Lauro Galzigna

The oxidative metabolism of catecholamines in the brain: a review.

This paper summarizes the strong evidence that we now have that the oxidative pathway of metabolism of the catecholamines, dopamine and norepinephrine via their respective quinones occurs in vivo in the brain. This fact is not yet widely appreciated. The evidence is based on the chemical structure of neuromelanin, advanced mass spectrometry techniques and the identification of intermediates of this system, such as 5-cysteinyl dopamine, in the brain. Supportive evidence is presented from a number of sources including enzymology. A suggestion as to the possible normal function of this system is made.

Mud pack therapy in osteoarthrosis. Changes in serum levels of chondrocyte markers

We have previously shown that thermal mud therapy is able to influence chondrocyte activity of osteoarthrosic patients by modulating the production of serum cytokines, such as interleukin 1, and this was related to the presence of an anti-inflammatory principle in mature thermal mud. Mud therapy influences many biochemical processes of the body, independently of the thermic stimulation alone and the present paper documents specific increases of insulin growth factor 1 and decreases of tumor necrosis factor alpha in serum of osteoarthrosic patients after 12 days of mud pack application.

TOXICITY OF AMINOCHROMES

The first part of the present review deals with the chemical and enzymatic synthesis of adrenochrome and other aminochromes from the corresponding catecholamines. A description of the most significant pathways of formation and the reactivity of the aminochromes is presented. In the second part of the toxicity of aminochromes, mainly at the cardiac and CNS level, is described and some of the molecular mechanisms of the toxic action are outlined. The toxicity of the aminochromes appears to depend mainly on the production of reduced oxygen species through redox cycling. The interaction of aminochromes with sulfhydryl groups and the induced depletion of oxygen, ascorbate and glutathione are additional mechanisms resulting in noxious effects at a cellular level.

Physical and biochemical changes of thermal mud after maturation

Thermal mud is a therapeutic agent whose antirheumatic effectiveness is optimized by a process of maturation. The maturation of thermal mud was followed at 48 degrees C under controlled conditions by measuring physical and biochemical changes due to the growth of colonizing thermophilic microorganisms. Thermogravimetric measurements allowed us to identify the building up of an organic component including phospholipids and in particular a previously recognized sulfoglycolipid, which was further purified. The compound may be responsible for the antirheumatic effect of the mud and is produced by the colonizing species which develop in a period of maturation subsequent to that of production of photosynthetic pigments.

Direct and respiratory chain-mediated redox cycling of adrenochrome

Adrenochrome is reduced by ascorbate in a reaction accompanied by a large and rapid oxygen uptake. The rates of adrenochrome reduction and the concomitant oxygen uptake are decreased in the presence of superoxide dismutase or catalase. The species formed on the one-electron reduction of adrenochrome (i.e., the semiquinone) was shown by pulse radiolysis to rapidly react with oxygen (9.10(8) M-1.s-1), indicating the occurrence of a redox cycling in a system formed by adrenochrome, a reducing agent, and oxygen. Adrenochrome is also reduced to the corresponding semiquinone by complex I of beef heart submitochondrial particles supplemented with NADH, while succinate is unable to support this reduction. The o-semiquinone is the intermediate species in the superoxide-generating cycle resulting from both non-enzymatic and enzymatic reduction. The toxic effects of adrenochrome and its pathophysiological role can be explained, at least in part, on the basis of the demonstrated cycle.

Reversible acetoacetylation of amino groups in proteins

A method is described by which amino groups of proteins such as ribonuclease (ribonucleate pyrimidinonucleotide-2′-transferase (cyclizing), EC 2.7.7.16) and lysozyme (N-acetyl-muramide glycanohydrolase, EC 3.2.1.17) can be acetoacetylated by reaction with diketene. The acetoacetyl group can be removed at 25° from the acetoacetylated enzymes by treatment with hydroxylamine hydrochloride at pH 7. The material thus obtained resembles native proteins in its properties and recovers the full enzymatic activity. The tryptic hydrolysis of acetoacetylated oxidized ribonuclease A has been studied in connection with the investigation of covalent structure in proteins. The lysyl bonds in the protein molecule are rendered resistant to hydrolysis by trypsin while the arginyl bonds are split off.

2,6-Diisopropylphenol, a general anesthetic, inhibits glutamate action on rat synaptosomes

Abstract2,6-diisopropylphenol (propofol), a general intravenous anesthetic, inhibits the glutamate-dependent Ca2+ entry in rat synaptosomes with an approximate IC50 of 3.0×10−5 M.Propofol, at concentrations above 10−6M, also inhibits the ATP-dependent uptake of glutamate in the presence of Ca2+, with an approximate IC50 of 3.5×10−5M, while it only has a slight inhibitory effect on the release of glutamate. The ouabain-insensitive synaptosomal ATPase is strongly inhibited by propofol, with an IC50 of about 2.5×10−6M, at concentrations which do not affect the luciferase system.

Enzymatic dopamine peroxidation in substantia nigra of human brain.

The main metabolic pathway affected in Parkinsons disease is that of dopamine oxidation and melanin formation in substantia nigra which involves both oxidative and reductive enzymes. The cyclic nature of the biosynthetic pathway from dopamine to melanin implies that a derangement at any of the steps may result in the disappearance of melanin. Possible pathogenetic events such as oxidative stress have therefore no clearcut interpretation since they may be both cause or consequence of the disease. This paper documents the existence of a peroxidase converting dopamine to dopaminochrome in the presence of hydrogen peroxide in the substantia nigra of autopsied human brain. The activatory effect of dopaminochrome on a purified peroxidase is shown, together with the inhibitory effect of dopaminochrome-derived melanin and the activatory effect of melanin/Fe. The toxic effect of dopaminochrome on murine neuroblastoma cells cultured in vitro is demonstrated together with the inhibition of dopaminochrome melanization induced by acetylcholine in vitro.

Colonization by diatoms and antirheumatic activity of thermal mud.

We have identified diatoms among other thermophilic microorganisms as the main agents for the colonization of thermal mud resulting in a ‘maturation’ which renders the mud suitable to be used for mud‐pack treatment of osteoarthrosis patients. The main effects of the diatom growth are the progressive enrichment of mud extracts in chlorophyll a parallel to the building up of a sulfoglycolipid endowed with an anti‐inflammatory action. The sulfoglycolipid was also produced by diatoms isolated from the mud and cultivated in vitro. Copyright

The biochemical basis of Parkinson's disease: The role of catecholamineo-quinones: A review-discussion

This paper reviews the possible role of catecholamineo-quinones (OQs) in the genesis of Parkinsons disease (PD). This disease is characterized by damage caused to the pigmented catecholaminergic cells in various areas of the brain. The pigment involved is neuromelanin that is the end product of catecholamine oxidation by theo-quinone route. Evidence is presented regarding the overproduction in PD of these catecholamine OQs that damage the electron chain in the mitochondria leading to cell death. The roles of glutathione S-transferase and reactive oxygen species in this are also surveyed. A review of all known biochemical properties of theseo-quinones is included. The hypothesis is put forward that an important factor in the genesis of PD may be the overload by environmental toxins of enzymes such as glutathioneS-transferase that also detoxify catecholamine OQs.