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May 2013

The recombinant hepatitis B surface antigen vaccine in persons with HIV: is seroconversion sufficient for long-term protection?

A cohort of human immunodeficiency virus (HIV)-infected individuals with documented vaccine-induced hepatitis B surface antibody (HBsAb) seroconversion was evaluated retrospectively to determine factors associated with loss of protective levels of HBsAb. After a median follow-up of 43 months, 111 of the 152 participants (73%) maintained protective levels of HBsAb. HIV RNA suppression at vaccination was associated with persistence of protective levels of HBsAb (odds ratio, 3.83; P < .01). Booster doses were provided for those with loss of protective antibody levels, and hepatitis B virus-specific immune memory, as evaluated with T-cell proliferation assays, was poor despite the observation that boosters successfully reinduced protective levels of HBsAb.

J Infect Dis. 2012 May 15;205(10):1534-8

Spleen tyrosine kinase inhibition in the treatment of autoimmune, allergic and autoinflammatory diseases.

Spleen tyrosine kinase (Syk) is involved in the development of the adaptive immune system and has been recognized as being important in the function of additional cell types, including platelets, phagocytes, fibroblasts, and osteoclasts, and in the generation of the inflammasome. Preclinical studies presented compelling evidence that Syk inhibition may have therapeutic value in the treatment of rheumatoid arthritis and other forms of arthritis, systemic lupus erythematosus, autoimmune cytopenias, and allergic and autoinflammatory diseases. In addition, Syk inhibition may have a place in limiting tissue injury associated with organ transplant and revascularization procedures. Clinical trials have documented exciting success in the treatment of patients with rheumatoid arthritis, autoimmune cytopenias, and allergic rhinitis. While the extent and severity of side effects appear to be limited so far, larger studies will unravel the risk involved with the clinical benefit.

Arthritis Res Ther. 2010;12(6):222

Future immunosuppression in organ transplantation: treating the innate immune system of the deceased donor—start tomorrow.

This article, based in part on an invited talk at the Annual International Conference of Saudi Society of Nephrology & Transplantation in 2012, reviews current notions of the emerging field of innate alloimmunity by highlighting novel thoughts regarding future immunosuppressive therapy in organ transplantation. In light of new insights into the mechanisms of innate immunity on one hand and the essential role of regulatory T cells in controlling alloimmune responses on the other hand, potential clinical tools to generate tolerogenic dendritic cells are explored. These cells have been shown to promote induction of regulatory T cells that possess the potential to prevent acute and chronic allograft rejection. Experimental findings from both research areas are discussed in support of the notion that presentation of alloantigens under subimmunogenic noninflammatory conditions, achieved by vigorous inhibition of oxidative injury-induced allograft inflammation (known to occur in both the deceased donor and the recipient during allograft reperfusion), may lead to the induction of tolerogenic dendritic cell-mediated regulatory T cells, thereby offering a realistic opportunity to induce allotolerance in transplant recipients. However, before planning clinical trials in recipients, the start of such a novel therapeutic strategy to prevent allograft rejection could consist of designing and performing a quadruple drug treatment of deceased (brain-dead) donors aimed at generating donor-derived tolerogenic dendritic cells. The combination use of (1) an antioxidant, (2) a complement-inhibiting agent, (3) an IL-1β inhibitor, and (4) a polyclonal antilymphocytic preparation is recommended as the preferred choice of such a donor treatment. If proven successful in organ donors, similar therapeutic modalities should subsequently be considered to apply to the recipient during allograft reperfusion under strict study conditions.

Exp Clin Transplant. 2012 Jun;10(3):195-208

The evolving role of mTOR inhibition in transplantation tolerance.

The mammalian target of rapamycin (mTOR) plays a key role in the immune response. mTOR inhibitors suppress T cell activation and proliferation and are effective immunosuppressants. Today there is growing interest in their potential role in inducing tolerance after transplantation. mTOR inhibitors induce anergy in naïve T cells, promote the expansion of regulatory T cells, and inhibit the maturation of dendritic cells, thus promoting immunologic tolerance. Here we review the mechanisms by which mTOR inhibitors promote tolerance. We discuss the clinical relevance of these mechanisms and suggest how they might be used in the design of future protocols to induce tolerance.

J Am Soc Nephrol. 2011 Mar;22(3):408-15

Investigating the role of immunomodulation for colon cancer prevention: results of an in vivo dose escalation trial of levamisole with immunologic endpoints.

The potential role of immunomodulatory agents for colon cancer prevention has not been studied systematically. Levamisole (LMS), which is immunostimulatory, is synergistic with 5-fluorouracil in the adjuvant therapy of patients with stage III colon cancer. This pilot study was initiated to explore the potential utility of LMS as a colon cancer prevention agent and to define the minimum dose at which it retains potentially beneficial effects on the immune system. Normal volunteers were treated over 3 days with LMS at four different dose levels and were monitored for toxicity and immunologic changes. Immunologic endpoints included lymphocyte antigen expression, serum cytokine levels, and two new ex vivo assays that defined LMS’s activity in modulating T-helper-1 (Th1) cytokine production. In addition, in vitro dose-response analyses of LMS’s effects on cellular immune function were performed. LMS was tolerated without toxicity at low dosages only. Significant increases (P < .0001) in the proportion of peripheral blood mononuclear cells expressing the natural killer antigen CD16 were noted at all dose levels. LMS did not alter serum cytokine levels and only minimally affected Th1 cellular immune function. In vitro analysis demonstrated that LMS is synergistic with interleukin 12 in the induction of a Th1 cytokine response at very low concentrations (1microM). This study suggests that short-term LMS is only minimally immunomodulatory but that immune activity is equivalent at low dosages where the medication is better tolerated. Additional, longer-term, studies of low-dose LMS as a potential colon cancer chemopreventive agent should be considered.

Cancer Detect Prev. 2001;25(2):183-91

Systemic therapies for psoriasis: methotrexate, retinoids, and cyclosporine.

Despite the current use and ongoing development of the biological therapies ‘traditional’ systemic agents will continue to form a key part of the therapeutic armamentarium for patients with severe psoriasis. Long-term maintenance therapy with retinoids and methotrexate is cost-effective and, for many patients with psoriasis, life changing. Regular monitoring is required for both treatments, particularly methotrexate to prevent significant bone marrow suppression and hepatotoxicity. Ideally, cyclosporine should be used for short courses of 3 to 4 months duration, within which it provides excellent disease control. Close assessment of renal function and blood pressure is essential.

Clin Dermatol. 2008 Sep-Oct;26(5):438-47

Systems biology approaches and tools for analysis of interactomes and multi-target drugs.

Systems biology is essentially a proteomic and epigenetic exercise because the relatively condensed information of genomes unfolds on the level of proteins. The flexibility of cellular architectures is not only mediated by a dazzling number of proteinaceous species but moreover by the kinetics of their molecular changes: The time scales of posttranslational modifications range from milliseconds to years. The genetic framework of an organism only provides the blue print of protein embodiments which are constantly shaped by external input. Indeed, posttranslational modifications of proteins represent the scope and velocity of these inputs and fulfil the requirements of integration of external spatiotemporal signal transduction inside an organism. The optimization of biochemical networks for this type of information processing and storage results in chemically extremely fine tuned molecular entities. The huge dynamic range of concentrations, the chemical diversity and the necessity of synchronisation of complex protein expression patterns pose the major challenge of systemic analysis of biological models. One further message is that many of the key reactions in living systems are essentially based on interactions of moderate affinities and moderate selectivities. This principle is responsible for the enormous flexibility and redundancy of cellular circuitries. In complex disorders such as cancer or neurodegenerative diseases, which initially appear to be rooted in relatively subtle dysfunctions of multimodal physiologic pathways, drug discovery programs based on the concept of high affinity/high specificity compounds (“one-target, one-disease”), which has been dominating the pharmaceutical industry for a long time, increasingly turn out to be unsuccessful. Despite improvements in rational drug design and high throughput screening methods, the number of novel, single-target drugs fell much behind expectations during the past decade, and the treatment of “complex diseases” remains a most pressing medical need. Currently, a change of paradigm can be observed with regard to a new interest in agents that modulate multiple targets simultaneously, essentially “dirty drugs.” Targeting cellular function as a system rather than on the level of the single target, significantly increases the size of the drugable proteome and is expected to introduce novel classes of multi-target drugs with fewer adverse effects and toxicity. Multiple target approaches have recently been used to design medications against atherosclerosis, cancer, depression, psychosis and neurodegenerative diseases. A focussed approach towards “systemic” drugs will certainly require the development of novel computational and mathematical concepts for appropriate modelling of complex data. But the key is the extraction of relevant molecular information from biological systems by implementing rigid statistical procedures to differential proteomic analytics.

Methods Mol Biol. 2010;662:29-58

Modulation of cytokine expression by traditional medicines: a review of herbal immunomodulators.

Modulation of cytokine secretion may offer novel approaches in the treatment of a variety of diseases. One strategy in the modulation of cytokine expression may be through the use of herbal medicines. A class of herbal medicines, known as immunomodulators, alters the activity of immune function through the dynamic regulation of informational molecules such as cytokines. This may offer an explanation of the effects of herbs on the immune system and other tissues. For this informal review, the authors surveyed the primary literature on medicinal plants and their effects on cytokine expression, taking special care to analyze research that utilized the multi-component extracts equivalent to or similar to what are used in traditional medicine, clinical phytotherapy, or in the marketplace. METHODOLOGY: MEDLINE, EBSCO, and BIOSIS were used to identify research on botanical medicines, in whole or standardized form, that act on cytokine activity through different models, i.e., in vivo (human and animal), ex vivo, or in vitro. RESULTS: Many medicinal plant extracts had effects on at least one cytokine. The most frequently studied cytokines were IL-1, IL-6, TNF, and IFN. Acalypha wilkesiana, Acanthopanax gracilistylus, Allium sativum, Ananus comosus, Cissampelos sympodialis, Coriolus versicolor, Curcuma longa, Echinacea purpurea, Grifola frondosa, Harpagophytum procumbens, Panax ginseng, Polygala tenuifolia, Poria cocos, Silybum marianum, Smilax glabra, Tinospora cordifolia, Uncaria tomentosa, and Withania somnifera demonstrate modulation of multiple cytokines. CONCLUSION: The in vitro and in vivo research demonstrates that the reviewed botanical medicines modulate the secretion of multiple cytokines. The reported therapeutic success of these plants by traditional cultures and modern clinicians may be partially due to their effects on cytokines. Phytotherapy offers a potential therapeutic modality for the treatment of many differing conditions involving cytokines. Given the activity demonstrated by many of the reviewed herbal medicines and the increasing awareness of the broad-spectrum effects of cytokines on autoimmune conditions and chronic degenerative processes, further study of phytotherapy for cytokine-related diseases and syndromes is warranted

Altern Med Rev. 2006 Jun;11(2):128-50

Immunomodulatory active compounds from Tinospora cordifolia.

ETHNOPHARMACOLOGICAL RELEVANCE: Tinospora cordifolia mentioned as “Rasayana” is extensively used in various herbal preparations for the treatment of different ailments for its general tonic, antiperiodic, antispasmodic, antiinflammatory, antiarthritic, antiallergic and antidiabetic properties. It is extensively used in Ayurveda due to its potential in improving the immune system and the body resistance against infections. AIM OF THE STUDY:  The aim of the study was to isolate and characterise the immunomodulatory active compounds of Tinospora cordifolia. MATERIALS AND METHODS: The immunomodulatory activity of different extracts, fractions and isolated compounds in relation to phagocytosis and reactive oxygen species production in human neutrophil cells have been investigated using the PMN phagocytic function studies, NBT, NO and chemiluminescence assay. RESULTS: The results obtained indicate that ethyl acetate, water fractions and hot water extract exhibited significant immunomodulatory activity with an increase in percentage phagocyctosis. Chromatographic purification of these fraction led to the isolation of a mixture of two compounds 2, 3 isolated for the first time from natural source and five known compounds 1, 4-7 which were characterized as 11-hydroxymustakone (2), N-methyl-2-pyrrolidone (3), N-formylannonain (1), cordifolioside A (4), magnoflorine (5), tinocordiside (6), syringin (7) by nuclear magnetic resonance (NMR) and mass spectrometry (MS) and comparing the spectral data with reported one. Cordifolioside A and syringin have been reported to possess immunomodulatory activity. Other five compounds showed significant enhancement in phagocytic activity and increase in nitric oxide and reactive oxygen species generation at concentration 0.1-2.5 µg/ml. CONCLUSIONS: Seven immunomodulatory active compounds belonging to different classes have been isolated and characterised indicating that the immunomodulatory activity of Tinospora cordifolia may be attributed to the synergistic effect of group of compounds.

J Ethnopharmacol. 2012 Jun 14;141(3):918-26

Comparative studies of the immunomodulatory activity of Tinospora cordifolia and Tinospora sinensis.

The water and ethanol extracts of stems of Tinospora cordifolia and T. sinensis inhibit immunosuppression produced by cyclophosphamide. Ethanol extracts of stems of both the plants inhibit cyclophosphamide-induced anemia. The water extract of T. sinensis is found to be more potent than the other extracts.

Fitoterapia. 2000 Jun;71(3):254-7

Tinospora cordifolia (Willd.) Hook. f. and Thoms. (Guduchi) - validation of the Ayurvedic pharmacology through experimental and clinical studies.

T. cordifolia (Guduchi) is a large, glabrous, perennial, deciduous, climbing shrub of weak and fleshy stem found throughout India. It is a widely used plant in folk and Ayurvedic systems of medicine. The chemical constituents reported from this shrub belong to different classes, such as alkaloids, diterpenoid lactones, glycosides, steroids, sesquiterpenoid, phenolics, aliphatic compounds and polysaccharides. Various properties of T. cordifolia, described in ancient texts of Ayurveda, like Rasayana, Sangrahi, Balya, Agnideepana, Tridoshshamaka, Dahnashaka, Mehnashaka, Kasa-swasahara, Pandunashaka, Kamla-Kushta-Vataraktanashaka, Jwarhara, Krimihara, Prameha, Arshnashaka, Kricch-Hridroganashak, etc., are acquiring scientific validity through modern research adopting “reverse pharmacological” approach. Potential medicinal properties reported by scientific research include anti-diabetic, antipyretic, antispasmodic, anti-inflammatory, anti-arthritic, antioxidant, anti-allergic, anti-stress, anti-leprotic, antimalarial, hepato-protective, immuno-modulatory and anti-neoplastic activities. This review brings together various properties and medicinal uses of T. cordifolia described in Ayurveda, along with phytochemical and pharmacological reports.

Int J Ayurveda Res. 2010 Apr;1(2):112-21

Effect of Tinospora cordifolia on blood glucose and total lipid levels of normal and alloxan-diabetic rabbits.

The aqueous, alcoholic, and chloroform extracts of the leaves of Tinospora cordifolia were administered in doses of 50, 100, 150 and 200 mg/kg body weight to normal and alloxan-diabetic rabbits. The blood glucose and total lipid levels were estimated before and 2, 4, 6, and 8 hours after administration of the extract. The extract exerted a significant (P less than 0.5) hypoglycaemic effect in normal as well as in alloxan-treated rabbits. The extracts, however, had no significant (P greater than 0.05) effect on total lipid levels in normal as well as in alloxan-treated diabetic rabbits. The doses used did not show acute toxicity or result in behavioural changes. From this study, it may be concluded that extracts of the leaves of Tinospora cordifolia have an insulin-like action and can significantly reduce the blood glucose but not the total lipid levels in normal rabbits and in alloxan-induced diabetic rabbits.

Planta Med. 1992 Apr;58(2):131-6

Cardioprotective activity of alcoholic extract of Tinospora cordifolia in ischemia-reperfusion induced myocardial infarction in rats.

It has been suggested that the beneficial effects of reperfusing the myocardium might be in part reversed by the occurrence of reperfusion injury. Oxidative stress was suggested to be implicating in the pathogenesis of ischemia-reperfusion (I/R) injury. Many antioxidative plants were shown to be cardioprotective in experimental models of myocardial ischemia-reperfusion (I/R) injury. The present study was designed to investigate the effects of pretreatment with alcoholic extract of Tinospora cordifolia in an in vivo rat model. The model adopted was that of surgically-induced myocardial ischemia, performed by means of left anterior descending coronary artery occlusion (LAD) for 30 min followed by reperfusion for another 4 h. Infarct size was measured by using the staining agent TTC (2,3,5-triphenyl tetrazolium chloride). Lipid peroxide levels in serum and in heart tissue were estimated spectrophotometrically by the methods developed by Yagi and Ohkawa et al. respectively. A lead II electrocardiogram was monitored at various intervals throughout the experiment. A dose dependent reduction in infarct size and in lipid peroxide levels of serum and heart tissue were observed with the prior treatment of T. cordifolia with various doses for 7 d compared to control animals. Hence, the present study suggests the cardioprotective activity of T. cordifolia in limiting ischemia-reperfusion induced myocardial infarction.

Biol Pharm Bull. 2005 Dec;28(12):2319-22

Immunotherapy with Tinospora cordifolia: a new lead in the management of obstructive jaundice.

OBJECTIVE: Immunosuppre-ssion associated with deranged hepatic function and sepsis results in poor surgical outcome in extrahepatic obstructive jaundice. The effect of an ayurvedic agent, Tinospora cordifolia (TC), which has been shown to have hepatoprotective and immunomodulatory properties in experimental studies, on surgical outcome in patients with malignant obstructive jaundice was evaluated.  METHODS: Thirty patients were randomly divided into two groups, matched with respect to clinical features, impairment of hepatic function (as judged by liver function tests including antipyrine elimination) and immunosuppression (phagocytic and killing capacities of neutrophils). Group I received conventional management, ie vitamin K, antibiotics and biliary drainage; Group II received Tinospora cordifolia (16 mg/kg/day orally) in addition, during the period of biliary drainage. RESULTS:  Hepatic function remained comparable in the two groups after drainage. However, the phagocytic and killing capacities of neutrophils normalized only in patients receiving Tinospora cordifolia (28.2 +/- 5.5% and 29.47 +/- 6.5% respectively). Post-drainage bactobilia was observed in 8 patients in Group I and 7 in Group II, but clinical evidence of septicemia was observed in 50% of patients in Group I as against none in Group II (p < 0.05). Post-operative survival in Groups I and II was 40% and 92.4% respectively (p < 0.01). CONCLUSION: Tinospora cordifolia appears to improve surgical outcome by strengthening host defenses.

Indian J Gastroenterol. 1993 Jan;12(1):5-8

Immunomodulatory role of Tinospora cordifolia as an adjuvant in surgical treatment of diabetic foot ulcers: a prospective randomized controlled study.

BACKGROUND: Chronic diabetic patients with wounds have deficient growth factors and impaired local and systemic cellular immunity. Treatment with growth factors is expensive with risk of infection transmission and these factors may not achieve optimum wound concentration. We evaluated the role of generalized immunomodulation in diabetic ulcers by using Tinospora cordifolia as an adjuvant therapy and studied its influence on parameters/determinants of healing, on bacterial eradication and on polymorphonuclear phagocytosis. MATERIALS AND METHODS: A prospective double-blind randomized controlled study lasting for over 18 months in 50 patients. The ulcer was classified by wound morphology and severity with Wound Severity Score (Pecoraro-Reiber system). Mean ulcer area, depth and perimeter were measured and swabs taken for culture. Blood was collected to assess polymorphonuclear % phagocytosis (PMN function by Lehrer-Cline C. albicans method). Medical therapy, glycemic control, debridement, wound care were optimized. At 4 weeks, parameters were reassessed. PMN function was reviewed at 3 months. RESULTS AND ANALYSIS: Forty-five patients completed the trial: study group - 23 (M:F = 17:1; mean age = 56.3 years; mean ulcer duration = 21.1 days); control group 22 (M:F = 19:3; mean age = 56.3 years; mean ulcer duration = 30.4 days). Net improvement was seen in 17 patients (73.9%) in the study group; while in the control group, in 13 patients (59.1%); P = 0.292. Specific parameters included rate of change of ulcer area - cm(2) /day (study - 0.15; control - 0.07; P = 0.145); rate of change of ulcer perimeter - mm/day (study - 0.09; control = - 0.07; P = 0.089); change of depth - mm (study - 2.2; control - 1.4; P = 0.096); change of wound score (study - 14.4; control - 10.6; P = 0.149); total number of debridements (study - 1.9; control - 2.5; P = 0.03) and change in % phagocytosis (study - 3.9; control - 2.3; P = 0.048). CONCLUSION: Diabetic patients with foot ulcers on T. cordifolia as an adjuvant therapy showed significantly better final outcome with improvement in wound healing. Reduced debridements and improved phagocytosis were statistically significant, indicating beneficial effects of immunomodulation for ulcer healing.

Indian J Med Sci. 2007 Jun;61(6):347-55

Subcutaneous immunotherapy for allergic rhinitis: an evidence based review of the recent literature with recommendations.

BACKGROUND: Allergic rhinitis is a common allergic disease with increasing prevalence in Western Societies. Medical therapy is first line treatment, and is aimed at reducing symptoms of immunoglobulin E (IgE)-mediated inflammation of the nasal passages. In patients with disease refractory to medical therapy, subcutaneous immunotherapy is an option. The aim of this study is to update a recent Cochrane review with available level 1 evidence for seasonal and perennial allergic rhinitis. METHODS: A systematic review of the literature was performed from 2006 to 2011 and compared with data from a 2007 Cochrane review on immunotherapy for seasonal allergic rhinitis. We included all studies of level 1 evidence. All forms of single extract immunotherapy were considered. Studies with primary asthma related end-points were excluded. Primary end-points were instruments of clinical efficacy (ie, symptom-medication scores) and adverse events. RESULTS: We retrieved 12 level 1 studies for review. In total, 1,512 patients were randomized into treatment groups, alternative study groups (alternative duration of therapy or sublingual immunotherapy [SLIT]), or placebo. Efficacy was evaluated based on reported symptom and/or medication score, validated quality of life instruments, immunological assays, challenge testing, and adverse events. CONCLUSION: Subcutaneous immunotherapy improves symptom and/or medication scores and validated quality of life measures. In addition, associated changes in surrogate markers of immunologic protection are observed. Subcutaneous immunotherapy is safe when administered to carefully selected patients and in settings capable of responding to systemic reactions. Subcutaneous immunotherapy is recommended for patients with seasonal or perennial allergic rhinitis not responsive to conservative medical therapy, and whose symptoms significantly affect quality of life.

Int Forum Allergy Rhinol. 2013 Jan 11

Th1/Th2 balance: the hypothesis, its limitations, and implications for health and disease.

One theory of immune regulation involves homeostasis between T-helper 1 (Th1) and T-helper 2 (Th2) activity. The Th1/Th2 hypothesis arose from 1986 research suggesting mouse T-helper cells expressed differing cytokine patterns. This hypothesis was adapted to human immunity, with Th1- and Th2-helper cells directing different immune response pathways. Th1 cells drive the type-1 pathway (“cellular immunity”) to fight viruses and other intracellular pathogens, eliminate cancerous cells, and stimulate delayed-type hypersensitivity (DTH) skin reactions. Th2 cells drive the type-2 pathway (“humoral immunity”) and up-regulate antibody production to fight extracellular organisms; type 2 dominance is credited with tolerance of xenografts and of the fetus during pregnancy. Overactivation of either pattern can cause disease, and either pathway can down-regulate the other. But the hypothesis has major inconsistencies; human cytokine activities rarely fall into exclusive pro-Th1 or -Th2 patterns. The non-helper regulatory T cells, or the antigen-presenting cells (APC), likely influence immunity in a manner comparable to Th1 and Th2 cells. Many diseases previously classified as Th1 or Th2 dominant fail to meet the set criteria. Experimentally, Th1 polarization is readily transformed to Th2 dominance through depletion of intracellular glutathione, and vice versa. Mercury depletes glutathione and polarizes toward Th2 dominance. Several nutrients and hormones measurably influence Th1/Th2 balance, including plant sterols/sterolins, melatonin, probiotics, progesterone, and the minerals selenium and zinc. The long-chain omega-3 fatty acids EPA (eicosapentaenoic acid) and DHA (docosahexaenoic acid) significantly benefit diverse inflammatory and autoimmune conditions without any specific Th1/Th2 effect. Th1/Th2-based immunotherapies, e.g., T-cell receptor (TCR) peptides and interleukin-4 (IL-4) injections, have produced mixed results to date.

Altern Med Rev. 2003 Aug;8(3):223-46

Cancer and immune response: old and new evidence for future challenges.

Cancer may occur as a result of abnormal host immune system tolerance. Recent studies have confirmed the occurrence of spontaneous and induced antitumor immune responses expressed as the presence of tumor-infiltrating T cells in the tumor microenvironment in some cancer models. This finding has been recognized as a good prognostic factor in several types of tumors. Some chemotherapy agents, such as anthracyclines and gemcitabine, are effective boosters of the immune response through tumor-specific antigen overexpression after apoptotic tumor cell destruction. Other strategies, such as GM-CSF or interleukin-2, are pursued to increase immune cell availability in the tumor vicinity, and thus improve both antigen presentation and T-cell activation and proliferation. In addition, cytotoxic T lymphocyte antigen 4-blocking monoclonal antibodies enhance immune activity by prolonging T-cell activation. Strategies to stimulate the dormant immune system against tumors are varied and warrant further investigation of their applications to cancer therapy in the future.

Oncologist. 2008 Dec;13(12):1246-54

Efficacy of Tinospora cordifolia in allergic rhinitis.

The efficacy of Tinospora cordifolia (TC) extract in patients of allergic rhinitis was assessed in a randomized double blind placebo controlled trial. Seventy-five patients were randomly given either TC or placebo for 8 weeks. They were clinically examined and Hb %, TLC, DLC and nasal smear was done. At the end of trial baseline investigations were repeated, drug decoded and results analyzed. With TC treatment 100% relief was reported from sneezing in 83% patients, in 69% from nasal discharge, in 61% from nasal obstruction and in 71% from nasal pruritus. In placebo group, there was no relief in 79% from sneezing, in 84.8% from nasal discharge, in 83% from nasal obstruction, and in 88% from nasal pruritus. The difference between TC and placebo groups was highly significant. TLC increased in 69% patients in drug treated group and in only 11% with placebo. After TC, eosinophil and neutrophil count decreased and goblet cells were absent in nasal smear. After placebo, decrease in eosinophil and neutrophil count was marginal and goblet cells were present. TC significantly decreased all symptoms of allergic rhinitis. Nasal smear cytology and leukocyte count correlated with clinical findings. TC was well tolerated.

J Ethnopharmacol. 2005 Jan 15;96(3):445-9