The findings on the association between fish intake and the risk of heart failure (HF) have been inconsistent. The purpose of this study was to clarify this potential association. We searched for relevant studies in the PubMed database through January 2012 and manually reviewed references. Five independent prospective cohort studies involving 5,273 cases and 144,917 participants were included. The summary relative risk estimates (SRRE) based on the highest compared with the lowest category of fish consumption were estimated by variance-based meta-analysis. In addition, we performed sensitivity and dose-response analyses to examine the association. Overall, an absence of an association between fish intake and HF was observed (SRRE=1.00; 95% CI, 0.81–1.24). However, fried fish intake positively associated with HF (SRRE=1.40; 95% CI, 1.22–1.61). In addition, dose-response analysis of fried fish suggested that each increment of six fried fish per month corresponded to a 37% increase of HF rate (RR=1.37; 95% CI, 1.20–1.56). In conclusion, our findings suggest that there is no significant association between fish intake and risk of HF, with the exception of a possible positive correlation with individuals comsuming fried fish, based on a limited number of studies. Future studies are required to confirm these findings.
fish; nutrition; heart failure; meta-analysis
Recent studies reported that rs2252004 at 10q26 was significantly associated with prostate cancer (PCa) risk in a Japanese population and was subsequently confirmed in a Chinese population. We aimed to assess the relationship between this locus and risk/aggressiveness of benign prostatic hyperplasia (BPH). The current study included 426 BPH cases and 1,008 controls from Xinhua Hospital in Shanghai, China. All BPH patients were treated with α-adrenergic blockers and 5α-reductase inhibitors for at least 9 months. Associations between rs2252004 and BPH risk/aggressiveness were tested using logistic regression. Associations between rs2252004 and clinical parameters including International Prostate Symptom Score (IPSS), total prostate volume (TPV), total PSA (tPSA), and free PSA (fPSA) were evaluated by linear regression. Allele “A” in rs2252004 was significantly associated with increased risk for aggressiveness of BPH in a Chinese population (OR = 1.42, 95% CI: 1.04–1.96, P = 0.03). Patients with the genotype “A/A” (homozygous minor allele) had an increase of IPSS and TPV after treatment (P = 0.045 and 0.024, resp.). No association was observed between rs2252004, BPH risk, and baseline clinicopathological traits (All P > 0.05). Our study is the first to show that rs2252004 at 10q26 was associated with BPH aggressiveness and efficacy of BPH treatment.
The retina is a light-sensitive tissue of the central nervous system that is vulnerable to ischemia. The pathological mechanism underlying retinal ischemic injury is not fully understood. The purpose of this study was to investigate structural and functional changes of different types of rat retinal neurons and visual behavior following transient global ischemia. Retinal ischemia was induced using a 4-vessel occlusion model. Compared with the normal group, the number of βIII-tubulin positive retinal ganglion cells and calretinin positive amacrine cells were reduced from 6 h to 48 h following ischemia. The number of recoverin positive cone bipolar cells transiently decreased at 6 h and 12 h after ischemia. However, the fluorescence intensity of rhodopsin positive rod cells and fluorescent peanut agglutinin positive cone cells did not change after reperfusion. An electroretinogram recording showed that the a-wave, b-wave, oscillatory potentials and the photopic negative response were completely lost during ischemia. The amplitudes of the a- and b-waves were partially recovered at 1 h after ischemia, and returned to the control level at 48 h after reperfusion. However, the amplitudes of oscillatory potentials and the photopic negative response were still reduced at 48 h following reperfusion. Visual behavior detection showed there was no significant change in the time spent in the dark chamber between the control and 48 h group, but the distance moved, mean velocity in the black and white chambers and intercompartmental crosses were reduced at 48 h after ischemia. These results indicate that transient global ischemia induces dysfunction of retinal ganglion cells and amacrine cells at molecular and ERG levels. However, transient global ischemia in a 17 minute duration does not appear to affect photoreceptors.
The current study presents the case of a patient with a rare adverse event characterized by sudden vision loss in the untreated eye following an intravitreal injection of bevacizumab for neovascular glaucoma (NVG). The patient was diagnosed with NVG refractory to Ahmed glaucoma valve implantation and a vitreous hemorrhage in the right eye, which was treated with 1.25 mg intravitreal bevacizumab. Ten days after the bevacizumab injection, the left eye exhibited sudden visual loss. The patient’s best-corrected visual acuity (BCVA) decreased from 80 to 25 letters [Early Treatment Diabetic Retinopathy Study (ETDRS) chart]. A fundus examination revealed a swollen optic disk with unclear boundaries, retinal hemorrhages and thinning retinal vessels. Fundus fluorescein angiography (FA) identified hyperfluorescence in the optic disk and an enlarged foveal avascular zone. The visual field revealed quadrantal defects that confirmed the diagnosis of anterior ischemic optic neuropathy associated with ischemic maculopathy. Six months later, following medical treatment, the patient’s BCVA was increased to 44 letters. However, a clinical examination found neovessels with one papilla disk (PD) above the disk. Laser photocoagulation treatment was administered immediately. The area of neovessels above the disk was reduced to 1/4 PD at the last follow-up. In conclusion, although intravitreal anti-vascular endothelial growth factor (Bevacizumab) is an effective treatment for neovascular ocular diseases, its adverse effects must be taken into consideration for the treatment of NVG. Photocoagulation remains an effective treatment for proliferative diabetic retinopathy.
anti-vascular endothelial growth factor; neovascular glaucoma; bevacizumab; anterior ischemic optic neuropathy
Age-related macular degeneration (AMD) is the main cause of blindness and the curative options are limited. The objective of this meta-analysis was to determine the association between aspirin use and risk of AMD.
A comprehensive literature search was performed in PubMed, Embase, Web of Science, and reference lists. A meta-analysis was performed by STATA software.
Ten studies involving 171729 individuals examining the association between aspirin use and risk of AMD were included. Among the included studies, 2 were randomized-controlled trials (RCTs), 4 were case-control studies and 4 were cohort studies. The relative risks (RRs) were pooled using a random-effects model. Relative risks with 95% confidence intervals (CIs) of aspirin use as a risk for AMD. The pooled RR of 10 included studies between the use of aspirin and risk of AMD was 1.09 (95% CI, 0.96–1.24). The same result was detected in early and late stage AMD subgroup analysis. In the subgroup analyses, the pooled RR of RCTs, case-control studies and cohort studies were 0.81 (95% CI, 0.64–1.02), 1.02 (95% CI, 0.92–1.14) and 1.08 (95% CI, 0.91–1.28), respectively.
The use of aspirin was not associated with the risk of AMD.
Background and aims: Large artery stiffness and endothelial dysfunction are the predominant characteristic of isolated systolic hypertension. Recently studies have revealed MMP1, 3, 9 and TIMP3 Genes polymorphism were associated with arterial stiffness, but the relationship with isolated systolic hypertension were not further studied. This study was to investigate the associations of MMP1,3,9 and TIMP3 Genes polymorphism with isolated systolic hypertension. Methods: We identified the genotype of the genes in 503 patients with isolated systolic hypertension, 481 essential hypertension patients with elevated diastolic blood pressure and 244 age-matched normotensive controls for 5 SNPs and detected the brachial-ankle pulse wave velocity, flow-mediated dilatation, endothelin-1 and nitric oxide among the participants. Results: Multinomial logistic analyses showed that the 5A allele of rs3025058(5A/6A) in MMP3 and the T allele of rs3918242(C-1562T) in MMP9 were significantly associated with isolated systolic hypertension after adjusted by age, triglyceride, low-density lipoprotein (P<0.001, Pcorr<0.003; P=0.009, Pcorr=0.027). The 5A/G/C and 6A/A/T haplotypes were significantly associated with isolated systolic hypertension (Permutation p=0.0258; Permutation p=0.000002). In addition, the brachial-ankle pulse wave velocity of different genotypes for the 5A/6A and C-1562T polymorphisms was significantly highest in 5A or T homozygotes (P<0.01), however, the flow-mediated dilatation and nitric oxide were markedly lowest in 5A or T homozygotes (P<0.01). Conclusion: MMP3 and MMP9 genes variant seem to contribute to the development of isolated systolic hypertension by affecting arterial stiffness and endothelial function.
artery stiffness; endothelial function; gene; isolated systolic hypertension; polymorphism.
The opinion of application of indocyanine green (ICG) in the macular hole surgery was contradictory. Here we conducted a meta-analysis to evaluate the effect of in internal limiting membrane (ILM) peeling for macular hole surgery.
Methods and Findings
We searched electronic databases for comparative studies published before July 2012 of ILM peeling with and without ICG. Twenty-two studies including 1585 eyes were included. Visual acuity (VA) improvement, including the postoperative rate of ≥20/40 VA gained (OR, 0.65; 95% CI, 0.43 to 0.97; P = 0.033) and increased LogMAR (WMD, −0.09; 95% CI, −0.16 to −0.02; P = 0.011), was less in the ICG group. The risk of visual field defects was greater in the ICG group than in the non-ICG group. There was no significant difference in the rate of anatomical outcomes between ILM peeling procedures performed with and without ICG. RPE changes and other postoperative complications were not significantly different between the ICG and non-ICG groups. An additional analysis showed that the VA improvement of the ICG group was less than the non-ICG group only within the first year of follow up. A subgroup analysis showed that the rate of VA improvement was lower in the ICG group than in other adjuncts group. A higher rate of secondary closure and less VA improvement were observed in a high proportion (>0.1%) of the ICG group. A sensitivity analysis after the randomized-controlled trials were excluded from the meta-analysis demonstrated no differences compared with the overall results.
This meta-analysis demonstrated that there is no evidence of clinical superiority in outcomes for ICG-assisted ILM peeling procedure over the non-ICG one. The toxicity of ICG should be considered when choosing the various staining methods.
Specific interactions of growth factors with heparan sulfate are thought to regulate stages of branching morphogenesis in developing mammalian organs, but the evidence derives mostly from studies of explanted tissues or cell culture. We recently provided in vivo evidence that inactivation of Ndst1, the predominant N-deacetylase/N-sulfotransferase gene essential for the formation of mature heparan sulfate, results in a highly specific defect in murine lobuloalveolar development. Here, we demonstrate a highly penetrant dramatic defect in primary branching by mammary epithelial-specific inactivation of Ext1, a subunit of the copolymerase complex that catalyzes the formation of the heparan sulfate chain. In contrast to Ext1 deletion, inactivation of Hs2st (which encodes an enzyme required for 2-O-sulfation of uronic acids in heparan sulfate) did not inhibit ductal formation but displayed markedly decreased secondary and ductal side-branches as well as fewer bifurcated terminal end buds. Targeted conditional deletion of c-Met, the receptor for HGF, in mammary epithelial cells showed similar defects in secondary and ductal side-branching, but did not result in any apparent defect in bifurcation of terminal end buds. Although there is published evidence indicating a role for 2-O sulfation in HGF binding, primary epithelial cells isolated from Hs2st conditional deletions were able to activate Erk in the presence of HGF and there appeared to be only a slight reduction in HGF-mediated c-Met phosphorylation in these cells compared to control. Thus, both c-Met and Hs2st play important, but potentially independent, roles in secondary and ductal side-branching. When considered together with previous studies of Ndst1-deficient glands, the data presented here raise the possibility of partially-independent regulation by heparan sulfate-dependent pathways of primary ductal branching, terminal end bud bifurcation, secondary branching, ductal side-branching and lobuloalveolar formation.
sulfotransferase; heparan sulfate; proteoglycans; branching morphogenesis; growth factor signaling
The aim of this research was to assess the value of the transitional zone index (TZI) and intravesical prostatic protrusion (IPP) from transrectal ultrasonography in evaluating the severity and progression of disease by analyzing the relationship between the 2 parameters and symptoms, clinical history, and urodynamics in benign prostatic hyperplasia (BPH) patients undergoing different treatment.
Materials and Methods
A total of 203 patients receiving medication and 162 patients who underwent transurethral resection of the prostate because of BPH were enrolled in this retrospective analysis. The clinical history and subjective and objective examination results of all patients were recorded and compared after being classified by TZI and IPP level. Linear regression was used to find correlations between IPP, TZI, and urodynamics.
The 2 parameters were found to differ significantly between patients receiving medication and patients undergoing surgical therapy (p<0.05). PSA, maximum flow rate (Qmax), detrusor pressure at Qmax (PdetQmax), and the bladder outlet obstruction index (BOOI) differed according to various TZI levels (p<0.05). In addition, the voiding symptom score, Qmax, and BOOI of subgroups with various IPP levels were also significantly different (p<0.05). Both TZI and IPP had significant effects on Qmax, BOOI, and PdetQmax (p<0.05) and the incidence of acute urinary retention (p=0.000).
The results demonstrated that both TZI and IPP had favorable value for assessing severity and progression in patients with BPH. Further studies are needed to confirm whether the two parameters have predictive value in the efficacy of BPH treatment and could be considered as factors in the selection of therapy.
Benign prostatic hyperplasia; Medication; Transurethral resection of the prostate; Ultrasonography; Urodynamics
Visceral leishmaniasis (VL) is endemic in western China, and becoming an important public health concern. Infected dogs are the main reservoir for Leishmania infantum, and a potential sentinel for human VL in endemic areas. In the present study we investigated the prevalence of Leishmania DNA in dogs from Wenchuan, Heishui and Jiuzhaigou County in Sichuan Province, southwestern China, which are important endemic areas of zoonotic VL, detected by real time PCR. The results will help to design control strategies against visceral leishmaniasis in dogs and humans.
The overall prevalence of Leishmania DNA in dogs was 24.8% (78/314) in Sichuan Province, with the positive rate of 23.5% (23/98) in Wenchuan County, 28.2% (20/71) in Heishui County, and 24.1% (35/145) in Jiuzhaigou County, and no significant difference was observed among the three counties (P > 0.05). The dogs were further allocated to different groups based on sexes, ages and external clinical symptoms. The logistic regression analysis revealed that a higher prevalence was found in older and external symptomatic dogs, compared to that of younger and asymptomatic dogs (P < 0.05).
The results revealed that L. infantum infection in dogs is widespread in Sichuan Province, southwestern China, which has a public health significance, due to its contribution to the transmission of the infection to humans by sandflies. It is necessary to take measures, including treatment or eradication of infected dogs, to control canine leishmaniasis, which could be helpful to reduce human VL in this area.
Leishmania; Dogs; Prevalence; Real time PCR; China
Certain microbes invade brain microvascular endothelial cells (BMECs) to breach the blood-brain barrier (BBB) and establish central nervous system (CNS) infection. Here we use the leading meningitis pathogen group B Streptococcus (GBS) together with insect and mammalian infection models to probe a potential role of glycosaminoglycan (GAG) interactions in the pathogenesis of CNS entry. Site-directed mutagenesis of a GAG-binding domain of the surface GBS alpha C protein impeded GBS penetration of the Drosophila BBB in vivo and diminished GBS adherence to and invasion of human BMECs in vitro. Conversely, genetic impairment of GAG expression in flies or mice reduced GBS dissemination into the brain. These complementary approaches identify a role for bacterial-GAG interactions in the pathogenesis of CNS infection. Our results also highlight how the simpler yet genetically conserved Drosophila GAG pathways can provide a model organism to screen candidate molecules that can interrupt pathogen-GAG interactions for future therapeutic applications.
Streptococcus agalactiae (Group B Streptococcus, GBS) is a leading cause of meningitis in human newborn infants. The bacterial and host factors that allow this pathogen to cross the blood-brain barrier (BBB) and cause central nervous system (CNS) infection are not well understood. Here we demonstrate that GBS expresses a specific protein on its surface that can bind to sugar molecules known as glycosaminoglycans (GAGs) on the surface of brain capillary cells, initiating infection of the BBB. Fruit flies or mice genetically engineered to have reduced GAGs showed decreased dissemination of GBS into the brain tissues following experimental infection. Our results identify a role for bacterial-GAG interactions in the pathogenesis of newborn meningitis and highlight how the simpler yet genetically conserved fruit fly GAG biosynthetic pathways make the fruit fly a good model organism to screen candidate molecules that can interrupt pathogen-GAG interactions for future therapeutic applications.
This study aims to evaluate immunization with polymeric microparticles containing recombinant antigen 85B (rAg85B) delivered directly to the lungs to protect against tuberculosis. rAg85B was expressed in Escherichia coli and encapsulated in poly(lactic-co-glycolic acid) microparticles (P-rAg85B). These were delivered as dry powders to the lungs of guinea pigs in single or multiple doses of homologous and heterologous antigens. Bacille Calmette–Guérin (BCG) delivered subcutaneously was employed as the positive control and as part of immunization strategies. Immunized animals were challenged with a low-dose aerosol of Mycobacterium tuberculosis (MTB) H37Rv to assess the extent of protection measured as reduction in bacterial burden (CFU) in the lungs and spleens of guinea pigs. Histopathological examination and morphometric analysis of these tissues were also performed. The heterologous strategy of BCG prime–P-rAg85B aerosol boosts appeared to enhance protection from bacterial infection, as indicated by a reduction in CFU in both the lungs and spleens compared with untreated controls. Although the CFU data were not statistically different from the BCG and BCG–BCG groups, the histopathological and morphometric analyses indicated the positive effect of BCG–P-rAg85B in terms of differences in area of tissue affected and number and size of granulomas observed in tissues. P-rAg85B microparticles appeared to be effective in boosting a primary BCG immunization against MTB infection, as indicated by histopathology and morphometric analysis. These encouraging observations are relevant to boosting adults previously immunized with BCG or exposed to MTB, commonly the case in the developing world, and should be followed by further assessment of an appropriate immunization protocol for maximum protection.
antigen 85B; BCG; boost immunization; microparticles; pulmonary delivery
The biosynthesis of heparan sulfate (HS), an essential glycan in many organisms, involves an array of specialized sulfotransferases. Here, we present a study aimed at engineering the substrate specificity of different HS 3-O-sulfotransferase isoforms. Based on the crystal structures, we identified a pair of amino acid residues responsible for selecting the substrates. Mutations at these residues altered the substrate specificities. Our results demonstrated the feasibility of tailoring the specificity of sulfotransferases to modify HS with desired functions.
Herpes simplex virus type 1 (HSV-1) infection of the corneal stroma remains a major cause of blindness. Primary cultures of corneal fibroblasts (CF) were tested and found susceptible to HSV-1 entry, which was confirmed by deconvolution imaging of infected cells. Plaque assay and real-time PCR demonstrated viral replication and hence a productive infection of CF by HSV-1. A role for glycoprotein D (gD) receptors in cultured CF was determined by gD interference assay. Reverse transcription-PCR analysis indicated expression of herpesvirus entry mediator and 3-O-sulfated (3-OS) heparan sulfate (HS)-generating enzyme 3-O sulfotransferase 3 (3-OST-3) but not nectin-1 or nectin-2. Subsequently, HS isolated from these cells was found to contain two distinct disaccharides (IdoUA2S-AnMan3S and IdoUA2S-AnMan3S6S) that are representative of 3-OST-3 activity. The following lines of evidence supported the important role of 3-OS HS as the mediator of HSV-1 entry into CF. (i) Blockage of entry was observed in CF treated with heparinases. The same enzymes had significantly less effect on HeLa cells that use nectin-1 as the entry receptor. (ii) Enzymatic removal of cell surface HS also removed the major gD-binding receptor, as evident from the reduced binding of gD to cells. (iii) Spinoculation assay demonstrated that entry blockage by heparinase treatment included the membrane fusion step. (iv) HSV-1 glycoprotein-induced cell-to-cell fusion was inhibited by either prior treatment of cells with heparinases or by HS preparations enriched in 3-OS HS. Taken together, the data in this report provide novel information on the role of 3-OS HS in mediating infection of CF, a natural target cell type.