Permissive hypothesis

Some, but not all, studies observe low CSF 5-HIAA in major depressive episodes. Numerous studies, though not all, have also reported no difference between patients with mania or depression in CSF 5-HIAA levels, consistent with both Prange et alls [15] permissive hypothesis for bipolar disorders and the indoleamine hypothesis. 

Clearly, a single neurotransmitter theory does not suffice to explain all known evidence. As a result, models that include two or more systems have been developed to encompass their modulatory interactions. One of the most cogent is the permissive hypothesis, which proposes that a decreased function in central serotonin transmission sets the stage for either a depressive or manic phase ( 60). This circumstance itself is not sufficient to produce the mood disturbance, however, with superimposed aberrations in NE function required to determine the phase of an affective episode (i.e., decreased 5-HT and decreased NE subserves depression decreased 5-HT and increased NE subserves mania). Data from animal studies to support this theory include the following ... 

The possible antimanic effect of this 5-HT precursor was postulated based on the permissive hypothesis concept of diminished 5-HT activity. When oral doses of L-tryptophan (1 to 4 g) are administered, there is evidence of increased 5-HT synthesis. Three of four double-blind studies yielded positive results, holding the promise of an effective antimanic treatment (275). An advantage of this drug is its relative lack of other adverse effects. 

The permissive hypothesis (10) emphasizes the importance of the balance between 5-HT and NE in regulating mood, not the absolute levels of these neurotransmitters or their receptors. If 5-HT levels are too low, the balanced control of the NE system is lost, permitting abnormal levels of NE to cause mania, as seen in bipolar disorders. If the NE levels fall, the balanced control of the 5-HT system is lost, allowing abnormal levels of 5-HT to cause the person to exhibit the symptoms of depression. 

Fig. 4.4 Simplified hypothesis of the mechanism of gpI20-induced dorsal root gangUon (DRG) neurotoxicity. CXCR4 binding on Schwann cells by SDF-Ia or gpI20 results in the release of RANTES, which induces tumor necrosis factor (TNF)-a production by DRG neurons, and subsequent TNFRl-mediated neurotoxicity in an autocrine/paracrine fashion. Reproduced with permission of John Wiley Sons, Inc. (Keswani et al. 2003b)...

Fig. 1.12. One hypothesis of the evolution of oxygen in the atmosphere in relation to the origin of life and the evolution of higher organisms. (From Earth (4th edn) by Press and Siever. Copyright 1986 W.H. Freeman and Company, with permission.)...

Figure 5.3 Diagram depicts the further-designed studies to test our hypothesis with respect to standardization of immunohistochemistry based on the antigen retrieval technique exemplified in a multiple direction to draw a conclusion, (a) Periods of formalin fixation, (b) Variable delay of fixation, (c) Storage of FFPE tissue blocks or sections, (d) Variable thickness of FFPE tissue sections, (e) Other variable conditions of processing FFPE tissue blocks. The stereoscopic frame of a cube represents the reliable limitation of quantitative IFIC demonstrated by serial studies as recommended in the text. Reproduced with permission from Shi et al., J. Histochem. Cytochem. 2007 55 105-109.

FIGURE 28-3 Two-dimensional fluorographs showing the 35S methionine-labeled polypeptides in the three major anterograde rate components of axonal transport SCa, slow component a SCb, slow component b FC, fast component. Note that rate component not only has a characteristic rate but a characteristic polypeptide composition. The discovery that each rate component has a different polypeptide composition led to the structural hypothesis. (With permission from Tytell, M. etal. SciencellA 179-181, 1981 [6] illustration provided by Dr. Michael Tytell.)... 

Figure 4.29 The adaptor hypothesis. (From Voet and Voet, 2004. Reproduced with permission from John Wiley Sons., Inc.)...

Fig. 6 Illustration from Chin and Klinman. Increased catalytic activity of horse-liver alcohol dehydrogenase in the oxidation of benzyl alcohol to benzaldehyde by NAD, measured by cat/ M (ordinate), correlates with the Swain-Schaad exponent for the -secondary isotope effect (abscissa), for which values above about four are indicators of tunneling. This is a direct test of the hypothesis that tunneling in the action of this enzyme contributes to catalysis. As the rate increases by over two orders of magnitude and then levels off, the anomalous Swain-Schaad exponents also increase and then level off. Reproduced from Ref. 28 with the permission of the American Chemical Society.

Fig. 4 Role of extracellular dopamine in responding for natural rewards (a) and for nicotine (b). This figure illustrates the way increased extracellular DA in the shell subdivision of the nucleus ac-cumbens is postulated to increase the pleasure associated with behaviours that generate rewards. It is proposed that the behavioural role of the process is to facilitate the acquisition of behaviours that result in reward. The hypothesis proposes that the powerful reinforcing properties of drugs of dependence, such as nicotine, reflect their ability to act directly on the dopamine neurones that project to this subdivision of the accumbens. Reproduced with permission from Balfour (2006)...

Fig. 11. Modes of action of fluorine on osteoblastic cells, (a) Tyrosine phosphatase hypothesis in osteoblastic cells, fluoride ion directly inhibits tyrosine phosphatase. Inhibition of this enzyme enhances the tyrosine phosphorylation of signalling molecules induced by receptor tyrosine kinase, which leads to activation of the extracellular signal-regulated kinase (ERK) through the Ras pathway and enhanced cell proliferation, (b) G-protein hypothesis in osteoblast-like cells, fluoride ions form a complex with aluminum, probably fluoroaluminate, which interacts with guanosine 5 -diphosphate (GDP) to form guanosine 5 -triphosphate (GTP)-like molecule. Activation of the G, protein stimulates the tyrosine phosphorylation of signalling molecules by a yet unknown tyrosine kinase (Tyr Kin) and activation of the ERK kinase through the Ras pathway leads to enhanced cell proliferation. (Reproduced by permission of Elsevier from Ref. [175] ...

Figure 4.24 N and B coimplanted in 4H-SiC and annealed in an inductively heated furnace at 1,600°C for 10 minutes within a SiC crucible and high-purity Ar atmosphere, (a) Comparison between as-implanted and annealed N and B profiles, (b) Comparison between the N annealed and simulated profile these were computed under the hypothesis of an N FED diffusion. (From [91]. 2002 Material Science Forum. Reprinted with permission.)...

Figure 12 Amyloid cascade hypothesis (modified after Hardy and Selkoe, 2002. Reprinted with permission. American Association for the Advancement of Science) Cholesterol is thouc it to be involved in the formation of f-amyloid (AP) in the brain. Inhibitors of cholesterol formation could then prevent the formation of (neurotoxic) amyloid.

Modified and reproduced, with permission, from Seeman P Dopamine receptors and the dopamine hypothesis of schizophrenia. Synapse 1987 1 133.)... 

The above mentioned ASME code [3] uses the type of calculation presented above and selects a safety factor of S=2 to complete plastic yielding according to the GE hypothesis or S=1.732 with respect to complete plastic yielding according to the shear hypothesis Hence the permissible internal pressure is ... 

Fig. 8. Working hypothesis for the development of pH-gated peptide structures. Specific conformations can be induced and stabilized by the formation of a side-chain host-guest complex between an ammonium group and a crown ether. (Reproduced with the permission of Ref. 11).

Figure 3.21 Hypothesis picture ofhydrate growth at a crystal. (Reproduced and modified from Elwell, D., Scheel, H.J. Crystal Growth from High Temperature Solution (1975). With permission from Academic Press.)...

FIG. 7 Lycopene and the prevention of chronic diseases The hypothesis. (Lycopene and the prevention of chronic diseases. Reprinted from Major findings from five international conferences. 2002. A.V. Rao, D. Heber, eds., p. 4. By permission of Caledonian Science Press.)... 

Figure 7.7. Oxide dissolution simple hypothesis on rate-determining step. [From Stumm (1986), with permission.]...

Table 12.5 Permissible Pairings According to the Wobble Hypothesis...

Let us examine separately the case of the cis and trans isomers of pentadiene. For the trans isomer the cis conformation is permissible so that one cannot assume a priori that this isomer won t coordinate to Ti by the two double bonds. This hypothesis, however, can be easily rejected by the following considerations. If the steric situation around Ti during the polymerization were to permit the coordination of the trans isomer of pentadiene by the two double bonds, in the cis conformation, butadiene or isoprene should also coordinate the same way. In this case, however, cis-1,4 units should be obtained both from butadiene and isoprene, and not 1,2 and 3,4, respectively, as observed. It seems reasonable to conclude, therefore, that the trans isomer of pentadiene coordinates to Ti by the vinyl group only, as butadiene or isoprene, before it is incorporated as a cis-1,4 unit. 

As it was mentioned above, one of the permissions of given hypothesis is homogeneous sensitivity and absolute medical resistance. Clinical experience testifies to the contrary situation. Cancerous tumors which begin to grow after realization of one or another scheme of chemotherapy usually are not completely resistant to this scheme in the case of its repeated application. Because of this reason we can t consider that all cases of chemotherapy inefficiency are caused by absolute medical resistance. There are two explanations of this phenomenon. Firstly, some tumors don t die as a result of chemotherapy because of temporary absolute medical resistance which then is reversed. Secondly, sensitive cells due to some reasons are erased not completely by preparation to which they are still sensitive. 

FIGURE 17.3. A Modified Barker Hypothesis the susceptibility exposure paradigm used as a model to assess the effects of prenatal exposure to polycyclic aromatic hydrocarhons. Adapted with permission Ifom Neurotoxicology and Brown et al. (2007). 

Fig. 17 Mapping of the 3D pharmacophore hypothesis onto compounds a and f (Fig. 16). The trigonal substitution pattern around Car is allowed to rotate yielding a novel scaffold in the 3D virtual screening campaign (the match is highlighted by the dashed rectangle). (Reprinted with permission from [130]. Copyright 2005 Elsevier Ltd.)...

All these studies indicate that the metabolic response to injury cannot be explained completely in terms of increased adrenocortical activity and confirm the hypothesis of Ingle (II) that the secretions of the adrenal cortex play a permissive rather than a causative role in postoperative metabolic changes. In other words, the presence of the adrenocortical secretions is necessary for the metabolic response to occur, but the secretions do not themselves initiate the response. 

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