Monday, May 7, 2007

Sinha Institute of Medical Science and Technology, A Success Story


By Prof. A.K Sinha D.Sc, Mau Bhattacharya M.Sc, Soumendra K. Karmahapatra M.Sc

Sinha Institute of Medical Science and Technology

*Calcutta (Branch office). 288, Kendua Main Road, Baishnabghata, Garia. Kolkata-700084, India
*Tamluk Branch (Head Office). Poddarpara Lane, Parbatipur, Tamluk. Midnapore- 721636, India

Telephone # +91-9903792100 Fax #-+91-33-24127905

Prologue: Our organization Sinha Institute of Medical Science and technology, an ECOSOC-special category IV, firmly believes that “the economic well being of any society heavily depends upon good public health.” To help society at large in its effort to improve public health our organization carries out basic medical research using novel approaches to control/cure incurable and debilitating diseases.

By following the old axion “prevention is better than cure” we in this organization for the last 12 years have been conducting research on the use of food items (neutraceutical) to prevent the progression of HIV infection which leads to AIDS, an incurable terminal disease that has become a formidable epidemic in those societies in the world which can least afford to stand the brunt of the disease. We are pleased to announce that eating 1-2 g (one to two g) of fresh garlic (not cooked, fried or garlic oil in capsule), could be beneficial in the progression of HIV to AIDS, through the production of interferon-α (IFN-α) in the body. IFN-α is a potent viricide (virus killer). For the uninitiated readers who are not familiar with the course of AIDS, a few words regarding the disease are written below:
Human immunodeficiency virus (HIV) after it infects a person it gradually progressed to acquired immunodeficiency syndrome (AIDS). Once HIV progressed to AIDS it always ends in death due to multitude of clinical problems. AIDS is treated by using highly active Retro active therapy (HAART which includes zidovudine, didanosine, zalcitabine, stavudine and others). Although these drugs improve many of the syndromes associated with AIDS they do not cure AIDS. Eventually these drugs fail to work and the victims usually develop hepatitis virus C (HVC) coinfection. Indeed more AIDS victims died due to HVC infection than due to AIDS related complications.
There are reports which indicated that the use of IFN-α in the HIV infective stage effectively stops the progression of HIV to AIDS. However IFN-α has little effect on the AIDS due to the immunodeficiency developed during the progression of the disease, although IFN-α is used for HVC infection associated in AIDS due to co-infection where HAART fails. Use of IFN α in HIV infective period is somewhat impractical; at this stage of the disease sometime there is no clinical problem and consequently the victim usually ignore the infections.
Secondly, IFN-α is needed to be injected (although oral IFN-α is available its use in HIV remains controversial) it is expensive and produces considerable toxic effects. In contrast systemic increase of IFN-α by garlic eating does not produce any discernable side effect ( it is well known that a compound which is produced in the body for beneficial effect against a condition when injected from outside source may produce considerable untoward effects, e.g., use of dopamine in parkinsonism).

Since chronic eating of small quantity of fresh garlic increase IFN-α in the system and the use of IFN-α in HIV infection has been reported by many investigators to be beneficial for the progression from HIV to AIDS, we asked several newly diagnosed HIV positive persons to eat fresh garlic on daily basis although the number of volunteers was small (only 9 between ages of 30-45 yrs, all male). They were fully explained what the purpose of the study was and advised according to the rules of Helsinki agreements on human right, although garlic is a food item it does not come under the definition of drugs. They were asked that their names will not be used in any report. After a year it was found that all participants gained weight, felt generally well and normal and none had in this time period developed any discernable syndrome. It must be mentioned here that the development of HIV to AIDS some time takes many years, and many clinical tests are needed to be done to determine the validity of the study. However, the study “looked” encouraging and apparently was beneficial for these subjects. Further work is in progress. A brief description on the effect of eating garlic on the production of IFN-α is given below. For greater details and scientific data please see the Journal of Interferon and Cytokine Research [Systemic Production of IFN-α by Garlic (Allium sativum) in Humans; © Mary Ann Liebert, Inc,].

Interferons (IFNS) are a family of heterogeneous small protein molecules well known for their antiviral activity. Garlic (Allium sativum) is used as a vegetable in cuisines of many countries. Fresh garlic has been eaten as a folk remedy for the common cold and for the prevention of infectious diseases in various parts of India from antiquity. We have reported before that feeding of fresh garlic to white Swiss mice resulted in an increase in the plasma nitric oxide (NO) level. Because NO is a biologic messenger molecule and has been reported to induce synthesis of anticancer proteins and IFN-α is a well known anticancer cytokine, we investigated the effect of an increased plasma NO level on the increase in the plasma IFN-α level in normal volunteers. Furthermore, we investigated the role of garlic-induced NO synthesis on the synthesis of IFN-α by exposing human neutrophils to garlic both in vivo and in vitro by determining the synthesis of IFN-α -mRNA in relation to the synthesis of NO in these cells.

Effect of ingestion of fresh garlic on plasma NO and IFN-α levels
Ingestion of fresh garlic (2 g wet weight) by normal volunteers were found to cause an increase in the basal plasma NO level of 2.7 ± 0.1 µM to 27.37 ± 0.87 µM after 4 h of eating the vegetable. The plasma IFN-α level increased from the basal 9.51 ± 0.26 nM to 50.7± 0.16 nM at 4 h (Fig. 1). The serum level of IFN-α has been reported to be 15.6± 500 pg/mL, but we have found that the basal plasma level of IFN-α was considerably higher.

FIGURE- 1. Plasma IFN-α and NO levels in normal volunteers at different times after eating fresh garlic. Normal volunteers (n =10, 5 men, 5 women) ate 2 g fresh garlic as described. Plasma levels of NO (solid line) and IFN-α (broken line) were determined at different times, as indicated. Each point represents the mean ±SD of 10 different experiments.

Maintenance of increased plasma IFN-α level by garlic
To determine the length of time the increased plasma IFN-α as a result of eating garlic was maintained in vivo, the volunteers ate 2 g fresh garlic once. The plasma NO and IFN-α levels were determined up to 3 days. Although the increased plasma NO level due to garlic ingestion returned to basal level (2.71 µM) after 12 h, the plasma level of IFN-α continued to increase at least up to 48 h. After 48 h, the plasma IFN-α level decreased, but even after 72 h, the plasma cytokine level was higher than that of the basal level at the beginning of the experiment. The increased cytokine level begins to decrease 2 days after ingestion of 2 g fresh garlic (Fig. 2). Furthermore eating 1 to 2 g fresh garlic on alternate days it is possible to maintain the increased plasma IFN-α level indefinitely.

FIGURE- 2. Effect of ingesting 2 g fresh garlic one time only on the plasma IFN-α level in normal volunteers at different times after eating. Normal volunteers (Fig. 1) ate 2 g fresh garlic once, and the plasma IFN-α levels were determined at the indicated day after garlic was consumed. Each point represents mean ± SD of 10 different experiments involving 10 different volunteers. The plasma NO level was also determined on the indicated day. The plasma NO level returned to the basal level at 12 h after garlic was eaten; consequently, the plasma NO is not shown.

As noted, the stimulated production of NO and, in turn, IFN-α by garlic was mediated by some heat labile factor present in the fresh garlic. These results suggest that the active principle in the fresh garlic might be proteinous in nature and mediated through synthesis of NO. We came to this conclusion because we have purified a protein from fresh garlic that was found to be a potent stimulator of NO synthesis. This protein, called “allimin” (Mr.4012.4Da), when added to the neutrophils suspension in vitro, was found to stimulate the synthesis of both NO and IFN-α (N. Sinha et al., unpublished observations).

IFN-α is used therapeutically in various viral and neoplastic diseases. Consequently, if the effect of fresh garlic on IFN-α could be reproduced in people with viral or proliferative disease, consumption of fresh garlic might be beneficial for such patients. A simple calculation on the systemic increase in the plasma IFN-α level in normal volunteers as a result of eating 2 g fresh garlic was determined to be approximately 300,000 IU (based on 11.1 µg/mL IFN-α =3 x106 units). This could be in the useful range as a supplement to the therapeutic doses of the cytokine used in several viral diseases.

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