The effect of 5-lipoxygenase inhibition on blood-brain barrier permeability in experimental brain tumors.

To determine if leukotrienes are important mediators of vascular permeability in brain tumors, the effect of 5-lipoxygenase inhibitors on blood-tumor barrier permeability in rats harboring HK Walker 256 brain tumors was examined using quantitative autoradiography with alpha-14C-aminoisobutyric acid. The 5-lipoxygenase enzyme converts arachidonic acid to leukotrienes. Three 5-lipoxygenase inhibitors were utilized: BW755C, nordihydroguaiaretic acid, and AA-861. All three 5-lipoxygenase inhibitors significantly decreased vascular permeability both within the tumors and in brain adjacent to tumor. This suggests that capillary permeability in and adjacent to tumors is influenced by endogenous leukotrienes and that leukotrienes play an important role in brain tumor edema.     

Selective blood-tumor barrier disruption by leukotrienes.

The authors have previously reported that intracarotid infusion of 5 micrograms leukotriene C4 (LTC4) selectively increases blood-tumor barrier permeability in rat RG-2 tumors. In this study, rats harboring RG-2 tumors were given 15-minute intracarotid infusions of LTC4 at concentrations ranging from 0.5 microgram to 50.0 micrograms (seven rats in each dose group). Blood-tumor and blood-brain barrier permeability were determined by quantitative autoradiography using 14C aminoisobutyric acid. The transfer constant for permeability (Ki) within the tumors was increased twofold by LTC4 doses of 2.5, 5.0, and 50.0 micrograms compared to vehicle alone (90.00 +/- 21.14, 92.68 +/- 15.04, and 80.17 +/- 16.15 vs. 39.37 +/- 6.45 microliters/gm/min, respectively; mean +/- standard deviation; p less than 0.01). No significant change in Ki within the tumors was observed at the 0.5-microgram LTC4 dose. Blood-brain barrier permeability was selectively increased within the tumors. At no dose in this study did leukotrienes increase permeability within normal brain. To determine the duration of increased opening of the blood-tumor barrier by LTC4 administration, Ki was measured at 15, 30, and 60 minutes after termination of a 15-minute LTC4 infusion (seven rats at each time point). The mean Ki value was still high at 15 minutes (92.68 +/- 15.04 microliters/gm/min), but declined at 30 minutes (56.58 +/- 12.50 microliters/gm/min) and 60 minutes (55.40 +/- 8.10 microliters/gm/min) after the end of LTC4 infusion. Sulfidopeptide leukotrienes LTC4, LTD4, LTE4 and LTF4 were infused to compare their potency in opening the blood-tumor barrier. The mean leukotriene E4 was the most potent, increasing the permeability value 3 1/2-fold compared with vehicle alone (139.86 +/- 23.95 vs. 39.37 +/- 6.45 microliters/gm/min).     

Effect of carrageenan-induced acute inflammation on corticosterone levels in mice

Changes in corticosterone levels in plasma and inflammatory exudase were studied in the 6-day-old air pouch of mice. The pouch inflammation in the test group was induced by the injection of carrageenan prepared in physiological saline while the control received only the physiological saline. The results show that exudate and plasma of both groups showed a rapid rise in corticosterone as measured after 30 min and this early rise was probably due to the resulting effect of the ether used during the injection of irritant or vehicle. In contrast, corticosterone levels in the inflammatory exudate of the test group increased with time, reaching a peak at 24 hours after the carrageenan injection. The increased corticosterone levels in the inflammatory exudate appeared to be closely correlated with the increased exudate cell accumulation. This suggests that the increased accumulation of exudate corticosterone in the pouch might play an important role at the inflammatory site by modulating intensity of the inflammatory reactivity caused by the irritant.     

Synthesis of 3-amino-ribofuranans having 1,5-α and -β structures by selective ring-opening polymerization of a 1,4-anhydro-3-azido-3-deoxy-α-D-ribopyranose derivative

Ring-opening polymerization of a new anhydro ribose-type monomer, 1,4-anhydro-3-azido-3-deoxy-2-O-tert-butyldimethylsilyl-α-D -ribopyranose (A3ASR), was investigated. The monomer was synthesized from 1,4-anhyro-α-D -xylopyranose by three steps comprising Walden inversion at the C3 position into ribose configuration. Ring-opening polymerization of A3ASR by Lewis acid catalysts such as boron trifluoride etherate and stannic chloride gave a stereoregular 3-azido-3-deoxy-2-O-tert-butyldimethylsilyl-(1→5)-α-D -ribofuranan having specific rotations of +246 ～ +271 deg · dm^?1 · g^?1 · cm³ and number-average molecular weights of 18,7 × 10³ ～ 25,1 × 10³. When the polymerization was carried out by antimony pentachloride at 0°C, the resulting polymer exhibited a negative specific rotation of ?6 deg · dm^?1 · g^?1 · cm³ and the C1 absorption in the ¹³C NMR spectrum shifted downfield to 107,5 ppm, suggesting that the polymer might consist of 1,5-β furanosidic unit. The reduction of the azido group of the 1,5-α and 1,5-β furanosidic polymers into amino group and subsequent desilylation gave 3-amino-3-deoxy-(1→5)-α- and -β-D -ribofuranans, respectively. In addition, copolymerization of A3ASR with 1,4-anhydro-2,3-di-O-tert-butyldimethylsilyl-α-D -ribopyranose (ADSR) in various feeds was performed by boron trifluoride etherate as catalyst to give copolymers with different monomeric components. The structural analysis of the homopolymers and copolymers was examined by means of ¹H and ¹³C NMR spectroscopies, IR spectroscopy, and optical rotation.     

A longitudinal analysis of methicillin-resistant Staphylococcus aureus in a Hong Kong teaching hospital.

OBJECTIVES: To review the incidence and trends of MRSA during a 12-year (1989-2000) period at a university teaching hospital and the relationship between strain distribution by antibiogram and molecular typing. DESIGN: Retrospective review of laboratory-based surveillance records on MRSA isolation and characterization of strains by antimicrobial susceptibility and PFGE. A patient episode was counted at the time when MRSA was first isolated. SETTING: A 1,350-bed university teaching hospital in Hong Kong. PATIENTS: Those with clinical isolates of MRSA. RESULTS: During 1989 to 2000, the hospital recorded 1,203,175 deaths and discharges (D&D) and encountered 5,707 patient episodes of new MRSA isolation. The overall incidence of patient episodes of MRSA was 0.47/100 D&D. In 1989, the incidence was 0.81/100 D&D and fell to a low of 0.33/100 D&D in 1995, but then rose to 0.50/100 D&D in 2000. Antibiogram and DNA typing identified 5 major types. PFGE type A constituted 68% (211/312) of isolates and was present throughout the 12-year period. PFGE type B constituted 13% (40/312) of isolates and was only present from 1995 to 2000. These isolates form a distinct clone and had unique antibiotic resistance profiles. CONCLUSIONS: The study showed the establishment of a dominant MRSA clone (PFGE type A group) in the intensive care, medical, and surgical units and the appearance of a new MRSA strain in 1995 (PFGE type B), which partly explained the rise in incidence of MRSA cases and a disproportionate rise in MRSA bacteremia from 1995 to 2000.     

Family involvement moderates the relationship between perceived recovery orientation of services and personal narratives among Chinese with schizophrenia in Hong Kong: a 1-year longitudinal investigation

Social Psychiatry and Psychiatric Epidemiology - Family has been found to have an influential role on clinical and recovery outcomes of people with schizophrenia. While recovery-oriented services...     

Validation of pulse dynamic blood pressure measurement by auscultation

BACKGROUND: The accurate measurement of arterial blood pressure is essential for the diagnosis and treatment of hypertension. The development of new automated methods of measurement that provide reliable determinations of blood pressure should be valuable in the assessment of hypertension not only in the clinic or hospital but also, in the home for self-monitoring. DESIGN: We evaluated a noninvasive method for the measurement of systolic and diastolic blood pressures in 132 subjects. METHODS: Measurements obtained using the pulse dynamic method of blood pressure determination were validated with simultaneous manual measurements. Two qualified nurses used Korotkoff sounds to determine systolic (phase I) and diastolic (phase IV) blood pressures according to the Association for the Advancement of Medical Instrumentation 1987 guidelines. RESULTS: Inter-nurse variability was 2.7 +/- 4.1 mmHg (mean +/- SD) for systolic blood pressure and 4.0 +/- 3.7 mmHg for diastolic blood pressure and correlations were r = 0.98 and 0.94, respectively. We observed excellent agreement between auscultatory and pulse dynamic methods for systolic (127 +/- 21 versus 132 +/- 20 mmHg; r = 0.97) and diastolic (72 +/- 10 versus 71 +/- 10 mmHg; r = 0.89) blood pressures. Bland-Altman analysis demonstrated that there was a mean difference (reference-device) between the two methods of - mmHg (pulse dynamic value higher) and SD of 5 mmHg for systolic blood pressure and a mean difference of 1 mmHg (pulse dynamic value lower) and SD of 5 mmHg for diastolic blood pressure. CONCLUSION: The results of this study demonstrate that this noninvasive method of measurement of blood pressure is accurate and reliable and should therefore be appropriate for the evaluation of hypertension both in the home and in clinical settings.     

Deep brain light stimulation effects on glutamate and dopamine concentration

Compared to deep brain electrical stimulation, which has been applied to treating pathological brain diseases, little work has been done on the effect of deep brain light stimulation. A fiber-coupled laser stimulator at 840 nm wavelength and 130 Hz pulse repetition rate is developed in this work for deep brain light stimulation in a rat model. Concentration changes in glutamate and dopamine in the striatum are observed using a microdialysis probe when the subthalamic nucleus (STN) is stimulated at various optical power levels. Experimental results show that light stimulation causes the concentration of glutamate to decrease while that of dopamine is increased. This suggests that deep brain light stimulation of the STN is a promising therapeutic strategy for dopamine-related diseases such as Parkinson’s disease. The stimulator developed for this work is useful for deep brain light stimulation in biomedical research.OCIS codes: (170.5180) Photodynamic therapy, (170.3660) Light propagation in tissues, (170.3890) Medical optics instrumentation, (170.1420) Biology, (170.1610) Clinical applications, (170.0170) Medical optics and biotechnology