Search

The multiplication of M. tuberculosis, var. bovis inoculated into the cornea of mice was studied by staining the whole cornea at various stages after inoculation. Four groups of animals were studied: untreated animals, animals treated with cortisone, animals previously immunized with the same bovine strain, and immunized animals treated with cortisone.In the untreated immunized group little or no multiplication occurred. In the other three groups multiplication did occur and was about the same for the first week after inoculation. After this stage, cortisone-treated animals, whether previously immunized or not, showed increased multiplication and massive cord formation, as compared with untreated animals in which little further multiplication was seen. The cortisone treatment had thus completely suppressed immunity. The significance of these results is discussed.

Trichlorethylene in a sub-anaesthetic concentration (0.5% v/v in oxygen) has an analgesic effect on mice, which develops slowly and reaches a maximum roughly equivalent to that produced by 5 mg/kg of methadone hydrochloride given by intraperitoneal injection. Ethyl chloride causes analgesia in sub-anaesthetic concentrations (3%) but is much less potent than trichlorethylene. Halothane (0.75%) produces slight but definite analgesia. Cyclopropane and diethyl ether have no appreciable analgesic effect. Concentrations of nitrous oxide (up to 90%) in oxygen lack any observable analgesic action on the mouse. Trichlorethylene is considerably potentiated by nitrous oxide, its anaesthetic rather than its analgesic action being affected. Nitrous oxide (40%) potentiates the analgesic rather than the anaesthetic action of halothane (0.75%). However, increasing the concentration of nitrous oxide to 60% causes the anaesthetic action of halothane to predominate.

The anti-inflammatory effect of various substances was measured in rats implanted with cotton wool pellets. Injection or implantation of irritant materials decreased the deposition of granulation tissue on the pellets. As the amount of irritant material increased there was a corresponding decrease in the amount of tissue deposited on the pellets. There is evidence that this could not be explained by a limit to the amount of granulation tissue available within the body, and competition for it between the cotton pellets and the implanted substances. An alternative hypothesis that an anti-inflammatory substance is produced at the site of irritation (the site of implantation of the irritant substance, such as polyester sponges) was investigated. The evidence obtained supports this hypothesis. Inflammatory exudate, squeezed from polyester sponges which had been implanted subcutaneously in the backs of adrenalectomized rats. The substance responsible for this effect is probably not a steroid, and is not normally present in the plasma of adrenalectomized animals. There is, however, some (although not conclusive) evidence that it is present in the plasma of animals in which sponges have been implanted. It does not appear to be produced by incubation in vitro of plasma with sponge. The significance of these observations is discussed.

5-Hydroxytryptamine (5HT) levels were measured in blood and tissues from pregnant mice. Blood levels remained constant during pregnancy and were the same as those in nonpregnant female mice. Placental levels of 5HT increased throughout pregnancy as did the foetal levels. The maternal blood volume of the placenta also increased with advancing gestation. 5HT levels were measured after treatment of the mother with 5HT, and the critical placental level of 5HT observed at about the time of death of the foetus was determined. The levels of 5HT in the placenta and foetus after treatment of the mother with several monoamine oxidase inhibitors were measured, and found to show no significant increase above the normal levels in these tissues. Treatment with cyproheptadine, a 5HT antagonist, did not delay parturition.

As 5-hydroxytryptamine can interrupt pregnancy in all its stages in mice and as pregnancy can be protected from the action of 5-hydroxytryptamine by either progesterone or by prolactin only in early (days 1 to 6) but not in late pregnancy (day 14), the present experiments with two antagonists of 5-hydroxytryptamine, namely methysergide and cyproheptadine, were carried out. Each compound antagonized the action of 5-hydroxytryptamine in late pregnancy. The toxic effects produced by 5-hydroxytryptamine are probably due to a direct action on the placental circulation which is prevented by the antagonists. In early pregnancy, methysergide prevented the effect of 5-hydroxytryptamine, which is believed then to act on the central nervous system, interfering with luteal activity. Cyproheptadine alone interrupted early pregnancy, an action which was prevented by progesterone.

An electrical method of testing for analgesia in mice has been developed for use with inhalation anaesthetics given in sub-anaesthetic concentrations. The anaesthetic drugs are administered in a gas chamber designed for the testing of analgesia without removal of the animals from the chamber.

Mice were infected intracorneally with Mycobacterium tuberculosis var. bovis and the infection allowed to develop for a period of 2 weeks. At this stage the animals were divided into two main groups; one received no treatment, the other was treated with large doses of isoniazid (3.0 mg./mouse/day). The effect of treatment on the primary lesion, the viability of the bacilli, the systemic spread of infection, and the production of immunity were observed. Treatment was continued for 11 months, after which the animals were observed for another 8 months. Within a few days of starting isoniazid treatment the primary lesion stopped increasing in size, regressed slightly and stabilized at a size of about one-third of that of the controls. There was little evidence of any clearing of the bacilli from the lesions; they remained strongly acid-fast and morphologically normal for many months after infection, although by 13 months about half of the organisms in both groups had become very granular. The evidence suggests that in control and treated animals the bacilli in the cornea had usually all died within 8 months after infection. In two treated corneas, living virulent bacilli were demonstrated 15 months after inoculation. In the untreated animals, the disease spread systemically to involve the lungs, liver, and spleen, and by one year after inoculation the systemic tuberculous infection was very heavy, though not enough to kill the animals. The lesions in these animals contained many acid-fast bacilli. In the treated group, systemic spread of infection as judged by the development of small macroscopic lung foci was slight; acid-fast bacilli were found in only one animal. In the treated animals, practically no immunity could be detected 5 months after inoculation and had not reappeared 2 months after cessation of treatment; in the untreated animals immunity was present.