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Biomedical subjects

A Kamada

Publications and source records attributed to A Kamada.

At least 37 records · Page 2Linked to original sources

Disaccharide analysis of chondroitin sulphate in human gingival crevicular fluid using high-performance liquid chromatography.

Gingival crevicular fluid (GCF) was collected into capillary tubes from healthy gingiva and sites of advanced periodontitis. Following digestion with Pronase E, the glycosaminoglycans were isolated by successive precipitation into 5% cetylpyridinium chloride and 95% ethanol. Unsaturated disaccharide isomers of chondroitin sulphate, obtained following chondroitinase ACII digestion, were analysed by high-performance liquid chromatography. Chondroitin sulphate was found in all GCF samples, with greater amounts in patients with periodontal disease than at control sites with a relatively healthy periodontium. The predominant isomer in the periodontal diseased group was delta Di-4S, while that in the control group and serum samples was delta Di-0S. Comparison of the relative proportions of the unsaturated disaccharides in GCF with previously reported values for alveolar bone, cementum, gingiva and periodontal ligament, as well as for serum, indicates that the chondroitin sulphate present in GCF of patients with periodontal disease originated from the mineralized connective tissues of the periodontium, notably alveolar bone, possibly with some contributions from soft connective tissues of gingiva and periodontal ligament and from serum.

Adult↗

Changes in glycosaminoglycan characteristics during progression of a human gingival carcinoma xenograft line in nude mice.

We investigated changes in the glycosaminoglycans (GAGs) during progression of a human gingival carcinoma xenograft line, GK -1, in nude mice. The GAGs extracted from cancers 3, 5, 7, 10 and 15 weeks after transplantation consisted of hyaluronic acid (HA), chondroitin sulfate (CS) and heparan sulfate (HS) as major components, and dermatan sulfate (DS) as a trace component for all cancers. HPLC analysis revealed that the HA content per defatted tissue dry weight increased in the cancers 5 weeks after transplantation compared to those of 3 weeks (p < 0.05), while CS for cancers at 10 weeks decreased compared with 7 weeks (p < 0.05). However, HS showed no significant change. Both the CS and DS contained primarily 4-sulfated disaccharide units. Immunohistochemical staining with antibody 2-B-6 for the PGs having delta DI-4S produced by chondroitinase ABC digestion showed that CS is located in the tissue surrounding the cancer nests and mass. These results indicate that the location of accumulation of CS, which primarily contains 4-sulfated disaccharide units, plays an important role in cancer progression.

Animals↗

Studies on orally active cephalosporins. I. Synthesis and structure-activity relationships of new 3-substituted carbamoyloxymethyl cephalosporins.

The synthesis and antibacterial activities of 7 beta-[2-(2-aminothiazol-4-yl)-2-hydroxyiminoacetamido]-3-N,N - dimethylcarbamoyloxymethyl-3-cephem-4-carboxylic acid (E1100) and its analogs are described, as well as oral absorbability and in vivo activities of the 1-(isopropoxycarbonyloxy)ethyl ester (E1101) and its analogous esters. The introduction of acyclic and cyclic lower alkyl groups at the N-position of 3-carbamoyloxymethyl cephems influences antibacterial activities, especially against H. influenzae, and oral absorbability of their prodrug esters. The structure-activity relationships are also discussed.

Administration, Oral↗

Studies on orally active cephalosporins. II. Synthesis and structure-activity relations of new [(E) or (Z) 3-substituted carbamoyloxy]-1-propenyl cephalosporins.

In an effort to find a new oral cephalosporin with well-balanced antibacterial spectrum, good oral absorbability and long plasma half-life, a series of oxyimino aminothiazolyl 3-[(E)- or (Z)-N-substituted carbamoyloxy]propenyl cephems was synthesized and evaluated for antibacterial activity and oral absorbability. The substituents of the carbamoyloxy group affected their in vitro activity and bioavailability after oral administration of their pivaloyloxymethyl esters at the C-4 position. The compound possessing an N,N-dimethylcarbamoyloxy moiety at the C-3 position showed good oral absorption and well-balanced antibacterial activity. In this report, the structure-activity relationships and the structure-oral absorbability relationships of 3-(N-substituted carbamoyloxy)-propenyl cephems are described.

Administration, Oral↗

High-performance liquid chromatography analysis of chondroitin sulfate isomers in human periodontium.

We investigated the chondroitin sulfate in human periodontal samples (gingiva, periodontal ligament, cementum and alveolar bone) collected for orthodontic reasons. Glycosaminoglycans (GAGs) were extracted from the periodontium by enzyme digestion, and unsaturated disaccharide isomers of chondroitin sulfate were obtained by chondroitinase ACII and hyaluronidase digestion. The isomers were analyzed by high-performance liquid chromatography. Chondroitin sulfate was found in all four types of periodontal tissue; its unsaturated disaccharide isomers consisted in delta Di-0S, delta Di-6S, delta Di-4S, delta Di-diSE and delta Di-triS. These four types of periodontal tissue showed different molar ratios of the unsaturated disaccharides. The ratio of delta Di-4S to delta Di-6S was greater in the calcified than in the uncalcified tissue.

Adolescent↗

Changes in synovial fluid N-acetyl-beta-glucosaminidase activity in the human temporomandibular joint with dysfunction.

beta-Glycosidases (N-acetyl-beta-glucosaminidase, N-acetyl-beta-galactosaminidase, beta-glucuronidase) were assayed in temporomandibular joint (TMJ) synovial fluid obtained from 23 patients with closed lock TMJ internal derangement (ID), four with closed-lock TMJ osteoarthritis (OA), and 13 with normal controls (N). Synovial fluid was collected from the upper joint space after injecting 1.5 ml of 1% lidocaine three times. The specific activity of N-acetyl-beta-glucosaminidase increased significantly both with ID (p < 0.01) and with OA (p < 0.001), along with increases in the activity of N-acetyl-beta-galactosaminidase (p < 0.05 with ID and p < 0.01 with OA) and in beta-glucuronidase (p < 0.05 both with ID and OA). The N-acetyl-beta-glucosaminidase activity with OA was also significantly higher (p < 0.001) than with ID. These findings suggest that N-acetyl-beta-glucosaminidase activity in the TMJ synovial fluid reflects the degree of TMJ dysfunction.

Acetylglucosaminidase↗

Age-related changes in central nervous system hyaluronic acid and chondroitin sulfate in senescence-accelerated mice.

Age-related changes in cerebral hyaluronic acid (HA) and chondroitin sulfate (CS) in senescence-accelerated mice (SAM-P/8 parallel Odu, P substrain) were investigated. SAM-R/1 parallel Odu (R substrain) mice were used as controls. Levels of both HA and CS extracted from the defatted dry cerebrums at 7, 17, 27 and 37 weeks of age were determined by HPLC analysis after conversion to unsaturated disaccharides following enzymatic digestion. Glycosaminoglycan content (determined as uronic acid) was lower in P substrain mice than in the age-matched controls at all ages tested. Though the ratio of HA to CS was increased at 17 and 27 weeks in control mice, this ratio for the P substrain was already high at the initial test at 7 weeks and remained so thereafter. The CS chain consisted mainly of delta Di-4S, with delta Di-0S and delta Di-6S present only as minor components at all ages in both substrains. The HA chain consisted only of delta Di-HA for all ages in both substrains. The relative amount of each unsaturated disaccharide was higher in the R substrain than in the P substrain mice at all ages. We found that qualitative and quantitative changes in cerebral CS and HA were expressed relatively early in the P substrain mice compared to controls. We propose that these changes are associated with and may cause physiological and functional alterations associated with senescence in the CNS.

Age Factors↗

Analysis of chondroitin sulfate isomers in the periodontium of the monkey using high-performance liquid chromatography.

Glycosaminoglycan (GAG) was extracted from monkey periodontium, consisting of gingiva, periodontal ligament, alveolar bone and cementum, and from dental pulp and dentin by digestion with Pronase E. Unsaturated disaccharide isomers formed by chondroitinase AC digestion from chondroitin sulfate were labeled with dansylhydrazine and analyzed by high-performance liquid chromatography. These tissues showed different molar ratios of the unsaturated chondroitin sulfate disaccharides. The ratio of delta Di-4S to delta Di-6S was lowest in the dental pulp, followed by the gingiva, periodontal ligament, dentin, alveolar bone, and cementum, in that order. It was greater in the calcified than in the uncalcified tissues.

Alveolar Process↗

In vitro transport of sodium diclofenac across rat abdominal skin: effect of selection of oleaginous component and the addition of alcohols to the vehicle.

The in vitro percutaneous transport of sodium diclofenac from various oil vehicles was examined using rat abdominal skin as a model skin membrane. The overall transport of diclofenac through the skin from the oleaginous vehicles was very poor because of a poor solubility of sodium diclofenac in nonpolar oils. To increase the solubility and the permeability of sodium diclofenac, ethanol and n-octanol were added to each oil (designated as the formulated vehicles). The addition of ethanol and n-octanol to the nonpolar vehicles resulted in an extreme increase in drug solubility in each vehicle, with a remarkable increase in the permeation of diclofenac. The effects of oil components in the formulated vehicle on the permeation of diclofenac across the skin were in the following order: squalane greater than or equal to squalene greater than liquid paraffin greater than middle chain triglyceride greater than olive oil greater than castor oil. In order to clarify the reason for the differences in permeation of diclofenac from these formulated vehicles, the release of diclofenac and n-octanol from these vehicles in vitro was studied. The release rates of n-octanol from the formulated vehicles were in the following order: liquid paraffin greater than squalene greater than or equal to squalane greater than middle chain triglyceride greater than or equal to olive oil greater than castor oil. On the other hand, a linear correlation was observed between the initial release rate of diclofenac from the formulated vehicle and the in vitro permeation of diclofenac through the vehicle to the skin.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

In vitro percutaneous transport of sodium diclofenac and diclofenac from oleaginous vehicle.

The penetration enhancement of sodium diclofenac and diclofenac by alcohols with various alkyl chains (C8 to C14) was evaluated by the steady state flux of diclofenac through rat abdominal skin. Decanol showed the greatest effect in this series. A more remarkable enhancing effect of the alcohols was observed in sodium diclofenac than in diclofenac. Diclofenac can penetrate through the ethylene-vinyl acetate membrane as a lipoid model membrane, but sodium diclofenac can not. Decanol enhanced the penetration of phenol red being dependent on its concentration in the vehicle. Therefore, decanol may interact with lipoid components of the skin and increase the aqueous pathway in the skin. These results indicate that sodium diclofenac and diclofenac may be penetrated through partially different pathways.

Animals↗

Alteration of cell-associated heparan sulfate proteoglycan in tumor-bearing rats.

Alteration of cell-associated heparan sulfate proteoglycan (HSPG) under tumor-bearing conditions was evaluated using microsomal membranes prepared from the liver of ascites Tawa sarcoma-bearing and age-matched control rats. Cell-associated HSPGs have been fractionated into two populations displaying different modes of membrane association; one is a NaCl-soluble HSPG and the other is recovered only after detergent treatment of the membranes. The former is thought to represent HSPG from the peripheral membrane and the latter, HSPG from the intercalated membrane. We extracted the cell-associated HSPGs from liver microsomal membranes with a NaCl solution followed by a deoxycholate (DCA) solution. Both were isolated by gel filtration and cetylpyridinium chloride precipitation. Glycosaminoglycans (GAGs) were isolated from the tumor cells and tumorous ascitic fluids by standard procedures. Using electrophoresis on a cellulose acetate membrane, it was confirmed that the cell-associated HSPGs contained no GAG chains other than HS, and that these HSPGs did not include PGs from tumor cells since hyaluronic acid predominates in tumor cells while chondroitin sulfate is present in ascitic fluids. The HSPG extracted with the DCA solution was markedly reduced under tumor-bearing conditions, with slight increase in the NaCl-soluble HSPG. The results suggests that this condition strongly influences the type of cell-associated HSPG related to the intracellular cytoskeleton.

Animals↗

Combined effect of alcohol and urea on the in vitro transport of indomethacin across rat dorsal skin.

An aqueous gel, prepared with hydrogenated soya phospholipid, increased the in vitro transport of indomethacin across rat dorsal skin. The addition of various alkanols further accelerated the transport, with an increasing effect as the chain length of the alkanol increased. The addition of urea alone did not significantly affect the transport of indomethacin. However, the addition of urea markedly accelerated the transport of indomethacin when included in an aqueous gel containing an alkanol such as 1-octanol, 1-decanol, or 1-dodecanol. Thus, it appears that a combination of urea and these alkanols strongly enhances the transdermal absorption of indomethacin. Urea appears to accelerate enhanced drug transport into the stratum corneum by a mechanism involving the transport of urea enhanced by these alkanols.

Alcohols↗

Effectiveness of insulin suppositories in diabetic patients.

Experimental insulin suppositories regulated postprandial hyperglycaemia in diabetic patients. The insulin suppositories seemed also to avoid hyperinsulinaemia. The formulation with more rapid dissolution of insulin, which contained a solid dispersed form of insulin, effectively reduced the insulin dose required.

Adult↗

Changes in rat submandibular gland N-acetyl-beta-glucosaminidase activity in streptozotocin-induced diabetes.

Changes were determined in the activity of submandibular gland N-acetyl-beta-glucosaminidase from streptozotocin-induced diabetic and insulin-treated rats. Most of the activity of this enzyme was localized histochemically in the ductal cells. The activities of this enzyme from both the subcellular supernatant and lysosomal fractions were increased in the diabetic group, and recovered to the level of the controls in the insulin-treated group. Although sex differences were observed in the activity of this enzyme, with the activity in the male rats of the control group being lower than that in the females, these differences disappeared in the diabetic group, suggesting that insulin may be related to the expression of androgen function. Both enzymes in the supernatant and lysosomal fractions were separated by isoelectric focusing into two enzymatic proteins with isoelectric points in the vicinities of pI 3 and pI 8. The effects of diabetes were reflected in an increase primarily in the activity in the vicinity of the pI 8 isoenzyme in the supernatant fraction, and in an increase in both isoenzymes in the lysosomal fraction. It is clear from these findings that the diabetic condition brings about an insulin-dependent increase in the activity of N-acetyl-beta-glucosaminidase in the rat submandibular gland, and imparts certain changes in the properties of the enzymatic proteins themselves.

Animals↗

Effect of streptozotocin-induced diabetes on the structure of heparan sulfate from rat kidneys.

The effect of streptozotocin-induced diabetes on the structure of heparan sulfate (HS) prepared from rat kidney glycosaminoglycans (GAG) was evaluated. GAG were isolated and purified from the kidneys of diabetic and age-matched control rats by standard procedures. HS was prepared from GAG by digestion with chondroitinase ABC and precipitation with cetylpyridinium chloride. The tissue dry weight of diabetic kidneys was greater than that of the controls. The amounts of protein and DNA per tissue dry weight were decreased in the diabetic group, while GAG and hydroxyproline remained unchanged. The above information indicates that the extracellular components are increased in diabetes. There was no significant difference in the amount of HS to tissue dry weight between the diabetic and control groups. When the molecular weight of the HS from both groups was compared by Sephacryl S-300 HR column chromatography, the HS peak for the diabetic kidney indicated a slightly higher molecular weight and the base of the peak was broader than that for the controls. A reduction in N-sulfate residues was observed in Sephadex G-50 profiles after nitrous acid degradation of the HS. The ratio of glucuronic acid to its epimer, iduronic acid, in diabetic kidney HS was slightly lower than that in the controls. This indicates that diabetes may influence the carbohydrate chain structure of the HS in the kidney. Quantitative and qualitative changes in the kidney HS may contribute to the symptoms associated with diabetic nephropathy.

Animals↗

[Variability of respiratory function variables in healthy aged men].

We studied six healthy young males (young group; mean age 30.0 +/- SD 1.8 years, FVC 4.5 +/- 80.45 l and FEV1.0/FVC 87.6 +/- 4.3%), and five aged healthy males (aged group; age 63.8 +/- 3.0 years, FVC 3.40 +/- 0.22 l and FEV1.0/FVC 75.9 +/- 3.2%) to evaluate the variability of pulmonary function. We measured flow-volume curves, closing volumes, functional residual capacities (FRC) and airway resistances (Raw) five times in different days in each person. The coefficients of variation in FVC and FEV1.0 in both groups were less than 5%, and there were no significant differences in these coefficients between the two groups. Although the coefficients in FEV1.0/FVC in both group were less than 5%, there was a significant difference between the two groups. The coefficients in flow at 50% FVC (V50), maximal midexpiratory flow (MMF) and peak expiratory flow rate (PEFR) in the aged group were significantly larger than those in the young group. The coefficients in closing volume, FRC, Raw and specific airway conductance (SGaw) using body plethysmography exceeded 10% in both groups, and the coefficients in Raw and SGaw in the aged group were significantly larger than those in the young group. These results suggest that aging worsens the variabilities of respiratory function in FEV1.0/FVC, MMF, V50, Raw and SGaw.

Adult↗

Effects of differences of oxygen affinity on circulatory response to hypoxia.

Studies were made on eighteen male patients with chronic obstructive pulmonary disease (COPD) to investigate whether differences of P50 affect the circulatory response to acute hypoxia as a model of acute exacerbation. Subjects were divided into two groups according to low (less than 26.6 torr) or high (greater than 26.6 torr) P50. Isocapnic hypoxia was induced progressively (final PaO2 = 45 torr) and maintained for 10 minutes. Blood gases and hemodynamic parameters were measured before and after hypoxia. Results before and after hypoxia and results between groups were compared. The low P50 group includes eleven subjects with a mean P50 of 25.8 +/- 0.2 torr. The high P50 group includes seven subjects with a mean P50 of 27.5 +/- 0.2 torr. Comparison between groups showed no significant differences. In the high P50 group cardiac output and heart rate increased, whereas cardiac output did not change in the low P50 group. We conclude that circulatory response to hypoxia is well preserved in the high P50 group but deteriorated in the low P50 group, and this suggests that patients with low P50 cannot compensate adequately to hypoxia during acute exacerbation.

Blood Pressure↗