Biochemical Observations

The diverse physiological actions of capsaicin described in the previous sections have motivated numerous, equally diverse, in vivo and in vitro studies in search of biochemical correlates. The most attention, however, has been focused on the sensory system since a direct effect of capsaicin on sensory nerves has been suspected for a long time. More recent observations of capsaicin-induced sensory neuron degeneration in neonatal animals have added further impetus to determine the resultant neurochemical deficits of this lesion. It is perhaps fortunate that the small type B neurons of dorsal root ganglia which appear anatomically to succumb to capsaicin after both neonatal and adult treatment are also among the neurons for which putative neurotransmitter markers have been identified. Accordingly, these markers, two of which are the peptides somatostatin and substance P, have provided both a means to assess the neurotoxic potential of capsaicin, and to some extent relate anatomical with neurochemical investigations. For the sake of coherence the biochemical aspects of some reports cited in the previous sections are discussed here. The major conclusions in these reports will be summarized in Section 13. 

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Saz, H.J., Lescure, O.L. and Bueding, E. (1968) Biochemical observations of Ascaris suum lung-stage larvae. Journal of Parasitology 54, 457 161. 

The intracellular distribution of steroid hormone receptors has long been the object of controversy. The first theoretical formulation on the intracellular location of the ERs was elaborated by Jensen in 1968 and is known as the two-step theory. Its execution was based entirely on biochemical observations obtained by means of tritium-marked estradiol. The ERs, in cells not exposed to hormones, are found abundantly in the soluble cell fraction, or cytosol (Fig. 1.1). Treatment with hormones confines the receptors to the particulated or nuclear fraction and causes their disappearance from the cytosol. The two-step theory established that the receptor is found in the cytoplasm naturally and upon the arrival of a hormone it is transformed into a complex hormone-receptor (first step) capable of translocating itself to the nucleus and of modifying gene expression (second step). 

Sakai, K., Kitagawa, T., and Yoshioka, K., An atypical case of tyrosinosis (1-parahydroxyphenyl lactic acid uria). 3. The outcome of the patient. Pathological and biochemical observations of the organ tissues. Jikeikai Med. J. 6, 15-24 (1959). 

Although the lysosome theory has stimulated much work in cytology, certain reservations remain with regard to the biochemical observations upon which it ultimately rests.57,58... 

Therapy with hydrochlorothiazide, up to 50 mg twice daily, or chlorthalidone, 50-100 mg daily, is recommended. Loop diuretics such as furosemide and ethacrynic acid should not be used because they increase urinary calcium excretion. The major toxicity of thiazide diuretics, besides hypokalemia, hypomagnesemia, and hyperglycemia, is hypercalcemia. This is seldom more than a biochemical observation unless the patient has a disease such as hyperparathyroidism in which bone turnover is accelerated. Accordingly, one should screen patients for such disorders before starting thiazide therapy and monitor serum and urine calcium when therapy has begun. 

Sewell AC, Poets CF, Degen I, Stoss H, Pontz BF (1996) The spectrum of free neuraminic acid storage disease in childhood clinical, morphological and biochemical observations in three non-Finnish patients. Am J Med Genet 63 203-208... 

Complex III Ubiquinone to Cytochrome c The next respiratory complex, Complex III, also called cytochrome focx complex or ubiquinone icytochrome c oxidoreductase, couples the transfer of electrons from ubiquinol (QH2) to cytochrome c with the vectorial transport of protons from the matrix to the intermembrane space. The determination of the complete structure of this huge complex (Fig. 19-11) and of Complex IV (below) by x-ray crystallography, achieved between 1995 and 1998, were landmarks in the study of mitochondrial electron transfer, providing the structural framework to integrate the many biochemical observations on the functions of the respiratory complexes. 

The work of Devi and associates [22] provided a potential molecular mechanism for mu-delta interactions and a physical basis to explain biochemical observations of a mu-delta opioid receptor complex [23,24]. Their work and the efforts of others [25] have clearly demonstrated that mu and delta receptors can form heterodimers, leading to synergistic interactions and the generation of novel signaling units. This work, in other words, provides a molecular mechanism to explain how it is possible for three basic types of opioid receptors to form a greater number of pharmacologically defined opioid receptor subtypes. 

The 5-hydroxylated analog of indolacetic acid is the principal urinary metabolite of serotonin. On the basis of two biochemical observations, the possible role of serotonin in inflammatory processes and the increase of urinary metabolites of tryptophan in rheumatic patients, Shen, from the Merck Laboratories, designed anti-inflammatory compounds derived from indolacetic acid. Among them he found indomethacin in 1963, one of the most powerful non-steroidal anti-inflammatory drugs currently known. ... 

V6. Van den Brenk, H. A. 8., and Jamieson, D., Brain damage and paralysis in animals exposed to high pressure oxygen—pharmacological and biochemical observations. Biochem. Pharmacol. 18, 165-182 (1964),... 

If the biochemical observations are correct, then novel treatments of schizophrenia might be ones that inhibit PLA2 and activate FACL. Eicosapentaenoic acid (EPA) is such a substance and has already generated promising therapeutic results, which are described in Chapter 20 (Peet, 1999). 

Protein C, like Factors II, VII, IX, and X, is a vitamin K-dependent protein. Activated protein C (PCa) can be derived by limited proteolysis of this zymogen by thrombin, trypsin, or by Russell s viper venom (VI). PCa, in contrast to the other vitamin K—activated ctors, exerts an anticoagulant activity by inhibiting Factors Va and Villa (Fll). A second activity identified for PCa is the release of plasminogen activator based on animal in vivo studies (CIO, Z2). These biochemical observations and the discovery of patients vnth recurrent thrombosis who are congenitally deficient in protein C make PCa a candidate for a central role in hemostasis (BIT). 

For the purpose of this review, we will limit our discussion to direct protein-protein interactions that are well characterized, are relevant for the biological function of the protein, and where structural information is available for the complex and the interactions sites. Much data from high-throughput proteomic analysis is at the level of biochemical observation and cataloguing of the interaction, hence, little or no information is known of the atomic details of many such interactions. However, a thorough structural understanding of the interaction is essential for FBDD. 

Chandra SV, Seth PK, Mankeshwar JK Manganese poisoning clinical and biochemical observations. Environ Res 7 374-380,1974 Charles JR Manganese toxaemia with special reference to the effects of liver feeding. Brain Journal of Neurology 50 30—43, 1927... 

Until the determination of the NMR structure of mPrP(121-231) in 1996 (Riek et al., 1996), knowledge of the three-dimensional structure of prpc 5 based on optical spectroscopy data (Pan et al., 1993 Safar et al, 1993), a wealth of biochemical observations, and physiochemical studies with synthetic polypeptide fragments of PrP that also included NMR investigations e.g., Zhang et al, 1995 see also Tagliavini et al, 2001). Given the scarcity of experimental data, for PrP as well as for PrP , much effort was devoted to three-dimensional molecular model-... 

These different conditions may be visualized in Figure I. This figure emphasizes that the biochemical observation of hyponatraemia gives no information about the volume of the ECF compartment, that information only being obtained from the patient s history and by clinical examination. 

Magil, A. B., V. Mavichak, N. L. Wong, G. A. Quamme, J. H. Dorks, and R. A. Surton. 1986. Long-term morphological and biochemical observations in cisplatin induced hypomagnesemia in rats. Nephron 43 223-230. 

Unfortunately, no histochemical or cytochemical studies of the involvement of lipolytic enzymes during the infection of potato leaves by P. infestans have yet been reported. Histochemical and biochemical observations of potato tubers infected by P. Infestans revealed elevated levels of esterase (measured with Q-naphthol acetate) in unidentified host organelles during infection (1 1). Cytochemical techniques were used to identify lipolytic activity in fungal and host cell walls during the infection of lettuce (Lactuca sativa L.) cotyledons by Bremia lactucae (12). 

Bonfante-Fasolo, R, Grippiolo, R., 1984. Cytochemical and biochemical observations on the cell-wall of the spore of Glomus epigaeum. Protoplasma 123, 140-151. 

The biosynthesis of bufotenine has not been entirely elucidated experimentally. Some biochemical observations, however, prompted Witkop (141) even at early stages of investigation to make the accepted (157) suggestion of the possibility of direct hydroxylation of the benzene ring in tryptophan prior to any reaction on the pyrrole part of the molecule. Since the hydroxyamino acid was found not only in toad secretions but later also in the mushrooms, it may be the precursor of serotonin and hence A/ -dimethyl derivative, bufotenine. 5-Hydroxytryptophan was first found... 

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