To determine the mechanism and pathway of entry of polar nonelectrolytes into bile, we studied first the permeation of [3H]H2O, [14C]urea, [14C]erythritol, [14C]mannitol, [3H]sucrose, [3H]inulin and [3H]dextran across an isolated, in situ perfused segment of the guinea pig's extrahepatic bile duct. All of these molecules, except [3H]dextran, permeated the bile duct. The diffusive permeability coefficients (cm per sec per 10(6) ranged from 248 for [3H]H2O to 1.2 for [3H]inulin. On the basis of these results, we formulated two models of solute biliary excretion. In Model I, permeation across both the canaliculus and ductule/duct was assumed to be by simple diffusion. In Model II, solute was assumed to enter the canaliculus by convection and diffusion, and the ductule/duct by diffusion. Reflection coefficients and/or permeability coefficients for the canalicular membrane were then determined by fitting the equations describing these processes to the bile-to-plasma ratios of [14C] erythritol, [14C]mannitol, [3H]sucrose and [3H]inulin observed at different rates of bile flow produced by partially clamping the bile duct cannula and subsequently infusing taurodehydrocholate. Only when convection was included as a mechanism of canalicular permeation (Model II) was excellent fitting observed. In such a case, the reflection coefficients and permeability coefficients for the carbohydrates in question were similar to those reported for other transporting epithelia. Cholestasis produced by taurolithocholate (10 to 40 mumoles per kg, i.v.) was associated with an irreversible increase in both the sieving coefficient and permeability coefficient for [3H]sucrose and [3H]inulin, even when the inhibition of bile flow was fully reversible. The permeability to [14C] erythritol and [14C]mannitol was either not affected or minimally increased. These findings suggest that, in the guinea pig: solutes as large as [3H]inulin enter the biliary tree both at the canaliculus and bile ductule/duct; [14C]erythritol and [14C]mannitol gain access into the canalicular lumen primarily by convection, whereas [3H]sucrose and [3H]inulin permeate mainly by diffusion; distal permeation of these carbohydrates is small, and accounts for 1 to 11% of their total biliary entry; the canalicular membrane permeability to [3H]sucrose and [3H]inulin is not functionally important in bile secretion, and a fraction of canalicular bile flows through the transjunctional shunt pathway.

Animals↗

PubMedDate not supplied

Virulence gene expression during conidial germination in Cochliobolus carbonum.

The fungal pathogen Cochliobolus carbonum race 1 produces a host-selective toxin (HC-toxin) that is responsible for increased virulence on susceptible genotypes of maize. The toxin is synthesized by a peptide synthetase, which is a product of the HTS1 gene. Because the toxin is not stored in dormant conidia, early expression of HTS1 is crucial for extensive colonization of susceptible leaf tissue. To detect the HTS1 transcript and determine the onset of HTS1 gene expression, we analyzed RNA preparations from ungerminated and germinated conidia by reverse transcription-polymerase chain reaction using oligonucleotide primers within the 15.7-kb open reading frame of HTS1. With primer pairs near both the 3'- and the 5'-termini, amplified products of the HTS1 transcript were detected in RNA prepared from dormant conidia. With all primer pairs used, the quantities of transcript increased substantially during germ tube emergence and elongation, indicating that expression of HTS1 is up regulated during spore germination. Digestion with restriction endonucleases confirmed the identity of the amplified products. Amplification of the constitutively expressed beta-tubulin transcript, which is processed to remove introns, as well as the absence of amplification products with primers spanning the HTS1 coding sequence established that cDNA was amplified and not contaminating genomic DNA.

Amino Acid Isomerases↗

PubMedDate not supplied

When leukemia complicates pregnancy.

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Adolescent↗

PubMedDate not supplied

Antagonism of pancuronium and its metabolites by neostigmine in cats.

Antagonism by neostigmine of neuromuscular blockade produced by pancuronium or its metabolites was studied in the cat anterior or tibialis muscle-peroneal nerve preparation using constant infusions of muscle relaxants. The ED50 of neostigmine (dose which caused a 50% antagonism) was 16, 11, 29, and 26 micrograms/kg for pancuronium, 3-hydroxypancuronium, 17-hydroxypancuronium, and 3, 17-hydroxypancuronium, respectively. Times of onset of neostigmine action were shorter when antagonizing 17-hydroxypancuronium neuromuscular blockade. Duration of neostigmine action when antagonizing 17- or 3, 17-hydroxypancuronium blockade was shorter than with pancuronium or 3-hydroxypancuronium. We conclude that more neostigmine is required to antagonize 17- or 3,17-hydroxypancuronium neuromuscular blockade than is required to antagonize pancuronium. Conversely, less neostigmine was required to antagonize 3-hydroxypancuronium blockade.

Animals↗

PubMedDate not supplied

Internet-based prescription of sildenafil: a 2104-patient series.

BACKGROUND: The Internet is becoming increasingly important as a way for patients to acquire medical information and as a means for patient-physician communication. Questions about appropriate use of this new technology have been brought to the fore by the many patients using the Internet to seek sildenafil prescriptions. OBJECTIVE: To present the first description of a physician designed and directed Internet-based prescribing system of sildenafil, together with data covering more than 2,100 patient encounters. METHODS: Retrospective analysis of a large case series from a medical practice that prescribes sildenafil based on medical and sexual histories obtained through a physician designed and directed World Wide Web (WWW) site, compared against patients from clinics at a Midwestern inner city medical center. We compared all 2,104 Internet patients seeking sildenafil prescriptions online between June 14, 1998, and March 1, 1999, with all 36 medical center patients obtaining sildenafil prescriptions during the same period. The outcome measures compared were: completeness of medical record; patient safety as noted by the follow up responses of all patients requesting refills, any comments received by the internet site (webmaster), and patient or physician comments noted in the clinic medical record; satisfaction as noted by the follow up responses of all patients requesting refills, any comments received by the internet site (webmaster), and patient or physician comments noted in the clinic medical record; examinations and laboratory tests. RESULTS: Fifty-six percent of Internet requests came from 46 states, and 44% from eight foreign countries. Of 2,104 requests, 2,100 were granted. Three hundred ten patients have requested medication refills: all reported erections sufficient for intercourse and 69% said their satisfaction exceeded all expectations; none were at all dissatisfied. Side effect rates were comparable to those in the literature. Comparison of the medical history obtained from Internet patients with that recorded in clinic patients' charts revealed that the former was far more complete. No clinic patient received any examination or laboratory test specific for erectile dysfunction or its causes. There were no reported deaths or serious complications in either group. CONCLUSIONS: Internet-based prescription of sildenafil provides the physician with a complete and very detailed medical and sexual history for 100% of patients without denying any information routinely obtained in a direct patient contact setting. Internet-based practice, which may be expected to require far fewer healthcare resources than traditional settings, rates very high in patient satisfaction among patients requesting a refill; no negative comments were received from all other patients. Overall, these data support the safety and effectiveness of Internet prescribing of selected medications.

Commerce↗

PubMedDate not supplied

Families must have information.

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Caregivers↗