchments varied from -30 kg ha(-1) year(-1) to 101 kg ha(-1) year(-1). Also, the monthly changes in soil nitrogen of each material flow unit is estimated at -55 kg ha(-1) as a maximum decrease and 114 kg ha(-1) as a maximum increase. These results indicate that the spatial distribution patterns of nutrient input and intake through agricultural activities should be considered when analyzing the material flows and nutritient movement in soil-water systems in rural areas for watershed environmental control and regional agricultural management.

The effects of Hochu-ekki-to in patients with atopic dermatitis resistant to conventional treatment.

Hochu-ekki-to is one of Kampo formulas containing Astragalus root, liquorice, jujube, ginseng, white Atractylodes rhizome, fresh ginger and Chinese angelica root. This formula has been identified as an effective drug to improve the function of digestive systems and to strengthen defensive systems against many kinds of infections. We examined serum IgE levels and eosinophils before and after the administration of Hochu-ekki-to in patients with recalcitrant atopic dermatitis. The increased numbers of eosinophils was statistically decreased after 3 months' use of this formula. Serum IgE levels showed a tendency to decrease after the administration of this substance.

Diet and Japanese herbal medicine for recalcitrant atopic dermatitis: efficacy and safety.

We have been utilizing Kampo, a Japanese herbal medicine, together with lifestyle advice, for recalcitrant atopic dermatitis. To estimate the safety and efficacy of the treatment, we administered Kampo formulas to patients in whom conventional treatment failed to improve symptoms, along with dietary advice recommending traditional Japanese food. The therapeutic effects of Kampo formulas were assessed in 95 patients with recalcitrant atopic dermatitis who consulted our clinic from January to June, 2000. The overall result was 'markedly effective" in 19 patients (20%), "moderately effective" in 33 (35%), "slightly effective" in 36 (38%) and "ineffective" in four (4%). Three patients dropped out of the study. No adverse reactions in laboratory data were noted in examined patients. The most commonly used formula was Hochu-ekki-to containing Astragalus root, liquorice, jujube, ginseng, white Atractylodes rhizome, fresh ginger and Chinese Angelica root. Diet and Japanese herbal medicine are thought to be useful as an alternative therapy of intractable atopic dermatitis.

Hochu-ekki-to suppresses development of dermatitis and elevation of serum IgE level in NC/Nga mice.

The Japanese herbal medicine Hochu-ekki-to (Chinese name: Bu-Zhong-Yi-Qi-tang) is composed of ten species of medical plants and is used for many therapeutic purposes such as recovery from weakness, dysfunction of the digestive system and fatigue. In certain groups of patients with intractable atopic dermatitis this prescription has shown clinical effectiveness. We examined the ability of Hochu-ekki-to to inhibit dermatitis and IgE production in atopic NC/Nga mice. Oral administration of Hochu-ekki-to suppressed spontaneous dermatitis and serum IgE levels in NC/Nga mice. This finding provides evidence that Hochu-ekki-to may have immunological effects in atopic dermatitis.

High frequency electrical stimulation attenuates progressive necrosis and cavitation following spinal cord injury.

This study evaluates the influence of preconditioning by following electrical stimulation on primary and secondary lesion formation following spinal cord injury in rats. The dorsal surface of the spinal cord was stimulated (500 Hz. 10 pulses/train, inter train interval of 10 sec. for 2 hrs) at the T7 level 24 hrs before a right side hemisection, carried out immediately after injury and maintained every 24 hrs for 7 days. Preconditioning by electrical stimulation of the spinal cord activates reactive astrocytes and significantly attenuates edema and progressive necrosis and cavitation, concerning especially the primary (1, 3 weeks post injury) and secondary (24 hrs, 1, 3 weeks post injury) lesion volume. The results suggest that pre-conditioning by electrical stimulation prevents spinal cord secondary lesion formation after injury, and that the beneficial effect is provided by astroglial cells with regard to their ability to attenuate trauma induced cellular cascades.

In vivo evaluation of a new sealant material on a rat lung air leak model.

The ability of an albumin-based hydrogel sealant (ABHS) to prevent air leakage through the suture line after pulmonary surgery was evaluated by comparison with that of a fibrin glue (FG). As an air-leak model, a rat lung was used in which a standard incision was made and the burst pressure for ABHS and FG was measured. The average burst pressures at time 0 for the FG and ABHS groups were 30.8+/-15.2 and 77.5 +/-19.1 mmHg, respectively. At Day 3, the value of ABHS (76.3 +/- 15.8 mmHg) was still significantly higher (P<0.05) than that of FG (60.0 +/- 21.9 mmHg). At Day 7, no statistical difference was observed between the FG group(71.2 +/- 18.6 mmHg) and the ABHS group(88.8 +/- 11.7 mmHg). Histological examination of the incision at Day 14 revealed that neither sealant was not visible at the incision site, and there was no evidence of adverse tissue reaction. It was concluded that ABHS had good sealing properties and is an alternative to FG for air leakage treatment in pulmonary surgery.