Xyloglucan nano-aggregates: Physico-chemical characterisation in buffer solution and potential application as a carrier for camptothecin, an anti-cancer drug

In this work, native xyloglucan was extracted from Tamarindus indica seeds (XGT), and its properties in phosphate buffer solution (PBS) were evaluated in comparison with a commercial tamarind kernel powder (TKP). The physico-chemical characteristics of the polysaccharides such as molar mass, critical concentration and intrinsic viscosity were determined. Furthermore, using spectroscopic and microscopy techniques, it was observed that the XGs tested can be considered macromolecules able to aggregate as nano-entities of 60-140 nm. The XGT tended to an ordered and compact spherical conformation determined by the Huggins constant, circular dichroism, atomic force microscopy and transmission electron microscopy. After the determination of the properties in PBS the XGs, at concentrations of 25% above their critical aggregation concentration, were used to encapsulate camptothecin, an anti-cancer drug. The XGT sample showed an encapsulation efficiency of 42% and first-order drug delivery kinetics. These results demonstrated the importance of knowledge of the physico-chemical properties of polysaccharides, for example, to better conduct their biotechnological applications as drug carriers. (C) 2010 Elsevier Ltd. All rights reserved.

Comparison of the structure of adolescent problem behavior in the United States and Australia

Some extant theory and empirical research suggests that youth problem behaviors, such as substance abuse and delinquency, reflect a single underlying dimension of behavior, whereas others suggest there are several different dimensions. Few studies have examined potential international differences in the structure of problem behavior, where cultural and policy differences may create more variation in behavior and different structures. This study explored the structure of problem behavior in two representative samples of youth (ages 12-17) from Maine and Oregon in the United States (N = 33,066) and Victoria, Australia (N = 8,500). The authors examined the degree to which data from the two countries produce similar model structures using indicators of problem behavior. Results show that the data are best represented by two factors, substance use and delinquency, and there appear to be more similarities than differences in the models across countries. Implications for understanding problem behavior across cultural and developmental groups and practical and policy implications are discussed.

A comparison study of cerebral protection using Ginkgo biloba extract and Losartan on stroked rats

It has been well documented that oxidative stress is involved in stroke. Currently, many neuroprotective strategies have been targeted at molecules that are able to act as an oxidant to intervene with free-radical mediated apoptosis in the ischemic penumbra. In particular, natural products which contain antioxidant properties have undoubtedly efficacious for stroke treatment. In the current study, therapeutic effects of Ginkgo biloba extract (EGb) against cerebral protection in Wistar rats underwent middle cerebral artery occlusion (MCAO) was evaluated. A comparison study was conducted by using Losartan, an antihypertensive drug. Gene expression levels of pro-apoptotic genes (AT2 receptor, Fas, Bax and Bcl-xS) have shown to have significant reduction by EGb- and Losartan-treated groups as compared to vehicle group. Significant reduction of immunoreactivity of protein production of these genes, together with least nuclear green fluorescence observed in TUNEL, EGb, as an antioxidant drug, is concluded to have potent and promising therapeutic effect for stroke treatment.

A cross-national comparison of risk and protective factors for adolescent substance use : the United States and Australia

Purpose
To compare risk and protective factors that influence youth substance use in Australia and the United States. The two countries have different policy orientations toward substance use: Australia has adopted harm-reduction policies, and the United States has adopted abstinence-focused polices.

Methods
Cross-sectional survey data were collected from independent samples of adolescents in the states of Maine (N = 16,861; 53% female, 7% Non-white) and Oregon (N = 15,542; 51% female, 24% Non-white) in the United States and Victoria in Australia (N = 8442; 54% Female, 11% Non-white) in 1998 (Maine and Oregon) and 1999 (Victoria). Chi-square tests, t-tests, effect size comparisons, and logistic regression analyses that accounted for age and gender were used to investigate cross-national similarities and differences in: (a) rates of cigarette, alcohol, and marijuana use; (b) levels of risk and protective factors; and (c) magnitudes of associations between risk and protective factors and substance use.

Results
More adolescents in Victoria reported using cigarettes and alcohol, whereas more of the U.S. adolescents reported using marijuana. Exposure to risk and protective factors was generally similar in the cross-national samples. However, adolescents in Maine and Oregon perceived handguns to be more readily available, reported more participation in religious activities, and were higher in sensation-seeking and social skills; and adolescents in Victoria had more favorable attitudes toward drug use and reported community norms and parental attitudes more favorable to drug use. Most of the risk and protective factors were strongly associated with substance use to a similar degree in Victoria, Maine, and Oregon. However, among adolescents in Maine and Oregon peer/individual risk and protective factors associated with social detachment were more strongly related to substance use, and among adolescents in Victoria, family protective factors were less strongly related to alcohol use.

Conclusions
Inter-country influences on youth substance use are generally similar despite different policy directions. Existing differences suggest that the abstinence policy context is associated with higher levels of illicit drug use and stronger relations between individual indicators of social detachment and substance use, whereas the harm reduction policy context is related to more cigarette and alcohol use, possibly from exposure to normative influences that are more tolerant of youth drug use.

Levels and family correlates of positive adolescent development: A cross national comparison

The article examines the levels of positive school engagement, and family characteristics associated with engagement, in adolescents in Australia and the United States. There are several modifiable family characteristics related to positive behavior. These include parents boosting both rewards for and opportunities to participate in prosocial activities, and the importance of expressing clear disapproval of antisocial behavior and drug use. Family management practices and family conflict influence adolescents' views about school and home and need to be addressed. There is evidence of the validity of ecological approaches to development, which underscores the inter-relationships between young people's developmental contexts.

Effect of dietary fatty acids on the intestinal permeability of marker drug compounds in excised rat jejunum

The aim of this study was to explore the effects of diets containing saturated fatty acids (SFA), monounsaturated fatty acids (MUFA), and ω-3 and ω-6 polyunsaturated fatty acids (ω-3 and ω-6 PUFA, respectively) on the passive and active transport properties of rat jejunum using marker compounds. Rats were fed diets supplemented with 18.4% (w/w) lipid (4 groups) or standard rat chow (1 group) for a period of 30 days. At the end of the dietary period, mucosal scrapings were taken for the determination of membrane phospholipids, and the apparent jejunal permeability of radiolabelled marker compounds was determined using modified Ussing chambers. Changes in the phospholipid content of the brush border membrane reflected the different lipid content of the diets. The passive paracellular permeability of mannitol was not significantly affected by the fatty acid composition of the diet, although there was a trend toward decreased mannitol permeability in the rats fed both the ω-3 and ω-6 PUFA diets. In comparison, the transcellular diffusion of diazepam was reduced by 20% (P < 0.05) in rats fed diets supplemented with ω-3 and ω-6 PUFA. In the lipid-fed rats, the serosal to mucosal flux of digoxin, an intestinal P-glycoprotein substrate, was reduced by 20% (P < 0.05) relative to the chow-fed group, however there were no significant differences between the different lipid groups. The active absorption of D-glucose via the Na+-dependent transport pathway was highest in the SFA, MUFA and PUFA ω-3 dietary groups, intermediate in the low-fat chow group and lowest in the PUFA ω-6 group, and was positively correlated with short-circuit current. These studies indicate that dietary fatty acid changes can result in moderate changes to the active and passive transport properties of excised rat jejunum.

Common structural basis for central nervous system drug design

The main theme of this thesis is that there is a common structural basis for drugs acting on the central nervous system (CNS), and that this concept may be used to design new CNS-active drugs which have greater specificity and hence less side-effects. To develop these ideas, the biological basis of how drugs modify CMS neurotransmission is described, and illustrated using dopaminergic pathways. An account is then given of the use of physicochemical concepts in contemporary drug design. The complete conformational analysis of several antipsychotic drugs is used to illustrate some of these techniques in the development of a model for antipsychotic drug action. After reviewing current structure-activity studies in several classes of CNS drugs (antipsychotics, anti-depressants, stimulants, hal1ucinogens, anticonvulsants and analgesics), a hypothesis for a common structural basis of CNS drug action is proposed- This is based on a topographical comparison of the X-ray structures of eight representative CNS-active drugs, and consists of three parts: 1.there is a common structural basis for the activity of many different CNS-active drug classes; 2. an aromatic ring and a nitrogen atom are the primary binding groups whose topographical arrangement is fundamental to the activity of these drug classes; 3. the nature and placement of secondary binding determines different classes of CNS drug activity. A four-Point model for this common structural basis is then defined using 14- CNS-active drug structures that include the original eight used in proposing the hypothesis. The coordinates of this model are: R1 (0. 3.5, 0), R2 (0, -3.5, O), N (4.8. -0.3, 1.4), and R3 (6.3, 1.3, 0), where R1 and R2 represent the point locations of a hydrophobic interaction of the common aromatic ring with a receptor, and R3 locates the receptor point for a hydrogen bond involving the common nitrogen, N. Extended structures were used to define the receptor points R1, R2 and R3, and the complete conformational space of each of the 14 molecules was considered. It is then shoun that the model may be used to predict whether a given structure is likely to show CNS activity: a search over 1,000 entries in the current Merck Index shows a high probability (82%) of CNS activity in compounds fitting the structural model. Analysis of CNS neurotransmitters and neuropeptides shows that these fit the common model well. Based on the available evidence supporting chemical evolution, protein evolution, and the evolution of neurotransmitter functions, it is surmised that the aromatic ring/nitrogen atom pharmacophore proposed in the common model supports the idea of the evolution of CNS receptors and their neurotransmitters, possibly from an aromatic amine or acety1cho1ine acting as a primaeval communicating molecule. The third point in the hypothesis trilogy is then addressed. The extensive conformation-activity analyses that have resulted in well-defined models for five separate CNS drug classes are used to map out the locations of secondary binding groups relative to the common model for anti-psychotics, antidepressants, analgesics, anticholinergics, and anticonvulsants. With this information, and knowledge derived from receptor-binding data, it is postulated that drugs having specified activity could be designed. In order to generate novel structures having a high probability of CNS-activity, a process of drug design is described in which known CNS structures are superimposed topographically using the common model as a template. Atoms regarded as superfluous may be selectively deleted and the required secondary binding groups added in predicted locations to give novel structures. It is concluded that this process provides the basis for the rational design of new lead compounds which could further be optimized for potent and specific CNS activity.

Quick fixes, drug culture and management culture : excellence and ecstasy, BPR and Brown

This paper critiques the prescriptions of management gurus by charting parallels between management culture and drug culture over the last two decades. I argue that the ‘quick fixes’ peddled by gurus mirror the illicit drug fix of choice popularised in the same era. I suggest that, in terms of the specific nature of their promised highs, Excellence mirrored Ecstasy, and Business Process Reengineering mirrored Heroin. By tracing resonance with drug fixes, I introduce another way to understand why particular corporate fixes are found so attractive, locating this in patterns of addiction and in the gurus’ ability to exploit wider shared cultural contexts. The paper ends by suggesting that the comparison with the world of illicit drugs has lessons not only for our understandings of management and management gurus, but also for critical management academics engagement with both the gurus and our wider audiences.

Prediction of Drug Dissolution Profiles Using Artificial Neural Networks

This paper investigates the efficacy and reliability of Artificial Neural Networks (ANNs) as an intelligent decision support tool for pharmaceutical product formulation. Two case studies have been employed to evaluate capabilities of the Multilayer Perceptron network in predicting drug dissolution/release profiles. Performances of the network were evaluated using similarity factor (&fnof[sub 2]) — an index recommended by the United States Food and Drug Administration for profile comparison in pharmaceutical research. In addition, the bootstrap method was applied to assess the network prediction reliability by estimating confidence intervals associated with the results. The Multilayer Perceptron network also demonstrated a superior performance in comparison with multiple regression models. The results reveal that the ANN system has potentials to be a decision support tool for profile prediction in pharmaceutical experimentation, and the bootstrap method could be used as a means to assess reliability of the network prediction. [ABSTRACT FROM AUTHOR].

Comparison of milling and solution approach for production of silk particles

Silk particles were produced by regenerating from silk solution, and using a milling method. In the regenerated silk particle production, two methods which are reported to render submicron silk particles were selected. Their particle sizes and structures were compared with particles of milling method already developed by us. The volume median average particle sizes (d(0.5)) of regenerated particles were much higher than what was reported previously. In contrast, milling method could produce particles with adjustable particle sizes ranging from micron to submicron level. All the milled particles had advantage of at least 15. °C higher thermal decomposition temperature than regenerated particles. They had silk II structure, and the crystallinity reduced as particle fineness increased, but remained higher than regenerated particles of similar sizes. © 2014 Elsevier B.V.

Comparison of Impurity Profiles of Lipiblock (R) vs. Orlistat using HPLC and LC-MS/MS

Comparative HPLC-UV and LC-MS/MS studies of impurity profiles of a reference sample (Xenical (R), F. Hoffmann La Roche Ltd., Switzerland) vs. generic (Lipiblock (R), EMS Sigma Pharma, a generic drug) were carried out with ethanol extracts of commercial samples. The generic formulation contained higher levels of common impurities as well as a considerable number of impurities not found in the reference product. The detected impurity profile of Lipiblock (R) revealed that it most likely is based on fermentation. Since the effect of the impurities is unknown, at this point fully synthetic Xenical (R) appears to offer a better safety margin than Lipiblock (R) which, however, compares quite well to other generic formulations.

Comparison of resazurin microtiter assay performance and BACTEC MGIT 960 in the susceptibility testing of Brazilian clinical isolates of Mycobacterium tuberculosis to four first-line drugs

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Comparison of caffeine-induced locomotor activity between adolescent and adult rats

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

A preliminary trial comparison of several anesthetic techniques in cats

The aim of this study was to investigate the effect of several drug combinations (atropine, xylazine, romifidine, methotrimeprazine, midazolam, or fentanyl) with ketamine for short term anesthesia in cats. Twelve cats were anesthetized 6 times by using a cross-over Latin square protocol: methotrimeprazine was combined with midazolam, ketamine, and fentanyi; midazolam and ketamine; romifidine and ketamine; and xylazine and ketamine. Atropine was combined with romifidine and ketamine, and xylazine and ketamine. Temperature, heart rate, and respiratory rate decreased in all groups. Apnea occurred in 1 cat treated with methotrimeprazine, romifidine, and ketamine, suggesting that ventilatory support may be necessary when this protocol is used. Emesis occurred in some cats treated with alpha(2)-adrenoceptor agonists, and this side effect should be considered when these drugs are used.

Comparison of risk factors among blood donors, volunteers and replacement individuals, infected or not by hepatitis C virus

Hepatitis C is transmitted primarily parenterally by contaminated blood and is often associated with: intravenous drug abuse, invasive procedures, blood transfusions, acupuncture, tattooing, and alcohol and tobacco use. This study aimed to quantify and evaluate the risk factors among blood donors, volunteer blood donors and replacement individuals, infected or not by the C virus. The main transmission routes of C virus were identified in 55 men and 25 women (GI) monitored by the Ambulatory Unit of the Department of Tropical Diseases, Botucatu Medical School, and in 24 men and 26 women (GII), all active blood donors at the Bauru State Hospital Transfusional Agency. Both groups were similar in: tobacco and alcohol consumption, sexual behavior, tattooing and illicit drug use. The duration of alcohol and tobacco consumption and blood transfusions in GI were longer, whereas the option for steady partners, condom use, disposable materials and piercings were predominant in GII. In conclusion, the risk factors for hepatitis C demonstrate the necessity of health policies that act on the primary and secondary prevention levels (respectively, reduction of infection incidence and hepatopathy risk).