Genotype and phenotype correlations in diabetic patients in Uruguay.

To differentiate among different types of diabetes is becoming an increasingly challenging task. We investigated whether the patient's genetic profile is useful to identify the particular type of diabetes, to determine the corresponding hyperglycemia pathogenesis and treat accordingly. Three hundred and thirty-eight diabetic patients, diagnosed according to American Diabetes Association criteria, were recruited from 2004 to 2008 in diabetes health reference centers. We analyzed the major gene for type 1 diabetes susceptibility (HLA DQ/DR). In order to improve our understanding of the pathogenesis of the resulting hyperglycemia and to implement a more adequate treatment for the patients, we reclassified our sample according to the presence or absence of the genetic markers. We found that a higher percentage of people than expected have immunological disease, independent of their phenotype, with a relative risk of 4.62 (95% confidence interval). This methodology allowed us to establish an association between the genotype and its resulting phenotype. We found significant differences; the phenotypic classification did not reflect immunological disease based on genotype. Moreover, when we examined markers, body mass index and age of onset, we found that many people have an intermediate phenotype between type 1 and type 2. This genetic data can help provide an accurate definition of the disease and would therefore provide the physician a better possibility of providing adequate treatment.

Comparative study of the sorption of clomipramine and viloxazine hydrochlorides in Stedim 6 and PVC bags.

The stability of two antidepressant drugs, clomipramine and viloxazine hydrochlorides, was studied as was their possible sorption on Stedim 6, a new multilayer polyethylene-lined film, which was considered comparatively to polyvinyl chloride (PVC) and glass surfaces. Appropriate amounts of the drugs were added to 500 ml of 5% dextrose and 0.9% sodium chloride solutions in Stedim 6 and PVC bags, and in glass flasks, in order to obtain the concentrations currently used in clinical practice. All the containers were stored at room temperature in daylight for 72 hours. Samples were taken at various times and evaluated for remaining drug concentrations by UV spectrometry. The two drugs appeared stable under the given conditions. No concentration decrease was observed in glass flasks. Viloxazine hydrochloride showed an excellent compatibility with the PVC bags, but a slight concentration decrease (about 6-7% in 72 hours) was observed for clomipramine hydrochloride, depending on the contact duration. The compatibility of the two drugs with the new material Stedim 6 was found to be perfect. The behavioral differences observed between the two drugs with regard to PVC are explained in terms of differences of lipophilicity of the drugs. Those observed for a given drug with regard to the two materials are due to the crystalline structure of polyethylene and the amorphous one of PVC.

Disposable devices for the dispensing of oral drops. Study of photoprotectiveness and compatibility.

Amber-coloured syringes designed for the distribution of unit-doses of oral drops were studied for the efficiency of the photoprotectiveness and the possible binding of eleven phenothiazine neuroleptics: alimemazine, chlorpromazine, cyamemazine, fluphenazine, levomepromazine, periciazine, pipotiazine, prochlorperazine, thioproperazine, thioridazine, and trifluoperazine, all very easily oxidized in solution in daylight. Spectrofluorimetry made it possible, in one operation, to determine the remaining concentrations of drugs after storage and to verify the absence of photo-oxidation. The storage was performed up to 13 days at 25 +/- 3 degrees C and without any precaution from daylight. All the drugs studied were stable and none bound on the syringes. However, the stability appeared to be due to the antioxidants in the drug preparations, and not to the coloured material, since oral drops were also stable in uncoloured syringes designed for injection. Nevertheless, the amber-coloured syringes efficiently protect the active principles in pure aqueous solutions, without preservative, and thus this physical protection reinforces the chemical one of the galenical formulation.

Stedim 6 and Clearflex, two new multilayer materials for infusion containers. Comparative study of their compatibility with five drugs versus glass flasks and polyvinyl chloride bags.

Stedim 6 and Clearflex, two new polyethylene-lined materials for infusion bags, were studied for their compatibility with disodium clodronate, chlorpromazine and maprotiline hydrochlorides, diazepam, and clorazepate dipotassium salt, comparatively with borosilicate glass flasks and polyvinyl chloride bags. Diazepam, the only drug to exhibit a marked sorption in PVC bags (the loss reached 25% of the initial concentration after a contact duration of 72 h), showed lower sorption in Stedim 6 bags (loss about 11% under the same conditions) and none in Clearflex bags. No significant difference was observed between the infusion solutions used as vehicles of the drugs (5% dextrose and 0.9% sodium chloride isotonic solutions). The results are discussed in terms of lipophilicity of the drugs and crystallinity of the polymers.

Interactions between six psychotherapeutic drugs and plastic containers. Influence of plastic material and infusion solutions.

The interactions of chlorpromazine, clomipramine, maprotiline and viloxazine hydrochlorides, and of clorazepate dipotassium salt and diazepam with polyvinyl chloride (PVC) and Stedim 6 infusion bags were studied. Stedim 6, is anew multilayer film whose inner layer is made of polyethylene. The drugs were in 5% dextrose and 0.9% sodium chloride isotonic solutions and the influence of these was also considered. The remaining concentrations of each drug were determined at regular time intervals in a 24-h period, by a spectrofluorometric method for chlorpromazine hydrochloride and by ultraviolet spectrophotometric methods for the other drugs. No binding was observed for viloxazine and maprotiline hydrochlorides whatever the infusion solution and the plastic container. A slight retention in PVC bags, but not in Stedim 6 ones, was noted for clomipramine hydrochloride and clorazepate dipotassium salt. This was more marked in the sodium chloride solution than in the dextrose one. Diazepam and chlorpromazine hydrochloride were bound both in PVC and Stedim 6 bags, but more in the former and more again in the sodium chloride solution than in the dextrose one. The results were explained in terms of the degree of crystallinity of the plastic material and the degree of lipophilicity of the drugs. Practical consequences are discussed.

Effects of temperature, solution composition, and type of container on the stability and absorption of carmustine.

The stability and absorption of carmustine were studied comparatively in glass flasks and Stedim 6 bags. Stedim 6 is a new, multilayer, polyethylene-lined film. When stored at room temperature (22 degrees C +/- 2 degrees C) in the dark, carmustine decomposed in 5% dextrose solution and more so in 0.9% sodium chloride solution. When stored at 4 degrees C +/- 0.5 degrees C, the losses were identical in the glass flasks and Stedim 6 bags (about 11% after 72 hours). As long as they are kept in the dark at 4 degrees C, carmustine admixtures can be prepared up to 48 hours before administration, in either dextrose or sodium chloride isotonic solutions, and stored in either glass flasks or Stedim 6 bags.

Sorption studies of dipotassium clorazepate salt (Tranxène) and midazolam hydrochloride (Hypnovel) in polyvinyl chloride and glass infusion containers.

The compatibilities of dipotassium clorazepate and midazolam hydrochloride with polyvinyl chloride (PVC) bags have been studied and compared with those observed with glass flasks. At room temperature, dipotassium clorazepate showed chemical instability which was independent of the container. At 4 degrees C, dipotassium clorazepate showed no decrease in concentration over 12 h, both in 5% dextrose solution and 0.9% sodium chloride solutions. When stored for longer periods of up to 72 h, a slight decrease not exceeding 5% was observed. The compatibility of midazolam with the PVC bags was found to be good at room temperature. It was slightly better in 5% dextrose solution than in 0.9% sodium chloride solution. High sorption of the drug was observed at pH 7.0 when the primary ring structure is maintained. The results make it possible for the hospital pharmacist to prepare dipotassium chlorazepate salt and midazolam admixtures up to 3 days before administration, provided the former are stocked in a refrigerator and the latter are prepared in dextrose isotonic solutions.

Comparative sorption of clomipramine, viloxazine, and maprotiline hydrochlorides in polyvinylchloride bags and glass vials.

The sorption of clomipramine, viloxazine, and maprotiline hydrochlorides was studied comparatively in polyvinylchloride (PVC) bags and glass flasks for up to 72 hours. When stored in glass flasks, no decrease in concentration was observed for any of the three drugs, either in dextrose or sodium chloride isotonic solution. When stored in PVC bags, a slight loss (about 7% within 72 hours), was noted for clomipramine hydrochloride in both isotonic solutions, but not for the other two drugs.

Leaching of antioxidants and vulcanization accelerators from rubber closures into drug preparations.

A thin-layer chromatographic method was used to highlight the leaching into drug preparations of several constituents of elastomeric closures. Among the 150 preparations analysed, the twenty-eight local anaesthetics presented in single-dose delivery syringe-cartridges, one Epinephrine injection in prefilled syringes, eight insulin preparations and two Prednisolone acetate suspensions in the form of small volume flasks (less than or equal to 20 ml) were contaminated by one or more of the following: 2-mercaptobenzothiazole (MBT), 2-mercaptobenzothiazole disulphide and 2-mercaptobenzimidazole (MBI). Prednisolone acetate suspensions also contained 2,2'-methylene-bis(4-methyl-6-alpha-methylcyclohexylphenol). No contamination was found in drug preparations presented in large volume flasks (250-1000 ml). 2-(2-Hydroxyethylthio)-benzothiazole was not present, which indicated that the rubbers had not been sterilized with ethylene oxide. Elastomeric parts of drug closures analysed in the same way contained the same compounds as those found in drugs, one case excepted, which confirms the origin of the contamination. The lowest and the highest concentrations were found in syringe-cartridges; they ranged from 8.3 to 13.8 micrograms ml-1 for MBT, from 2.9 to 9.3 micrograms ml-1 for MBTS and from 2.8 to 11.1 micrograms ml-1 for MBI. Variable results were obtained, for a same preparation, depending upon the batches analysed, which indicates that rubber formulations and/or vulcanization conditions differed. The allergenic, toxic, embryotoxic and mutagenic properties of the compounds leached are discussed.

Thin-layer chromatography of amine antioxidants and antiozonants used in elastomers.

Fifty-four amines used as antioxidants and/or antiozonants for elastomers were separated on silica gel thin-layer plates with benzene and benzene-ethyl acetate-acetone (100:5:1) as developing solvents and N-chloro-2,6-dichloro-p-benzoquinone monoimine in buffered alkaline medium as spray reagent. Benzene-n-hexane (50:50) was used to separate diheptyl- and dioctyldiphenylamines. The active agents of several imprecisely defined products were identified and the relationships between some mixtures were elucidated. The method highlights the numerous minor components of these very impure industrial compounds. Some theoretical correlations between the chemical structures, the RF values and the colours of the spots were also established.

Identification of phenolic antioxidants in elastomers for pharmaceutical and medical use.

Phenolic antioxidants were identified by thin-layer chromatography (TLC) in 102 samples of pharmaceutical and medical rubber articles. Despite the large number of antioxidants proposed for elastomers, only eight compounds were found in the articles analyzed. The choice of antioxidants apparently does not depend on the sterilizing processes or on the use or brand of articles.

Thin-layer chromatographic analysis of phenolic age resisters in elastomers in contact with the body, drugs and foods.

Phenolic antioxidants were identified by thin-layer chromatography in 102 samples of medical and pharmaceutical rubber articles. Acetone extracts of rubber were spotted on silica gel plates with a concentrating zone. Benzene, benzene-hexane (75:25) and benzene-ethyl acetate-acetone (100:5:1) were used as developing solvents and N-chloro-2,6-dichloro-p-benzoquinone monoimine as spray reagent. Only 8 sterically hindered phenols among the 57 previously listed were found in current use. Reasons for choosing these compounds and the experimental conditions are discussed.

[Characterization by thin layer chromatography of benzothiazole derivatives and beta-sitosterol leached by disposable syringes]. / Caractérisation par chromatographie sur couche mince des composés benzothiazoliques et du beta-sitostérol cédés par les seringues non réutilisables.

A thin-layer chromatographic study of 2-mercaptobenzothiazole, 2-(methylthio)benzothiazole, 2-(2-hydroxy-ethylthio)benzothiazole, 2-hydroxybenzothiazole, zinc 2-mercaptobenzothiazolate, mercaptobenzothiazole disulfide, and beta-sitosterol with three developing solvents and eleven spray reagents is reported. A simple method is described which highlights the leaching of 2-mercaptobenzothiazole and 2-(2-hydroxy-ethylthio)benzothiazole from the rubber plunger-seals of disposable syringes: contact of rubber with bidistilled water, extraction of this liquid with chloroform, chromatography on silica gel with the solvents previously studied and spraying with N-chloro-2,6-dichloro-p-benzoquinone monoimine. The method may also be used to discriminate those syringes sterilized with ethylene oxide, the only ones able to leach 2-(2-hydroxy-ethylthio)benzothiazole, from those sterilized by irradiation. Owing to the beta-sitosterol traces leached, it may also be used to investigate whether the plunger-seals are made of natural rubber. The toxic effects of the compounds leached are briefly reported.

Mass spectral identification of benzothiazole derivatives leached into injections by disposable syringes.

Five benzothiazole derivatives leached into injections by the rubber plunger-seals of disposable syringes were identified by electron impact (EI) and chemical ionization (CI) mass spectrometry. These are 2-hydroxybenzothiazole, 2-mercaptobenzothiazole, 2-(methylmercapto)benzothiazole, 2-(2-hydroxyethoxy)benzothiazole and 2-(2-hydroxyethylmercapto)benzothiazole. 2-Mercaptobenzothiazole is used as a vulcanization accelerator. The other four compounds are formed from the zinc derivative of 2-mercaptobenzothiazole during sterilization with ethylene oxide. Toxicological, technological and legal consequences of the leaching are discussed briefly.