Modern diets and diseases: NO-zinc balance. Under Th1, zinc and nitrogen monoxide (NO) collectively protect against viruses, AIDS, autoimmunity, diabetes, allergies, asthma, infectious diseases, atherosclerosis and cancer.

Thanks to progress in zinc research, it is now possible to describe in more detail how zinc ions (Zn++) and nitrogen monoxide (NO), together with glutathione (GSH) and its oxidized form, GSSG, help to regulate immune responses to antigens. NO appears to be able to liberate Zn++ from metallothionein (MT), an intracellular storage molecule for metal ions such as zinc (Zn++) and copper (Cu++). Both Zn++ and Cu++ show a concentration-dependent inactivation of a protease essential for the proliferation of the AIDS virus HIV-1, while zinc can help prevent diabetes complications through its intracellular activation of the enzyme sorbitol dehydrogenase (SDH). A Zn++ deficiency can lead to a premature transition from efficient Th1-dependent cellular antiviral immune functions to Th2-dependent humoral immune functions. Deficiencies of Zn++, NO and/or GSH shift the Th1/Th2 balance towards Th2, as do deficiencies of any of the essential nutrients (ENs) - a group that includes methionine, cysteine, arginine, vitamins A, B, C and E, zinc and selenium (Se) - because these are necessary for the synthesis and maintenance of sufficient amounts of GSH, MT and NO. Via the Th1/Th2 balance, Zn++, NO, MT and GSH collectively determine the progress and outcome of many diseases. Disregulation of the Th1/Th2 balance is responsible for autoimmune disorders such as diabetes mellitus. Under Th2, levels of interleukin-4 (II-4), II-6, II-10, leukotriene B4 (LTB4) and prostaglandin E2 (PGE2) are raised, while levels of II-2, Zn++, NO and other substances are lowered. This makes things easier for viruses like HIV-1 which multiply in Th2 cells but rarely, if ever, in Th1 cells. AIDS viruses (HIVs) enter immune cells with the aid of the CD4 cell surface receptor in combination with a number of co-receptors which include CCR3, CCR5 and CXCR4. Remarkably, the cell surface receptor for LTB4 (BLTR) also seems to act as a co-receptor for CD4, which helps HIVs to infect immune cells. The Th2 cytokine II-4 increases the number of CXCR4 and BLTR co-receptors, as a result of which, under Th2, the HIV strains that infect immune cells are precisely those that are best able to accelerate the AIDS disease process. The II-4 released under Th2 therefore not only promotes the production of more HIVs and the rate at which they infect immune cells, it also stimulates selection for the more virulent strains. Zn++ inhibit LTB4 production and numbers of LTB4 receptors (BLTRs) in a concentration-dependent way. Zn++ help cells to keep their LTB4 'doors' shut against the more virulent strains of HIV. Moreover, a sufficiency of Zn++ and NO prevents a shift of the Th1/Th2 balance towards Th2 and thereby slows the proliferation of HIV, which it also does by inactivating the HIV protease. Research makes it look likely that deficiencies of ENs such as zinc promote the proliferation of Th2 cells at the expense of Th1 cells. Zinc deficiency also promotes cancer. Under the influence of Th1 cells, zinc inhibits the growth of tumours by activating the endogenous tumour-suppressor endostatin, which inhibits angiogenesis. The modern Western diet, with its excess of refined products such as sugar, alcohol and fats, often contains, per calorie, a deficiency of ENs such as zinc, selenium and vitamins A, B, C and E, which results in disturbed immune functions, a shifted Th1/Th2 balance, chronic (viral) infections, obesity, atherosclerosis, autoimmunity, allergies and cancer. In view of this, an optimization of dietary composition would seem to give the best chance of beating (viral) epidemics and common (chronic) diseases at a realistic price.

Cysteine, glutathione (GSH) and zinc and copper ions together are effective, natural, intracellular inhibitors of (AIDS) viruses.

Sufficient essential nutrients such as methionine, cysteine, copper, selenium, zinc and vitamins C and E are indispensable for the maintenance of optimal (immune) cell functions. Parasitic organisms such as protozoa, fungi, bacteria and viruses also depend on these essential nutrients for their multiplication and functioning. An evolutionarily developed optimal distribution of available nutrients between host (cells) and parasitic organisms normally prevents diseases, the nature of which will depend on genetic and environmental factors. The way in which the right amount of cysteine, glutathione (GSH), and copper and zinc ions made available in the right place at the right time and in the right form can prevent an unchecked multiplication of (AIDS) viruses in a more passive or active way forms the basis for the AIDS zinc-deficiency hypothesis (A-Z hypothesis) presented in this article. Zinc and copper ions stimulate/inhibit/block in a concentration-dependent way the (intracellular) activation of essential protein-splitting enzymes such as HIV proteases. Zinc and copper ions as 'passive' virus inhibitors. Apart from this, zinc ions directly or indirectly regulate, via zinc finger protein molecular structures, the activities of virus-combating Th-1 cells such as cytotoxic T-cells (CTLs). Zinc ions as regulators of the active, virus-combating Th-1 cells. Zinc and copper ions that remain available in sufficient amounts via cysteine/GSH are effective natural inhibitors/combaters of (AIDS) viruses and thereby prevent the development of chronic virus diseases that can lead to AIDS, autoimmune diseases, (food) allergies and/or cancer. A safe, relatively inexpensive and extensively tested medicine such as N-acetylcysteine (NAC) can help in supplying extra cysteine. The anti-HIV peptide T22, synthesized on the basis of two natural peptides from the Tachypleus tridentatus and Limnus polyphemus crabs, appears to be able to serve as supplier/carrier molecule of cysteine and zinc and/or to hinder the entry of HIVs into cells by way of the CD4 receptor.

Zinc-controlled Th1/Th2 switch significantly determines development of diseases.

Functional, excessive-possibly temporary-deficiencies of the trace element zinc can change immune functions prematurely from predominantly cellular Th1 responses to humoral Th2 responses. T helper (Th1) cells produce cytokines such as interleukin-2 (IL-2) and interferon gamma, thereby controlling viral infections and other intracellular pathogens more effectively than Th2 responses through cytokines such as IL-4, IL-5, IL-6 and IL-10. The accelerated shift from the production of extra Th1 cells during these cellular immune activities to more Th2 cells with their predominantly humoral immune functions, caused by such a zinc deficiency, adversely influences the course of diseases such as leprosy, schistosomiasis, leishmaniasis and AIDS, and can result in allergies. It is noteworthy that AIDS viruses (HIVs) do not replicate in Th1 cells, which probably contain more zinc, but preferentially in the Th0 and Th2 cells; all the more so, because zinc and copper ions are known to inhibit intracellular HIV replication. Considering the above Th1/Th2 switch, real prospects seem to be offered of vaccination against such parasites as Leishmania and against HIVs.

Diabetes can be prevented by reducing insulin production.

Hypersecretion of insulin increases the chance of the incidence of diabetes type I and II, while inhibiting insulin secretion helps prevent diabetes. Trace elements like zinc and vanadium prevent hyperinsulinemia, partly because of their own insulin activity, which is also a property of interleukin-1 (IL-1), particularly during periods of illness and stress. Like vanadium, IL-1 can replace insulin for many hours and regulate glucose metabolism. Vanadium, zinc and IL-1 ensure that insulin-producing beta-cells in the pancreas do not lose too much zinc, which leaves the beta-cells together with insulin. Zinc forms a complex with metallothionein in beta-cells that provides protection against free (oxygen) radicals, which become active during immune responses triggered by bacteria and viruses, for instance. In addition, zinc is the only non-toxic trace element in the body that regulates concentration-dependent immune responses on many levels. Avoiding deficiencies of trace elements will enable the reduction of the incidence of diabetes.

[Is anaemia of veal calves normochromic or hypochromic? (author's transl)]. / Is de anemie bij het mestkalf normochroom of hypochroom?

The anaemia resulting from iron deficiency is described as hypochromic in the medical literature. In the veterinary literature, anaemia of veal calves is usually regraded as normochromic. In order to examine the correctness of this view, the present authors studied the Hb and haematocrit (Hc) levels of the blood of veal calves in a comparative feeding trial for sixteen weeks. Three groups of male Dutch-Friesian calves, each group consisting of approximately thirty animals, were fed a milk replacer which contained 5, 10 or 25 ppm of iron respectively. The calculated mean Hb-concentration in the erythrocytes of the animals given 5 and 10 ppm of iron dropped during the trial period to below levels occurring at the age of two weeks. In the group given 25 ppm of iron, the erythrocyte Hb showed a rapid increase from the age of ten weeks and continuing throughout the rest of the trial period. At the age of sixteen weeks, the groups showed significant differences (P less than 0.01) in their mean erythrocyte Hb-concentrations. In veal calves, fed milkreplacers having an iron content below 25 ppm of Fe, the anaemia therefore is hypochromic.

[Haemoglobin and haematocrit levels in veal calves (author's transl)]. / Het verloop van het hemoglobinegehalte en de hematocrietwaarde van het bloed van mestkalveren.

The haemoglobin and haematocrit levels were studied in three groups of about thirty male Dutch-Friesian veal calves. The iron content of the milk replaces was 5, 10 and 25 ppm. During the experiment which was continued for sixteen weeks, the haemoglobin and haematocrit levels decreased in all groups. The decrease was confined to the first six weeks in the calves fed the milk replacer containing 25 ppm of iron. In the two other groups, the decrease of the two criteria continued throuhgout period. Regardless of the iron content of the milk replacer, the decrease of Hb- and haematocrit levels of the individual calves was greater in those having the highest initial level. The borderline for anaemia in a group of sixteen-week-old veal calves is estimated at approximately 10 g. Hb/100 ml. blood. For an individual calf, the borderline is estimated at 8 g. Hb/100 ml. blood.

Relation between methionine and inorganic sulphate in broiler rations.

In two experiments with 0-5 weeks old broiler chicks in battery-cages, it was examined whether the requirements for sulphur-containing amino acids in the ration could be reduced by addition of inorganic sulphate. The basal diet was a high energy practical-type broiler ration. The mineral mix included in this diet did not contain sulphates. The basal diet contained 0.73% methionine + cystine. By addition of synthetic methionine, experimental rations with 0.78, 0.82, 0.92 and 1.02% methionine + cystine, respectively, were obtained. The addition of methionine to the basal ration effected significant effects on weight gain (maximum 6-7% at 5 weeks of age) and on feed conversion (maximum 7-8% at 5 weeks of age). The addition of 0.1% Na2 SO4 (=0.068% inorganic sulphate) to the basal and the methionine supplemented diets resulted in an overall increase in weight gain at 5 weeks of age of 0.9% and a reduction in feed conversion of 1.2%; both effects were significant (P less than .05). However, the size of this effect proved to be independent on the contents of sulphur-containing amino acids in the ration. This indicates a small deficiency of the basal ration for inorganic sulphate.