Penicillamine Research Articles

Investigation of the response to some haptenic determinants in penicillin allergy by skin and in vitro allergy tests.

The role of three penicillin metabolites in human allergic reaction to penicillin has been assessed using sensitive in vitro tests in addition to skin testing. Conjugates of the benzylpenicilloyl (BPO), benzylpenicillenate (BPE) and penicillamine (PA) groups with human serum albumin (HSA) and bovine gamma globulin (BGG) have been made. In the passive haemagglutination test antibodies specific for all three determinants were found but there was no difference between allergic and non-allergic groups. However, the ratio IgG/IgM, specific for each determinant, was higher in normals than in allergics. In skin tests, histamine release from leucocytes and the lymphocyte transformation test, the BPO group was confirmed as the major determinant, but in some individuals the BPE or PA groups are more important.

Influence of concomitant treatment with D-penicillamine and beta-aminopropionitrile on mechanical properties of rat connective tissue (author's transl)

In order to study the influence of D-penicillamine (DPA) and beta-aminopropionitrile (BAPN) as well as of a combination of both substances (proportion by weight 1:1) on the collagen of skin, aorta, and femoral epiphysial cartilage, the mechanical properties of these fibrous organs were examined, after having performed tests on onset and dissipation of action, measured by the decrease of ultimate load of excised strips of skin using the two individual compounds. The action of 320 mg/kg of DPA sets in within 7 days reaching a maximum value after 14 days. After discontinuance of the substance the control values are reached within 15 days. BAPN shows its maximal effect on the 18th test day. After discontinuance of treatment the control value is not reached within 35 days. DPA and BAPN show organo-specific actions: DPA has a considerably stronger influence on the collagen of skin than on the collagen of the aorta; under the present test conditions it does, however, not affect the collagen of the distal femoral epiphysial cartilage. As compared to DPA, BAPN exerts a less pronounced influence on the collagen of the skin, similar influence on the collagen of the aorta, and a strong influence on the collagen of the distal femoral epiphysial cartilage. If both substances are administered together, the organospecific actions of DPA on the one hand and BAPN on the other hand are maintained. It is discussed whether the different chemical compositions of the collagen (Type I--IV) may be connected with the organospecific effects of the test substances.

Collagen and mechanical strength in various organs of rats treated with D-penicillamine or amino-acetonitrile.

After oral treatment with D-penicillamine (D-Pc) or with aminoacetonitrile (AAn) for 10 days, mechanical and chemical parameters were studied simultaneously in various organs of Sprague Dawley rats. Tensile strength of skin strips and of tail tendons, breaking strength of femur bones and tensile strength of granuloma tissue (induced by implanted glass rods) were measured and calculated. In the same tissue the soluble collagen fractions and the insoluble collagen were determined. Total collagen and the ratio insoluble vs. soluble collagen were calculated. Tensile strength of skin, tendon and granuloma tissue were greatly reduced by D-Pc treatment but only minimally influenced by AAN treatment. On the other hand only AAN significantly reduced the breaking strength of bone. All these changes were closely correlated with the content of insoluble collagen in the respective tissues. The correlation coefficients to total collagen were similar but lower. The correlation coefficients between strength and the ratio insoluble vs. soluble collagen were generally still lower. Earlier findings in aged and corticoid treated rats, proving that insoluble collagen content determines mechanical strength of connnective and supporting tissue thus could be confirmed.

The treatment of elevated serum digoxin levels with penicillamine: an experimental study

Abstract This study was undertaken in the search for an agent to dissipate the cardiac effects of digoxin by lowering its concentration in the serum. Digoxin, 0.1 mg. per kilogram, was administered intravenously to two groups of dogs. After two hours, electrocardiograms were recorded and one animal group was treated with penicillamine in the dosage of 1 Gm. per kilogram, given intravenously. This treatment was omitted in the control animals. Two hours after the treatment, venous blood samples were collected and the electrocardiographic recordings were repeated. The average serum digoxin levels in the treated group was 2.60 ± 0.29 ng. per milliliter as compared to 3.73 ± 0.30 ng. per milliliter in the control group. Thus, the serum digoxin levels in the pencillamine-treated animals were significantly lower, P

Points from Letters: Penicillamine and Creaking Joints

Points from Letters: Penicillamine and Creaking Joints

Letter: Penicillamine and creaking joints.

Letter: Penicillamine and creaking joints.

JUVENILE WILSON'S DISEASE: HISTOLOGICAL AND FUNCTIONAL CORRELATIONS DURING PENICILLAMINE THERAPY

Clinical improvement and cupruresis occur during penicillamine(PCN) therapy for Wilson's Disease(WD), but long-term effects of the drug on hepatic morphology are virtually unknown. We studied 6 patients(pts) with WD (diagnosed at 7-24 yrs) who were clinically asymptommatic at follow-up(f/u) liver biopsy 2-7 yrs after onset of treatment. By comparison to pre-treatment biopsies (3 pts), there was marked reduction in portal fibrosis in 1 (7 yr f/u) and significant but less impressive decreases in 2 (2 yr f/u). Portal inflammation was greatly diminished in all 3, with periportal necrosis still present in 1 (2 yr f/u). None had complete restitution of normal architecture. At f/u, 3 pts on therapy for 3,5 or 7 yrs (without initial biopsy) had dense portal cirrhosis; in 2, portal lymphocytic infiltration was prominent; in 1, there was marked fatty change. Hepatocellular non-bilirubin pigment was abundant in 5/6 f/u specimens. Hepatic Cu++ levels were 80-750 μg/g (n1<50) and did not correlate with the degree of pigment deposition or healing. Liver function reverted to normal in 5/6 pts; serum Cu++ levels fell 50% and remained low. Hypoceruloplasminemia persisted in all. K-F rings faded or disappeared. One pt has hepatic dysfunction, cirrhosis and K-F rings despite therapy. The data show that morphological improvement occurs in some PCN-treated pts with WD, but that this is not predicted by function tests. Sequential biopsies are needed to evaluate fully the extent of healing.

Protocollagen proline hydroxylase activity in experimental pulmonary fibrosis of rats.

Abstract The activity of the enzyme protocollagen proline hydroxylase which synthesizes the hydroxyproline in collagen by hydroxylating proline in protocollagen was determined in rat lung tissue. About 80 per cent of the enzyme activity was recovered in the 100,000 × g supernatant fraction of the lung homogenate, and the enzyme required ascorbic acid, α-ketoglutarate, and ferrous iron for its activity. When ferrogluconate (100 mg. per kilogram per day) was injected into rats for 10 days, the enzyme activity increased into 134 per cent of the control value. Injections of ascorbate (100 mg. per kilogram per day) or cortisone (20 mg. per kilogram per day), or administration of d-penicillamine (200 mg. per kilogram per day) in drinking water did not change the enzyme activity. The protocollagen proline hydroxylase activity was determined in the lung tissue of rats with experimental silicosis induced by an intratracheal injection of silica dust. The enzyme activity was increased at 5 weeks in silicotic rats and reached a maximum, 259 per cent of the control value, at 16 weeks after the induction of silicosis. The enzyme activity was increased before fibrosis could be demonstrated by means of histological staining or chemical hydroxyproline analyses.

Treatment of Lead Poisoning: A Comparison between the Effects of Sodium Calciumedetate and Penicillamine Administered Orally and Intravenously

In 16 workers with lead poisoning of varying degrees, a comparison was made between the therapeutic efficacy of sodium calciumedetate (Ca-EDTA) and penicillamine (PCA), administered intravenously and orally. The question of comparable dosages of ligands, forming metal complexes in different ways, is discussed. With the dosages given, intravenous Ca-EDTA promoted the greatest output of lead in the urine, followed by intravenous and oral PCA. These three agents also had a very satisfactory effect on the output δ-aminolaevulinic acid (ALA) in urine. Oral Ca-EDTA was found to be greatly inferior in both these respects. In order to study the absorption of the agents and the renal excretion of the formed lead complexes, the urine was collected quantitatively and fractionated in consecutive 4-hour periods, after which the lead excretion during each period was determined. It was found that the oral absorption of PCA was rapid and quantitatively great, whereas the oral absorption of Ca-EDTA was very slow and quantitatively small. The possible resorption of ligand-lead complexes is discussed and indications were found of resorption of the Ca-EDTA-lead complex but not of the PCA-lead complex. The renal excretion of the different ligand-lead complexes was very effective and reached its maximal level within four hours. However, in some subjects excretion of the Ca-EDTA-lead complex showed some delay. An investigation, in four subjects, of a blocking effect of probenecid on the renal excretion of PCA and/or PCA-lead complexes gave no conclusive results. It is concluded that oral PCA is satisfactory in most cases of lead poisoning. However, in more severe cases intravenous treatment is preferable. Which agent should be chosen, Ca-EDTA or PCA, appears to be unimportant as both are quite satisfactory from the point of view of treatment, but it seems that Ca-EDTA may cause more serious side-effects. Oral Ca-EDTA is quite unsatisfactory and there is good evidence to indicate that the agent causes a resorption of Ca-EDTA-lead complexes from the gastro-intestinal tract.

Hypercupremia in a patient with multiple myeloma.

Abstract The laboratory and clinical investigation of a patient with marked hypercupremia and multiple myeloma is described. The majority of the copper was found to be associated with the IgG myeloma protein. This IgG myeloma protein showed normal immunological reactivity, no significant abnormality in amino acid composition, and no gross increase in copper-binding capacity. Penicillamine therapy did not produce a statistically significant increase in urinary copper excretion.

Penicillamine in the treatment of patients with cystiuria

Penicillamine in the treatment of patients with cystiuria

The use of penicillamine in cystinuria

The use of penicillamine in cystinuria

Intra-articular dissociation of the rheumatoid factor.

Abstract It has been shown that the macroglobulins of Waldenstrom's macroglobulinemia and cold agglutinin hemolytic anemia can be dissociated in vivo by the administration of penicillamine. The rheumatoid factor is a macroglobulin. The results of in vitro dissociation of the rheumatoid factor by sulfhydryl compounds are presented. While penicillamine was effective in achieving in vitro dissociation, oral administration of this thiol to rheumatoid patients for 14 days failed to produce in vivo dissociation. When sulfhydryl compounds were introduced directly into the joint space, however, dissociation of the rheumatoid macroglobulin was consistently produced. Immunologic reactivity was lost and the latex test became negative for short periods. The feasibility of in vivo dissociation of the rheumatoid factor has thus been established and lends encouragement to the possibility that this substance may be reduced in the serum with more potent sulfhydryl compounds.

446. Syntheses from phthalimido-acids. Part X. Derivatives of DL- penicillamine

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