Effect of Control Strategies on Prevalence, Incidence and Re-infection of Clonorchiasis in Endemic Areas of China

Clonorchiasis is a liver fluke disease prevalent in East Asia, which is transmitted to humans mainly by eating raw freshwater fish. It induces various complications in the liver or bile duct including cholelithiasis, cholecystitis, cholangitis, and cirrhosis. Clonorchis sinensis has been known to cause cholangiocarcinoma, and is still a major health problem in endemic areas. People in endemic areas are repeatedly infected with C. sinensis, as they continue to consume raw freshwater fish in spite of control activities and availability of a highly effective drug, praziquantel. Reservoir hosts such as cats, dogs, and pigs supply eggs continuously to the environment and act as a source of infection. The present study analyzed the data produced by the Korea-China collaborative project for helminthiasis control in China during 2001–2004 to find out effective chemotherapeutic control strategies with praziquantel in endemic areas and to evaluate their effects on the transmission of C. sinensis infection by repeated mass or selective treatment. The four-year control trial found that repeated treatment is essential to the effective reduction of prevalence and infection intensity in heavily endemic areas. Mass chemotherapy is more effective than selective treatment, and more repeated treatments produce better outcomes in clonorchiasis control. Health education to change the habit of consuming raw or undercooked fish is an important and practical measure to prevent and reduce human infections in endemic areas. Together with chemotherapy, health education could be highly effective and produce sustainable effects in clonorchiasis control. Treatment of reservoirs, if applicable, will contribute to reduce the source of infection

Botulinum toxin injection versus lateral internal sphincterotomy in the treatment of chronic anal fissure: a non-randomized controlled trial

BACKGROUND: Although lateral internal sphincterotomy is the gold-standard treatment for chronic anal fissure, intrasphincteric injection of botulinum toxin seems to be a reliable new option. The aim of this non-randomized study is to compare the effect of lateral internal sphincterotomy and botulinum toxin injection treatments on the outcome and reduction of anal sphincter pressures in patients with chronic anal fissure. METHODS: Patients with chronic anal fissure were treated with either botulinum toxin injection or lateral internal sphincterotomy by their own choice. Maximal resting pressure and maximal squeeze pressure measurements were performed before and 2 weeks after treatments by anal manometry. Patients were followed for fissure relapse during 14 months. RESULTS: Twenty-one consecutive outpatients with posterior chronic anal fissure were enrolled. Eleven patients underwent surgery and ten patients received botulinum toxin injection treatment. Before the treatment, anal pressures were found to be similar in both groups. After the treatment, the maximal resting pressures were reduced from 104 ± 22 mmHg to 86 ± 15 mmHg in the surgery group (p < 0.05) and from 101 ± 23 mmHg to 83 ± 24 mmHg in the botulinum toxin group (p < 0.05). The mean maximal squeeze pressures were reduced from 70 ± 27 mmHg to 61 ± 32 mmHg (p > 0.05) in the surgery group, and from 117 ± 62 mmHg to 76 ± 34 (p < 0.01) in the botulinum toxin group. The fissures were healed in 70 percent of patients in the botulinum group and 82 percent in the surgery group (p > 0.05). There were no relapses during the 14 months of follow up. CONCLUSION: Lateral internal sphincterotomy and botulinum toxin injection treatments both seem to be equally effective in the treatment of chronic anal fissure

A lack of association between adiponectin polymorphisms and coronary artery disease in a Chinese population

We investigated the association between two single nucleotide polymorphisms (SNPs) in the adiponectin gene (rs822395 and rs266729) and coronary artery disease (CAD) in a case-control study of 198 unrelated Chinese CAD patients (with ≥ 70% coronary stenosis or previous myocardial infarction) and 237 non-CAD controls. The ligase reaction was used to detect SNPs rs822395 and rs266729, and the allelic association of these SNPs with the occurrence and severity of CAD was assessed. There were no significant differences in the genotypic or allelic frequencies of the two SNPs between control and CAD individuals. In addition, there was no association between the two SNPs and the severity of CAD based on the number of diseased vessels. The frequencies of alleles C and G at rs266729 differed significantly between females in the CAD and control groups, but not between males. Female carriers of allele G at rs266729 had a higher risk of CAD compared with allele C carriers (OR = 1.30, 95% CI: 1.09-2.64, p = 0.02). These results indicate a gender-specific effect of the adiponectin gene rs266729 variant in modulating the risk of CAD in women

LBH589, a deacetylase inhibitor, induces apoptosis in adult T-cell leukemia/lymphoma cells via activation of a novel RAIDD-caspase-2 pathway

Adult T-cell leukemia/lymphoma (ATLL), an aggressive neoplasm etiologically associated with human T-lymphotropic virus type-1 (HTLV-1), is resistant to treatment. In this study, we examined the effects of a new inhibitor of deacetylase enzymes, LBH589, on ATLL cells. LBH589 effectively induced apoptosis in ATLL-related cell lines and primary ATLL cells and reduced the size of tumors inoculated in SCID mice. Analyses, including with a DNA microarray, revealed that neither death receptors nor p53 pathways contributed to the apoptosis. Instead, LBH589 activated an intrinsic pathway through the activation of caspase-2. Furthermore, small interfering RNA experiments targeting caspase-2, caspase-9, RAIDD, p53-induced protein with a death domain (PIDD) and RIPK1 (RIP) indicated that activation of RAIDD is crucial and an event initiating this pathway. In addition, LBH589 caused a marked decrease in levels of factors involved in ATLL cell proliferation and invasion such as CCR4, IL-2R and HTLV-1 HBZ-SI, a spliced form of the HTLV-1 basic zipper factor HBZ. In conclusion, we showed that LBH589 is a strong inducer of apoptosis in ATLL cells and uncovered a novel apoptotic pathway initiated by activation of RAIDD

A Piezoelectric Immunosensor Using Hybrid Self-Assembled Monolayers for Detection of Schistosoma japonicum

BACKGROUND: The parasite Schistosoma japonicum causes schistosomiasis disease, which threatens human life and hampers economic and social development in some Asian countries. An important lesson learned from efforts to reduce the occurrence of schistosomiasis is that the diagnostic approach must be altered as further progress is made towards the control and ultimate elimination of the disease. METHODOLOGY/PRINCIPAL FINDINGS: Using mixed self-assembled monolayer membrane (mixed SAM) technology, a mixture of mercaptopropionic acid (MPA) and mercaptoethanol (ME) was self-assembled on the surface of quartz crystals by gold-sulphur-bonds. Soluble egg antigens (SEA) of S. japonicum were then cross-linked to the quartz crystal using a special coupling agent. As compared with the traditional single self-assembled monolayer immobilization method, S. japonicum antigen (SjAg) immobilization using mixed self-assembled monolayers exhibits much greater immunoreactivity. Under optimal experimental conditions, the detection range is 1:1500 to 1:60 (infected rabbit serum dilution ratios). We measured several infected rabbit serum samples with varying S. japonicum antibody (SjAb) concentrations using both immunosensor and ELISA techniques and then produced a correlation analysis. The correlation coefficients reached 0.973. CONCLUSIONS/SIGNIFICANCE: We have developed a new, simple, sensitive, and reusable piezoelectric immunosensor that directly detects SjAb in the serum. This method may represent an alternative to the current diagnostic methods for S. japonicum infection in the clinical laboratory or for analysis outside the laboratory

Immunohistochemical expression of insulin-like growth factor binding protein-3 in invasive breast cancers and ductal carcinoma in situ: implications for clinicopathology and patient outcome

INTRODUCTION: Insulin-like growth factor binding protein-3 (IGFBP-3) differentially modulates breast epithelial cell growth through insulin-like growth factor (IGF)-dependent and IGF-independent pathways and is a direct (IGF-independent) growth inhibitor as well as a mitogen that potentiates EGF (epidermal growth factor) and interacts with HER-2. Previously, high IGFBP-3 levels in breast cancers have been determined by enzyme-linked immunosorbent assay and immunoradiometric assay methods. In vitro, IGFBP-3's mechanisms of action may involve cell membrane binding and nuclear translocation. To evaluate tumour-specific IGFBP-3 expression and its subcellular localisation, this study examined immunohistochemical IGFBP-3 expression in a series of invasive ductal breast cancers (IDCs) with synchronous ductal carcinomas in situ (DCIS) in relation to clinicopathological variables and patient outcome. METHODS: Immunohistochemical expression of IGFBP-3 was evaluated with the sheep polyclonal antiserum (developed in house) with staining performed as described previously. RESULTS: IGFBP-3 was evaluable in 101 patients with a variable pattern of cytoplasmic expression (positivity of 1+/2+ score) in 85% of invasive and 90% of DCIS components. Strong (2+) IGFBP-3 expression was evident in 32 IDCs and 40 cases of DCIS. A minority of invasive tumours (15%) and DCIS (10%) lacked IGFBP-3 expression. Nuclear IGFBP-3 expression was not detectable in either invasive cancers or DCIS, with a consistent similarity in IGFBP-3 immunoreactivity in IDCs and DCIS. Positive IGFBP-3 expression showed a possible trend in association with increased proliferation (P = 0.096), oestrogen receptor (ER) negativity (P = 0.06) and HER-2 overexpression (P = 0.065) in invasive tumours and a strong association with ER negativity (P = 0.037) in DCIS. Although IGFBP-3 expression was not an independent prognosticator, IGFBP-3-positive breast cancers may have shorter disease-free and overall survivals, although these did not reach statistical significance. CONCLUSIONS: Increased breast epithelial IGFBP-3 expression is a feature of tumorigenesis with cytoplasmic immunoreactivity in the absence of significant nuclear localisation in IDCs and DCIS. There are trends between high levels of IGFBP-3 and poor prognostic features, suggesting that IGFBP-3 is a potential mitogen. IGFBP-3 is not an independent prognosticator for overall survival or disease-free survival, to reflect its dual effects on breast cancer growth regulated by complex pathways in vivo that may relate to its interactions with other growth factors

Mitochondrial division inhibitor-1 is neuroprotective in the A53T-α-synuclein rat model of Parkinson’s disease

Alpha-synuclein (α-syn) is involved in both familial and sporadic Parkinson’s disease (PD). One of the proposed pathogenic mechanisms of α-syn mutations is mitochondrial dysfunction. However, it is not entirely clear the impact of impaired mitochondrial dynamics induced by α-syn on neurodegeneration and whether targeting this pathway has therapeutic potential. In this study we evaluated whether inhibition of mitochondrial fission is neuroprotective against α-syn overexpression in vivo. To accomplish this goal, we overexpressed human A53T-α- synuclein (hA53T-α-syn) in the rat nigrostriatal pathway, with or without treatment using the small molecule Mitochondrial Division Inhibitor-1 (mdivi-1), a putative inhibitor of the mitochondrial fission Dynamin-Related Protein-1 (Drp1). We show here that mdivi-1 reduced neurodegeneration, α-syn aggregates and normalized motor function. Mechanistically, mdivi-1 reduced mitochondrial fragmentation, mitochondrial dysfunction and oxidative stress. These in vivo results support the negative role of mutant α-syn in mitochondrial function and indicate that mdivi-1 has a high therapeutic potential for PD