S-(4-Chlorophenyl) 3-aryl-3-hydroxypropanethioates as antibacterial agents.

A series of S-(4-chlorophenyl) 3-aryl-3-hydroxypropanethioates was prepared and shown to have in vitro activity against several selected bacterial species.

Protective effect of Pepto-Bismol liquid on the gastric mucosa of rats.

Pepto-Bismol liquid (primary active constituent, bismuth subsalicy-late) protected the gastric mucosa of rats against the formation of hemorrhagic lesions or erosions in response to cold + restraint stress, to a combination of aspirin and cold + restraint stress, and to ethyl alcohol. The protective effect of Pepto-Bismol in these studies was clearly demonstrated. Although the mechanism of action of Pepto-Bismol was not delineated, there was a suggestion that the degree of coating of the gastric mucosa was related to protection.

Effect of antibacterial therapy on renal lysozyme levels in rats developing bacterial pyelonephritis.

In animals developing unilateral Proteus mirabilis-induced pyelonephritis, the total soluble renal lysozyme (SRL) of both kidneys undergoes a biphasic elevation. The second phase of elevated SRL is associated with the onset of chronicity in the infected kidney. To discover whether effective antibacterial therapy altered the second elevation of SRL, levels of SRL were determined in rats developing unilateral chronic pyelonephritis with and without effective regimens of antibacterial agents. Therapeutic doses of ampicillin and nitrofurantoin caused elevations of SRL in both kidneys of infected animals, but these differences were not statistically significant (P > 0.05). Both agents produce elevations of SRL in uninfected animals which were significant (P < 0.05) when compared with normal animals. Kanamycin sulfate at a therapeutic dose induced great elevations of SRL in kidneys of both infected and uninfected animals. It is concluded that infection per se is not the cause of the elevated SRL.

Renal lysozyme levels in animals developing "sterile pyelonephritis".

The induction of sterile unilateral pyelonephritis in rats with heat-killed Proteus mirabilis cells is described. The lesions were identical to those produced with viable bacteria. Lysozyme levels in both kidneys of rats developing unilateral sterile pyelonephritis underwent biphasic elevations similar to those produced with viable bacteria. In the injected kidney, the first elevation, associated with the trauma of injection, could be produced by injecting sterile saline. The second elevation was associated with the onset of chronicity in the injected kidney. The nonmanipulated, contralateral kidney showed a similar biphasic elevation, of equal duration but of greater magnitude.

Renal lysozyme levels in animals developing Proteus mirabilis-induced pyelonephritis.

In animals developing experimentally induced unilateral pyelonephritis, both the infected kidney (IK) and the contralateral noninfected kidney (NIK) showed an immediate increase in renal lysozyme activity of about 5 days' duration after the unilateral injection of viable Proteus mirabilis into the renal cortex. Lysozyme activities of the NIK were consistently higher than those of the IK. This initial increase was followed by a second increase which lasted throughout the period of observation (17 days), and enzyme activities of the NIK were consistently higher than those of the IK. In saline punctured kidneys of control animals, both the saline punctured kidney (SP) and the non-saline punctured kidney (NSP) showed only the immediate increase in renal lysozyme activity, which persisted until the SP was completely healed. These enzyme activities were less than those observed in the infected animals, but the response of the NSP was greater than that of the SP. Trauma not directed to the kidney does not produce a similar response of renal lysozyme. The elevated renal lysozyme of the NIK could not be shown to protect it from bacterial infection.

Pyelonephritis therapy in rats: random association with excreted urinary antibacterial activity.

In vitro activities or excreted urinary activities of 56 generic and experimental drugs against two organisms commonly associated with human pyelonephritis, Escherichia coli and Proteus mirabilis, are not correlated with the in vivo activities of these compounds as measured by reduction of viable organisms in kidneys in experimental pyelonephritis.

Rat pyelonephritis model suitable for primary or secondary screening.

A rat Proteus and Escherichia pyelonephritis model is described in which (i) reproducible chronic infections are achieved and (ii) the efficacy of clinically effective agents is reliably demonstrable with five rats in 17 days. It can serve as a primary screen in which one technician can evaluate 180 compounds per month with 900 rats. The manner of inoculation will inherently allow the study of and distinction between metabolism which is peculiar to infection and that which is characteristic of trauma and healing in general for the elucidation of chemical correlations with effective therapy.