Trabeculectomy with mitomycin C versus trabeculectomy alone for juvenile primary open-angle glaucoma

PURPOSE: We compare the intermediate-term outcome of initial trabeculectomy with adjunctive mitomycin C use versus initial trabeculectomy alone for juvenile primary open-angle glaucoma. METHODS: This retrospective consecutive analysis included 44 eyes from 36 patients with juvenile primary-open angle glaucoma, all of whom underwent either initial trabeculectomy with adjunctive mitomycin C use (15 eyes) or initial trabeculectomy alone without mitomycin C use (29 eyes). We compared the success rate and complications between the two groups in a three-year follow-up period following surgery. RESULTS: Three years subsequent to surgery, the cumulative success probability was 73% for the mitomycin C group and 68% for the control group, there being no real difference between the two groups (p = 0.89). A greater incidence of hypotony maculopathy was found amongst the mitomycin C group than was the case for the control group (20 versus 0%, respectively, p = 0.034). A lower intraocular pressure amongst the mitomycin C group was noted as compared with the control group (10.8 +/- 3.0 versus 13.3 +/- 3.8 mm Hg, respectively, p = 0.017) amongst the successfully treated patients. CONCLUSIONS: Despite the lower intraocular pressure level for the successfully treated patients from the trabeculectomy with mitomycin C group, and a greater incidence of resultant hypotony maculopathy for this group as compared with the trabeculectomy alone group, there appeared to be no significant difference in the cumulative success probability for this group as compared with the trabeculectomy alone group. Therefore, we caution against the use of an initial trabeculectomy with mitomycin C for juvenile primary open-angle glaucoma.     

Association of tumour necrosis factor alpha -308 gene polymorphism with primary open-angle glaucoma in Chinese

PURPOSE: Genetic factors are known to play a role in the aetiology of glaucoma, and in particular the role of the immune system is highly suspected. In this study, we evaluated the association between tumour necrosis factor alpha -308 (TNF alpha -308) and primary open-angle glaucoma (POAG). METHODS: A total of sixty POAG patients and 103 healthy volunteers as control group were enrolled in this case-controlled study. Furthermore, we used polymerase chain reaction based analysis to resolve the TNF alpha -308 polymorphism. Statistical analysis for the relative risk of TNF alpha -308 polymorphism was compared by the chi(2) test. RESULTS: There were significant differences in the distribution of the polymorphism between the POAG patients and the control subjects (P = 0.00016; P < 0.05) and it was found that the A(-308) allele occurred more frequently in POAG patients (odds ratio: 2.72; 95% confidence interval: 1.66-4.45). CONCLUSION: The results of our study concluded that the distribution of TNF alpha -308 was significantly higher in the POAG patients than in the control group. Therefore, the A(-308) allele appears to be associated with POAG and, therefore, could be used as a genetic marker for disease mapping. POAG is a complex disease, and a single gene could not be responsible. Understanding the role of genetic polymorphisms, like TNF alpha, could be a prediction of the disease and useful for developing new treatments for POAG.     

Comparison of subjective visual acuity with visual acuity predicted from C-scan topography

PURPOSE: To compare the capability of objective measures of visual acuity (potential visual acuity from C-scan) to predict subjective visual acuity (best spectacle-corrected visual acuity [BSCVA]). METHODS: Patients with BSCVA > or = 20/20 were enrolled in four groups (Group 1: normal [33 eyes]; Group 2: < -7.00 D myopia [43 eyes]; Group 3: > or = -7.00 D myopia [28 eyes]; Group 4: At least 1 month after LASIK [93 eyes]). Videokeratography was performed with the ray tracing Technomed C-scan. The potential visual acuity from C-scan was obtained with pupils undilated and intact precorneal tear films. All visual acuity was recorded in logMAR, and the significance of differences between acuities was assessed with a one-way ANOVA test. RESULTS: The potential visual acuity from C-scan ray tracing of normal and myopic eyes in response to both photopic and mesopic stimuli did not differ. In a given eye, the potential visual acuity from C-scan ray tracing was better than BSCVA, and the difference was statistically significant. Although the potential visual acuity from C-scan of postoperative LASIK eyes in response to photopic stimuli was the same, it decreased under mesopic conditions. CONCLUSIONS: Potential visual acuity from C-scan overestimates subjective visual acuity due to the inadequate assumptions in ray tracing or individual retinal resolution ability. In addition, the potential visual acuity from C-scan ray tracing varies with pupil diameter in different illumination.     

The effects of intrathecal tramadol on spinal somatosensory-evoked potentials and motor-evoked responses in rats

Tramadol has been proven to exert a local anesthetic-type effect on peripheral nerves in both clinical and laboratory studies. In this study, we evaluated the effects of tramadol on sensory and motor neural conduction when administered intrathecally in the rat. Tramadol (0, 1, or 2 mg) was administered through an intrathecal catheter. Spinal somatosensory-evoked potentials (SSEPs) were recorded at the thoracolumbar junction after stimulation of the sciatic nerve. An evoked compound muscle action potential (CMAP) was recorded in the intrinsic muscles of the foot in response to electric stimulation of the lower thoracic (T1213) interspinous space. Both SSEP and CMAP were obtained before drug application as the pretreatment baseline and at 5, 15, and 30 min after treatment, and at 30- or 60-min intervals thereafter for another 4.5 h. SSEP was averaged from 20 responses, whereas CMAP was obtained from a single stimulation. Reproducible SSEPs and CMAP were consistently recorded in all rats. Intrathecal tramadol dose-dependently reduced the amplitude and delayed the latency in both SSEPs and CMAP. Generally, the suppressive effects occurred immediately after injection and recovered over 2 h. Combined administration with 20 micro g of intrathecal naloxone did not attenuate the inhibition of spinal SSEPs. We conclude that intrathecal tramadol causes a dose-related suppressive effect on both sensory and motor neural conduction in the spinal cord. IMPLICATIONS: Spinal somatosensory-evoked potentials and evoked compound muscle action potential were used to evaluate the effects of intrathecal tramadol on sensory and motor neural conduction. Intrathecal tramadol dose-dependently reduced the amplitude and delayed the latency of both spinal somatosensory-evoked potentials and compound muscle action potential. These results indicate that tramadol exerts a dose-related central neural blockade.     

Locally administered nerve growth factor suppresses ginsenoside Rb1-enhanced peripheral nerve regeneration

A high-dose of nerve growth factor (NGF) mixed with ginsenoside Rb1 (GRb1) was encapsulated by collagen and placed in silicone rubber chambers, which were used to repair dissected Sprague-Dawley rat sciatic nerves with 15 mm gaps. Six weeks after surgery, no axons or Schwann cells were seen in these chambers. By comparison, nerves treated with collagen-GRb1 alone had regenerated axons and Schwann cells in their endoneurial areas. We suggest that excessive NGF may not promote but, rather, suppress developing nerves.     

c-Abl stabilizes p73 by a phosphorylation-augmented interaction

The proapoptotic function of c-Abl is in part mediated by its functional interaction with p73, a p53 homologue. Although it has been shown that c-Abl-mediated p73 activation in response to genotoxic stress is associated with an increase of p73 protein levels, the underlying mechanism remains unclear. We show here that c-Abl increases the cellular p73 abundance through a mode of posttranslational regulation. Analogous to its functional activation of p73, the kinase activity is essential for c-Abl to up-regulate p73 protein levels. Analysis of phosphorylation-resistant mutants of p73 reveals that the effect of c-Abl is mediated by its direct phosphorylation on the p73 protein. Consequence to the phosphorylation is a marked increase of the association between c-Abl and p73 via the binding of tyrosine-phosphorylated p73 to the c-Abl Src homology 2 (SH2) domain. Of functional importance of this phosphorylation-induced interaction in p73 stabilization is the demonstration that expression of a c-Abl SH2 domain peptide, which impedes phosphorylation-dependent association, results in an almost complete abrogation of c-Abl-dependent p73 accumulation. Importantly, expression of the c-Abl SH2 domain peptide also leads to an efficient inhibition of cisplatin-induced accumulation of endogenous p73, highlighting the biological significance. In keeping with its retained phosphorylation sites, the NH(2)-terminal truncated (Delta N) isoforms of p73, which are antiapoptotic, are also phosphorylated and stabilized by c-Abl, suggesting a possibility that c-Abl contributes to either pro- or antiapoptotic process depending on the expression profile of p73 isoforms.     

Black cohosh, a menopausal remedy, does not have estrogenic activity and does not promote breast cancer cell growth

Black cohosh is an increasingly popular alternative to estrogen replacement therapy for the relief of menopausal symptoms, primarily hot flushes. However, an important consideration for long-term therapy is potential toxicity and carcinogenicity. Therefore, we undertook a study to assess the estrogenic activity of black cohosh to examine its safety for those with, or at high risk of developing, breast cancer. Several assays were utilized as listed: RNAse protection assays, which ascertain the regulation of the expression of E2-responsive genes; estrogen-responsive-element (ERE)-luciferase, which determines modulation of the ER function by transactivation of the ERE; the Ishikawa cell system, which has an E2-regulated endogenous alkaline phosphatase; and colony formation of ER-expressing breast cancer cells, which indicates possible progression of early stage breast cancer into a more aggressive state. Black cohosh extracts did not demonstrate estrogenic activity in any of these assay systems. This is an encouraging step in the assessment of the safety of black cohosh for treatment of menopausal hot flushes.     

The anti-inflammatory effect of honokiol on neutrophils: mechanisms in the inhibition of reactive oxygen species production

Reactive oxygen species produced by neutrophils contribute to the pathogenesis of focal cerebral ischemia/reperfusion injury and signal the inflammatory response. We have previously shown that honokiol, an active principle extracted from Magnolia officinalis, has a protective effect against focal cerebral ischemia/reperfusion injury in rats that paralleled a reduction in reactive oxygen species production by neutrophils. To elucidate the underlying mechanism(s) of the antioxidative effect of honokiol, peripheral neutrophils isolated from rats were activated with phorbol-12-myristate-13-acetate (PMA) or N-formyl-methionyl-leucyl-phenylalanine (fMLP) in the presence or absence of honokiol. In this study, we found that honokiol inhibited PMA- or fMLP-induced reactive oxygen species production by neutrophils by three distinct mechanisms: (1) honokiol diminished the activity of assembled-NADPH oxidase, a major reactive oxygen species producing enzyme in neutrophils by 40% without interfering with its protein kinase C (PKC)-dependent assembly; (2) two other important enzymes for reactive oxygen species generation in neutrophils, i.e., myeloperoxidase and cyclooxygenase, were also inhibited by honokiol by 20% and 70%, respectively; and (3) honokiol enhanced glutathione (GSH) peroxidase activity by 30%, an enzyme that triggers the metabolism of hydrogen peroxide (H2O2). These data suggested that honokiol, acting as a potent reactive oxygen species inhibitor/scavenger, could achieve its focal cerebral ischemia/reperfusion injury protective effect by modulating enzyme systems related to reactive oxygen species production or metabolism, including NADPH oxidase, myeloperoxidase, cyclooxygenase, and GSH peroxidase in neutrophils.     

A cytotoxic butenolide,two new dolabellane diterpenoids,a chroman and a benzoquinol derivative formosan Casearia membranacea

Investigation of a cytotoxic chloroform-soluble fraction of the stem of Casearia membranacea (Flacourtiaceae) led to the isolation of five new compounds, including one butenolide, casealactone (1), one chroman, caseamemin (2), two dolabellane diterpenoids, casearimene A (3) and casearimene B (4), one benzoquinol ether, casearinone (5), together with fifteen known compounds, including two amides, N- trans-feruloyltyramine (6) and N- cis-feruloyltyramine (7), six steroids, beta-sitosterol (8), stigmast-5-ene-3beta,7alpha-diol (9), stigmast-5-ene-3beta,7beta-diol (10), stigmastane-3beta,5alpha,6beta-triol (11), beta-sitostenone (12), beta-sitosterol 3- O-beta-glucoside (13), two triterpenoids, squalene (14) and friedelin (15), one lignan, (+/-)-syringaresinol (16), two benzenoids, syringaldehyde (17) and vanillic acid (18), one ester, methyl hexadecanoate (19), and anthraquinone (20), respectively. Among these isolates, 1 showed cytotoxicity against P-388 and HT-29 cancer cell lines in vitro, and 6 and 7 showed cytotoxicity against the P-388 cancer cell line. The structures of these compounds were determined by means of spectroscopic techniques, and the structure of 3 was confirmed by X-ray crystallographic analysis.