Evaluation of leukocyte dynamics in choroidal circulation with indocyanine green-stained leukocytes

PURPOSE: To develop a new method with which to visualize leukocytes moving through the choroidal vessels of pigmented animals and enable the evaluation of leukocyte dynamics in the choroidal microcirculation. METHODS: Pigmented rabbits and monkeys were used in this study. Leukocytes, collected by centrifugal separation of autologous blood, were stained with indocyanine green (ICG) dye. The ICG-stained leukocyte fluid was injected into the vein, and the fundus image was obtained with a scanning laser ophthalmoscope. The image was recorded on videotapes and analyzed with a personal computer-based image analysis system. RESULTS: In pigmented rabbits, fluorescent leukocytes moving in the choroidal circulation were clearly visible for more than 1 hour. In monkeys, distinct fluorescent dots were seen moving approximately 50 to 200 microm in the foveal avascular zone for more than 30 minutes after the injection of the ICG-stained leukocyte fluid. Dim fluorescent dots were seen moving in the fundus. Although the movement of these dim dots was difficult to trace, they seemed to be moving in the choroidal vessels. In the rabbits, the mean flow velocity of leukocytes moving without plugging was 0.48 +/- 0.14 mm/sec in the peripheral choriocapillaris. In the monkeys, the mean flow velocity of distinct fluorescent leukocytes without plugging was 2.45 +/- 0. 48 mm/sec in the posterior choroid. CONCLUSIONS: In pigmented rabbits and monkeys, this method allows visualization of leukocytes passing through the choroidal vessels and provides a new way to investigate, noninvasively and in vivo, leukocyte dynamics in the choroidal microcirculation.     

Reduction of cisplatin ototoxicity by fosfomycin in animal model

The protective effect of fosfomycin against cisplatin-induced ototoxicity was studied in rats. Sixty-four Fischer rats were injected intravenously with daily doses of 1, 2, 5, and 10 mg/kg of cisplatin with or without 300 mg/kg of fosfomycin for a varying period from 1 to 10 days. The total dose of 10 mg/kg of cisplatin was given equally in all animals. Inner ear damage appeared to be more reduced histopathologically in animals given both cisplatin and fosfomycin than in animals given cisplatin alone. Similarly, renal damage appeared to be reduced histopathologically and functionally by the combined administration of cisplatin and fosfomycin.     

Large Bielschowsky head-tilt phenomenon and inconspicuous vertical deviation in the diagnostic positions in congenital superior oblique palsy

PURPOSE: To report a case of congenital superior oblique palsy with an unusually large Bielschowsky head-tilt phenomenon (BHP) and disproportional inconspicuous vertical deviation. METHODS: Case report. RESULTS: An 18-year-old woman presented with slight compensatory head tilting and a Bielschowsky head-tilt phenomenon of 50 Delta on left tilting. Magnetic resonance imaging revealed atrophy of the left superior oblique muscle. A Hess screen test showed a slight underaction of the left superior oblique muscle, but neither an obvious overaction of the ipsilateral inferior oblique muscle nor inhibitory palsy of the contralateral superior rectus muscle was found. With a 3-mm recession of the ipsilateral superior rectus muscle, Bielschowsky head-tilt phenomenon decreased to 25 Delta. CONCLUSION: A large Bielschowsky head-tilt phenomenon was possibly caused by an increased gain of the otolith-ocular reflex affecting the vertical rectus muscle.     

Avascular necrosis of bone in neuroblastoma treated with combination chemotherapy

We treated two children with neuroblastoma and during the course of chemotherapy, avascular necrosis of the femoral head occurred. The main pathogenetic factor of this necrosis may be the toxic effect of cyclophosphamide.Abbreviations VMA vanillylmandelic acid - HVA homovanillic acid     

Calcium regulation by troponin and its genetic disorder in striated muscle contraction

Contraction of skeletal and cardiac muscles is regulated by Ca2+ through specific Ca(2+)-regulatory proteins, troponin and tropomyosin, located in the thin filament. Troponin is a Ca2+ receptive protein consisting of three differet components, troponins C, I, and T. The essential mechanisms of Ca(2+)-regulation are the inhibition of contractile interaction between myosin and actin by the inhibitory action of troponin I and the reversal of the inhibition by troponin I through the Ca(2+)-binding to troponin C. All three components of troponin are required for the Ca(2+)-regulation of contraction. This article reviews following aspects of troponin researches: 1) early studies on the structure and function of troponin, 2) molecular mechanisms of Ca(2+)-regulation, 3) principles of troponin-exchange in skinned fibers and properties of troponin isoforms thereafter clarified under physiological conditions, 4) recent studies on the functional consequences of the mutations in human cardiac troponins T and I that cause genetic disorders, familial hypertrophic cardiomyopathy (HCM), and familial dilated cardiomyopathy (DCM).     

ATA2 is predominantly expressed as system A at the blood-brain barrier and acts as brain-to-blood efflux transport for L-proline

Although system A is present at the blood-brain barrier (BBB), the physiological roles of system A have not been clarified. The efflux transport of the substrates of system A, such as L-proline (L-Pro), glycine (Gly), and alpha-methylaminoisobutyric acid (MeAIB), across the BBB was investigated using the in vivo Brain Efflux Index method. Over a period of 40 min, L-[(3)H]Pro and [(3)H]Gly underwent efflux from the brain, whereas [(3)H]MeAIB did not. The efflux of L-[(3)H]Pro was inhibited by the presence of unlabeled L-Pro and MeAIB, suggesting that carrier-mediated efflux transport of L-Pro across the BBB is involved in system A. L-[(3)H]Pro uptake by TR-BBB cells, used as an in vitro BBB model, was Na(+)-dependent with high-affinity (K(m1) = 425 microM) and low-affinity (K(m2) = 10.8 mM) saturable processes. The manner of inhibition of L-[(3)H]Pro uptake for amino acids was consistent with system A. Although GlnT, ATA2, and ATA3 mRNA were all expressed in TR-BBB cells, ATA2 mRNA was predominant. Under hypertonic conditions, ATA2 mRNA in TR-BBB cells was induced by up to 373%, and it activated [(3)H]MeAIB uptake. In light of these observations, our results indicate that L-Pro and Gly are transported from the brain across the BBB, whereas MeAIB is retained in the brain. System A is involved in efflux transport for L-Pro at the BBB. The predominantly expressed ATA2 mRNA at the BBB may play a role in maintaining the concentration of small neutral amino acids and cerebral osmotic pressure in the brain under pathological conditions.     

Neuritogenesis of herbal (+)- and (-)-syringaresinols separated by chiral HPLC in PC12h and Neuro2a cells

Syringaresinol isolated from Epimedium koreanum NAKA1 and Magnolia officinalis REHD. et WILS. was subjected to optical resolution by chiral HPLC to give (+)- and (-)-enantiomers. The two syringaresinol enantiomers, as well as a mixture of their glucosides, showed dose-dependent neuritogenesis in a concentration range from 0.24 to 24 microM in PC12h cells.