Cycloetherification of hydroxyoleanenes by N-bromosuccinimide

Treatment of 28-hydroxyolean-12-enes with N-bromosuccinimide (NBS) in acetonitrile at room temperature afforded 12 alpha-bromooleanan-13beta, 28-epoxides in high yield. This reaction resulted in the formation of olean-9 (11), 12-diene-18alpha, 29-epoxides from 29-hydroxy isomers but recovered only starting materials from 30-hydroxy isomers. NBS will be used a reagent for diagnostic tool to distinguish between isomers bearing a primary hydroxyl group on D/E rings of olean-12-enes.     

Reproductive counselling for adolescent females with phenylketonuria

It is our goal to provide young adolescents with the information needed to make an informed choice, and a support system for them and their families, in whatever they choose. 1. Sterilization is not advocated. 2. Pregnancy is not advocated. 3. Reliable birth control methods are encouraged. 4. Organized reproductive counseling is essential using concrete problem solving--diagram, taste tests, etc. 5. Diet trial before or during pregnancy requires an informed understanding of the responsibilities of parenthood.     

Maximum Tolerated Osmolarity for Peripheral Administration of Parenteral Nutrition in Pediatric Patients

Background: Limited data support a recommended maximum osmolarity for administration of peripheral parenteral nutrition (PPN). In this retrospective, matched‐cohort study, we evaluated the incidence of phlebitis or infiltration associated with administration of PPN with an osmolarity >1000 mOsm/L vs ≤1000 mOsm/L. Materials and Methods: Patients ≤18 years old who received PPN in a 2‐year period were included in the study. Data related to patient demographics, PPN constituents, and adverse effects were analyzed. Results: A total of 352 patients met entry criteria. Overall, 139 (40%) patients experienced phlebitis or infiltration. There were no differences between patients who did or did not develop adverse events in terms of age or weight. Administration of PPN with osmolarity >1000 mOsm/L vs ≤1000 mOsm/L significantly increased infiltration (17% vs 7%; odds ratio [OR, 2.47]; 95% confidence interval [CI], 1.24–4.94; P = .01) and the combined composite end point of phlebitis or infiltration (45% vs 34%; OR, 1.65; 95% CI, 1.07–2.54; P = .02). In multivariate analysis, osmolarity >1000 mOsm/L vs ≤1000 mOsm/L was an independent risk factor for developing complications (OR, 1.67; 95% CI, 1.08–2.52; P = .02). Conclusion: Two of every 5 children experienced phlebitis or infiltration during administration of PPN. These adverse effects were more often observed in those who received PPN with osmolarity >1000 mOsm/L vs ≤1000 mOsm/L. With this high incidence of adverse effects, we recommend that if PPN is used, the osmolarity should not exceed 1000 mOsm/L. More important, PPN should only be used temporarily until central access is obtained.     

2-Oxo-3,23-isopropylidene-asiatate (AS2006A), a wound-healing asiatate derivative,exerts anti-inflammatory effect by apoptosis of macrophages

2-Oxo-3,23-isopropylidene-asiatate (AS2006A), a wound-healing asiatate derivative, exerts anti-inflammatory effect. Macrophages produce cytokines that recruit other inflammatory cells and are responsible for the diverse effects of inflammation. In the present study, we comparatively evaluated the cytotoxicity of AS2006A to Raw264.7, H4IIE and L-929 cells as part of the studies on its anti-inflammatory effect. Among the cells examined, AS2006A was selectively cytotoxic to Raw264.7 cells, a macrophage cell line. AS2006A increased the number of cells positively stained with TdT-mediated dUTP nick end labeling (TUNEL), and upregulated the expression of the genes implicated with apoptosis, which included caspase-8, c-myc, iNOS, mdm2, NF-kappaB1, I-kappaBalpha and NF-kappaB p105 genes, as assessed by the membrane DNA array technique. The expression of the genes related with cell cycle control was not changed. Thus, the primary targets of AS2006A in macrophages might include the genes implicated with apoptosis. Immunoblot analysis revealed that AS2006A caused the release of cytochrome c from the mitochondria to the cytoplasm in macrophages. Caspase-3 activity and poly(ADP-ribose) polymerase cleavage were both increased by AS2006A in macrophages, indicating that AS2006A induced apoptosis. Viability of macrophages activated by lipopolysaccharide and their NO production were also decreased by AS2006A in a concentration-dependent manner. These results demonstrated that AS2006A selectively induces apoptosis of macrophages with cytochrome c release, caspase 3 activation and poly(ADP-ribose) polymerase cleavage, and that cytotoxicity of AS2006A to macrophages may contribute to anti-inflammatory and wound-healing effects.     

Radiation-induced meningiomas involving the orbit

PURPOSE: To review the clinical features and outcomes of patients with radiation-induced meningiomas involving the orbit. DESIGN: Retrospective case series. PARTICIPANTS: Eight patients with radiation-induced meningiomas affecting the orbit. METHODS: Clinical and pathologic data of the patients were reviewed. MAIN OUTCOME MEASURES: Age at diagnosis, mean interval between radiation therapy and meningioma diagnosis, tumor recurrence, histologic atypia, and mean follow-up time after initial diagnosis. RESULTS: The mean age at diagnosis was 42 years (range, 21 years to 70 years). The mean interval between radiation therapy and meningioma diagnosis was 26 years (range, 3 years to 54 years). All patients underwent gross total resection or subtotal resection of the meningioma. Five tumors (62.5%) recurred, based on clinical findings and CT imaging. The mean interval between resection of the meningioma and recurrence was 3 years (range, 9 months to 9 years). Three patients (37.5%) had atypical meningiomas. One patient (12.5%) had multiple tumors. The mean follow-up interval was 7 years after initial diagnosis of the meningioma (range, 15 months to 19 years). CONCLUSIONS: This series of radiation-induced meningiomas, the first in the ophthalmic literature, illustrates the aggressive nature of this tumor.     

Is the mitral valve passive flap theory overstated? An active valve is hypothesized

The concept that the mitral valve of the heart is a passive flap that opens and closes like a barn door has been emphasized for decades by medical and biology professors to their students. But experimental findings, which are outlined in this report, support the theory of an active valve. We hypothesize that the two leaflets of the mitral valve are actively contractile; that physical forces generated in the valve itself may stabilize and add precision to the sum of forces that regulate valve movement. This precision could be of critical significance both in the moments preceding, and during, valve opening and closing. Evidence supporting our active valve hypothesis includes the profuse innervation of motor and sensory nerves that are present in the mitral valves of all animals studied. In addition, multiple contractile cell types have been found in the mitral valve, including cardiac muscle cells, smooth muscle cells, and cardiac valvular interstitial cells. In vitro work in our laboratories using the rat mitral valve shows that not only are the valves capable of contraction and relaxation, but that the contractions and relaxations are nerve-mediated. We theorize that the rich innervation and contractile cells in the mitral valve work together to modulate fine-tuning of valve movements and tone, thereby ensuring the integrity of the valve seal. Other investigators have reported that the mitral valve demonstrates contractile activity and that denervation localized to the mitral valve affects valve competence. The evidence for an active mitral valve presented by these and other experimental studies warrant a reexamination of the validity of the passive valve concept. An accurate and full understanding of the precise movements of the valve leaflets and the mechanisms that regulate these movements is likely to provide the information needed to understand and develop treatments for many different cardiac valve problems, including mitral valve diseases such as prolapse and myxomatous degeneration. In view of the available experimental evidence, the concept that the mitral valve functions only as a passive structure is challenged by numerous anomalies. A reinterpretation of the concept of valve function that incorporates active as well as passive roles for the valve leaflets and other components of the valve apparatus would have significant implications both for the directions taken in research involving the cardiac valves and for the approaches to treatment.