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Abstracts

Life Extension Magazine January 2010
Abstracts

Influenza

Preventing the common cold with a garlic supplement: a double-blind, placebo-controlled survey.

One hundred forty-six volunteers were randomized to receive a placebo or an allicin-containing garlic supplement, one capsule daily, over a 12-week period between November and February. They used a five-point scale to assess their health and recorded any common cold infections and symptoms in a daily diary. The active-treatment group had significantly fewer colds than the placebo group (24 vs 65, P < .001). The placebo group, in contrast, recorded significantly more days challenged virally (366 vs 111, P < .05) and a significantly longer duration of symptoms (5.01 vs 1.52 days, P < .001). Consequently, volunteers in the active group were less likely to get a cold and recovered faster if infected. Volunteers taking placebo were much more likely to get more than one cold over the treatment period. An allicin-containing supplement can prevent attack by the common cold virus

Adv Ther. 2001 Jul-Aug;18(4):189-93

Allium sativum potentiates suicide gene therapy for murine transitional cell carcinoma.

This study evaluated the synergistic effect of Allium sativum (AS) with suicide gene therapy for transitional cell carcinoma (TCC) of the bladder. Subcutaneous TCCs were established in syngeneic C3H/He mice with 1 x 10(5) MBT-2 cells. AS liquid extract was injected at the site of tumor transplantation on Day 1 for three weeks (Experiment I) and into the established tumors weekly for five weeks (Experiment II) in combination with or without gene therapy using a replication-defective adenoviral vector containing a herpes simplex virus thymidine kinase (HSV-TK) gene under the transcriptional control of Rous sarcoma virus (RSV) promoter (Ad-RSV-TK, 5 x 10(8) plaque-forming units) plus ganciclovir (20 mg/kg/day i.p.). AS demonstrated a statistically significant reduction in incidence of TCC (cumulative dose 25 mg of AS). Combination AS-suicide gene therapy significantly inhibited the tumor growth compared with the controls, which was evidenced by apoptosis on histomorphological and immunohistochemical studies. These results suggest that AS had a definite antitumor effect in inhibiting tumorigenesis and growth of TCC in a murine model. AS treatment combined with suicide gene therapy had significant additive antitumor effects on TCC and may provide a novel and effective treatment modality for TCC of the bladder.

Nutr Cancer. 2000;38(1):98-105

In vitro virucidal effects of Allium sativum (garlic) extract and compounds.

Garlic (Allium sativum) has been shown to have antiviral activity, but the compounds responsible have not been identified. Using direct pre-infection incubation assays, we determined the in vitro virucidal effects of fresh garlic extract, its polar fraction, and the following garlic associated compounds: diallyl thiosulfinate (allicin), allyl methyl thiosulfinate, methyl allyl thiosulfinate, ajoene, alliin, deoxyalliin, diallyl disulfide, and diallyl trisulfide. Activity was determined against selected viruses including, herpes simplex virus type 1, herpes simplex virus type 2, parainfluenza virus type 3, vaccinia virus, vesicular stomatitis virus, and human rhinovirus type 2. The order for virucidal activity generally was: ajoene > allicin > allyl methyl thiosulfinate > methyl allyl thiosulfinate. Ajoene was found in oil-macerates of garlic but not in fresh garlic extracts. No activity was found for the garlic polar fraction, alliin, deoxyalliin, diallyl disulfide, or diallyl trisulfide. Fresh garlic extract, in which thiosulfinates appeared to be the active components, was virucidal to each virus tested. The predominant thiosulfinate in fresh garlic extract was allicin. Lack of reduction in yields of infectious virus indicated undetectable levels of intracellular antiviral activity for either allicin or fresh garlic extract. Furthermore, concentrations that were virucidal were also toxic to HeLa and Vero cells. Virucidal assay results were not influenced by cytotoxicity since the compounds were diluted below toxic levels prior to assaying for infectious virus. These results indicate that virucidal activity and cytotoxicity may have depended upon the viral envelope and cell membrane, respectively. However, activity against non-enveloped virus may have been due to inhibition of viral adsorption or penetration.

Planta Med. 1992 Oct;58(5):417-23

Immunomodulatory effects of aged garlic extract.

Using various kinds of models, we examined the effects of aged garlic extract (AGE) on immune functions. In the immunoglobulin (Ig)E-mediated allergic mouse model, AGE significantly decreased the antigen-specific ear swelling induced by picryl chloride ointment to the ear and intravenous administration of antitrinitrophenyl antibody. In the transplanted carcinoma cell model, AGE significantly inhibited the growth of Sarcoma-180 (allogenic) and LL/2 lung carcinoma (syngenic) cells transplanted into mice. Concomitantly, increases in natural killer (NK) and killer activities of spleen cells were observed in Sarcoma-180--bearing mice administered AGE. In the psychological stress model, AGE significantly prevented the decrease in spleen weight and restored the reduction of anti-SRBC hemolytic plaque-forming cells caused by the electrical stress. These studies strongly suggest that AGE could be a promising candidate as an immune modifier, which maintains the homeostasis of immune functions; further studies are warranted to determine when it is most beneficial.

J Nutr. 2001 Mar;131(3s):1075S-9S

The effect of cimetidine on survival of mice infected with herpes simplex virus type 2, murine encephalomyelitis virus and vesicular stomatitis virus infections.

The effect of cimetidine on survival was investigated in mice infected with herpes simplex virus type 2 (HSV-2), murine encephalomyelitis virus (GD-VII), and vesicular stomatitis virus (VSV). BALB/c mice, 5 weeks of age, were injected intraperitoneally (i.p.) with 5.5 x 10(5) plaque-forming units (PFU) of virus/0.5 ml, and cimetidine (1 mg/0.5 ml) was administered simultaneously. The survival rates of 80% and 85% in the cimetidine groups were significantly greater than the 10% and 23% for the control groups. The GD-VII- and VSV-infected control mice were dead at 3 days after virus inoculation. However, more cimetidine-treated mice survived than control mice. When anti-mouse T-cell serum or cyclosporine, which is a helper T-cell suppressor, was administered to BALB/c mice; the effect of cimetidine against the HSV-2 infection could be observed. When injected with anti-asialo GM1, BALB/c mice or beige mice with low natural killer (NK) cell activity were not affected by cimetidine. Lastly, cimetidine was shown to activate the cytotoxic action on NK cells. The above results indicate that the antiviral effects of cimetidine depend on NK cell activation.

Kurume Med J. 1989;36(3):95-9

Dehydroepiandrosterone enhances influenza immunization in aged mice.

The effect of DHEA administration on the age-associated decline in immunity against influenza vaccine was studied. Increased humoral response was observed in 16- and 24-month-old mice immunized by live A/PR/8/34 (H1N1) influenza virus following DHEA treatment (a single injection adjacent to immunization). Furthermore, DHEA-treated mice demonstrated increased resistance to postvaccination intranasal challenge with live influenza virus. Thus, DHEA treatment overcomes the age-related defect in the immunity of old mice against influenza.

Ann N Y Acad Sci. 1995 Dec 29;774:297-9

Dehydroepiandrosterone (DHEA) treatment reverses the impaired immune response of old mice to influenza vaccination and protects from influenza infection.

Dehydroepiandrosterone (DHEA) is a native steroid with an immunomodulating activity. Recently it was suggested that its age-associated decline is related with immunosenescence. To examine whether DHEA administration could effectively reverse the age-associated decline of immunity against influenza vaccine, aged mice were simultaneously vaccinated and treated with DHEA. Reversal of the age-associated decline and a significant constant increase of humoral response was observed in treated mice. Increased resistance to post-vaccination intranasal challenge with live influenza virus was observed in DHEA-treated aged mice. Thus, DHEA treatment overcame the age-related defect in the immunity of old mice against influenza.

Vaccine. 1995;13(15):1445-8

Dehydroepiandrosterone treatment is not beneficial to the immune response to influenza in elderly subjects.

BACKGROUND: Dehydro-epiandrosterone (DHEA) is a native steroid with an immunomodulating activity that was suggested to counter-regulate some phenomena of immunosenescence. Recently, it was shown to reverse the age-associated decline of immune response against influenza vaccine in aged mice. The present study was designed to evaluate the effect of DHEA on the immunization of elderly volunteers against influenza. METHODS: Seventy-one elderly volunteers age 61-89 yr were enrolled in a prospective randomized, double-blind study to receive either DHEA (50 mg qd p.o. for four consecutive days starting two days before immunization) or placebo. Antibody response to the vaccine was measured before and 28 days after vaccination. RESULTS: DHEA treatment significantly increased serum DHEA-sulfate (DHEA-S). No enhancement in established immunity was observed. A significant decrease in attainment of protective antibody titer (1:40 or higher) against the A/Texas strain in subjects with nonprotective baseline antibody titer was recorded following DHEA treatment compared with placebo (52% vs. 84%, P < 0.05). Baseline DHEA-S serum levels were inversely related to attainment of immunization in DHEA-treated subjects. Influenza-like morbidity during the winter was low in the study group with no difference between the DHEA and placebo groups. CONCLUSIONS: Although highly effective in aged rodents, a short course of DHEA treatment did not improve the age-related declined response to immunization against influenza in human subjects. Higher baseline DHEA-S levels are not predictive of better immunization against influenza in the elderly.

J Clin Endocrinol Metab. 1997 Sep;82(9):2911-4

Endocrine regulation of the immune response to influenza virus infection with a metabolite of DHEA-androstenediol.

In these studies the influence of androstenediol on the course of an experimental virus infection was examined. Pretreatment with 320 mg/kg AED protected male mice from lethal influenza virus infection. In addition, AED enhanced antigen-induced trafficking of mononuclear cells into the draining lymph node and augmented antigen-specific activation of helper-T cells, which are important for control of viral pathogenesis. Furthermore, AED prevented the characteristic increase in serum corticosterone noted during influenza A virus infection. Although steroid hormones, at least corticosteroids, typically suppress host immune and inflammatory responses in vivo, these data suggest that AED may function to augment host immune and inflammatory responses in contrast to corticosteroids.

J Neuroimmunol. 1997 Sep;78(1-2):203-11

Relationship between the response to influenza vaccination and the nutritional status in institutionalized elderly subjects.

BACKGROUND: Influenza is a major health problem among elderly people in industrialized countries. Nursing homes may be a particularly good setting for outbreaks of influenza. Thus, the aim of the present study was to evaluate some aspects of the nutritional status of institutionalized elderly subjects in relation to their response to influenza vaccination. Certain aspects of the cellular immune response were also investigated. METHODS: Twenty-three patients participated in this cross-sectional study. All patients were vaccinated on day 0 with FluviralR, 1994-95 preparation: A/Shangdong/09/93, A/Texas/36/91, B/Panama/45/90. At the same time the prevaccination antibody titer, the nutritional status by the Mini Nutritional Assessment, biochemical parameters, and lymphocyte proliferation were assessed. On day 28, the postvaccination antibody titer was determined. The determination of pre- and postvaccination antibody titers against the various influenza antigens was carried out by the hemagglutination inhibition test. An increase of 4x for any of the virus antigens was considered as a seroconversion. A titer higher than 40 at the prevaccination period was considered as protective. RESULTS: Eleven elderly subjects were responsive and 12 were not. We have shown that the nutritional parameters such as hemoglobin, hematocrit, total protein, iron and vitamin E levels, as well as the DHEA level and the cellular immune response were significantly lower in the nonresponsive group as compared to the responsive group. Thus, they might be associated with the influenza vaccine responsiveness of institutionalized elderly subjects. CONCLUSIONS: These results will help design intervention studies for improving the immune response by achieving an optimal nutritional status, mainly in the frail elderly population, that could have a great public health impact.

J Gerontol A Biol Sci Med Sci. 1999 Feb;54(2):M59-64

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