H+ and HCO3- flux across apical surface of rat distal colon.

Colonic ion transport is postulated to occur via simultaneous operation of Na(+)-H+ exchange and Cl(-)-HCO3- exchange. Accordingly H+ and HCO3- should be transported simultaneously by the colon. To assess simultaneous H+ and HCO3- transport, net acid-base flux was measured in isolated segments of rat distal colon. When both tissue surfaces were bathed in symmetrical solutions containing Cl-, net base was secreted (-1.0 +/- 0.1 mu eq.cm-2.h-1). Cl- substitution with gluconate in the mucosal medium caused net base flux to switch from secretion to absorption (2.0 +/- 0.2 mu eq.cm-2.h-1). To evaluate whether base absorption was dependent on H+ secretion via Na(+)-H+ exchange, mucosal Na+ was substituted with N-methylglucamine, and amiloride, an inhibitor of Na(+)-H+ exchange, was applied. Na+ substitution and 1 mM amiloride inhibited base absorption by 37 and 38%, respectively, suggesting operation of Na(+)-H+ exchange. Because base absorption persisted, an additional mechanism was considered, HCO3- absorption via Cl(-)-HCO3- exchange. This was evaluated with an inhibitor of Cl(-)-HCO3- exchange 4-acetamido-4'-isothiostilbene-2,2'-disulfonic acid (SITS). SITS (1 mM) inhibited HCO3- absorption by 40%. The effects of amiloride and SITS were additive, suggesting that the Na(+)-H+ and Cl(-)-HCO3- exchangers operate simultaneously. Amiloride also inhibited H+ secretion when net HCO3- was secreted, suggesting that the direction of HCO3- movement does not influence Na(+)-H+ exchange activity. These data suggest that the colon transports both H+ and HCO3- across the apical surface via Na(+)-H+ exchange and Cl(-)-HCO3- exchange; H+ is secreted via Na(+)-H+ exchange, whereas HCO3- can be secreted or absorbed via Cl(-)-HCO3- exchange.

Base secretion in rat distal colon: ionic requirements.

To evaluate the ionic requirements of colonic base secretion, segments of rat distal colon were studied under short-circuited conditions. Net base flux was composed of an active secretory component and a diffusive component. Studied in the absence of a transepithelial HCO3- concentration gradient, active base secretion was dependent on the HCO3- concentration of the bathing solution but was not influenced by the CO2 tension or pH. Base secretion appeared to saturate with a Km of 33 +/- 9 mM and was inhibited by ouabain. The diffusive component was characterized by an apparent permeability coefficient to HCO3- of 8.9 +/- 0.9 x 10(-6) cm/s. In addition to requiring HCO3- on the serosal surface, net base secretion was inhibited by reducing the Na+ concentration in the serosal medium and the Cl- concentration in the mucosal medium. These data suggest that colonic base secretion involves HCO3- entry across the basolateral surface, energized by the Na+ gradient, and HCO3- exit across the apical surface in exchange for Cl-.

Occupational exposure to zeranol, an animal growth promoter.

Zeranol (3,4,5,6,7,8,9,10,11,12-Decahydro-7,14,16-trihydroxy-3-methyl-1H-2 - benzoxacyclotetradecin-1-one) is a synthetic oestrogenic agent used as an animal growth promoter. The effects of occupational exposure to zeranol in 11 exposed workers from a pelletising plant and 14 nonexposed subjects were assessed. A questionnaire showed that more breast symptoms were reported by male and female plant workers compared with non-exposed subjects, although the difference was not statistically significant. Clinical assessment showed no cases of gynaecomastia in all the male participants. Blood samples analysed by high performance liquid chromatography for zeranol, its precursor zearalenone, and its main metabolites did not show any of these compounds above the laboratory limit of detection. Serum levels of follicle stimulating hormone (FSH), luteinising hormone (LH), prolactin, and oestradiol showed no striking differences between the exposed and the non-exposed subjects. Total and low density lipoprotein cholesterol (LDL cholesterol) levels did not significantly differ between the two groups but mean high density lipoprotein cholesterol (HDL cholesterol) levels were higher in the exposed group; this could be due to relatively high HDL cholesterol in two women exposed to zeranol or relatively low HDL cholesterol in three non-exposed men.

Health hazards of tertiary amine catalysts.

Tertiary amine catalysts are widely employed in foundry and polyurethane foam manufacture operations. These highly reactive amines have been associated with graphic disturbances in vision and systemic health effects. Prominent among the reported effects on vision are mydriasis (dilated pupils), cycloplegia (loss of accommodation), and corneal edema, which may result in hazy (looking through smoke) or blurry (out of focus) vision and halo perception. Systemic symptoms, possibly due to a release of endogenous histamine, are consistent with pharmacologic actions of amines and have also been described. These symptoms, as well as the disturbances in vision, are transient. Nevertheless, employees who work with or around machinery, or drive vehicles, may be at an increased risk of accident and injury when experiencing these symptoms.

Pulmonary and immunologic evaluation of foundry workers exposed to methylene diphenyldiisocyanate (MDI).

A cross-sectional evaluation was performed of workers in a steel foundry in which methylene diphenyldiisocyanate (MDI) was used as a component of a binder system used to make cores and molds. Preshift and postshift spirometry and clinical evaluations were performed on 26 currently exposed (group I), on six formerly exposed (group II), and on 14 nonexposed workers to MDI (group III). Serum samples were assayed for total antibody binding, specific IgG by ELISA, and specific IgE by the RAST method to MDI-human serum albumin (HSA). Symptoms compatible with occupational asthma were elicited from seven (27%) of 26 group I workers and from three of six group II workers. No symptoms were reported by group III workers. Intrashift change in FEV1 (a mean decrease of 0.049 L) in group I workers was significantly decreased compared to that in unexposed group III workers (a mean increase of 65 ml; p = 0.043). Specific IgG and total antibody responses to MDI-HSA were detected only in workers with current or former exposure to MDI. Only one worker was identified with IgE-mediated occupational asthma exhibiting a positive prick test and elevated RAST to MDI-HSA of 25.5% bound. In this occupational setting, polyclonal immune responses to MDI-HSA and clinical sensitization to MDI were demonstrated to occur.

Bicarbonate secretion modulates ammonium absorption in rat distal colon in vivo.

Although the mammalian colon is thought to absorb large quantities of total ammonia, principally in the form of NH3, quantitative support for this hypothesis is lacking. In rat distal colon, we observed that NH3 was approximately 400 times more permeant than NH+4. In addition, colonic HCO-3 secretion influenced total ammonia (NH3 plus NH+4) absorption; that is, alteration of HCO-3 secretion caused a parallel change in total ammonia absorption. Perfusion with total ammonia also caused net HCO-3 secretion to switch to net absorption, and, in the setting of preexisting HCO-3 absorption, perfusate containing total ammonia enhanced HCO-3 absorption. These events suggest that colonic HCO-3 secretion titrates luminal NH+4 to NH3, permitting NH3 to diffuse from the lumen, while HCO-3 is titrated to carbon dioxide and also diffuses from the lumen. In support of titration of NH+4 and HCO-3, the magnitude of induced HCO-3 absorption approximated total ammonia absorption. This titration relationship suggests that, in kinetic studies, total ammonia absorption will be limited by a fixed rate of HCO-3 secretion. A model was developed that simulated these events.

Bicarbonate secretion in rat distal colon in vitro: a measurement technique.

To study HCO3- secretion in rat distal colon, we utilized a technique that permits control of electrical and chemical transepithelial gradients. With symmetrical solutions (pH 7.4, [HCO3-] 25 mM, and CO2 tension 40 mmHg) bathing both tissue surfaces and under short-circuit conditions, HCO3- secretion remained stable for greater than 4 h at 1 mueq. h-1.cm-2. As the mucosal solution was alkalinized, the serosal solution was acidified at 3.1 mueq.h-1.cm-2. Ninety-four percent of serosal acidification was accounted for by the rate of metabolic lactic acid generation and transepithelial HCO3- secretion. Clamping transepithelial voltage reversibly affected net HCO3- secretion, and a linear relationship existed between clamped mucosal voltage and net HCO3- flux (r = 0.99); mucosal voltage of -68 mV completely inhibited net secretion. The apparent permeability coefficient of the colon to HCO3- is 2.8 X 10(-6) cm/s. One millimolar ouabain completely inhibited net HCO3- secretion. Acetazolamide (10(-4) M) inhibited secretion by approximately 50%, whereas a 10(-3) M concentration inhibited secretion by 90%. These data demonstrate that net colonic HCO3- secretion can be measured without imposed electrical and chemical gradients and that this flux is voltage sensitive and depends on carbonic anhydrase and Na+-K+-ATPase activities.