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TRANSFER FACTORS

 

Transfer Factor – Current status and future prospects

H. Sherwood Lawrence and William Borkowsky

Infectious Disease and Immunology Division, Departments of Medicine and Pediatrics, New York University Medical Center, 550 First Avenue, New York, NY 10016, USA

We have detected new clues to the composition and function of “Transfer Factor” using the direct Leucocyte Migration Inhibition (LMI) test as an in vitro assay of Dialysates of Leucocyte Extracts (DLE). This approach has revealed two opposing antigen-specific activities to be present in the same >3500 <12,000 DA dialysis fraction – one activity is possessed of Inducer/Helper function (Inducer Factor). The opposing activity is possessed of Suppressor function (Suppressor Factor).

When non-immune leucocyte populations are cultured with Inducer Factor they acquire the capacity to respond to specific antigen and inhibition of migration occurs. This conversion to reactivity is antigen-specific and dose-dependent. When immune leucocyte populations are cultured with Suppressor Factor their response to specific antigen is blocked and Inhibition of Migration is prevented.

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AIDS and Transfer Factor: Myths, Certainties and Realities.
Dimitri Viza

Laboratoire d’Immunobiologie, Faculté de Médecine des Saints-Pères, Paris.

At the end of the 20th century, the triumph of biology is as indisputable as that of physics was at the end of the 19th century, and so is the might of the inductive thought. Virtually, all diseases have been seemingly conquered and HIV, the cause of AIDS, has been fully described ten years after the onset of the epidemic. However, the triumph of biological science is far from being complete. The toll of several diseases, such as cancer, continues to rise and the pathogenesis of AIDS remains elusive.

In the realm of inductive science, the dominant paradigm can seldom be challenged in a frontal attack, especially when it is apparently successful, and only what Kuhn calls “scientific revolutions” can overthrow it. Thus, it is hardly surprising that the concept of transfer factor is considered with contempt, and the existence of the moiety improbable: over forty years after the introduction of the concept, not only its molecular structure remains unknown, but also its putative mode of action contravenes dogmas of both immunology and molecular biology. And when facts challenge established dogmas, be in religion, philosophy or science, they must be suppressed. Thus, results of heterodox research become henceforth nisi, i.e. valid unless cause is shown for rescinding them, because they challenge the prevalent paradigm.

However, the triumph of biological science is far from being complete. The toll of several diseases continues to rise and the pathogenesis of AIDS, twelve years after the identification of the virus, remains by and large mysterious, while TF has been used successfully for treating viral infections including AIDS, as reported elsewhere. But when observations pertain to lethal disorders, their suppression in the name of dogmas may become criminal. Because of the failure of medical science to manage the AIDS pandemic, transfer factor, which has been successfully used for treating or preventing viral infections, may today overcome a priori prejudice and rejection more swiftly. In science, as in life, certainties always end up by dying, and Copernicus’ vision by replacing that of Ptolemy.

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Preliminary observations using HIV-specific transfer factor in AIDS.

Giancarlo Pizza(1), Francesco Chiodo(2), Vincenzo Colangeli(2), Francesco Gritti(3), Enzo Raise(3), Hugh H. Fudenberg(4), Caterina De Vinci(1) & Dimitri Viza(5).

(1)Immunodiagnosis and Immunotherapy Unit, 1st Division of Urology, Ospedale S. Orsola-Malpighi, Bologna, Italy; (2)Institute of Infectious Diseases, Ospedale S. Orsola-Malpighi, Bologna, Italy; (3)Dept. of Infectious Diseases and Immunopathology Unit, Ospedale Maggiore, Bologna, Italy; (4)Neuro ImmunoTherapeutics Found. Spartanburg, SC, USA; (5)Laboratoire d’Immunobiologie, URA 1294 CNRS, Faculté de Médecine des Saints-Pères, Paris, France.

Twenty five HIV-1-infected patients, at various stages (CDC II, III and IV) were treated orally with HIV-1-specific transfer factor (TF) for periods varying from 60 to 1870 days. All patients were receiving antiviral treatments in association with TF. The number of lymphocytes, CD4 and CD8 subsets were followed and showed no statistically significant variations. In 11/25 patients the number of lymphocytes increased, whilst in 11/25 decreased; similarly an increase of the CD4 lymphocytes was observed in 11/25 patients and of the CD8 lymphocytes in 15/25. Clinical improvement or a stabilized clinical condition was noticed in 20/25 patients, whilst a deterioration was seen in 5/25. In 12/14 anergic patients, daily TF administration restored delayed type hypersensitivity to recall antigens within 60 days. These preliminary observations suggest that oral HIV-specific TF administration, in association with antiviral drugs, is well tolerated and seems beneficial to AIDS patients, thus warranting further investigation.

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ACTIVITIES AND CHARACTERISTICS OF TRANSFER FACTORS

Charles H. Kirkpatrick

Innovative Therapeutics, Inc., Denver, CO, USA

This report summarizes three components of our transfer factor research program. Several clinical studies have used oral administration of transfer factor containing materials. Sceptics have rejected these findings by assuming that the acidic and enzymatic environment of the gastrointestinal tract would destroy the factors. To further examine this issue, we have conducted dose-response studies of the delayed-type hypersensitivity reaction in mice that were given transfer factor either by gavage or subcutaneously. There were no difference in the responses that were related to the route of administration. We conclude that oral route of administration is efficacious and should be used when possible.

We have also studied the effects of transfer factors on immune responses by recipients. The details of this research are presented in the paper by Dr. Alvarez-Thull. Briefly, the study showed that recipients of a specific transfer factor responded to the antigen for which the factor was specific by secreting gamma-IFN, but no other cytokines.

The structures of transfer factor molecules are unknown. We have developed a process for isolating transfer factors in pure form and we have obtained preliminary data concerning amino acid sequences. Our goal is to obtain the complete primary structure of several transfer factor molecules.

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In vitro studies during long term oral administration of specific transfer factor.

Giancarlo Pizza(1), Caterina De Vinci(1), Vittorio Fornarola(1), Aldopaolo Palareti(2), Olavio Baricordi(3) & Dimitri Viza(4).

(1)Immunodiagnosis and Immunotherapy Unit 1st-Division of Urology, S. Orsola Malpighi Hospital, Bologna, Italy; (2)Department of Statistics, University of Bologna, Bologna, Italy;(3)Department of Genetics, University of Ferrara, Ferrara Italy; (4)URA 1294 CNRS, Laboratoire d’Immunobiologie, Faculté de Médecine des Saints-Pères, Paris, France.

153 patients suffering from recurrent pathologies, i.e. viral infections (keratitis, keratouveitis, genital and labial herpes) uveitis, cystitis, and candidiasis were treated with in vitro produced transfer factor (TF) specific for HSV-1/2, CMV and Candida albicans. The cell-mediated immunity of seropositive patients to HSV-1/2 and/or CMV viruses was assessed using the leucocyte migration inhibition test (LMT) and lymphocyte stimulation test (LST) in presence of the corresponding antigens, and the frequency of positive tests before, during and after TF administration was studied. The data were stratified per type of test, antigen and the recipients’ pathology, and statistically evaluated. For the LMT, a total of 960 tests were carried out for each antigen dilution, 3 different antigen dilutions were used per test. 240/960 tests (25.4%) were found positive during non-treatment or treatment with unspecific TF, whereas 147/346 tests (42.5%) were found positive when the antigen corresponding to the specificity of the TF administered to the patient was used (P<0.001). When the data were stratified following pathology, a significant increased incidence of positive tests during specific treatment was also observed (0.0001<P<0.05). In the LST (1174 tests), a significant increase of thymidine uptake was observed in the absence of antigen (control cultures), during treatment with both specific and unspecific TF, but also in the presence of antigen and/or autologous serum during specific TF administration (P<0.0001).

TF administration also significantly increased the soluble HLA class I antigens level, in 40 patients studied to this effect.

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The effect of DLE fractions on GM-progenitors of haematopoietic stem cells in vitro.

Barnet K., Vacek A., Cech K. & Pekerek J.

SEVAC a.s., Praha, Czech Republic.

Dialysable leucocyte extracts (DLE) prepared from buffy coats of human blood, potentiates the effect of Colony-stimulating factor (CSF) on the growth of granulocyte-macrophage colony forming cell (GM-CFC) colonies in vitro. This relative increase of the number of colonies is apparent when diluted CSF (present in lung conditioning medium) as a control, and DLE, in a wide range of concentrations are added to the culture of mouse bone marrow cells. Fractionation of DLE on Amicon membranes revealed that the activity resides in molecules of 0-5kD. Molecules 5-10kD have no potentiating effect. DLE and its fractions (0-5kD, 0-1kD), except fractions 0-500 D and 5-10kD, when added undiluted i.e. at the initial concentration, exerted a suppressive effect: colonies are not formed despite the presence of CSF. In a pilot experiment, it was shown that DLE is able to stimulate colony-forming activity of earlier progenitors of erythroid cells (BFUe), under the influence of erythropoietin.

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The use of transfer factors in chronic fatigue syndrome: prospects and problems

Paul H. Levine

Viral Epidemiology Branch, National Cancer Institute, Bethesda, MD USA.

Chronic fatigue syndrome (CFS) is a heterogeneous disorder characterized by severe prolonged unexplained fatigue and a variety of associated symptoms such as arthralgias, myalgias, cognitive dysfunction, and severe sleep disturbances. Many patients initially present with an acute onset of apparent infectious origin with either an upper respiratory or gastrointestinal illness, fever, chills, tender lymphadenopathy, and malaise suggestive of a flu-like illness. In some cases, specific viral infections can be identified at the outset, particularly herpes viruses such as Epstein-Barr virus (EBV), human herpes virus-6 (HHV-6), and cytomegalovirus (CMV). Transfer factors (TF) with specific activity against these herpes viruses has been documented. With some studies suggesting that persistent viral activity may play a role in perpetuation of CFS symptoms, there appears to be a rationale for the use of TF in patients with CFS and recent reports have suggested that transfer factor may play a beneficial role in this disorder. This report focuses on the heterogeneity of CFS, the necessity for randomized coded studies, the importance of patient selection and sub-classification in clinical trials, and the need to utilize specific end-points for determining efficacy of treatment.

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Lessons from a Pilot Study of Transfer Factor in Chronic Fatigue Syndrome

Caterina De Vinci(1), Paul H. Levine(2), Giancarlo Pizza(1), Hugh H. Fudenberg(3), Perry Orens(4), Gary Pearson(2) & Dimitri Viza(5).

(1)Immunodiagnosis and Immunotherapy Unit, 1st Division of Urology Sant’Orsola-Malpighi Hospital, Bologna, Italy; (2)Georgetown University, Washington DC, USA; (3)NeuroImmuno Therapeutics Foundation, Spartanburg SC, USA; (4)Great Neck, New York, NY, USA; (5)Laboratoire d’Immunobiologie, URA 1294 CNRS, Faculté de Médecine, Paris, France.

Transfer Factor (TF) was used in a placebo controlled pilot study of 20 patients with chronic fatigue syndrome (CFS). Efficacy of the treatment was evaluated by clinical monitoring and testing for antibodies to Epstein-Barr virus (EBV) and human herpes virus-6 (HHV-6). Of the 20 patients in the placebo-controlled trial, improvement was observed in 12 patients, generally within 3-6 weeks of beginning treatment. Herpes virus serology seldom correlated with clinical response. This study provided experience with oral TF, useful in designing a larger placebo-controlled clinical trial.

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Use of anti HHV-6 transfer factor for the treatment of two patients with chronic Fatigue Syndrome (CFS). Two case reports

Darham V. Ablashi(1&2), Paul H. Levine(3), Caterina De Vinci(4), John E. Whitman Jr.(1), Giancarlo Pizza(4) & Dimitri Viza(5).

(1)Advanced Biotechnologies Inc, 9108 Guilford Road, Columbia, MD 21046 USA; (2)Department of Microbiology & Immunology, Georgetown University School of Medicine, Washington, DC 20007 USA; (3)Viral Epidemiology Branch, National Cancer Institute, Rockville, MD 20892 USA; (4)Immunotherapy Unit 1st Division of Urology, St. Orsola-Malpighi Hospital, Bologna, Italy;(5)URA 1294 CNRS Laboratoire d’lmmunobiologie, Faculté de Médecine des Saints-Pères, Paris, France.

Specific Human Herpes virus-6 (HHV-6) transfer factor (TF) preparation, administered to two chronic fatigue syndrome patients, inhibited the HHV-6 infection. Prior to treatment, both patients exhibited an activated HHV-6 infection. TF treatment significantly improved the clinical manifestations of CFS in one patient, who resumed normal duties within weeks, whereas no clinical improvement was observed in the second patient. It is concluded that, HHV-6 specific TF may be of significant value in controlling HHV-6 infection and related illnesses.

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The influence of age on transfer factor treatment of cellular immunodeficiency, chronic fatigue syndrome and/or chronic viral infections.

Ivo Hana(1), Jiri Vrubel(1), Jan Pekarek(2) & Karel Cech(2)

(1)Dept. of Immunology, Institute for Clinical and Experimental Medicine; (2)Institute of Sera and Vaccines, Prague, Czechia.

A group of 222 patients suffering from cellular immunodeficiency (CID), frequently combined with chronic fatigue syndrome (CFS) and/or chronic viral infections by Epstein-Barr virus (EBV) and/or cytomegalovirus (CMV), were immunologically investigated and treated with transfer factor (TF). The age range was 17-77 years. In order to elucidate the influence of aging on the course of the disease and on treatment, 3 subgroups were formed: 17-43 years, 44-53 years, and 54-77 years. Six injections of Immodin (commercial preparation of TF by SEVAC, Prague) were given in the course of 8 weeks. When active viral infection was present, IgG injections and vitamins were added. Immunological investigation was performed before the start of therapy, and subsequently according to need, but not later than after 3 months.

The percentages of failures to improve clinical status of patients were in the individual subgroups, respectively: 10.6%, 11.5% and 28.9%. The influence of age in increasing the low numbers of T cells was evident: 10.6%, 21.2% and 59.6%. In individuals uneffected by therapy, persistent absolute lymphocyte numbers below 1,200 cells were found in 23.1%, 54.5% and 89.3% in the oldest group. Statistical analysis by Pearson’s Chi-square test, and the test for linear trend proved that the differences among the individual age groups were significant. Neither sex, not other factors seemed to influence the results.

The results of this pilot study show that age substantially influences the failure rate of CID treatment using TF. In older people, it is easier to improve the clinical condition than CID: this may be related to the diminished number of lymphocytes, however, a placebo effect cannot be totally excluded.

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Rationale and clinical results of using leucocyte-derived immunosupportive therapies in HIV disease

A.A. Gottlieb, R.C. Sizemore, M.S. Gottlieb & C.H. Kern

Tulane University, 1430 Tulane Avenue, New Orleans, LA 70112; Imreg, Inc. 144 Elk Place Suite 1400, New Orleans, LA 70112

Leucocyte dialysates contain a number of substances which exert important effects on human cell-mediated immunity. In this report, we describe several properties of a designated subfraction, IMREG(R)-1, which is obtained by a second dialysis against a membrane having a 3500 m.w. cutoff. These include the ability to augment and accelerate reactions of delayed hypersensitivity against antigens to which the text subject has been previously sensitized, and the ability to enhance the expression in vitro on CD4 lymphocytes of the p55 subunit of the receptor for Interleukin-2. We also report our observation that in a patient with advanced HIV disease whose lymphocytes had lost there ability to properly express the IL-2 receptor, treatment with IMREG(R)-1 over a period of months restored the expression of the IL-2 receptor on the patient’s CD4+ lymphocytes towards normal.

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Preliminary results in HIV-1-infected patients treated with transfer factor (TF) and Zidovudine (ZDV)

Enzo Raise(1), Luca Guerra(1), Dimitri Viza(2), Giancarlo Pizza(3), Caterina De Vinci(3), Maria Luisa Schiattone(1), Leonarda Rocaccio(1), Maria Cicognani(1) & Francesco Gritti(1).

(1)Dept. of Infectious Diseases and Immunopathology Unit, Clinical Pathology, Maggiore Hospital, Bologna, Italy; (2)Laboratoire d’Immunobiologie, Faculté de Médecine des Saints-Pères, Paris, France; (3)Immunotherapy Unit, 1st Division of Urology, Malpighi Hospital, Bologna, Italy.

The efficiency of HIV-1 specific transfer factor (TF) administration, combined with Zidovudine (ZDV), in asymptomatic persistent generalised lymphadenopaty, or AIDS related complex (ARC) patients was evaluated.

Twenty patients were randomly assigned to receive only ZDV (1st group) or ZDV together with HIV-1-specific TF (2nd group). HIV-1-specific TF was administered orally at 2 x 107 cell equivalent daily for 15 days, and thereafter once a week for up to 6 months. There were no significant differences between the two groups in clinical evolution, red blood cells, haemoglobin, lymphocytes, CD20 subset, transaminases, a-2-microglobulin, p24 antigen. White blood cells, CD8 lymphocytes as well as IL-2 levels increased in the second group, while the CD4 subset increased in the first group. The combination treatment with ZDV and TF appeared to be safe and well tolerated. Furthermore, levels of serum cytokines were investigated in 10 patients (8 asymptomatic and 2 ARC) treated with ZDV, and compared with 5 patients of the 2nd group (3 asymptomatic and 2 ARC) treated with ZDV plus HIV-1-specific TF. Peripheral lymphocytes, CD4, CD8 subsets, IL-2, TNFa, IL-6, p24 antigen, IL-2 soluble lymphocyte receptors (sR), CD4sR, CD8sR and a-2-microglobulin were evaluated at the baseline and at the 3rd month. The CD4 subset was not significantly different in the two groups, whilst IL-2 increased in the 2nd group, receiving ZDV plus TF, suggesting an activation of the Th1 secretion pattern.

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Inhibition of in vitro HIV infection by dialysable leucocyte extracts.

C Fernandez-Ortega(1), M Dubed(2), O Ruibal(2), OL Vilarrubia(2), JC Menéndez de San Pedro(2), L Navea(2), M Ojeda1 & MJ Arana1.

(1)Department of Cellular Biology, Center for Biological Research and Center for Genetic Engineering and Biotechnology, Havana, Cuba. (2)Laboratory for AIDS Research, Havana, Cuba.

Dialysable Leucocyte Extract (DLE) is a low molecular weight dialysable material of disrupted peripheral human leucocytes with widespread effects on the immune system. We described the in vitro anti-HIV activity of DLE as well as its three chromatographic fractions (Fa, Fb and Fc). To determine the levels of inhibition on HIV replication by DLE we infected MT-4 cell cultures, using the Bru viral isolate at 0.05, 0.1, 0.5 and 1 m.o.i. Previously, MT-4 cells cultures were treated with DLE or fractions at non-toxic concentrations. Reverse transcriptase (RT) activity and p24 antigen were evaluated in culture supernatants at seven days postinfection. No effect was observed when MT-4 cells were incubated with DLE for 3 h. Whereas inhibition of HIV production was observed when MT-4 cells were pre-treated for a longer periods of time. DLE inhibited p24 production and RT activity more than 50% at 0.1 m.o.i. More than 80% of inhibition was observed for all doses of DLE tested at 0.05 m.o.i. Higher viral doses (m.o.i. 0.5 and 1) were used to assess the antiviral activity of DLE fractions. Fraction Fb inhibits viral production more than 80%. Otherwise, fractions Fa and Fc did not show inhibitory effect for any viral dose used. These results indicate that DLE is able to modulate cell susceptibility to Vvral infection in vitro.

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Dialysable leucocyte extract (DLE) reduces lipopolysaccharide-induced tumour necrosis factor secretion in human leucocytes.

Miriam Ojeda Ojeda, Celia B. Fernandez Ortega & Manuel de J. Arana Rosanz.

Department of Cell Biology, Center for Biological Research, P.O. Box 6996, Havana, Cuba.

Dialysable leucocyte extract (DLE), obtained from lysed leucocytes, provide clinical effectiveness in a broad spectrum of diseases. Tumour necrosis factor (TNF) is raised in AIDS patients leading to increasing in human immunodeficiency virus (HIV) replication in vitro [1,2]. Whereas progression to AIDS in asymptomatic HIV infected individuals is retarded under treatment with DLE. In the present study we tested the DLE effect in vitro on both TNF biological activity (cytotoxicity) in L929 cells and its induction by lipopolysaccharide (LPS) in human monocytes as well as in whole blood from healthy donors. When monocytic cells were simultaneously exposed to LPS and DLE during a period of 5 1/2 hours, the induction of TNF was strongly diminished. The same inhibitory effect of DLE on TNF induction was observed when LPS was added to the culture medium prior to DLE. No significant effect of DLE on TNF-mediated cytotoxicity, even in the presence of the highest concentrations of DLE tested, was detected. DLE treatment of whole human blood regulates responses to LPS: simultaneous in vitro expose to endotoxin provokes a remarkable decrease (4- and 1.6-fold) of TNF release. In pre-incubation experiments, TNF production was largely reduced or completed abrogated. These results could, in part, explain the in vivo observed effect, when under treatment with this extract, the progression to AIDS of HIV-infected individuals was retarded. The results suggest that ‘natural’ substances like DLE may be important immunomodulators in inflammatory diseases.

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Effect of anti-herpes specific transfer factor.

J. Byston, K. Cech, J. Pekarek & J. Jilkova

Dept. of Allergology and Clinical Immunology, Faculty Hospital, Pavlova 6, Olomouc, Czech Republic

Using a blood cell separator, lymphocytes were collected from otherwise healthy convalescents suffering from herpetic infections. A specific anti-herpes dialysate (AH-DLE) was prepared from the lymphocytes, using standard procedures. Patients with recurrent herpetic infections were treated with a single dose of the dialysate, at the initial signs of herpetic infection (group A), in two doses (group B) or in three doses (group C). A total number of 37 patients (29 women, 8 men, age range 15-73 years) were treated. No improvement was observed in 7 patients (18.9%), whilst 7 patients did not manifest any exacerbation of their herpetic infection in the course of the one-year follow-up. The remaining 62.2% of the patients showed a marked improvement: decrease of the frequency and/or duration or relapses. Before AH-DLE administration, the mean number of herpes relapses in this group of patients was 12 p.a.. After therapy, the number of relapses decreased to 3.5 p.a.. No statistically significant difference was observed between groups A and B. The least favourable results were registered in group C. However, this group included 6 female patients extremely resistant to the previously therapeutic attempts, including inosiplex, non-specific DLE or acyclovir. Thus, even in this group, the therapy was successful in 50% of the patients.

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Orally administered HSV-specific transfer factor (TF) prevents genital or labial herpes relapses

Giancarlo Pizza(1), Dimitri Viza(2), Caterina De Vinci(1), Aldopaolo Palareti(3), Diego Cuzzocrea(1), Vittorio Fornarola(1) & Roberto Baricordi(4)

(1)Immunodiagnosis and Immunotherapy Unit, 1st-Division of Urology, S.Orsola-Malpighi Hospital, Bologna Italy; (2)Laboratoire d’Immunobiologie, URA 1294 CNRS, Faculté de Médecine des Saints-Pères, Paris, France; (3)Department of Statistics, University of Bologna, Italy; (4)Department of Genetics, University of Ferrara, Italy.

Forty-four patients, suffering from genital (22) and labial (22) herpes were orally treated with HSV-1/2-specific transfer factor(TF). TF was obtained by in vitro replication of a HSV-1/2-specific bovine dialysable lymphocyte extract. Treatment was administered bi-weekly the first 2 weeks, and then weekly for 6 months, most patients received 2-3 courses. The total observation period for all patients before treatment was 26660 days, with 544 relapses, and a relapse index of 61.2, whereas the cumulative observation period during and after treatment was 16945 days, with a total of 121 relapsing episodes and a cumulative RI of 21.4 (P<0.0001). Results were equally significant when the 2 groups of patients (labial and genital) were considered separately. These observations confirm previous results obtained with the bovine HSV-specific TF, and warrant further studies to establish HSV-specific TF as a choice of treatment for preventing herpes recurrences.

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Efficacy of transfer factor in treating patients with recurrent ocular herpes infections.

Renato Meduri(1), Emilio Campos(1), Lucia Scorolli(1), Caterina De Vinci(2), Giancarlo Pizza(2) & Dimitri Viza(3).

(1)Eye Physiopathology Clinical Service, University of Bologna, Italy; (2)Immunotherapy Unit, 1st Division of Urology, Ospedale O. Malpighi, Bologna, Italy; (3)Laboratoire d’Immunobiologie, URA 1294 CNRS, Faculté de Médecine des Saints-Pères, Paris, France.

Recurrent ocular herpes is an insoluble problem for the clinician. As cellular immunity plays an important role in controlling herpes relapses, and other studies have shown the efficacy of HSV-specific transfer factor (TF) for the treatment of herpes patients, an open clinical trial was undertaken in 134 patients (71 keratitis, 29 kerato-uveitis, 34 uveitis) suffering from recurrent ocular herpetic infections. The mean duration of the treatment was 358 days, and the entire follow-up period 189121 before, and 64062 days after TF treatment. The cell-mediated immune response to the viral antigens, evaluated by the lymphocyte stimulation test (LST) and the leucocyte migration test (LMT) (P<0.001), was significantly increased by the TF treatment. The total number of relapses was decreased significantly during/after TF treatment, dropping from 832 before, to 89 after treatment, whereas the cumulative relapse index (RI) dropped, during the same period, from 13.2 to 4.17 (P<0.0001). No side effects were observed. It is concluded that patients with relapsing ocular herpes can benefit from treatment with HSV-specific TF.

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Transfer Factor as an adjuvant to non-small cell lung cancer (NSCLC) therapy

Vladimiro Pilotti(1), Mario Mastrorilli(1), Giancarlo Pizza(2), Caterina De Vinci(2), Luciano Busutti(3), Aldopaolo Palareti(4), Giuseppe Gozzetti(1) & Antonino Cavallari(1).

(1)Istituto di Clinica Chirurgica II, S. Orsola-Malpighi, Bologna, Italy; (2)Modulo di Immunoterapia Divisione di Urologia I, (3)Divisione di Radioterapia, Policlinico S. Orsola-Malpighi, Bologna, Italy; (4)Dipartimento di Statistica Universita degli Studi di Bologna, Italy.

The rationale for using transfer factor (TF) in lung cancer patients is that the possibility of improving their cell-mediated immunity to tumour associated antigens (TAA) may improve their survival. From Jan 1984 to Jan 1995, 99 non- small cell lung cancer (NSCLC) resected patients were monthly treated with TF, extracted from the lymphocytes of blood bank donors. In the same period, 257 NSCLC resected patients were considered as non-treated controls. The survival rates of the TF treated group appear significantly improved both for patients in stages 3a and 3b, and patients with histological subtype “large cell carcinoma” (P<0.02). Survival of TF treated patients is also significantly higher (P<0.02) for patients with lymphnode involvement (N2 disease). The results of this study suggest that the administration of TF to NSCLC resected patients may improve survival.

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Transfer factor with anti-EBV activity as an adjuvant therapy for nasopharyngeal carcinoma: A pilot study

Umapati Prasad(1), Mohd Amin bin Jalaludin(1), Pathmanathan Rajadurai(1), Giancarlo Pizza(2), Caterina De Vinci(2), Dimitri Viza(3) & Paul H. Levine(4)

(1)University of Malaya, Kuala Lumpur, Malaysia; (2)Sant’Orsola-Malpighi Hospital, Bologna, Italy; (3)CNRS URA 1294, Laboratoire d’Immunobiologie, Faculté de Médecine des Saints-Pères, Paris, France; (4)National Institutes of Health, Bethesda, MD and George Washington University Cancer Center, Washington, DC, USA

Overall survival of nasopharyngeal carcinoma (NPC) at UICC stage IV still remains unsatisfactory even with combination chemotherapy (CT) and radio-therapy (RT). In view of the association of reactivation of Epstein-Barr virus (EBV) with the development and recurrence of NPC, immunotherapy in the form of transfer factor (TF) with specific activity against EBV (TF-B1) was suggested as an adjuvant to a combination of CT and RT in order to improve the survival. In the present study, 6 UICC Stage IV patients received TF-B1 and another 6 patients matched for disease stage were given TF prepared from peripheral blood leucocytes (TF-PBL). Results were compared with another 18 patients matched by age, sex, and stage of disease who received standard therapy without TF during the same period (C group). After a median follow up of 47.5 months, the survival for the TF-B1 group was found to be significantly better (P=3D<0.05) than the PBL and C group. While the 8 patients with distant metastasis (DM) not treated with TF-B1 (6 in the control and 2 in the PBL group) died due to progressive disease (average survival being 14.3 months), both patients with DM in the TF-B1 group had complete remission: one died of tuberculosis after surviving for 3.5 years and another is still alive, disease free, after 4.2 years. Although the series involved a small number of cases, the apparent effect of adjuvant immunotherapy in the form of TF with anti-EBV activity is of considerable interest.

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A preliminary report on the use of transfer factor for treating stage D3 hormone-unresponsive metastatic prostate cancer

Giancarlo Pizza(1), Caterina De Vinci(1), Diego Cuzzocrea(1), Domenico Menniti(1), Ernesto Aiello(1), Paolo Maver(1), Giuseppe Corrado(1), Piero Romagnoli(1), Ennio Dragoni(1), Giuseppe LoConte(1), Umberto Riolo(2), Aldopaolo Palareti(3), Paolo Zucchelli(4), Vittorio Fornarola(1) & Dimitri Viza(5).

(1)Immunodiagnosis and Immunotherapy Unit 1st-Division of Urology, (2)Pharmacy, S.Orsola-Malpighi Hospital, Bologna; (3)Department of Statistics, University of Bologna, Bologna, Italy; (4)Blood Bank Service, Maggiore Hospital, Bologna. (5)Faculté de Médecine des Saints-Pères, Paris, France.

As conventional treatments are unsuccessful, the survival rate of stage D3 prostate cancer patients is poor. Reports have suggested the existence of humoral and cell-mediated immunity (CMI) against prostate cancer tumour-associated antigens (TAA). These observations prompted us to treat stage D3 prostate cancer patients with an in vitro produced transfer factor (TF) able to transfer, in vitro and in vivo, CMI against bladder and prostate TAA. Forty four patients entered this study and received one intramuscular injection of 2-5 units of specific TF monthly. Follow-up, ranging from 1 to 9 years, showed that complete remission was achieved in 2 patients, partial remission in 6, and no progression of metastatic disease in 14. The median survival was 126 weeks, higher than the survival rates reported in the literature for patients of the same stage.

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Transfer factor in the age of molecular biology; A review.

John M. Dwyer

The Division of Clinical Immunobiology of the Prince Henry and Prince of Wales Hospitals of the University of New South Wales, Sydney, 2031, Australia

Current data suggests that the transferring of immunologically specific information by transfer factor molecules requires interaction with a cell that has been genetically programmed to be antigen reactive but at the time of interaction is unprimed. Contact with transfer factor molecules would allow a naive recipient, on a first encounter with antigen, to make a secondary rather than a primary immunological response. Transfer factor molecules for each and every antigenic determinant are thus necessary. Transfer factors made from animals or humans are capable of transferring antigen specificity across a species barrier. Even primitive species have cells from which one can make transfer factors. The molecules are, therefore, well conserved and it is reasonable to suggest that they are important for normal immunological functioning. Proposed mechanisms of action must explain the fact that transfer factors obtained from the cells of high responder animals are capable of transferring delayed hypersensitivity to low responder animals while the reverse is not true. Transfer factor molecules are likely to interact with the variable regions of the alpha and/or beta chain of T cell receptors to change their avidity and affinity for antigen in a way that otherwise would only occur after an encounter with antigen.

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Dialysable lymphocyte extract (DLyE) in infantile onset autism: A pilot study.

H.H. Fudenberg
NeuroImmunoTherapeutics Research Foundation Spartanburg, S.C.

40 infantile autistic patients were studied. They ranged from 6 years to 15 years of age at entry. 22 were cases of classical infantile autism; whereas 18 lacked one or more clinical defects associated with infantile autism (“pseudo-autism”). Of the 22 with classic autism, 21 responded to transfer factor (TF) treatment by gaining at least 2 points in symptoms severity score average (SSSA); and 10 became normal in that they were main-streamed in school and clinical characteristics were fully normalized. Of the 18 remaining, 4 responded to TF, some to other therapies. After cessation of TF therapy, 5 in the autistic group and 3 of the pseudo-autistic group regressed, but they did not drop as low as baseline levels.

****

An attempt to inhibit the course of amyotrophic lateral sclerosis (ALS) by suppressor factor.

Oldrich Nevsimal(1), Jan Pekarek(2) & Karel Cech(2).

(1)Neurological Clinic of the Medical Faculty, Charles’s University, Praha, Czech Republic. (2)SEVAC Ltd. Praha, Czech Republic.

Forty amyotrophic lateral sclerosis (ALS) patients were treated with suppressor factor. The therapy led to the normalization of the immunoregulatory index in approximately two thirds of the patients. The responder patients had a better clinical response, i.e. the degenerative process slowed down or it was even arrested. This favourable effect was accompanied with a significant increase in the patients’ life span. When the therapy had no effect on the CD8 cells, it was discontinued. Stopping the therapy led to disease progression and death; thus, in some patients, therapy was carried out despite its failure to increase the CD8 cell numbers. Substantial clinical improvement was noticed in these patients. The mean survival of patients with ALS was 2-3 years, whereas ALS patients treated with the suppressor factor survived on the average more than 5 years.

****

Some properties and protective activity of specific DLE against Salmonella cholera suis infection.

Atanas Arnaudov(1), Nicola Tziporkov(2).

(1)Regional Veterinary Research Institute – Nezavisimost boul. 111, Plovdiv 46; (2)Higer Institute of Food and Flavour Industry, Biochemistry Dept.-Maritza boul. 26, Plovdiv 42, Bulgaria.

From a rabbit lymphoid tissue, twice immunized with a Salmonella ch. suis vaccine, it was obtained a dialysable leucocyte extract (DLE) (m.w. 10000Da; protein content 1.14 mg/ml; content of ribose 2.7 mg/ml; A260/A280 ratio 2.17 and pH 6.8). By gel filtration on Sephadex G-25, six peaks were obtained and actively was found in peak IV. The activity of the extract was determined by a dermo-application test (DAT) on 10 cows. The protective effect was tested by challenge with Salmonella ch. suis and Salmonella dublin pathogen strains on white mice intraperitoneally treated with DLE. The DAT proved to be positive in 8 of the 10 cows. When applied on white mice, it induced a high specific protective effect against Salmonella ch. suis (70%), but not against Salmonella dublin infection.

**** Dialyzable lymphoid extract (DLE) from mice resistant to STZ-induced diabetogenesis can interrupt the progress of diabetes in STZ-treated CD-1 mice.

Wm. Borkowsky, Robert Pilson, and H.S. Lawrence.
New York University Medical Center.

Departments of Paediatrics and Medicine, Divisions of Infectious Diseases and Immunology, New York, NY, USA.

DLE was prepared from the minority of euglycemic CD-1 mice, previously injected with STZ, and was administered to hyperglycemic CD-1 male mice 1, 2 and 3 weeks after completion of multidose STZ. Mice treated with DLE derived from 2 x 107 (1X) or 108 lymphocyte equivalents (lymph.equ.) were significantly less hyperglycemic than the saline treated controls (P<0.001). The effects of DLE remained evident for more than 10 weeks after the final DLE treatment. Mice treated with DLE prepared from diabetic mice (hg DLE) developed a somewhat more rapid onset of hyperglycemia than the STZ treated control animals, although this effect did not achieve statistical significance (P=0.1). This DLE was absorbed on a rat insulinoma cell line (RIN), which contains interspecies cross-reacting islet antigens, and compared to the unabsorbed DLE. Mice treated with hg DLE preabsorbed on RIN cells, showed a slower onset of hyperglycemia. DLE prepared from euglycemia mice and the RIN-absorbed fraction were equally capable of preventing hyperglycemia (P<0.05).

In order to determine whether the DLE effects were genetically restricted, DLE was prepared from BALB/c mice, normally resistant to the diabetogenic effects of multidose STZ, both before and after STZ treatment. STZ primed CD-1 mice treated with 3 weekly doses of 2 x 10^7 lymph. equ. of untreated BALB/c derived DLE, STZ treated BALB/c derived DLE, and STZ treated CD-1 DLE were all less hyperglycemic than the control mice, who received saline (P<0.001). However, mice treated with CD-1 DLE were less hyperglycemic than the mice given BALB/c derived DLE (P<0.05). These effects were relatively long-lived.

Mice that were given the >3,500 Dalton fraction of CD-1 DLE were significantly less hyperglycemic than either the control mice or those treated with the 3,500 Dalton fraction of CD-1 DLE (P<0.05). Effects remained evident for more than 3 months after the last dose of DLE. Pancreatic tissue from the mice treated with the >3,500 Dalton fraction of CD-1 derived DLE revealed slightly more islets of a slightly greater size with less surrounding inflammation than either control mice or mice treated with the <3,500 Dalton fraction of DLE.

****

Influence of a DLE-extracted lymphocytic suppressor factor on CsA-induced immunosuppression

V.E.M. Rosso di San Secondo, A. Aniasi, G. Piccolo, P.C. Montecucchi & G.Sirchia.

Transplantation Immunology and Blood Transfusion Center, University-Hospital Policlinico, Via F.Sforza 35, 20122 Milano, Italy.

From dialysable leucocyte extracts (DLE) we have purified a hydrophilic low-mol. wt. factor (about 1 kDa) which we have named lymphocytic suppressor factor (LSF) as it is able to suppress antigen- and mitogen-induced lymphocyte transformation and to prolong allograft survival in C57b/6N mice (H-2b) transplanted with fully mismatched skin from C3H/HeN mice (H-2k). At the molecular level LSF acts by inhibiting DNA replicational and transcriptional processes in activated lymphocytes, isolated rat hepatocyte nuclei, and cell-free systems. Amino acid analysis indicates that LSF is a peptide composed of Asp, Glu, Ser, Thr, Ala, Gly, Arg and probably Met, with the N-terminus blocked, possibly by pyroglutamic acid. When combined “in vitro” with cyclosporine A (CsA), LSF increased about 20 times the potency of CsA in inducing suppression of mitogen-stimulated lymphocytes. In C57b/6N mice with skin graft from C3H/HeN mice and undergoing immunosuppression with CsA (50 mg/kg/day), the splenocyte LSF content increased about 5 times. However, LSF values returned to normal in mice recovering normal responsiveness due to progressive withdrawal of CsA. These data show that LSF has an important role in the development and maintenance of CsA-induced immunosuppression. We suggest that, by influencing DNA replicational and transcriptional processes of lymphocytes, LSF may play a role also in the onset and progression of retro-viral diseases including AIDS.

****

Transfer factor in chronic mucocutaneous candidiasis

Massimo Masi(1), Caterina De Vinci(2), Olavio Roberto Baricordi(3).

(1)Allergology and Clinical Immunology Center, Department of Pediatrics, University of Bologna; (2)Experimental Urology Unit, Division of Urology – S.Orsola-Malpighi Hospital, Bologna, Italy. (3)Department of Genetics, University of Ferrara, Italy

Fifteen patients suffering from chronic mucocutaneous candidiasis were treated with an in vitro produced TF specific for Candida albicans antigens and/or with TF extracted from pooled buffy coats of blood donors. CMI of the patients was assessed using the LMT and the LST in presence of candidine. The aim of the study was the clinical evaluation of TF treatment and the incidence of positive tests before, during, and after therapy. Immunological data were matched using the Chi square test. 87 LMT were performed for each antigen dose and, at the dilution of 1/50, 58.9% (33/56) tests were positive during non-treatment or non-specific TF treatment. On the contrary 83.9% (26/31) were positive during specific TF treatment (P<0.05). In the LST, a significant decrease of thymidine uptake in the control cultures in presence of autologous or AB serum was observed when patients were matched according to non-treatment, and both non specific (P<0.05) and specific TF treatment (P<0.01). Only during specific TF treatment was a significant increase of reactivity against the Candida antigen at the highest concentration noticed when compared with the period of non specific treatment (P<0.01). Clinical observations were encouraging: all but one patient experienced significant improvement during treatment with specific TF. These data confirm that orally administered specific TF, extracted from induced lymphoblastoid cell-lines, increases the incidence of reactivity against Candida antigens in the LMT. LST reactivity appeared not significantly increased with respect to the periods of non treatment, but was significantly increased when it was compared to the non-specific TF treatment periods. At the same time, a clinical improvement was noticed.

****

Profiles of cytokine production in recipients of transfer factors

Linda Alvarez-Thull# and Charles H. Kirkpatrick

Innovative Therapeutics, Inc. and #The Divisions of Allergy and Clinical Immunology National Jewish Center for Immunology and Respiratory Medicine and the University of Colorado Health Sciences Center Denver, Colorado.

Transfer factors (TF) are proteins that transfer the ability to express cell-mediated immunity from immune donors to non-immune recipients. The mechanisms of these effects have not been defined. The experiments described in this report were undertaken to test the hypothesis that a mechanism through which the beneficial effects of TF are expressed in clinical situation is through “education” of the immune system to produce certain cytokines in response to antigenic stimulation.

BALB/c mice were sensitized to Herpes simplex virus (HSV) either by sublethal systemic or cutaneous infections by administration of a HSV-specific TF. One week later their spleen cells were collected and single cell suspensions were stimulated in vitro with irradiated HSV or concanavalin A. Culture supernatants were collected and assayed for content of IL-2, IL-4, IL-10 and IFN-g.

Spleen cells from infected mice responded to concanavalin A and to HSV by secreting large amounts of IL-2 and IFN-g, modest amounts of IL-10, and no IL-4. Transfer factor recipients produced similar cytokine profiles in response to concavalin A. These mice, however, responded to HSV by secreting IFN-g, but no IL-2. Thus, TF treatment selectively affects cytokine production in response to antigenic stimulation.

****

Use of transfer factor for the treatment of recurrent non-bacterial female cystitis (NBRC): A preliminary report.

Caterina De Vinci(1), Giancarlo Pizza(1), Diego Cuzzocrea(1), Domenico Menniti(1), Ernesto Aiello(1), Paolo Maver(1), Giuseppe Corrado(1), Piero Romagnoli(1), Ennio Dragoni(1), Giuseppe LoConte(1), Umberto Riolo(2), Massimo Masi(3), Giuseppe Severini(4), Vittorio Fornarola1 & Dimitri Viza(5).

(1)Immunodiagnosis and Immunotherapy Unit, 1st-Division of Urology, Bologna; (2)Pharmacy, S.Orsola-Malpighi Hospital, Bologna; (3)Department of Pediatrics, S.Orsola-Malpighi Hospital, and Faculty of Medicine, University of Bologna, Bologna, Italy; (4)Division of Urology, S.Maria delle Croci Hospital, Ravenna, Italy; (5)Laboratoire d’Immunobiologie, URA 1294 CNRS, Faculté de Médecine des Saints-Pères, Paris, France

Results of conventional treatment of female non-bacterial recurrent cystitis (NBRC) are discouraging. Most patients show an unexpected high incidence of vaginal candidiasis, while their cell mediated immunity to Herpes simplex viruses (HSV) and Candida antigens seems impaired, and it is known that the persistence of mucocutaneous chronic candidiasis is, mainly, due to a selective defect of CMI to Candida antigens.

Twenty nine women suffering of NBRC, and in whom previous treatment with antibiotics and non-steroid anti-inflammatory drugs was unsuccessful, underwent oral transfer factor (TF) therapy. TF specific to Candida and/or to HSV was administered bi-weekly for the first 2 weeks, and then once a week for the following 6 months. No side effects were observed before treatment. The total observation period of our cohort was 24379 days, with 353 episodes of cystitis recorded and a cumulative relapse index (RI) of 43. The observation period during and after treatment was 13920 days with 108 relapses and a cumulative RI of 23 (P<0.0001). It, thus, seems that specific TF may be capable of controlling NBRC and alleviate the symptoms.

**** THE EFFECTS OF SOME BIOLOGICAL PRODUCTS ON BONE MARROW CELLS PROLIFERATION IN MICE.

Zou Zhao Fen, Hua Bao Lai, Liu Xiao Feng & Xue Jin Qi.

Institute of Zoology, Chinese Academy of Sciences, Beijing, China Biochemistry Pharmaceutical Industry, Weixiuyvan of Beijing University, China

The multipotential stem cells of bone marrow produce various kinds of cells in the blood stream and in the immune system, which play important roles in haemopoiesis and immune reactions. Proliferation of stem cells of bone marrow is the result of complex and precise inductions by cellular factors. In our experiments, the mitotic index (MI) of bone marrow in mice was measured in vivo by treating them with IFN (Interferon), DLE (Dialysable Leucocyte Extracts) and BMP (Bone Marrow Peptides) respectively.

The results are as follows:
1. IFN decreased the M.I of the control group to 62%; IFN has an inhibitory effect on stem cell proliferation.
2. BMP has a stimulating effect on the proliferation of bone marrow cells, increasing MI by 140%.
3. DLE has an immunoregulating function consisting in the maintenance of the M.I of bone marrow cells at the “normal” level, preventing, for instance, the proliferation of stem cells from being decreased by the side effects of IFN.

Oral administration of DLE for longer time periods, increased the M.I of bone marrow cells of aged mice, from 44% to 104%, suggesting that DLE can enhance haemopoietic and immune functions of aged organisms and has, thus, anti-aging effects.

****

THE SUPPRESSIVE EFFECT OF SALMONELLA LIPOPOLYSACCHARIDE.
Borisova E.V., Cheusova Z.V., Lolo A.A., Borisov V.A.

Taras Shevchenko University, Biological Faculty, Kiev, Ukraine

The influence of Salmonella Virchow extracts (both culture filtrate and lipopolisaccharide (LPS) extract) on delayed type hypersensitivity (DTH) to xenogeneic test-antigens in CBA mice has been examined. The LPS fraction is removed from the culture filtrate by gel filtration. It has been shown that intraperitoneal injection of live or killed bacteria, native or heated culture filtrates, and the LPS fraction suppress DTH. The immune-suppressive activity of the fractions disappears as soon as they are treated by phenol or trichloracetic acid, as well as by specific antibody adsorbtion. It was observed that transplantation of thymocytes from donor mice, which were previously treated by the culture filtrate or LPS, inhibits DTH to test-antigens in recipient mice. The transplant of bone marrow cells does not influence DTH in the recipients. The application on T-helper lymphocytes of levamisole treatment does not prevent Salmonella LPS immune-suppression. Furthermore, it has been shown that Salmonella-LPS inhibits activity of DTH-effector cells, whilst LPS induces T-cells to reduce activity of the T-effector cells which were not sensitized to LPS. The transfer factor of T-cells that have been processed by LPS lacks activity. It is hypothesized that failure of transfer factor treatment in Salmonella infections might be related to the LPS action.

****

TRANSFER FACTOR AND POST-HERPETIC NEURITIS.

Ferrer V., Hernandez L., Miranda E., Gutierrez M. Mexico City, Mexico

Post-herpetic neuritis (PHN) can be a dreadful complication of herpes, particularly in older patients, in whom it may last for months or years with severe pain, requiring strong pain relief medication with rather disappointing results. Furthermore, patients may present various degrees of disability due to the lack of strength of the affected region. We have tried Nonspecific Transfer Factor (NTF), extracted from leucocytes of normal blood donors, for the treatment of PHN in 17 patients with an evolution time of 8 days to 12 years. The patients with longer evolution times had received all types of pain relievers, e.g. carbamazepine and nerve blocks, with poor results. For instance, patient no.13 could hardly walk with the aid of a stroller. After receiving 3 to 12 Units of TF, all patients experienced a clear improvement of the pain, with total disappearance of the symptoms in 15 patients and residual light occasional pain in patients no.5 and no.11. We, thus, conclude that: 1) TF seems useful in the treatment of PHN and 2) the success of TF in the treatment of PHN suggests an active and continuous damage of the nerve by the herpes virus.

****

HUMAN SPECIFIC TRANSFER FACTOR TO STAPHYLOCOCCUS ANTIGENS. Vershigora A.E., Lyubchenko T.A., Goleva E.G., Kholodna L.S., Pozur V.K., Stepanchuk V.A., Latysh G.I. Immunobiotechnological Center, Kiev University of T.Shevcenko, Ukraine. Forty-five male volunteers – donors of antistaphylococcal serum – were immunized with Staphylococcus anatoxin three times at weekly intervals. Fifteen additional volunteers were included in the control group. Dialyzable leukocyte extract (DLE) was obtained by conventional methods from the leukocytes of peripheral blood. Using both the agarose and capillary tube tests, it was shown that the DLE with Transfer Factor activity caused antigen-specific inhibition of macrophage and leucocyte migration. Furthermore, it increased rosette formation and lymphocyte transformation (blast formation). It is worth noting that DLE obtained from two of the immunized donors lacked in vitro activity, and also failed to transfer in vivo. ****

 

¯ Dark chocolate beats fatigue, study

By Catherine Boal

20/12/2006- Further evidence of the health benefits of chocolate has come to light in a new study – giving manufacturers yet another route into the functional food niche.

Eating a small amount of dark chocolate each day can help combat the symptoms of Chronic Fatigue Syndrome (CFS), according to UK researchers.

Dark chocolate has been frequently touted as a ‘healthy’ indulgence thanks to its high levels of polyphenols and flavanols which work to protect the body from cell damage. Sales of the product have risen as a result of its new health-conscious image and market analysts Leatherhead International say they now make up 19 per cent of global chocolate sales.

In the study, the results of which are available on the Hull and East Yorkshire Hospitals NHS Trust website, researchers fed a group of adults 45g of specially formulated dark chocolate – containing 85 per cent cocoa and rich in polyphenols – every day for eight weeks.

The participants reported feeling less fatigued after eating the chocolate and complained of greater tiredness when fed a placebo. None of those who took part reported any weight gain as a result of the study.

Researchers believe chocolate enhances the action of neurotransmitters such as serotonin, responsible for regulating mood and sleep, which could explain why the product can alleviate CFS.

Consultant endocrinologist at the NHS Trust, Professor Steve Atkin said: “No one has examined the effects of chocolate on CFS before and so this is a very interesting and exciting result for us.”

“We now hope to look at some of the other potential benefits of chocolate which is high in these natural chemicals.”

Extensive research into the healthy properties of dark chocolate has already been undertaken by confectionery giants Mars and Barry Callebaut in an effort to capitalise on scientifically-proven benefits which have recently come to light.

And earlier this month, Barry Callebaut launched a website aiming to educate consumers on the science behind their cocoa processing method, Acticoa, which claims to reduce the loss of polyphenols common in ordinary manufacturing methods.

 

 

¯ Curcumin could cut plaque build-up linked to Alzheimer’s

 

04/10/2006- Curcumin, found extensively in curries, could boost the body’s ability to clear the build up of plaques in the brain that are linked to Alzheimer’s disease, suggest results from a small laboratory study from the US.

Alzheimer’s disease is the most common form of dementia and currently affects over 13 million people worldwide. The direct and indirect cost of Alzheimer care is over $100bn (€81bn) in the US alone. The direct cost of Alzheimer care in the UK was estimated at £15bn (€22bn).

Although the mechanism of Alzheimer’s is not clear, significant data exists supporting the build-up of plaque from beta-amyloid deposits. The new research appears to indicate that curcumin, the natural pigment that gives the spice turmeric its yellow colour, could help the body’s immune system clear away these deposits and reduce the risk of developing the disease.

“Curcumin improved ingestion of amyloid beta by immune cells in 50 percent of patients with Alzheimer’s disease. These initial findings demonstrate that curcumin may help boost the immune system of specific Alzheimer’s disease patients,” said Dr Milan Fiala from the David Geffen School of Medicine at UCLA.

Curcumin has increasingly come under the scientific spotlight in recent years, with studies investigating its potential benefits for reducing cholesterol levels, improving cardiovascular health and cancer-fighting abilities.

The research, published in the Journal of Alzheimer’s Disease (Vol. 10, pp. 1-7), adds to this by reporting on a small laboratory study using blood from six Alzheimer’s disease patients (aged 65 to 84) and three healthy controls. The focus was on macrophages, the ‘foot soldiers’ of the immune system that clean up harmful waste products in the body, including beta-amyloid deposits.

The isolated macrophages were exposed to a curcumin-derived compound (provided by phytonutrient manufacturer Sabinsa Corporation) for 24 hours and then introduced beta-amyloid. It was found that macrophages from three out of six Alzheimer’s disease patients showed improved uptake or ingestion of the waste product compared to the patients’ macrophages not treated with curcumin.

The age of the patient and the stage of the Alzheimer’s disease appeared to be key factors in the effectiveness of the curcumin compound, report the researchers, with younger patients and patients with early-stage Alzheimer’s apparently more receptive to the benefits.

No effects were reported for the macrophages from the healthy controls when exposed the curcumin-derived compound.

“We are hopeful that these positive results in a test tube may translate to clinical use, but more studies need to be done before curcumin can be recommended,” said Fiala.

The mechanism behind these apparent effects is not clear and significant further study is needed to further examine the potential effects. Some caution is also warranted due to curcumin levels in some patients already being relatively high due to participation in another UCLA study.

“Our next step will be to identify the factors that helped these immune cells respond,” said co-researcher Laura Zhang from UCLA.

“Immunomodulation of the innate immune system by curcuminoids might be a safe approach to immune clearance of amyloidosis in Alzheimer’s Disease brain,” concluded the researchers.

The new study extends previous findings examining the neuroprotective effects of curcumin. Experts recommend however that consumers wishing to make use of curcumin’s properties consume it in supplement form rather than eating more curries, which tend to be rather high in fat in their Western form.

 

¯ Curcumin linked to better performance for elderly brains

 

 

 

10/27/2006- Curcumin, the natural pigment that gives the spice turmeric its yellow colour, could slow mental decline in elderly people by 49 per cent, suggests a study of non-demented Asian people.

Cognitive performance declines naturally with age, but the results of the new study, published in the American Journal of Epidemiology (Vol. 164, pp. 898-906) suggests that eating curries “often or very often” had significantly better cognitive performance than those who “never or rarely” ate the dish.  The study adds to previous laboratory-based studies that showed that curcumin could boost the body’s ability to clear the build up of plaques in the brain that are linked to Alzheimer’s disease.

Although the mechanism of Alzheimer’s is not clear, significant data exists supporting the build-up of plaque from beta-amyloid deposits. Recent research (Journal of Alzheimer’s Disease, Vol. 10, pp. 1-7) from the US appeared to indicate that curcumin could help the body’s immune system clear away these deposits and reduce the risk of developing the disease.  The Singapore National Mental Health Survey of the Elderly, led by Tze-Pin Ng from the National University of Singapore, recruited 1,010 elderly Asian subjects (average age 68.9) and compared scores for the Mini-Mental State Examination (MMSE).  The researchers report that for three different categories of curry consumption – “often or very often”, “occasionally” and “never or rarely” – and compared this with MMSE performance.  Ng and co-workers report that 43 per cent of the cohort consumed curry at least once a month to daily, while16 per cent never or rarely consumed the dish.

When the researchers looked at the consumption of curry with measures of cognitive impairment (scores below 23 on the MMSE), it was reported that those who consumed curry “often or very often” were associated with a 49 per cent reduced risk of cognitive impairment, compared to those who never or rarely consumed. Eating curry “occasionally” was associated with a 38 per cent reduced risk.  “These findings present the first epidemiological evidence supporting a link between curry consumption and cognitive performance that was suggested by a large number of earlier experimental evidence,” wrote the researchers. The study has several limitations, including not taking into account vegetable and fat intake, which form part of curries, and the accuracy of the self-reporting of curry consumption.  Given these limitations, the researchers noted that the results should be “interpreted with caution,” and stated that dietary intakes may have changed as a result of the onset of dementia in some of the subjects. Despite such comments, the researchers point at turmeric as the potential source of the observed benefits.  “Interestingly, it has also been purported that the prevalence of Alzheimer’s disease in India among elderly between 70 and 79 years of age is four-fold less than that of the United States,” said Ng.  “The results reported here are therefore significant, as they point to a significant beneficial effect on cognitive functioning with even low-to-moderate levels of curry consumption.”  Curcumin has increasingly come under the scientific spotlight in recent years, with studies investigating its potential benefits for reducing cholesterol levels, improving cardiovascular health and cancer-fighting abilities. Some experts recommend however that consumers wishing to make use of curcumin’s properties consume it in supplement form rather than eating more curries, which tend to be rather high in fat in their Western form.