Efficacy and tolerability of ophthalmic epinastine: a randomized, double-masked, parallel-group, active- and vehicle-controlled environmental trial in patients with seasonal allergic conjunctivitis

BACKGROUND: Epinastine hydrochloride is an antihistamine with mast cell-stabilizing and anti-inflammatory activity. OBJECTIVE: The aim of this study was to assess the efficacy and tolerability of ophthalmic epinastine in patients with seasonal allergic conjunctivitis (SAC) exposed to environmental allergens. METHODS: This randomized (age-stratified), double-masked, parallel-group, active- and vehicle-controlled, environmental, Phase III clinical trial was conducted at 6 ophthalmology clinics in the United States. Patients aged >or=9 years diagnosed with SAC and who had a positive reaction in a conjunctival allergen challenge were enrolled. Patients were randomly assigned in a 2:2:1 ratio to receive 1 drop/eye BID of epinastine hydrochloride 0.05% ophthalmic solution, levocabastine hydrochloride 0.05% ophthalmic suspension, or vehicle of epinastine, respectively, for 8 weeks. The primary end point was ocular itching, and secondary end points included ocular hyperemia, chemosis, ocular mucous discharge (all assessed on a 5-point scale), eyelid swelling (assessed on a 4-point scale), and tearing (present or absent). Efficacy analyses used assessments from the two 1-week periods with the highest pollen counts. For tolerability assessment slit-lamp biomicroscopy and visual acuity examinations were conducted at each study visit (weeks 0, 2, 4, 6, and 8). RESULTS: Two-hundred ninety-eight patients (159 females, 139 males; mean [SD] age, 32.7 [14.6] years [range, 9-71 years]) entered the study; 118 received epinastine, 118 received levocabastine, and 62 received vehicle. Epinastine-treated patients reported significantly less ocular itching than those receiving vehicle (P=0.045); scores for hyperemia were similar between these 2 groups. Ocular itching and hyperemia scores were similar between the epinastine and levocabastine groups. No clinically or statistically significant between-group differences were seen in slit-lamp biomicroscopy findings, changes in visual acuity from baseline, or the incidence of treatment-related adverse effects. CONCLUSIONS: In this study of patients with SAC, ophthalmic epinastine instilled twice daily was more effective than vehicle for the control of ocular itching and was similar in efficacy to levocabastine for control of ocular itching and hyperemia. Epinastine was well tolerated.     

The complete sequence of Drosophila beta-spectrin reveals supra-motifs comprising eight 106-residue segments.

The alpha and beta chains of spectrin are homologous, yet they have acquired different structural features that work in synergy to give the multimer its overall properties. The primary amino acid sequence of each spectrin subunit is dominated by tandemly repeated 106-residue motifs. By comparing the complete Drosophila beta-spectrin sequence with other spectrins we have discovered evidence that a higher-order, 848-amino acid supra-motif is tandemly repeated in both alpha- and beta-spectrin. These data argue that alpha- and beta-spectrin, rather than evolving independently from sequences encoding the ancestral 106-residue motifs, must have arisen after the establishment of a large supra-motif composed of eight of the 106-residue motifs. Our data suggest the segment structure of a progenitor gene that gave rise to both alpha- and beta-spectrin as well as dystrophin. The structural differences that evolved after the split between the alpha- and beta-spectrin genes confer the independent functions that exist in their products today.     

Marked microglial reaction in normal aging human substantia nigra: correlation with extraneuronal neuromelanin pigment deposits

Multiple reports have documented an age-related loss, estimated at about 10% per decade, of the pigmented neurons in the substantia nigra. This is associated with motor dysfunction, including bradykinesia, stooped posture and gait disturbance. As microglia are activated by cell death and neuromelanin pigment, we hypothesized that there should be a significant microglial reaction in normal aging human substantia nigra. Sections of substantia nigra from elderly subjects (N = 15; mean 81.3; SD 7.0) and younger subjects (N = 7; mean 30.3; SD = 8.7), all of which had no specific neurologically or neuropathologically defined disorders, were stained immunohistochemically for MHC Class II and the area occupied by microglia was quantified in substantia nigra pars compacta. All elderly subjects showed a pronounced microglial reaction in the substantia nigra, with frequent, intensely stained hypertrophic microglia, while immunoreactive nigral microglia were much less frequent in the younger subjects. Quantification showed that in older subjects, the percentage of substantia nigra area occupied by microglial bodies and processes was significantly greater than for younger subjects (mean 19.6 vs. 3.6; P = 0.005). Extraneuronal neuromelanin deposits were present in all the older subjects but were absent or rare in the younger subjects. The neuromelanin deposit abundance score in the older subjects correlated significantly with the area occupied by immunoreactive microglia. The marked microglial reaction in normal aging human substantia nigra, together with the previously reported 35–80% pigmented neuron loss, indicates the presence of a powerful pathologic process that may be additive with specific age-related neurodegenerative diseases, including Parkinson’s disease.     

Naproxen, meloxicam and methylprednisolone inhibit urokinase plasminogen activator and inhibitor and gelatinases expression during the early stage of osteoarthritis

BACKGROUND: To test the hypothesis that naproxen, meloxicam and methylprednisolone down-regulate the plasminogen activator (PA)/plasmin system and gelatinases [matrix metalloproteinase (MMP)-2 and MMP-9] expression during early development of osteoarthritis (OA). METHODS: Samples of human OA articular cartilage, meniscus and synovium were obtained at knee arthroscopy and cultured ex vivo with or without naproxen, meloxicam or methylprednisolone. MMP-2 and MMP-9 levels were evaluated by gelatin zymography and urokinase-type PA (u-PA) and PA inhibitor-1 (PAI-1) levels were measured by enzyme-linked immunosorbent assay (ELISA). RESULTS: Gelatin zymography revealed that naproxen, meloxicam and methylprednisolone could suppress MMP-2 secretion in all tissue cultures and MMP-9 production in meniscal and synovial cultures. ELISA showed that naproxen and meloxicam reduced u-PA secretion in chondral and synovial cultures at 48 h except in naproxen-treated chondral cultures. On PAI-1 secretion, naproxen and meloxicam had the suppressive effects in all cultures at 48 h but not in naproxen-treated meniscal cultures. Methylprednisolone also decreased u-PA secretion in chondral and synovial cultures and PAI-1 production in synovial cultures at 48 h. CONCLUSION: Naproxen, meloxicam and methylprednisolone can down-regulate the PA/plasmin system and gelatinases expression in the early osteoarthritic knee of humans, thereby possibly have a potential structure-modifying activity in a limited use.     

Coronary artery diameters in infants and children with congenital heart disease as determined by computed tomography

This study was conducted to establish reference curves and formulas for the diameters of the coronary arteries in infants and children using computed tomography. A total of 145 children (57 female, 88 male) ranging in age from 2 days to 19 years, 11 months (mean 5 years, 10 months), were retrospectively identified, and the diameters of their coronary arteries were quantified. The measurability of the coronary arteries, coronary arterial size differences between the genders, and relations of the diameters of the coronary arteries to age, height, weight, body surface area, and the diameter of the descending aorta were examined. Independent-samples Student's t tests, 2-tailed Pearson's correlations, and linear regression were used in statistical analysis. The measurability of all coronary arteries was 73.3%. No difference in coronary arterial size was found between the genders. The diameter of the descending aorta correlated most strongly with coronary arterial size. In conclusion, predictive formulas and reference curves for coronary arterial diameters in infants and children were obtained.     

Up-regulation of estrogen responsive genes in hypospadias: microarray analysis

PURPOSE: An unexplained increase in the incidence of hypospadias has been reported, and yet to our knowledge the molecular events and their regulation leading to hypospadias remain unknown, although environmental compounds capable of endocrine activity are suspected. We screened on a global scale abnormalities in gene expression in human hypospadiac tissue compared to those in nonhypospadiac tissue. Additionally, microarray analysis of tissue from a pair of fraternal twins, including 1 with and 1 without hypospadias, served as a control for genetic variability. We hypothesized that gene expression would differ between hypospadiac vs nonhypospadiac tissue and fraternal twin data would show patterns similar to those of group data on hypospadiac and nonhypospadiac tissue. MATERIALS AND METHODS: Microarray analysis was performed on tissue from patients with and without hypospadias, and from a pair of fraternal twins, including 1 with and 1 without hypospadias. Analysis incorporated the expression of 22,000 genes. RESULTS: We found significant differences in gene expression, specifically with a group of genes, including CYR61, CTGF, ATF3 and GADD45beta, known to be responsive to estrogen or to interact with estrogen receptor. CONCLUSIONS: Our findings provide support for the hypothesis that endocrine active environmental compounds may contribute to the development of hypospadias. Additionally, regulation of these genes may have a role in formation of the urethra.     

广东地区223例皮肌炎与其并发症的临床分析

目的:探讨广东地区皮肌炎与其各种并发症的关系及特点。方法:收集近20年来广东各地在中山大学孙逸仙纪念医院住院治疗的223例皮肌炎患者资料相关数据输入计算机,用数据库软件Microsoft Visual FoxPro version 5.0进行统计处理。结果:223例患者中并发心电图异常者80/178例(44.9％),肺部病变44例(19.7％),食道功能异常44例(19.7％),恶性肿瘤26例(11.7％),糖尿病13例(5.8％),与系统性红斑狼疮重叠8例(3.6％),高血压及血管炎各6例(2.7％),类风湿性关节炎4例(1.8％),红皮病3例(1.3％),肾功能衰竭1例。结论:广东地区皮肌炎患者常见的并发症是糖尿病、系统性红斑狼疮;恶性肿瘤发生率比北京地区高,以鼻咽癌为主,年龄偏低。间质性肺炎发生率相对较低;心电图异常及食道功能异常两地相近。