Regulation of chloride channels by protein kinase C in normal and cystic fibrosis airway epithelia

Apical membrane chloride channels control chloride secretion by airway epithelial cells. Defective regulation of these channels is a prominent characteristic of cystic fibrosis. In normal intact cells, activation of protein kinase C (PKC) by phorbol ester either stimulated or inhibited chloride secretion, depending on the physiological status of the cell. In cell-free membrane patches, PKC also had a dual effect: at a high calcium concentration, PKC inactivated chloride channels; at a low calcium concentration, PKC activated chloride channels. In cystic fibrosis cells, PKC-dependent channel inactivation was normal, but activation was defective. Thus it appears that PKC phosphorylates and regulates two different sites on the channel or on an associated membrane protein, one of which is defective in cystic fibrosis.     

Induction of mating behavior in rats by luteinizing hormone-releasing factor

Ovariectomized female rats treated with estrogen, in dosages too low to provoke mating, displayed this behavior when given subcutaneous injections of synthetic luteinizing hormone-releasing factor (LRF) 48 hours later. Two hours after the injection of LRF, components of female sexual behavior appeared. The lordosis reflex followed mounting by the male, and darting and hopping behavior was quite prevalent. On the other hand, treatment with estrogen followed by luteinizing hormone, follicle-stimulating hormone, or thyrotropin-releasing factor did not induce copulatory behavior. The results suggest that LRF may play a role in induction of mating behavior.     

Polyamine metabolism: a potential therapeutic target in trypanosomes

alpha-Difluoromethylornithine (RMI 71,782), a specific irreversible inhibitor of the first step in polyamine biosynthesis, that is, the formation of putrescine from ornithine by ornithine decarboxylase, cures mice infected with a virulent, rodent-passaged strain of Trypanosoma brucei brucei. This parasite is closely related to the trypanosomes that cause human sleeping sickness. The drug, which is remarkably nontoxic, was effective when administered in drinking water or by intubation. The ability of the compound to inhibit ornithine decarboxylase in vitro was demonstrated by the reduced amounts of putrescine synthesized from tritiated ornithine in Trypanosoma brucei suspensions. These observations direct attention to polyamine metabolism as a target for chemotherapy of parasitic diseases.     

Equine grazing preferences among winter annual grasses and clovers adapted to the southeastern united states

Forage acceptability of five cool season annual grasses and four annual clovers to yearling horses was evaluated in Georgia during winter and spring of two years. With cafeteria grazing trials, preference in consumption was determined by difference in forage harvested from mower strips before and after grazing. In four test grazing periods,annual ryegrass was preferred (P<.05) by the yearlings, averaging 75% apparent consumption of the dry forage. Oats and wheat were second in preference, averaging 47 and 41% respectively. Rye and triticale were least preferred, averaging only 35 and 32% apparent consumption, respectively. Of the annual clovers tested, crimson, berseem, and subterranean were all highly palatable (P<.05) to horses with an average consumption of 71% across all three clover varieties. Arrowleaf clover was unacceptable (P<.05), having only 22% apparent consumption. Yearling horses avoided grazing rye, triticale, and arrowleaf clover when other forages were available.     

In vitro effects and in vivo efficacy of a novel cyclooxygenase-2 inhibitor in cats with lipopolysaccharide-induced pyrexia

OBJECTIVE: To determine cyclooxygenase (COX)-2 selectivity, pharmacokinetic properties, and in vivo efficacy of firocoxib (ML-1,785,713) in cats. ANIMALS: 5 healthy male and 14 healthy female domestic shorthair cats. PROCEDURE: Selectivity of firocoxib for inhibiting COX-2 was determined by comparing the potency for inhibiting COX-1 with that of COX-2 in feline blood. Pharmacokinetic properties were determined after i.v. (2 mg/kg) and oral (3 mg/kg) administration in male cats. In vivo efficacy was evaluated in female cats with lipopolysaccharide (LPS)-induced pyrexia with administration of firocoxib 1 or 14 hours before LPS challenge. RESULTS: Blood concentrations resulting in 50% inhibition of COX-1 and COX-2 activity in vitro were 75 +/- 2 microM and 0.13 +/- 0.03 microM, respectively, and selectivity for inhibiting COX-2 relative to COX-1 was 58. Firocoxib had moderate to high oral bioavailability (54% to 70%), low plasma clearance (4.7 to 5.8 mL/min/kg), and an elimination half-life of 8.7 to 12.2 hours. Firocoxib at doses from 0.75 to 3 mg/kg was efficacious in attenuating fever when administered to cats 1 or 14 hours before LPS challenge. CONCLUSIONS AND CLINICAL RELEVANCE: Firocoxib is a potent COX-2 inhibitor and is the only selective COX-2 inhibitor described for use in cats to date. It is effective in attenuating febrile responses in cats when administered 14 hours before LPS challenge, suggesting it would be suitable for once-a-day dosing. Because selective COX-2 inhibitors have an improved therapeutic index relative to nonselective nonsteroidal anti-inflammatory drugs in humans, firocoxib has the potential to be a safe, effective anti-inflammatory agent for cats.     

Influence of endophyte-infected tall fescue on serum prolactin and progesterone in gravid mares.

Thirty mares in late gestation were used in a 3-yr study to assess effects of the tall fescue endophyte Acremonium coenophialum on serum prolactin (PRL) and progesterone. Two paddocks of each treatment, 0 or 100% infected 'Kentucky 31' tall fescue, were grazed by the mares for 21 d. Blood was collected three times per week until parturition. At 7-d intervals, mares were challenged with thyrotropin-releasing hormone (TRH) while grazing and blood was collected postinjection. Mares grazing 100% infected tall fescue (E+) had decreased serum PRL compared with mares grazing the 0% infected tall fescue (E-) in 2 of 3 yr. Within 8 d postgrazing, serum PRL for E+ mares equaled or surpassed values of the E- mares. Serum PRL was not different during the 3rd yr. In response to TRH, serum PRL rate of increase was similar between treatments but remained elevated (P less than .01) in the E+ mares at the 180-, 240-, and 300-min sample times. Serum progesterone was lowered (P less than .05) by E+ but increased to control values within 10 d postgrazing. It is concluded that serum PRL and progesterone in the gravid mare were decreased by the presence of A. coenophialum in 'Kentucky 31' tall fescue grass but normal levels were reestablished within 2 to 3 wk.     

Clinical anatomy of the equine sphenopalatine sinus

REASONS FOR PERFORMING STUDY: Disorders of the equine sphenopalatine sinus, including empyema and neoplasia, have been reported to cause damage to cranial nerves II and V. However, the clinical anatomy of these sinuses is not well described in horses. OBJECTIVE: To examine the anatomy of the sphenopalatine sinuses in a range of equidae and, in particular, to examine the relationship of these sinuses to adjacent major nerves and vessels. METHODS: The anatomy of the sphenoidal and palatine paranasal sinuses was examined in 16 equidae, primarily using transverse skull sections. Relevant structures were documented and photographed. RESULTS: There was much variation between individual horses in sphenopalatine sinus anatomy. The sphenoidal sinuses were small in young horses and appeared to become larger and more complex with age. Variation was present in the extent that the sphenopalatine sinus extended into the basisphenoid bone. The septum dividing left and right sphenoidal sinuses was frequently not midline, but was intact in all cases. The sphenoidal and palatine sinuses communicated in most horses. In such cases, what could accurately be termed the (combined) sphenopalatine sinuses usually drained directly into the caudal maxillary sinuses. Additionally, in 5 out of 16 cases, some compartments of the sphenoidal sinus also drained into the ethmoidal sinus. The dorsal and lateral walls of the sphenoidal sinus were very thin and directly adjacent to cranial nerves II, III, IV, V and VI and major blood vessels. CONCLUSIONS: The equine sphenoidal and palatine sinuses are very variable in their anatomy, but are always in close proximity to multiple cranial nerves and major blood vessels. POTENTIAL RELEVANCE: Many cranial nerves and blood vessels could be damaged with disorders involving the sphenopalatine sinus, potentially causing major and variable neurological syndromes, haemorrhage and extension of sepsis.     

In vitro effects and in vivo efficacy of a novel cyclooxygenase-2 inhibitor in dogs with experimentally induced synovitis

OBJECTIVE: To determine cyclooxygenase-2 (COX-2) selectivity, pharmacokinetic properties, and in vivo efficacy of ML-1,785,713 in dogs. ANIMALS: 21 healthy male and female mixed-breed dogs and 24 healthy male Beagles. PROCEDURE: Selectivity of ML-1,785,713 for inhibiting COX-2 was determined by comparing the potency for inhibiting cyclooxygenase-1 (COX-1) with that of COX-2 in canine blood. Pharmacokinetic properties were determined after i.v. (2 mg/kg) and oral (8 mg/kg) administration in female mixed-breed dogs. In vivo efficacy was evaluated in male mixed-breed dogs with urate crystal-induced synovitis. Prophylactic efficacy was evaluated by administering ML-1,785,713 two hours before induction of synovitis whereas therapeutic efficacy was determined by administering ML-1,785,713 one hour after induction of synovitis. RESULTS: Blood concentrations that resulted in 50% inhibition of COX-1 and COX-2 activity in vitro were 119.1 microM and 0.31 microM, respectively, and selectivity ratio for inhibiting COX-2 relative to COX-1 was 384. ML-1,785,713 had high oral bioavailability (101%), low systemic clearance (77 mL/min/kg), and an elimination half-life of 5.9 hours. ML-1,785,713 was efficacious when administered prophylactically and therapeutically to dogs with urate crystal-induced synovitis. CONCLUSIONS AND CLINICAL RELEVANCE: ML-1,785,713 is a novel, potent COX-2 inhibitor that is the most selective COX-2 inhibitor described for use in dogs to date. ML-1,785,713 has oral bioavailability and low systemic clearance that is comparable to other non-steroidal anti-inflammatory drugs. It is effective after prophylactic and therapeutic administration in attenuating lameness in dogs with urate crystal-induced synovitis. Drugs that specifically inhibit COX-2 and not COX-1 at therapeutic doses may have an improved tolerability profile, compared with nonselective non-steroidal anti-inflammatory drugs.     

Technology characteristics, choice architecture, and farmer knowledge: the case of phytase

Phytase is an enzyme that frees the phosphorus bound in feed grains and thus reduces the amount of dicalcium phosphate supplementation required for non-ruminants, reducing phosphorous excretion and thus reducing water pollution. This innovation has been widely adopted by feed companies in the US due to decreased phytase production costs and increased dicalcium phosphate costs. The roles played by phytase characteristics and choice architecture in the widespread use of this win–win technology are examined. A recent survey has also revealed that Midwestern farmers are largely unaware of this technology even though they are using it. One implication is that further research on win–win technologies that will be adopted by industries, rather than being dependent on adoption by individuals, may be beneficial.     

Effect of sodium chloride on gluten network formation,dough microstructure and rheology in relation to breadmaking

Sodium chloride (NaCl) is an essential ingredient to control the functional properties of wheat dough and bread quality. This study investigated the effect of NaCl at 0, 1 and 2%, (w/w, flour base) on the gluten network formation during dough development, the dough rheology, and the baking characteristics of two commercial flours containing different levels of protein (9.0 and 13.5%) and with different glutenin-to-gliadin ratios. Examination of the dough structure by confocal microscopy at different stages of mixing show that the gluten network formation was delayed and the formation of elongated fibril protein structure at the end of dough development when NaCl was used. The fibril structure of protein influenced the dough strength, as determined by strain hardening coefficient and hardening index obtained from the large deformation extension measurements. NaCl had a greater effect on enhancing the strength of dough prepared from the low protein flour compared to those from the high protein flour. The effect of NaCl on loaf volume and crumb structure of bread followed a similar trend. These results indicate that the effect of NaCl on dough strength and bread quality may be partially compensated by choosing flour with an appropriate amount and quality of gluten protein.