Molecular dynamics, physical stability and solubility advantage from amorphous indapamide drug.

This study for the first time investigates physicochemical properties of amorphous indapamide drug (IND), which is a known diuretic agent commonly used in the treatment of hypertension. The solid-state properties of the vitrified, cryomilled and ball-milled IND samples were analyzed using X-ray powder diffraction (XRD), mass spectrometry, nuclear magnetic resonance (NMR), infrared spectroscopy (FT-IR), differential scanning calorimetry (DSC) and broadband dielectric spectroscopy (BDS). These analytical techniques enabled us (i) to confirm the purity of obtained amorphous samples, (ii) to describe the molecular mobility of IND in the liquid and glassy state, (iii) to determine the parameters describing the liquid-glass transition i.e. Tg and dynamic fragility, (iv) to test the chemical stability of amorphous IND in various temperature conditions and finally (v) to confirm the long-term physical stability of the amorphous samples. These studies were supplemented by density functional theory (DFT) calculations and apparent solubility studies of the amorphous IND in 0.1 M HCl, phosphate buffer (pH=6.8), and water (25 and 37 °C).

Determination of polydimethylsiloxanes by 1H-NMR in wine and edible oils.

Fourier transform (1)H-nuclear magnetic resonance (NMR) spectroscopy was suitable for the quantitative determination of polydimethylsiloxanes (PDMS) in wine and edible oil samples. This approach offers highly specific qualitative and quantitative analysis due to silicone-specific location of proton signals linked to carbon atoms located directly next to silicon atoms (0-0.5 ppm), as well as a different location of signals in the range for different organosilicon structures. The method can be used for the control of PDMS at regulatory limits in foodstuffs (10 mg kg(-1)) using hexamethyldisiloxane (HDMS) as an internal standard. Samples were prepared by extraction under suitable conditions to separate the analyte, and with analyte enrichment before (1)H-NMR analysis. Analytical procedures were developed to permit the determination of PDMS at 0.06 mg kg(-1) in wine and at 6 mg kg(-1) in edible oils samples using readily available NMR instrumentation. It was, however, possible to lower the limit of detection to 6 microg kg(-1) for wine and to 60 microg kg(-1) for edible oils using a higher field instrument (500 MHz). Relative standard deviations (S(r)) were obtained for wine (0.028) and for oil samples (0.043), which when compared with values obtained for samples spiked with PDMS (0.021) indicated that the sample preparation was the main factor determining the precision of the method. The average recovery rates for PDMS were 97 and 95% for wine and edible oils, respectively. PDMS was detected in four brands of Italian wine, with Chianti-Rafaello containing the highest concentration (0.35 mg kg(-1)), and in four types of edible oils, highest concentration (11.9 mg kg(-1)) being found in Italian corn oil. None of the levels of PDMS found in the food samples exceeded the permissible standards laid down by the Codex Alimentarius Commission (10 mg kg(-1)), with the exception of the one corn oil sample.

[Hygienic conditions and the quality of nutrition in workers' canteens in the province of Ciechanow]. / Stan sanitarny i jakosc zywienia w stolówkach pracowniczych w województwie ciechanowskim.

In 1987 the hygienic condition was analysed of 28 workers' canteens in the Province of Ciechanów considering also the quality of lunches or the se called regenerative-fortifying meals. The inspection showed that the hygienic condition of 14 canteens (40%) was unsatisfactory. The microbiological cleanliness of the equipment was questioned most frequently in these canteens in which the hygienic condition was below standard. In 28 canteens controlled the nutrition was incorrect in view of deviations from the accepted standard content of protein, fats and carbohydrates as well as energy. The food rations expressed in 12 groups of products in 21 canteens differed from the recommended values for partial nutrition. It was found also that the occupational qualifications and the level of knowledge on rational nutrition of the staff and personnel in the canteens were unsatisfactory.

Evaluation of the metabolizing capacity of S9 liver preparations from rats and mice using a test with Salmonella typhimurium TA100.

The S9 phenobarbital-induced preparations from Albino rats and 6 strains of inbred and outbred Pzh: SFISS mice were tested by an Ames test for their ability to metabolize the two promutagens 2-aminofluorene (2AF) and cyclophosphamide (CP), and to influence the mutagenic activity of the two directly acting mutagens methyl methanesulphonate (MMS) and N-methyl-N'-nitro-N-nitrosoguanidine (MNNG). 2AF showed a mutagenic activity after incubation with all kinds of microsomal preparations. S9 from B10. mice (Ah+Ah+) was twice as active as that from D2.BN mice (Ah- Ah-). CP was mutagenic exclusively in the presence of S9 from Pzh: SFISS or B10. mice and from rats. Neither fraction deactivated significantly the mutagenicity of MMS. Microsomal preparations from Albino rats and outbred mice were most active in deactivating the mutagenicity of MNNG.

Protective action of ascorbic acid against mutagenicity of aminopyrine plus nitrite.

Mutagenicity of aminopyrine and of aminopyrine plus nitrite was tested by the micronucleus test in bone marrow of mice and by host mediated mutagenicity assay with mice as host animals and S. typhimurium strain G 46. In parallel the possibility of the protective action of ascorbic acid was studied. Aminopyrine at the dose of 90 mg/kg po when administered to mice together with potassium nitrite induced a significant increase in the frequency of micronuclei in polychromatic erythrocytes and proved to be mutagenic for a Salmonella strain. In both systems mutagenicity of the combination of aminopyrine at this dose plus nitrite was abolished completely by ascorbic acid (373 or 622 mg/kg po). Ascorbic acid neither induced a significant increase in the frequency of micronuclei nor was mutagenic for the strain G 46. A formulation of aminopyrine with ascorbic acid is proposed.

Mutagenicity of oxytetracycline.

Oxytetracycline hydrochloride, potassium nitrite and a combination of this antibiotic with the nitrite were tested for their mutagenicity in the host-mediated assay with mice as the host animals. The Salmonella typhimurium strain used was his G46. The bacteria were injected intraperitoneally, and the test compounds were administered by a stomach tube. Neither oxytetracycline nor potassium nitrite were mutagenic for strain G46, but the combination of the compounds administered in the highest tolerated doses proved to be mutagenic for this Salmonella strain. The mutagenicity of the compounds was further evaluated by the micronucleus test in the bone marrow of Swiss mice. The test compounds were administered p.o., half the dose 30 h and the rest 6 h before the animals were killed. Oxytetracycline and the combination of oxytetracycline with potassium nitrite induced a significant increase in the frequency of micronuclei in polychromatic erythrocytes. Dose-response experiments with oxytetracycline and with the combination of the antibiotic with nitrite revealed an apparent no-effect level at 2 X 50 to 2 X 500 mg/kg. At higher doses both oxytetracycline and oxytetracycline with nitrite significantly influenced the ratio of erythrocytes to nucleated cells. The findings were compared with data obtained with dimethylnitrosamine included in both kinds of experiment.

Effect of excess methionine on methotrexate cell-killing action in vitro.

Methionine at the concentrations 10, 15 and 20 times higher than in complete Fischer's medium produced a transient impairment or a transient block in the growth of L 5178 Y cells in culture without influencing their viability. Autoradiographic data revealed that methionine-induced inhibition of DNA synthesis was followed by a partial synchronization of cells in the phase of DNA synthesis. Methionine at a high concentration (1.5 mg/ml) enhanced the cell-killing action of methotrexate under conditions of delayed drug addition and did not diminish it when added with the drug simultaneously.

Dependence on exogenous methionine of rat sarcoma and murine leukemia cells in culture.

A comparative study was performed on methionine auxotrophy of rat sarcoma and murine leukemia cells taken directly from the organism and grown in culture in media lacking methionine or in which methionine was substituted by homocysteine. Methionine auxotrophy was observed in both kinds of cells. At low levels of methionine in the media containing homocysteine rat sarcoma cells showed an increase in growth. Addition of homocysteine to the media with low levels of methionine did not influence the survival of murine leukemia cells.

On the combined action of drugs on the lambda prophage induction in Escherichia coli K12 cells.

The capability of methotrexate, jododeoxyuridine and 5-fluorouracil to induce lambda prophage was compared when given alone or in combination. All these drugs were found to cause inducing conditions in Escherichia coli K12(lambda) cells. Combined action of jododeoxyuridine and methotrexate resulted in a pronounced increase in the number of free phages compared with that resulting the treatment either with methotrexate of jododeoxyuridine alone. Treatment with 5-fluorouracil caused inactivation of plaque forming ability in cells induced with methotrexate.