Tyrosinase inhibitors from natural and synthetic sources: structure, inhibition mechanism and perspective for the future.

Tyrosinase is known to be a key enzyme in melanin biosynthesis, involved in determining the color of mammalian skin and hair. Various dermatological disorders, such as melasma, age spots and sites of actinic damage, arise from the accumulation of an excessive level of epidermal pigmentation. In addition, unfavorable enzymatic browning of plant-derived foods by tyrosinase causes a decrease in nutritional quality and economic loss of food products. The inadequacy of current conventional techniques to prevent tyrosinase action encourages us to seek new potent tyrosinase inhibitors. This article overviews the various inhibitors obtained from natural and synthetic sources with their industrial importance.

Enzymatic synthesis of a catechin conjugate of polyhedral oligomeric silsesquioxane and evaluation of its antioxidant activity.

The antioxidant activity of catechin was amplified by conjugation with amine-terminated polyhedral oligomeric silsesquioxane (POSS) using horseradish peroxidase as catalyst. Compared to intact catechin, the scavenging activity of the POSS-catechin conjugate against superoxide anion was greatly improved. In addition, the conjugate strongly inhibited xanthine oxidase activity.

Enzymatic synthesis of cross-linkable polyesters from renewable resources.

Enzymatic synthesis of a new class of cross-linkable polyesters has been achieved. Polymerization of divinyl sebacate and glycerol using Candida antarctica lipase as catalyst in the presence of unsaturated higher fatty acids produced the polyesters having an unsaturated group in the side chain. The polyester was subjected to hardening by cobalt naphthenate catalyst or thermal treatment, yielding cross-linked transparent film.

[Two cases of exercise-induced acute renal failure with idiopathic renal hypouricemia].

Acute renal failure without oliguria developed in a 25-year-old male and a 19-year-old male after exercise. Marked hypouricemia became apparent during improvement of their renal function. Increased excretion of uric acid into the urine, increased fractional excretion of uric acid(clearance ratio of uric acid against creatinine), and normal concentration of plasma xanthine and hypoxanthine were observed in both cases. Probenecid and pyrazinamide loading test suggesting decreased reabsorption of uric acid in the proximal convoluted tubules revealed that presecretory reabsorption defect of uric acid resulted in the hypouricemia in both cases. These two cases were diagnosed as having idiopathic renal hypouricemia.

Enhanced expression of plasminogen activator inhibitor 1 in patients with nephrotic syndrome.

Hypercoagulability is present in patients with nephrotic syndrome. However, alterations in coagulation and fibrinolysis reflected in the glomeruli and urine are not fully understood. We examined plasma and urine concentrations of tissue-type plasminogen activator (tPA) and type 1 plasminogen activator inhibitor (PAI-1) in 33 patients with nephrotic syndrome (nephrotic group). We compared these concentrations with the concentrations in 30 nonnephrotic patients with chronic glomerulonephritis (nonnephrotic group) and with the concentrations in 30 healthy volunteers (control group). We also examined fibrin/fibrinogen degradation products in serum and urine and plasma D-dimers. The expression of tPA and PAI-1 was examined in isolated glomeruli using RT-PCR methods. Deposition of fibrinogen/fibrin-related antigen was observed by direct immunofluorescence. The incidence of fibrinogen/fibrin-related antigen deposition in the nephrotic group was significantly higher than that in the nonnephrotic group. The concentrations of fibrin/fibrinogen degradation products in serum and urine and of plasma D-dimers were significantly elevated in the nephrotic group as compared with the nonnephrotic and control groups. The plasma concentrations of tPA in the nephrotic group were significantly higher than those in the control group. The urinary excretion of tPA in the nephrotic group was also significantly higher than in the nonnephrotic and control groups. The urinary excretion of PAI-1 in the nephrotic group was higher than that in the control group. The ratio of PAI-1 mRNA to tPA mRNA in glomeruli was increased in the nephrotic group as compared with the nonnephrotic group. These results indicate that the fibrinolytic activity is increased in patients with nephrotic syndrome despite urinary losses of tPA. However, a relatively enhanced expression of PAI-1 may be involved in the intraglomerular fibrinogen/fibrin-related antigen deposition seen in nephrotic syndrome.

In vitro biosynthesis of polyesters.

In vitro synthesis of polyesters using isolated enzymes as catalyst via non-biosynthetic pathways is reviewed. In most cases, lipase was used as catalyst and various monomer combinations, typically oxyacids or their esters, dicarboxylic acids or their derivatives/glycols, and lactones, afforded the polyesters. The enzymatic polymerization often proceeded under mild reaction conditions in comparison with chemical processes. By utilizing characteristic properties of lipases, regio- and enantioselective polymerizations proceeded to give functional polymers, most of which are difficult to synthesize by conventional methodologies.

Artificial urushi.

A new concept for the design and laccase-catalyzed preparation of "artificial urushi" from new urushiol analogues is described. The curing proceeded under mild reaction conditions to produce the very hard cross-linked film (artificial urushi) with a high gloss surface. A new cross-linkable polyphenol was synthesized by oxidative polymerization of cardanol, a phenol derivative from cashew-nut-shell liquid, by enzyme-related catalysts. The polyphenol was readily cured to produce the film (also artificial urushi) showing excellent dynamic viscoelasticity.

Lipase-catalyzed degradation of polyesters in organic solvents. A new methodology of polymer recycling using enzyme as catalyst.

Enzymatic hydrolytic degradation of aliphatic polyesters in organic solvents has been examined. The degradation of poly(epsilon-caprolactone) took place using Candida antarctica lipase as catalyst in toluene at 60 degrees C to give oligomers with molecular weight of less than 500. The degradation behavior catalyzed by lipase was quite different than an acid-catalyzed degradation (random bond cleavage of polymer). After the removal of the solvent from the reaction mixture, the residual oligomer was polymerized in the presence of the same catalyst of lipase. These data provide a basic concept that the degradation-polymerization could be controlled by presence or absence of the solvent, providing a new methodology of plastics recycling.

Chemoselective oxidative polymerization of m-ethynylphenol by peroxidase catalyst to a new reactive polyphenol.

Enzymatic oxidative polymerization of m-ethynylphenol possessing two reactive groups, phenol and acetylene moieties, was carried out in aqueous methanol under air. Horseradish peroxidase and hydrogen peroxide were used as catalyst and oxidizing agent, respectively. 1H NMR and IR analysis showed that only the phenolic moiety was polymerized to produce the polymer having the ethynyl group in the side chain. The reaction of the monomer using a copper/amine catalyst, a conventional catalyst for oxidative coupling, exclusively produced a diacetylene derivative. From these data, it was found that the peroxidase catalysis induced the chemoselective polymerization of the monomer. The resulting polymer was converted to carbonized polymer in a much higher yield than enzymatically synthesized poly(m-cresol) and is expected to have potential applications as a reactive starting polymer.

Enzymatic synthesis of polyesters from lactones, dicarboxylic acid divinyl esters, and glycols through combination of ring-opening polymerization and polycondensation.

Enzymatic copolymerization of lactones, divinyl esters, and glycols has been performed using lipase as catalyst to produce ester copolymers. The monomers used in this study were 12-, 13-, and 16-membered lactones, divinyl esters of adipic and sebasic acids, and alpha,omega-glycols. Candida antarctica and Pseudomonas cepacia lipases showed relatively high catalytic activity for the present copolymerization, yielding the copolymer having relatively high molecular weight in moderate yields. From 13C NMR analysis, the resulting product was not a mixture of homopolymers, but a copolymer derived from the monomers. NMR data and reaction monitoring results indicate that two different modes of polymerization, ring-opening polymerization and polycondensation, simultaneously take place through enzyme catalysis in one-pot to produce ester copolymers.

Lipase-catalyzed ring-opening polymerization of lactones to polyesters and its mechanistic aspects.

Lipase catalysis induced a ring-opening polymerization of lactones with different ring-sizes. Small-size (four-membered) and medium-size lactones (six- and seven-membered) as well as macrolides (12-, 13-, 16-, and 17-membered) were subjected to lipase-catalyzed polymerization. The polymerization behaviors depended primarily on the lipase origin and the monomer structure. The macrolides showing much lower anionic polymerizability were enzymatically polymerized faster than epsilon-caprolactone. The granular immobilized lipase derived from Candida antartica showed extremely efficient catalysis in the polymerization of epsilon-caprolactone. Single-step terminal functionalization of the polyester was achieved by initiator and terminator methods. The enzymatic polymerizability of lactones was quantitatively evaluated by Michaelis-Menten kinetics.

Deposition at low substrate temperatures of high-quality TiO2 films by radical beam-assisted evaporation.

We deposited high-quality TiO2 films by an oxygen-radical beam-assisted evaporation (RBE) method at a lower substrate temperature (Ts) than that for a TiO2 film deposited by conventional thermal evaporation (TE) with neutral-oxygen gas. The films were then evaluated in terms of refractive index, shift of wavelength of a peak in the reflection curve, and absorption coefficient. The TiO2 films deposited by RBE at Ts < 473 K showed higher refractive indices, were more compact, and had lower absorption coefficients than the film deposited by TE at Ts = 473 K.

Discordance between retinopathy and nephropathy in type 2 diabetes.

The aim of this study was to investigate the relationship between the grade of retinopathy and the severity of glomerular lesions in patients with type 2 diabetes and to describe 5 patients without diabetic retinopathy for whom renal biopsy specimens demonstrated advanced diabetic nephropathy. A total of 221 patients with type 2 diabetes (139 males and 82 females) who consectively underwent renal biopsy between 1982 and 1996 were investigated. The severity of diffuse glomerular lesions was graded using the criteria of Gellman and coworkers, and diabetic retinopathy was classified as absent, nonproliferative, or proliferative. The incidence of advanced nephropathy without retinopathy for all 221 cases was 2.3%. Advanced nephropathy was present in 5 of the 122 (4.1%) patients without retinopathy. These 5 patients were all males and aged 50-70 (mean 61) years. Their clinical characteristics were not uniform, and no special clinical features distinguished the patients who were regarded as having possible advanced nephropathy without retinopathy. In our study, although concordance of retinopathy and nephropathy is relatively common, a little discordance was pronounced in Japanese type 2 diabetic patients. Our findings are consistent with the hypothesis that there are important differences in some aspects of the pathogenesis of retinopathy and nephropathy.

Polymer-coated hollow fiber for CO(2) laser delivery.

Hollow fibers for CO(2) laser light have been fabricated with a cyclic olefin polymer as the inner dielectric. A film of cyclic olefin polymer was coated inside the glass capillary tubing by a simple liquid-flowing process. A polymer-coated fiber with a 700-microm bore showed a loss of 0.06 dB/m for CO(2) laser light because cyclic olefin polymer has low absorption at a 10.6-microm wavelength.

Refractive indices and extinction coefficients of polymers for the mid-infrared region.

Refractive indices and extinction coefficients of several polymers have been measured for the wide infrared wavelength region. The polymers used as coating materials have also been found useful for low-loss hollow waveguides for the transmission of Er:YAG, CO, and CO(2) laser light, respectively.

Cyclic olefin polymer-coated silver hollow glass waveguides for the infrared.

Cyclic olefin polymer (COP) is newly used as the inner dielectric of infrared, hollow glass waveguides because of its low extinction coefficient in the mid-infrared region. A liquid-flow coating and dry-cure process are employed to form the COP layer on the inside of a silver-coated hollow glass tube. In the coating process, cyclohexane is chosen as the solvent of COP to form a smooth and uniform COP layer. It is shown that COP-coated silver hollow glass waveguides show low loss properties for CO(2), CO, and Er:YAG laser light when the thickness of the COP layer is properly chosen.

[An elderly patient with purpura nephritis that appeared after extracorporeal shock wave lithotripsy].

We report a 63-year-old male patient with purpura nephritis, which appeared 7 days after extracorporeal shock wave lithotripsy (ESWL). He was referred to our clinic because of a petechial rash on both lower extremities, pretibial edema and massive proteinuria. Urinalysis showed proteinuria and hematuria and some hyaline casts. A 24-hour urine sample contained 5.0 g of protein. Renal function on admission was decreased: serum creatinine was 1.5 mg/dl and creatinine clearance, 21 ml/min. Immunoserological tests demonstrated an increase in serum IgA (424.3 mg/dl). A skin biopsy revealed leukocytoclastic vasculitis. A renal biopsy showed endocapillary proliferation in a diffuse, but segmental fashion. However, no crescent formation was seen. Immunofluorescence microscopy disclosed mesangial staining for IgA and C3. Electron microscopy demonstrated severe injury to endothelial and epithelial cells: detachment of endothelial and epithelial cells, foot process effacement and macrophage infiltration. Electron-dense deposits were observed in the subendothelial and paramesangial areas. Because renal function was deteriorating rapidly, methylprednisolone pulse therapy and immunosuppressive treatment were implemented. Treatment was effective and the patient's renal function and proteinuria improved remarkably. The electron microscopic findings in this case of purpura nephritis seemed to be more severe than usual, suggesting that ESWL may aggravate glomerular damage.

Reversible glomerular hypertrophy in adult patients with primary focal segmental glomerulosclerosis.

The present study was performed to assess the pathogenetic role of glomerular hypertrophy in patients with primary focal segmental glomerulosclerosis (FSGS). We studied 14 patients with FSGS by morphometry. In seven patients, minimal change nephrotic syndrome (MCNS) was diagnosed on the first renal biopsy, but FSGS was diagnosed on the second biopsy (MCNS-FSGS group). Seven other patients with FSGS on the first biopsy underwent second biopsies while in remission (FSGS-R group). Biopsy results were compared with biopsies from 10 patients with MCNS and seven control subjects. Nonsclerotic glomeruli were examined. The mean glomerular tuft area, whole glomerular area, and number of mesangial cells were significantly increased in both biopsies from the MCNS-FSGS group and in the first biopsies obtained during the nephrotic stage of the FSGS-R group, compared with control subjects and patients with MCNS. Biopsies from FSGS patients in remission showed that the mean glomerular tuft area and number of mesangial cells were significantly decreased. The fractional extracellular matrix area (extracellular matrix area/glomerular tuft area) and mesangial cell density (mesangial cell number/glomerular tuft area) in FSGS during both nephrotic and remission stages were the same as those in control subjects and patients with MCNS. The present study suggests that glomerular hypertrophy precedes the development of glomerulosclerosis in FSGS and is reversible when patients are in remission. These features support the pathogenetic importance of glomerular hypertrophy in patients with primary FSGS.