Allografts of CNS tissue possess a blood-brain barrier. II. Angiogenesis in solid tissue and cell suspension grafts

Angiogenesis and patency of blood vessels were analyzed qualitatively in solid CNS and peripheral tissue syngeneic, allogeneic, and xenogeneic grafts and in individual cell suspension grafts of astrocytes, fibroblasts, PC12, and three additional tumor cell lines placed intracerebrally in adult host mice. Postgrafting survival times were 1 day through 4 weeks. The patency of graft vessels was determined in sections from immersion-fixed tissues incubated to reveal the endogenous peroxidase activity of host red cells trapped within the lumen of blood vessels. Additionally, horseradish peroxidase (HRP) was administered intravenously to live hosts; HRP labels host brain and graft vessels on the luminal surface and reveals the presence or absence of a blood-brain barrier (BBB) within the grafts. The origins of blood vessels supplying solid tissue xenografts were identified immunohistochemically with primary antibodies against host (athymic AKR mice) and donor (fetal Lewis rats) major histocompatibility complex (MHC) class I. Blood vessels supplying solid CNS grafts at 1-7 days post-transplantation were identified ultrastructurally and possessed interendothelial tight junctional complexes; however, they were not perfused with either host blood or blood-borne HRP prior to 8 days. Graft vessels at 10 days were outlined consistently by peroxidase-positive red cells in immersion-fixed material and labeled with blood-borne HRP. These vessels provided a BBB to the circulating HRP and exhibited interendothelial tight junctions. Evidence of angiogenesis within solid anterior pituitary grafts and the variety of cell suspension grafts was obtained prior to 3 days post-transplantation in immersion-fixed preparations; the vessels, with the notable exception of those supplying astrocyte cell suspensions, failed to present a BBB to blood-borne peroxidase. Endothelia in the solid pituitary allografts and the PC12 cell grafts were highly fenestrated and exhibited open interendothelial junctions; those in the tumor and fibroblast cell grafts, for the most part, appeared nonfenestrated, and many possessed open interendothelial junctional complexes. Immunostaining for host and donor MHC class I revealed that donor blood vessels predominate over host vessels in CNS xenografts and supply pituitary xenografts exclusively; in both preparations, donor vessels were not identified within the host CNS. Because cell suspension grafts were derived from endothelia-free preparations grown in culture, blood vessels supplying these grafts were necessarily of host CNS origin and manifested a morphological transformation from a BBB to a non-BBB endothelium. The data suggest that angiogenesis in solid CNS grafts placed into the adult host CNS, compared to similarly placed solid peripheral tissue/cell suspension grafts, is not rapid.(ABSTRACT TRUNCATED AT 400 WORDS)     

Effect of bezafibrate on low levels of high density lipoprotein cholesterol in normolipidemia. Study in coronary patients and their first degree relatives

A pharmacological study was carried out in a group of 20 subjects composed of 13 coronary patients and 7 normal close relatives (first degree) who were considered at a high risk for coronary heart disease (CHD) because of their low levels of high density lipoprotein cholesterol (HDLch) (mean +/- SD: 34.1 +/- 5.2 mg/dl) and their high total cholesterol/HDLch (Tch/HDLch) ratio (mean +/- SD:6.7 +/- 1.1), despite their normal serum lipid values. With the purpose of normalizing these parameters they were submitted to a 4-month treatment with bezafibrate, a hypolipidemic agent which has a known effect in increasing HDLch and in decreasing the Tch/HDLch ratio. At the end of the study total serum cholesterol and triglycerides decreased significantly by 10 and 30%, respectively (p less than 0.01). HDL increased in its cholesterol content by 33% reaching a value of 45.4 +/- 9.8 mg/dl (mean +/- SD, p less than 0.01) as well as in its apolipoprotein A1 (Apo A1) content (13%, p less than 0.02). HDL2 subfraction also rose in cholesterol and in Apo A1: by 90 and 38%, respectively (p less than 0.01). HDL3 subfraction rised only its cholesterol content by 24% (p less than 0.01). Tch/HDLch ratio was significantly reduced (p less than 0.01) to a value of 4.6 +/- 0.9 (mean +/- SD). Total serum Apo B diminished by 14% (p less than 0.01). No adverse effects were observed during the follow-up.(ABSTRACT TRUNCATED AT 250 WORDS)     

Studies of the blood lipid peroxide status and vitamin E levels in patients with chronic active hepatitis and alcoholic liver disease

As free radicals and lipid peroxidation are involved in the pathogenesis of different inflammatory diseases of the liver, the blood malondialdehyde content, the activity or quantity of free radical eliminating enzymes and the natural antioxidant, vitamin E serum level has been studied in ten patients with chronic active hepatitis and in six subjects with alcoholic liver disease. Thirty healthy volunteers served as controls. The serum malondialdehyde/thiobarbituric acid reactive substance and its concentrations increased significantly in both hepatitis groups. The superoxide dismutase content was also raised in the patients' sera. The serum glutathione peroxidase (GSH-Px) activity was decreased in both groups, while the red blood cell GSH-Px showed a significantly lower activity in the alcoholic hepatitis patients. Serum catalase activity and vitamin E levels in both types of chronic hepatitis were not significantly different from the healthy controls.     

Modeling the effects of health status and the educational infrastructure on the cognitive development of Tanzanian schoolchildren.

This paper models the proximate determinants of school attendance and scores on cognitive and educational achievement tests and on school examinations of over 600 schoolchildren from the Control group of a randomized trial in Tanzania, where children in the Intervention group heavily infected with hookworm and schistosomiasis received treatment. The modeling approach used a random effects framework and incorporated the inter-relationships between school attendance and performance on various tests, controlling for children's health status, socioeconomic variables, grade level, and the educational infrastructure. The empirical results showed the importance of variables such as children's height and hemoglobin concentration for the scores, especially on educational achievement tests that are easy to implement in developing countries. Also, teacher experience and work assignments were significant predictors of the scores on educational achievement tests, and there was some evidence of multiplicative effects of children's heights and work assignments on the test scores. Lastly, some comparisons were made for changes in test scores of treated children in the Intervention group with the untreated children in the Control group.     

Targeted therapy for brain metastases: improving the therapeutic ratio.

Brain metastasis is the most common intracranial malignancy in adults. Improvements in modern imaging techniques are detecting previously occult brain metastases, and more effective therapies are extending the survival of patients with invasive cancer who have historically died from extracranial disease before developing brain metastasis. This combination of factors along with increased life expectancy has led to the increased diagnosis of brain metastases. Conventional treatment has been whole brain radiotherapy, which can improve symptoms, but potentially results in neurocognitive deficits. Several strategies to improve the therapeutic ratio are currently under investigation to either enhance the radiation effect, thereby preventing tumor recurrence or progression as well as reducing collateral treatment-related brain injury. In this review article, we discuss new directions in the management of brain metastases, including the role of chemical modifiers, novel systemic agents, and the management and prevention of neurocognitive deficits.     

Comparative analysis of the effect of gestagens,antiestrogencytostatics, and androstenes on the viability of tumor and normal cells

The hormonal compound with the highest cytostatic activity against MCF-7 tumor cells (human breast cancer, BC) and the lowest activity against normal cells (rat skin fibroblasts) was sought among gestagens, androstenes, and antiestrogencytostatics. It was found that antiestrogencytostatics and androstenes had the highest cytostatic activity against tumor cells whereas gestagens and antiestrogencytostatics were least active against fibroblasts. Studies of the activity of the hormonal compounds in combination with doxorubicin on the viability of MCF-7 and rat skin fibroblasts found that all investigated compounds with the exception of dehydroepiandrosterone (DHEA) intensify the cytostatic activity of doxorubicin against tumor cells, the greatest effect seen for antiestrogencytostatics. A chemoprotective effect of androstenes on normal cells was noted. __________ Translated from Khimiko-Farmatsevticheskii Zhurnal, Vol. 41, No. 7, pp. 3–7, July, 2007.