Experimental evidences from animals

Animals have been used as models for the demonstration of action of potentized homeopathic medicines. If homeopathic medicines act on human patients they must act on animals. In allopathic medicine, animals particularly rats, mice, hamsters, 

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Cross-national correlations between the incidence of colon cancer and dietary habits have been used to select hypotheses for testing in case-control and cohort studies. These studies have shown that certain food preferences appear to be associated with either a high- or a low-risk for colon cancer. When such correlations are supported by experimental evidence from animal studies, the hypothesis could be attractive. 

The most common adverse effects of auranofin are gastrointestinal. About half of all users have loose stools at some time during treatment this effect can be transient, can occur at any time, and is rarely severe. No infective cause or signs of malabsorption has been found in any case and neither was gold absorption adversely affected. In a long-term study, diarrhea was mainly observed in the first 6 months of therapy with auranofin 6 mg/day in 8% of the cases this was a reason for withdrawal (44). There is experimental evidence in animals of a direct effect of auranofin on ion and water absorption from the intestine with inhibition of enterocjde Na+/K+-ATPase activity (SED-12, 525). 

Respiratory Tract Clearance. This portion of the model identifies the principal clearance pathways within the respiratory tract. The model was developed to predict the retention of various radioactive materials. Figure 3-7 presents the compartmental model and is linked to the deposition model (Figure 3-6) and to reference values presented in Table 3-9. Table 3-9 provides clearance rates and deposition fractions for each compartment for insoluble particles. The table provides rates of insoluble particle transport for each of the compartments, expressed as a fraction per day and also as half-time. ICRP (1994a) also developed modifying factors for some of the parameters, such as age, smoking, and disease status. Parameters of the clearance model are based on human evidence for the most part, although particle retention in airway walls is based on experimental data from animal experiments. 

Nevertheless, there is evidence from animal experiments and from cell culture systems that Al affects many biochemical and neurochemical metabolic events (for reviews, see Crapper McLachlan et al., 1991 Van der Voet et al., 1991 Mera, 1991). The experimental administration of Al or its salts by intracerebral or subcutaneous injection results in encephalopathies and in the production of Al-containing NFT (Wisniewski et al., 1980 Trancoso et al., 1982), due to accumulation of neurofilaments in the cell body and processes (axon, dendrites) of large neurons. However, the individual fibrils making up NFT in AD appear as PHF and are ultrastructurally different from the normal neurofilaments and those induced by Al (Munoz-Garcia et al., 1986). On the other hand, AD-type tangles share determinants with normal and Al-induced neurofilaments and also appear to contain MAPs, tau and MAP-2 (Langui et al.. 

Recently, these epidemiologic evidences and experimental data from animal studies [14-20] are highly suggestinig their benefrcial effects of isoflavones (2) on human health, however the supportive clinical data of such effects are either not available, or are awaiting the design and execution of appropriate large-scale clinical studies. Nevertheless, the data from limited small pilot studies are promising, and these data have spurred the current interest in this area [1, 13],... 

There are two main approaches to research into anxiety. The first is to establish experimental models of anxiety in animals and humans in order to discover its neurobiological basis. The second is to investigate the actions of anti-anxiety drugs in the brain in the hope that this will give some clues to the cause(s) of anxiety. This chapter will discuss evidence from both these lines of research. 

The overall evidence from studies in animals supports the observations of lead neurobehavioral effects in humans. As pointed out by Cory-Slechta (1995), studies in animals have provided a direct measurement of the behavioral process per se, and have done so in the absence of the covariates (e.g., socioeconomic status, parental IQ) known to affect IQ scores in human studies. It is also worth noting that animal studies, in which the experimental design is carefully controlled, have shown that the timing of exposure is crucial, that different neurobehavioral outcomes are affected differently (different thresholds), and that some behavioral alterations last longer than others. 

There is no experimental evidence available to assess whether the toxicokinetics of -hexane differ between children and adults. Experiments in the rat model comparing kinetic parameters in weanling and mature animals after exposure to -hexane would be useful. These experiments should be designed to determine the concentration-time dependence (area under the curve) for blood levels of the neurotoxic /7-hcxane metabolite 2,5-hexanedione. w-Hcxanc and its metabolites cross the placenta in the rat (Bus et al. 1979) however, no preferential distribution to the fetus was observed. -Hexane has been detected, but not quantified, in human breast milk (Pellizzari et al. 1982), and a milk/blood partition coefficient of 2.10 has been determined experimentally in humans (Fisher et al. 1997). However, no pharmacokinetic experiments are available to confirm that -hexane or its metabolites are actually transferred to breast milk. Based on studies in humans, it appears unlikely that significant amounts of -hexane would be stored in human tissues at likely levels of exposure, so it is unlikely that maternal stores would be released upon pregnancy or lactation. A PBPK model is available for the transfer of M-hcxanc from milk to a nursing infant (Fisher et al. 1997) the model predicted that -hcxane intake by a nursing infant whose mother was exposed to 50 ppm at work would be well below the EPA advisory level for a 10-kg infant. However, this model cannot be validated without data on -hexane content in milk under known exposure conditions. 

There is no experimental evidence adequate to evaluate whether metabolism of M-hcxanc is different in children. Similarly, there is no information available from animal experiments. The initial step in -hexane metabolism in animals is a hydroxylation step catalyzed by a P-450 enzyme. Since some of these enzymes are developmentally regulated, it would be of interest to know (1) if there are specific P-450 isozymes involved in -hexane hydroxylation and, (2) if so, are these isozymes known to be developmentally regulated ... 

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