3-(aminoalkyl)-1,2,3,4-tetrahydro-5H-[1]benzopyrano[3,4-c] pyridin-5-ones as potential anticholinergic bronchodilators.

A series of 3-(aminoalkyl)benzopyrano[3,4-c]pyridin-5-ones was prepared and tested as potential orally active anticholinergic bronchodilators. Inhibition of methacholine-induced collapse in guinea pigs and inhibition of pilocarpine-induced bronchoconstriction in dogs served as in vivo models. Simultaneous measurement of salivary inhibition in the dog model allowed determination of a pulmonary selectivity ratio.

Physiologic regulation and distribution of the renal vasopressin receptor.

Previous studies suggest that circulating levels of vasopressin (AVP) influence the responsiveness of the kidney to AVP. To determine how changes in renal AVP receptors and adenylate cyclase (AC) contribute to such altered responsiveness, we analyzed AVP receptors and AVP-sensitive AC in kidneys from Sprague-Dawley, Long-Evans and homozygous Brattleboro rats. In autoradiographic studies, the distribution of [3H]AVP binding sites was similar in all groups, corresponding to the location of AVP-sensitive AC: collecting ducts greater than outer medullary collecting ducts greater than medullary thick ascending limb greater than cortical collecting ducts.

Calcium channel binding characteristics in the human heart.

The number, affinity, pharmacologic specificity and regional distribution of calcium channel binding sites in human hearts obtained at autopsy and open heart surgery were characterized using the radioligand [3H]nitrendipine. Scatchard analyses of saturation data from 6 autopsy hearts revealed a homogeneous distribution of high affinity binding sites (affinity-1 [KD] = 0.44 +/- 0.

Lyme disease and its neurologic complications.

Lyme disease is recognized as a cause of illness involving multiple organ systems. The transmission of the Borrelia burgdorferi spirochete depends on a complicated vector life cycle, involving multiple mammalian and avian hosts. Although the illness is reported worldwide, variable clinical presentations on different continents raise questions about disease mechanisms.

Solubilization of calcium channel antagonist binding sites from rat brain.

Calcium antagonist binding sites were solubilized from rat brain membranes using the detergent 3-[(3-cholamidopropyl)dimethylammonio] 1-propanesulfonate (CHAPS). CHAPS-solubilized [3H]nitrendipine binding sites are saturable over a range of 0.05-4 nM and Scatchard analysis reveals a single, high-affinity (KD = 0.

Correlation of changes in cardiac calcium channels with hemodynamics in Syrian hamster cardiomyopathy and heart failure.

We compared hemodynamics with [3H]nitrendipine (calcium channel) binding to cardiac membranes from Bio 14.6 cardiomyopathic Syrian hamsters at 4 and 10 months with their F1B controls. A 50% increase in the number (Bmax) of nitrendipine binding sites (calcium channels) was seen only in the 4 month old myopathic vs controls (Bmax = 468 +/- 11 vs 309 +/- 10 fmol/mg prot with no change in affinity (KD) (KD = .

[Immunological effectiveness of secondary revaccination against tetanus performed at prolonged intervals].

After primary immunization with adsorbed DPT vaccine antitetanus immunity was retained for 9-10 years in 90.6-98.4% of children covered by this study.

[Immunological effectiveness of a 2d revaccination against diphtheria performed at intervals extended up to 7-10 years].

The present article deals with the data on the duration of antidiphtheria immunity, induced by the primary cycle of immunization with adsorbed DPT vaccine, with the aim of considering the problems of optimizing the immunization schedule for children. The prolongation of the interval before the second booster immunization to 7-10 years produces no negative influence on the effectiveness of immunization. Besides, the study has shown that after the main complex of immunizations with adsorbed DPT vaccine protective immunity to diphtheria is retained in 90.

CI-922--a novel, potent antiallergic compound--II. Activity in animal models of allergy.

CI-922 (3,7-dimethoxy-4-phenyl-N-1H-tetrazol-5-yl-4H-furo [3,2-b]indole-2-carboxamide, L-arginine salt) is an effective antiallergic in guinea pig, rat, and canine models. This in vivo activity is attributed to its ability to inhibit inflammatory mediator release following antigen challenge in these species. Antigen-induced anaphylaxis in guinea pigs (collapse), which is mediated predominantly by histamine, was prevented by i.

Secretin receptors in the rat kidney: adenylate cyclase activation and renal effects.

In previous studies it has been demonstrated that pharmacological administration of secretin can alter urine output. Whether the effect is due to a direct action on kidney was investigated by examining the effect of secretin on renal output, and determining whether there were secretin receptors and a secretin sensitive adenylate cyclase in the kidney. Secretin had an antidiuretic action on kidney when administered intravenously to anesthetized hydrated rats.

Employee benefits in the 1980s.

The author reviews changes in the provision of health care benefits that have occurred in this decade and observes that the '80s could be labeled "the market-oriented era" in health care delivery. She stresses the importance of employee cooperation and involvement in any successful cost containment effort.

The effects of repeated mechanical trauma in the meat industry.

Meat handlers are more prone to traumatic hand lesions and wound infections than most other occupational groups. This paper deals with the carpal tunnel syndrome (CTS), which is thought to be a major occupationally related condition affecting thousands of workers engaged in repetitive hand motion tasks. The literature reveals a high prevalence of CTS among meat handlers.

Warts among meat handlers.

The Amalgamated Meat Cutters and Retail Food Store Employees, Local 342, which represents meat handlers in the greater New York City area, wanted to determine whether warts were a significant problem among their membership. Findings from a prevalence study showed that the proportion of meat handlers who reported having warts (23.1%) was significantly higher than that for non-meat handlers (9.

Adenosine uptake sites in dog heart and brain; interaction with calcium antagonists.

[3H] Nitrobenzylthioinosine (NBI) binding is characterized in dog heart and brain. Evidence is presented suggesting that [3H]NBI is binding to the adenosine uptake site in both tissues. Physiologic studies in open-chested dogs clearly demonstrate that NBI acts as a coronary vasodilator, consistent with an action at the adenosine uptake site.

[3H]nitrendipine binding to adrenal capsular membranes.

The physiologic regulation of aldosterone secretion is dependent on extracellular calcium and appears to be mediated by increases in cytosolic free calcium concentration in the zona glomerulosa cell. A specific role for voltage-dependent calcium channels was suggested by previous studies with the calcium channel antagonist verapamil. We therefore studied the [3H]nitrendipine calcium channel binding site in adrenal capsules.

The Orphan Drug Act and the Federal Government's Orphan Products Development Program.

Through the combined efforts of agencies and organizations in the public and private sector, drugs have been made available that would not have been at hand without a specific focus on the orphan drug issue. It is anticipated that these cooperative efforts will continue beyond the first enthusiastic burst engendered by the inception of new and interesting activities.

Important considerations for the clinical evaluation of drugs: appropriate dosing regimens.

A major aspect of clinical trials is the determination of a dosing regimen that will be effective and reasonably safe. The author presents a brief overview of the major considerations that govern the choice of dosage regimens for clinical trials and dosage recommendations for the labeling of marketed products. They include: (1) determination of the lowest effective dose, (2) determination of a safe dose for patients with liver or renal disease, (3) recommendations for doses in the elderly, (4) determination of the effect of concomitant drugs on drug disposition, and (5) examination of dose proportionality.

Second opinion for urologic surgery.

Second opinion elective surgery programs provide a mechanism to obtain consultation from a board-certified specialist by patients to whom an elective operation has been recommended. We focus on a second opinion program for urologic cases. Of 931 individuals who received a second opinion for urologic surgery the need was confirmed in 692 (74.