Using scanning electron microscopy for statistical characterization of the diameter and shape of airborne particles at an urban location

Particles in the air are characterized not only by their effective diameters but by their shapes as well. In this study electron microscopy was used to provide detailed information about individual particles, including diameter and shape. Following image analysis, statistical methods were used to describe diameter and shape distribution. From using this technique for repeated measuring at a particular location an interesting finding was made: the diameter and shape factor distributions had a constant nature.     

Validity of the BPRS, the BDI and the BAI in dual diagnosis patients

AIM: The psychometric properties of the Brief Psychiatric Rating Scale, the Beck Anxiety Inventory (BAI), and the Beck Depression Inventory (BDI) were tested in a sample of 134 patients with a substance use disorder and a non-substance related psychiatric disorder in a special inpatient dual diagnosis treatment unit. METHODS: Subjects were assessed at baseline. At discharge on average 6 months post-intake, 78% of patients were re-assessed using the same instruments. All instruments were tested in (1) their ability to discriminate patients with different diagnoses at baseline and follow-up using comparison of area under the curves, and (2) their temporal stability. Moderator regression was used to test whether thought disorder at baseline had any effect on the test-retest rank-order stability of other instruments. FINDINGS: The BPRS Thought Disorder scale was able to discriminate between patients with and without schizophrenia spectrum diagnoses, and the BDI was able to discriminate between patients with and without mood disorders and schizoaffective disorders at intake to treatment, and each instrument was significantly better than the other at discriminating relevant diagnostic groups. Discriminant correlations between the BDI and the BAI were high and statistically significant. Moderator regression analyses showed no indication that any of the scales were less stable at higher levels of thought disorder. CONCLUSIONS: It is concluded that dual diagnosis patients can be reliably assessed for symptoms using the BDI and some subscales of the BPRS.     

Spectroscopic techniques in the study of protein binding. A fluorescence technique for the evaluation of the albumin binding and displacement of warfarin and warfarin-alcohol

1. The binding of racemic mixtures of warfarin and warfarin-alcohol to human serum albumin (HSA) is accompanied by an increase in the fluorescence quantum yield of these compounds. This property has been used to measure the characteristics of the binding of warfarin and warfarin-alcohol to HSA at 22 degrees C and 37 degrees C. Within the limits of the technique, no significant differences between the number of binding sites and strength of binding at the tight site at either temperature were observed. 2. The fluorescence of warfarin and warfarin-alcohol was used to label their binding site on HSA and to study the effects of other drugs on their binding. The results indicate that these two molecules are bound to the same site on HSA. 3. The validity of using changes in the fluorescence of warfarin as a measure of its displacement from HSA was investigated. Good correlations were observed between drug-induced decreases in the fluorescence of bound warfarin and displacement as measured by equilibrium dialysis. The displacement of warfarfin, as detected by fluorescence, correlates well with the increase in free warfarin resulting from addition of therapeutic drug concentrations to undiluted human serum. 4. The most potent displacing agents, by all the methods used, were iophenoxic acid, phenylbutazone and oxyphenylbutazone. The first of these is no longer used clinically, but the latter two are and have been reported to cause hypoprothrominaemia by displacing warfarin from HSA. The present study indicates that changes in the fluorescence of warfarin bound to HSA can be used to measure displacement of bound warfarin and to screen drugs that may cause clinically significant interactions by this mechanism.     

Evaluation of the antioxidant activity of different flavonoids by the chemiluminescence method

The objective of the present investigation was to study the antioxidant action of different flavonoids (quercetin, glabridin, red clover, and Isoflavin Beta, an isoflavones mixture) in order to determine if they could be added to a topical formulation used to treat damage caused by free radicals. Samples of 10 μL of the test compounds at different concentrations were mixed with 0.1 M phosphate buffer, pH 7.4, and a luminol solution was added to yield a final concentration of 0.113 mM. Hydrogen peroxide was then added at a final concentration of 0.05 mM. The reaction was started by introducing the horse-radish peroxidase enzyme at a final concentration of 0.2 IU/mL, in a final volume of 1.0 mL. Chemiluminescence was measured for 10 minutes at room temperature, and dimethylsulfoxide (DMSO) was used as a control. All samples showed marked inhibition of oxidative stress, with a concentration-dependent action for quercetin and Isoflavin Beta. The highest inhibition was observed with glabridin and the dry red clover extract. All flavonoids proved to be adequate for addition to topical formulations because of their high antioxidant activity.     

Metabolic actions of some sympathomimetic amines and their acetyl derivatives in the rabbit

To study how acetylation affects the activity of sympathomimetic amines the effects of tyramine, amphetamine, ephedrine, phenylephrine, orciprenaline and salbutamol and of their O- and N-acetyl derivatives on blood glucose and free fatty acid concentrations were studied in the rabbit. Hyperglycemia was induced by all parent compounds except amphetamine which tended to have a weak hypoglycaemic action. Hyperlipaemia in the doses used was induced by ephedrine and orciprenaline but not by the other parent compounds. Usually acetylation decreased the metabolic effects of the compounds but O-acetylation of tyramine and salbutamol caused hyperlipaemia and O-acetylation of ephedrine increased its fatty acid-mobilizing action, perhaps as a consequence of increased lipid solubility of the compounds. The ultimate effects of the O-acetyl derivatives were probably at least partly due to deacetylation at their sites of action. However O-acetylation of sympathomimetics could perhaps be used to induce drug latentiation.     

The influence of porosity upon the distribution of reserpine in calcium sulphate granules

Batches of calcium sulphate granules, all of the same size fraction but of widely differing porosities, were prepared from primary granules of different sizes. Each batch was coated with reserpine by spraying a solution of the drug in methylene chloride onto the granules whilst they were tumbled in a coating pan. The relation between the macroporous nature of the granules and their reserpine content was investigated. Low-pressure mercury porosimetry was used to obtain a quantitative estimate of the porosity and macropore size distribution of the granules, and their surface areas were determined by an air permeability method. Linear relations were obtained when the reserpine content was plotted against either the volume of mercury penetrating per gram of granules at 106·5 kN m^?2 or their surface area.     

Relationship Between the Phasic Period of Interdigestive Migrating Contraction and the Systemic Bioavailability of Acetaminophen in Dogs

The relationships of the phasic period of interdigestive migrating contraction to gastrointestinal (GI) transit of drugs and their oral absorption were investigated in mongrel dogs by simultaneous oral dosing of acetaminophen (AAP) and salicylazosulfapyridine (SASP) at the starting points of the phase I and phase III periods of gastric contractions. Strain-gauge force transducers were surgically sutured onto the serosa of the GI tracts in the dogs to measure the interdigestive migrating contractions. The mean absorption time of AAP and the time for the first appearance of sulfapyridine (a bacterial metabolite of SASP in the colon) in plasma were used as the indices of gastric emptying time (GET) and small intestinal transit time (SITT), respectively. In individual dogs, the GET and the SITT at phase I showed a clear delay in comparison with those at phase III. For AAP used as a marker compound here, the systemic bioavailability after oral dosing to intact beagle dogs at doses of 3, 10, and 20 mg/kg was about 55, 63, and 79%, suggesting that AAP undergoes a non-linear hepatic clearance. At a dose of AAP 20 mg/kg, the systemic bioavailability of AAP was 100% in the case of dosing at phase III, but was reduced by half when dosing at phase I. These results indicate that, in oral dosing, the transit of drugs through the GI tract was clearly affected by the phases of gastric contractions. Phasic GI motility is thus concluded to be a cause for the inter- and intraindividual variations in the systemic bioavailability of drugs such as AAP that undergo a non-linear hepatic clearance, as a result of either gradual or rapid transport of drugs to enzymes on their first pass through the liver.     

Inhibition of the activation of the first component of complement, C1, by various amino acids or peptides

The effects of various amino acids (or their analogues) and peptides on the activation or consumption of human complement by erythrocytes bound with hemolysin or heat-aggregated immunoglobulin G (aggIgG) were studied by using the hemolysis of hemolysin-bound erythrocytes, the consumption of complement by aggIgG in the serum, the hydrolysis of acetyl tyrosine ethyl ester by activated Cl (Cls), Cl hemolysis and a newly developed enzyme immunoassay, which directly measures interaction between Clq and aggIgG. Amino acids or peptides which were proposed to comprise Clq binding sites of the C2 region of IgG or their analogues were used. CH50 was inhibited by lysine or arginine to the largest extent, but other amino acids, including tranexamic acid and epsilon-amino caproic acid were not inhibitory up to 60 mM. The consumption of serum complement by aggIgG was prevented by arginine or lysine (about 60% inhibition at 60 mM) and by histidine to a lesser extent. The activation of Cls in the Cl complex by aggIgG precipitated at pH 5.5 was most inhibited by lysine, and to a lesser extent by tranexamic acid, arginine and epsilon-aminocaproic acid, but not glutamic acid or glycine. The results of Cl hemolysis indicated that, of all amino acids soluble at neutral pH, lysine and arginine were most effective in the inhibition of Cl hemolysis. Tranexamic acid and epsilon-aminocaproic acid were less effective, and glycine and norleucine were hardly effective. Among the dipeptides used, those that are composed of aromatic amino acids were very effective in the inhibition of Cl hemolysis.(ABSTRACT TRUNCATED AT 250 WORDS)     

Toxicity of boehmite nanoparticles: impact of the ultrafine fraction and of the agglomerates size on cytotoxicity and pro-inflammatory response

Abstract

Boehmite (γ-AlOOH) nanoparticles (NPs) are used in a wide range of industrial applications. However, little is known about their potential toxicity. This study aimed at a better understanding of the relationship between the physico-chemical properties of these NPs and their in vitro biological activity. After an extensive physico-chemical characterization, the cytotoxicity, pro-inflammatory response and oxidative stress induced by a bulk industrial powder and its ultrafine fraction were assessed using RAW264.7 macrophages. Although the bulk powder did not trigger a significant biological activity, pro-inflammatory response was highly enhanced with the ultrafine fraction. This observation was confirmed with boehmite NPs synthesized at the laboratory scale, with well-defined and tightly controlled physico-chemical features: toxicity was increased when NPs were dispersed. In conclusion, the agglomerates size of boehmite NPs has a major impact on their toxicity, highlighting the need to study not only raw industrial powders containing NPs but also the ultrafine fractions representative of respirable particles.     

Elucidation of the structural requirements for the bioactivation of mianserin in-vitro

Abstract— The aim of this study was to investigate structure-activity relationships among a series of compounds related to the antidepressant drug, mianserin, with respect to their ability to produce cytotoxic metabolites. Human peripheral lymphocytes were used as target cells and these were exposed to the individual compounds, in the presence or absence of a drug metabolizing system derived from human liver. The individual enantiomers of mianserin showed differences in their cytotoxicity profiles; the R-(–) isomer giving NADPH-dependent cytotoxicity while the S-(+) isomer showed direct cytotoxicity at high concentrations. Cytotoxicity was reduced by removal from mianserin of the nitrogen atom at the 5 position and by substitution of a methyl group for a hydrogen atom at position 14b. In contrast, insertion of an oxygen atom at position 10 of the drug molecule, precluding the formation of a carbonium ion, had little effect on cytotoxic metabolite formation. The data are consistent with the proposal that one or more iminium ions derived from mianserin are responsible for the cytotoxicity observed in this in-vitro system and that appropriate chemical modification may preclude bioactivation of mianserin by P450 enzymes.     

A survey of the use and educational value of the hospital formularly manual

The medical and nursing staffs of two affiliated hospitals were surveyed on their frequency and purpose of use of their hospital's formulary manual. A numerical rating of the perceived educational value of the manuals was also requested. Twenty-two per cent (141/650) of those surveyed completed their questionnaires. Ninety-six per cent of the respondents indicated use of the formulary manuals at least once a month; 62% used the manuals at least once a week. The frequency and character of use of various sections of the formulary manuals are presented. The perceived educational value of the manuals was rated 3 or greater on a scale of 1 (no value) to 5 (greatest value) by 80% of the respondents. The hospitals' formulary manuals are frequently referred to for various types of drug information. The professional staffs perceive the formulary manuals to be educationally valuable sources of drug information. Reasons for the low rate of response to the survey are presented. A plan of how to increase the response rate in a planned future survey is also presented.     

An improved method for the determination of betaine in Echinacea products

A rapid and sensitive HPLC method for the separation and quantification of betaine in Echinacea products has been developed. Strong cation-exchange (SCX) material was used as stationary phase, and a mixture of methanol and 50 mM choline buffer (pH 3.5) as mobile phase. After formation of the bromophenacyl derivative, betaine was detected at 254 nm with a detection limit of 0.2 microgram/ml. The method was successfully used to analyze several Echinacea market products, and significant variations in their betaine content from 0.04 to 0.64% were observed.     

Investigation of the chemical stability of an erythromycin-tretinoin lotion by the use of an optimization system

A combination of 2% erythromycin and 0.05% tretinoin in an alcohol-isopropanol lotion was prepared. Two parameters were investigated for their influence on the stability of erythromycin and/or tretinoin, namely pH and the concentration of butylhydroxytoluene (BHT) as antioxidant. To investigate these two parameters, an optimization technique was used with two factors (pH and concentration of BHT) at two levels. Accelerated stability analysis was performed at 45 degrees C in the dark to exclude isomerization of tretinoin. To analyse erythromycin and tretinoin in the combination preparation, a TLC method, previously developed in the laboratory, was used. The degradation of erythromycin seemed to be much faster than the tretinoin degradation. Optimal stability is shown in the pH range of 8.2-8.6 for erythromycin and 7.2-8.2 for tretinoin while the concentration of BHT had no significant influence.     

Aspartame and the rat brain monoaminergic system

A high dose of aspartame (APM) was administered to rats to study possible effects on brain monoaminergic systems. APM and its metabolite phenylalanine (Phe) were given orally at doses of 1000 and 500 mg/kg, respectively. Significant increases were seen in brain Phe and tyrosine (Tyr) levels. Two different approaches were used to study monoaminergic systems: whole tissue measurements by HPLC-ED and in vivo voltammetry in freely moving rats. Dopamine, serotonin and their metabolites were taken as indexes of neuronal activity. In spite of the high dose used, no modification was found in monoamines or their metabolites in striatum, hippocampus and nucleus accumbens.     

Long-term stability of diluted solutions of the monoclonal antibody rituximab

As it is an important challenge for pharmacists to access the stability of monoclonal antibodies because of the widespread of centralized preparation units, we conducted a study to evaluate the physicochemical and biological stability of diluted rituximab at 1mg/mL over six months at 4°C. We also conducted the study at 40°C to demonstrate that all methods employed were stability indicating. Various protein characterization methods were used to determine changes in physicochemical properties of rituximab, including size-exclusion chromatography, dynamic light scattering, turbidimetry, cation-exchange chromatography, second-derivative ultraviolet and infrared spectroscopy, and peptide mapping. Cell culture was used to assess biological stability. We demonstrated that diluted rituximab stored at 4°C in polyolefine bags remained stable for at least six months. No physical or chemical instability was observed, and the biological activity was fully maintained. Size exclusion chromatography did not show polymerization or fragmentation. No difference was noticed in the hydrodynamic diameter of RTX. No additional peak or decrease in the areas under curve was found by cation exchange chromatography. The thermal aggregation curves and their derived thermodynamic parameters were unchanged. The primary, secondary and tertiary structures of the protein were not modified. Finally, the direct cytotoxic effect of rituximab was fully maintained.     

Adolescents' perceptions of the internet as a health information source

The internet offers young people easy and anonymous access to information about health and medicines A series of focus groups with United Kingdom school students explored their perceptions of the internet as a health information source Less than one‐third of the students had looked for health information online; those who did were as likely to look for information about a family member's illness as their own health concerns (including diet/exercise, sexual health) Most health information seekers had used a search engine for their query, and their success was determined by their skill at evaluating the search results that they received There are opportunities for educational interventions through schools and pharmacies to help young adults to optimise their use of the internet for health information     

The use of isoniazid as a marker to monitor the self-administration of medicaments.

1. Isoniazid was used as a marker to monitor the regularity of drug self-administration in a trial of chemoprophylaxis against natural influenza infection. Two hundred and sixty-two volunteers were treated for five weeks with a synthetic isoquinoline compound (U.K. 2371) or a matching placebo. 2. Five marker tablets containing isoniazid (150 mg) were incorporated into each regimen and their ingestion monitored by testing for acetylisoniazid in the urine. 3. Positive evidence of marker tablet consumption was obtained on 75% of the occasions on which urine samples were requested. The results obtained among the volunteers from each treatment group who returned urine specimens as requested (92%) indicated that they had swallowed at least 81% of their prescribed tablets. 4. The findings of the study suggest that when used in this way isoniazid is a very suitable compound for use on a few occasions for monitoring the self-administration of drugs in clinical trials.     

Synthesis and evaluation of the thiosemicarbazone, dithiocarbazonate, and 2'-pyrazinylhydrazone of pyrazinecarboxaldehyde as agents for the treatment of iron overload

Three prototype tridentate ligands (i.e., pyrazinecarboxaldehyde thiosemicarbazone, sodium pyrazinecarboxaldehyde dithiocarbazonate, and pyrazinecarboxaldehyde 2'-pyrazinylhydrazone) were prepared and evaluated for their relative abilities to remove iron from model systems designed to mimic particular aspects of chronic transfusional iron overload. These compounds were synthesized by condensation of pyrazinecarboxaldehyde with the appropriate substituted hydrazide. Iron-binding properties were determined, and the ability to remove iron from the proteins transferrin and ferritin was ascertained. An in vivo model system employing iron-loaded mice was used to demonstrate that all three compounds were effective at reducing tissue iron levels.