Book Reviews Editor

INLANDER, CHARLES B., LEVIN, LOWELL B., AND WEINER, E.D. Medicine on Trial: The Appalling Story of Medical Ineptitude and the Arrogance that Overlooks It.     

Neurochemical mechanisms mediating the behavioral and cognitive effects of nicotine

Data are reviewed, largely from experiments in the authors'laboratory, that suggest three modes of action of systemic nicotine in producing three different types of effect upon behavior and cognitive function. (1) Preexposure of a stimulus without consequence makes it harder subsequently to form associations to that stimulus, a form of selective attention known as latent inhibition. Latent inhibition is blocked by nicotine, an effect that is apparently mediated by a nicotine-induced increase in dopamine release in the nucleus accumbens. (2) A single dose of nicotine proactively increases the partial reinforcement extinction effect measured several weeks later: that is, resistance to extinction is decreased by nicotine in animals that have been trained on a continuous reinforcement schedule, and increased in animals trained on a partial reinforcement schedule. This effect appears to be due to increased synthesis of tyrosine hydroxylase in the cell bodies of noradrenergic neurons in the locus coeruleus, followed by axonal transport to the hippocampus and increased synthesis and release of noradrenaline in that structure. (3) Nicotine improves vigilance in animals with cognitive deficits due to destruction of the forebrain cholinergic projection system, either as a consequence of excitotoxic lesions of the nuclei of origin of this system or after prolonged alcohol consumption; and also in human subjects with Alzheimer's disease (in which this system undergoes degeneration). This effect is most likely due to an action at denervated cholinergic synapses in the hippocampus and neocortex. © 1994 Wiley-Liss, Inc.     

Cytoprotective actions of 2,4-dimethoxybenzylidene anabaseine in differentiated PC12 cells and septal cholinergic neurons

The potential cytoprotective actions of a novel nicotinic agent 2,4-dimethoxybenzilidene anabaseine (DMXB) were investigated in differentiated PC12 cells and transected rat septal cholinergic neurons in vivo. In NGF-differentiated PC12 cells, removal of both NGF and serum led to cell loss, a reduced % of cells expressing neurites, the release of lactate dehydrogenase, and a decrease in total cellular protein. Cell loss was apparent within 24 h, and remained constant between 4–8 days post-NGF removal. NGF alone (100 ng/ml), DMXB (10 μM), but not nicotine (10 μM), prevented these cell and neurite losses. DMXB-induced cytoprotection was blocked by 1 μM mecamylamine. DMXB (1 mg/kg, ip) injected twice but not once per day protected cholinesterase-staining septal neurons from retrograde degeneration following unilateral fimbrial transections. The twice per day DMXB injection-protocol also decreased cell roundness among cholinesterase-staining cells in the lesioned septal hemisphere compared to saline-injected animals. These studies suggest that DMXB may exert cytoprotective activity in NGF-sensitive neuronal populations. © 1994 Wiley-Liss, Inc.     

Marine biodiversity as a source of chemical diversity

Total global biodiversity is estimated at between 3 and 500 × 10⁶ species of prokaryote and eukaryote organisms spread across 70 or more phyla. The marine macrofauna alone are estimated between 0.5 and 30 × 10⁶ species and represents a broader range of taxonomic diversity than that found in the terrestrial environment, which has been the traditional source of natural products. With a typical eukaryote possessing 50,000 genes, the global marine macrofauna are the source of 2.5 × 10¹⁰ to 1.5 × 10¹² primary products and an associated extensive range of secondary products. However, only a few thousand novel compounds from marine organisms have been described. These compounds have proven unique in chemical and pharmacological terms but, as yet, no therapeutic agents have resulted. Given a broader drug discovery strategy, and facilitated by technological advances, it is predicted that the characterisation of marine chemical diversity will be accelerated. Strategies for drug discovery from the virtually untapped chemical diversity of marine organisms are discussed. © 1994 Wiley-Less, Inc.     

An Assessment of Recent Pharmacy Graduates' Knowledge and Competency,Professional Practice Functions,and Involvement in Pharmacy Teaching Programs

Study Objectives . To determine self-evaluated professional knowledge and competency, functions, demographic information, lifelong learning, degree and training status, practice sites, involvement in pharmacy teaching programs, and salary for recent pharmacy graduates. Design . A survey of recent Bachelor of Science (B.S.) pharmacy graduates of the University of Wisconsin School of Pharmacy. Measurements and Main Results . A total of 371 B.S. pharmacy graduates (55% response rate) provided information. Graduates who had an advanced degree or training (from many programs) after completing their B.S. pharmacy degree, and those who were teaching in pharmacy programs generally had higher self-rated levels of knowledge and competencies. Hospital pharmacists spent less of their work time in dispensing activities (33.82% ± 30.39%) than community pharmacists (61.04% ± 19.97%; t =8.78, df = 288, p<0.001); community pharmacists spent twice as much of their work time counseling and educating patients (16.65% ± 10.47% vs 7.13% ± 7.39%; t = 9.06, df = 288, p<0.001). The amount of time pharmacists spent in dispensing functions had a negative association with knowledge and competencies in the sections on pharmacokinetic and disease process (r=−0.277, p<0.01), patient communications (r=−0.272, p<0.01), and administrative and economic aspects of practice (r=−0.210, p<0.01) for all respondents. Pharmacists reported that they spent 13.78 ± 14.06 hours per month outside work in professional lifelong learning. There was a negative association between the time pharmacists spent dispensing and the time they spent in professional lifelong learning (r=−0.239, p<0.001), and a positive relationship between the time spent in such learning and the time providing information to prescribers and other health care professionals (r=0.214, p<0.001), monitoring patients (r=0.216, p<0.001), and performing primary care activities (r=0.176, p<0.001). Graduates reported a mean yearly salary of $46,879 ± $8183. More hospital pharmacists were involved in teaching (48, 37%) than those practicing in a community setting (19, 12%). Conclusions . Practice site, advanced degree or training, lifelong learning, involvement in teaching programs, and time spent in various professional functions were associated with pharmacists' self-rated knowledge and competencies. (Pharmacotherapy 1994;14(6):712–723)     

RENIN GENE POLYMORPHISM ASSOCIATED WITH ALDOSTERONE RESPONSIVENESS TO THE RENINANGIOTENSIN SYSTEM IN PATIENTS WITH ALDOSTERONE-PRODUCING ADENOMAS

1. Aldosterone levels in patients with unilateral aldosterone-producing adenomas may be responsive or unresponsive to the renin-angiotensin system, with the former often previously misdiagnosed as bilateral adrenal hyperplasia. 2. In tumours from patients in the responsive subgroup, renin mRNA is expressed in greater amounts than in tumours from patients in the unresponsive subgroup, or in normal adrenals. 3. We compared the frequency of four renin gene polymorphisms in peripheral blood DNA from the two subgroups and found significant associations between BglI, TaqI and HinfI restriction fragment length polymorphisms (RFLP) and aldosterone responsiveness. 4. Allelic variation in the constitutive renin gene was associated with a specific cause of hypertension.