Bilateral tinea nigra plantaris and tinea nigra plantaris mimicking melanoma.

Tinea nigra, a superficial fungal infection caused by Phaeoannellomyces werneckii, presents as a hyperpigmented, nonscaling macule of variable size and shape. Typically lacking induration, erythema, or pruritus, these "ink spot" lesions may resemble junctional nevi or malignant melanoma. Rapid, noninvasive diagnosis can be provided by potassium hydroxide examination, demonstrating numerous large, dematiaceous hyphae.     

photodynamic therapy for Taiwanese patients with pathologic myopia: a 2-year follow-up

PURPOSE: To examine the efficacy of photodynamic therapy with verteporfin (VPDT) for treatment of subfoveal choroidal neovascularization (CNV) in patients with pathologic myopia. METHODS: In a prospective study, adult patients (18 years of age or older) with new onset subfoveal CNV were treated in two tertiary centers with the standard protocol of VPDT. Snellen best-corrected visual acuity was measured at baseline and at 1 month, 3 months, 6 months, 12 months, 15 months, 18 months, and 24 months after VPDT. Stratified analyses for single and multiple treatments and different age groups were performed by paired t-tests, and the results were compared with baseline findings. RESULTS: Thirty-three patients with single VPDT and 13 patients with multiple treatments were enrolled for analysis. Significant improvement in measurement of visual acuity was found after 24 months of follow-up for the group with single therapy. For patients receiving multiple treatments, an improving trend was not as clear. In prognosis analysis by age groups in the single-treatment group, the younger group had better mean visual acuity at the end of the 24-month study period than the older group. Improvement was much more evident in the younger group, although it was not statistically significant at every follow-up time point. CONCLUSION: In patients with response to single VPDT, visual acuity significantly improved over a 2-year period. In patients receiving multiple treatments, improvement was not as distinctive, suggesting alternative treatment options might be relevant for this subgroup.     

Evaluation of visual acuity and color vision in normal human eyes with a sutureless temporary amniotic membrane patch

PURPOSE: To evaluate how sutureless amniotic membrane patches may affect visual functions in normal human eyes. DESIGN: Prospective intervention study. METHODS: Ten sets of sutureless amniotic membrane patch manufactured as PROKERA were inserted in one eye of six normal patients. Four sets (one each) were inserted in four patients, while six sets (three each) were inserted in two patients. Uncorrected distant and near visual acuities, color vision, amniotic membrane thickness measured by pachymetry, and total symptom scores were compared before and after insertion. RESULTS: Within 30 minutes after insertion, mean distant visual acuities decreased from -0.22 +/- 0.06 to 0.92 +/- 0.45 logarithmic minimum angle of resolution (logMAR). Among 10 sets of PROKERA inserted, the largest optotype (1.0 logMAR) of the near vision chart could not be recognized in five, but color vision evaluated by Panel D-15 was still preserved in all. Total symptom scores increased to 47.8 +/- 9.1 points (maximum, 100 points). Among symptoms, total scores for foreign body sensation (17.8 +/- 3.6) and blurred vision (17.8 +/- 4.4) were high. Loss of distant visual acuity and increases of symptom scores were not correlated with amniotic membrane thickness, of which the mean was 67.6 +/- 25.2 mum. However, amniotic membrane that was less opaque tended to provide relatively good visual acuities. CONCLUSION: Because of the relative non-transparency of sutureless amniotic membrane patches in PROKERA, distant and near visual acuities decreased in normal human eyes. The foreign body sensation noted after insertion is primarily derived from the rigid supporting skirt.     

黄精药理作用研究进展

黄精为我国常用传统中药,在长江以南大部分地区广泛分布,具有补益肝肾、延年益寿等作用,是自古以来的道家养生圣药。因其含有多糖、皂苷、黄酮、木脂素、氨基酸、醌类化合物、维生素、生物碱及多种微量元素等成分,从而具有较高的药用价值和营养价值,国内各研究机构对其进行了较深入的研究,国外对其仍处于初步研究阶段。目前实验研究主要集中在黄精多糖、黄精醇、黄精皂苷提取物或黄精水提物上,以动物实验或单方和复方制剂的临床研究为主。其多种黄精制剂已广泛应用于临床,如黄精口服液、黄精茶、苁蓉精颗粒、黄精赞育胶囊、黄精精油眼罩等,发挥着不同的效用。查阅有关黄精的研究文献,对其药理作用进行全面的综合分析,多角度总结其效用价值,为黄精的深入开发与应用提供参考。     

Detection of chymase activity using a specific peptide probe conjugated onto gold nanoparticles

Gold nanoparticles (AuNPs) can be applied in biosensors using fluorescence resonance energy transfer (FRET) technique. Based on this technique, we have established a sensitive and efficient biosensing method by modifying a peptide-probe onto AuNPs to detect proteinase enzyme activity in this study. This biosensing method was designed for chymase activity detection and applied in kidney disease diagnosis. In this study, 16 nm-AuNPs were used to construct the AuNPs-based fluorescence peptide probe (named AuNPs-peptide probe) for chymase activity determination. The peptide sequence is FITC-Acp-DRVYIHPFHLDDDDDC, which comprises a fluorophore at the N-terminal end, an enzyme (chymase) substrate (DRVYIHPFHL), a spacer (DDDDD) and cysteine (C) to conjugate to AuNPs surface. When the enzyme catalyzes the substrate sequence, the fluorophore drifts away from AuNPs and the fluorescence emitting signal can be excited at 495 nm and detected at 515 nm. The results indicate that the time required for the AuNPs-peptide probe for activity detection of chymase was only 15 min, and a linear correlation from 10 to 100 ng mL⁻¹ of chymase was acquired. The chymase reaction would be significantly inhibited by addition of specific chymase inhibitor chymostatin. The AuNPs-peptide probe was tested for the detection of high concentrations of trypsin and chymotrypsin, but only minor emitted fluorescence intensity was detected. According to these results, sensitivity and specificity of the AuNPs-peptide probe for chymase detection have been confirmed. AuNPs-peptide probe was successfully used for the detection of renal chymase activity; and the results indicate the pathogenically increased chymase activity in kidney tissue of nephropathic mice from aristolochic acid I treatment.

The gold nanoparticles (AuNPs) peptide probe functionalized with specific peptide sequences was developed for the sensitive and efficient detection of chymase activity.     

Betulinic acid exerts anti-hepatitis C virus activity via the suppression of NF-κB- and MAPK-ERK1/2-mediated COX-2 expression

Background and Purpose

This study was designed to evaluate the effect of betulinic acid (BA), extracted from Avicennia marina, on the replication of hepatitis C virus (HCV) and to investigate the mechanism of this BA-mediated anti-HCV activity.

Experimental Approach

HCV replicon and infectious systems were used to evaluate the anti-HCV activity of BA. Exogenous COX-2 or knock-down of COX-2 expression was used to investigate the role of COX-2 in the anti-HCV activity of BA. The effects of BA on the phosphorylation of NF-κB and on kinases in the MAPK signalling pathway were determined. The anti-HCV activity of BA in combination with other HCV inhibitors was also determined to assess its use as an anti-HCV supplement.

Key Results

BA inhibited HCV replication in both Ava5 replicon cells and in a cell culture-derived infectious HCV particle system. Treatment with a combination of BA and IFN-α, the protease inhibitor telaprevir or the NS5B polymerase inhibitor sofosbuvir resulted in the synergistic suppression of HCV RNA replication. Exogenous overexpression of COX-2 gradually attenuated the inhibitory effect of BA on HCV replication, suggesting that BA reduces HCV replication by suppressing the expression of COX-2. In particular, BA down-regulated HCV-induced COX-2 expression by reducing the phosphorylation of NF-κB and ERK1/2 of the MAPK signalling pathway.

Conclusions and Implications

BA inhibits HCV replication by suppressing the NF-κB- and ERK1/2-mediated COX-2 pathway and may serve as a promising compound for drug development or as a potential supplement for use in the treatment of HCV-infected patients.     

Distinct regulations by calcium of cyclic GMP levels and catecholamine secretion in isolated bovine adrenal chromaffin cells

The effects of various calcium-dependent secretagogues on cyclic GMP levels and catecholamine (CA) secretion were measured in a preparation of bovine adrenal chromaffin cells. The secretory effect of acetylcholine (ACh; 8--10 fold stimulation) was mimicked by nicotine but not muscarine. Three--five fold stimulations of cyclic GMP levels were also obtained with ACh and muscarine but not nicotine. High concentration of K+, and the ionophore A23187, also elevated cyclic GMP levels. However, secretion produced by veratridine, ouabain, and the ionophore X537A was not accompanied by any rise in cyclic GMP levels. Removal of extracellular calcium significantly decreased both basal levels of CA secretion and of cyclic GMP and completely abolished their stimulation by ACh. The half-maximal effects of calcium on the cholinergic stimulations of cyclic GMP levels and of CA secretion were observed at 0.2 and 2.5 mM, respectively. Substitution of Ca2+ by Sr2+ was more effective in maintaining the cyclic GMP response than the secretory response. The calcium channel blockers Co2+, Mg2+ and Ni2+ inhibited the cholinergic stimulation of cyclic GMP more than that of CA release. On the other hand, the organic calcium channel blockers, verapamil and methoxyverapamil (D--600) were more effective antagonists of the secretory response. These data indicate that the cholinergic stimulations of CA secretion and of cyclic GMP levels in bovine adrenal chromaffin cells are regulated by calcium via two distinct mechanisms.     

A NOD2-NALP1 complex mediates caspase-1-dependent IL-1beta secretion in response to Bacillus anthracis infection and muramyl dipeptide

NOD2, a NOD-like receptor (NLR), is an intracellular sensor of bacterial muramyl dipeptide (MDP) that was suggested to promote secretion of the proinflammatory cytokine IL-1beta. Yet, the molecular mechanism by which NOD2 can stimulate IL-1beta secretion, and its biological significance were heretofore unknown. We found that NOD2 through its N-terminal caspase recruitment domain directly binds and activates caspase-1 to trigger IL-1beta processing and secretion in MDP-stimulated macrophages, whereas the C-terminal leucine-rich repeats of NOD2 prevent caspase-1 activation in nonstimulated cells. MDP challenge induces the association of NOD2 with another NLR protein, NALP1, and gel filtration analysis revealed the formation of a complex consisting of NOD2, NALP1, and caspase-1. Importantly, Bacillus anthracis infection induces IL-1beta secretion in a manner that depended on caspase-1 and NOD2. In vitro, Anthrax lethal toxin strongly potentiated IL-1beta secretion, and that response was NOD2 and caspase-1-dependent. Thus, NOD2 plays a key role in the B. anthracis-induced inflammatory response by being a critical mediator of IL-1beta secretion.