alpha-Chlorohydrin inhibits glyceraldehyde-3-phosphate dehydrogenase in multiple organs as well as in sperm.

Numerous studies have documented inhibitory effects of alpha-chlorohydrin (ACH) on glyceraldehyde-3-phosphate dehydrogenase (G3PDH) activity in spermatozoa. A sperm-specific G3PDH isoform has been described. The possibility that ACH may inhibit G3PDH in cell types other than sperm was investigated in this work. In addition, the onset of ACH-induced epididymal toxicity was described. Changes to epididymal histology occurred 6 h following a single dose of ACH (50 mg/kg po) and were confined to the proximal initial segment. By 24 h, no epithelial cells lined the basement membrane of that region. Three h after ACH administration (50 mg/kg po), G3PDH activity was significantly decreased in sperm (85%) as well as in kidney (31%), liver (49%), and epididymis (35%). Enzyme activity remained inhibited at 6 and 24 h. G3PDH was immunolocalized in the epididymis and staining was highest in the efferent ducts and initial segment as well as in smooth muscle. Since G3PDH is a microtubule-associated protein and microtubule-dependent endocytosis occurs in the epididymis, beta-tubulin was also immunolocalized. beta-tubulin densely stained the apical region of initial segment and caput epithelial cells. Disruption of beta-tubulin immunostaining correlated with the localization and onset of the lesion. Co-localization of G3PDH and beta-tubulin immunostaining was not observed although both antibodies most densely stained the initial segment. Our data indicate that histologic changes to the proximal initial segment of the epididymis occur rapidly, but subsequent to G3PDH inhibition. Moreover, ACH inhibition of G3PDH is not confined to sperm, although the sperm enzyme is most sensitive to inhibition.

alpha-chlorohydrin induced changes in sperm fertilizing ability in the rat: association with diminished sperm ATP levels and motility.

In the present study, alpha-chlorohydrin (ACH) (5, 10, 25, 50 and 75 mg/kg, po) was administered to rats and the effects on sperm ATP levels, sperm motility, and the ability of sperm to bind and penetrate rat oocytes were determined. Groups of rats were killed 5 days and 3 h following treatment. At both time points, sperm from ACH-treated rats (>/=10 mg/kg) had significantly lower levels of ATP when diluted in media containing glucose. No diminution of ATP was seen in sperm diluted in phosphate-buffered saline (PBS). Computer analysis of sperm motility indicated that straight-line velocity (VSL) was the most sensitive parameter to ACH treatment and was significantly decreased in rat sperm three hours after ACH exposure (25 mg/kg). A clear drop in percent penetration (35% vs. 85% in control) of zona-free rat oocytes by rat sperm of both ACH groups was observed at 10 mg/kg. Higher dose levels produced no significant further decrease in percent penetration. Overall, the fertilizing ability of sperm was highly sensitive to ACH doses that caused minor but significant changes in sperm ATP levels and no significant changes in motility. These data are consistent with the spermatozoan's need for an uncompromised energy supply to maintain its ability to bind and penetrate the oocyte.

Asthma care in community health centers: a study by the southeast regional clinicians' network.

Federally funded community health centers (CHCs) were surveyed to assess their ability to serve low-income asthma patients in the southeastern United States. Data were collected on CHC clinicians, pharmacy services, and patient characteristics. Twenty-six (74%) of 35 participating CHCs provided data on 83 distinct clinic sites in eight states, representing 898,977 billable patient visits to 318,920 people during the one-year study period. Participating CHCs provided 23% of all CHC patient visits in Region IV in 1995. Sixty-two percent of patients had a family income below poverty level. Almost 75% of the patients were uninsured or receiving Medicaid. Asthma was the diagnosis code for 2.04% of all medical encounters. Twenty-nine percent of sites were unable to provide medications for uninsured asthma patients, while 66% could provide drug samples. Thirty-three percent of CHCs had in-house pharmacies and 33% offered pharmacy vouchers. Eighty-two percent could provide beta-agonist inhalers, 54% could provide steroid inhalers, and 17% could provide peak flow meters. Federally funded CHCs provide care to many asthma patients from the highest risk segments of the population, but often do not have the resources needed to follow current clinical guidelines.