Effects of drug solubility, drug loading, and polymer molecular weight on drug release from Polyox tablets

BACKGROUND: This study augments a randomized controlled trial to analyze the cost-effectiveness of 2 standardized treatments for major depression relative to each other and to the "usual care" provided by primary care physicians. METHODS: A randomized controlled trial was conducted in which primary care patients meeting DSM-III-R criteria for current major depression were assigned to pharmacotherapy (where nortriptyline hydrochloride was given) or interpersonal psychotherapy provided in a standardized framework or a primary physician's usual care. Two outcome measures, depression-free days and quality-adjusted days, were developed using information on depressive symptoms over time. The costs of care were calculated. Cost-effectiveness ratios comparing the incremental outcomes with the incremental costs for the different treatments were estimated. Sensitivity analyses were performed. RESULTS: In terms of both economic costs and quality-of-life outcomes, patients assigned to the pharmacotherapy group did slightly better than those assigned to interpersonal psychotherapy. Both standardized therapies provided better outcomes than primary physician's usual care, but each consumed more resources. No meaningful cost-offsets were found. The incremental direct cost per additional depression-free day for pharmacotherapy relative to usual care ranges from $12.66 to $16.87 which translates to direct cost per quality-adjusted year gained from $11270 to $19510. CONCLUSIONS: Standardized treatments for depression lead to better outcomes than usual care but also lead to higher costs. However, the estimates of the cost per quality-of-life year gained for standardized pharmacotherapy are comparable with those found for other treatments provided in routine practice.     

A hydrogel based on a polyaspartamide: characterization and evaluation of in-vivo biocompatibility and drug release in the rat

This paper deals with the characterization of a new microparticulate hydrogel obtained by gamma irradiation of alpha, beta-poly[N-(2-hydroxyethyl)-DL-aspartamide] (PHEA). When enzymatic digestion of PHEA hydrogel was evaluated using various concentrations of pepsin and alpha-chymotrypsin no degradation occurred within 24 h. In-vivo studies showed that this new material is biocompatible after oral administration to rats. PHEA hydrogel was also studied as a system for delivery of diflunisal, an anti-inflammatory drug. In-vitro release studies in simulated gastrointestinal juice (pH 1 or 6.8) showed that most of the drug was released at pH 6.8. In-vivo studies indicated that diflunisal-loaded PHEA microparticles significantly improved the gastric tolerance and oral bioavailability of the drug in comparison with free diflunisal. These results suggest the potential application of PHEA hydrogel as a new delivery system for the oral administration of anti-inflammatory drugs.     

Properties controlling the diffusion and release of water-soluble solutes from poly(ethylene oxide) hydrogels: 3. Device geometry

The diffusive release from hydrogels can be determined by both composition and geometry. This paper presents a theoretical and experimental comparison of the release characteristics of proxyphylline in water-swollen slabs, spheres, and cylinders of a urethane cross-linked poly(ethylene oxide). Contrary to general conventional wisdom it was found that practically cylinders and spheres, which have considerable potential advantages for oral delivery, can provide good 'anomalous' rates for which the 'exponent of release' into water from the dry xerogels is c. 0.8 compared with 1.0 for zero order. An exponent of 0.94 was found for release into water from 'larger' xerogel flat slabs thus confirming that these configurations can provide essentially constant delivery formulations from which the active agent cannot be 'dumped'. For up to 40% total drug release, the theoretical release profiles were essentially of identical form for all three geometries in the swollen state and, as expected in theory and practice, showed an exponent for release of close to 0.5. However, the experimental release of proxyphylline was found to be more sustained from swollen spheres of these polymers than theory would predict. The half life times for release were further extended by approximately two and a half times for the initially dry devices compared with the initially swollen ones.     

An estimate of the rate of direct drug diffusion from the surface of heart and kidney--implications for their representation as compartments

In many regional pharmacokinetic experiments and models, the anatomical boundaries of the heart and kidney are intrinsically assumed to be barriers for drug diffusion such that these organs can be represented as one or more compartments. To test this, an experimental preparation was developed in which the heart and kidney of anaesthetized sheep were surrounded with 0.9% saline. The rate of drug diffusion from the surface of the organs into the saline was examined during constant-rate i.v. drug infusions. It was found that the maximum clearances of lidocaine and procainamide into the pericardial saline were 10.3-11.6 and 0.6-2.1 ml min-1 respectively, and the values for the kidney were 0.3-0.6, 0.1-1.0 and 0.4-1.3 ml min-1, for lidocaine, procainamide, and meperidine respectively. These corresponded to calculated times of 4-481 min to reach the steady-state saline concentration depending on the drug and the organ. The steady-state ratio of the saline concentrations over the arterial blood drug concentrations usually ranged from 0.5-1.0. It is concluded that drugs can rapidly enter regions of low or no perfusion surrounding these organs, and that the concept of treating the heart and kidney as compartments may not be valid in certain 'worst-case' situations.     

Drug use and AIDS: Developments from the International Conference on AIDS.

This article presents recent information about injection drug use as it relates to the human immunodeficiency virus (HIV) epidemic. Presentations from the VIII International Conference on AIDS, held in Amsterdam in July 1992, are highlighted. Several recent developments are noteworthy for psychologists coping with addictive behaviors, including the return of tuberculosis as a communicable disease affecting people with acquired immunodeficiency syndrome (AIDS), advancements in prevention of HIV infection, and treatment of AIDS in drug users. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

In vitro/in vivo comparison of drug release and polymer erosion from biodegradable P(FAD-SA) polyanhydrides--a noninvasive approach by the combined use of electron paramagnetic resonance spectroscopy and nuclear magnetic resonance imaging

PURPOSE: The purpose of this study was to compare drug release and polymer erosion from biodegradable P(FAD-SA) polyanhydrides in vitro and in vivo in real time and with minimal disturbance of the investigated system. METHODS: P(FAD-SA) 20:80 and P(FAD-SA) 50:50 polymer tablets were loaded with the spin probe 3-carboxy-2,2,5,5-tetramethyl-pyrrollidine-1-oxyl (PCA) and implanted subcutaneously in the neck of rats or placed in 0.1 M phosphate buffer. 1.1 GHz EPR spectroscopy experiments and 7T MRI studies (T1 and T2 weighted) were performed. RESULTS: A front of water penetration was visible by MRI in vitro in the case of P(FAD-SA) 20:80, but not for P(FAD-SA) 50:50. For both polymers, the thickness of the tablets decreased with time and a insoluble, easy deformable residue remained. Important processes such as edema, deformation of the implant, encapsulation and bioresorption were observable by MRI in vivo. P(FAD-SA) 50:50 was almost entirely absorbed by day 44, whereas an encapsulated residue was found for P(FAD-SA) 20:80 after 65 days. The EPR studies gave direct evidence of a water penetration induced changes of the microenvironment inside the tablet. EPR signals were still detectable in P(FAD-SA) 20:80 implants after 65 days, while the nitroxide was released in vitro within 16 days. CONCLUSIONS: Important parameters and processes such as edema, deformation of the tablet, microviscosity inside the tablet and encapsulation can be monitored in real time by the combined use of the noninvasive techniques MRI and EPR leading to better understanding of the differences between the in vitro and in vivo situation.     

Prevalence of substance use disorders among veterans and comparable nonveterans from the National Survey on Drug Use and Health.

The Department of Veterans Affairs (VA) operates over 200 substance abuse treatment programs. Historically, planning for these services has not been informed by population-level prevalence data. Accordingly, the authors analyzed the National Survey on Drug Use and Health data from 2000 to 2003 to estimate substance use and substance use disorder prevalence among all veterans. The authors present the data in comparison to comparable nonveterans. Data show notable rates of substance use among veterans; 22.6% and 4.4% of veterans reported binge drinking and any illicit drug use in the past month, respectively. In addition, prevalence varied by geographic location. Monitoring substance use prevalence is needed to ensure the VA and other substance use providers can plan appropriate substance use disorder services for current and future enrollees, including veterans of the current military operations in Iraq and Afghanistan. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Effects of graded duodenal infusions of glucose on yield and composition of milk from dairy cows. 1. Diets based on corn silage

Four fistulated Holstein cows were arranged in a 4 x 4 Latin square design to study the effects of graded amounts of glucose (0, 500, 750, and 1500 g/d) infused in the duodenum on milk yield and composition and plasma metabolites. Cows were fed a basal diet of 50% corn silage, 17% dehydrated alfalfa, and 33% concentrate. The treatments (feed plus infusions) were isoenergetic. Increased amounts of glucose did not affect milk yield or protein content. Fat yield and content decreased in a curvilinear manner; the lowest fat content was obtained with about 750 g of glucose. The decrease in milk fat resulted from a reduced yield of long-chain fatty acids (C16 and C18), probably caused by lower mobilization of fat. The glucose treatments significantly affected profiles of medium-chain fatty acids, which promoted the elongation process. The most important change in the plasma concentration of amino acids concerned decreased branched-chain amino acids. The lactose content was not greatly affected by infusions of glucose despite a significant linear increase in the concentration of milk glucose. In conclusion, an increase in the supply of glucose had no effect on milk yield and had a slight, positive effect on protein yield but induced a dramatic decrease in fat yield.     

Factors predicting the use of technology: Findings from the center for research and education on aging and technology enhancement (create).

The successful adoption of technology is becoming increasingly important to functional independence. The present article reports findings from the Center for Research and Education on Aging and Technology Enhancement (CREATE) on the use of technology among community-dwelling adults. The sample included 1,204 individuals ranging in age from 18-91 years. All participants completed a battery that included measures of demographic characteristics, self-rated health, experience with technology, attitudes toward computers, and component cognitive abilities. Findings indicate that the older adults were less likely than younger adults to use technology in general, computers, and the World Wide Web. The results also indicate that computer anxiety, fluid intelligence, and crystallized intelligence were important predictors of the use of technology. The relationship between age and adoption of technology was mediated by cognitive abilities, computer self-efficacy, and computer anxiety. These findings are discussed in terms of training strategies to promote technology adoption. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Temperature and activity responses to sucrose concentration reductions occur on the 1st but not the 2nd day of concentration shifts, and are blocked by low, constant glucocorticoids.

Previous findings (N. Pecoraro, J. Chou-Green, & M. F. Dallman, 2003; N. Pecoraro & M. F. Dallman, 2005) indicated that unexpected reductions in sucrose concentration in once daily meals result in a febrile response on the 1st, but not the 2nd day of a concentration shift. This study shows that this day-specific fever is blocked by adrenalectomy accompanied by constant low corticosterone replacement. Rats implanted with telemetry probes were adrenalectomized and given low-corticosterone pellets or were sham operated. Food-restricted rats were given 2 rounds of sucrose concentration downshifts, as follows: 32% sucrose (14 days), 4% sucrose (6 days), 32% sucrose (4 days), and 4% sucrose (4 days). Intact rats showed more pronounced anticipation of the sucrose than did rats having low, clamped corticosterone. Only intact rats showed a 4-hr, postshift temperature burst on the 1st, but not the 2nd day of the shift to 4% sucrose, during both rounds of shifting. Increased activity accompanied the fever. These data confirm previous findings, show them to be dependent on high corticosterone, and appear to be related to a host of day-specific alterations in other motor outflows following unexpected downward shifts in palatable sucrose concentrations. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Effect of the A and B protomers of choleragen on release of trapped glucose from liposomes containing or lacking ganglioside GM1

Liposomes containing trapped glucose were used to examine the interaction of the A and B protomers of choleragen with ganglioside GM1 and lipid model membranes. The B protomer (choleragenoid) was as effective as choleragen in causing release of trapped glucose from liposomes containing GM1; the A protomer did not release glucose from GM1 liposomes. Neither choleragen nor the A or B protomers caused release of trapped glucose from glycolipid-free liposomes. Anti-choleragen and complement, however, caused release of trapped glucose from ganlioside-free liposomes previously incubated with the A protomer but not from those incubated with the B protomer or choleragen. These results suggest that the A protomer, but not intact choleragen or B protomer, bound to ganglioside-free liposomes. Presumably, the A protomer must be freed of the constraints present in the intact choleragen in order to interact with the liposomal model membrane system.     

Lipocortin-1 and the control of arachidonic acid release in cell signalling. Glucocorticoids (changed from glucorticoids) inhibit G protein-dependent activation of cPLA2 activity

In pre-labelled A549 cells epidermal growth factor (EGF) (10 nM) stimulates the release of [5,6,8,9,11,12,14,15-3H(N)]-arachidonic acid (3H-AA) by approximately 70%. Increasing Ca2+i with thapsigargin (50 nM) stimulates 3H-AA release by approximately 120%. However, the combined use of these two agents results in a synergistic stimulation of 3H-AA release by over 700%. The EGF stimulated release is sensitive to pertussis toxin (10 ng/mL) and guanosine 5'-O-(2-thiodiphosphate) suggesting a G protein-mediated event. This is supported by the fact that the G protein activators AlF-4 and guanosine 5'-O-(2-thiotriphosphate) both stimulate 3H-AA release. The stimulation of 3H-AA release by both EGF or direct G protein activation is completely blocked following pre-treatment for 3 hr with 1 nM dexamethasone. This effect is reversed with a neutralizing antibody to lipocortin-1 (1 microgram/mL) suggesting that this protein mediates the inhibitory effects of glucocorticoids on agonist activated 3H-AA release. Thapsigargin stimulation of 3H-AA release is insensitive to dexamethasone treatment. A peptide fragment from the N-terminus of lipocortin-1-Lc13-25 (20-200 micrograms/mL) mimics the effect of glucocorticoid in suppressing both EGF and G protein activated 3H-AA release. A peptide with Me-Tyr substituting Tyr21 is much reduced in activity suggesting that the presence of this residue is essential. As peptide Lc13-25 is not derived from the Ca2+/phospholipid binding domain of the native protein then sequestration of phospholipid substrate for PLA2 remains an unlikely mechanism of action for this peptide.     

Arsenic, lead and cadmium in the customary homemade fruit and vegetable preserves from earlier decades. 1. Cherries from the harvest year 1911 on

Levels of arsenic, lead and cadmium in cherries of harvest years 1911 to 1986, home-sterilized in glass jars, were determined by atomic absorption spectrometry. Concentrations of arsenic showed a decreasing trend during that period, presumably reflecting the discontinuation of the use of arsenic-containing pesticides. Unexpectedly, some of the older samples also contained more lead or more cadmium than more recent samples.