Immunohistochemical localization of vanilloid receptor subtype 1 (TRPV1) in the guinea pig respiratory system

Transient receptor potential vanilloid-1 (TRPV1) containing nerves are implicated in cough and bronchoconstriction although the significance of their documentation on non-neuronal cells is unclear. We have investigated the anatomical distribution and location of TRPV1 in an animal species often utilized in models of cough and airway inflammation. The distribution and localization of TRPV1 immunoreactivity in the lung was studied using confocal microscopy. Double labelling were carried out using the panaxonal marker, protein gene product 9.5 (PGP) and the neuropeptide substance P. TRPV1 was localized to fine axons within the epithelium of the trachea, however this represented only a fraction of the total axonal innervation of the epithelium. TRPV1 immunoreactive axons were also found in and around subepithelial regions of the airways, including smooth muscle and blood vessels and within the lower airways, found in the vicinity of bronchi and bronchioles, and in and around alveolar tissue. TRPV1 in the epithelium of the trachea was co-localized with substance P containing axons, although TRPV1 immunoreactive neuropeptide negative axons were also discernible. We found evidence for TRPV1 localization to axons throughout the respiratory tract. The distribution was heterogeneous and represented a fraction of the total neuronal innervation of the airways. No TRPV1 was found localized to airway epithelial cells. TRPV1 was often co-localized with the sensory neuropeptide substance P but there was evidence of TRPV1 positive neurones that did not express substance P. This suggests a role for TRPV1 in the airway that is independent of sensory neuropeptides.     

Alpha-naphthyl-isothiocyanate-induced cholestasis in the rat: studies of liver plasma membrane enzymes.

Oral administration of a single dose of alpha-naphthyl-isothiocyanate (ANIT) to rats produced a conjugated hyperbilirubinaemia, maximal at 2 days and which subsided by 7. The activities of 3 liver plasma membrane enzymes, Mg-2+-ATPase, (Na-+-K-+)-ATPase and 5-nucleotidase, and serum bilirubin levels were studied for up to 7 days after treatment. Activities of the 3 enzymes were significantly decreased at 2 days after treatment and returned to normal by 7, thus varying inversely with the degree of hyperbilirubinaemia. Enzyme histochemistry used to demonstrate canalicular localization of Mg-2+-ATPase in sections of whole liver and of isolated plasma membrane pellets showed that the reduction in activity was not a uniform partial loss, but represented a range of reductions in most canaliculi with a few retaining normal staining intensity. The results suggest that after ANIT intoxication there is a membrane lesion which may be responsible for the observed hyperbilirubinaemia due to the failure of secretion of biliary constituents into the canaliculus. However, more direct studies are necessary to determine whether any one of these enzymes is directly involved in the transport of biliary constituents across the bile canalicular membrane.     

Managing ischemic skin ulcers.

Etiologic elements in ischemic ulcers include physical factors (pressure, shearing forces, friction and heat), nutrition and infection, as well as circulatory, metabolic and neurologic problems. Prevention is the primary objective of the management program. For patients in nursing homes who have already developed ulcers, low-intensity direct electric current (LIDC) has proved to be a useful adjunct to conventional management. The infection was more rapidly controlled and the wound size more quickly reduced. LIDC is readily accepted by the patient.     

Experience with central high flow arteriovenous fistulas in patients requiring chronic parenteral chemotherapy or hemodialysis

Fifty central high flow arteriovenous fistulas were constructed using bovine arterial heterograft during the past four years to provide vascular access in forty-four patients requiring cyclic infusion chemotherapy or chronic hemodialysis. Overall long-term patency of thirty-six axillary-axillary and fourteen axillary-internal jugular fistulas was approximately 80 per cent, and of those fistulas that failed, 87 per cent were successfully revised. All failures occurred within the first year after construction and were confined to the group of patients receiving cyclic infusion chemotherapy. Most of the failures could be directly related to constant rather than intermittent use of the fistulas. Complications other than graft occlusion occurred in three patients and prompted surgical intervention—in one patient for brachial artery thrombosis, in one for unilateral facial edema after axillary-internal jugular fistula, and in one for aneurysmal degeneration of the midsegment of one axillary-axillary graft. There was no operative mortality, and there were no septic, hemorrhagic, or significant wound healing complications in this high risk group of patients. Hemodynamic evaluations of both acute and chronic fistulas showed an approximate 20 per cent increase in cardiac output, cardiac index, and right ventricular stroke work index which were subjectively and objectively well tolerated in those patients studied. Ease and comfort of cannulation of these fistulas for blood sampling, infusion chemotherapy, and hemodialysis were uniformly acceptable to both nurses and patients.Central high flow arteriovenous fistulas have proved a safe, durable, well tolerated means of providing vascular access in patients whose usual routes have been exhausted but who remain candidates for cyclic infusion chemotherapy or chronic hemodialysis.