In vivo inhibition of foam cell development by probucol in Watanabe rabbits

Previous studies from this laboratory have shown that oxidative modification of low-density lipoprotein (LDL) causes it to be recognized by the scavenger receptor of the macrophage. Consequently, the rate of degradation of oxidized LDL by macrophages can be 3 to 10 times that of native LDL. Antioxidants, such as probucol, are highly effective in preventing the oxidative modification of LDL. Our recent studies show that probucol treatment of LDL receptor-deficient Watanabe heritable hyperlipidemic (WHHL) rabbits selectively inhibits the degradation of LDL in fatty streak lesions (which are rich in macrophage-derived foam cells) without inhibiting degradation in nonlesioned areas (where degradation is predominantly in smooth muscle cells, which do not express the scavenger receptor). Furthermore, the rate of progression of lesions in probucol-treated animals was significantly slower than in a lovastatin-treated group maintained at equal total plasma cholesterol levels. These results strongly suggest that probucol, through an antioxidant activity not necessarily related to its ability to lower plasma cholesterol levels, can slow the progression of the foam-cell-rich fatty streak lesion of atherosclerosis.     

Inhibition of atherosclerosis in low-density lipoprotein receptor-negative mice by sesame oil

Diet has profound effects on the development of atherosclerosis. Fatty acid composition, antioxidants, and other components such as lignans have major effects on the atherosclerotic process. Sesame oil has both mono- and polyunsaturated fatty acid constituents in equal proportions. In addition, it also has high levels of numerous antioxidants and inducers of peroxisome proliferator-activated receptor. The objective of this study was to determine the anti-atherosclerotic effects of sesame oil. In this study, male low-density lipoprotein (LDL) receptor (LDLR) -/- mice were fed atherogenic diet or atherogenic diet reformulated with the same level of sesame oil (sesame oil diet). Plasma lipids and atherosclerotic lesions were quantified after 3 months of feeding. Sesame oil-containing diet significantly reduced the atherosclerotic lesion formation and plasma cholesterol, triglyceride, and LDL cholesterol levels in LDLR -/- mice. These findings suggest that sesame oil could inhibit atherosclerosis lesion formation effectively, perhaps because of the synergistic actions of fatty acid and nonsaponifiable components.     

CONFORMATIONAL ENERGY CALCULATIONS ON ENKEPHALINS AND ENKEPHALIN ANALOGS:

Conformational energy calculations were carried out on the peptide enkephalins (ENK) and selected analogs to find those conformers of low energy. The analogs studied include [D-Ala²]Enk-NH₂, [D-Ala²]Enk, [D-Met², Pro⁵]Enk-NH₂, [D-Ala², D-Phe⁵]Enk, [D-Ala², D-Leu⁵]Enk, [D-Ala², (N-Me)Phe⁴, Met⁵] Enk-NH₂ and [D-Ala², (N-Me)Met⁵]Enk-NH₂. When the low-energy conformers for all the analogs are compared, different allowed backbone conformations are found which orient the functional side-chains such that three classifications of structures appear. Each classification shows a unique configuration of side- chain positions in space even though different backbone conformations are found within each classification.     

Doxorubicin hydrochloride (Adriamycin) cardiotoxicity evaluated by sequential radionuclide angiocardiography

A prospective study was carried out to evaluate the role of radionuclide angiocardiography (CEF) in accessing subclinical cardiotoxicity secondary to Adriamycin (doxorubicin) therapy in 73 women with gynecologic malignancies. Based on the findings of this study, the authors conclude that all patients should have an initial CEF before Adriamycin therapy. In patients with an initial CEF of greater than or equal to 55, frequent determinations are not necessary unless there is a significant decrease from the initial CEF. Patients with low normal initial CEF or significant difference between the initial CEF and minimum CEF should have CEF studies performed at more frequent intervals. Patients who develop below normal CEF should have Adriamycin withheld and CEF should be repeated at more frequent intervals. If the CEF returns to normal Adriamycin therapy can be reinstated. Patients requiring continuation of Adriamycin past 550 mg/m2, can safely do so as long as the CEF values remain normal.     

High expression of p63 combined with a large N/C ratio defines a subset of human limbal epithelial cells: implications on epithelial stem cells

PURPOSE: To characterize human limbal epithelial cells based on the expression levels of nuclear protein p63 and the nucleus-to-cytoplasm (N/C) ratio. METHODS: Limbal, peripheral, and central corneal epithelia were separated from the stroma by Dispase II and subsequently were treated with trypsin to obtain single-cell suspensions. Cytospin smears of the cell suspensions were double immunostained for p63 and then stained for any one of the markers (acidic cytokeratins [AE1], K5, K3, or connexin 43 [Cx43]). They were counterstained with propidium iodide. More than 100 cells from each zone were analyzed for p63 expression levels and nuclear/cellular area using quantitative confocal microscopy. RESULTS: A gradient of p63-positive cells was observed in corneal and limbal epithelial cells. The percentage of p63-positive cells and the level of p63 expression were significantly higher in the limbal than in the peripheral or central corneal epithelium. Two-parameter (p63 levels and N/C ratio) analysis revealed the presence of a distinct population of small cells with higher levels of p63 and a large N/C ratio in the limbal epithelium. Such limbal epithelial cells were positive for AE1 and K5 but negative for K3 and Cx43. CONCLUSIONS: These results suggest that this distinct group of small cells in the limbal epithelium with greater N/C ratio, expressing high levels of nuclear protein p63, probably represent corneal epithelial stem cells.     

Five-year trajectories of health care utilization and cost in a drug and alcohol treatment sample

BACKGROUND: The study examined the effect of individual characteristics on longitudinal patterns of health care utilization and cost among individuals entering chemical dependency (CD) treatment. METHOD: Structured interviews and computerized administrative databases were linked to obtain severity, utilization and cost data. Total medical costs and their components were examined for the 6 months prior to intake through 5 years post-intake. Statistical analyses were conducted using the hierarchical linear modeling framework. RESULTS: Age was positively correlated with total medical costs. Women had higher inpatient utilization and higher inpatient, primary care and total cost at baseline (p<.05). However, they had steeper decline in primary care costs. While age was not related to inpatient and ER use at baseline (after controlling for psychiatric and medical severity), older individuals had smaller declines in hospital days and inpatient cost over time. Individuals with high medical and psychiatric severity had higher utilization and costs (p<.01). Those who were abstinent had higher costs. CONCLUSIONS: There are important differences in patient characteristics and treatment outcomes that influence utilization and cost trajectories. The relationship between medical severity at intake and primary care cost pre-intake among patients with drug and alcohol problems suggests an opportunity to identify and treat drug and alcohol problems in primary care settings. It also suggests that medical evaluations and treatment should not be overlooked during CD treatment. The positive association between abstinence and trajectories of primary care and total medical costs suggests that maintaining abstinence over a long term requires some kind of continuing care either in primary care settings or via additional contacts with specialty CD departments.     

Immunomodulatory activity of triphala on neutrophil functions

Immune activation is an effective as well as protective approach against emerging infectious diseases. The immunomodulatory activities of Triphala (Terminalia chebula, Terminalia belerica and Emblica officinalis) were assessed by testing the various neutrophil functions like adherence, phagocytosis (phagocytic index (P.I) and avidity index (A.I)) and nitro blue tetrazolium (NBT) reduction in albino rats. In recent years much attention is being focused on the immunological changes occur during stress. Noise (100 dB) stress for 4 h/d for 15 d, was employed to alter the neutrophil functions. The neutrophil function tests and corticosterone levels were carried out in eight different groups of animals, namely control, Triphala, noise-stress, Triphala noise-stress, and corresponding immunized groups were used. Sheep red blood cells (SRBC 5 x 10(9) cells per ml) were used for immunizing the animals that belongs to immunized groups. In Triphala administration (1 g/kg/d for 48 d), A.I was found to be significantly enhanced in the Triphala group, while the remaining neutrophil functions and steroid levels were not altered significantly. However the neutrophil functions were significantly enhanced in the Triphala immunized group with a significant decrease in corticosterone level was observed. Upon exposure to the noise-stress, the neutrophil functions were significantly suppressed and followed by a significant increase in the corticosterone levels were observed in both the noise-stress and the noise-stress immunized groups. These noise-stress-induced changes were significantly prevented by Triphala administration in both the Triphala noise-stress and the Triphala noise-stress immunized groups. Hence our study has divulged that oral administration of Triphala appears to stimulate the neutrophil functions in the immunized rats and stress induced suppression in the neutrophil functions were significantly prevented by Triphala.     

Quantitative analysis of aqueous phase composition of model dentin adhesives experiencing phase separation

There have been reports of the sensitivity of our current dentin adhesives to excess moisture, for example, water-blisters in adhesives placed on over-wet surfaces, and phase separation with concomitant limited infiltration of the critical dimethacrylate component into the demineralized dentin matrix. To determine quantitatively the hydrophobic/hydrophilic components in the aqueous phase when exposed to over-wet environments, model adhesives were mixed with 16, 33, and 50 wt % water to yield well-separated phases. Based upon high-performance liquid chromatography coupled with photodiode array detection, it was found that the amounts of hydrophobic BisGMA and hydrophobic initiators are less than 0.1 wt % in the aqueous phase. The amount of these compounds decreased with an increase in the initial water content. The major components of the aqueous phase were hydroxyethyl methacrylate (HEMA) and water, and the HEMA content ranged from 18.3 to 14.7 wt %. Different BisGMA homologues and the relative content of these homologues in the aqueous phase have been identified; however, the amount of crosslinkable BisGMA was minimal and, thus, could not help in the formation of a crosslinked polymer network in the aqueous phase. Without the protection afforded by a strong crosslinked network, the poorly photoreactive compounds of this aqueous phase could be leached easily. These results suggest that adhesive formulations should be designed to include hydrophilic multimethacrylate monomers and water compatible initiators.