[The treatment of rheumatic and related diseases in general practice with a combined pyrazole preparation (Tomanol)].
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The study with soil incubation test under constant temperature and humidity showed that compared with DCD, DL-1 could significantly inhibit the oxidation of soil ammonium. In the first 3 weeks of incubation, DL-1 had an inhibitory effect of >70% on soil nitrification, with the best effect during 14-28 d of incubation. On the 14, 21, and 28 d of incubation, DL-1 with its dosage being 1.0 % of (NH4)2SO4-N decreased the soil NO3- -N content by 26.23%, 33.27% and 23.31%, respectively, compared with the same dosage of DCD, and by 71.12%, 69.10% and 55.14%, respectively, compared with no inhibitors applied. When the dosage of DL-1 accounted for 2.0% of applied N, soil nitrification was strongly inhibited, and soil NO3- -N content remained at a lower level till to the end (90 d) of incubation.
A series of 4-diazopyrazole-5-carboxamides 1 d-n has been synthesized and their antibacterial activity against a number of Gram-negative and Gram-positive strains has been tested. Some of the compounds resulted quite active and the whole set allowed to further study the SAR of the class. Substituents in position 5 affect Gram-negative and Gram-positive activities via bulk and electronic properties respectively; position 3 mostly affects the Gram-negative activity, while the presence of the charged diazo group in position 4 is crucial for both antibacterial activities.
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Some pyrimidines, pyrazolo[3,4-d]pyrimidines and imidazo[4,5-d]pyrimidines bearing the 5-nitro- and 5-aminothienyl-2-sulfide functionalities on the pyrimidine nucleus were synthesized and evaluated for their antifungal activity against several strains of yeasts and dermatophytes. 4-Amino-2-pyrimidinyl-5'-nitro-2'-thienylsulfide (Va) resulted active against both yeasts and dermatophytes (about 30 fold less potent than Miconazole). Compds. (II b), (V b) and (VIII b) showed only a slight activity against dermatophytes, while the other compounds were inactive.
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Some of the factors influencing the likelihood of the appearance of adverse drug reactions in patients are identified and discussed. Ways of quantifying some of the risks of adverse reactions in different patients are demonstrated. It is pointed out that adverse reaction data can give valuable guidance for both day-to-day patient management and for the initiation or guidance of research projects. In this latter connection, this study highlights the difference in time of onset between aplastic anaemia and agranulocytosis, suggesting different mechanisms of reaction. The majority of adverse reactions occur during the first three weeks of treatment and it is during this time that patients must be most carefully supervised. The old patients should be watched with particular care. It is concluded that age, sex, disease being treated, length of treatment and even the geographical location where the patient lives, can affect the time, type, frequency and outcome of an adverse drug reaction.
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The research on the change of antibacterial activity due to the introduction of a nitro group in the benzene nucleus linked at the heterocyclic nitrogen of N-phenylsulfanilamidopyrazoles is continued with the preparation of 1-(2'-nitrophenyl)-4-sulfanilamidopyrazole (IIa: -NO2 in 2'; R=-H), 1-(3'-nitrophenyl)-4-sulfanilamidopyrazole (IIb: -NO2 in 3'; R=-H) and 1-(4'-nitrophenyl)-4-sulfanilamidopyrazole (IIc: -NO2 in 4'; R=-H). By analogy with the results obtained for the derivatives of 4-sulfanilamidopyrazole (I) previously prepared, enhancement of the bacteriostatic activity in vitro against S. aureus and E. coli, have been observed in almost all the cases, especially with 1-(3-nitrophenyl)-4-sulfanilamidopyrazole (IIb).
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