Microencapsulated dopamine (DA)-induced restitution of function in 6-OHDA-denervated rat striatum in vivo: comparison between two microsphere excipients.

Biodegradable controlled-release microsphere systems made with the biocompatible biodegradable polyester excipient poly [DL lactide-co-glycolide] constitute an exciting new technology for drug delivery to the central nervous system (CNS). The present study describes functional observations indicating that implantation of dopamine (DA) microspheres encapsulated within two different polymer excipients into denervated-striatal tissue assures a prolonged release of the transmitter in vivo. Moreover, in this regard, the results show that there were clear cut temporal differences in the effect of the two DA microsphere formulations compared in this study, probably reflecting variations in the actual composition (i.e., lactide to glycolide ratio) of the two copolymer excipients examined. This technology has considerable potential for basic research with possible clinical application.     

Encapsulated liquid crystals as probes for remote thermometry.

A temperature probe based on the magnetic resonance properties of an encapsulated liquid crystal has been investigated. Large changes in magnetic resonance signals occur as the liquid crystal undergoes a phase transition from an anisotropic (nematic) state to the isotropic liquid. The low latent heat of such phase transitions allows for rapid phase changes during a hyperthermia treatment. Transition temperatures can be tailored by adding suitable compounds such as analogues of the liquid crystal or various solvents. Encapsulation is required to maintain the integrity of the liquid crystal, particularly for applications in vivo. Results of preliminary studies designed to demonstrate the technical feasibility of the concept are presented.     

Influence of anesthesia on the threshold of pacing-induced ischemia.

Increased myocardial oxygen demand, induced by increased heart rate, may cause myocardial ischemia in the presence of significant coronary artery disease. Alterations in anesthetic depth or technique might put at risk or protect myocardium with compromised blood flow. In 20 dogs with critical left anterior descending coronary artery (LAD) stenosis, atrial pacing rates from 100 to 160 beats/min were achieved, with end-tidal halothane 0.7% (LowH) and 1.1% (HighH), end-tidal isoflurane 1.1% (LowI) and 1.5% (HighI), as well as with continuous fentanyl plus midazolam (FM) infusion anesthesia. Despite significantly different mean arterial and coronary perfusion pressures, rate-pressure product, and left ventricular dP/dtmax, the pacing rate at which systolic shortening decreased below the lower limit of the physiologic response, indicating regional dysfunction, was the same in all investigated anesthesia conditions (LowH: 127 +/- 4 beats/min; HighH: 128 +/- 5 beats/min; LowI: 125 +/- 4 beats/min; HighI: 122 +/- 5 beats/min; FM: 124 +/- 4 beats/min [mean +/- SEM], P greater than 0.05). None of the investigated anesthesia conditions either increased ischemia tolerance or showed a detrimental effect on myocardium with compromised coronary blood flow.     

Modulation of glial cell signaling by adenosine and pharmacological reinforcement

In view of the increasing evidence that a pathological glial activation plays a significant role in the development of neurodegenerative diseases, we investigated the underlying molecular signaling as a possible target for a pharmacological therapy. Here, we are particularly focusing on the endogenous modulation of the Ca²⁺ and cyclic nucleotide-dependent signaling by the nucleoside adenosine and its reinforcement by the xanthine derivative propentofylline (PPF). As an experimental model, we used cultured rat microglial cells and astrocytes that are immature, show a high proliferation rate, and resemble in several aspects pathologically activated glial cells. A prolonged increase of the cellular cAMP level favored the differentiation of cultured astrocytes and associated properties required for the physiological nerve cell function. On the other hand, a strengthening of the cyclic nucleotide-dependent signaling inhibited potentially neurotoxic properties of cultured microglial cells. Similar effects were obtained by treatment with propentofylline, which mimicked modulatory adenosine effects and increased the intracellular level of cAMP and cGMP. Such a pharmacological glial cell conditioning, obtained by modifying the strength and the timing of these second messengers, may provide a therapy of neurodegenerative diseases in which a pathological activation of microglial cells and astrocytes is discussed to play a pathogenic role.     

Hereditary Characteristic that Varies Among Isolates of Mycobacterium leprae

Isolates of Mycobacterium leprae in mouse foot pads were found to differ in two related properties, the average rate of growth between inoculation and harvest (G) and the number of bacilli in the harvest (H). For “fast” strains the median values for G were less than 25 days per generation, and the median values for H were above 10^6.1. For “slow” strains the median values for G were above 30, and the median values for H were below 10^5.6. The G and H values for the 59 isolates for which data were available formed a continuous spectrum between the two extremes; there was no correlation with dapsone resistance. The fastness characteristic was stable; it did not change on passage in mice and was in agreement when more than one isolate had been made from the same patient. No important differences were apparent according to geographic origin of the infection of the patient. Histological studies showed that fast strains grew to a higher level without inducing the infiltrate of lymphocytes and macrophages that appears at the end of the logarithmic phase of growth in mouse foot pads. Although fast strains often had higher ratios of solidly staining (and presumably viable) bacilli in the inoculum, the fast-slow difference was not accounted for by the solid ratio. Slow strains differed from fast by having longer times until harvest and by having fewer generations of growth, even when their frequently lower solid ratios were taken into account.     

Rural/urban differences in chemical dependency treatment. Results from the Minnesota Adult Household Survey

Research at the national level suggests fairly similar rates of substance abuse in rural and urban areas, with data for 1996 showing a slightly higher rate of drug use in urban areas but no difference in the rates of heavy alcohol use. The current study assesses differences between rural and urban areas in substance abuse and dependence, service utilization, and perceived barriers to services in Minnesota. Analysis of responses of a random sample of 7,508 adults stratified by residence reveals few differences between rural and urban settings. While urban residents have a slightly higher (marginally significant) rate of dependence on drugs and rural residents have a significantly greater tendency to talk to clergy about their problem, the subsamples exhibit remarkably similar patterns of abuse, need for treatment, propensity to seek treatment, service utilization, and perceived barriers to treatment.     

Providing an integrated program of low intensity tobacco cessation services in a health maintenance organization

This paper reports on the development, promotion and use of a coordinated program of low intensity intervention services designed to appeal to smokers (and smokeless tobacco users) at various stages of change. An initial package of four components: a telephone advice line, self-help materials, single session group meetings and bi-monthly newsletter was offered to subjects in a variety of different settings (outpatient clinics, dental offices, worksites, hospitals) within a health maintenance (HMO) program project. Based upon consumer response and formative evaluations, these components were modified during the course of the year-long intervention. Results revealed differences in use of the various components of the program, with greatest use of self-help materials (manuals, 'tobacco substitutes' and a computerized smoking cessation aid) and least response to group meetings and the advice line. Most encouraging was the finding that it was possible to reach heavy smokers and to engage them in tobacco cessation activities through a centralized program of low intensity services. Data are presented on member characteristics associated with use/non-use of the various low intensity resources and suggestions are made for wider use of such interventions in other health care systems.