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The aim of this work was to measure the disintegrating force concomitantly with tablet disintegration, in order to evaluate the disintegration propensity of tablets. Disintegration and dissolution were measured on tablets containing two poorly soluble drugs (diclofenac sodium or ketoprofen), including different percentages of two disintegrants (Explotab or Ac-Di-Sol). Because of the experimental setup, the disintegrating force measured was the result of the force generated by disintegrant swelling and dissipated by tablet disintegration. The disintegrating force versus time curves had shapes ranging from a skewed distribution curve to a bell-shaped curve, depending on slow or rapid disintegration of tablets, respectively. Interestingly, the shape of the resulting curves was very sensitive to the composition of the tablet. When the disintegrant in the formula was increased, the force-time curve approached the bell-like shape. The disintegration propensity of the tablet can be evaluated by the disintegrating force development during disintegration. The disintegration improvement of the formula can be predicted. The disintegrating force curve allows for the clear identification of the optimal percentage of disintegrant to be used.

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2-Amino- and 2-guanidinothiazole derivatives having in position 5 a methylthioalkyl side-chain with urea-equivalent moieties were prepared for comparison with H2-antagonists of cimetidine and tiotidine series. Examination of the pharmacological results obtained from experiments on guinea pig atria and in cat gastric fistula, suggests some general observations about the structure-activity relationship of the compounds synthesized. The activity trend of these products is different from that of H2-imidazole antagonists while it is similar to that of the tiotidine series. Unlike the tiotidine similar compounds, the 2-guanidino-5-thiazolyl derivatives are less potent than the corresponding 2-amino-5-thiazolyl products. The activity of the latter ones is reduced in comparison to that of tiotidine or cimetidine.

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Hydroxyproline and zinc excretion was evaluated in 87 patients with neoplastic breast disease; 40 of these had carcinoma, without radiological and scintigraphy demonstration of bone metastases. In the group of patients with breast cancer, the mean values of hydroxyproline and zinc excretion were found to be significantly higher than in the group with benign breast disease; only 12 of the patients with histologically detected breast cancer had hydroxyprolinuria levels which were higher than the upper limit of the values obtained in the control group. The authors, therefore, conclude that the patients in this group must be considered as being at greater risk.

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Hepatic encephalopathy may complicate chronic liver diseases and portosystemic shunting. Recently it has been suggested that a change in the blood amino acid pattern (with elevated phenylalanine, tyrosine, methionine and depressed branched chain amino acids) and increased levels of octopamine and phenylethanolamine (a false neurotransmitter) are related causally to neurological symptoms. Previous works have suggested that an amino acid mixture of special formulation (enriched in branched chain amino acids and poor in aromatic amino acids) can normalize the plasma amino acid levels and consequently improve the neurological state. In order to test the actual therapeutic effect of these specially formulated solutions, the following therapeutic protocols were administered to 3 groups of cirrhotic patients: group 1 (15 cases): lactulose; group 2 (8 cases): special amino acid solutions; group 3 (8 cases): special amino acid solutions and lactulose. Clinical, laboratory and EEG examinations in a preliminary experiment, before and after treatment, showed that the best effect was obtained by the combined treatment with amino acid solutions and lactulose.

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The authors have pointed out a monosodium-urate (MSU) skin test in vivo, showing a practical usefulness in short-time evaluation of effects of non-steroidal antiphlogistic drugs (NSAID) in man; the isotopic curves, in the area of the skin test, reproduce those obtained in endogenous articular phlogosis. THe authors have studied, at the same time, the actions of NSAID on other skin tests (SK-SD; PHA) which reproduce, in earlier phases of cutaneous reaction, some aspects (erythema, thermographic values, isotopic curves) of 'immediators' phlogosis. The results show that the MSU skin test is more useful in studying the effects of NSAID for the feature of other skin test reactions are affected by many factors.

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The effects of cimetidine have been evaluated in 10 normal subjects on cutaneous delayed reactions in vivo, and on E rosette forming cells in vitro, in order to define the significance of the lymphocytes H2 receptors in cell-mediated immunity. The results show the immuno-suppressive activity of histamine, but do not allow us to hypothesize an immuno-regulatory action of cimetidine.

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The LFER model was used to study quantitatively the interrelations between chemical structure and auxinic activity of some methyl esters of 1,2-benzisothiazol-3-ylacetic acids, using as biological response the cell enlargement induced in etiolated stems of Pisum sativum, var. Alaska. Having demonstrated that activity, expressed as log 1/C, is correlated, by Eq. 8, with factionary charge (-- Qs) calculated for the sulfur atom and with the logarithm of retention time (log t), determined by reverse phase HPLC, the AA. deal with the influences of the latter parameters on the effect registered.

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