Biomedical subjects

K Sakai

Publications and source records attributed to K Sakai.

At least 181 records · Page 10Linked to original sources

PubMed2000

Spatial pooling in the second-order spatial structure of cortical complex cells.

We investigate what computational mechanisms give rise to the nonlinearity of complex cell responses in the primary visual cortex. Complex cells are characterized by their nonlinear spatial properties such as spatial phase invariance and nonlinear spatial additivity. We carried out network simulations to estimate the second-order Wiener-like kernels for several different models. Models with nonlinear spatial pooling of simple-cell-like linear subunits reproduce the second-order kernels in good agreement with physiologically estimated kernels, while models without the pooling mechanism fail to reproduce the kernel. The results support the cascade mechanism consisting of simple cells' local feature extraction followed by spatial pooling.

Humans↗

PubMed2000

Temperature-dependent modulation of blood platelet movement and morphology on poly(N-isopropylacrylamide)-grafted surfaces.

Poly(N-isopropylacrylamide) (PIPAAm) exhibits a reversible, temperature-dependent soluble/insoluble transition at its lower critical solution temperature (LCST) of 32 degrees C in aqueous media. The temperature-responsive PIPAAm was grafted onto tissue culture polystyrene (TCPS) dish surfaces by electron beam irradiation. Blood platelet behaviors on PIPAAm-grafted surface were examined by computerized image analysis and scanning electron microscopy. Platelet behaviors on this surface were dramatically dependent upon temperature, but those on poly(ethylene glycol)(PEG)-grafted or polystyrene remained unchanged. Below the 32 degrees C (LCST), platelets on PIPAAm-grafted surfaces retained a rounded shape and an oscillating vibratory microbrownian motion for extended times, similarly to those on PEG-grafted surfaces. Above the LCST, platelets readily adhered, spread and developed characteristic pseudopodia on PIPAAm-grafted surface similarly to those on TCPS. An ATP synthesis inhibitor failed to hinder prevention of platelet adhesion onto PIPAAm-grafted surface (below the LCST) suggesting that the preventive mechanism is ATP-independent similarly to that of PEG-grafted surfaces. These results correlate platelet surface activation state with the hydration and structure of polymer surfaces, and demonstrate the ability to modulate such reactions by a small temperature change in situ.

Acrylamides↗

PubMed2000

Bradykinin enhances insulin receptor tyrosine kinase in 32D cells reconstituted with bradykinin and insulin signaling pathways.

We have previously shown that bradykinin potentiated insulin-induced glucose uptake through GLUT4 translocation in canine adipocytes and skeletal muscles. The aim of this study was to determine the molecular mechanism of bradykinin enhancement of the insulin signal. For this purpose, 32D cells, which express a limited number of insulin receptors and lack endogenous bradykinin B2 receptor (BK2R) or insulin receptor substrate (IRS)-1 were transfected with BK2R cDNA and/or insulin receptor cDNA and/or IRS-1 cDNA, and analyzed. In 32D cells that expressed BK2R and insulin receptor (32D-BKR/IR), bradykinin alone had no effect on the phosphorylation of the insulin receptor, but it enhanced insulin-stimulated tyrosine phosphorylation of the insulin receptor. In 32D cells that expressed BK2R, insulin receptor and IRS-1 (32D-BKR/IR/IRS1), bradykinin also enhanced insulin-stimulated tyrosine phosphorylation of the insulin receptor and IRS-1. An increase in insulin-stimulated phosphorylation of IRS-1 by treatment with bradykinin in 32D-BKR/IR/IRS1 cell was associated with increased binding of 85 kD subunit of phosphatidylinositol 3 (PI 3)-kinase and increased IRS-1 associated PI 3-kinase activity. These effects of bradykinin were not observed in 32D cells which lack the expression of BK2R (32D-IR/IRS1) or insulin receptor (32D-BKR/IRS1). Furthermore, tyrosine phosphatase activity against insulin receptor beta-subunit in plasma membrane fraction of 32D-BKR/IR cells was significantly reduced by bradykinin, suggesting that the effect of bradykinin was in part mediated by inhibition of protein tyrosine phosphatase(s). Our results clearly demonstrated that bradykinin enhanced insulin-stimulated tyrosine kinase activity of the insulin receptor and downstream insulin signal cascade through the BK2R mediated signal pathway.

Animals↗

PubMed2000

High plasma cardiac natriuretic peptides associated with enhanced cyclic guanosine monophosphate production in preascitic cirrhosis.

BACKGROUND/AIMS: The initial abnormalities of renal sodium handling in cirrhosis remain unclear. The aim of this study was to characterize sodium metabolism in preascitic cirrhosis. METHODS: Ten patients with preascitic cirrhosis and ten controls were studied. All subjects ate a diet providing 120 mmol sodium during an equilibration period lasting 5 days and the study day. On the study day, after remaining in bed, plasma levels of atrial natriuretic peptide, brain natriuretic peptide, renin activity, aldosterone, noradrenaline, and cyclic guanosine monophosphate were measured at 7 am. Thereafter, they were instructed to maintain an upright posture until dinner and the measurements were repeated at 9 am and 6 pm. After having dinner, all subjects were asked to remain in bed and the measurements were repeated at 11 pm. To measure renal sodium and cyclic guanosine monophosphate excretion, 24-h urine collections were performed, starting from 7 pm on the day before the experimental day. RESULTS: Plasma levels of atrial natriuretic peptide, brain natriuretic peptide and cyclic guanosine monophosphate in patients with preascitic cirrhosis were significantly elevated compared with those in controls at every sampling time (p=0.03 or less, p= 0.04 or less, and p=0.01 or less). In contrast, plasma renin activities at every sampling time were significantly lower in patients than in controls (p= 0.04 or less). Plasma aldosterone and noradrenaline levels were not significantly different at every sampling time in the two groups. No significant differences in daily renal sodium excretion were found. However, urinary cyclic guanosine monophosphate excretion was significantly higher in patients than in controls (p<0.01). CONCLUSIONS: The initial abnormalities of sodium metabolism in cirrhosis might be characterized by blunted renal responsiveness to natriuretic peptides. The results of the study also provide indirect evidence that the impairment is mainly located at postreceptor levels of signal transduction pathway to the peptides, if the activation of antinatriuretic factors other than renin-angiotensin or sympathoadrenergic systems does not play a role.

Adult↗

PubMed2000

Modulation of presumed cholinergic mesopontine tegmental neurons by acetylcholine and monoamines applied iontophoretically in unanesthetized cats.

The mesopontine tegmentum, which contains both cholinergic and non-cholinergic neurons, plays a crucial role in behavioral state control. Using microiontophoresis in unanesthetized cats, we have examined the effect of cholinergic and monoaminergic drugs on two putative cholinergic neurons located mostly in the laterodorsal tegmental nucleus and X area (or the cholinergic part of the nucleus tegmenti pedunculopontinus, pars compacta): one (type I-S) exhibiting slow tonic discharge during both waking and paradoxical sleep, and the other (PGO-on) displaying single spike activity during waking and burst discharges in association with ponto-geniculo-occipital (PGO) waves during paradoxical sleep. We found that: (i) application of carbachol, a potent cholinergic agonist, inhibited single spike activity in both PGO-on and type I-S neurons, but had no effect on the burst activity of PGO-on neurons during paradoxical sleep; the inhibition was associated with either blockade or increased latency of antidromic responses, suggesting membrane hyperpolarization; (ii) application of glutamate, norepinephrine, epinephrine, or histamine resulted in increased tonic discharge in both PGO-on and type I-S neurons; this was state-independent and resulted in a change in the firing mode of PGO-on neurons from phasic to tonic; (iii) application of serotonin had only a weak state-dependent inhibitory effect on a few type I-S neurons; and (iv) application of dopamine had no effect on either type of neuron. The present findings suggest that cholinergic, glutamatergic and monoaminergic (especially noradrenergic, adrenergic and histaminergic) inputs have the capacity to strongly modulate the cholinergic neurons, altering both their rate and mode of discharge, such as to shape their state specific activity, and thereby contribute greatly to their role in behavioral state control.

Acetylcholine↗

PubMed2000

The human hand motor area is transiently suppressed by an unexpected auditory stimulus.

OBJECTIVE: To study the effect of a loud auditory stimulus on the excitability of the human motor cortex. METHODS: Ten normal volunteers participated in this study. The size of responses to transcranial magnetic or electrical cortical stimulation (TMS or TES) given at different times (ISIs) after a loud sound were compared with those to TMS or TES alone (control response). Different intensities and durations of sound were used at several intertrial intervals (ITIs). In addition, we examined how the presence of a preceding click modulated the effect of a loud sound (prepulse inhibition). The incidence of startle response evoked by various stimuli was also studied. RESULTS: A loud auditory stimulus suppressed EMG responses to TMS when it preceded the magnetic stimulus by 30-60 ms, whereas it did not affect responses to TES. This suggests that the suppression occurred at a cortical level. Significant suppression was evoked only when the sound was louder than 80 dB and longer than 50 ms in duration. Such stimuli frequently elicited a startle response when given alone. The effect was not evoked if the ITI was 5 s, but was evoked when it was longer than 20 s. A preceding click reduced the suppression elicited by loud sounds. CONCLUSIONS: Auditory stimuli that produced the greatest effect on responses to TMS had the same characteristics as those which yielded the most consistent auditory startle. We suggest that modulation of cortical excitability occurs in parallel with the auditory startle and both may arise from the same region of the brain-stem.

Acoustic Stimulation↗

PubMed2000

Production of recombinant protein by baculovirus-infected insect cells in immobilized culture using porous biomass support particles.

Immobilization of insect cells using porous biomass support particles (BSPs) and production of a recombinant protein by the immobilized cells after infection with a baculovirus were investigated in a shake-flask culture. Sf9 cells were passively immobilized in reticulated polyvinyl formal (PVF) resin BSPs (2 x 2 x 2 mm cubes) with matrices of 60 mum mean pore diameter in situ in shake-flasks. The cell density in the BSPs was over 5 x 10(7) cells/cm3-BSP in cultures with regular replacement of the culture medium, as estimated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. After infection with a recombinant baculovirus carrying the beta-galactosidase gene, immobilized cells within the BSPs showed a high specific productivity, comparable to the maximum productivity in shake-flask cultures of non-immobilized cells, as long as nutrients in the medium were not depleted. Even when immobilized cells at a high density of 5 x 10(7) cells/cm3-BSP were infected with the baculovirus, efficient beta-galactosidase production with a high specific productivity was possible by replacing the medium at appropriate intervals to avoid nutrient depletion.

Journal Article↗

PubMed2000

Two catalytic domains of Chlorella virus CVK2 chitinase.

VChti-1 chitinase encoded by the Chlorella virus CVK2 contained two catalytic domains belonging to family 18 glycosyl hydrolases. The first catalytic domain on a C-terminal-truncated derivative of vChti-1 generated exclusively chitobiose from chitotetraose, chitohexaose, and colloidal high-molecular mass chitin in the enzyme reaction, a typical characteristic of an exochitinase. In contrast, N-acetylglucosamine was produced from chitobiose as well as from chitooligosaccharides by the second catalytic domain on an N-terminal-truncated derivative of vChti-1. Therefore, the second domain possessed N-acetylglucosaminidase activity as well as endochitinase activity. The presence of two catalytic domains with different enzymatic properties in the viral enzyme seems to be necessary for hydrolyzing natural substrates in a cooperative fashion.

Journal Article↗

PubMed2000

Dietary short-chain fructooligosaccharides increase calbindin-D9k levels only in the large intestine in rats independent of dietary calcium deficiency or serum 1,25 dihydroxy vitamin D levels.

Dietary short-chain fructooligosaccharides (Sc-FOS) increase mucosal calbindin-D9k (CaBP) levels in the large intestine whereas levels in the small intestine are decreased in rats. In the present study, we investigated the mechanism by which Sc-FOS induce this increase in CaBP in the large intestine by measuring intestinal CaBP levels in rats fed normal and calcium-deficient diets. Dietary groups included a calcium-containing (0.5%) diet with or without Sc-FOS (100 g/kg diet) and a calcium-deficient (abt. 0.01%) diet with or without Sc-FOS (100 g/kg diet). The rats were fed these diets for 10 days following which they were killed and the intestine removed for collection of the entire mucosa which was divided into four segments, i.e., proximal and distal segments of the small intestine, the cecum and the colorectum. Mucosal CaBP and plasma calcium (Ca), 1,25-dihydroxycholecalciferol (1,25(OH)2D3), 25-hydroxycholecalciferol (25(OH)D3), parathyroid hormone (PTH) and calcitonin levels were measured. Feeding of calcium deficient diet resulted in an increase in CaBP levels in the small intestine, but did not influence levels in the large intestine. Moreover, a significant positive correlation between plasma 1,25(OH)2D3 and CaBP levels in the case of both small intestinal segments (proximal, r = 0.77012, p < 0.00007; distal, r = 0.75056, p < 0.00014) was observed, but not in the case of the large intestinal segments. Sc-FOS increased CaBP levels in the large intestine. These results suggest that the large intestinal CaBP levels do not change in response to dietary calcium conditions and are not regulated by circulating 1,25(OH)2D3 indicating that the effect of Sc-FOS on CaBP levels in the large intestine is independent of the action of 1,25(OH)2D3.

Animals↗

PubMed2000

Interaction of isoflurane and cromakalim, a KATP channel opener, on coronary and systemic haemodynamics in chronically instrumented dogs.

BACKGROUND: Although isoflurane has been shown to cause coronary and systemic vasodilation through KATP channel activation, the interaction of KATP channel openers and isoflurane has not been fully investigated. The present study was carried out to determine the haemodynamic actions of cromakalim, a KATP channel opener, under the conscious state and during isoflurane anaesthesia in chronically instrumented dogs. METHODS: Fourteen dogs were chronically instrumented to measure systemic and coronary haemodynamics. Each dog was randomly assigned to receive doses of either cromakalim, 4 and 10 microg x kg(-1) i.v., or isoflurane, 2.1% end-tidal (1.5 MAC), plus cromakalim, 4 and 10 microg x kg(-1) i.v. RESULTS: Cromakalim dose-relatedly decreased mean arterial pressure and systemic vascular resistance and increased coronary blood flow in both conscious and anaesthetized states. With isoflurane, the duration of effects of cromakalim were prolonged. Isoflurane exerted an additive effect on the increase in coronary blood flow induced by a low-dose cromakalim, whereas it did not influence the effect of a high-dose cromakalim. The maximum rate of increase in left ventricular pressure and segment shortening were increased by cromakalim in the conscious state but unchanged during isoflurane anaesthesia. CONCLUSION: The results suggest that the coronary vasodilating effects of isoflurane and cromakalim are basically additive until cromakalim exerts the maximal effect, and that the action of cromakalim on the coronary vasculature is prolonged by isoflurane.

ATP-Binding Cassette Transporters↗

PubMed2000

A phase I dose escalation study of multicyclic, dose-intensive chemotherapy with peripheral blood stem cell support for small cell lung cancer.

A phase I dose-escalation study of multicyclic, ifosfamide, carboplatin, and etoposide (ICE) with sequential reinfusion of peripheral blood stem cells (PBSCs) was conducted to determine the maximum-tolerated dose (MTD) of ICE. Twenty-four patients with SCLC (LD: 6, ED: 18) were treated with ifosfamide (3000-9000 mg/m2, 24-h infusion), carboplatin (300-400 mg/m2), and etoposide (300 mg/m2) followed by subcutaneous filgrastim (75 microg/day) from day 4 to the day of PBSC collection. PBSC were harvested when the WBC count reached >/=5 x 109/l. The leukapheresis product was cryopreserved and reinfused on day 4 of the next cycle, which was started 48 h after the last PBSC collection. The ifosfamide dose was escalated as follows: 3000 mg/m2 (level 1), 5000 mg/m2 (level 2), 7000 mg/m2 (level 3), 9000 mg/m2 (level 4). Patients with LD were treated with concurrent radiotherapy at 1.5 Gy twice daily for the initial 3 weeks to a total dose of 45 Gy and MTD, defined separately. Patients were evaluated for hematologic and non-hematologic toxicity, actual dose intensities, as well as response to therapy. The maximum-tolerated dose (MTD) was defined as the dose level at which more than 5 days of grade 4 myelo- suppression or non-hematologic toxicity greater than grade 3 developed in two thirds of the patients. For ED cases, MTD was level 4 and the recommended dose of ifosfamide was 7000 mg/m2. For LD cases, the recommended dose of ifosfamide was 5000 mg/m2. The dose limiting toxicity of multicyclic ICE was hemato- logic toxicity and CNS toxicity which manifested as ataxia. Tumor responses were seen in all patients, with 14 patients showing a complete response. The actual total dose-intensity at the recommended dose level was 2.2 and 1.74, for ED and LD, respectively, compared with previously reported ICE regimens. PBSC support for dose-intensive ICE regimen permitted dose escalation of ifosfamide with a mean interval of 16-17 days. We conclude that this regimen is well tolerated, with acceptable hematological and non-hematological toxicity. Bone Marrow Transplantation (2000) 25, 5-11.

Adult↗

PubMed2000

Phosphorylation of retinoblastoma protein in rat brain after transient middle cerebral artery occlusion.

Although mature neurones do not replicate genomic DNA, some cell cycle-related kinases are aberrantly activated in neurones after ischaemia. As hyper-phosphorylation of retinoblastoma (Rb) protein is the common pathway in mitotic signal cascade, this study investigated the phosphorylation state of the Rb protein as well as its mRNA level in rat brain after transient middle cerebral artery (MCA) occlusion. Immunohisto-chemical analysis revealed that neurones in the sham-operated brain expressed Rb protein without the hyperphosphorylated form. Immunoreactivity for the hyperphosphorylated form of Rb protein progressively increased from 1 h to 3 days after ischaemia in neurones in the MCA territory. Western blot analysis demonstrated a similar change. However, reverse transcription-polymerase chain reaction study revealed that Rb showed no definite change at the mRNA level. These results suggest that Rb protein is progressively hyper-phosphorylated in the brain after ischaemia, which may activate apoptotic mechanisms in neuronal cells of the brain after ischaemia.

Animals↗

PubMed2000

Endoscopic neodymium:yttrium aluminium garnet (Nd:YAG) laser irradiation of a bladder hemangioma associated with Klippel-Weber syndrome.

A case of endoscopic neodymium:yttrium aluminium garnet (Nd:YAG) laser coagulation of a bladder hemangioma associated with Klippel-Weber syndrome is presented. The patient presented with extensive nevus and swelling of the left lower limb since birth. She was diagnosed with Klippel-Weber syndrome by angiography at the age of 1 year. Gross hematuria had been observed since she was 1 year old and, in addition, endoscopic examination revealed diffuse bladder hemangiomas. At 8 years of age, gross hematuria became worse and gait disturbance also appeared. She was referred to the Department of Urology at Tohoku University School of Medicine for endoscopic treatment in June 1998. Under general anesthesia, the bladder was inflated with CO2 gas and the hemangiomas were coagulated by Nd:YAG laser photonic irradiation endoscopically. Gross hematuria was markedly improved immediately following this treatment. Klippel-Weber syndrome is a rather uncommon disease which shows various types of vascular anomaly and hypertrophy of the lower extremities. Three to 6% of the patients have associated bladder hemangiomas. Although Nd:YAG laser irradiation provides results superior to alternative therapy and is the preferred treatment for most patients with bladder hemangioma, in this case, hemangiomas are multiple and present the possibility of re-bleeding, therefore long-term and close follow up is important.

Child↗

PubMed2000

Role of leukocyte adhesion molecules in monocyte/ macrophage infiltration in weanling rats with unilateral ureteral obstruction.

BACKGROUND: Unilateral ureteral obstruction (UUO) of rats is a well-established model for studying obstructive nephropathy. Meanwhile, pathophysiology of pediatric obstructive nephropathy is not well understood. In this report, we studied monocyte/macrophage infiltration and expression of intercellular adhesion molecule 1 (ICAM-1) and macrophage antigen 1 (Mac-1) in weanling rats with UUO. METHODS: Three-week-old male Sprague-Dawley rats underwent left unilateral ureteral ligation. Both obstructed kidneys (OBK) and contralateral kidneys (CLK) were harvested at 3, 6, 12, 24, 72 and 120 h after surgery. Monocyte/macrophage infiltration and expression of ICAM-1 and Mac-1 were evaluated immunohistochemically, and results were compared with those of sham-operated control rats (SOK). RESULTS: Monocyte/macrophage infiltration was observed in the interstitium and perivascular region in the cortex of OBK within 6 h. The CLK and SOK showed slight monocyte/macrophage infiltration. Expression of ICAM-1 was markedly observed in the periarterial and peritubular interstitium and in renal cortical peritubular capillaries 12 h after obstruction. In CLK and SOK, ICAM-1 was slightly expressed in the endothelium of microvessels and parietal linings of Bowman's capsule. Expression of Mac-1 was detected mainly in cells infiltrating the perivascular interstitium in OBK. In CLK and SOK, few Mac-1-positive cells were observed. CONCLUSIONS: Adhesion molecules, ICAM-1 and Mac-1, are expected to recruit monocyte/macrophage infiltration into OBK of weanling rats with UUO.

Animals↗

PubMed2000

Engineering analysis of diamond-like carbon coated polymeric materials for biomedical applications.

Diamond-like carbon (DLC) films have received much attention recently owing to their properties, which are similar to diamond: hardness, thermal conductivity, corrosion resistance against chemicals, abrasion resistance, good biocompatibility, and uniform flat surface. Furthermore, DLC films can be deposited easily on many substrates for wide area coat at room temperature. DLC films were developed for applications as biomedical materials in blood contacting-devices (e.g., rotary blood pump) and showed good biocompatibility for these applications. In this study, we investigated the surface roughness by Atomic Force Microscopy (AFM) and Hi-vision camera, SEM for surface imaging. The DLC films were produced by radio frequency glow discharge plasma decomposed of hydrocarbon gas at room temperature and low pressure (53 Pa) on several kinds of polycarbonate substrates. For the evaluation of the relation between deposition rate and platelet adhesion that we investigated in a previous study, DLC films were deposited at the same methane pressure for several deposition times, and film thickness was investigated. In addition, the deposition rate of DLC films on polymeric substrates is similar to the deposition rate of those deposited on Si substrates. There were no significant differences in substrates' surface roughness that were coated by DLC films in different deposition rates (16-40 nm). The surface energy and the contact angle of the DLC films were investigated. The chemical bond of DLC films also was evaluated. The evaluation of surface properties by many methods and measurements and the relationship between the platelet adhesion and film thickness is discussed. Finally, the presented DLC films appear to be promising candidates for biomedical applications and merit investigation.

Anticoagulants↗

PubMed2000

Experience with the pedicled latissimus dorsi flap for finger reconstruction.

The pedicled latissimus dorsi flap was used for the reconstruction of finger function in 12 patients with severely disabled hands. The fascial origin of the muscle was sutured directly to finger flexors in 6 patients, and to extensors in the other 6 patients in the forearm without severing the neurovascular pedicle. Voluntary contraction of the muscle was obtained in all patients. Useful tendon gliding was achieved in 6 patients, thereby providing total active motion of fingers of >100 degrees. In the remaining 6 patients, however, several problems such as stiff finger joints prevented appropriate tendon gliding, resulting in total active motion of <60 degrees. When these problems are overcome, the pedicled latissimus dorsi muscle can yield satisfactory excursion for extrinsic tendons of the fingers. In contrast to free muscle transplantation, early and predictable recovery of function can be obtained using this particular technique without any risk of denervation of the muscle.

Adolescent↗

PubMed2000

Involvement of bradykinin in acute exercise-induced increase of glucose uptake and GLUT-4 translocation in skeletal muscle: studies in normal and diabetic humans and rats.

Acute exercise induces glucose uptake in skeletal muscle in vivo, but the molecular mechanism of this phenomenon remains to be identified. In this study, we evaluated the involvement of bradykinin in exercise-induced glucose uptake in humans and rats. In human studies, plasma bradykinin concentrations increased significantly during an ergometer exercise (20 minutes) in 8 healthy normoglycemic subjects and 6 well-controlled type 2 diabetic patients (mean hemoglobin A1c [HbA1c], 6.4% +/- 0.6%), but not in 6 poorly controlled type 2 diabetics (mean HbA1c, 11.6% +/- 2.6%). In rat studies, plasma bradykinin concentrations also significantly increased after 1 hour of swimming in nondiabetic and mildly diabetic (streptozotocin [STZ] 45 mg/kg intravenously [IV]) rats, but not in rats with severe diabetes (STZ 65 mg/kg IV). Glucose influx (maximum velocity [Vmax]) and GLUT-4 translocation in skeletal muscle of nondiabetic rats significantly increased after 1 hour of swimming, but these increases were abrogated by subcutaneous infusion of bradykinin B2 receptor antagonist HOE-140 (400 microg x kg(-1) x d(-1)). Insulin-stimulated tyrosine phosphorylation and phosphatidylinositol (PI) 3-kinase activity in response to insulin injection (20 U/kg IV) in the portal vein were significantly attenuated in exercised rats pretreated with HOE-140 compared with saline-treated exercised rats. Our results suggest that plasma bradykinin concentrations increase in response to acute exercise and this increase is affected by blood glucose status in diabetic patients. Moreover, the exercise-induced increase in bradykinin may be involved in modulating exercise-induced glucose transport through an increase of GLUT-4 translocation, as well as enhancement of the insulin signal pathway, during the postexercise period in skeletal muscle, resulting in a decrease of blood glucose.

Adult↗

PubMed2000

Inhibition of tyrosinase by flavonoids, stilbenes and related 4-substituted resorcinols: structure-activity investigations.

Several flavonoids, stilbenes and related 4-substituted resorcinols, obtained from Artocarpus incisus and other plants or synthesized, were tested for their inhibitory activity against tyrosinase. The structure-activity relationships suggested that specific natural or synthesized compounds having the 4-substituted resorcinol skeleton have potent tyrosinase inhibitory ability. Kinetic studies have indicated that specific compounds having the 4-substituted resorcinol skeleton exhibit competitive inhibition of the oxidation of DL-beta-(3,4-dihydroxyphenyl)alanine (DL-DOPA) by mushroom tyrosinase. These findings could lead to the design and discovery of new tyrosinase inhibitors.

Enzyme Inhibitors↗