Effects of Antimitotic Agents on Secretion and Detergent Extractibility of Adrenal Nicotinic Acetylcholine Receptors

1. Evidence exists that associations of adrenal nicotinic acetylcholine receptors (nAChRs) with the cytoskeleton play an important role in signal transduction pathways by maintaining these receptors in a functional state. These studies were designed to explore this possibility and elucidate the mechanism by which antimitotic agents inhibit activation of adrenal nAChRs.2. Functional studies demonstrated that vincristine, tubulozole, podophyllotoxin, and demecolcine inhibited nAChR-stimulated catecholamine release noncompetitively and in a concentration-dependent manner, with IC₅₀ values of 3 (1–10), 5 (2–10), 8 (4–15), and 19 (9–39) M, respectively.3. Detergent extraction experiments indicated that approximately 36% of adrenal nAChRs were associated with the detergent-insoluble cytoskeletal fraction. When chromaffin cells were first treated with antimitotic agents and then detergent solubilized, a significant reduction occurred in the population of adrenal nAChRs associated with the detergent-insoluble cytoskeleton.4. These studies support an association of adrenal nAChRs with microtubules and suggest that the mechanism by which the antimitotic drugs interfere with the signal transduction pathway is by inducing dissociation of nAChRs from the microtubular network.     

Susceptibility of Salmonellae to Cephalosporins and to Nine Other Antimicrobial Agents

Three cephalosporin-related antibiotics and nine other antimicrobial agents were studied for in vitro effectiveness against 54 recently isolated strains of Salmonella. Minimal inhibitory concentrations determined by the plate dilution method demonstrated the following percentages of resistance: ampicillin, 6%; tetracycline, 13%; streptomycin, 52%; sulfadiazine, 94%; cephaloglycin, 96%; and lincomycin, 100%. No strains were resistant to cephalothin, cephaloridine, chloramphenicol, colistimethate, kanamycin, and polymyxin B. The commonest serotype studied, S. typhimurium, showed the greatest antibiotic resistance, with 21% resistant to ampicillin, 36% resistant to tetracycline, and 71% resistant to streptomycin. Cephalothin and cephaloridine were highly effective in vitro but inhibitory concentrations of 20 to 40 mug of cephaloglycin per ml were required for the majority of Salmonella strains.     

THE EVOLUTION OF ENDOTHERMY: TESTING THE AEROBIC CAPACITY MODEL

One of the most important events in vertebrate evolution was the acquisition of endothermy, the ability to use metabolic heat production to elevate body temperature above environmental temperature. Several verbal models have been proposed to explain the selective factors leading to the evolution of endothermy. Of these, the aerobic capacity model has received the most attention in recent years. The aerobic capacity model postulates that selection acted mainly to increase maximal aerobic capacity (or associated behavioral abilities) and that elevated resting metabolic rate evolved as a correlated response. Here we evaluate the implicit evolutionary and genetic assumptions of the aerobic capacity model. In light of this evaluation, we assess the utility of phenotypic and genetic correlations for testing the aerobic capacity model. Collectively, the available intraspecific data for terrestrial vertebrates support the notion of a positive phenotypic correlation between resting and maximal rates of oxygen consumption within species. Interspecific analyses provide mixed support for this phenotypic correlation. We argue, however, that assessments of phenotypic or genetic correlations within species and evolutionary correlations among species (from comparative data) are of limited utility, because they may not be able to distinguish between the aerobic capacity model and plausible alternatives, such as selection acting directly on aspects of thermoregulatory abilities. We suggest six sources of information that may help shed light on the selective factors important during the evolution of high aerobic metabolic rates and, ultimately, the attainment of endothermy. Of particular interest will be attempts to determine, using a combination of mechanistic physiological and quantitative-genetic approaches, whether a positive genetic correlation between resting and maximal rates of oxygen consumption is an ineluctable feature of vertebrate physiology.     

Recent Advancement of Chitosan-Based Nanoparticles for Oral Controlled Delivery of Insulin and Other Therapeutic Agents

Nanoparticles composed of naturally occurring biodegradable polymers have emerged as potential carriers of various therapeutic agents for controlled drug delivery through the oral route. Chitosan, a cationic polysaccharide, is one of such biodegradable polymers, which has been extensively exploited for the preparation of nanoparticles for oral controlled delivery of several therapeutic agents. In recent years, the area of focus has shifted from chitosan to chitosan derivatized polymers for the preparation of oral nanoparticles due to its vastly improved properties, such as better drug retention capability, improved permeation, enhanced mucoadhesion and sustained release of therapeutic agents. Chitosan derivatized polymers are primarily the quaternized chitosan derivatives, chitosan cyclodextrin complexes, thiolated chitosan, pegylated chitosan and chitosan combined with other peptides. The current review focuses on the recent advancements in the field of oral controlled release via chitosan nanoparticles and discusses about its in vitro and in vivo implications.     

Enhancement by Potassium of Carbachol-Stimulated Inositol Phospholipid Breakdown in Rat Cerebral Cortical Miniprisms: Comparison with Other Depolarising Agents

Increasing the [K+] in the assay medium from 5.7 to 17.8 mM produces a large enhancement of the inositol phospholipid breakdown response to the muscarinic agonist carbachol in rat cerebral cortical miniprisms, with minor effects on basal inositol phospholipid breakdown. This effect is also found with Rb+. The enhancement by a raised [K+] is not accompanied by a change in the composition of the labelled polyphosphoinositides. The carbachol-stimulated inositol phospholipid breakdown at 17.8 and 42.7 mM K+ was antagonised by veratrine (5-80 microM), 4-aminopyridine (5 mM), and tetraethylammonium (20 mM). These compounds, however, also inhibited the binding of [3H]quinuclidinyl benzilate to cortical membranes. BRL 34915 (0.2-20 microM) was without significant effect on carbachol-stimulated inositol phospholipid breakdown at either 5.7 or 17.8 mM K+.Mg2+ (10 mM) considerably reduced the carbachol-stimulated inositol phospholipid breakdown at 17.8, but not 42.7, mM K+. Inositol phospholipid breakdown was also stimulated, albeit to a small extent, by L-glutamate (100-3,000 microM) and quisqualate (1-100 microM), with the stimulation being additive to that produced by carbachol at both 5.7 and 17.8 mM K+. N-Methyl-D-aspartate (10-1,000 microM in Mg2+-free medium) had no significant effect on basal inositol phospholipid breakdown and had little or no effect on carbachol-stimulated inositol phospholipid breakdown at either 5.7 or 17.8 mM K+. It is concluded that it may not be correct to ascribe wholly the enhancement by K+ of carbachol-stimulated inositol phospholipid breakdown to the tissue-depolarising actions of this ion and that other actions of K+ may be involved.     

Memory for Expectation-Violating Concepts: The Effects of Agents and Cultural Familiarity

Previous research has shown that ideas which violate our expectations, such as schema-inconsistent concepts, enjoy privileged status in terms of memorability. In our study, memory for concepts that violate cultural (cultural schema-level) expectations (e.g., “illiterate teacher”, “wooden bottle”, or “thorny grass”) versus domain-level (ontological) expectations (e.g., “speaking cat”, “jumping maple”, or “melting teacher”) was examined. Concepts that violate cultural expectations, or counter-schematic, were remembered to a greater extent compared with concepts that violate ontological expectations and with intuitive concepts (e.g., “galloping pony”, “drying orchid”, or “convertible car”), in both immediate recall, and delayed recognition tests. Importantly, concepts related to agents showed a memory advantage over concepts not pertaining to agents, but this was true only for expectation-violating concepts. Our results imply that intuitive, everyday concepts are equally attractive and memorable regardless of the presence or absence of agents. However, concepts that violate our expectations (cultural-schema or domain-level) are more memorable when pertaining to agents (humans and animals) than to non-agents (plants or objects/artifacts). We conclude that due to their evolutionary salience, cultural ideas which combine expectancy violations and the involvement of an agent are especially memorable and thus have an enhanced probability of being successfully propagated.     

Modulation of KvAP Unitary Conductance and Gating by 1-Alkanols and Other Surface Active Agents

The actions of alcohols and anesthetics on ion channels are poorly understood. Controversy continues about whether bilayer restructuring is relevant to the modulatory effects of these surface active agents (SAAs). Some voltage-gated K channels (Kv), but not KvAP, have putative low affinity alcohol-binding sites, and because KvAP structures have been determined in bilayers, KvAP could offer insights into the contribution of bilayer mechanics to SAA actions. We monitored KvAP unitary conductance and macroscopic activation and inactivation kinetics in PE:PG/decane bilayers with and without exposure to classic SAAs (short-chain 1-alkanols, cholesterol, and selected anesthetics: halothane, isoflurane, chloroform). At levels that did not measurably alter membrane specific capacitance, alkanols caused functional changes in KvAP behavior including lowered unitary conductance, modified kinetics, and shifted voltage dependence for activation. A simple explanation is that the site of SAA action on KvAP is its entire lateral interface with the PE:PG/decane bilayer, with SAA-induced changes in surface tension and bilayer packing order combining to modulate the shape and stability of various conformations. The KvAP structural adjustment to diverse bilayer pressure profiles has implications for understanding desirable and undesirable actions of SAA-like drugs and, broadly, predicts that channel gating, conductance and pharmacology may differ when membrane packing order differs, as in raft versus nonraft domains.     

非诱变剂对姐妹染色单体交换的诱导效应

检测了16种非诱变剂对大麦根端分生细胞姐妹染色单体交换(SCE)的影响及其中9种成份对人外周血淋巴细胞SCE的影响。在大麦细胞中,用高浓度的葡萄糖、氯化钠、维生素、氨基酸及脱氧核糖核苷三磷酸(dNTP)处理均能显著提高SCE频率。维生素、氨基酸和dNTP对人外周血淋巴细胞中的SCE频率也有显著影响。实验结果表明,不只是诱变剂能提高SCE频率,非诱变剂在一定高剂量时也能提高SCE频率。非诱变剂影响SCE具有特殊的S CE增长曲线,SCE频率达一定值后不再随处理浓度的增大而提高。     

Increased Viability of a Strain of Neurospora crassa After Treatment with Ultraviolet Radiation or Other Agents

A strain of Neurospora crassa with low viability but near normal germination shows a two- to sixfold increase in the number of colonies formed after treatment with ultraviolet radiation, X radiation, nitrous acid, or heat (50 C). Effective dosages of these agents produce moderate killing of the wild type.     

BEYOND ALTRUISTIC AND COMMERCIAL CONTRACT MOTHERHOOD: THE PROFESSIONAL MODEL

It has become common to distinguish between altruistic and commercial contract motherhood (or ‘surrogacy’). Altruistic arrangements are based on the ‘gift relationship’: a woman is motivated by altruism to have a baby for an infertile couple, who are free to reciprocate as they see fit. By contrast, in commercial arrangements both parties are motivated by personal gain to enter a legally enforceable agreement, which stipulates that the contract mother or ‘surrogate’ is to bear a child for the intending parents in exchange for a fee. She is required to undergo medical examinations and to refrain from behaviour that could harm the foetus. The intending parents are the child's legal parents from the outset. The parties to the contract can, but are not expected to, maintain contact after the transaction is completed. We argue that contract motherhood should not be organized according to the norms of the gift relationship, and that contract mothers should be compensated for their labour. However, we accept that there are good reasons for rejecting the commercial model as a suitable framework for contract pregnancy, and argue, instead, in favour of viewing it as a profession.