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• The outcomes of patients with chronic kidney disease (CKD) and coronary instent restenosis after drug-coated balloon (DCB) angioplasty remain unclear. • Patients with CKD after DCB angioplasty had a significantly higher risk of adverse cardiac events. • The majority of adverse cardiac events were driven by severe CKD or end-stage renal disease (ESRD) patients. • Different revascularization strategies may be considered for severe CKD or ESRD patients. Patients with chronic kidney disease (CKD) and coronary instent restenosis (ISR) treated with drug-coated balloon (DCB) angioplasty have been excluded from randomized controlled trials. We aimed to investigate the clinical impact of CKD stratified by severity, on clinical outcomes for patients with ISR treated with DCB angioplasty. This cohort study enrolled 1,376 patients treated with DCB angioplasty; 639 CKD patients defined as having an estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m2 and 737 patients with preserved renal function were identified. Risks of target vessel failure (TVF), all-cause mortality, and any repeated revascularization were analyzed. The CKD group had a significantly higher risk of TVF [adjusted hazard ratio (HR): 1.337; 95% confidence interval (CI): 1.125-1.590; p = 0.0010], all-cause mortality (adjusted HR: 2.553; 95% CI: 1.494-4.361; p = 0.0006), and any repeated revascularization (adjusted HR: 1.447; 95% CI: 1.087-1.927; p = 0.0114) compared with the non-CKD group. After multivariable adjustment, patients with severe CKD (eGFR = 15–29 mL/min/1.73 m2) and end-stage renal disease (ESRD) (eGFR <15 mL/min/1.73 m2) had a significantly higher risk of adverse events comparable to that in patients with preserved renal function. In this cohort study, patients with CKD and ISR undergoing DCB angioplasty had a significantly higher risk of adverse events compared with patients with preserved renal function, whereas subgroups with mild to moderate CKD did not display this difference. Different revascularization strategies may be considered for patients with severe CKD or ESRD with ISR. [Display omitted] [ABSTRACT FROM AUTHOR]

Background: Elevated intraocular pressure (IOP) is a major risk factor for glaucoma that has been found to induce matrix metalloproteinase-9 (MMP-9) activation and result in eventual retinal dysfunction. Proinflammatory cytokines such as monocyte chemoattractant protein-1 (MCP-1) and interleukin-1β (IL-1β) were also found to be involved in disease progression by mediating MMP-9 production. We previously reported that fungal derivative theissenolactone C (LC53) could exert ocular protective effects by suppressing neuroinflammation in experimental uveitis.Purpose: The aim of this study was to investigate the retinoprotective effects of natural compound LC53 on the high IOP-induced ischemia/reperfusion (I/R)-injury model of glaucoma and its cellular mechanisms.Methods: A high IOP-induced I/R-injury model was manipulated by normal saline injection into the anterior chamber of the rat eye. MCP-1-stimulated monocytes and IL-1β-activated primary astrocytes were used to investigate the cellular mechanisms of LC53. Retinal function was evaluated with the scotopic threshold response (STR) and combined rod-cone response by electroretinography (ERG). As a positive control, rats were treated with memantine. MMP-9 gelatinolysis, mRNA expression and protein expression were analyzed by gelatin zymography, RT-PCR, and Western Blot, respectively. The phosphorylation levels of MAPKs and NF-κB p65 were tested by Western Blot. Additionally, the levels of inflammatory MCP-1 and IL-1β were determined by ELISA.Results: The present study revealed that LC53 preserved the retina functional deficiency assessed by scotopic threshold response (STR) and combined rod-cone response of ERG after high IOP-induced I/R injury. These retinal protective effects of LC53 were positively correlated with inhibitory activities in I/R injury-elicited ocular MMP-9 activation and expression. The increased level of MCP-1 was not affected, and the enhanced IL-1β production was partially reduced by LC53 in the retina after I/R injury. According to cellular studies, LC53 significantly and concentration-dependently abrogated MMP-9 activation and expression in MCP-1-stimulated THP-1 monocytes. We found the inhibitory activities of LC53 were through the ERK- and NF-κB-dependent pathways. In addition, LC53 dramatically suppressed IL-1β-induced MMP-9 activation and expression in primary astrocytes. The phosphorylation of 65-kD protein (p65) of NF-κB was substantially blocked by LC53 in IL-1β-stimulated primary astrocytes.Conclusion: LC53 exerted a retinal protective effect through NF-κB inhibition and was highly potent against MMP-9 activities after high IOP-induced I/R injury, suggesting that LC53 would be a promising drug lead for glaucoma or related medical conditions attributed to retinal ischemia. [ABSTRACT FROM AUTHOR]

The apelin pathway has emerged as a critical regulator of cardiovascular homeostasis and disease. However, the exact role of pyr1-apelin-13 in angiotensin (Ang) II-mediated heart disease remains unclear. We used apelin-deficient (APLN-/y) and apolipoprotein E knockout mice to evaluate the regulatory roles of pyr1-apelin-13. The 1-year aged APLN-/y mice developed myocardial hypertrophy and dysfunction with reduced angiotensin-converting enzyme 2 levels. Ang II infusion (1.5 mg kg-1 d-1) for 4 weeks potentiated oxidative stress, pathological hypertrophy, and myocardial fibrosis in young APLN-/y hearts resulting in exacerbation of cardiac dysfunction. Importantly, daily administration of 100 μg/kg pyr1-apelin-13 resulted in upregulated angiotensin-converting enzyme 2 levels, decreased superoxide production and expression of hypertrophy- and fibrosis-related genes leading to attenuated myocardial hypertrophy, fibrosis, and dysfunction in the Ang II-infused apolipoprotein E knockout mice. In addition, pyr1-apelin-13 treatment largely attenuated Ang II-induced apoptosis and ultrastructural injury in the apolipoprotein E knockout mice by activating Akt and endothelial nitric oxide synthase phosphorylation signaling. In cultured neonatal rat cardiomyocytes and cardiofibroblasts, exposure of Ang II decreased angiotensin-converting enzyme 2 protein and increased superoxide generation, cellular proliferation, and migration, which were rescued by pyr1-apelin-13, and Akt and endothelial nitric oxide synthase agonist stimulation. The increased superoxide generation and apoptosis in cultured cardiofibroblasts in response to Ang II were strikingly prevented by pyr1-apelin-13 which was partially reversed by cotreatment with the Akt inhibitor MK2206. In conclusion, pyr1-apelin-13 peptide pathway is a negative regulator of aging-mediated and Ang II-mediated adverse myocardial remodeling and dysfunction and represents a potential candidate to prevent and treat heart disease. [ABSTRACT FROM AUTHOR]

Background Granuloma annulare (GA) is a benign, usually self-limited, inflammatory skin disease. Although there have been several studies that review pathoclinical features about GA, the relevant epidemiological study in Taiwan was lacking. The purpose of this study is to evaluate the pathoclinical features and treatment outcome of GA in Taiwan. Methods This study was performed by retrospective review of medical records and pathological slides of the patients diagnosed as GA in a tertiary referral medical center in Taiwan. Fisher exact test was performed to compare remission rate between adults and children, treatment and nontreatment groups. Result The study included 44 patients with GA: 23 male and 21 female. The incidence of GA showed a bimodal age distribution (peaks below 20 years and above 50 years). Localized type is most common, followed by generalized variant. Perforating GA is the rarest subtype and was exclusively found in children. The pathology of GA is characterized by necrobiosis (100%), palisading granuloma (81.8%), and mucin deposition (93.2%); 13.6% and 6.8% of GA patients had history of diabetes mellitus and dyslipidemia, respectively. Conclusion In contrast to the reported studies, the incidence of GA showed a bimodal age incidence with slight male preponderance. Our patients had higher prevalence of diabetes mellitus than the general Taiwanese population but had no increase in incidence of dyslipidemia. Whether patients received treatment or not does not affect the disease outcome. Overall, children have better prognosis than adults. [ABSTRACT FROM AUTHOR]

There is much evidence indicating that human leukemic cells and monocytes/macrophages synthesize, and secrete, several matrix metalloproteinases (MMPs), and participate in the degradation of extracellular matrix components in tissue lesions. In this study, we investigated the effects and mechanisms of andrographolide, extracted from the herb Andrographis paniculata, on human monocytic MMPs expression and activation. Andrographolide (1-50 μM) exhibited concentration-dependent inhibition of MMP-9 activation, induced by either tumor necrosis factor-α (TNF-α), or lipopolysaccharide (LPS), in THP-1cells. In addition, andrographolide did not present an inhibitory effect on MMP-9 enzymatic activity at a concentration of 50 μM. By contrast, enzyme-linked immunosorbent assay (ELISA) showed that andrographolide partially affect TIMP-1 levels. Western blot analysis showed that both TNF-α, and LPS stimulators attenuated MMP-9 protein expression in a concentration-dependent manner. Using reverse transcription polymerase chain reaction (RT-PCR), we found that andrographolide suppressed expression of MMP-9 messenger RNA. Furthermore, we also found that andrographolide could significantly inhibit the degradation of inhibitor-κB-α (IκB-α) induced by TNF-α. We used electrophoretic mobility shift assay and reporter gene detection to show that andrographolide also markedly inhibited NF-κB signaling, anti-translocation and anti-activation. In conclusion, we demonstrate that andrographolide attenuates MMP-9 expression, and its main mechanism might involve the NF-κB signal pathway. These results provide new opportunities for the development of new anti-inflammatory and leukemic therapies. [ABSTRACT FROM AUTHOR]

Abstract: There is much evidence indicating that human leukemic cells and monocytes/macrophages synthesize, and secrete, several matrix metalloproteinases (MMPs), and participate in the degradation of extracellular matrix components in tissue lesions. In this study, we investigated the effects and mechanisms of andrographolide, extracted from the herb Andrographis paniculata, on human monocytic MMPs expression and activation. Andrographolide (1–50μM) exhibited concentration-dependent inhibition of MMP-9 activation, induced by either tumor necrosis factor-α (TNF-α), or lipopolysaccharide (LPS), in THP-1cells. In addition, andrographolide did not present an inhibitory effect on MMP-9 enzymatic activity at a concentration of 50μM. By contrast, enzyme-linked immunosorbent assay (ELISA) showed that andrographolide partially affect TIMP-1 levels. Western blot analysis showed that both TNF-α, and LPS stimulators attenuated MMP-9 protein expression in a concentration-dependent manner. Using reverse transcription polymerase chain reaction (RT-PCR), we found that andrographolide suppressed expression of MMP-9 messenger RNA. Furthermore, we also found that andrographolide could significantly inhibit the degradation of inhibitor-κB-α (IκB-α) induced by TNF-α. We used electrophoretic mobility shift assay and reporter gene detection to show that andrographolide also markedly inhibited NF-κB signaling, anti-translocation and anti-activation. In conclusion, we demonstrate that andrographolide attenuates MMP-9 expression, and its main mechanism might involve the NF-κB signal pathway. These results provide new opportunities for the development of new anti-inflammatory and leukemic therapies. [Copyright &y& Elsevier]

Abstract: Background: Inflamed epidermal cysts are common clinical conditions, and they frequently form abscesses. We designed a study to delineate the bacteriology of inflamed epidermal cysts. Methods: We enrolled 61 adult patients with inflamed epidermal cysts characterized by surface erythema, with or without tenderness, or localized abscess formation within the cyst cavity. Incision and drainage of the cysts were performed, and the contents were sent for aerobic and anaerobic bacterial culture. The locations of the cyst and culture results were recorded for statistical analysis. Results: A total of 61 cysts and 122 cultures were obtained. The most common locations of the inflamed cysts were the face, neck, and scalp (34.4%), followed by the trunk (32.8%), then the buttocks, inguinal areas, perineum, and axillae (16.4%), and the extremities (16.4%). The culture results were positive in 88.5% of patients, and anaerobes were more frequently isolated than were aerobes. Pure aerobes represented 31.1% of the cultures; pure anaerobes, 36.1%, and combined aerobes and anaerobes, 21.3% (n = 13). The most common anaerobic organisms found were Propionibacterium spp (40.8%), followed by Peptostreptococcus spp (36.7%), Staphylococcus saccharolyticus (14.4%), Prevotella (4.1%), Bacteroides fragilis (2.0%), and Fusobacterium spp (2.0%). The most commonly isolated aerobes were Staphylococcus spp (40%), followed by Enterobacter spp (11.3%), Proteus mirabilis (8.5%), Citrobacter diversus (8.5%), Klebsiella pneumoniae (5.7%), Corynebacterium (5.7%), Morganella morganii (2.9%), Enterococcus faecalis (2.9%), group A β-hemolytic streptococcus (2.9%), Pseudomonas aeruginosa (2.9%), and Providencia rettgeri (2.9%). Conclusions: Both aerobic and anaerobic microorganisms were present in the inflamed epidermal cysts, although the anaerobic bacteria, specifically, Propionibacterium spp and Peptostreptococcus spp, were isolated slightly more frequently. Antibiotics directed against anaerobes may be considered in the treatment regimen for inflamed epidermal cysts. [Copyright &y& Elsevier]

Background: Pityriasis rubra pilaris (PRP) is a papulosquamous dermatosis uncommon in juveniles. Large-scale studies are limited, especially from Asian countries. Objective: We sought to analyze the clinical manifestations of juvenile PRP in Taiwanese patients and compare them with reported series in the literature. Methods: The diagnosis of juvenile PRP was made based on clinical–histopathologic correlation. The therapeutic response and disease course were followed up by re-examination of the patients or by telephone. Results: A total of 47 patients were identified, with histopathologic confirmation of the clinical diagnosis of juvenile PRP in 28 cases. A preponderance of Griffiths'' type IV PRP (85.7%) rather than type III PRP (14.3%) was found. Palmoplantar hyperkeratosis appeared to be a cardinal feature. In patients with type IV PRP, skin lesions in areas other than the elbows/knees and palms/soles were common. Treatment with systemic acitretin in 6 patients failed to effect a dose- or time-dependent improvement. In contrast with other studies, two thirds of our patients with type III and IV juvenile PRP had a protracted course lasting more than 3 years. Limitations: This study was a retrospective review. Patient compliance with treatment was frequently poor. Conclusions: Type IV juvenile PRP predominated but our cases showed a wider distribution of skin lesions than is typically described. When children present with an acute onset of diffuse palmoplantar hyperkeratosis, a diagnosis of juvenile PRP should be considered. Because of the divergent clinical manifestations of juvenile PRP in different populations, there is a need to modify and re-evaluate classification systems based on regional differences. [Copyright &y& Elsevier]

Background/Purpose: Skin diseases are common in children. Epidemiologic studies of skin diseases in schoolchildren performed by direct inspection by dermatologists are limited in Taiwan. The current study surveyed the prevalence of selected childhood dermatoses in Magong City, Penghu, the largest offshore island of Taiwan. Methods: A cross-sectional study was carried out in June 2005, in which a total of 3273 children aged 6−11 years living in Magong were examined by at least two board-certified dermatologists, with regard to the point prevalence of acne, ephelides, atopic dermatitis, warts, keloids, vitiligo, fungal infections, alopecia areata and psoriasis. The skin of the scalp, face, neck, trunk and extremities were inspected; that of the breast, genitalia and feet were skipped for privacy. Results: Acne vulgaris was found at the age of 7 in both genders, with comedones being the earliest manifestation. The overall prevalence of acne was 17.3% (95% CI, 16−18.6%). Ephelides were frequently observed in the children (prevalence rate, 15.24%; 95% CI, 14−16.47%). The prevalence of atopic dermatitis was 4.33% (95% CI, 3.63−5.03%), with more boys affected than girls (1.49:1) (p = 0.03). The prevalence of warts on the hands was 2.81% (95% CI, 2.24−3.38%). Keloids were identified in seven boys and four girls, accounting for 0.33% of the children (95% CI, 0.13−0.53%). Three children had vitiligo (prevalence rate, 0.09%; 95% CI, 0−0.19%). The prevalence of fungal infection including tinea nigra, tinea versicolor and tinea corporis was 0.24% (95% CI, 0.07−0.41%). Neither alopecia areata nor psoriasis was identified. Conclusion: Compared with our previous study in Kaohsiung County using similar methodology, the point prevalence of atopic dermatitis and ephelides was significantly higher whereas that of fungal infection was lower in Penghu. Unexpectedly, tinea nigra was not rare in Penghu. [Copyright &y& Elsevier]