Effect of ascorbic acid on tumour growth

The growth of tumours in guinea-pigs was observed for 20 weeks after placing them on various doses of vitamin C. Complete tumour regression occurred in 55% of those animals receiving 0-3 mg/kg/day ascorbic acid, whereas animals given 10 mg/kg/day showed tumour inhibition but no regression. In contrast, tumours in animals maintained on 1 g/kg/day ascorbic acid grew without sign of retardation. When increased amounts of ascorbic acid were restored to the diet of scorbutic tumour-bearing animals, tumours which had not regressed responded with enhanced growth. Likewise, animals previously maintained on 10 mg/kg ascorbic acid responded in turn to the additional vitamin with enhanced tumour growth. In contrast, all tumour-bearing animals maintained on 1 g/kh ascorbic acid died within 3 weeks when this dose was replaced with 0-3 mg/kg.     

Interleukin-12 is required for control of the growth of attenuated aromatic-compound-dependent salmonellae in BALB/c mice: role of gamma interferon and macrophage activation

The attenuated S. typhimurium SL3261 (aroA) strain causes mild infections in BALB/c mice. We were able to exacerbate the disease by administering anti-interleukin-12 (IL-12) antibodies, resulting in bacterial counts in the spleens and livers of anti-IL-12-treated mice that were 10- to 100-fold higher than the ones normally observed in premortem mice; yet the animals showed only mild signs of illness. Nevertheless, they eventually died of a slow, progressive disease. Mice infected with salmonellae become hypersusceptible to endotoxin. We found that IL-12 neutralization prevented the death of infected mice following subcutaneous injection of lipopolysaccharide. Granulomatous lesions developed in the spleens and livers of control animals, as opposed to a widespread infiltration of mononuclear cells seen in the organs of anti-IL-12-treated mice. In the latter (heavily infected), salmonellae were seen within mononuclear cells, indicating an impairment of the bactericidal or bacteriostatic ability of the phagocytes in the absence of biologically active IL-12. Gamma interferon (IFN-gamma) levels were reduced in the sera and tissue homogenates from anti-IL-12-treated mice compared to those in control animals. Furthermore, fluorescence-activated cell sorter analysis on spleen cells showed that IL-12 neutralization impaired the upregulation of I-Ad/I-Ed antigens on macrophages from infected mice. Inducible nitric oxide synthase and IFN-gamma mRNA production was down-regulated in anti-IL-12-treated mice, which also showed an increased production of IL-10 mRNA and a decrease in nitric oxide synthase activity in the tissues. Administration of recombinant IFN-gamma to anti-IL-12-treated mice was able to restore host resistance, granuloma formation, and expression of major histocompatibility complex class II antigens in F4/80(+) and CD11b+ spleen cells.     

Developments in the treatment of alcoholism

The treatment of alcoholism has changed during the past 2 decades. Notable developments have occurred in pharmacotherapy, psychotherapy, and health-care delivery. A better understanding of the biologic basis for addiction has led to clinical trials of medications that target neuroreceptors. One such medication is the opiate antagonist naltrexone, which decreases the craving for alcohol. Psychosocial interventions continue to be the mainstay of alcohol treatment programs. The efficacy of three different therapies was demonstrated in a study called Project MATCH (Matching Alcoholism Treatments to Client Heterogeneity). This study, however, did not prove the patient-treatment "matching" hypothesis. In addition to therapies provided by addiction specialists, interest is growing in the use of brief motivational techniques in primary-care settings. As the field of addiction responds to an unfolding health-care delivery system, a broader range of treatment options in conjunction with a greater opportunity to individualize patient care is evolving.     

Effects of agitation on size distribution of particulate matter in large-volume parenterals

The particle-size distributions of six types of large-volume parenterals subjected to different degrees of agitation were determined using an automatic particle counter. Data acquired from each solution, which had been maintained in a stored condition, subjected to agitation by inverting 20 times, and then mechanically shaken for 30 min, produced a linear relationship between log N greater than D and log D. Both the slope (K) and the number of particles per milliliter exceeding 1 micrometer in diameter (N greater than 1) exhibited a dependence on the degree of agitation. Their combined effect indicates that agitation by 20 hand inversions removed particulate matter from the surface of the container, which increased the total number of particles in solution (greater than 1 micrometer) but did not significantly alter the relative size distribution. Agitation for 30 min, however, disintegrated agglomerates and produced a particle-size distribution with a greatly increased number of particles whose diameters were less than 1 micrometer and a corresponding decrease in the number of particles exceeding 1 micrometer in diameter. The particle-size distribution of a parenteral solution determined by this in situ instrumental method was, therefore, dependent upon the degree of agitation to which the parenteral was subjected prior to examination.     

Renaturation of formyltetrahydrofolate synthetase from urea and guanidinium chloride solutions

Formyltetrahydrofolate synthetase from Clostridium cylindrosporum and Clostridium acidi-urici was denatured in 6 M urea and 4 M guanidinium chloride. Viscometric, fluorimetric and ultracentrifugal measurements were used to determine that the protein is completely unfolded under these conditions. The polypeptide chains refold upon dilution of the denaturant-protein solutions to give final concentrations of 0.5 M urea or 0.1 M guanidinium chloride. In the presence of NH4+, but not in its absence, the refolded proteins associate to produce the catalytically active tetramer. Refolding and reassociation were followed by measuring changes in protein fluorescence and by determination of sedimentation constants. Under most conditions 80% of the enzymic activity is recovered.