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Biomedical subjects

A Lorber

Publications and source records attributed to A Lorber.

At least 73 records · Page 4Linked to original sources
PubMed1983

Sjögren's syndrome with pseudolymphoma treated with chrysotherapy.

A 72-year-old woman presented with a 10 X 10 cm pseudolymphoma of the lung and Sjögren's syndrome. She was treated with weekly chrysotherapy for 4 years and had gradual diminution of the lung mass over this period along with normalization of her parotid gland scintiscan. In addition her rheumatoid factor titer (RF) of 1:160,000 fell to zero, IgM level became normal and lymphocyte mitogen response improved. On 5-year followup the patient remains stable with a negative RF, normal IgM and stable chest radiographs.

Aged↗
PubMed1981

Assessment of immune response during chrysotherapy. Comparison of gold sodium thiomalate vs. auranofin.

Auranofin (AF) differs significantly from gold sodium thiomalate (GST) in formulation, i.e., aurous gold is stabilized by dual sulfur and phosphorus ligands, has hydrophobic rather than hydrophilic characteristics, and lacks ionic charge. These attributes facilitate: oral absorption of AF, plasma membrane penetration, increase in intracellular lymphocyte gold concentration and perhaps thereby influence lymphocyte function. AF therapy was observed to affect primarily T rather than B lymphocyte function in 16 RA subjects receiving 6 mg of AF per day for an average of 45 weeks (range 20-74 weeks) compared with GST-treated RA subjects. Lymphocytes from AF-treated subjects manifested prompt and sharp declines in mitogen-induced lymphoproliferative response (LPR); suppressed response to skin testing with dinitrochlorobenzene (DNCB); and blebbing of lymphocyte membranes as shown by scanning electron microscopy. Suppression of LPR with AF was approximately 60% after the first week and 80% after 20 weeks of therapy, contrasting with 0% and 30% for the respective intervals in GST-treated subjects. DNCB skin testing of AF patients, indicated 11 of 14, failed to respond, whereas all GST patients responded. Local or systemic fungal, bacterial and/or opportunistic infections were not encountered. The effect of AF on B cell effector function, e.g., suppression of immunoglobulins and rheumatoid factor titer, was less marked when contrasted with GST therapy in RA subjects, as previously reported.

Arthritis, Rheumatoid↗
PubMed1981

Screening trial with the coordinated gold compound auranofin using mouse lymphocyte leukemia P388.

The coordinated gold compound, 2,3,4,6-tetra-O-acetyl-1-thio-beta-D-glucopyranosato-S-triethylphosphine-gold (auranofin) was found to be effective in increasing the life span of C57BL x DBA/2 F1 mice inoculated with the lymphocytic leukemia P388. A number of dose schedules were used, the lowest dose being 6 mg/kg every fourth day and the highest dose being 6.0 mg/kg twice daily for 9 days; the lowest and highest doses produced treated versus control ratios of 140 and 220%, respectively. All treatment groups achieved the minimum treated versus control ratio of 125%. Animal weights remained stable at twice-daily and high-dose-daily regimens. Increased life span and weight changes were both found to correlate with drug concentration and/or dose frequency.

Animals↗
PubMed1979

Inhibitory effects of a new oral gold compound on HeLa cells.

Auranofin (AF), a recently introduced oral antirheumatic coordinated gold compound, was investigated for its antitumor potential. Due to certain similarities with the antitumor-coordinated compound, cis-Diamminedichloroplatinum II, we studied the effects of AF on cell proliferation. These studies included assessing DNA, RNA, and protein synthesis as measured by incorporation of 3H-thymidine, 3H-uridine, and 3H-leucine, respectively, into HeLa cells. AF was shown to exert a dose-dependent inhibition on DNA synthesis and to inhibit 3H-thymidine uptake more rapidly and persistently than 3H-uridine or 3H-leucine uptake at a gold concentration of 75--100 micrograms/dl. These three parameters were inhibited with a 24-hour exposure to 100 micrograms/dl. The inhibition of 3H-thymidine uptake in HeLa pretreated for 6 hours with 50 or 100 micrograms/dl of gold was found to be irreversible. No change in tracer uptake was observed in the acid-soluble pool or in the uptake of 3H-2-deoxy-D-glucose in these cells. Furthermore, HeLa cells demonstrated marked reductions in viability and oxygen uptake after exposure to AF. Dose-dependent surface morphological changes, e.g., blebbing, pitting, were noted in these cells after a brief treatment period. These results suggest this coordinated gold compount exerts a significant inhibitory effect on essential biological processes and functions.

Aurothioglucose↗
PubMed1979

Effect of chrysotherapy on parameters of immune response.

Thirty-nine subjects with classical or definite rheumatoid arthritis received weekly intramuscular gold sodium thiomalate (GST) to sustain gold blood levels of more than 320 microgram/dl. Statistical analysis revealed significant declines from pre-treatment values for IgM, IgG, and IaA. Rheumatoid factor titer decreased in 29 of 39 subjects, 15 becoming seronegative. Circulating lymphocytes decreased by 27%. The maximal suppressive effect on IgM was not achieved until the 3rd and 4th years of GST administration. Auranofin (AF) 6 mg/day was administered to 15 patients for an average interval of 45 weeks. In vitro and in vivo suppression of lymphocyte mitogen response with AF was more rapid in onset and significantly greater than with GST. Suppression of dinitrochlorobenzene skin sensitization was observed in AF patients. The clinical response in GST treated subjects correlated with suppression of immunoglobulins, rheumatoid factor titer, and circulating lymphocytes. A significant decline in these variables was not achieved for a corresponding interval with AF treatment. It is suggested that chrysotherapy may be applied more widely to immunologically-mediated disorders and perhaps be used to affect selectively B versus T mediated dysfunction.

Antibody Formation↗
PubMed1979

Cellular antiproliferative action exerted by auranofin.

Auranofin (AF) is a new orally absorbed coordinated gold compound currently undergoing Phase I studies for its use in the treatment of rheumatoid arthritis. Our investigations with RAJI lymphoma, HeLa carcinoma, and EBV-transformed cells indicate AF exerts an inhibitory effect on DNA, RNA, and protein synthesis as assessed by 3H-thymidine, 3H-uridine, and 3H-leucine uptake, respectively. A rapid and persistent dose dependent inhibition of 3H-thymidine uptake was observed at gold concentrations of 50-100 microgram/dl while all parameters were inhibited after a 24 hr exposure to 100 microgram/dl. Reductions in viability and surface morphological changes were also observed. These results suggest AF exerts a significant inhibitory effect on essential biological processes and functions.

Aurothioglucose↗
PubMed1975

Protein sulphydryl depression during adjuvant arthritis.

The changes in plasma protein sulphydryl level were measured during the course of adjuvant-induced arthritis in rats. Major depressions in the plasma sulphydryl level occurred at the onset of adjuvant disease, and the extent of the depression was related to the severity of the disease. Plasma sulphydryl levels remain unchanged when the systemic arthritis is suppressed by inclusion of a competing antigen in the adjuvant. Changes in sulphydryl content of the plasma were shown not to be due to weight loss or decrease in plasma protein level.

Animals↗
PubMed1975

Chrysotherapy: pharmacological and clinical correlates.

Relationships between gold administration and serum gold content were observed in 56 RA subjects receiving up to five years of weekly chrysotherapy. Wide fluctuations in serum gold responses to standard 50 mg IM injections were noted. Individual adjustments to dosage schedules were made as dictated by patient serum gold responses. Enhanced clinical and laboratory response was prolonged with higher sustained serum gold concentration greater than 300 mug per cent. Maintaining serum levels greater than 300 mug per cent is postulated to facilitate access of gold to "effector sites" within the deeper compartments by providing higher sustained gradients between superficial (blood) and deeper body compartments. The complexity of the system of effector sites responsive to gold and their divergent location within the body likely affects the accessibility of the agent for these sites; hence, affecting the correlation between gold levels and therapeutic response. The application of pharmacokinetic principles in chrysotherapy, nevertheless, provides the basis for optimizing accessibility of the agent and the therapeutic response. (J Rheumatol 2: 401-410, 1975).

Arthritis, Rheumatoid↗