Antimalarial action of alloxan and 5,6-diamino-2,4-dihydroxy-pyrimidine in Plasmodium berghei

Three hours after iv administration of alloxan and 5,6-diamino-2,4-dihydroxy-pyrimidine to mice infected with chloroquine-sensitive (CS) and chloroquine-resistant (CR) strains of Plasmodium berghei, the 2 compounds showed remarkable antimalarial actions. Parasitemia in CS and CR infected mice were reduced by about 50%. Slight hemolysis was seen in mice treated with alloxan but not in mice treated with 5,6-diamino-2,4-dihydro-pyrimidine. Alloxan did not inhibit glutathione reductase activity and no alloxan-glutathione complex was produced. No relationship between the antimalarial effects of alloxan and hemolysis or GSH content were found. It is suggested that the antimalarial effects of the two agents may be due to the inhibition of dihydroorotic acid dehydrogenase.     

Preliminary study on the nucleic acid hybridization technic in detecting HSV-2 DNA corresponding sequence of cancer tissues of the uterine cervix

In this paper, 34 samples, 25 from 18 cervical carcinoma patients and 9 from 8 non-cervical carcinoma patients, were assayed using (alpha-32P) dCTP HSV-2 DNA probe and nucleic acid hybridization technic. It was shown that the positive rates of HSV-2 DNA corresponding sequence were 50% (2/4), 36% (5/14) and 12% (1/8) in the in situ cancer, invasive cancer and non-cervical cancer tissues. No HSV was isolated from 7 cancer specimens which showed a positive reaction by nucleic acid hybridization.     

Neuroendocrine and neurochemical measurements in depression

The authors performed dexamethasone suppression tests (DST), TRH infusions, 72-hour urine collections, and lumbar punctures on a group of male depressed patients. Approximately 60% of the patients were DST positive and 33% had a blunted TSH response. Two biologic variables, the 8 a.m. postdexamethasone cortisol and the postprobenecid CSF 5-hydroxyindoleacetic acid (5-HIAA), accounted for over half of the variance in the behavioral measure, the Hamilton score. Plasma cortisol elevation was associated with high 3-methoxy-4-hydroxyphenyl glycol (MHPG) excretion; TSH blunting was associated with low urinary MHPG excretion. Comprehensive biologic measures showed certain significant interrelationships and correlations with the severity of depression.     

A PRELIMINARY STUDY OF THE ACTION OF MALE HOR MONE ON HIGH DENSITY LIPOPROTEIN-CHOLESTEROL

Plasma testosterone and estradiol are determined in 72 patients with abnormal high density lipoprotein. cholesterol (HDL-C) and high density lipoprotein cholesterol/total cholesterol (H/T) ratio values, and in 72 randomly chosen males with normal HDLC and H/T values. The results showed that plasma testosterone levels in the groups with abnormal HDL-C and H/T were obviously lower than those in the controls. Statistically significant differences were found in all the abnormal groups in comparison with the controls (P0.20). Testosterone levels lowered further with increasing age in the groups with abnormal HDL-C and H/T., the most obvious drops were in the groups around 56 years of age (P<0.005). The data indicate that male hormone deficiency may reduce HDL-C and H.'T and facilitate the process of atherosclero_is. Therefore, it seems rational to treat such patients with male sex hormone preparations or to use the traditional Chinese medicines which strengthen Yang (maleness) in a new attempt to treat and prevent CHD.     

Adeno-associated virus vector-mediated systemic delivery of IFN-beta combined with low-dose cyclophosphamide affects tumor regression in murine neuroblastoma models.

PURPOSE: Type I IFNs (IFN-alpha/beta) have shown significant antitumor activity in preclinical models but limited efficacy and significant toxicity in clinical trials. We hypothesized that the antitumor activity of type I IFNs could be enhanced by chronic, low-dose systemic delivery and sought to test this in murine neuroblastoma models. EXPERIMENTAL DESIGN: Continuous liver-generated expression of human IFN-beta (hINF-beta) was achieved through a gene therapy-mediated approach using adeno-associated virus vectors encoding hIFN-beta (AAV hINF-beta). Orthotopic localized retroperitoneal and disseminated models of neuroblastoma were established using three different xenografts. Immunohistochemical analysis and ELISA were used to evaluate the antiangiogenic effect of therapy. RESULTS: The development of both localized orthotopic (retroperitoneal) and disseminated neuroblastoma was prevented in all mice expressing hINF-beta. Continued growth of established retroperitoneal tumors, treated with AAV hINF-beta as monotherapy, was significantly restricted, and survival for mice with established, disseminated disease was significantly prolonged following administration of AAV hINF-beta. Analysis of treated tumors revealed a significant antiangiogenic effect. Mean intratumoral vessel density was diminished and expression of the angiogenic factors vascular endothelial growth factor and basic fibroblast growth factor were both decreased. Finally, combination therapy in which AAV hIFN-beta was used together with low-dose cyclophosphamide resulted in regression of both established retroperitoneal and disseminated disease. CONCLUSIONS: AAV-mediated delivery of hIFN-beta when used as monotherapy was able to restrict neuroblastoma growth due in part to inhibition of angiogenesis. When used in combination with conventional chemotherapy, AAV hIFN-beta was able to effect complete tumor regression.