Microbial carcinogenic toxins and dietary anti-cancer protectants

Several toxins are known which account for the ability of some bacteria to initiate or promote carcinogenesis. These ideas are summarised and evidence is discussed for more specific mechanisms involving chymotrypsin and the bacterial chymotryptic enzyme subtilisin. Subtilisin and Bacillus subtilis are present in the gut and environment and both are used commercially in agriculture, livestock rearing and meat processing. The enzymes deplete cells of tumour suppressors such as deleted in colorectal cancer (DCC) and neogenin, so their potential presence in the food chain might represent an important link between diet and cancer. Over-eating increases secretion of chymotrypsin which is absorbed from the gut and could contribute to several forms of cancer linked to obesity. Inhibition of these serine proteases by Bowman–Birk inhibitors in fruit and vegetables could account for some of the protective effects of a plant-rich diet. These interactions represent previously unknown non-genetic mechanisms for the modification of tumour suppressor proteins and provide a plausible explanation contributing to both the pro-oncogenic effects of meat products and the protective activity of a plant-rich diet. The data suggest that changes to farming husbandry and food processing methods to remove these sources of extrinsic proteases might significantly reduce the incidence of several cancers.     

Effect of a restricted diet on the in vitro glucose-induced insulin release of aging rats.

To study the effect of a sudden loss of body weight on the beta-cell function of aging rats, basal and glucose-induced insulin secretion was measured in pancreatic islets obtained from young (2-month-old), adult (12-month-old) and aging (24-month-old) rats, either fed ad libitum or fed a restricted diet (50% caloric restriction). Basal insulin secretion was similar in islets of young, adult and older rats. Glucose stimulated insulin release was significantly reduced in aging rats as compared to young animals. Animals fed a restricted diet showed a prolonged and higher secretory rate during first phase release when compared to animals fed ad libitum.     

Effect of a restricted diet on the in vitro glucose-induced insulin release of aging rats

To study the effect of a sudden loss of body weight on the -cell function of aging rats, basal and glucose-induced insulin secretion was measured in pancreatic islets obtained from young (2-month-old), adult (12-month-old) and aging (24-month-old) rats, either fed ad libitum or fed a restricted diet (50% caloric restriction). Basal insulin secretion was similar in islets of young, adult and older rats. Glucose stimulated insulin release was significantly reduced in aging rats as compared to young animals. Animals fed a restricted diet showed a prolonged and higher secretory rate during first phase release when compared to animals fed ad libitum.     

Timed bromocriptine administration reduces body fat stores in obese subjects and hyperglycemia in type II diabetics.

Obese postmenopausal female volunteers were given timed daily oral dosages of bromocriptine, and tested for reduction of body fat stores. This dopamine agonist has been shown to reset circadian rhythms that are altered in obese animals and to reduce body fat levels in several animal models. The participants were instructed not to alter their existing exercise and eating behavior during treatment. Skinfold measurements were taken on 33 subjects as indices of body fat. The measurements (e.g., suprailiac) were reduced after six weeks by about 25%, which represents a reduction of 11.7% of the total body fat. These dramatic decreases in body fat, which are equivalent to that produced by severe caloric restriction, were accompanied by more modest reductions of body weight (2.5%), indicating a possible conservation of protein that is usually lost as a consequence of such caloric restriction. The effects of bromocriptine treatment on body fat and hyperglycemia were also examined in non-insulin dependent diabetics being treated with oral hypoglycemics (7 subjects) or insulin (7 subjects). Total body fat was reduced by 10.7% and 5.1% in diabetics on oral hypoglycemics and insulin, respectively, without any significant reductions in body weight. Hyperglycemia was reduced in most of the 15 diabetic subjects treated leading to euglycemia and even cessation of hypoglycemic drugs in 3 of the 7 subjects during 4-8 weeks of bromocriptine treatment. These findings support the hypothesis that obesity and type II diabetes may be treated effectively with bromocriptine when administered at the proper times and dosages.     

A philosophical study of the transition from the caloric theory of heat to thermodynamics: Resisting the pessimistic meta-induction

I began this study with Laudan's argument from the pessimistic induction and I promised to show that the caloric theory of heat cannot be used to support the premisses of the meta-induction on past scientific theories. I tried to show that the laws of experimental calorimetry, adiabatic change and Carnot's theory of the motive power of heat were (i) independent of the assumption that heat is a material substance, (ii) approximately true, (iii) deducible and accounted for within thermodynamics.I stressed that results (i) and (ii) were known to most theorists of the caloric theory and that result (iii) was put forward by the founders of the new thermodynamics. In other words, the truth-content of the caloric theory was located, selected carefully, and preserved by the founders of thermodynamics.However, the reader might think that even if I have succeeded in showing that laudan is wrong about the caloric theory, I have not shown how the strategy followed in this paper can be generalised against the pessimistic meta-induction. I think that the general strategy against Laudan's argument suggested in this paper is this: the empirical success of a mature scientific theory suggests that there are respects and degrees in which this theory is true. The difficulty for — and and real challenge to — philosophers of science is to suggest ways in which this truth-content can be located and shown to be preserved — if at all — to subsequent theories. In particular, the empirical success of a theory does not, automatically, suggest that all theoretical terms of the theory refer. On the contrary, judgments of referential success depend on which theoretical claims are well-supported by the evidence. This is a matter of specific investigation. Generally, one would expect that claims about theoretical entities which are not strongly supported by the evidence or turn out to be independent of the evidence at hand, are not compelling. For simply, if the evidence does not make it likely that our beliefs about putative theoretical entities are approximately correct, a belief in those entities would be ill-founded and unjustified. Theoretical extrapolations in science are indespensable , but they are not arbitrary. If the evidence does not warrant them I do not see why someone should commit herself to them. In a sense, the problem with empricist philisophers is not that they demand that theoretical beliefs must be warranted by evidence. Rather, it is that they claim that no evidence can warrant theorretical beliefs. A realist philosopher of science would not disagree on the first, but she has good grounds to deny the second.I argued that claims about theoretical entities which are not strongly supported by the evidence must not be taken as belief-worthy. But can one sustaon the more ambitious view that loosely supported parts of a theory tend to be just those that include non-referring terms? There is an obvious excess risk in such a generalisation. For there are well-known cases in which a theoretical claim was initially weakly supported by the evidence     

Involutive morphological modifications in the rat adrenal glomerular zone after a low-sodium diet

Summary We have studied glomerular zone involution in the rat's adrenal gland after a period of hyperfunction brought about by a low-sodium diet. The changes observed in this zone affect those organoids that are more directly involved in steroid genesis; mitochondria, smooth endoplasmic reticulum and liposomes. The Golgi complexes appear very developed, often, showing, a positive acid phosphatase activity. Lysosomes suffered a considerable increase in their number, and carried out their digestive function on liposomes. All those changes discussed here are seen as an accomodation of this zone to the new normofunctional situation.     

Timed bromocriptine administration reduces body fat stores in obese subjects and hyperglycemia in type II diabetics

Obese postmenopausal female volunteers were given timed daily oral dosages of bromocriptine, and tested for reduction of body fat stores. This dopamine agonist has been shown to reset circadian rhythms that are altered in obese animals and to reduce body fat levels in several animal models. The participants were instructed not to alter their existing exercise and eating behavior during treatment. Skinfold measurements were taken on 33 subjects as indices of body fat. The measurements (e.g., suprailiac) were reduced after six weeks by about 25%, which represents a reduction of 11.7% of the total body fat. These dramatic decreases in body fat, which are equivalent to that produced by severe caloric restriction, were accompanied by more modest reductions of body weight (2.5%), indicating a possible conservation of protein that is usually lost as a consequence of such caloric restriction. The effects of bromocriptine treatment on body fat and hyperglycemia were also examined in non-insulin dependent diabetics being treated with oral hypoglycemics (7 subjects) or insulin (7 subjects). Total body fat was reduced by 10.7% and 5.1% in diabetics on oral hypoglycemics and insulin, respectively, without any significant reductions in body weight.Hyperglycemia was reduced in most of the 15 diabetic subjects treated leading to euglycemia and even cessation of hypoglycemic drugs in 3 of the 7 subjects during 4–8 weeks of bromocriptine treatment. These findings support the hypothesis that obesity and type II diabetes may be treated effectively with bromocriptine when administered at the proper times and dosages.This is a process patented by Louisiana State University and licensed to Ergo, Inc., Newport, Rhode island. A. H. Meier and A. H. Cincotta have financial interest in the process.     

Carcinogenicity examination of betel nuts and piper betel leaves.

A dry powder of betel nuts, piper betel leaves and lime was administered to rats. Epidermal thickening was frequently observed in the upper digestive tracts of rats in groups fed the betel nut diet mixed with lime and the betel leaves diet, and a forestomach papilloma was seen in 1 rat given betel leaves diet. These epidermal changes were scarcely seen in rats given either betel nut or normal diet alone.     

Carcinogenicity examination of betel nuts and piper betel leaves

Summary A dry powder of betel nuts, piper betel leaves and lime was administered to rats. Epidermal thickening was frequently observed in the upper digestive tracts of rats in groups fed the betel nut diet mixed with lime and the betel leaves diet, and a forestomach papilloma was seen in 1 rat given betel leaves diet. These epidermal changes were scarcely seen in rats given either betel nut or normal diet alone.This work was supported by a grant from the U.S.-Japan Cooperative Medical Science Program     

In vivo inhibition of citrate cleavage enzyme by polychlorinated biphenyls

Summary Polychlorinated biphenyls (Aroclor 1254, PCB) administered in the diet (0.01%, w/v) to rats inhibited citrate cleavage enzyme. The results suggest that the decreased activity might in part account for decreased fatty acid synthesis in the livers of PCB-treated rats.This research was supported by a grant from the National Institutes of Health (ES-00040). Aroclor 1254 was a gift of Monsanto Company, St. Louis, Missouri, USA.     

Renal effects of a high unsaturated fat diet in renal artery stenosis in rats

The renal effects of an unsaturated fat (UNSAT) diet in mild to moderate two-kidney, one-clip (2K1C) renovascular hypertension were evaluated. An UNSAT diet (37% by energy) prevented the development of hypertension compared to 2K1C rats fed a high saturated fat (SAT) (37% by energy) and a normal fat (CONTROL) (11% by energy) diet. Urinary sodium and fractional sodium excretion increased in 2K1C rats as compared to SHAM operated controls, regardless of the diet received. In the early weeks of the experiment (weeks 2–4 post-surgery to induce hypertension), an enhanced natriuresis occurred in the 2K1C UNSAT as compared to the 2K1C CONTROL and SAT diet groups. This resulted from an increase in the glomerular filtration rate (GFR in mls·min^–1) as measured using the single-injection [⁵¹Cr] EDTA method (2K1C UNSAT; 1.99±0.18 versus 2K1C SAT; 1.27±0.09, p<0.02; and versus SHAM CONTROL; 1.45×0.01; p<0.02). The increased GFR was not associated with alterations in effective renal plasma flow (ERPF) as measured using the single-injection [¹²⁵I] Na hippurate method. No differences in sodium excretion; GFR; ERPF or renal blood flow (microsphere technique) were noted between the 2K1C UNSAT and SAT diet groups at weeks 6–8 post-surgery, despite a continued antihypertensive effect of the UNSAT diet. Hence, the antihypertensive effect of an unsaturated fat diet in 2K1C renovascular hypertension in rats is associated with transient glomerular changes leading to an enhanced natriuresis.     

Ultrastructural changes of the luminal plasma membrane of the transitional epithelium of the rat urinary tract in essential fatty acid deficiency

Summary Rats fed an essential fatty acid deficient diet (EFAD) showed a statistically significant decrease in the thickness and ultrastructural asymmetry of the luminal membrane and cytoplasmic vesicles of transitional epithelium of the urinary tract, due to a marked thinning of the peculiar thick luminal leaflet. These changes were reversed by adding EFA to the diet. This indicates that the unusual EM appearance of urothelial membrane depends on its content in EFA.Acknowledgment is due to Mrs.M. G. Iwakawa andN. T. Benítez for technical help and Mr.J. Hiza for animal care.D. Lis andA. Eynard are research fellows of Consejo Nacional de Investigaciones Científicas y Técnicas. Work supported in part by CONICET, Argentina.     

Possible mechanism of rubidium-induced hyperactivity in the rat.

This study suggests that replacement of intracellular potassium by rubidium ions might lower the resting membrane potential. Thus rubidium-treated rats were more responsive to depolarizing influences and generated more cyclic AMP in the brainstem and consequently the behavioral changes.     

The role of caloric load and mitochondrial homeostasis in the regulation of the NLRP3 inflammasome

Sterile inflammation is a cornerstone of immune activation in obesity and type 2 Diabetes Mellitus. The molecular underpinnings of this inflammation include nutrient excess-mediated activation of the innate immune NLRP3 inflammasome. At the same time, disruption of mitochondrial integrity is emerging as an integral control node in NLRP3 inflammasome activation and is also associated with caloric overload conditions including obesity and diabetes. Conversely, caloric restriction and fasting mimetic interventions alleviate these caloric excess-linked diseases and reduce inflammation and the NLRP3 inflammasome. The objective of this review is to integrate the findings linking mitochondrial integrity to the activation of the NLRP3 inflammasome and to evaluate how caloric restriction or caloric restriction mimetic compounds may play a role in attenuating the NLRP3 inflammasome and sterile inflammation.     

Importance de la lysine et du tryptophane dans la nutrition deTenebrio molitor L.

Summary Experiments were undertaken in order to ascertain whether an insect,Tenebrio molitor, requires lysine and tryptophane for growing. Young larvæ were fed, from the day of hatching, on a diet containing a purified protein as sole source for amino acids and all the other nutrients required by this species.It was found that lysine and tryptophane are both essential for the growing ofTenebrio. The various protteins tested can be listed from point of view of their nutritive value according to their content of both amino acids. Further evidence for this relationship is presented by the fact that zein, a protein deficient in both lysine and tryptophane, is incapable to sustain growth unless it is supplemented with both amino acids. On the other hand, gliadin which is devoid of lysine but contains small amounts of tryptophane can be improved when lysine only is added.     

A role for <Emphasis Type="Italic">N</Emphasis>-acetylglucosamine as a nutrient sensor and mediator of insulin resistance

The ability to regulate energy balance at both the cellular and whole body level is an essential process of life. As western society has shifted to a higher caloric diet and more sedentary lifestyle, the incidence of type 2 diabetes (non-insulin-dependent diabetes mellitus) has increased to epidemic proportions. Thus, type 2 diabetes has been described as a disease of 'chronic overnutrition'. There are abundant data to support the relationship between nutrient availability and insulin action. However, there have been multiple hypotheses and debates as to the mechanism by which nutrient availability modulates insulin signaling and how excess nutrients lead to insulin resistance. One well-established pathway for nutrient sensing is the hexosamine biosynthetic pathway (HSP), which produces the acetylated aminosugar nucleotide uridine 5′-diphospho-N-acetylglucosamine (UDP-GlcNAc) as its end product. Since UDP-GlcNAc is the donor substrate for modification of nucleocytoplasmic proteins at serine and threonine residues with N-acetylglucosamine (O-GlcNAc), the possibility of this posttranslational modification serving as the nutrient sensor has been proposed. We have recently directly tested this model in adipocytes by examining the effect of elevated levels of O-GlcNAc on insulin-stimulated glucose uptake. In this review, we summarize the existing work that implicates the HSP and O-GlcNAc modification as nutrient sensors and regulators of insulin signaling. RID="*" ID="*"Corresponding author.     

Physiological changes in hairless mice maintained on an antioxidant supplemented diet

Summary Several physiological parameters were measured in hairless mice maintained on a diet supplemented with antioxidants. Comparisons to animals on control diet revealed higher water-soluble antioxidant content of skin and increased liver weight. Only small differences in body weight occurred and no distinct histological changes were observed in skin or liver.This investigation was supported by National Research Service Award 1 F32 CAO5062, awarded by the National Cancer Institute, and USPHS Grant CA13464-04 from the NCI.     

Latent iron deficiency alters gamma-aminobutyric acid and glutamate metabolism in rat brain

Summary A diet containing 18–20 mg iron/kg to young weaned rats for 8 weeks altered the metabolism of gamma-aminobutyric acid and glutamate in the central nervous system without affecting blood hemoglobin. Subsequent rehabilitation with 390 mg iron/kg diet for 2 weeks normalized these changes.     

Increased sensitivity to pentobarbital in rats fed a diet lacking flavonoids.

Pentobarbital-sensitivity is highly increased in rats fed a diet lacking flavonoids; sleeping time was found to be increased by 42 and 30% as compared with rats fed a normal diet. These studies confirm our previous statement according to which for the rat, benzopyrones are vitamins.