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Biomedical subjects

B E Cham

Publications and source records attributed to B E Cham.

At least 19 recordsLinked to original sources

Topical treatment of malignant and premalignant skin lesions by very low concentrations of a standard mixture (BEC) of solasodine glycosides.

A cream formulation containing high concentrations (10%) of a standard mixture of solasodine glycosides (BEC) has been shown to be effective in the treatment of malignant and benign human skin tumours. We now report that a preparation (Curaderm) which contains very low concentrations of BEC (0.005%) is effective in the treatment of keratoses, basal cell carcinomas (BCCs) and squamous cell carcinomas (SCCs) of the skin of humans. In an open study, clinical and histological observations indicated that all lesions (56 keratoses, 39 BCCs and 29 SCCs) treated with Curaderm had regressed. A placebo formulation had no effect on a smaller number of treated lesions. Curaderm had no adverse effect on the liver, kidneys or haematopoietic system.

Administration, Topical

Solasodine glycosides. In vitro preferential cytotoxicity for human cancer cells.

Solamargine [(22R,25R)-spiro-5-en-3 beta-yl-alpha-L-rhamnopyranosyl- (1----2glu)-O-alpha-L-rhamnopyranozyl (1----4glu)-beta-D-glucopyranoze], a glycoside of solasodine preferentially inhibits the uptake of tritiated thymidine by cancer cells. In contrast, solamargine at equivalent concentration, and the mono- and diglycosides of solasodine have a limited effect on the uptake of tritiated thymidine for other cell types, including unstimulated lymphocytes and lymphocytes stimulated with Con A. In contrast the solasodine glycosides do not inhibit the uptake of tritiated thymidine by lymphocytes stimulated with PHA or PWM. The inhibition of tritiated thymidine uptake by solamargine and the mono- and di-glycosides of solasodine are dependent upon their cellular uptake by endogenous endocytic lectins (EELs). The mode of action of the solasodine glycosides, in particular solamargine, appears to be the induction of cell lysis, as determined by morphological examination.

Carbohydrate Sequence

Solasodine glycosides. Selective cytotoxicity for cancer cells and inhibition of cytotoxicity by rhamnose in mice with sarcoma 180.

BEC, a standard mixture of solasodine glycosides is effective in vivo against murine sarcoma 180 (S180), whereas the aglycone solasodine at equimolar concentrations is ineffective. The efficacy of BEC against S180 in vivo can be inhibited by rhamnose. Mice which are in their terminal stage with S180 can tolerate and become symptom-free of cancer by single dose administration of BEC at concentrations of BEC three times the LD100 for normal mice. These observations suggest that the binding of solasodine glycosides on tumour cells may be mediated through the monosaccharide rhamnose, which forms part of solasonine, solamargine and di-glycosides of solasodine in BEC. Furthermore, these results provide evidence that BEC selectively destroys tumour cells relative to normal cells in vivo.

Animals

Ascorbic acid deficiency affects the metabolism of cytosolic ferritin but not lipid-associated ferritin in livers of guinea pigs.

Two physicochemically and metabolically separate pools of ferritin, namely cytosolic ferritin and lipid-associated ferritin, are present in the livers of guinea pigs. In this paper we establish that the iron content of cytosolic ferritin is dependent on and linearly related to ascorbic acid concentration, whereas changes in concentration of this vitamin do not affect the iron content of lipid-associated ferritin. In livers of ascorbic acid-deficient guinea pigs both synthesis and degradation of cytosolic ferritin are diminished equally. Consequently cytosolic ferritin is metabolized more slowly without changes in its pool size. In contrast with cytosolic ferritin, the metabolism of lipid-associated ferritin is unaffected by ascorbic acid deficiency. The differential effects of ascorbic acid deficiency on the physicochemical characteristics as well as on the metabolism of cytosolic ferritin and lipid-associated ferritin suggest that the two forms of ferritin have different functional roles.

Animals

Cytosolic ferritin and lipid-associated ferritin are metabolically different in guinea-pig livers.

A distinct pool of liver ferritin has been described in man, guinea pigs and rats [Cham, Roeser, Nikles & Ridgway (1986) Clin. Chim. Acta 158, 71-79]. This ferritin accounts for approx. 30% of total intracellular ferritin. It differs from previously described cytosolic and 'microsomal-fraction' ferritin by its firm association with lipid and by the absence of heat-stability at 75 degrees C. The present study demonstrates that cytosolic ferritin and lipid-associated ferritin in guinea-pig livers have distinctly different rates of turnover. Cytosolic ferritin has a rate of turnover approx. 3.5 times as high as lipid-associated ferritin. The apparent metabolic heterogeneity suggests that the two forms of ferritin may have different functional roles.

Animals

Curaderm.

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Alkaloids

Simultaneous liquid-chromatographic determination of vitamin K1 and vitamin E in serum.

We describe a high-performance liquid chromatographic procedure for the simultaneous measurement of vitamins K1 and E in human serum. Delipidated human serum (free of vitamins K1 and E) was used to make standard solutions of these vitamins, and cetyl naphthoate and alpha-tocopheryl acetate were the internal standards for vitamin K1 and vitamin E, respectively. A simple, novel separation method utilizing liquid-liquid partition chromatography was used as a preparative "clean-up" procedure. Cetyl naphthoate and vitamin K1 (after post-column reduction) were detected by fluorescence, alpha-tocopheryl acetate and vitamin E by ultraviolet absorption. Sensitivity (detection limit) of the assay was 30 pg for vitamin K1 and 5 ng for vitamin E per injection. The method is specific, precise, and more rapid than previously described procedures. Within- and between-assay CVs were 8.1% and 12.9%, respectively, for vitamin K1; 3.5% and 6.0%, respectively, for vitamin E. Analytical recoveries of vitamins K1 and E were 80% and 93%, respectively, from serum and from delipidated serum (standards). The average neonatal serum concentration of vitamin K1 was 83 ng/L, 2.5 mg/L for vitamin E; for normolipidemic adults, the values were 343 ng/L and 7.9 mg/L, respectively, and for hyperlipidemic adults, 541 ng/L and 11.1 mg/L, respectively.

Adult

Effects of non-ionic and anionic detergents on lipid-associated tissue ferritin.

Lipid-associated ferritin from homogenates of guinea pig liver is released from its conjugate(s) by incubation with the non-ionic detergents Triton X-100 and Nonidet P-40 but not by incubation with the anionic detergent deoxycholate. The amount of lipid-associated ferritin released from its conjugate(s) depends on the concentration of the non-ionic detergents. At a final non-ionic detergent concentration of about 20 g/L, all lipid-associated ferritin is released from its conjugate(s) in a liver homogenate. The amount released is identical with the amount of the lipid-associated ferritin obtained by extraction of the same liver homogenate with a mixture of butanol and diisopropyl ether.

Animals

Glycoalkaloids from Solanum sodomaeum are effective in the treatment of skin cancers in man.

A cream formulation containing glycoalkaloids purified from the plant species Solanum sodomaeum L. is effective in the treatment of the malignant human skin tumours; basal cell carcinomas (BCCs), squamous cell carcinomas (SCCs) and the benign tumours; keratoses and keratoacanthomas. Histological analyses of biopsies taken before, during and after treatment give compelling evidence of the efficacy of the formulation. The treated lesions did not recur for at least 3 years after cessation of therapy. The observed complete regressions were; 20/24 for the BCCs; 5/6 for the SCCs; 23/23 for the keratoses; and, 9/9 for the keratoacanthomas. Biochemical, haematological and urinanalytical studies demonstrated that there were no adverse effects on the liver, kidneys or haematopoietic system during treatment. Normal skin treated with the formulation likewise was free from adverse histological or clinical effects. The data indicate that glycoalkaloids of this type are therefore potentially useful in the treatment of several types of human skin cancers.

Aged

Lipid associated tissue ferritin.

Delipidation of liver homogenates, using an organic solvent system which does not denature proteins, increases measurable ferritin by 25-33%, compared to ferritin concentrations by standard heat supernatant assays. When applied to polyacrylamide gradient gels, lipid-associated ferritin does not enter the gel but after delipidation, this ferritin co-migrates with cytosolic ferritin and with purified liver ferritin. The biological significance of the association of ferritin with lipid has yet to be examined.

Animals

A procedure for the purification of ferritin from human liver by heating a methanol-treated homogenate.

A simple, rapid technique for purification of ferritin from human liver tissue is described. Methanol, at a final concentration of 40% (v/v) in liver homogenate, precipitates the majority of proteins but does not affect ferritin. Subsequent heating of this homogenate at 75 degrees C for 10 min results in a purified ferritin preparation as judged by immunoelectrophoresis and polyacrylamide gel electrophoresis. The resultant purified ferritin contained the same amount of iron as the original endogenous ferritin. There were no significant differences (paired t tests) in the amount of protein in the purified ferritin preparation when measured by rocket immunoelectrophoresis and by the Lowry procedure, suggesting that the antigenecity of ferritin was unaffected by the methanol and heat treatment. Both endogenous liver ferritin and radiolabeled human liver ferritin added to liver homogenates were recovered after methanol and heat treatment with similar yields (77 +/- 7% and 70 +/- 2%, respectively) when compared with the standard treatment of heating a homogenate at 75 degrees C. The overall ferritin yield with this rapid procedure was 40%.

Chromatography, High Pressure Liquid

Importance of apolipoproteins in lipid metabolism.

Lipids, which serve as a source of energy and are an important constituent of cell membrane structure, are readily stored in the body. By definition they are insoluble in water. Specific proteins called apolipoproteins interact with lipids to form soluble lipid-protein complexes called lipoproteins. It is in this form that the major lipids--cholesterol, triglyceride and phospholipid--circulate in plasma. Unesterified fatty acids, another major lipid group, are bound to albumin in the circulation. The plasma lipoproteins are complex macromolecules composed of lipids, apolipoproteins and carbohydrates. The relative proportions of these components differ markedly between lipoprotein classes. Hyperlipidemia is a term used for increased concentrations of plasma cholesterol and/or triglycerides. Any one plasma lipid is present in several types of lipoproteins. Thus, hyperlipidemia implies the presence of hyperlipoproteinemia. The latter has important therapeutic implications. Most of the recent attempts at classification have been directed at the lipoprotein level of plasma lipid organization. Decreased concentrations of lipids in plasma can be achieved by altering the rates of metabolism of lipoproteins. Decrease in lipoprotein synthesis, increased catabolism or impaired release from cells into the blood stream may all result in a decrease of plasma lipids. Drugs which affect one or more of these factors are used to treat hyperlipoproteinemia. In order to elucidate the mechanism of action of hypolipidemic drugs it is necessary to understand the lipoprotein defect at the molecular level. This requires a more detailed knowledge of lipoprotein metabolism than is presently available for most of the hyperlipoproteinemias. This paper will review some of the generally accepted properties of the plasma lipoproteins, describe some difficulties which hamper the understanding of lipoprotein metabolism, and identify possible mechanisms by which drugs may affect lipoprotein metabolism.

Apolipoproteins

In vitro partial relipidation of apolipoproteins in plasma.

In vitro recombination of lipids with apolipoproteins is achieved when a concentrated solution of plasma lipids in petroleum ether is mixed with delipidated plasma. Combination of phospholipids and unesterified fatty acids are observed in amounts comparable with those originally present in the native unextracted plasma; triglycerides combine partially and cholesterol only slightly. On agarose gel immunoelectrophoresis, a component in the delipidated plasma which is reactive with high density lipoprotein antibodies migrates more slowly than high density lipoprotein in the undelipidated control plasma. However, the component reacting with low density lipoprotein antibodies in the delipidated plasma moves more rapidly than low density lipoprotein in the native plasma. These changes are reversed by recombination of lipid with delipidated plasma. All lipids present in the plasma phase after relipidation travel with the lipoproteins during zonal electrophoresis. The apparent concentrations of proteins reacting with high density and low density lipoprotein antibodies decrease when no lipid is present in plasma on assay by single radial immunodiffusion and immunoelectrophoresis, using commercially available lipoprotein antibodies. On relipidation, full immunochemical properties of high density lipoprotein are restored, but relipidated low density lipoprotein exhibits only partial immunochemical restoration.

Apolipoproteins

Changes in electrophoretic mobilities of alpha-and beta-lipoproteins as a result of plasma delipidation.

A two-phase system containing the ternary mixture butanol/disopropyl ether/plasma in different proportions yields ordered delipidation of alpha-lipoproteins, pre-beta-lipoproteins- and beta-lipoproteins in plasma, as quantitated by densitometry after electrophoresis. As a consequence of delipidation the electrophoretic mobilities of pre-beta-lipoproteins and beta-lipoprotein increased, that of alpha-lipoprotein decreased.

Cholesterol

Nature of the interaction between low-density lipoproteins and polyanions and metal ions, as exemplified by heparin and Ca2+.

I examined the effect of lipid concentration on the interaction of the very-low density and low-density lipoproteins in serum with heparin and calcium. A precipitate forms when partly delipidated serum is subjected to the polyanion-metal ion system. Although this precipitate is less turbid than the complexed lipoprotein-polyanion-metal ion in undelipidated serum, the two precipitates contain identical amounts of apolipoprotein. Totally delipidated serum produces only a slight precipitate with heparin and calcium, and this precipitate contains only a fraction of the appolipoproteins. Cholesterol and triglycerides are the major determinants of turbidity when serum is mixed with heparin and calcium, but have no effect on the precipitation of the protein moiety. Phospholipids contribute a small proportion of the turbidity in the lipoprotein-polyanion-metal ion interaction. Precipitation of the low-density lipoproteins by heparin and calcium depends on the protein moiety and on the chemical composition of the lipid moiety. Phospholipid is required, but cholesterol and triglyceride are not, for total precipitation of the complex.

Calcium