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Biomedical subjects

A Kamada

Publications and source records attributed to A Kamada.

At least 19 recordsLinked to original sources

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

Pharmacological effects on hemoglobin-oxygen affinity in vitro and in patients with chronic obstructive pulmonary disease.

We examined the effects of pentoxifylline, coenzyme Q10 (CoQ10) and calcium hopantenate on hemoglobin-oxygen affinity in vivo and in vitro. In vitro study, pentoxifylline at 3 and 15 micrograms/ml significantly increased P50 from the placebo (27.0 +/- 0.3 Torr, mean +/- SE) to 28.2 +/- 1.7 and 28.1 +/- 1.3 Torr respectively (p less than 0.05) after 4 hours incubation. With 75 micrograms/ml pentoxifylline, P50 increased slightly to 27.8 +/- 1.4 Torr (0.05 less than p less than 0.1). 2,3-DPG was slightly higher (0.05 less than p less than 0.1) with pentoxifylline of 3 (11.15 +/- 4.12 mumol/gHb) and 75 micrograms/ml (10.62 +/- 2.32 mumol/gHb) than placebo. Other agents, 1-100 micrograms/ml of CoQ10 and 0.01-1 mg/ml of calcium hopantenate, neither P50 nor 2,3-DPG, Hb,ATP and glucose were changed compared to placebo. In vivo study, after administration of pentoxifylline 300 mg per day orally for 4 weeks to seven patients with COPD, P50 increased significantly from 29.0 +/- 0.6 to 30.4 +/- 0.6 Torr (p less than 0.05) and 2,3-DPG increased slightly from 11.67 +/- 0.56 to 14.33 +/- 1.12 mumol/gHb (p less than 0.1). These results suggest that pentoxifylline reduces hemoglobin-oxygen affinity by increasing 2,3-DPG and improves oxygen delivery to the tissues in patients with COPD.

Carbon Dioxide

Arterial H+ as a determinant for interindividual variability of respiratory chemosensitivity to hypoxia in man.

Ventilatory response to normocapnic progressive hypoxia (A/BSA) was measured in 76 healthy males to examine how arterial blood gases and acid base status are involved in interindividual variability of hypoxic chemosensitivity. A/BSA and HCO3- were significantly higher in Group 1 (26 subjects, mean age = 15.8 +/- S.D. 0.9 years) than those in Group III (26 subjects, mean age = 46 +/- 7.1 years). A/BSA and HCO3- in Group II (24 subjects, mean age = 29.8 +/- 6 years) were in the middle of Groups I and III. Arterial blood gases and H+ were similar among the 3 groups. Arterial H+ correlated inversely with A/BSA (subjects with lower arterial H+ on air had higher hypoxic response) in Group I, while the correlation was positive (subjects with higher H+ on air had higher hypoxic response) in Group III. The correlation was not seen in Group II. PaCO2 and H+ correlated positively in the 3 groups. Intrasubject stability was equivalent among H+, PaCO2, and HCO3- (mean coefficients of variation = 1.81, 1.83, and 1.65, respectively), but smaller than that in PaO2 (3.28%). These results indicate that interindividual variability in hypoxic ventilatory response is related to arterial H+ in adolescent and middle age groups but the relation is opposite between the 2 groups.

Acid-Base Equilibrium

[Effects of differences in oxygen affinity on circulatory response to hypoxia].

It is well known that tissue hypoxia is an important prognostic predictor in patients with chronic obstructive pulmonary disease (COPD). Compensatory responses to acute hypoxia occur in various organs and the magnitude of such response may also be an important factor in prognosis. P50, (oxygen tension at which the hemoglobin is 50% saturated with oxygen) is recognized as one of the factors affecting oxygen supply to the tissue. These studies were made to determine whether differences of P50 affect the circulatory response to acute hypoxia. Studies were made on nineteen male patients with COPD. They 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 with the patients being under right cardiac catheterization. The low P50 (25.8 +/- SD 0.6 torr) group included ten patients, and the high P50 (27.4 +/- 0.6 torr) group included nine patients. No differences could be detected in respect of pH, PaCO2, PaO2 or any hemodynamic parameters. Heart rate increased in both low and high P50 groups but the degree of the increase (delta HR/HR ROOM AIR x 100) in the high P50 group (20.7 +/- 9.2%) was significantly greater than in the low P50 group (9.4 +/- 10.9%). An increase in cardiac output was observed in the high P50 group (4.4 +/- 0.8 to 5.3 +/- 0.6 1/min), but not in the low P50 group (4.5 +/- 1.0 to 5.0 +/- 0.9 1/min). There was a significant positive relationship (r = 0.903) between hypoxic circulatory response and oxygen transport (TO2).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult

Effect of phenothiazines, disodium ethylenediaminetetraacetic acid and diethyl maleate on in vitro rat colonic transport of cefmetazole and inulin.

An in vitro rat colonic sac method developed in this study was found to be suitable for frequent collection of samples and determination of transport of compounds from serosal and mucosal medium, since the volume of both was large. Under no a treatment condition, both cefmetazole and inulin penetrated the intestinal mucosa via the paracellular route, but did so very poorly. Phenothiazines as well as disodium ethylenediaminetetraacetic acid increased the transport of cefmetazole and inulin, probably via the paracellular route, while diethyl maleate increased the transport of only cefmetazole, probably via the intracellular route. The effect of phenothiazines in increasing the clearance rate for both cefmetazole and inulin showed dependency on their initial concentrations in the mucosal medium with maximum action at a concentration of 30 microM for trifluoperazine, 20 microM for perphenazine, 75 microM for profenemine and 50 microM for propericiazine.

Animals