Activity of phenolsulfotransferases in the human gastrointestinal tract.

Sulfate conjugation by sulfotransferase enzymes is an important pathway for the detoxication of xenobiotics and endogenous compounds. The large surface area of the gastrointestinal tract exposes the body to a range of potential toxins, and hence local metabolism is likely to be important. The ability of different regions of the gut to sulfate micromolar concentrations of simple phenols and catecholamines has been determined throughout the gut using 4-nitrophenol and dopamine as standard substrates. The pattern of sulfation of both compounds was similar, with activity highest in the small bowel >right colon >left colon >rectum >stomach >esophagus. High concentrations of sulfotransferases in the reservoir areas of the right and left colon indicate possible importance in detoxication by sulfation and also perhaps in activating mutagens in the same areas. Nutritional factors, such as a high-fat diet may, however, alter sulfotransferase activity.

Diagnostic exercise: astrocytoma with involvement of medulla oblongata, spinal cord, and spinal nerves in a raccoon (Procyon lotor).

Neoplasms affecting the central and peripheral nervous systems of wild animals are extremely rare. Described are clinical signs and pathologic and immunohistochemical findings in an adult female raccoon (Procyon lotor) with an astrocytoma that involved medulla, cervical spinal cord, and roots of the cervical spinal nerves. Microscopically, the neoplastic cells revealed some pleomorphism but generally had fusiform morphology and showed moderate numbers of mitotic figures. Glial fibrillary acidic protein was demonstrated within the neoplastic cells by immunohistochemistry. This appears to be the only reported case of astrocytoma that involved multiple anatomic sites in the central nervous system of this raccoon.

Impaired detoxication of hydrogen sulfide in ulcerative colitis?

Impaired butyrate oxidation and raised counts of sulfate-reducing bacteria in the colon of patients with ulcerative colitis (UC) indicate that the disease may be induced or aggravated by hydrogen sulfide toxicity. We aimed to examine enzymatic removal of H(2)S in erythrocytes and colonic mucosa from controls and patients with UC and Crohn's disease (CD). Rhodanese (RHOD) and thiol methyltransferase (TMT) activities were measured in rectal mucosa and erythrocytes, and plasma thiocyanate was determined. Four groups were analyzed: patients with UC, patients with CD, hospital controls (patients with dyspepsia or IBS), and a group of healthy volunteers. RHOD and TMT activity in rectal biopsies did not differ significantly between controls and patients with UC or CD (n=56). Control levels of RHOD were significantly higher in men than in women (212+/-25 and 132+/-14 nmol/mg/min, respectively; P<0.01). In erythrocytes (n=128) RHOD activity was significantly higher in UC patients than in hospital or volunteer controls (1.15+/-0.12 compared with 0.88+/-0.12 and 0.66+/-0.02 nmol/mg/min; P<0.05 and P<0.02, respectively). TMT activity was also significantly higher in erythrocytes from UC patients and hospital controls than volunteer controls (2.02+/-0.13 pmol/mg/min [P<0.001], 1.51+/-0.21 pmol/mg/min [P<0.05], and 1.17+/-0.18 pmol/mg/min, respectively). We found no evidence of defective enzymic detoxication of sulfide by RHOD or TMT in patients with UC or CD.

Neuronal vacuolation in raccoons (Procyon lotor).

Microscopic vacuolar changes in neuronal perikaryon are described in two free-ranging raccoons (Procyon lotor) from different geographic locations in the United States. Both animals were negative for rabies and scrapie-associated antigens. Microscopically, lesions were not seen in the neuropil. Neuronal vacuolations have previously been documented in brains of normal animals and in diseases such as rabies and prion-associated encephalopathies. Although experimental transmission of a spongiform mink encephalopathy has been documented in raccoons, a naturally occurring spongiform encephalopathy has not been described in this species. The presence of neuronal vacuolations in the raccoons is novel and requires further investigation to elucidate the mechanism of this phenomenon.

Mucosal protection against sulphide: importance of the enzyme rhodanese.

BACKGROUND: Hydrogen sulphide (H(2)S) is a potent toxin normally present in the colonic lumen which may play a role in ulcerative colitis (UC). Two enzymes, thiol methyltransferase (TMT) and rhodanese (RHOD), are thought to be responsible for sulphide removal but supportive evidence is lacking. AIMS: To determine the distribution of TMT and RHOD in different sites throughout the gastrointestinal tract and their efficacy as detoxifiers of H(2)S. METHODS: Enzyme activities were measured in normal tissue resected from patients with cancer. TMT and RHOD activities were determined using their conventional substrates, 2-mercaptoethanol and sodium thiosulphate, respectively. For measurement of H(2)S metabolism, sodium sulphide was used in the absence of dithiothreitol. Thiopurine methyltransferase (TPMT), which in common with TMT methylates sulphydryl groups but is not thought to act on H(2)S, was also examined. RESULTS: TMT, RHOD, and TPMT activities using their conventional substrates were found throughout the gastrointestinal tract with highest activity in the colonic mucosa. When H(2)S was given as substrate, no reaction product was found with TMT or TPMT but RHOD was extremely active (Km 8.8 mM, Vmax 14.6 nmol/mg/min). Incubation of colonic homogenates with a specific RHOD antibody prevented the metabolism of H(2)S, indicating that RHOD is responsible for detoxifying H(2)S. A purified preparation of RHOD also detoxified H(2)S. CONCLUSIONS: RHOD, located in the submucosa and crypts of the colon, is the principal enzyme involved in H(2)S detoxication. TMT does not participate in the detoxication of H(2)S.