In vivo observation of crystalline lens changes in the early post-vitrectomy stage]

Crystalline lens changes of 17 cases of eye undergoing simple vitrectomy were observed from the post-operative 1st to 21st month. Changes in the crystalline lenses were detected through a slitlamp microscope or by methods of image analysis, the Opacity Lensmeter and the laser scattering spectroscopy. Increases of the scattering light intensity of the anterior and posterior deep cortical layers were observed from the early post-operative stage in 9 cases. Seven cases progressed to nuclear opacification during the observation period, however, one case showed no nuclear changes even at the 12 post-operative month. No relationships were observed between the early cortical changes and surgical invasion, patient age, or cause of vitreous opacification. Quantitative evaluation by image analysis revealed early post-operative crystalline lens changes in cases undergoing vitreous surgery.     

Choroidal dye filling velocity in patients with Vogt–Koyanagi–Harada disease

Purpose To evaluate quantitative choroidal dye filling velocity in patients with Vogt-Koyanagi-Harada disease (VKH) before and after corticosteroid treatment using indocyanine green (ICG) angiography.Methods ICG angiography was performed in seven VKH patients before and after systemic corticosteroid treatment. Choroidal dye curves were obtained by image analysis software and analyzed using an exponential model. The model’s time constant (τ) was used to evaluate choroidal dye filling velocity.Results Compared with controls, acute phase choroidal τ values in VKH patients were significantly longer, suggesting choroidal circulation disturbance. During the recovery phase, choroidal τ values were significantly shortened, suggesting choroidal circulatory disturbance improvement.Conclusion Choroidal dye filling velocity may be useful for VKH diagnosis and verification of corticosteroid treatment effectiveness.     

Human urotensin-II potentiates the mitogenic effect of mildly oxidized low-density lipoprotein on vascular smooth muscle cells: comparison with other vasoactive agents and hydrogen peroxide.

Human urotensin-II (U-II) is the most potent vasoactive peptide identified to date, and may be involved in hypertension and atherosclerosis. We investigated the effects of the interactions between U-II or other vasoactive agents and mildly oxidized low-density lipoprotein (mox-LDL) or hydrogen peroxide (H2O2) on the induction of vascular smooth muscle cell (VSMC) proliferation. Growth-arrested rabbit VSMCs were incubated with vasoactive agents (U-II, endothelin-1, angiotensin-II, serotonin, or thromboxane-A2) in the presence or absence of mox-LDL or H2O2. [3H]Thymidine incorporation into DNA was measured as an index of VSMC proliferation. On interaction with mox-LDL or H2O2, U-II induced the greatest increase in [3H]thymidine incorporation among these vasoactive agents. A low concentration of U-II (10 nmol/l) enhanced the potential mitogenic effect of low concentrations of mox-LDL (120 to 337%) and H2O2 (177 to 226%). U-II at 50 nmol/l showed the maximal mitogenic effect (161%), which was abolished by G protein inactivator (GDP-beta-S), c-Src tyrosine kinase inhibitor (radicicol), protein kinase C (PKC) inhibitor (Ro31-8220), extracellular signal-regulated kinase (ERK) kinase inhibitor (PD98059), or Rho kinase inhibitor (Y27632). Mox-LDL at 5 microg/ml showed the maximal mitogenic effect (211%), which was inhibited by free radical scavenger (catalase), intracellular and extracellular antioxidants (N-acetylcysteine and probucol), nicotinamide adenine dinucleotide phosphate oxidase inhibitor (diphenylene iodonium), or c-Jun N-terminal kinase (JNK) inhibitor (SP600125). These results suggested that U-II acts in synergy with mox-LDL in inducing VSMC DNA synthesis at the highest rate among these vasoactive agents. Activation of the G protein/c-Src/PKC/ERK and Rho kinase pathways by U-II together with the redox-sensitive JNK pathway by mox-LDL may explain the synergistic interaction between these agents.     

Serial diffusion-weighted MRI (DWI) in a patient with sporadic Creuztfeldt-Jakob disease]

Serial DWIs were performed in a patient with CJD who developed symptoms acutely and progressed rapidly. DWI discloed an increased signal in the frontal and parietal inner cortical areas, and in the caudate nuclei and putamina 20 days after the onset of symptoms. T2-weighted images showed only signal abnormality in the caudate nuclei and putamina, but not in the cerebral cortex. In the CSF obtained 15 days after the onset of symptoms, total tau protein was markedly elevated and 14-3-3 protein was positive. Measurement of these proteins are highly specific and sensitive for the diagnosis of CJD, but not available as a rapid routine examination at present. DWI is not specific, but useful for making the diagnosis of CJD in the early stage of the disease.     

Xamoterol in patients with dilated cardiomyopathy: an increase in beta-receptors in lymphocytes

Xamoterol, a partial-beta 1 agonist, was administered orally (100 mg, twice daily) to healthy volunteers (n = 8) and to patients with heart failure (n = 8) for one week. The density (Bmax) and affinity (Kd) of lymphocyte beta-receptors were lower in the patients with heart failure than in the healthy volunteers (Bmax = 931 +/- 214 vs 1466 +/- 373 sites/cell, and Kd = 0.60 +/- 0.11 vs 1.07 +/- 0.14 nM). During treatment with xamoterol, Bmax (7169 +/- 3768 and 7749 +/- 3807 sites/cell) and Kd (6.01 +/- 3.84 and 9.06 +/- 4.66 nM) increased strikingly (p less than 0.01) in both groups. For 12 months, xamoterol (100 mg bd) was given in the same manner to 10 patients with dilated cardiomyopathy. The long-term effects after three and 12 months were assessed. Xamoterol reduced the cardiothoracic ratio from 57 +/- 6% to 55 +/- 5% after three months and 54 +/- 5% after 12 months of treatment (both p less than 0.05), and increased exercise tolerance from 5 +/- 2 min to 7 +/- 2 min and to 7 +/- 2 min (p less than 0.01, p less than 0.05). Echocardiographic fractional shortening increased from 13 +/- 6% to 20 +/- 8% (p less than 0.01) and to 20 +/- 10% (p less than 0.05). Pulmonary wedge pressure during exercise at the same work load decreased from 40 +/- 12 mmHg to 25 +/- 9 mmHg (p less than 0.01) in three months; whereas pulmonary wedge pressures during exercise or at rest in 12 months were unchanged. Exercise heart rate decreased from 118 +/- 9 beats/min to 106 +/- 6 beats/min in three months (p less than 0.01), but was unchanged in 12 months. Bmax and Kd of the beta-receptors increased from 1024 +/- 413 sites/cell and 0.67 +/- 0.27 nM to 1976 +/- 497 sites/cell and 1.60 +/- 0.42 nM (both p less than 0.01), respectively, in three months, and 1584 +/- 650 sites/cell (NS) and 1.21 +/- 0.54 nM (p less than 0.05), respectively, in 12 months. It is concluded that xamoterol improves exercise tolerance, hemodynamics and resolves subjective symptoms for certain patients with dilated cardiomyopathy by its actions as a beta-agonist and beta-antagonist during longterm treatment.     

Substance P induces inositol 1,4,5-trisphosphate and intracellular free calcium increase in cultured normal human epidermal keratinocytes

Abstract Substance P is a neuropeptide which is present in peripheral C nerve endings and released from them. Free nerve endings of C nerve are present in human epidermis. The effects of substance P on the transmembrane signaling system of pig epidermal sheets were previously reported. In these studies, a small amount of cells other than keratinocytes contaminated the epidermal sheets and the species difference from human was also noticed. Therefore we investigated the effects of substance P on cultured normal human epidermal keratinocytes. Alteration of intracellular free calcium (Ca²⁺) in single living keratinocytes was studied using an inverted fluorescence microscope and Ca²⁺ -sensitive dye, Fura 2-AM. Treatment of normal human epidermal kertinocytes with substance P resulted in an increase in inositol 1,4,5-trisphosphate and in intracellular Ca²⁺. Substance P inhibited DNA synthesis of the keratinocytes in a dose-dependent manner. These results are consistent with the view that substance P stimulates phosphatidylinositol-4,5-bisphosphate hydrolysis of human keratinocytes, resulting in inositol 1,4,5-trisphosphate-Ca²⁺ signal.     

Development of a fetal circadian rhythm after disruption of the maternal circadian system

The role of maternal circadian rhythms in the development of the fetal circadian system was investigated in the rat. Pregnant females were subjected to procedures known to disrupt circadian function, ablation of the maternal suprachiasmatic nuclei (SCN) or housing in constant illumination, on gestational day 10. Circadian function was assessed in fetuses at gestational day 22 by analysis of glucose utilization in hypothalamic slices in vitro using the 2-deoxyglucose method. Fetuses from control females exhibit a robust rhythm in glucose utilization in the SCN. In contrast, the SCN of fetuses from females with SCN lesions, or housed in constant illumination, show no significant day-night difference in glucose utilization. Analysis of individual brains indicates, however, that this apparent disruption in the development of circadian rhythmicity in metabolism in the fetal SCN is due to a desynchronization of individual fetuses resulting from the loss of maternal entraining influences. Thus, the fetal SCN is capable of developing a circadian rhythm in glucose utilization independent of the maternal circadian system.     

Antiinflammatory properties of the new antirheumatic agent 4-acetylaminophenylacetic acid

The antiinflammatory activity of 4-acetylaminophenylacetic acid (MS-932) was investigated. MS-932 did not suppress the acute inflammation of carrageenin-induced paw edema in rats or of primary swelling in adjuvant arthritic rats. However, prophylactic treatment with MS-932 inhibited secondary inflammation in adjuvant arthritic rats. MS-932 also restored to normal the weight of the spleen and the serum albumin/globulin ratio of adjuvant arthritic rats. In addition to its prophylactic effect, MS-932 had a therapeutic effect on adjuvant arthritis. In in vitro tests, MS-932 did not inhibit prostaglandin E2 biosynthesis from arachidonic acid by sheep seminal vesicle microsomal enzyme or superoxide generation by guinea pig neutrophils stimulated with opsonized zymosan. MS-932 had no analgesic effect in mice and no antipyretic effect in rats. These results indicate that MS-932 suppresses adjuvant arthritis through modulation of the immune system.