Significant Adjuvant Effect Research Articles

Effect of lovastatin alone and as an adjuvant chemotherapeutic agent on hepatoma tissue culture-4 cell growth

Cholesterol is essential for cell viability and growth. Interference with the cholesterol biosynthetic pathway with a 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor (e.g., lovastatin) may preferentially slow malignant cell growth and offer a new approach to cancer chemotherapy. To test this hypothesis, we evaluated the effect of lovastatin alone, and as an adjuvant chemotherapeutic agent, on the growth and function of hepatoma tissue culture-4 (HTC-4) cells. HTC-4 cells were treated with lovastatin at concentrations of 1, 3, 5, and 10 microM, with mitomycin-C at concentrations of 10, 25, 50, and 100 nM, or with combinations of the two drugs. Cell growth was evaluated by daily cell counts and substrate adhesion to fibronectin. Lovastatin alone slowed HTC-4 cell growth at concentrations as low as 1 microM (p < 0.01). Mitomycin-C alone slowed HTC-4 cell growth at concentrations of 25 nM and above (p < 0.01). Lovastatin added to mitomycin-C-treated cells resulted in a significant adjuvant effect, with cell growth slowed by an additional 20-30% by 1 microM lovastatin and by an additional 43-63% by 5 microM lovastatin, compared to mitomycin-C alone (p < 0.01). Lovastatin-treated cells also exhibited decreased adherence to substrate (p < 0.05). Lovastatin is effective alone and as an adjuvant to mitomycin-C in slowing the growth of HTC-4 cells. These in vitro results support further investigation of lovastatin as an adjuvant chemotherapeutic agent in animal models.

Biological and Biochemical Properties of Venoms from Medically Important Loxosceles (Araneae) Species in Brazil

Abstract1. The biological, immunochemical and biochemical properties of venoms from Loxosceles gaucho, L. laeta and L. intermedia were studied.2. Venom from Loxosceles sp causes typical dermonecrotic lesion in bitten patients and rabbits but not in mice.3. The dermonecrotic and lethal activities of the L. gaucho venom were located in its higher mol. wt components (33.000–35.000).4. The higher molecular component of the venom is the most immunogenic component in both patients and rabbits.5. Analysis by SDS-PAGE showed the existence of many common components in the three venoms but no individual antigen was found.6. Antiserum to each one of these venoms was able to neutralize the dermonecrotic and lethal activities of all three venoms.7. Venom from L. gaucho has a significant adjuvant effect that was associated with its higher mol. wt components.8. The amino terminal sequence of 35 residues of L. gaucho active component was determined. A high level of identity (60%) and similarity (86%) was found between th...

Adjuvant activity of QS-21 for experimental E. coli 018 polysaccharide vaccines

Three types of experimental vaccines containing O-side-chain polysaccharide from the enterotoxigenic strain Escherichia coli 018 were evaluated. The immunogenicity of free O-polysaccharide (PS), a polysaccharide-diphtheria toxoid conjugate (PS-conj), and detoxified lipopolysaccharide (dLPS) was tested in female ICR mice, either alone or in combination with QS-21, a purified saponin adjuvant derived from the bark of the tree Quillaja saponaria Molina. Both the number of individual mice responding and the titres of O-polysaccharide specific antibodies in pools of sera were increased by the addition of QS-21. The immune response to both O-specific polysaccharide and carrier was primarily IgM and IgG1. The addition of QS-21 not only increased the level of IgG1, but also had a significant adjuvant effect on antigen-specific IgG2a, IgG2b and IgG3.

Adjuvant effect of Loxosceles gaucho (South American brown spider) venom

Injection of L. gaucho venom and antigens (ovalbumin, ovomucoid and bovine gamma globulin) into rabbit skin induced an intense local inflammatory lesion and resulted in a significant increase in the level of IgG antibodies to the antigen in both the primary and secondary humoral immune response. The adjuvant activity of the venom was associated with its high mol. wt components, which are responsible for the inflammatory lesion. Rabbits rendered unresponsive to the venom and injected with venom plus antigen presented a very mild local inflammatory reaction and no increase in antibody formation. When venom and antigen were injected simultaneously but at different skin sites no adjuvant effect was induced. However, when antigen was injected 4 hr after venom injection but at the same skin site a significant adjuvant effect was produced. Furthermore, when venom plus antigen was injected intradermally into mice, a species in which the venom does not cause an inflammatory skin lesion, no adjuvant effect was detected. It is suggested that the adjuvant effect of L. gaucho venom in rabbits is probably due to its ability to cause a local severe inflammatory reaction.

Impact of Ten Spray Adjuvants on Leaf Gas Exchange of Pecan, Blueberry, Photinia, and Azalea

Abstract Three separate factorial experiments were designed to evaluate the effect of 10 adjuvants on net CO2 assimilation rate (A), leaf conductance to water vapor (g1), and transpiration rate (E) of pecan [Carya illinoensis (Wagenh.) C. Koch] ‘Elliott’, blueberry (Vaccinium ashei Reade) ‘Chaucer’, red top photinia (Photinia × Fraseri Dress), and azalea (Rhododendron × ‘Pink Ruffles’). Single applications of Bond, Leaf Act 80A, Nu-Film-17, Ortho X-77, Penetrator 3, Plyac, Sorba Spray ZNP, Sun Spray 7E, Triton CS-7, or Triton B-1956 at recommended rates did not affect A, g1, or E compared to a water spray. The main effect of plant species was highly significant in all three studies without adjuvant-species interactions. A significant adjuvant effect on A occurred with a second application of Nu-Film-17, Plyac, and Triton B-1956. The only significant effect, when treatments were analyzed separately by species, was that A of Plyac-treated blueberry was less than the control.

Cellular requirements for lipopolysaccharide adjuvanticity. A role for both T lymphocytes and macrophages for in vitro responses to particulate antigens.

By employing primary cultures of purified spleen cells from lipopolysaccharide (LPS) responder (C3H/HeN or C57BL/10Sn) or nonresponder (C3H/HeJ or C57BL/10ScN) mice incubated with particulate antigen and LPS prepared by phenol-water extraction (Ph), we have presented evidence that both T cells and macrophages (MO) are required for LPS-induced adjuvanticity. First, MO derived from C3H/HeN spleen cells, when mixed with responder, C3H/HeN lymphocytes and Ph-LPS, elicited enhanced antibody responses to sheep erythrocytes (SRC) antigen, whereas lymphocytes from the nonresponder, C3H/HeJ mouse strain did not evoke this response. Similarly, purified T cells from C3H/HeN spleens, when cultured with responder, nu/nu spleen cells, and Ph-LPS yielded enhanced anti-TNP PFC responses; whereas, C3H/HeJ T cells did not potentiate immune responses when mixed with optimal concentrations of Ph-LPS. LPS prepared by butanol-water extraction elicited significant adjuvant effects with all cell combinations. Finally, purified responder T cells and MO enabled either responder or nonresponder B cells to elicit LPS potentiation. These data indicate that T cells and MO are controlling LPS-induced augmentation of B-cell responses.

Induction of cell-mediated immunity to Mycobacterium leprae in guinea pigs

Guinea pigs immunized with intact or disrupted armadillo-grown human Mycobacterium leprae administered in aqueous or oil vehicles were tested with various dilutions of M. leprae suspended in saline, water-soluble M. leprae extract, purified protein derivative, and a water-soluble extract of normal armadillo tissue. The results demonstrated the following. (i) Under no conditions was any skin test reactivity found to normal armadillo tissue extract. (ii) Positive sensitization to both M. leprae and its water-soluble extract was achieved by sensitizing guinea pigs with M. leprae suspended in Hanks solution or saline. Autoclaved M. leprae in Hanks solution or saline inoculated intradermally was an effective immunogen. Oil suspensions or emulsions were effective at sensitization, but appeared to be no better and, in general, slightly weaker, than simple inoculation in aqueous suspension. (iii) Living BCG failed to reveal a significant adjuvant effect on sensitization to M. leprae. However, cord factor appeared to potentiate slightly the sensitization to M. leprae in aqueous suspension. (iv) The minimum dose required for sensitization with M. leprae in aqueous suspension was 55 micrograms of purified bacilli. (v) Animals inoculated with M. leprae in saline or with M. leprae together with BCG showed positive skin test reactivity to the first skin test application made fully 1 year after the initial sensitization. The efficacy of autoclaved, irradiated M. leprae in aqueous, oil-free medium suggests a relatively safe approach to human vaccination studies.

Antiparkinson drugs as causal agents in tardive dyskinesia.

The cases of three patients are described in whom a phenothiazine-induced tardive dyskinesia was aggravated by benztropine. It is suggested that in some cases antiparkinson drugs may have a significant adjuvant effect in provoking tardive dyskinesia.

The adjuvant effects of a tubercle bacillary lipid and lecithin: The immunization of mice by tetanus toxoid

Summary Mice were immunized by a single subcutaneous injection of tetanus toxoid (a) alone (b) with a tubercle bacillary lipid or (c) with a synthetic lecithin. The tubercle bacillary lipid or the lecithin were injected at the same time as the toxoid. The mice were challenged fourteen days later with a lethal dose of tetanus toxin. The tubercle bacillary lipid augmented the protection given to the mice if it were injected mixed with the toxoid, but not if it were injected by the intraperitoneal route. The augmenting effect appeared to be significant only with doses of toxoid that were effective alone, and increased with increasing dosage of the lipid Lecithin displayed a significant adjuvant effect only when injected in large doses together with the toxoid.