The new anthracycline glycosides 4-demethoxy-4'-deoxydaunorubicin and 4-demethoxy-4'-O-methyldaunorubicin, synthesized by coupling 4-demethoxydaunomycinone with 1-chloro-derivatives of protected 4-O-methyl and 4-deoxydaunosamine derivatives, have been converted into the corresponding doxorubicin analogs. The new compounds have been compared for antitumor effect with the parent drugs and with the previously described 4-demethoxydaunorubicin, 4-demethoxy-4'-epidaunorubicin, and their doxorubicin analogs. All of the new analogs were more cytotoxic against HeLa cells in vitro and were more toxic and more potent in mice than the parent drugs. Comparison at optimal antitumor doses showed that the new analogs were as active as the parent drugs against ascitic P388 leukemia and disseminated Gross leukemia. They were also active when administered orally. The new doxorubicin analogs were slightly more active than doxorubicin against ascitic L1210 leukemia and were markedly more active against disseminated L1210 leukemia. In a parallel activity-cardiotoxicity test in C3H mice repeatedly treated iv, 4-demethoxydoxorubicin, 4-demethoxy-4'-epidoxorubicin, 4-demethoxy-4'-O-methyldoxorubicin, and 4-demethoxy-4'-deoxydoxorubicin showed antitumor activity against mammary carcinoma without inducing the typical myocardial lesions observed after doxorubicin treatment, 4-Demethoxy-4'-O-methyldoxorubicin, because of its high antitumor effectiveness, lack of cardiac toxicity in mice, and activity by the oral route, deserves further study.

Animals↗

PubMedDate not supplied

Sex differences in headache sufferers' responsiveness to painful overdistension of the hand-forearm veins.

A short-lasting overdistension of the hand-forearm veins, through the application of the Hand Arm Vein Distension (HAVD) test was carried out on patients suffering from migraine (no. = 102) and females with chronic daily headache (no. = 26): chronic tension-type headache (CTH) and migraine with interparoxysmal headache (MIH). Comparisons were made with a group of healthy controls (no. = 20). The HAVD test induced pain more often in female (65%) than in male migraineurs (14%) and female controls (p < 0.01). No significant difference appeared between male migraineurs and male controls. No significant difference was evidenced between female migraineurs in headache and headache-free periods. Patients with CTH showed less sensitivity to HAVD than those with MIH and migraine (respectively p < 0.01 and p < 0.05) and even a longer latency before the onset of pain. The findings show a stronger extracephalic pain sensitivity in migraineurs than in healthy controls, but sex must be taken into account. The results suggest that pain sensitivity is not correlated with the presence of headache.

Chronic Disease↗

PubMedDate not supplied

[Splenosis: report of a case studied with ultrasonography and computerized tomography].

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Humans↗