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Biomedical subjects

K C James

Publications and source records attributed to K C James.

At least 19 recordsLinked to original sources

The use of electron spin resonance to measure microviscosity.

The viscosities of a series of mixtures of glycerol and water were measured by electron spin resonance (ESR), photon correlation spectroscopy and Ostwald viscometry. Close agreement was obtained between the last two methods but viscosity as measured by ESR was always significantly lower. The difference, the magnitude of which depended on the spin probe used, was attributed to interaction between water and glycerol. Similar results were obtained using water-sorbitol and water-sucrose mixtures.

Electron Spin Resonance Spectroscopy↗

Biochemical and trichological characterization of diffuse alopecia in women.

One hundred women who presented with diffuse alopecia, were quantitatively evaluated for hair variables and compared with 20 controls. Fifty were selected for biochemical and haematological investigations, 44 of whom also underwent endocrine evaluation. Compared to controls, significant changes in hair values were found in the frontal area of all subjects, while 84% had significant changes in the occipital area. A biphasic distribution of hair diameter was evident in subjects who had percentages of vellus hair and telogen hair less than or equal to 30 mm in length that were above the control ranges. No significant difference between the mean hormonal values of women with diffuse alopecia and controls could be found. No correlation between hair values and individual or combined hormonal levels could be established. In 18 subjects (40.9%) hormonal values were within the control ranges and these apparently normal findings were often associated with adverse hair profiles. A raised dihydrotestosterone was found in 13 subjects (29.5%) and was the most frequently elevated androgenic finding. Seventeen (34.0%) had changes in iron metabolism, while in 36 (72.0%) serum ferritin levels were below the lowest control value. All had a decrease in the percentage of hair in the anagen growth phase compared to controls. The hair changes were similar to those observed in genetic hair loss in men, a proven androgen-dependent condition. We propose that diffuse androgen-dependent alopecia is the appropriate name to describe this condition in these women.

Adolescent↗

Amino-acid composition in trichorrhexis nodosa.

Trichorrhexis nodosa is a common shaft defect affecting scalp hair. Two-hundred scalp hairs exhibiting trichorrhexis nodosa were obtained from two normal females; samples were prepared from proximal shaft, pre-nodule, nodule and post-nodule sections and analysed for their respective amino-acid compositions. Significant reductions in cystine (P less than 0.001) of the pre-nodule, nodule and post-nodule sections, which decreased by 17.2%, 19.8% and 14.3%, respectively, and an increase in the acidic amino acids (P less than 0.03) were found, compared to values obtained from proximal shaft of the same hairs. The majority of nodules occurred within the last 10% of the shaft, and the similarity in amino-acid compositions between pre-nodule, nodule and post-nodule sections suggests that 'weathering' is the major factor influencing nodule occurrence. It is postulated that nodule formation requires a specific degree of exposure to 'weathering' together with a reduction in cuticle cell coverage. It is suggested that an initial structural defect, created by a change in the DNA coding for a cuticle polypeptide fraction, could be responsible for the selective and isolated presentation of the nodule within a 'weathered' section of hair shaft.

Adolescent↗

Quantitative assessment of 2% topical minoxidil in the treatment of male pattern baldness.

Forty-seven men with male pattern baldness were treated in a double-blind clinical trial with topical 2% minoxidil or placebo. Twelve were randomly selected for quantitative hair measurement using the unit area trichogram and visual counting. There was no significant difference after 6 or 12 months of treatment with a 2% minoxidil solution for total hair density (THD; hair cm-2), meaningful hair density (MHD; hair greater than 40 microns in diameter greater than 30 mm in length cm-2), per cent of hair in the anagen growth phase, or the per cent of meaningful hair in the anagen growth phase. Significantly fewer hairs were recorded with the visual hair counting method, compared to values obtained from adjacent sites with the unit area trichogram. In addition, a significantly larger mean total hair count was recorded by an experienced observer, compared to an inexperienced observer. Increased pigmentation was observed within the vellus hair population of treated subjects. Our findings indicate that minoxidil appears unlikely to affect the long-term course of male pattern baldness. However, we found no significant deterioration in total hair density, or meaningful hair density in treated subjects, suggesting minoxidil may have a prophylactic effect. Further long-term studies employing the unit area trichogram are required to evaluate this finding.

Administration, Topical↗

The effect of gelatin grade and concentration on the migration of solutes into and through glycerogelatin gels.

The diffusion of 4-hydroxybenzoic acid and phenobarbitone through glycerogelatin gels was found to be independent of the type of gelatin used. Three types of gelatin, two acid-processed and one alkali-processed were studied, and the bulk viscosities of gels prepared from them was seen to vary considerably. However, the microviscosities of the gels, as measured by ESR, showed no significant differences. Thus microviscosity was the factor governing diffusion. Gelatin concentration in aqueous solutions without glycerol influenced microviscosity and hence diffusion. This is believed to be caused by dissolution of water-soluble fractions of the gelatin. Interstices in the gelatin matrix, though reduced in size when gelatin concentration is raised, are still too large to act as physical barriers to diffusing molecules. It is suggested that hydrated gelatin forms the matrix of glycerogelatin mixtures and that the interstitial fluid, through which migration occurs, consists almost entirely of glycerol and water.

Chromatography, Gel↗

The influence of viscosity on the migration of chloramphenicol and 4-hydroxybenzoic acid through glycerogelatin gels.

Migration of chloramphenicol and 4-hydroxybenzoic acid from solutions in 1-octanol into Glycerol Suppository Base, BP and soft gelatin capsule shells is reported. Rates of migration through the gels, quantified in terms of diffusion coefficients, are given. An electron spin resonance probing technique was used to determine the microscopic viscosity. The latter, rather than the bulk viscosity, was shown to be the major rheological influence on the rate of diffusion.

Chloramphenicol↗

Influence of solvent on the availability of testosterone propionate from oily, intramuscular injections in the rat.

The suggestion that the biological response to an oily intramuscular injection of testosterone ester is regulated by rapid accumulation of the steroid in body fat, followed by a slow release, has been tested by comparing the release rates of 14C-labelled testosterone propionate from different solvents following intramuscular injection into rats. Disappearance from the injection site was rectilinearly related to in-vitro partition coefficients, but elimination of radioactivity in urine and faeces was significantly longer, and the same for all four solvents. Testosterone and testosterone propionate were found in equal concentration in body fat, 2 and 3 days after injection, but their concentrations were too low to form an effective depot. It is suggested that the delay in release, and the independence of the delay on the nature of the solvent is a consequence of biliary recycling of testosterone.

Adipose Tissue↗

An in-vitro investigation of drug availability from lipophilic solutions.

An in-vitro model, previously described, has been modified and used to investigate the effects of volume and concentration on the release of 4-hydroxybenzoic acid from 1-octanol and isopropyl myristate. Solutions encapsulated in soft gelatin shells have also been examined. The quantity of solute released can be increased by reducing the volume of solvent used to prepare the solution, or by increasing the concentration of the solution. The release profile from an encapsulated solution is different from that obtained with the same, unencapsulated solution. The difference is attributed to absorption of the solute by the capsule shell.

1-Octanol↗

Drug migration into soft gelatin capsule shells and its effect on in-vitro availability.

Analysis of the shells and contents of soft gelatin capsules containing acetomenaphthone, ephedrine, 4-hydroxyenzoic acid or phenobarbitone, dissolved in isopropyl myristate, revealed that the percentage of solute taken up by the shells increased with increasing aqueous solubility of the substrate. Thus no acetomenaphthone, which has a negligible aqueous solubility, was found in the shells, in comparison with 92% of the 4-hydroxybenzoic acid, which has a significant solubility in water. Uptake was not influenced by the solubility in isopropyl myristate. The effect of the oily solvent was studied using blends of 1-octanol and isopropyl myristate in which either 4-hydroxybenzoic acid or phenobarbitone were dissolved. Solute release shows that both release and migration can be predicted from a knowledge of the aqueous solubility of the solute and its partition coefficient between water and the non-polar solvent. Samples of capsules containing 4-hydroxybenzoic acid in isopropyl myristate were withdrawn at various stages of the manufacturing process, and the distributions between shell and contents noted. Most of the transfer took place while the capsules were being dried in rotating basket driers, and at this point 67% of the acid had migrated. This increased to 92% during tray drying, and remained so for at least 6 months after manufacture.

1-Octanol↗

The unit area trichogram in the assessment of androgen-dependent alopecia.

The unit area trichogram was defined in the frontal and occipital areas of ten normal men and ten normal women and the results compared with the findings in ten male and fifteen female patients with androgenic alopecia. The epilation technique provided accurate data of normal hair density (higher than previously reported) and the phases of hair growth. The measurement of hair diameter showed that of 7603 hairs, 1241 were less than 40 microns in diameter, of which only 21 were more than 80 mm in length. Variation in the diameter of individual hair fibres was recorded. The number of hairs less than 40 microns diameter per cm2 of scalp was increased in both men and women with androgenic alopecia. It was concluded that the number of hairs greater than 40 microns in diameter per cm2 (meaningful density) reflected most closely the amount of hair usefully contributing to an individual's clinical appearance.

Adolescent↗

Extended Hildebrand solubility approach: testosterone and testosterone propionate in binary solvents.

Solubilities of testosterone and testosterone propionate in binary solvents composed of the inert solvent, cyclohexane, combined with the active solvents, chloroform, octanol, ethyl oleate, and isopropyl myristate, were investigated with the extended Hildebrand solubility approach. Using multiple linear regression, it was possible to obtain fits of the experimental curves for testosterone and testosterone propionate in the various binary solvents and to express these in the form of regression equations. Certain parameters, mainly K and log alpha 2, were employed to define the regions of self-association, nonspecific solvation, specific solvation, and strong solvation or complexation.

Chemistry, Pharmaceutical↗

Some solute-solvent complexes involving testosterone and testosterone propionate.

Solute-solvent interactions have been studied by observing the influences of carbon tetrachloride, carbon disulphide, ethyl oleate, isopropyl myristate and octanol on the solubilities of testosterone and testosterone propionate in an inert solvent (cyclohexane). Complexation with testosterone was detected, but there was no evidence of complexation between testosterone propionate and these solvents. The solvent-induced infrared shifts were due to non-specific solvent effects. The existence of solute-solvent complexes between the two solutes and chloroform, previously detected by infrared absorption, was confirmed. The solubility technique, which has previously only been used with solid complexing agents, is adaptable to liquid complexing agents, but has limitations.

Solubility↗

Availability of tritium from non-aqueous solutions of [1,2-3H]methyltestosterone, administered orally to rats.

The solvent-water distribution coefficients of 17 alpha-methyltestosterone have been determined in selected alkanes, alkanols and alkane-alkanol blends. The oral availability of tritium from solutions of [3H]methyltestosterone in these solvents and blends was studied in rats by measuring radioactivity in plasma, faeces and urine. Disappearance of radioactivity from the gut and biliary recirculation of 3H were also examined. Variation of the solvent led to marked changes in the absorption of radioactivity, suggesting a possible method of varying bioavailability from soft gelatin capsules. Neither distribution coefficients nor tritium concentrations changed significantly from one homologue to another, but there was a marked difference when the alkane series was compared with the alkanol series. Blends of octane and octanol, together with the pure solvents, provided a suitable spread of distribution coefficients and tritium concentrations, but no simple relationship could be established between the two properties.

Administration, Oral↗