Tumor inhibiting properties of stereoisomeric [1,2-bis(3-hydroxyphenyl) ethylenediamine]dichloroplatinum(II)-complexes, Part II: Biological properties

The activity of stereoisomeric [1,2-bis(3-hydroxyphenyl)ethylenediamine] dichloroplatinum(II)-complexes (1-PtCl2,R,S; 2-PtCl2, R,R/S,S; 3-PtCl2, R,R; 4-PtCl2, S,S) on several tumor models (MDA-MB 231 breast cancer cell line; P 388 leukemia, mouse; L 1210 leukemia, mouse; L 5222 leukemia, rat; Ehrlich ascites tumor, mouse--wildtype; cisplatin-, etoposide-, cyclophosphamide-, and daunomycin-resistant, resp.) is described. For comparison the analogous [1,2-bis(4-hydroxyphenyl)ethylendiamine]dichloroplatinum (II)-complexes (5-PtCl2, R, S; 6-PtCl2, R,R/S,S; 7-PtCl2, R,R; 8-PtCl2, S,S) and cisplatin are used. 1-PtCl2 to 4-PtCl2 (OH in 3,3'-positions) show their maximum antitumor effect at lower doses than 5-PtCl2 to 8-PtCl2 (OH in 4,4'-positions). 2-PtCl2 and 6-PtCl2 (R,R/S,S) are more active than 1-PtCl2 and 5-PtCl2 (R,S). 4-PtCl2 and 8-PtCl2 (S,S) are superior to 3-PtCl2 and 7-PtCl2 (R,R). On the L 5222 leukemia 2-PtCl2 (R,R/S,S), 4-PtCl2 (S,S) and 8-PtCl2 (S,S) markedly surpass cisplatin. Strong effects are produced by 2-PtCl2 to 4-PtCl2 on the Ehrlich ascites tumor (wildtype, cisplatin-, etoposide-, cyclophosphamide-, and daunomycin-resistant, resp.). The combination of 4-PtCl2 with cisplatin results in a weakly synergistic effect.     

Volar scaphotrapezial dislocation.

We present a case of volar luxation of the scaphotrapezial bone, in which radiographs suggested luxation of the scaphoid, but unclear relations to the other carpal bones. Computer tomographic reconstruction showed an isolated scaphotrapezial luxation. This was treated by closed reduction and a plaster cast, after which the patient regained normal function of her wrist.     

Infection of the upper extremity byMycobacterium marinum in a 3-year-old boy — Diagnosis by 16S-rDNA analysis

Summary A 3-year-old boy developed several subcutaneous nodular lesions on his right arm. Based on the histological examination of one of these nodules furunculosis was suspected and cefuroxime was tentatively given. However, acid-fast bacilli were then detected in the tissue specimen and a few colonies of acid fast, gram-positive rods grew on blood agar. Definitive species diagnosis (Mycobacterium marinum) was rapidly achieved by automated sequencing of amplified 16S-rDNA and antimicrobial therapy was adjusted according to the available literature. After 3 weeks of treatment with clarithromycin, rifampicin and protionamid regression of the nodular lesions was evident.

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Infektion der oberen Extremität durchMycobacterium marinum — Diagnose mit Hilfe von 16S-rDNA Analyse

Zusammenfassung Wir berichten von einem 3-jährigen Jungen, der verschiedene subkutane Knoten im rechten Arm entwickelte. Nach histologischer Untersuchung wurde zunächst der Verdacht auf Furunkulose geäußert und eine vorläufige Therapie mit Cefuroxim begonnen. Es wurden dann jedoch säurefeste Stäbchen im entnommenen Gewebe nachgewiesen und eine Woche später auf Blutagar grampositive, säurefeste Stäbchen angezüchtet. Die definitive Speziesdiagnose (Mycobacterium marinum) wurde rasch mit automatischer 16S-rDNA Sequenzbestimmung erzielt und die Therapie entsprechend der verfügbaren Literatur korrigiert. Nach drei Wochen einer Behandlung mit Clarithromycin, Rifampicin und Protionamid war ein Rückgang der subkutanen Knoten erkennbar.

     

Cold tolerance and metabolic heat production in male C57BL/6J mice at different times of day.

Nine-month-old male C57BL/6J mice were subjected to three-hour cold stress tests (partial restraint at 6 degrees C) at 9:00 a.m. or at 1:00 p.m. Tests were repeated three times at two-week intervals at the same time of day. Body temperature was measured by colonic thermoprobe, and metabolic heat production was measured by indirect calorimetry during each test. All mice showed habituation to repeated cold exposures (an improvement of cold tolerance across tests) due to an increase in metabolic heat production. The levels of metabolic heat production were similar during morning and afternoon testing; however, mice tested in the afternoon had consistently poorer cold tolerance, which indicated increased heat loss. Increased heat loss in mice of similar body weight and presumably similar body composition, suggests that there is less effective cold-induced skin vasoconstriction during the afternoon. We hypothesize that the compromised skin vasomotor response during the afternoon cold exposure results from competing effects of vasodilation due to local autoregulation stimulated by a circadian reduction of cardiac output during the sleep phase, and vasoconstriction due to the cold stress.     

Effect of ethanol on ascorbate release in the nucleus accumbens and striatum of freely moving rats.

An in vivo voltammetry technique was used to monitor the extracellular ascorbate (AA) concentration in the nucleus accumbens and striatum of unanesthetized, freely moving rats. A single injection of ethanol, 1.0 g/kg intraperitoneally (IP), induced a significant increase in extracellular AA concentration in both the nucleus accumbens and striatum. This effect was dose dependent within a dose range from 0.5-2.0 g/kg. 4-Methylpyrazole (50 mg/kg, IP), which inhibits alcoholdehydrogenase, could not prevent the increase in AA concentration, evoked by ethanol. Furthermore, systemic administration of acetaldehyde (20 mg/kg, IP), the main metabolite of ethanol, did not have any effect on the level of AA in the nucleus accumbens or striatum. These results show that ethanol can alter the brain extracellular AA levels and that this effect seems to be attributed to ethanol itself and not to acetaldehyde. Consequently, these results indicate that a role for AA in the action of ethanol in the brain should be considered.