Effect of toxic thioureas on resistance of rats to growth in the lungs of intravenously and intratracheally seeded tumour cells.

Clonogenic growth (colony-forming efficiency, CFE) of i.v. injected allogeneic W256 tumour cells in the lungs was markedly enhanced by treatment of rats with alpha-naphthyl thiourea (ANTU) injected i.p. from 2 h before to 2 h after the tumour cells. ANTU specifically increases pulmonary vascular permeability in adult rats and causes acute pulmonary oedema and pleural effusion. Inhibition of drug toxicity to the lungs by tachyphylaxis, specific antimetabolites or iodides did not abolish the effect of ANTU on CFE. CFE was not increased when cells were seeded by i.v. injection the lungs affected by advanced pulmonary oedema at 6 to 24 h after treatment with drug. ANTU did not enhance growth of intratracheally injected cells. Although ANTU has no cytotoxic or immunosuppressive action, treatment of tumour-immunized rats with ANTU caused apparent "breakdown" of tumour immunity in 50% of rats, by causing growth of tumour colonies in the lungs. Possible mechanisms for the ANTU-induced decrease in innate resistance to growth of tumour in the lungs are discussed.     

"Akinetic depression" in schizophrenia.

It is possible that some "postpsychotic depressions" may be a toxic effect of antipsychotic drugs. Out of a total of 94 schizophrenic patients, 28 developed a mild akinesia and 32 never developed extrapyramidal symptoms. Those who developed akinesia became less psychotic, but they also experienced a significant, although modest, increase in depression ratings. Successful treatment of the akinesia resulted in significant improvements in depression, somatic concern, anxiety, emotional withdrawal, blunted affect, and motor retardation on both physicians' and nurses' ratings. A high association between akinesia and both objectively rated and subjectively experienced sedative effect indicates that an 'akinetic depression' is not likely if the patient does not look or feel drowsy. The 32 nonakinetic patients also became less psychotic, but not more depressed.     

The canine eye: in vitro dissolution of the barriers to aqueous outflow.

Facility of aqueous outflow and time-dependent changes in its hyaluronidase-sensitive and hyaluronidase-resistant components were evaluated in freshly excised canine eyes by constant pressure quantitative aqueous perfusion. Mean baseline facility of outflow was 0.24 microliter/min/mm Hg. With prolonged perfusion at constant intraocular pressure, facility of outflow was observed to increase almost linearly for at least 3 hr and continued to increase for up to 10 hr, reaching a maximum several times the initially measured facility. Perfusion with pooled dog aqueous humor did not prevent the time-dependent increase in measured facility. Rapid exchange of anterior chamber contents with perfusion solution alone produced an immediate threefold increase in facility, again followed by a gradual time-dependent facility increase. Rapid exchange of anterior chamber contents with hyaluronidase produced an immediate fivefold increase in facility with stabilization of measured facility over 3 hr and subsequent perfusion. The time-dependent changes in measured facility of outflow or "washout phenomenon" appeared to result from the gradual dissolution of the hyaluronidase-sensitive component of the barriers to aqueous outflow in the canine eye.     

Cerebral disseminated coagulation

Summary The distribution of cytarabine in the ventricular CSF was studied after lumbar intrathecal administration. In the ventricular fluid peak concentrations up to 1.5×10^–4 M (37 g/ml) were achieved 4–8 h after lumbar injection of cytarabine of 45 mg/m². The concentration of cytarabine decreased slowly with a half-time of 2.16 h thus providing therapeutic concentrations in the cerebral ventricles for more than 24 h.

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Zusammenfassung Die Verteilung von Cytosinarabinosid nach lumbaler intrathekaler Injektion im ventrikulären Liquor cerebrospinalis wurde untersucht.Nach lumbaler intrathekaler Injektion von 45 mg Cytosinarabinosid (Alexan®) pro m² Körperoberfläche wurde im ventrikulären Liquor eine Höchstkonzentration von 1,5×10^–4 M (37 g/ml) 4–8 h nach Applikation erreicht. Die Konzentration von Cytosinarabinosid im ventrikulären Liquor fiel langsam mit einer Halbwertszeit von 2,16 h ab. Bei lumbaler Applikation wurden bei dieser Untersuchung therapeutische Konzentrationen von Cytosinarabinosid in den cerebralen Ventrikeln für mehr als 24 h erreicht.

     

Synthesis,physical properties and microbiological activities of more water soluble silver sulfadiazine derivatives

In this study the preparation of five hydrophilic derivatives of sulfadiazine is reported. The common structural element in the compounds is the 2-sulfonamidopyrimidine moiety. Three of these compounds are suitable for the preparation of a photostable 1∶1 silver compound. These silver compounds are five to ten times more water soluble than silver sulfadiazine. TheIr,¹H- and¹³C-Nmr data point to a similar co-ordination of silver in these compounds as with silver sulfadiazine. The microbiological activity of these silver compounds againstSt. aureus is slightly lower.