Expression profile of the Schistosoma japonicum degradome reveals differential protease expression patterns and potential anti-schistosomal intervention targets.

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Shuai Liu

2014-10-01

Full Text Available Blood fluke proteases play pivotal roles in the processes of invasion, nutrition acquisition, immune evasion, and other host-parasite interactions. Hundreds of genes encoding putative proteases have been identified in the recently published schistosome genomes. However, the expression profiles of these proteases in Schistosoma species have not yet been systematically analyzed. We retrieved and culled the redundant protease sequences of Schistosoma japonicum, Schistosoma mansoni, Echinococcus multilocularis, and Clonorchis sinensis from public databases utilizing bioinformatic approaches. The degradomes of the four parasitic organisms and Homo sapiens were then comparatively analyzed. A total of 262 S. japonicum protease sequences were obtained and the expression profiles generated using whole-genome microarray. Four main clusters of protease genes with different expression patterns were identified: proteases up-regulated in hepatic schistosomula and adult worms, egg-specific or predominantly expressed proteases, cercaria-specific or predominantly expressed proteases, and constantly expressed proteases. A subset of protease genes with different expression patterns were further validated using real-time quantitative PCR. The present study represents the most comprehensive analysis of a degradome in Schistosoma species to date. These results provide a firm foundation for future research on the specific function(s of individual proteases and may help to refine anti-proteolytic strategies in blood flukes.

The temperature--dependent expression of GST of Schistosoma japonicum (Philippine strain).

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Cai, Z H; Song, G C; Xu, Y X; Liu, S X

1993-03-01

Obtained from pSj5, the cDNA gene encoding GST antigen of Schistosoma japonicum (Philippine strain) was ligated with efficient temperature-dependent PBV220 vector which was constructed in CAPM, and then introduced into host bacterium-DH5 alpha (E. coli) by transformation. Transformants were selected by ampicillin and recombinant clones were identified by restriction mapping. The result showed that recombinant clone 43 was the one carrying recombinant plasmid PBV 220 with the correct insertion of the gene fragment. The GST expression ability of clone 43 was investigated by GST enzymic activity assay and SDS-PAGE. A relatively high level of GST enzymic activity was expressed by this clone under the temperature-dependent condition, that is, cultured at 30 degrees C and expressed at 42 degrees C. A more strongly stained 26 kDa protein band was identified by SDS-PAGE. The result indicated that GST of S. japonicum (Philippine strain) could be expressed not only by IPTG induction, but also by the temperature-dependent method.

Field testing of Schistosoma japonicum DNA vaccines in cattle in China.

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Shi, Fuhui; Zhang, Yaobi; Lin, Jiaojiao; Zuo, Xin; Shen, Wei; Cai, Yiumin; Ye, Ping; Bickle, Quentin D; Taylor, Martin G

2002-11-01

Vaccines are needed to reduce the zoonotic reservoir of Schistosoma japonicum infection in bovines in China. We have developed two experimental DNA vaccines and have already shown these to be capable of inducing partial protection in water buffalo naturally exposed to the risk of S. japonicum infection in the field. We now report a similar field trial in cattle, the other major bovine reservoir host species in China. Groups of cattle were vaccinated with the VRSj28 vaccine or the VRSj23 vaccine, or, to test whether protection could be enhanced by combination vaccination, with both these DNA vaccines together. After vaccination, the cattle were exposed to natural infection in the field for a period of 54 days. Worm and egg counts carried out at the end of the experiment showed that each of the vaccine groups showed partial resistance, and that combined vaccination was not more effective than vaccination with the individual plasmids.

Studies on Antigenic Communities between the Yamanashi and Chinese Strains of Schistosoma japonicum Eggs and Oncomelania Snails by Immunoelectrophoresis

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Iwanaga, Yuzuru; Tsuji, Moriyasu; Tanaka, Noriyasu

1988-01-01

Antigenic communities were studied with sera from rabbits immunized with the Yamanashi and Chinese strains of Schistosoma japonicum eggs, and the antigens of five subspecies of Oncomelania snails, by immunoelectrophoresis. With regard to antigenic communities defined by the Yamanashi strain of S. japonicum eggs and Oncomelania snails, the schistosome egg produced 5 to 6 bands with Oncomelania hupensis nosophora, 3 to 4 bands with O.h.hupensis, 3 bands with O.h.chiui, 2 bands with O.h.quad...

Detection of the circulating antigen 14-3-3 protein of Schistosoma japonicum by time-resolved fluoroimmunoassay in rabbits

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Wang Jie

2011-05-01

Full Text Available Abstract Background Schistosomiasis remains a major public health concern that afflicts millions of people worldwide. Low levels of Schistosoma infection require more sensitive diagnostic methods. In this study, a time-resolved fluoroimmunoassay (TRFIA was developed for detecting the signal transduction protein 14-3-3, a circulating antigen of Schistosoma japonicum. Results The detection limit of 14-3-3-TRFIA was 0.78 ng/ml, with a linear measurement range from 0.78 to 800 ng/ml. The average intra-assay and inter-assay variability of this TRFIA was 8.9% and 12.2% respectively, and the mean recovery rate ranged from 92.1% to 115.5%. Within the first 21 days post-infection in rabbits, the positive rates of the 14-3-3-TRFIA were distinctly higher compared to ELISA. All these findings illustrate that 14-3-3-TRFIA has a higher detection efficacy and is a good early diagnostic method for active Schistosoma infection. Conclusions A sandwich TRFIA for detecting the circulating antigen 14-3-3 of S. japonicum has been developed, and has demonstrated to be a good potential diagnostic method for schistosomiasis.

Polymorphic microsatellites in the human bloodfluke, Schistosoma japonicum, identified using a genomic resource

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Spear Robert

2011-02-01

Full Text Available Abstract Re-emergence of schistosomiasis in regions of China where control programs have ceased requires development of molecular-genetic tools to track gene flow and assess genetic diversity of Schistosoma populations. We identified many microsatellite loci in the draft genome of Schistosoma japonicum using defined search criteria and selected a subset for further analysis. From an initial panel of 50 loci, 20 new microsatellites were selected for eventual optimization and application to a panel of worms from endemic areas. All but one of the selected microsatellites contain simple tri-nucleotide repeats. Moderate to high levels of polymorphism were detected. Numbers of alleles ranged from 6 to 14 and observed heterozygosity was always >0.6. The loci reported here will facilitate high resolution population-genetic studies on schistosomes in re-emergent foci.

Nested-PCR assay for detection of Schistosoma japonicum infection in domestic animals.

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Zhang, Xin; He, Chuan-Chuan; Liu, Jin-Ming; Li, Hao; Lu, Ke; Fu, Zhi-Qiang; Zhu, Chuan-Gang; Liu, Yi-Ping; Tong, Lai-Bao; Zhou, De-Bao; Zha, Li; Hong, Yang; Jin, Ya-Mei; Lin, Jiao-Jiao

2017-04-13

Schistosomiasis japonica is a common zoonosis. Domestic animals are the primary source of infection and play an important role in disease transmission. The prevalence and infectivity of this disease in domestic animals in China have significantly decreased and, for this reason, diagnostics with a higher sensitivity have become increasingly necessary. It was reported that polymerase chain reaction (PCR)-based methods could be used to detect schistosome infection in humans and animals and presented a high sensitivity and specificity. The present study aimed to develop a PCR-based method for detection of Schistosoma japonicum infection in domestic animals. A specific nested-PCR assay was developed to detect S. japonicum infection in domestic animals via amplification of a 231-bp DNA fragment of retrotransposon SjR2. The developed assay was first used in sera and dry blood filter paper (DBFP) from goats and buffaloes at different time points of infection. Then, 78 DBFPs from 39 artificially-infected bovines at 14 and 28 days post-infection and 42 DBFPs from schistosome-negative bovines from the city of Huangshan in the Anhui province were used to evaluate the diagnostic validity. Furthermore, this assay was used to detect S. japonicum infection in domestic animals in Dongzhi and Wangjiang counties. The expected PCR product was detected in eggs and adult worms of S. japonicum and blood samples from S. japonicum-infected goats and water buffaloes, but not from Fasciola and Haemonchus contortus worms. The nested-PCR assay could detect the target S. japonicum DNA in DBFPs from goats and buffaloes after day 3 post-infection. The sensitivity in buffaloes at 14 and 28 days post-infection was 92.30% (36/39) and 100% (39/39), respectively. The specificity was 97.60% (41/42). The positivity rates in Dongzhi and Wangjiang counties were 6.00% and 8.00% in bovines and 22.00% and 16.67% in goats, respectively. The positivity rates in goats in both counties were higher than those

Transmission dynamics of Schistosoma japonicum in the lakes and marshlands of China.

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Darren J Gray

Full Text Available Schistosoma japonicum is a major public health concern in China, with over one million people infected and another 40 million living in areas at risk of infection. Unlike the disease caused by S. mansoni and S. haematobium, schistosomiasis japonica is a zoonosis, involving a number of different mammalian species as reservoir hosts. As a result of a number of published reports from China, it has long been considered that bovines, particularly water buffaloes, play a major role in human S. japonicum transmission there, and a drug-based intervention study (1998-2003 around the Poyang Lake in Jiangxi Province provided proof of concept that water buffaloes are, indeed, major reservoirs of human infection in this setting.In this study we incorporated recently obtained epidemiological information to model the steady-state S. japonicum transmission as well as the impact of the removal of S. japonicum transmission attributable to water buffaloes on human infection rates across six different endemic scenarios within three villages in the Dongting (Hunan and Poyang (Jiangxi lakes of southern China. Similar results were obtained for all scenarios. Steady-state S. japonicum infection rates remained constant and human prevalence and incidence were predicted to fall considerably over time. The model showed that the contribution of S. japonicum water buffalo transmission to human infection ranged from 39.1% to 99.1% and predicted that the removal of water buffalo transmission would reduce parasite reproductive rates below 1. This indicates that without the contribution of water buffaloes, S. japonicum transmission is interrupted and unsustainable. These scenarios are generalizable to other endemic villages in the lake and marshland areas of China where a similar cycle of snail infection and infection/reinfection of humans and bovines occurs.Along with previous epidemiological data, our findings strongly support water buffaloes as an important component of the

Taurine drinking ameliorates hepatic granuloma and fibrosis in mice infected with Schistosoma japonicum.

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Yu, Yan-Rong; Ni, Xian-Qiang; Huang, Jie; Zhu, Yong-Hong; Qi, Yong-Fen

2016-04-01

In schistosomiasis, egg-induced hepatic granuloma formation is a cytokine-mediated, predominantly CD4(+) Th2 immune response that can give rise to hepatic fibrosis. Hepatic fibrosis is the main cause of increased morbidity and mortality in humans with schistosome infection. Taurine has various physiological functions and hepatoprotective properties as well as anti-inflammatory and immunomodulatory activity. However, little is known about the role of taurine in schistosome egg-induced granuloma formation and fibrosis. We aimed to evaluate the therapeutic potential of taurine as preventative treatment for Schistosoma japonicum infection. Mice infected with S. japonicum cercariae were supplied with taurine drinking water (1% w/v) for 4 weeks starting at 4 weeks post-infection. Taurine supplementation significantly improved the liver pathologic findings, reduced the serum levels of aminotransferases and area of hepatic granuloma, and prevented fibrosis progression. In addition, taurine decreased the expression of the granulomatous and fibrogenic mediators transforming growth factor β1, tumor necrosis factor α, monocyte chemotactic protein 1α and macrophage inflammatory protein 1α as well as the endoplasmic reticulum stress marker glucose-regulated protein 78. Thus, taurine can significantly attenuate S. japonicum egg-induced hepatic granuloma and fibrosis, which may depend in part on the downregulation of some relevant cytokine/chemokines and reducing the endoplasmic reticulum stress response.

Vitamin E reduces hepatic fibrosis in mice with Schistosoma japonicum infection.

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Wang, Xuefeng; Zhang, Rongbo; Du, Jiuwei; Hu, Youying; Xu, Lifa; Lu, Jun; Ye, Song

2012-02-01

To investigate whether vitamin E protects against hepatic fibrosis in mice with Schistosoma japonicum infection, 24 pathogen-free Kunming mice were selected and randomly divided into four groups: control (uninfected, untreated), model (infected, untreated), low-dose intervention (infected, vitamin E-treated, 30 mg/g bodyweight/day) and high-dose intervention (infected, vitamin E-treated, 60 mg/g bodyweight/day). Mice were infected with Schistosoma japonicum by inoculating abdominal skin with snail hosts. The activities of malondialdehyde (MDA), superoxide dismutase (SOD), glutathione peroxidase (GPx) and catalase (CAT) were detected in hepatic tissue by colorimetry. The expression levels of laminin (LN), hyaluronic acid (HA), procollagen type Ⅲ (PC-III) and type Ⅳ collagen (IV-C) were detected in the serum by radioimmunoassay. Finally, areas and numbers of granulomas were assessed through histopathology 42 days following treatment. The results revealed that mean areas of granulomas were smaller in the low- and high-dose intervention groups compared to those in the model group. Furthermore, the higher dose of vitamin E resulted in smaller granulomas than the low dose. The levels of LN, HA, PC-III and IV-C in the serum were lower following vitamin E treatment than in the model group. By contrast, activity of SOD, GPx and CAT in hepatic tissue was higher following vitamin E treatment compared to the model group. The activity of MDA was lower in hepatic tissue following vitamin E treatment compared to the model group, but was higher compared to controls. In general, the higher dose of vitamin E affected measurements to a greater extent than the lower dose. In conclusion, vitamin E treatment may reduce the growth of granulomas, slowing the process of hepatic fibrosis, and this effect may be the result of the altered activity of the oxidation-reduction enzyme system.

Comparative Analysis of Proteome-Wide Lysine Acetylation in Juvenile and Adult Schistosoma japonicum

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Qing Li

2017-11-01

Full Text Available Schistosomiasis is a devastating parasitic disease caused by tremotodes of the genus Schistosoma. Eggs produced by sexually mature schistosomes are the causative agents of for pathogenesis and transmission. Elucidating the molecular mechanism of schistosome development and sexual maturation would facilitate the prevention and control of schistosomiasis. Acetylation of lysine is a dynamic and reversible post-translational modification playing keys role in many biological processes including development in both eukaryotes and prokaryotes. To investigate the impacts of lysine acetylation on Schistosoma japonicum (S. japonicum development and sexual maturation, we used immunoaffinity-based acetyllysine peptide enrichment combined with mass spectrometry (MS, to perform the first comparative analysis of proteome-wide lysine acetylation in both female and male, juvenile (18 days post infection, 18 dpi and adult (28 dpi schistosome samples. In total, we identified 874 unique acetylated sites in 494 acetylated proteins. The four samples shared 47 acetylated sites and 46 proteins. More acetylated sites and proteins shared by both females and males were identified in 28 dpi adults (189 and 143, respectively than in 18 dpi schistosomula (76 and 59, respectively. More stage-unique acetylated sites and proteins were also identified in 28 dpi adults (494 and 210, respectively than in 18 dpi schistosomula (73 and 44, respectively. Functional annotation showed that in different developmental stages and genders, a number of proteins involving in muscle movement, glycometabolism, lipid metabolism, energy metabolism, environmental stress resistance, antioxidation, etc., displayed distinct acetylation profiles, which was in accordance with the changes of their biological functions during schistosome development, suggesting that lysine acetylation modification exerted important regulatory roles in schistosome development. Taken together, our data provided the first

Schistosoma japonicum: An ultraviolet-attenuated cercarial vaccine applicable in the field for water buffaloes

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Shi, Y.E.; Jiang, C.F.; Han, J.J.; Li, Y.L.; Ruppel, A.

1990-01-01

Water buffaloes were vaccinated three times with 10,000 Schistosoma japonicum cercariae irradiated with ultraviolet (uv) light at a dose of 400 microW x min/cm2. The irradiation was performed with cheap, simple, and portable equipment in a rural area of Hubei Province (People's Republic of China). A challenge infection of 1000 untreated cercariae was given to six vaccinated and six naive control buffaloes, while two vaccinated animals were not challenged. The experiment was terminated 6 weeks after the challenge. Control animals had lost body weight and harbored a mean of 110 worms and 37 eggs per gram of liver. The vaccinated animals gained weight after the challenge and developed 89% resistance to infection with S. japonicum. Since schistosomiasis japonica is nowadays transmitted in China predominantly by domestic livestock, a uv-attenuated cercarial vaccine for bovines may contribute to the control of this disease

Spatial risk profiling of Schistosoma japonicum in Eryuan county, Yunnan province, China

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Peter Steinmann

2007-11-01

Full Text Available Bayesian spatial risk profiling holds promise to enhance our understanding of the epidemiology of parasitic diseases, and to target interventions in a cost-effective manner. Here, we present findings from a study using Bayesian variogram models to map and predict the seroprevalence of Schistosoma japonicum in Eryuan county, Yunnan province, China, including risk factor analysis. Questionnaire and serological data were obtained through a cross-sectional survey carried out in 35 randomly selected villages with 3,220 people enrolled. Remotely-sensed environmental data were derived from publicly available databases. Bivariate and non-spatial Bayesian multiple logistic regression models were used to identify associations between the local seroprevalence and demographic (i.e. age and sex, environmental (i.e. location of village, altitude, slope, land surface temperature and normalized difference vegetation index and socio-economic factors. In the spatially-explicit Bayesian model, S. japonicum seroprevalence was significantly associated with sex, age and the location of the village. Males, those aged below 10 years and inhabitants of villages situated on steep slopes (inclination ≥20° or on less precipitous slopes of >5° above 2,150 m were at lower risk of seroconversion than their respective counterparts. Our final prediction model revealed an elevated risk for seroconversion in the plains of the eastern parts of Eryuan county. In conclusion, the prediction map can be utilized for spatial targeting of schistosomiasis control interventions in Eryuan county. Moreover, S. japonicum seroprevalence studies might offer a convenient means to assess the infection pressure experienced by local communities, and to improve risk profiling in areas where the prevalence and infection intensities have come down following repeated rounds of praziquantel administration.

High Prevalence of Schistosoma japonicum and Fasciola gigantica in Bovines from Northern Samar, the Philippines

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Gordon, Catherine A.; Acosta, Luz P.; Gobert, Geoffrey N.; Jiz, Mario; Olveda, Remigio M.; Ross, Allen G.; Gray, Darren J.; Williams, Gail M.; Harn, Donald; Li, Yuesheng; McManus, Donald P.

2015-01-01

The cause of zoonotic schistosomiasis in the Philippines is Schistosoma japonicum, which infects up to 46 mammalian hosts, including humans and bovines. In China, water buffaloes have been identified as major reservoir hosts for schistosomiasis japonica, contributing up to 75% of human transmission. In the Philippines, water buffaloes (carabao; Bubalus bubalis carabanesis) have, historically, been considered unimportant reservoirs. We therefore revisited the possible role of bovines in schistosome transmission in the Philippines, using the recently described formalin-ethyl acetate sedimentation (FEA-SD) technique and a qPCR assay to examine fecal samples from 153 bovines (both carabao and cattle) from six barangays in Northern Samar. A high prevalence of S. japonicum was found using qPCR and FEA-SD in both cattle (87.50% and 77.08%, respectively) and carabao (80.00% and 55.24%, respectively). The average daily egg output for each bovine was calculated at 195,000. High prevalence and infection intensity of F. gigantica was also found in the bovines by qPCR and FEA-SD (95.33% and 96.00%, respectively). The identification of bovines as major reservoir hosts for S. japonicum transmission suggests that bovine treatment and/or vaccination, as one becomes available, should be included in any future control program that aims to reduce the disease burden due to schistosomiasis in the Philippines. PMID:25643317

High prevalence of Schistosoma japonicum and Fasciola gigantica in bovines from Northern Samar, the Philippines.

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Catherine A Gordon

2015-02-01

Full Text Available The cause of zoonotic schistosomiasis in the Philippines is Schistosoma japonicum, which infects up to 46 mammalian hosts, including humans and bovines. In China, water buffaloes have been identified as major reservoir hosts for schistosomiasis japonica, contributing up to 75% of human transmission. In the Philippines, water buffaloes (carabao; Bubalus bubalis carabanesis have, historically, been considered unimportant reservoirs. We therefore revisited the possible role of bovines in schistosome transmission in the Philippines, using the recently described formalin-ethyl acetate sedimentation (FEA-SD technique and a qPCR assay to examine fecal samples from 153 bovines (both carabao and cattle from six barangays in Northern Samar. A high prevalence of S. japonicum was found using qPCR and FEA-SD in both cattle (87.50% and 77.08%, respectively and carabao (80.00% and 55.24%, respectively. The average daily egg output for each bovine was calculated at 195,000. High prevalence and infection intensity of F. gigantica was also found in the bovines by qPCR and FEA-SD (95.33% and 96.00%, respectively. The identification of bovines as major reservoir hosts for S. japonicum transmission suggests that bovine treatment and/or vaccination, as one becomes available, should be included in any future control program that aims to reduce the disease burden due to schistosomiasis in the Philippines.

Serologic and ultrasonographic parameters of praziquantel treatment of hepatic fibrosis in Schistosoma japonicum infection.

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Ohmae, H; Tanaka, M; Nara, T; Utsunomiya, H; Taguchi, H; Irie, Y; Yasuraoka, K

1991-09-01

We describe the parameters useful in evaluating the development of hepatic fibrosis in Schistosoma japonicum infection, as well as its improvement after treatment with praziquantel (PZQ). Various serologic parameters and ultrasonographic images were examined, and their changes were monitored using rabbits infected with 200 or 300 cercariae of S. japonicum. Infected rabbits were administered one oral treatment of PZQ at a dosage of 100 mg/kg at 6, 12, or 24 weeks after infection. Histopathologic examinations revealed that PZQ had a strong and rapid effect, even on damage that developed long after the infection. The improvement of moderate hepatic fibrosis that developed over 24 weeks after infection was also detected by histopathologic examinations. The serum level of total bile acid was the most sensitive parameter in evaluating the severity of hepatic fibrosis and its improvement after treatment with PZQ. The level of serum procollagen-III-peptide was also useful in evaluating the development of hepatic fibrosis, but not in its improvement. Ultrasonography revealed specific echogenic bands and nodules according to the progress of granuloma formation and fibrosis, and the reversal of these changes could also be observed after treatment with PZQ.

Approaches to genotyping individual miracidia of Schistosoma japonicum.

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Xiao, Ning; Remais, Justin V; Brindley, Paul J; Qiu, Dong-Chuan; Carlton, Elizabeth J; Li, Rong-Zhi; Lei, Yang; Blair, David

2013-12-01

Molecular genetic tools are needed to address questions as to the source and dynamics of transmission of the human blood fluke Schistosoma japonicum in regions where human infections have reemerged, and to characterize infrapopulations in individual hosts. The life stage that interests us as a target for collecting genotypic data is the miracidium, a very small larval stage that consequently yields very little DNA for analysis. Here, we report the successful development of a multiplex format permitting genotyping of 17 microsatellite loci in four sequential multiplex reactions using a single miracidium held on a Whatman Classic FTA indicating card. This approach was successful after short storage periods, but after long storage (>4 years), considerable difficulty was encountered in multiplex genotyping, necessitating the use of whole genome amplification (WGA) methods. WGA applied to cards stored for long periods of time resulted in sufficient DNA for accurate and repeatable genotyping. Trials and tests of these methods, as well as application to some field-collected samples, are reported, along with the discussion of the potential insights to be gained from such techniques. These include recognition of sibships among miracidia from a single host, and inference of the minimum number of worm pairs that might be present in a host.

Bayesian spatio-temporal modeling of Schistosoma japonicum prevalence data in the absence of a diagnostic 'gold' standard.

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Wang, Xian-Hong; Zhou, Xiao-Nong; Vounatsou, Penelope; Chen, Zhao; Utzinger, Jürg; Yang, Kun; Steinmann, Peter; Wu, Xiao-Hua

2008-06-11

Spatial modeling is increasingly utilized to elucidate relationships between demographic, environmental, and socioeconomic factors, and infectious disease prevalence data. However, there is a paucity of studies focusing on spatio-temporal modeling that take into account the uncertainty of diagnostic techniques. We obtained Schistosoma japonicum prevalence data, based on a standardized indirect hemagglutination assay (IHA), from annual reports from 114 schistosome-endemic villages in Dangtu County, southeastern part of the People's Republic of China, for the period 1995 to 2004. Environmental data were extracted from satellite images. Socioeconomic data were available from village registries. We used Bayesian spatio-temporal models, accounting for the sensitivity and specificity of the IHA test via an equation derived from the law of total probability, to relate the observed with the 'true' prevalence. The risk of S. japonicum was positively associated with the mean land surface temperature, and negatively correlated with the mean normalized difference vegetation index and distance to the nearest water body. There was no significant association between S. japonicum and socioeconomic status of the villages surveyed. The spatial correlation structures of the observed S. japonicum seroprevalence and the estimated infection prevalence differed from one year to another. Variance estimates based on a model adjusted for the diagnostic error were larger than unadjusted models. The generated prediction map for 2005 showed that most of the former and current infections occur in close proximity to the Yangtze River. Bayesian spatial-temporal modeling incorporating diagnostic uncertainty is a suitable approach for risk mapping S. japonicum prevalence data. The Yangtze River and its tributaries govern schistosomiasis transmission in Dangtu County, but spatial correlation needs to be taken into consideration when making risk prediction at small scales.

Immunization of pigs against infection with Schistosoma japonicum using ultraviolet-attenuated cercariae

International Nuclear Information System (INIS)

Shi, Y.-E.; Jiang, C.-F.; Han, J.-J.; Li, Y.-L.

1993-01-01

Since pigs are important in the zoonotic transmission of schistosomiasis japonica in China, a veterinary vaccine might contribute to the control of the disease in humans. Pigs were immunized with three doses each of 10 000 cercariae of Schistosoma japonicum attenuated with ultraviolet light (400 μWatt.min/cm 2 ). The experiment was performed with portable irradiation equipment in a rural area of the Hubei Province (P.R. China). A challenge infection of 1000 untreated cercariae was given 2.5 or 6 months after the last immunization, and age-matched naive pigs were challenged as a control. Immunized pigs developed about 90% resistance against the challenge. The liver egg load of these animals was reduced by over 90%. Less than 0.01% of the immunizing cercariae developed to adult parasites and the vaccination had no apparent adverse influence on the pig's health. (Author)

Repeated Schistosoma japonicum infection following treatment in two cohorts: evidence for host susceptibility to helminthiasis?

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Elizabeth J Carlton

Full Text Available In light of multinational efforts to reduce helminthiasis, we evaluated whether there exist high-risk subpopulations for helminth infection. Such individuals are not only at risk of morbidity, but may be important parasite reservoirs and appropriate targets for disease control interventions.We followed two longitudinal cohorts in Sichuan, China to determine whether there exist persistent human reservoirs for the water-borne helminth, Schistosoma japonicum, in areas where treatment is ongoing. Participants were tested for S. japonicum infection at enrollment and two follow-up points. All infections were promptly treated with praziquantel. We estimated the ratio of the observed to expected proportion of the population with two consecutive infections at follow-up. The expected proportion was estimated using a prevalence-based model and, as highly exposed individuals may be most likely to be repeatedly infected, a second model that accounted for exposure using a data adaptive, machine learning algorithm. Using the prevalence-based model, there were 1.5 and 5.8 times more individuals with two consecutive infections than expected in cohorts 1 and 2, respectively (p<0.001 in both cohorts. When we accounted for exposure, the ratio was 1.3 (p = 0.013 and 2.1 (p<0.001 in cohorts 1 and 2, respectively.We found clustering of infections within a limited number of hosts that was not fully explained by host exposure. This suggests some hosts may be particularly susceptible to S. japonicum infection, or that uncured infections persist despite treatment. We propose an explanatory model that suggests that as cercarial exposure declines, so too does the size of the vulnerable subpopulation. In low-prevalence settings, interventions targeting individuals with a history of S. japonicum infection may efficiently advance disease control efforts.

The induction of specific immunity against Schistosoma japonicum by exposure of mice to ultraviolet attenuated cercariae

International Nuclear Information System (INIS)

Moloney, N.A.; Bickle, Q.D.; Webbe, G.

1985-01-01

Mice can be partially protected against Schistosoma japonicum by prior exposure to ultraviolet (UV)-attenuated infections which fail to survive to the adult stage and produce no overt pathology in the host. Optimum resistance was induced by parasites exposed to 40 seconds of UV, significantly lower levels of resistance being stimulated by both shorter and longer exposures. No consistent relationship between the degree of resistance induced and the number of irradiated cercariae given could be demonstrated and equivocal results were obtained when comparing the efficacy of single and multiple vaccinations. Vaccinations with UV-attenuated cercariae given intraperitoneally (i.p.) were as efficacious as those given percutaneously but mice were as or more resistant to challenges given by the i.p. route, the possible reasons are discussed. There was no observed delay in the migration of the challenge, vaccinated mice being as resistant when perfused 6 or 3.5 weeks after challenge. Vaccination was species specific since mice exposed to either UV-attenuated S. japonicum cercariae or gamma-attenuated S. mansoni cercariae were resistant to homologous but not heterologous challenge. (author)

Bayesian spatio-temporal modeling of Schistosoma japonicum prevalence data in the absence of a diagnostic 'gold' standard.

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Xian-Hong Wang

Full Text Available BACKGROUND: Spatial modeling is increasingly utilized to elucidate relationships between demographic, environmental, and socioeconomic factors, and infectious disease prevalence data. However, there is a paucity of studies focusing on spatio-temporal modeling that take into account the uncertainty of diagnostic techniques. METHODOLOGY/PRINCIPAL FINDINGS: We obtained Schistosoma japonicum prevalence data, based on a standardized indirect hemagglutination assay (IHA, from annual reports from 114 schistosome-endemic villages in Dangtu County, southeastern part of the People's Republic of China, for the period 1995 to 2004. Environmental data were extracted from satellite images. Socioeconomic data were available from village registries. We used Bayesian spatio-temporal models, accounting for the sensitivity and specificity of the IHA test via an equation derived from the law of total probability, to relate the observed with the 'true' prevalence. The risk of S. japonicum was positively associated with the mean land surface temperature, and negatively correlated with the mean normalized difference vegetation index and distance to the nearest water body. There was no significant association between S. japonicum and socioeconomic status of the villages surveyed. The spatial correlation structures of the observed S. japonicum seroprevalence and the estimated infection prevalence differed from one year to another. Variance estimates based on a model adjusted for the diagnostic error were larger than unadjusted models. The generated prediction map for 2005 showed that most of the former and current infections occur in close proximity to the Yangtze River. CONCLUSION/SIGNIFICANCE: Bayesian spatial-temporal modeling incorporating diagnostic uncertainty is a suitable approach for risk mapping S. japonicum prevalence data. The Yangtze River and its tributaries govern schistosomiasis transmission in Dangtu County, but spatial correlation needs to be taken

An IL-13 promoter polymorphism associated with liver fibrosis in patients with Schistosoma japonicum.

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Xin Long

Full Text Available The aim of this study was to determine whether two polymorphisms in the gene encoding IL13 previously associated with Schistosoma hematobium (S. hematobium and S. mansoni infection are associated with S. japonicum infection. Single nucleotide polymorphisms (SNPs rs1800925 (IL13/-1112C>T and rs20541 (IL13R130Q were genotyped in 947 unrelated individuals (307 chronically infected, 339 late-stage with liver fibrosis, 301 uninfected controls from a schistosomiasis-endemic area of Hubei province in China. Regression models were used to evaluate allelic and haplotypic associations with chronic and late-stage schistosomiasis adjusted for non-genetic covariates. Expression of IL-13 was measured in S. japonicun-infected liver fibrosis tissue and normal liver tissue from uninfected controls by immunohistochemistry (IHC. The role of rs1800925 in IL-13 transcription was further determined by Luciferase report assay using the recombinant PGL4.17-rs180092 plasmid. We found SNP rs1800925T was associated with late-stage schistosomiasis caused by S. japonicum but not chronic schistosomiasis (OR = 1.39, 95%CI = 1.02-1.91, p = 0.03 and uninfected controls (OR = 1.49, 95%CI = 1.03-2.13, p = 0.03. Moreover, the haplotype rs1800925T-rs20541C increased the risk of disease progression to late-stage schistosomiasis (OR = 1.46, p = 0.035, whereas haplotype rs1800925C-rs20541A showed a protective role against development of late-stage schistosomiasis (F = 0.188, OR = 0.61, p = 0.002. Furthermore, S. japonicum-induced fibrotic liver tissue had higher IL13 expression than normal liver tissue. Plasmid PGL4.17-rs1800925T showed a stronger relative luciferase activity than Plasmid PGL4.17-rs1800925C in 293FT, QSG-7701 and HL-7702 cell lines. In conclusion, the functional IL13 polymorphism, rs1800925T, previously associated with risk of schistosomiasis, also contributes to risk of late-stage schistosomiasis caused by S. japonicum.

Geographic strain differentiation of Schistosoma japonicum in the Philippines using microsatellite markers.

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Kharleezelle J Moendeg

2017-07-01

Full Text Available Microsatellites have been found to be useful in determining genetic diversities of various medically-important parasites which can be used as basis for an effective disease management and control program. In Asia and Africa, the identification of different geographical strains of Schistosoma japonicum, S. haematobium and S. mansoni as determined through microsatellites could pave the way for a better understanding of the transmission epidemiology of the parasite. Thus, the present study aims to apply microsatellite markers in analyzing the populations of S. japonicum from different endemic areas in the Philippines for possible strain differentiation.Experimental mice were infected using the cercariae of S. japonicum collected from infected Oncomelania hupensis quadrasi snails in seven endemic municipalities. Adult worms were harvested from infected mice after 45 days of infection and their DNA analyzed against ten previously characterized microsatellite loci. High genetic diversity was observed in areas with high endemicity. The degree of genetic differentiation of the parasite population between endemic areas varies. Geographical separation was considered as one of the factors accounting for the observed difference between populations. Two subgroups have been observed in one of the study sites, suggesting that co-infection with several genotypes of the parasite might be present in the population. Clustering analysis showed no particular spatial structuring between parasite populations from different endemic areas. This result could possibly suggest varying degrees of effects of the ongoing control programs and the existing gene flow in the populations, which might be attributed to migration and active movement of infected hosts from one endemic area to another.Based on the results of the study, it is reasonable to conclude that genetic diversity could be one possible criterion to assess the infection status in highly endemic areas. Genetic

Identification and characterization of microRNAs and endogenous siRNAs in Schistosoma japonicum

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Wang Heng

2010-01-01

Full Text Available Abstract Background Small endogenous non-coding RNAs (sncRNAs such as small interfering RNA (siRNA, microRNA and other small RNA transcripts are derived from distinct loci in the genome and play critical roles in RNA-mediated gene silencing mechanisms in plants and metazoa. They are approximately 22 nucleotides long; regulate mRNA stability through perfect or imperfect match to the targets. The biological activities of sncRNAs have been related to many biological events, from resistance to microbe infections to cellular differentiation. The development of the zoonotic parasite Schistosoma japonicum parasite includes multiple steps of morphological alterations and biological differentiations, which provide a unique model for studies on the functions of small RNAs. Characterization of the genome-wide transcription of the sncRNAs will be a major step in understanding of the parasite biology. The objective of this study is to investigate the transcriptional profile and potential function of the small non-coding RNAs in the development of S. japanicum. Results The endogenous siRNAs were found mainly derived from transposable elements (TE or transposons and the natural antisense transcripts (NAT. In contrast to other organisms, the TE-derived siRNAs in S. japonicum were more predominant than other sncRNAs including microRNAs (miRNAs. Further, there were distinct length and 3'end variations in the sncRNAs, which were associated with the developmental differentiation of the parasite. Among the identified miRNA transcripts, there were 38 unique to S. japonicum and 16 that belonged to 13 miRNA families are common to other metazoan lineages. These miRNAs were either ubiquitously expressed, or they exhibited specific expression patterns related to the developmental stages or sex. Genes that encoded miRNAs are mainly located in clusters within the genome of S. japonicum. However, genes within one cluster could be differentially transcribed, which suggested

Mefloquine in combination with hemin causes severe damage to adult Schistosoma japonicum in vitro.

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Xiao, Shu-hua; Qiao, Chunhua; Xue, Jian; Wang, Lili

2014-03-01

In order to explore the interaction of mefloquine with hemin against adult Schistosoma japonicum in vitro, the 50% and 95% lethal concentration (LC50 and LC95) of mefloquine and hemin against schistosomes, some factors, such as other iron providing agents, iron chelaters, zinc protoporphyrin-IX, and biological relevant reductants, that might impact on antischistosomal activity induced by interaction of mefloquine with hemin, and preliminary analysis of chemical interaction of both compounds were undertaken. The LC50 and LC95 of mefloquine and hemin alone against schistosomes were determined to be 6.5μg/ml and 7.8μg/ml as well as 232μg/ml and 355μg/ml, respectively. The LC50 and LC95 of mefloquine in the presence of hemin 100μg/ml was 0.24μg/ml and 0.59μg/ml, respectively. On the other hand the LC50 and LC95 of hemin in the presence of mefloquine 1μg/ml was 23.2μg/ml and 77.2μg/ml, respectively. Meanwhile, mefloquine/hemin combinations showed potential synergistic effects against adult S. japonicum, with combination index (CI) values vitamine C or cysteine showed no apparent worm protection effect from toxic mefloquine-hemin even at higher concentrations (242.3-614.6μg/ml, i.e., 6.4-17.8-fold higher than the concentration of hemin). Chemical interaction of mefloquine with hemin was studied in 40% DMSO-Tris buffer solution. Both UV-Vis spectrum and mass spectrum demonstrated the strong interaction of mefloquine with hemin, which resulted in a reduction of hemin color and emergence of an adduct formed by mefloquine and hemin. The results confirm that mefloquine combined with hemin exhibits potential synergistic effect against adult S. japonicum in vitro. Copyright © 2013 Elsevier B.V. All rights reserved.

Cross-species prophylactic efficacy of Sm-p80-based vaccine and intracellular localization of Sm-p80/Sm-p80 ortholog proteins during development in Schistosoma mansoni, Schistosoma japonicum, and Schistosoma haematobium.

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Molehin, Adebayo J; Sennoune, Souad R; Zhang, Weidong; Rojo, Juan U; Siddiqui, Arif J; Herrera, Karlie A; Johnson, Laura; Sudduth, Justin; May, Jordan; Siddiqui, Afzal A

2017-11-01

Schistosomiasis remains a major global health problem. Despite large-scale schistosomiasis control efforts, clear limitations such as possible emergence of drug resistance and reinfection rates highlight the need for an effective schistosomiasis vaccine. Schistosoma mansoni large subunit of calpain (Sm-p80)-based vaccine formulations have shown remarkable efficacy in protecting against S. mansoni challenge infections in mice and baboons. In this study, we evaluated the cross-species protective efficacy of Sm-p80 vaccine against S. japonicum and S. haematobium challenge infections in rodent models. We also elucidated the expression of Sm-p80 and Sm-p80 ortholog proteins in different developmental stages of S. mansoni, S. haematobium, and S. japonicum. Immunization with Sm-p80 vaccine reduced worm burden by 46.75% against S. japonicum challenge infection in mice. DNA prime/protein boost (1 + 1 dose administered on a single day) resulted in 26.95% reduction in worm burden in S. haematobium-hamster infection/challenge model. A balanced Th1 (IFN-γ, TNF-α, IL-2, and IL-12) and Th2 (IL-4, IgG1) type of responses were observed following vaccination in both S. japonicum and S. haematobium challenge trials and these are associated with the prophylactic efficacy of Sm-p80 vaccine. Immunohistochemistry demonstrated that Sm-p80/Sm-p80 ortholog proteins are expressed in different life cycle stages of the three major human species of schistosomes studied. The data presented in this study reinforce the potential of Sm-p80-based vaccine for both hepatic/intestinal and urogenital schistosomiasis occurring in different geographical areas of the world. Differential expression of Sm-p80/Sm-p80 protein orthologs in different life cycle makes this vaccine potentially useful in targeting different levels of infection, disease, and transmission.

Intake of Erythrocytes Required for Reproductive Development of Female Schistosoma japonicum

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Wang, Jipeng; Wang, Shuqi; Liu, Xiufeng; Xu, Bin; Chai, Riyi; Zhou, Pan; Ju, Chuan; Sun, Jun; Brindley, Paul J.; Hu, Wei

2015-01-01

The reproductive development and maturation of female schistosomes are crucial since their released eggs are responsible for the host immunopathology and transmission of schistosomiasis. However, little is known about the nutrients required by female Schistosoma japonicum during its sexual maturation. We evaluated the promoting effect of several nutrients (calf serum, red blood cells (RBCs), ATP and hypoxanthine) on the reproductive development of pre-adult females at 18 days post infection (dpi) from mixed infections and at 50 dpi from unisexual infections of laboratory mice in basic medium RPMI-1640. We found RBCs, rather than other nutrients, promoted the female sexual maturation and egg production with significant morphological changes. In 27% of females (18 dpi) from mixed infections that paired with males in vitro on day 14, vitelline glands could be positively stained by Fast Blue B; and in 35% of females (50 dpi) from unisexual infections on day 21, mature vitelline cells were observed. Infertile eggs were detected among both groups. To analyze which component of mouse RBCs possesses the stimulating effect, RBCs were fractionated and included in media. However, the RBC fractions failed to stimulate development of the female reproductive organs. In addition, bovine hemoglobin hydrolysate, digested by neutral protease, was found to exhibit the promoting activity instead of untreated bovine hemoglobin. The other protein hydrolysate, lactalbumin hydrolysate, exhibited a similar effect with bovine hemoglobin hydrolysate. Using quantitative RT-PCR, we found the expression levels of four reproduction-related genes were significantly stimulated by RBCs. These data indicate that RBCs provide essential nutrients for the sexual maturation of female S. japonicum and that the protein component of RBCs appeared to constitute the key nutrient. These findings would improve laboratory culture of pre-adult schistosomes to adult worms in medium with well-defined components

MicroRNA-gene expression network in murine liver during Schistosoma japonicum infection.

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Pengfei Cai

Full Text Available BACKGROUND: Schistosomiasis japonica remains a significant public health problem in China and Southeast Asian countries. The most typical and serious outcome of the chronic oriental schistosomiasis is the progressive granuloma and fibrosis in the host liver, which has been a major medical challenge. However, the molecular mechanism underling the hepatic pathogenesis is still not clear. METHODOLOGY AND PRINCIPAL FINDINGS: Using microarrays, we quantified the temporal gene expression profiles in the liver of Schistosoma japonicum-infected BALB/c mice at 15, 30, and 45 day post infection (dpi with that from uninfected mice as controls. Gene expression alternation associated with liver damage was observed in the initial phase of infection (dpi 15, which became more magnificent with the onset of egg-laying. Up-regulated genes were dominantly associated with inflammatory infiltration, whereas down-regulated genes primarily led to the hepatic functional disorders. Simultaneously, microRNA profiles from the same samples were decoded by Solexa sequencing. More than 130 miRNAs were differentially expressed in murine liver during S. japonicum infection. MiRNAs significantly dysregulated in the mid-phase of infection (dpi 30, such as mmu-miR-146b and mmu-miR-155, may relate to the regulation of hepatic inflammatory responses, whereas miRNAs exhibiting a peak expression in the late phase of infection (dpi 45, such as mmu-miR-223, mmu-miR-146a/b, mmu-miR-155, mmu-miR-34c, mmu-miR-199, and mmu-miR-134, may represent a molecular signature of the development of schistosomal hepatopathy. Further, a dynamic miRNA-gene co-expression network in the progression of infection was constructed. CONCLUSIONS AND SIGNIFICANCE: This study presents a global view of dynamic expression of both mRNA and miRNA transcripts in murine liver during S. japonicum infection, and highlights that miRNAs may play a variety of regulatory roles in balancing the immune responses during the

Treatment for Schistosoma japonicum, reduction of intestinal parasite load, and cognitive test score improvements in school-aged children.

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Amara E Ezeamama

Full Text Available To determine whether treatment of intestinal parasitic infections improves cognitive function in school-aged children, we examined changes in cognitive testscores over 18 months in relation to: (i treatment-related Schistosoma japonicum intensity decline, (ii spontaneous reduction of single soil-transmitted helminth (STH species, and (iii ≥2 STH infections among 253 S. japonicum-infected children.Helminth infections were assessed at baseline and quarterly by the Kato-Katz method. S. japonicum infection was treated at baseline using praziquantel. An intensity-based indicator of lower vs. no change/higher infection was defined separately for each helminth species and joint intensity declines of ≥2 STH species. In addition, S. japonicum infection-free duration was defined in four categories based on time of schistosome re-infection: >18 (i.e. cured, >12 to ≤18, 6 to ≤12 and ≤6 (persistently infected months. There was no baseline treatment for STHs but their intensity varied possibly due to spontaneous infection clearance/acquisition. Four cognitive tests were administered at baseline, 6, 12, and 18 months following S. japonicum treatment: learning and memory domains of Wide Range Assessment of Memory and Learning (WRAML, verbal fluency (VF, and Philippine nonverbal intelligence test (PNIT. Linear regression models were used to relate changes in respective infections to test performance with adjustment for sociodemographic confounders and coincident helminth infections.Children cured (β = 5.8; P = 0.02 and those schistosome-free for >12 months (β = 1.5; P = 0.03 scored higher in WRAML memory and VF tests compared to persistently infected children independent of STH infections. A decline vs. no change/increase of any individual STH species (β:11.5-14.5; all P12 months post-treatment and those who experienced declines of ≥2 STH species scored higher in three of four cognitive tests. Our result suggests that sustained

[Preservation of live eggs of Schistosoma japonicum].

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Lan, Wei-ming; Xie, Shu-ying; Wang, Qin; Jiang, Wei-sheng; Hu, Ren-mei; Ge, Jun; Zeng, Xiao-jun

2015-10-01

To observe the preservation time and activity of miracidium hatching from schistosome eggs preserved in different solutions, so as to obtain the optimal preservation conditions and then provide quality control products for field application. The rectum stool of rabbits infected with Schistosoma japonicum was collected and the coarse fecal residue was removed with a series of sample sieves of 80, 100, 160 and 200 meshes respectively, and then the schistosome eggs were concentrated with the sample sieve of 260 meshes. The concentrated eggs were preserved in 0.9% sodium chloride solution, 1.2% sodium chloride solution, phosphate buffered saline solution (PBS, PH 7.2), 1.0% sucrose solution, and Mili-Q water, respectively, and then were conserved in a 4 °C refrigerator and 15 °C constant temperature incubator, respectively. The preserved eggs were hatched in different time (7-day interval) , the vitality and quantity of the miracidia were observed, and the hatching rates were calculated. Under the condition of 4 °C, the hatching rates of eggs dropped to 0 in 1.0% sucrose solution and 1.2% sodium chloride solution at the 49th and 126th day, respectively, and the hatching rates of eggs in the 0.9% sodium chloride solution and PBS solution dropped to 10% at the 112th day, and the activity of miracidium was weakened since 140th. In the Mili-Q water, the hatching rate dropped less than 10% at the 196th day and the activity of miracidia was weakened since the 280th day. Under the condition of 15 °C, the hatching rate of eggs in different solutions gradually dropped to 0 from the 49th day to 105th day. The eggs preserved in Mili-Q water at the temperature of 4 °C can be used as the positive reference for hatching tests within 196 days.

Changes in NK and NKT cells in mesenteric lymph nodes after a Schistosoma japonicum infection.

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Luo, Xueping; Xie, Hongyan; Chen, Dianhui; Yu, Xiuxue; Wu, Fan; Li, Lu; Wu, Changyou; Huang, Jun

2014-03-01

The mesenteric lymph node (MLN) is the main draining lymph node in mouse enterocoelia, which contains many types of immune cells. Among these cells, natural killer (NK) and natural killer T (NKT) cells belong to innate lymphoid cells (ILCs), which have potent activities for controlling a variety of pathogenic infections. In this study, C57BL/6 mice were infected with Schistosoma japonicum for 5-7 weeks. Lymphocytes were isolated from the MLN to detect changes in the phenotype and function of NK and NKT cells using a fluorescence activating cell sorter (FACS). These results demonstrated that a S. japonicum infection could significantly increase the percentage of NK cells in the mouse MLN, (P cell number of both NK and NKT cells. In addition, we found that NK and NKT cells from infected mice expressed higher levels of CD69 compared to normal mice (P NKT cell activation. Moreover, we found that the expression of CD4 was increased in infected MLN NK cells (P NKT cells of infected mice after phorbol 12-myristate 13-acetate (PMA) and ionomycin stimulation (P NKT cells might play roles in modulating the classical T cell response. Finally, our results indicated that the expression of CD94 was decreased in NK cells, suggesting that the downregulation of CD94 expression might served as a mechanism in NK cell activation.

What is the role of health education in the integrated strategy to control transmission of Schistosoma japonicum in China?

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Liu, Rong; Dong, Hui-Fen; Jiang, Ming-Sen

2012-05-01

In 2009, Wang et al.'s field trial published in the New England Journal of Medicine, reported that a comprehensive strategy aiming to reduce the roles of humans and cattle as sources of Schistosoma japonicum infection in snails was implemented and proved effective and promising in dramatically reducing the percentage of infected humans and snails, which had been extended to other endemic provinces in China afterwards. This implies that the integrated schistosomiasis-control strategies of interventions including political will, financial support and residents' participation to control human and bovine sources of S. japonicum infection in snails may direct to successfully interrupt the parasitic transmission and to ultimately eliminate schistosomiasis. Confusingly, however, the role of health education, which is a critical part of the integrated strategy and should play an active role in schistosomiasis control, was not reflected. We wish the authors to provide the readers a better and clearer statement of the role of health education as part of the integrated control strategy and so we write this comment.

Comparison of worm development and host immune responses in natural hosts of schistosoma japonicum, yellow cattle and water buffalo

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Yang Jianmei

2012-03-01

Full Text Available Abstract Background Yellow cattle and water buffalo are two of the most important natural hosts for Schistosoma japonicum in China. Previous observation has revealed that yellow cattle are more suited to the development of S. japonicum than water buffalo. Understanding more about the molecular mechanisms involved in worm development, as well as the pathological and immunological differences between yellow cattle and water buffalo post infection with S japonicum will provide useful information for the vaccine design and its delivery procedure. Results The worm length (p p p + T cells was higher in yellow cattle, while the percentage of CD8+ T cells was higher in water buffalo from pre-infection to 7 w post infection. The CD4/CD8 ratios were decreased in both species after challenge with schistosomes. Comparing with water buffalo, the IFN-γ level was higher and decreased significantly, while the IL-4 level was lower and increased gradually in yellow cattle from pre-infection to 7 w post infection. Conclusions In this study, we confirmed that yellow cattle were more suited to the development of S. japonicum than water buffalo, and more serious pathological damage was observed in infected yellow cattle. Immunological analysis suggested that CD4+ T cells might be an integral component of the immune response and might associate with worm development in yellow cattle. A shift from Th1 to Th2 type polarized immunity was only shown clearly in schistosome-infected yellow cattle, but no shift in water buffalo. The results provide valuable information for increased understanding of host-schistosome interactions, and for control of schistosomiasis.

Rapid detection and identification of four major Schistosoma species by high-resolution melt (HRM) analysis.

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Li, Juan; Zhao, Guang-Hui; Lin, RuiQing; Blair, David; Sugiyama, Hiromu; Zhu, Xing-Quan

2015-11-01

Schistosomiasis, caused by blood flukes belonging to several species of the genus Schistosoma, is a serious and widespread parasitic disease. Accurate and rapid differentiation of these etiological agents of animal and human schistosomiasis to species level can be difficult. We report a real-time PCR assay coupled with a high-resolution melt (HRM) assay targeting a portion of the nuclear 18S rDNA to detect, identify, and distinguish between four major blood fluke species (Schistosoma japonicum, Schistosoma mansoni, Schistosoma haematobium, and Schistosoma mekongi). Using this system, the Schistosoma spp. was accurately identified and could also be distinguished from all other trematode species with which they were compared. As little as 10(-5) ng genomic DNA from a Schistosoma sp. could be detected. This process is inexpensive, easy, and can be completed within 3 h. Examination of 21 representative Schistosoma samples from 15 geographical localities in seven endemic countries validated the value of the HRM detection assay and proved its reliability. The melting curves were characterized by peaks of 83.65 °C for S. japonicum and S. mekongi, 85.65 °C for S. mansoni, and 85.85 °C for S. haematobium. The present study developed a real-time PCR coupled with HRM analysis assay for detection and differential identification of S. mansoni, S. haematobium, S. japonicum, and S. mekongi. This method is rapid, sensitive, and inexpensive. It has important implications for epidemiological studies of Schistosoma.

Gene Gun Bombardment with DNA-Coated Golden Particles Enhanced the Protective Effect of a DNA Vaccine Based on Thioredoxin Glutathione Reductase of Schistosoma japonicum

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Yan Cao

2013-01-01

Full Text Available Schistosomiasis, caused by infection with Schistosoma species, remains an important parasitic zoonosis. Thioredoxin glutathione reductase of Schistosoma japonicum (SjTGR plays an important role in the development of the parasite and for its survival. Here we present a recombinant plasmid DNA vaccine, pVAX1/SjTGR, to estimate its protection against S. japonicum in BALB/c mice. The DNA vaccine administrated by particle bombardment induced higher protection than by intramuscular injection. All animals vaccinated with pVAX1/SjTGR developed significant specific anti-SjTGR antibodies than control groups. Moreover, animals immunized by gene gun exhibited a splenocyte proliferative response, with an increase in IFN-γ and IL-4. The recombinant plasmid administrated by gene gun achieved a medium protective efficacy of 27.83–38.83% ( of worm reduction and 40.38–44.51% ( of liver egg count reduction. It suggests that different modes of administering a DNA vaccine can influence the protective efficacy induced by the vaccine. Interestingly, from the enzymatic activity results, we found that worms obtained from pVAX1/SjTGR-vaccinated animals expressed lower enzymatic activity than the control group and the antibodies weakened the enzymatic activity of SjTGR in vitro, too. It implies that the high-level antibodies may contribute to the protective effects.

Correlative and dynamic imaging of the hatching biology of Schistosoma japonicum from eggs prepared by high pressure freezing.

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Malcolm K Jones

Full Text Available BACKGROUND: Schistosome eggs must traverse tissues of the intestine or bladder to escape the human host and further the life cycle. Escape from host tissues is facilitated by secretion of immuno-reactive molecules by eggs and the formation of an intense strong granulomatous response by the host which acts to exclude the egg into gut or bladder lumens. Schistosome eggs hatch on contact with freshwater, but the mechanisms of activation and hatching are poorly understood. In view of the lack of knowledge of the behaviour of egg hatching in schistosomes, we undertook a detailed dynamic and correlative study of the hatching biology of Schistosoma japonicum. METHODOLOGY/PRINCIPAL FINDINGS: Hatching eggs of S. japonicum were studied using correlative light and electron microscopy (EM. The hatching behaviour was recorded by video microscopy. EM preparative methods incorporating high pressure freezing and cryo-substitution were used to investigate ultrastructural features of the miracidium and extra-embryonic envelopes in pre-activated and activated eggs, and immediately after eggshell rupture. Lectin cytochemistry was performed on egg tissues to investigate subcellular location of specific carbohydrate groups. CONCLUSIONS/SIGNIFICANCE: The hatching of S. japonicum eggs is a striking phenomenon, whereby the larva is liberated explosively while still encapsulated within its sub-shell envelopes. The major alterations that occur in the egg during activation are scission of the outer envelope-eggshell boundary, autolysis of the cellular inner envelope, and likely hydration of abundant complex and simple polysaccharides in the lacunal space between the miracidial larva and surrounding envelopes. These observations on hatching provide insight into the dynamic activity of the eggs and the biology of schistosomes within the host.

MicroRNAs Are Involved in the Regulation of Ovary Development in the Pathogenic Blood Fluke Schistosoma japonicum.

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Lihui Zhu

2016-02-01

Full Text Available Schistosomes, blood flukes, are an important global public health concern. Paired adult female schistosomes produce large numbers of eggs that are primarily responsible for the disease pathology and critical for dissemination. Consequently, understanding schistosome sexual maturation and egg production may open novel perspectives for intervening with these processes to prevent clinical symptoms and to interrupt the life-cycle of these blood-flukes. microRNAs (miRNAs are key regulators of many biological processes including development, cell proliferation, metabolism, and signal transduction. Here, we report on the identification of Schistosoma japonicum miRNAs using small RNA deep sequencing in the key stages of male-female pairing, gametogenesis, and egg production. We identified 38 miRNAs, including 10 previously unknown miRNAs. Eighteen of the miRNAs were differentially expressed between male and female schistosomes and during different stages of sexual maturation. We identified 30 potential target genes for 16 of the S. japonicum miRNAs using antibody-based pull-down assays and bioinformatic analyses. We further validated some of these target genes using either in vitro luciferase assays or in vivo miRNA suppression experiments. Notably, suppression of the female enriched miRNAs bantam and miR-31 led to morphological alteration of ovaries in female schistosomes. These findings uncover key roles for specific miRNAs in schistosome sexual maturation and egg production.

MicroRNAs Are Involved in the Regulation of Ovary Development in the Pathogenic Blood Fluke Schistosoma japonicum.

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Zhu, Lihui; Zhao, Jiangping; Wang, Jianbin; Hu, Chao; Peng, Jinbiao; Luo, Rong; Zhou, Chunjing; Liu, Juntao; Lin, Jiaojiao; Jin, Youxin; Davis, Richard E; Cheng, Guofeng

2016-02-01

Schistosomes, blood flukes, are an important global public health concern. Paired adult female schistosomes produce large numbers of eggs that are primarily responsible for the disease pathology and critical for dissemination. Consequently, understanding schistosome sexual maturation and egg production may open novel perspectives for intervening with these processes to prevent clinical symptoms and to interrupt the life-cycle of these blood-flukes. microRNAs (miRNAs) are key regulators of many biological processes including development, cell proliferation, metabolism, and signal transduction. Here, we report on the identification of Schistosoma japonicum miRNAs using small RNA deep sequencing in the key stages of male-female pairing, gametogenesis, and egg production. We identified 38 miRNAs, including 10 previously unknown miRNAs. Eighteen of the miRNAs were differentially expressed between male and female schistosomes and during different stages of sexual maturation. We identified 30 potential target genes for 16 of the S. japonicum miRNAs using antibody-based pull-down assays and bioinformatic analyses. We further validated some of these target genes using either in vitro luciferase assays or in vivo miRNA suppression experiments. Notably, suppression of the female enriched miRNAs bantam and miR-31 led to morphological alteration of ovaries in female schistosomes. These findings uncover key roles for specific miRNAs in schistosome sexual maturation and egg production.

Identification and characterization of argonaute protein, Ago2 and its associated small RNAs in Schistosoma japonicum.

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Pengfei Cai

Full Text Available BACKGROUND: The complex life cycle of the genus Schistosoma drives the parasites to employ subtle developmentally dependent gene regulatory machineries. Small non-coding RNAs (sncRNAs are essential gene regulatory factors that, through their impact on mRNA and genome stability, control stage-specific gene expression. Abundant sncRNAs have been identified in this genus. However, their functionally associated partners, Argonaute family proteins, which are the key components of the RNA-induced silencing complex (RISC, have not yet been fully explored. METHODOLOGY/PRINCIPAL FINDINGS: Two monoclonal antibodies (mAbs specific to Schistosoma japonicum Argonaute protein Ago2 (SjAgo2, but not SjAgo1 and SjAgo3, were generated. Soluble adult worm antigen preparation (SWAP was subjected to immunoprecipitation with the mAbs and the captured SjAgo2 protein was subsequently confirmed by Western blot and mass spectrometry (MS analysis. The small RNA population associated with native SjAgo2 in adult parasites was extracted from the immunoprecipitated complex and subjected to library construction. High-through-put sequencing of these libraries yielded a total of ≈50 million high-quality reads. Classification of these small RNAs showed that endogenous siRNAs (endo-siRNAs generated from transposable elements (TEs, especially from the subclasses of LINE and LTR, were prominent. Further bioinformatics analysis revealed that siRNAs derived from ten types of well-defined retrotransposons were dramatically enriched in the SjAgo2-specific libraries compared to small RNA libraries constructed with total small RNAs from separated adult worms. These results suggest that a key function of SjAgo2 is to maintain genome stability through suppressing the activities of retrotransposons. CONCLUSIONS/SIGNIFICANCE: In this study, we identified and characterized one of the three S. japonicum Argonautes, SjAgo2, and its associated small RNAs were found to be predominantly derived

Detection of early and single infections of Schistosoma japonicum in the intermediate host snail, Oncomelania hupensis, by PCR and loop-mediated isothermal amplification (LAMP) assay.

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Kumagai, Takashi; Furushima-Shimogawara, Rieko; Ohmae, Hiroshi; Wang, Tian-Ping; Lu, Shaohong; Chen, Rui; Wen, Liyong; Ohta, Nobuo

2010-09-01

Polymerase chain reaction (PCR) with the specific primer set amplifying 28S ribosomal DNA (rDNA) of Schistosoma japonicum was able to detect genomic DNA of S. japonicum, but not S. mansoni, at 100 fg. This procedure enabled us to detect the DNA from a single miracidium and a snail infected with one miracidium at just 1 day after infection. We compared these results with those from loop-mediated isothermal amplification (LAMP) targeting 28S rDNA and found similar results. The LAMP could amplify the specific DNA from a group of 100 normal snails mixed with one infected snail A PCR screening of infected snails from endemic regions in Anhui Province revealed schistosomal DNA even in snails found negative by microscopy. PCR and LAMP show promise for monitoring the early infection rate in snails, and they may be useful for predicting the risk of infection in the endemic places.

DNA detection of Schistosoma japonicum: diagnostic validity of a LAMP assay for low-intensity infection and effects of chemotherapy in humans.

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Xu, Jing; Guan, Zhi-Xun; Zhao, Bo; Wang, Yan-Yan; Cao, Yun; Zhang, Hui-Qin; Zhu, Xing-Quan; He, Yong-Kang; Xia, Chao-Ming

2015-04-01

Schistosomiasis has decreased significantly in prevalence and intensity of infection in China, thus more accurate and sensitive methods are desperately needed for the further control of schistosomiasis. The present work aimed to assess the utility of the loop-mediated isothermal amplification (LAMP) for detection of light intensity infection or false-negative patients and patients post-treatment, targeting the highly repetitive retrotransposon SjR2 of Schistosoma japonicum. LAMP was first assessed in rabbits with low intensity infection (EPGLAMP. Meanwhile, 42 sera from healthy individuals in a non-endemic area, and 60 sera from "healthy" residents who were identified as being negative for feces examination and immuno-methods in an endemic area were also examined. The results showed that LAMP could detect S. japonicum DNA in sera from rabbits at 3rd day post-infection. Following administration of praziquantel, the S. japonicum DNA in rabbit sera became negative at 10 weeks post-treatment. Of 110 sera from patients, LAMP showed 95.5% sensitivity, and even for 41 patients with less than 10 EPG, the sensitivity of LAMP still reached to 95.1%. For 47 patients after treatment, the negative conversion rate of S. japonicum DNA in patient sera increased from 23.4%, 61.7% to 83.0% at 3 months, 6 months and 9 months post-treatment, respectively. No false-positive result was obtained for 42 human sera from non-endemic area, while for the 60 "healthy" individuals from endemic area, 10 (16.7%) individuals were positive by LAMP, which suggested that these individuals might be false-negative patients. The present study demonstrated that the LAMP assay is sensitive, specific, and affordable, which would help reduce schistosomiasis transmission through targeted treatment of individuals, particularly for those with negative stool examinations who may yet remain infected. The LAMP assay may provide a potential tool to support schistosomiasis control and elimination strategies.

Developmental gene expression profiles of the human pathogen Schistosoma japonicum

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McManus Donald P

2009-03-01

Full Text Available Abstract Background The schistosome blood flukes are complex trematodes and cause a chronic parasitic disease of significant public health importance worldwide, schistosomiasis. Their life cycle is characterised by distinct parasitic and free-living phases involving mammalian and snail hosts and freshwater. Microarray analysis was used to profile developmental gene expression in the Asian species, Schistosoma japonicum. Total RNAs were isolated from the three distinct environmental phases of the lifecycle – aquatic/snail (eggs, miracidia, sporocysts, cercariae, juvenile (lung schistosomula and paired but pre-egg laying adults and adult (paired, mature males and egg-producing females, both examined separately. Advanced analyses including ANOVA, principal component analysis, and hierarchal clustering provided a global synopsis of gene expression relationships among the different developmental stages of the schistosome parasite. Results Gene expression profiles were linked to the major environmental settings through which the developmental stages of the fluke have to adapt during the course of its life cycle. Gene ontologies of the differentially expressed genes revealed a wide range of functions and processes. In addition, stage-specific, differentially expressed genes were identified that were involved in numerous biological pathways and functions including calcium signalling, sphingolipid metabolism and parasite defence. Conclusion The findings provide a comprehensive database of gene expression in an important human pathogen, including transcriptional changes in genes involved in evasion of the host immune response, nutrient acquisition, energy production, calcium signalling, sphingolipid metabolism, egg production and tegumental function during development. This resource should help facilitate the identification and prioritization of new anti-schistosome drug and vaccine targets for the control of schistosomiasis.

Molecular characterization and expression profile of nanos in Schistosoma japonicum and its influence on the expression several mammalian stem cell factors.

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Giri, Bikash Ranjan; Du, Xiaoli; Xia, Tianqi; Chen, Yongjun; Li, Hao; Cheng, Guofeng

2017-07-01

Pluripotent stem cells, called neoblasts, are well known for the regenerative capability and developmental plasticity in flatworms. Impressive advancement has been made in free-living flatworms, while in case of its parasitic counterpart, neoblast-like stem cells have attracted recent attention for its self-renewal and differentiation capacity. Nanos is a key conserved post-transcriptional regulator critical for the formation, development, and/or maintenance of the pluripotent germ line stem cell systems in many metazoans including schistosomes. In the present study, we report the molecular cloning and expression of nanos orthologous genes nanos in Schistosoma japonicum (Sjnanos). The cDNA of Sjnanos is 826 bp long, containing an open reading frame (ORF) for 223 amino acid long protein. qRT-PCR analysis shown that Sjnanos was differently expressed in several stages of schistosomes with relatively high level in schistosomula. Additionally, Sjnanos was expressed highly in adult females compared to adult males. Transfection of recombinant plasmid for expressing Sjnanos resulted in significant proliferation and increased expression of several stem cell factors in mammalian cells. Overall, our preliminary study provides the molecular basis to further functionally characterize Sjnanos in S. japonicum.

Immunoglobulins and complement in the skin of Rhesus monkeys immunized with X-irradiated cercariae of Schistosoma japonicum

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Li-Hsue, S.Y.; Hsue, H.F.; Hanson, H.O.

1981-01-01

Skin sections of Rhesus monkeys immunized with X-irradiated Schistosoma japonicum cercariae were stained by an unlabeled antibody enzyme method for the detection of IgG, IgM, IgA, IgE, and C3. While all of them could be found in the skin lesions, their distribution patterns varied with time and reactions. In whealing reaginic reactions, IgE appeared prominent, having an affinity to the mast cells. In Arthus-like reactions, IgG was predominant. IgG complexes were found on the schistosomula, on the walls of blood vessels, and in granulocytes near the schistosomula. In the late stage of Arthus-like reactions and in delayed hypersensitive reactions, IgA was predominant in granulocytes, mononuclear cells, and macrophages. Characteristics of each immunoglobulin pattern seemed to reflect its function in the effector mechanism. It may be speculated that these immunoglobulins and C3, together with effector cells, synergistically and sequentially destroy schistosomula in the skin. (orig.)

Immunoglobulins and complement in the skin of Rhesus monkeys immunized with X-irradiated cercariae of Schistosoma japonicum

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Li-Hsue, S.Y.; Hsue, H.F.; Hanson, H.O.

1981-01-01

Skin sections of Rhesus monkeys immunized with X-irradiated Schistosoma japonicum cercariae were stained by an unlabeled antibody enzyme method for the detection of IgG, IgM, IgA, IgE, and C3. While all of them could be found in the skin lesions, their distribution patterns varied with time and reactions. In whealing reaginic reactions, IgE appeared prominent, having an affinity to the mast cells. In Arthus-like reactions, IgG was predominant. IgG complexes were found on the schistosomula, on the walls of blood vessels, and in granulocytes near the schistosomula. In the late stage of Arthus-like reactions and in delayed hypersensitive reactions, IgA was predominant in granulocytes, mononuclear cells, and macrophages. Characteristics of each immunoglobulin pattern seemed to reflect its function in the effector mechanism. It may be speculated that these immunoglobulins and C3, together with effector cells, synergistically and sequentially destroy schistosomula in the skin.

DNA detection of Schistosoma japonicum: diagnostic validity of a LAMP assay for low-intensity infection and effects of chemotherapy in humans.

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Jing Xu

2015-04-01

Full Text Available Schistosomiasis has decreased significantly in prevalence and intensity of infection in China, thus more accurate and sensitive methods are desperately needed for the further control of schistosomiasis. The present work aimed to assess the utility of the loop-mediated isothermal amplification (LAMP for detection of light intensity infection or false-negative patients and patients post-treatment, targeting the highly repetitive retrotransposon SjR2 of Schistosoma japonicum.LAMP was first assessed in rabbits with low intensity infection (EPG<10. Then 110 patient sera from Hunan Province, China, and 47 sera after treatment by praziquantel were used to evaluate the diagnostic validity of LAMP. Meanwhile, 42 sera from healthy individuals in a non-endemic area, and 60 sera from "healthy" residents who were identified as being negative for feces examination and immuno-methods in an endemic area were also examined. The results showed that LAMP could detect S. japonicum DNA in sera from rabbits at 3rd day post-infection. Following administration of praziquantel, the S. japonicum DNA in rabbit sera became negative at 10 weeks post-treatment. Of 110 sera from patients, LAMP showed 95.5% sensitivity, and even for 41 patients with less than 10 EPG, the sensitivity of LAMP still reached to 95.1%. For 47 patients after treatment, the negative conversion rate of S. japonicum DNA in patient sera increased from 23.4%, 61.7% to 83.0% at 3 months, 6 months and 9 months post-treatment, respectively. No false-positive result was obtained for 42 human sera from non-endemic area, while for the 60 "healthy" individuals from endemic area, 10 (16.7% individuals were positive by LAMP, which suggested that these individuals might be false-negative patients.The present study demonstrated that the LAMP assay is sensitive, specific, and affordable, which would help reduce schistosomiasis transmission through targeted treatment of individuals, particularly for those with

Comprehensive Transcriptome Analysis of Sex-Biased Expressed Genes Reveals Discrete Biological and Physiological Features of Male and Female Schistosoma japonicum.

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Pengfei Cai

2016-04-01

Full Text Available Schistosomiasis is a chronic and debilitating disease caused by blood flukes (digenetic trematodes of the genus Schistosoma. Schistosomes are sexually dimorphic and exhibit dramatic morphological changes during a complex lifecycle which requires subtle gene regulatory mechanisms to fulfil these complex biological processes. In the current study, a 41,982 features custom DNA microarray, which represents the most comprehensive probe coverage for any schistosome transcriptome study, was designed based on public domain and local databases to explore differential gene expression in S. japonicum. We found that approximately 1/10 of the total annotated genes in the S. japonicum genome are differentially expressed between adult males and females. In general, genes associated with the cytoskeleton, and motor and neuronal activities were readily expressed in male adult worms, whereas genes involved in amino acid metabolism, nucleotide biosynthesis, gluconeogenesis, glycosylation, cell cycle processes, DNA synthesis and genome fidelity and stability were enriched in females. Further, miRNAs target sites within these gene sets were predicted, which provides a scenario whereby the miRNAs potentially regulate these sex-biased expressed genes. The study significantly expands the expressional and regulatory characteristics of gender-biased expressed genes in schistosomes with high accuracy. The data provide a better appreciation of the biological and physiological features of male and female schistosome parasites, which may lead to novel vaccine targets and the development of new therapeutic interventions.

Comprehensive Transcriptome Analysis of Sex-Biased Expressed Genes Reveals Discrete Biological and Physiological Features of Male and Female Schistosoma japonicum.

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Cai, Pengfei; Liu, Shuai; Piao, Xianyu; Hou, Nan; Gobert, Geoffrey N; McManus, Donald P; Chen, Qijun

2016-04-01

Schistosomiasis is a chronic and debilitating disease caused by blood flukes (digenetic trematodes) of the genus Schistosoma. Schistosomes are sexually dimorphic and exhibit dramatic morphological changes during a complex lifecycle which requires subtle gene regulatory mechanisms to fulfil these complex biological processes. In the current study, a 41,982 features custom DNA microarray, which represents the most comprehensive probe coverage for any schistosome transcriptome study, was designed based on public domain and local databases to explore differential gene expression in S. japonicum. We found that approximately 1/10 of the total annotated genes in the S. japonicum genome are differentially expressed between adult males and females. In general, genes associated with the cytoskeleton, and motor and neuronal activities were readily expressed in male adult worms, whereas genes involved in amino acid metabolism, nucleotide biosynthesis, gluconeogenesis, glycosylation, cell cycle processes, DNA synthesis and genome fidelity and stability were enriched in females. Further, miRNAs target sites within these gene sets were predicted, which provides a scenario whereby the miRNAs potentially regulate these sex-biased expressed genes. The study significantly expands the expressional and regulatory characteristics of gender-biased expressed genes in schistosomes with high accuracy. The data provide a better appreciation of the biological and physiological features of male and female schistosome parasites, which may lead to novel vaccine targets and the development of new therapeutic interventions.

Exosomes Derived from Dendritic Cells Treated with Schistosoma japonicum Soluble Egg Antigen Attenuate DSS-Induced Colitis

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Lifu Wang

2017-09-01

Full Text Available Exosomes are 30–150 nm small membrane vesicles that are released into the extracellular medium via cells that function as a mode of intercellular communication. Dendritic cell (DC-derived exosomes modulate immune responses and prevent the development of autoimmune diseases. Moreover, Schistosoma japonicum eggs show modulatory effects in a mouse model of colitis. Therefore, we hypothesized that exosomes derived from DCs treated with S. japonicum soluble eggs antigen (SEA; SEA-treated DC exosomes would be useful for treating inflammatory bowel disease (IBD. Exosomes were purified from the supernatant of DCs treated or untreated with SEA and identified via transmission electron microscopy, western blotting and NanoSight. Acute colitis was induced via the administration of dextran sulfate sodium (DSS in drinking water (5.0%, wt/vol. Treatment with exosomes was conducted via intraperitoneal injection (i.p.; 50 μg per mouse from day 0 to day 6. Clinical scores were calculated based on weight loss, stool type, and bleeding. Colon length was measured as an indirect marker of inflammation, and colon macroscopic characteristics were determined. Body weight loss and the disease activity index of DSS-induced colitis mice decreased significantly following treatment with SEA-treated DC exosomes. Moreover, the colon lengths of SEA-treated DC exosomes treated colitis mice improved, and their mean colon macroscopic scores decreased. In addition, histologic examinations and histological scores showed that SEA-treated DC exosomes prevented colon damage in acute DSS-induced colitis mice. These results indicate that SEA-treated DC exosomes attenuate the severity of acute DSS-induced colitis mice more effectively than DC exosomes. The current work suggests that SEA-treated DC exosomes may be useful as a new approach to treat IBD.

SjCRT, a recombinant Schistosoma japonicum calreticulin, induces maturation of dendritic cells and a Th1-polarized immune response in mice

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Lizhen Ma

2017-11-01

Full Text Available Abstract Background It is well known that immunization of radiation-attenuated (RA schistosoma cercariae or schistosomula can induce high levels of protective immunity against schistosoma cercariae reinfection in many animals. Many studies have shown that the Th1 cellular immune response is crucial for the protective effect elicited by RA schistosomula. However, the molecular mechanism of this strong protective immunity remains unclear. Methods The expression profiles of Schistosoma japonicum calreticulin (SjCRT in RA and normal schistosoma-derived cells were investigated by flow cytometry. The effect of recombinant SjCRT (rSjCRT on mouse dendritic cells (DCs was determined by FACS, ELISA and RT-PCR analysis. We also analyzed the effects of SjCRT on the activation of spleen cells from mice immunized with rSjCRT by detecting lymphocyte proliferation and the cytokine profiles of splenocytes. Results We found that the expression level of SjCRT in the cells from RA larvae was significantly higher than that in cells from normal schistosomula at early stages of development (day 4. The results of effect of rSjCRT on mouse DCs showed that rSjCRT could induce phenotypic and functional maturation of DCs, and SjCRT bound to the surface of DCs through the CD91 receptor and could be engulfed by DCs. The results of activation of splenocytes from mice immunized with rSjCRT also demonstrate that rSjCRT can effectively stimulate the proliferative response of splenic lymphocytes, elicit splenocytes from immunized mice to secrete high levels of IFN-γ, TNF-α and IL-4, and activate CD4+ T cells to produce high levels of IFN-γ. Conclusion SjCRT is one of the immunostimulatory molecules released from RA schistosomula cells, might play a crucial role in conferring a Th1-polarized immune response induced by RA cercariae/schistosomula in mice, and is a candidate molecule responsible for the high levels of protective immunity induced by RA schistosomula.

The nature and combination of subunits used in epitope-based Schistosoma japonicum vaccine formulations affect their efficacy

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Liu Feng

2010-11-01

Full Text Available Abstract Background Schistosomiasis remains a major public health problem in endemic countries and is caused by infections with any one of three primary schistosome species. Although there are no vaccines available to date, this strategy appears feasible since natural immunity develops in individuals suffering from repeated infection during a lifetime. Since vaccinations resulting in both Th1- and Th2-type responses have been shown to contribute to protective immunity, a vaccine formulation with the capacity for stimulating multiple arms of the immune response will likely be the most effective. Previously we developed partially protective, single Th- and B cell-epitope-based peptide-DNA dual vaccines (PDDV (T3-PDDV and B3-PDDV, respectively capable of eliciting immune responses against the Schistosoma japonicum 22.6 kDa tegument antigen (Sj22.6 and a 62 kDa fragment of myosin (Sj62, respectively. Results In this study, we developed PDDV cocktails containing multiple epitopes of S. japonicum from Sj22.6, Sj62 and Sj97 antigens by predicting cytotoxic, helper, and B-cell epitopes, and evaluated vaccine potential in vivo. Results showed that mice immunized with a single-epitope PDDV elicited either Tc, Th, or B cell responses, respectively, and mice immunized with either the T3- or B3- single-epitope PDDV formulation were partially protected against infection. However, mice immunized with a multicomponent (3 PDDV components formulation elicited variable immune responses that were less immunoprotective than single-epitope PDDV formulations. Conclusions Our data show that combining these different antigens did not result in a more effective vaccine formulation when compared to each component administered individually, and further suggest that immune interference resulting from immunizations with antigenically distinct vaccine targets may be an important consideration in the development of multicomponent vaccine preparations.

Oral delivery of the Sj23LHD-GST antigen by Salmonella typhimurium type III secretion system protects against Schistosoma japonicum infection in mice.

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Guo Chen

2011-09-01

Full Text Available BACKGROUND: Schistosomiasis japonica is a zoonotic parasitic disease and oral vaccine delivery system would be benefit for prevention of this disease. Although attenuated salmonella has been used as an antigen expression vector for oral vaccine development, the membrane-bound vacuoles in which bacteria reside hinders the presentation of expressed heterologous antigens to the major histocompatibility complex (MHC molecules. The present work used an attenuated Salmonella typhimurium strain VNP20009 to secretory expression of Sj23LHDGST bivalent antigen from Schistosoma japonicum and tested the protective efficacy against S. japonicum infection in orally immunized mice. METHODOLOGY/PRINCIPAL FINDINGS: Promoters (nirB or pagC were used to express the antigen (Sj23LHDGST and the Salmonella type III or α-hemolysin secretion system was employed to secrete it. The immunoblotting analysis and fluorescent microscopy revealed that the antigen was effectively expressed and delivered to the cytosol of macrophages in vitro. Among recombinant vaccine strains, an engineered VNP20009 which expressed the antigen by nirB promoter and secreted it through type III secretion system (nirB-sopE(1-104-Sj23LHD-GST efficiently protected against S. japonicum infection in a mouse model. This strain elicited a predominantly IgG(2a antibody response and a markedly increase in the production of IL-12 and IFN-γ. The flow cytometric analysis demonstrated that this strain caused T cell activation as evidenced by significantly increased expression of CD44 and CD69. CONCLUSION/SIGNIFICANCE: Oral delivery of antigen by nirB-driven Salmonella typhimurium type III secretion system is a novel, safe, inexpensive, efficient and convenient approach for schistosome vaccine development.

Influence of Schistosoma japonicum programmed cell death protein 10 on the growth and development of schistosomula.

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Gao, Yan Ru; Huang, Wen Ling; Tang, Chun Lian; Liu, Rong; Zhao, Qin Ping; Ming, Zhen Ping; Dong, Hui Fen

2018-01-18

Schistosomiasis caused by Schistosoma japonicum is among the most serious endemic zoonoses in China. To study interactions between schistosomula, the pre-adult juvenile stage, and hosts, it is important to study the functions of key genes involved in schistosomula growth and development. Programmed cell death protein 10 (pcdp10) is an important apoptosis-related gene with various biological functions. This study described the molecular characterization of S. japonicum PCDP10 (SjPCDP10) and evaluated its functions in schistosomula. Real-time quantitative polymerase chain reaction (qPCR) and western blot were used to detect Sjpcdp10 mRNA and protein levels, respectively, at different developmental stages. Immunolocalization was performed to determine SjPCDP10 expression in the parasite. RNA interference (RNAi) experiments were used to assess gene functions associated with SjPCDP10 in schistosomula growth and development. Real-time qPCR revealed that Sjpcdp10 was expressed during all investigated developmental stages and upregulated during schistosomula growth and development. Histochemical localization showed that SjPCDP10 was mainly distributed in the teguments of schistosomula in all investigated stages and part of the parenchymal area of 14-, 18-, and 21-day-old schistosomula. Following Sjpcdp10 knockdown by RNAi, the lengths, widths, areas, and volumes of schistosomula were significantly lower than those in the control group. Scanning electron microscopy showed that the body surfaces of schistosomula subjected to RNAi were seriously damaged, with few tegumental spines and sensory papillae. Transmission electron microscopy indicated that the teguments of Sjpcdp10-knockdown schistosomula were incomplete, the number of layers was reduced, and the thickness decreased significantly as compared with those in the control group. Furthermore, terminal deoxynucleotidyl transferase dUTP nick-end labelling results showed that the rate of apoptosis in Sjpcdp10-knockdown

NCBI nr-aa BLAST: CBRC-MMUR-01-0199 [SEVENS

Lifescience Database Archive (English)

Full Text Available CBRC-MMUR-01-0199 emb|CAX76110.1| putative tubulin, beta, 2 [Schistosoma japonicum]... emb|CAX76111.1| putative tubulin, beta, 2 [Schistosoma japonicum] emb|CAX76112.1| putative tubulin, beta, 2 [Schistosoma jap...onicum] emb|CAX76113.1| putative tubulin, beta, 2 [Schistosoma japonicum] emb|CAX76114.1| p...utative tubulin, beta, 2 [Schistosoma japonicum] emb|CAX76115.1| putative tubulin..., beta, 2 [Schistosoma japonicum] emb|CAX76116.1| putative tubulin, beta, 2 [Schistosoma japonicum] CAX76110.1 2e-31 82% ...

Utilization of real time PCR for the assessment of egg burden in the organs of Schistosoma japonicum experimentally infected mice.

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Dang-Trinh, Minh-Anh; Angeles, Jose Ma M; Moendeg, Kharleezelle J; Macalanda, Adrian Miki C; Higuchi, Luna; Oto, Chiho; Kirinoki, Masashi; Chigusa, Yuichi; Kawazu, Shin-Ichiro

2018-06-01

Schistosoma japonicum, causing zoonotic intestinal schistosomiasis, is found in China, the Philippines and parts of Indonesia. Severe disease manifestations are basically due to the deposition of eggs in some vital organs such as the liver, spleen and brain. Traditionally, histopathological microscopic examination of the egg burden was used to evaluate the intensity of infection in the affected organs. However, this technique is laborious, time-consuming and requires trained personnel. In this study, real time PCR targeting the mitochondrial NADH dehydrogenase I gene was used to compare with microscopic examination of tissue sections in evaluating the egg burdens in different affected organs. Livers, spleens and brains of the S. japonicum infected mice after 8 and 18 weeks post-infection (p.i) were harvested and examined. Results showed that there were statistically significant correlations between the egg burden evaluated by tissue section examination, and the Ct values of the real time PCR of livers with heavy egg burden at 8 (r = -0.81) and 18 (r = -0.80) weeks p.i. Furthermore, a correlation (r = -0.56) between the egg burden assessed by the microscopic examination and Ct value of the real time PCR of spleens with moderate egg burden after 18 weeks p.i and not 8 weeks p.i was also observed. Brains with low egg burden showed no schistosome eggs in the microscopic examination, however one sample tested positive by real time PCR. These results suggested that real time PCR is useful in evaluating schistosome egg burden in the organs of the experimentally infected mice model that will give further insights into the pathology of schistosomiasis. Copyright © 2018 Elsevier Inc. All rights reserved.

Mini-review: the ultrasonographical and serological chanbges and their improvement after praziquantel treatment Schistosoma japonicum infected patients in Leyete, Philippines

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Manami Tanaka

1992-01-01

Full Text Available We have identified the specific ultrasonographical (US changes in Schistosoma japonicum infected patients with the serological changes in general liver function markers. The US examination with the following haematological and biochemical serum analysis was performed on 102 patients in Shistosomiasis Hospital, Leyte, Philippines. The US liver images were classified into 4 patterns according to the development of periportal fibrosis and the patterns of echogenic bands. Among various haematological and biochemical serum parameters of liver damage. The serum levels of total bile acid (TBA and procollagen-III-peptide (P-III-P correlated well with the development of hepatic fibrosis and the portal hypertension. These patients were subsequently treated with praziquantel (3 x 20 mg/kg, and improvement of the thickening of the portal vein wall and the dintensity of the echogenic band formation was detected 6 months after treatment. The significant US changes could not be detected in the patients with severe hepatic fibrosis caused in the long term infection. The results revealed that the US examination with the serum TBa level would provider a sensitive tool monitor the severity of the infection and also the improvement occured shortly after praziquantel treatment.

Distinct genetic diversity of Oncomelania hupensis, intermediate host of Schistosoma japonicum in mainland China as revealed by ITS sequences.

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Qin Ping Zhao

Full Text Available BACKGROUND: Oncomelania hupensis is the unique intermediate host of Schistosoma japonicum, which causes schistosomiasis endemic in the Far East, and especially in mainland China. O. hupensis largely determines the parasite's geographical range. How O. hupensis's genetic diversity is distributed geographically in mainland China has never been well examined with DNA sequence data. METHODOLOGY/PRINCIPAL FINDINGS: In this study we investigate the genetic variation among O. hupensis from different geographical origins using the combined complete internal transcribed spacer 1 (ITS1 and ITS2 regions of nuclear ribosomal DNA. 165 O. hupensis isolates were obtained in 29 localities from 7 provinces across mainland China: lake/marshland and hill regions in Anhui, Hubei, Hunan, Jiangxi and Jiangsu provinces, located along the middle and lower reaches of Yangtze River, and mountainous regions in Sichuan and Yunnan provinces. Phylogenetic and haplotype network analyses showed distinct genetic diversity and no shared haplotypes between populations from lake/marshland regions of the middle and lower reaches of the Yangtze River and populations from mountainous regions of Sichuan and Yunnan provinces. The genetic distance between these two groups is up to 0.81 based on Fst, and branch time was estimated as 2-6 Ma. As revealed in the phylogenetic tree, snails from Sichuan and Yunnan provinces were also clustered separately. Geographical separation appears to be an important factor accounting for the diversification of the two groups of O. hupensis in mainland China, and probably for the separate clades between snails from Sichuan and Yunnan provinces. In lake/marshland and hill regions along the middle and lower reaches of the Yangtze River, three clades were identified in the phylogenetic tree, but without any obvious clustering of snails from different provinces. CONCLUSIONS: O. hupensis in mainland China may have considerable genetic diversity, and a more

Whole Genome Amplification and Reduced-Representation Genome Sequencing of Schistosoma japonicum Miracidia.

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Jonathan A Shortt

2017-01-01

Full Text Available In areas where schistosomiasis control programs have been implemented, morbidity and prevalence have been greatly reduced. However, to sustain these reductions and move towards interruption of transmission, new tools for disease surveillance are needed. Genomic methods have the potential to help trace the sources of new infections, and allow us to monitor drug resistance. Large-scale genotyping efforts for schistosome species have been hindered by cost, limited numbers of established target loci, and the small amount of DNA obtained from miracidia, the life stage most readily acquired from humans. Here, we present a method using next generation sequencing to provide high-resolution genomic data from S. japonicum for population-based studies.We applied whole genome amplification followed by double digest restriction site associated DNA sequencing (ddRADseq to individual S. japonicum miracidia preserved on Whatman FTA cards. We found that we could effectively and consistently survey hundreds of thousands of variants from 10,000 to 30,000 loci from archived miracidia as old as six years. An analysis of variation from eight miracidia obtained from three hosts in two villages in Sichuan showed clear population structuring by village and host even within this limited sample.This high-resolution sequencing approach yields three orders of magnitude more information than microsatellite genotyping methods that have been employed over the last decade, creating the potential to answer detailed questions about the sources of human infections and to monitor drug resistance. Costs per sample range from $50-$200, depending on the amount of sequence information desired, and we expect these costs can be reduced further given continued reductions in sequencing costs, improvement of protocols, and parallelization. This approach provides new promise for using modern genome-scale sampling to S. japonicum surveillance, and could be applied to other schistosome species

Whole Genome Amplification and Reduced-Representation Genome Sequencing of Schistosoma japonicum Miracidia.

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Shortt, Jonathan A; Card, Daren C; Schield, Drew R; Liu, Yang; Zhong, Bo; Castoe, Todd A; Carlton, Elizabeth J; Pollock, David D

2017-01-01

In areas where schistosomiasis control programs have been implemented, morbidity and prevalence have been greatly reduced. However, to sustain these reductions and move towards interruption of transmission, new tools for disease surveillance are needed. Genomic methods have the potential to help trace the sources of new infections, and allow us to monitor drug resistance. Large-scale genotyping efforts for schistosome species have been hindered by cost, limited numbers of established target loci, and the small amount of DNA obtained from miracidia, the life stage most readily acquired from humans. Here, we present a method using next generation sequencing to provide high-resolution genomic data from S. japonicum for population-based studies. We applied whole genome amplification followed by double digest restriction site associated DNA sequencing (ddRADseq) to individual S. japonicum miracidia preserved on Whatman FTA cards. We found that we could effectively and consistently survey hundreds of thousands of variants from 10,000 to 30,000 loci from archived miracidia as old as six years. An analysis of variation from eight miracidia obtained from three hosts in two villages in Sichuan showed clear population structuring by village and host even within this limited sample. This high-resolution sequencing approach yields three orders of magnitude more information than microsatellite genotyping methods that have been employed over the last decade, creating the potential to answer detailed questions about the sources of human infections and to monitor drug resistance. Costs per sample range from $50-$200, depending on the amount of sequence information desired, and we expect these costs can be reduced further given continued reductions in sequencing costs, improvement of protocols, and parallelization. This approach provides new promise for using modern genome-scale sampling to S. japonicum surveillance, and could be applied to other schistosome species and other

Clinical diagnostic value of viable Schistosoma japonicum eggs detected in host tissues.

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Gu, Kongzhen; Li, Yuesheng; Driguez, Patrick; Zeng, Qingren; Yu, Xinlin; Sun, Hui; Cai, Liting; He, Yongkang; Wang, Wenyang; McManus, Donald P

2017-04-04

Schistosomiasis, one of the neglected tropical diseases, is endemic in more than 70 countries. However, the clinical diagnosis of patients with a low degree of infection is an unsolved technical problem. In areas endemic for schistosomiasis japonica, proctoscopy detection of eggs has been one method used for clinical diagnosis. However, it is often a challenge to find typical live eggs and it is difficult to distinguish live eggs from large numbers of partially degraded and/or completely degraded eggs within colon biopsy tissue. To address this problem, we tested six different morphological and biochemical/molecular markers (ALP; morphological characteristics of egg; CalS (calcified substance); AOS (antioxidase); SDHG (succinic dehydrogenase) and SjR2 mRNA (retrotransposons 2 of S.japonicum genome mRNA)), including four new markers (CalS; AOS; SDHG and SjR2 mRNA.), to determine the viability of S. japonicum eggs deposited in human and mouse colon tissues. Our ultimate aim is to obtain a new method that is more sensitive, practical and accurate to clinically diagnose schistosomiasis. Tissue samples were collected from mice at six different time points during S. japonicum infection with or without treatment with praziquantel (PZQ). Four new biochemical or molecular markers were used for the detection of egg viability from mouse liver and intestinal samples: CalS; AOS; SDHG and SjR2 mRNA. Subsequently, all markers were employed for the detection and analysis of eggs deposited in biopsy materials from patients with suspected schistosomiasis japonica for clinical evaluation. Microscopic examination of the egg morphology, worm burden in vivo and ALP (alkaline phosphatase) levels were used as a reference standard to evaluate the sensitivity and reliability of four new markers detecting egg viability. The results of the study showed that the morphology of S. japonicum eggs deposited in tissues of hosts with schistosomiasis, especially cases with chronic schistosomiasis, is

Low Transmission to Elimination: Rural Development as a Key Determinant of the End-Game Dynamics of Schistosoma japonicum in China

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Robert Spear

2017-08-01

Full Text Available Rural development has been a critical component of China’s economic miracle since the start of economic reform in the early 1980s, both benefiting from and contributing to the nation’s rapid economic growth. This development has yielded substantial improvements of public health relevance, including contributing to major reductions in schistosomiasis prevalence. The history of schistosomiasis elimination in Japan suggests that development played a dominant causal role in that nation. We argue that it is highly probable that a similar story is playing out in at least some large regions of China. In particular, we summarize evidence from Sichuan Province which supports the case that economic development has led to improvements in rural irrigation and water supply which, together with changes in crop selection and agricultural mechanization, have all contributed to sustainable reductions in the prevalence of Schistosoma japonicum. The two major factors that have experienced major reductions are the area of snail habitat and the degree of human exposure, both through a variety of mechanisms which differ by region and economic circumstance. However, hotspots of transmission remain. Overall, however, economic development in traditionally endemic areas has provided the resources to carry out projects that have had major beneficial impacts on disease transmission that are likely to be sustainable.

NCBI nr-aa BLAST: CBRC-MMUR-01-0199 [SEVENS

Lifescience Database Archive (English)

Full Text Available CBRC-MMUR-01-0199 emb|CAX75788.1| Tubulin beta-2C chain [Schistosoma japonicum] emb...|CAX75790.1| Tubulin beta-2C chain [Schistosoma japonicum] emb|CAX75791.1| Tubulin beta-2C chain [Schistosoma japonicum] CAX75788.1 2e-31 82% ...

Schistosoma japonicum risk in Jiangsu province, People’s Republic of China: identification of a spatio-temporal risk pattern along the Yangtze River

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Kun Yang

2013-11-01

Full Text Available The risk for Schistosoma japonicum infection in Jiangsu province, People’s Republic of China, was investigated by a mouse bioassay. Various investigations were conducted in the period 2009-2011 with the presentation here representing the summary of the results from 45-50 sites in the marshlands along the Yangtze River’s course through the province. Indices representing three aspects of the infection were collected to assess risk: (i the proportion of sentinel points where at least one mouse infection was recorded; (ii the proportion of infected mice at each of these sites; and (iii the average worm burdens. Directional distribution analysis and scan statistics were used to explore the spatio-temporal risk pattern. The spatial distribution was oriented along the Yangtze River and the directional distributions for the proportion of infected mice and mean worm burdens were similar for the positive sentinel sites. Four statistically significant clusters were detected in 2009, but only one in 2010 and 2011, respectively. Temporal windows for infection risk were seen in June and September. The study illustrates the utility of spatio-temporal analysis in assessing the risk for schistosomiasis. This approach should be useful with respect to surveillance and response that can be expected to be increasingly applied when moving from morbidity control to transmission control.

Phosphagen kinase in Schistosoma japonicum: characterization of its enzymatic properties and determination of its gene structure.

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Tokuhiro, Shinji; Uda, Kouji; Yano, Hiroko; Nagataki, Mitsuru; Jarilla, Blanca R; Suzuki, Tomohiko; Agatsuma, Takeshi

2013-04-01

Phosphagen kinases (PKs) play a major role in the regulation of energy metabolism in animals. Creatine kinase (CK) is the sole PK in vertebrates, whereas several PKs are present in invertebrates. Here, we report the enzymatic properties and gene structure of PK in the trematode Schistosoma japonicum (Sj). SjPK has a unique contiguous dimeric structure comprising domain 1 (D1) and domain 2 (D2). The three states of the recombinant SjPK (D1, D2, and D1D2) show a specific activity for the substrate taurocyamine. The comparison of the two domains of SjPK revealed that D1 had a high turnover rate (kcat=52.91) and D2 exhibited a high affinity for taurocyamine (Km(Tauro) =0.53±0.06). The full-length protein exhibited higher affinity for taurocyamine (Km(Tauro) =0.47±0.03) than the truncated domains (D1=1.30±0.10, D2=0.53±0.06). D1D2 also exhibited higher catalytic efficiency (kcat/Km(Tauro) =82.98) than D1 (40.70) and D2 (29.04). These results demonstrated that both domains of SjTKD1D2 interacted efficiently and remained functional. The three-dimensional structure of SjPKD1 was constructed by the homology modeling based on the transition state analog complex state of Limulus AK. This protein model of SjPKD1 suggests that the overall structure is almost conserve between SjPKD1 and Limulus AK except for the flexible loops, that is, particularly guanidino-specificity (GS) region, which is associated with the recognition of the corresponding guanidino substrate. The constructed NJ tree and the comparison of exon/intron organization suggest that SjTK has evolved from an arginine kinase (AK) gene. SjTK has potential as a novel antihelminthic drug target as it is absent in mammals and its strong activity may imply a significant role for this protein in the energy metabolism of the parasite. Copyright © 2013 Elsevier B.V. All rights reserved.

Genetic variation and differentiation of three Schistosoma species from the Philippines, Laos, and Peninsular Malaysia.

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Woodruff, D S; Merenlender, A M; Upatham, E S; Viyanant, V

1987-03-01

Electrophoretically-detected allozyme variation is described in strains of Schistosoma japonicum (4 Philippine strains), S. mekongi (Laos), and an undescribed anthropophilic S. japonicum-like schistosome from Peninsular Malaysia. Result, together with those reported previously for 8 other strains (S. japonicum, China, Formosa, Japan, Philippines; S. mekongi, 2 substrains; Malaysian schistosome, 2 strains) permit a composite genetic characterization of 15 strains of Asian schistosomes at 9-18 presumptive loci. The proportion of polymorphic loci (P) and the mean heterozygosity per locus (H) were zero in all strains. Although this was expected for strains that had been in laboratory culture for up to 50 years, we expected to detect variation in strains based on 10-50 recently field-collected infected snails. We expected S. japonicum to be as variable as S. mansoni (P = 0.13 (0-0.33), H = 0.04, 18 loci, 22 strains) as it is believed to reproduce sexually, has an evolutionary history of several million years, inhabits a wide geographic range, coevolved with a genetically variable intermediate snail host, and has a diversity of mammalian hosts. No differences were detected between the 5 S. japonicum strains from Leyte and Luzon (Philippines), between the 3 S. mekongi strains, or between the 3 Malaysian schistosome strains; these groups and the remaining S. japonicum strains representing Mindoro (Philippines), China, Formosa, and Japan each have distinctive multilocus electromorphic patterns. Nei's genetic distances (D) were calculated to estimate interstrain and interspecific divergence. Interstrain genetic distances in S. japonicum averaged greater than 0.3; much higher than those reported previously for S. mansoni (D = 0.06, D(max) = 0.24). S. japonicum (Mindoro) was moderately differentiated from the Leyte-Luzon strains (D = 0.29, 12 loci). Estimates of the S. japonicum China-Philippine distance (D greater than 0.4, 11 loci) are high for conspecific populations and

The South-to-North Water Diversion Project: effect of the water diversion pattern on transmission of Oncomelania hupensis, the intermediate host of Schistosoma japonicum in China.

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Liang, You-Sheng; Wang, Wei; Li, Hong-Jun; Shen, Xue-Hui; Xu, Yong-Liang; Dai, Jian-Rong

2012-03-20

The South-to-North Water Diversion Project (SNWDP) is the largest national water conservancy project in China. However, the Eastern Route Project (ERP) of SNWDP will refer to the habitats of Oncomelania hupensis, the intermediate host of Schistosoma japonicum. The present study was aimed at investigating the effects of some factors relating to the water diversion pattern on the spread north of O. hupensis and transmission of S. japonicum. Marked snails were attached to the floating debris, and then placed on the water surface, the passage of snails through water pumps was observed. Some marked living adult snails were placed under water in the 5 spots, 15, 30, 60, 90 and 120 days later, their survival and transfer under water were investigated. 2, 4, 8, 16, 32, 64 and 128 juvenile snails, with a male: female ratio of about 1, were caged, 1 year later, their reproductions were calculated. The snails attached on the floating debris at 100-, 50- and 20-cm-distance from the inlet pipe of the big pump (with a diameter of 80 cm), could be absorbed into the pumps, with passing rates of 2.45%, 3.93% and 43.46%, respectively, compared with 72.07% and 91.00% for the snails at 20 cm and 10 cm-distance from the inlet pipe of the small pump (with a diameter of 20 cm). A total of 36,600 marked living snails were put into 5 ponds and ditches, with the water depths of 1-1.6 m, 15-120 days later, no marked ones were found along the ponds and ditches or in the straw packages. The juvenile snails did not reproduce until their density reached up to 8 snails (ratio of male: female of 1)/0.16 m2. During the construction of ERP of SNWDP, the risk of northward spread of schistosomiasis japonica will be decreased or eliminated as long as long-term reliable interventions for snail control are implemented.

Microarray analysis of gene expression profiles of Schistosoma japonicum derived from less-susceptible host water buffalo and susceptible host goat.

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Jianmei Yang

Full Text Available BACKGROUND: Water buffalo and goats are natural hosts for S. japonicum in endemic areas of China. The susceptibility of these two hosts to schistosome infection is different, as water buffalo are less conducive to S. japonicum growth and development. To identify genes that may affect schistosome development and survival, we compared gene expression profiles of schistosomes derived from these two natural hosts using high-throughput microarray technology. RESULTS: The worm recovery rate was lower and the length and width of worms from water buffalo were smaller compared to those from goats following S. japonicum infection for 7 weeks. Besides obvious morphological difference between the schistosomes derived from the two hosts, differences were also observed by scanning and transmission electron microscopy. Microarray analysis showed differentially expressed gene patterns for parasites from the two hosts, which revealed that genes related to lipid and nucleotide metabolism, as well as protein folding, sorting, and degradation were upregulated, while others associated with signal transduction, endocrine function, development, immune function, endocytosis, and amino acid/carbohydrate/glycan metabolism were downregulated in schistosomes from water buffalo. KEGG pathway analysis deduced that the differentially expressed genes mainly involved lipid metabolism, the MAPK and ErbB signaling pathways, progesterone-mediated oocyte maturation, dorso-ventral axis formation, reproduction, and endocytosis, etc. CONCLUSION: The microarray gene analysis in schistosomes derived from water buffalo and goats provide a useful platform to disclose differences determining S. japonicum host compatibility to better understand the interplay between natural hosts and parasites, and identify schistosome target genes associated with susceptibility to screen vaccine candidates.

[Influence of kaempferol on TGF-β1/Smads signal path in liver tissue of mice with Schistosoma japonicum infection].

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Cai, Wen; Zhao, Lei; Li, Hua-rong; Zhang, Shu-ling

2014-08-01

To investigate the influence of kaempferol on transforming growth factor(TGF-β1/Smads signal tiransduction in liver tissue of mice with schistosomiasis liver fibrosis. Forty BALB/c mice were randomly divided into a normal control group (8 mice), a praziquantel group (8 mice ), and 4 praziquantel + kaempferol groups with different kaempferol dosages (5, 10, 15, 20 mg/kg respectively, 6 mice each group). Besides the normal control group, all the mice in the other 5 groups were infected with Schistosoma japonicum. After the infection for 6 weeks, the praziquantel group and the 4 praziquantel + kaempferol groups were treated with praziquantel 500 mg/(kg.d) for 2 d, then the mice in the praziquantel group were drenched with normal saline for 6 weeks, and those in the 4 praziquantel + kaempferol groups were drenched with kaempferol 5, 10, 15, 20 mg/kg respectively for 6 weeks. After the treatment, all the animals were sacrificed by the cervical dislocation method, and the area of egg granuloma and the degree of fibrosis in the livers of the mice were observed by HE and Masson staining. The expressions of TGF-β1, Smad2/3, Smad7 proteins were measured by the immunohistochemical method, and the mRNA levels of the 3 proteins were detected by RT-PCR. Compared with the mice in the praziquantel group, the areas of egg granuloma of the liver of the mice in the 4 praziquantel + kaempferol groups were smaller, and the degrees of the hepatic fibrosis of the mice were lesser, and their expressions of Smad2 and Smad3 at protein and their mRNA levels were significantly lower (all P kaempferol can significantly reduce the degrees of hepatic fibrosis and granuloma caused by schistosome eggs after the praziquantel treatment.

Evidence That Rhesus Macaques Self-Cure from a Schistosoma japonicum Infection by Disrupting Worm Esophageal Function: A New Route to an Effective Vaccine?

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Xiao-Hong Li

Full Text Available Rhesus macaques are unusual among schistosome hosts, self-curing from an established infection and thereafter manifesting solid immunity against a challenge, an ideal model for vaccine development. Previously, the immunological basis of self-cure was confirmed; surviving worms had ceased feeding but how immunological pressure achieved this was unclear. The schistosome esophagus is not simply a conduit for blood but plays a central role in its processing. Secretions from the anterior and posterior esophageal glands mix with incoming blood causing erythrocyte lysis and tethering and killing of leucocytes.We have analysed the self-cure process in rhesus macaques infected with Schistosoma japonicum. Faecal egg output and circulating antigen levels were used to chart the establishment of a mature worm population and its subsequent demise. The physiological stress of surviving females at perfusion was especially evident from their pale, shrunken appearance, while changes in the structure and function of the esophagus were observed in both sexes. In the anterior region electron microscopy revealed that the vesicle secretory process was disrupted, the tips of lining corrugations being swollen by greatly enlarged vesicles and the putative sites of vesicle release obscured by intense deposits of IgG. The lumen of the posterior esophagus in starving worms was occluded by cellular debris and the lining cytoplasmic plates were closely adherent, also potentially preventing secretion. Seven proteins secreted by the posterior gland were identified and IgG responses were detected to some or all of them. Intrinsic rhesus IgG colocalized with secreted SjMEGs 4.1, 8.2, 9, 11 and VAL-7 on cryosections, suggesting they are potential targets for disruption of function.Our data suggest that rhesus macaques self-cure by blocking esophagus function with antibody; the protein products of the glands provide a new class of potential vaccine targets.

Schistosoma japonicum UDP-glucose 4-epimerase protein is located on the tegument and induces moderate protection against challenge infection.

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Pingping Liu

Full Text Available Schistosomiasis is an important global public health problem, as millions of people are at risk of acquiring this infection. An ideal method for sustainable control of schistosomiasis is using a vaccine alone or in combination with drugs. In the present study, we cloned the SjGALE gene and generated the expression product in E. coli. The expression level of SjGALE during different developmental stages of S. japonicum was evaluated by real-time RT-PCR and western blotting. Immunolocalization indicated that the protein was mainly located on the tegument of the parasite. Infection of rSjGALE-immunized mice demonstrated a 34% and 49% reduction of the mean worm burden and liver egg burden, respectively, in two independent experiments, indicating immune protection. The liver egg count from each female adult worm was significantly reduced by 63% in the two trials. The cytokine profile and IgG isotype analysis demonstrated the induction of a Th1 immune profile in response to immunization with this protein, further suggesting protection against infection. In conclusion, these findings indicated that SjGALE is a potential vaccine against S. japonicum.

A cluster-randomised intervention trial against Schistosoma japonicum in the Peoples' Republic of China: bovine and human transmission.

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Darren J Gray

2009-06-01

Full Text Available Zoonotic schistosomiasis japonica is a major public health problem in China. Bovines, particularly water buffaloes, are thought to play a major role in the transmission of schistosomiasis to humans in China. Preliminary results (1998-2003 of a praziquantel (PZQ-based pilot intervention study we undertook provided proof of principle that water buffaloes are major reservoir hosts for S. japonicum in the Poyang Lake region, Jiangxi Province.Here we present the results of a cluster-randomised intervention trial (2004-2007 undertaken in Hunan and Jiangxi Provinces, with increased power and more general applicability to the lake and marshlands regions of southern China. The trial involved four matched pairs of villages with one village within each pair randomly selected as a control (human PZQ treatment only, leaving the other as the intervention (human and bovine PZQ treatment. A sentinel cohort of people to be monitored for new infections for the duration of the study was selected from each village. Results showed that combined human and bovine chemotherapy with PZQ had a greater effect on human incidence than human PZQ treatment alone.The results from this study, supported by previous experimental evidence, confirms that bovines are the major reservoir host of human schistosomiasis in the lake and marshland regions of southern China, and reinforce the rationale for the development and deployment of a transmission blocking anti-S. japonicum vaccine targeting bovines.Australian New Zealand Clinical Trials Registry ACTRN12609000263291.

Characterization of a gene family encoding SEA (sea-urchin sperm protein, enterokinase and agrin-domain proteins with lectin-like and heme-binding properties from Schistosoma japonicum.

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Evaristus Chibunna Mbanefo

Full Text Available BACKGROUND: We previously identified a novel gene family dispersed in the genome of Schistosoma japonicum by retrotransposon-mediated gene duplication mechanism. Although many transcripts were identified, no homolog was readily identifiable from sequence information. METHODOLOGY/PRINCIPAL FINDINGS: Here, we utilized structural homology modeling and biochemical methods to identify remote homologs, and characterized the gene products as SEA (sea-urchin sperm protein, enterokinase and agrin-domain containing proteins. A common extracellular domain in this family was structurally similar to SEA-domain. SEA-domain is primarily a structural domain, known to assist or regulate binding to glycans. Recombinant proteins from three members of this gene family specifically interacted with glycosaminoglycans with high affinity, with potential implication in ligand acquisition and immune evasion. Similar approach was used to identify a heme-binding site on the SEA-domain. The heme-binding mode showed heme molecule inserted into a hydrophobic pocket, with heme iron putatively coordinated to two histidine axial ligands. Heme-binding properties were confirmed using biochemical assays and UV-visible absorption spectroscopy, which showed high affinity heme-binding (K D = 1.605×10(-6 M and cognate spectroscopic attributes of hexa-coordinated heme iron. The native proteins were oligomers, antigenic, and are localized on adult worm teguments and gastrodermis; major host-parasite interfaces and site for heme detoxification and acquisition. CONCLUSIONS: The results suggest potential role, at least in the nucleation step of heme crystallization (hemozoin formation, and as receptors for heme uptake. Survival strategies exploited by parasites, including heme homeostasis mechanism in hemoparasites, are paramount for successful parasitism. Thus, assessing prospects for application in disease intervention is warranted.

Characterization of a Gene Family Encoding SEA (Sea-urchin Sperm Protein, Enterokinase and Agrin)-Domain Proteins with Lectin-Like and Heme-Binding Properties from Schistosoma japonicum

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Mbanefo, Evaristus Chibunna; Kikuchi, Mihoko; Huy, Nguyen Tien; Shuaibu, Mohammed Nasir; Cherif, Mahamoud Sama; Yu, Chuanxin; Wakao, Masahiro; Suda, Yasuo; Hirayama, Kenji

2014-01-01

Background We previously identified a novel gene family dispersed in the genome of Schistosoma japonicum by retrotransposon-mediated gene duplication mechanism. Although many transcripts were identified, no homolog was readily identifiable from sequence information. Methodology/Principal Findings Here, we utilized structural homology modeling and biochemical methods to identify remote homologs, and characterized the gene products as SEA (sea-urchin sperm protein, enterokinase and agrin)-domain containing proteins. A common extracellular domain in this family was structurally similar to SEA-domain. SEA-domain is primarily a structural domain, known to assist or regulate binding to glycans. Recombinant proteins from three members of this gene family specifically interacted with glycosaminoglycans with high affinity, with potential implication in ligand acquisition and immune evasion. Similar approach was used to identify a heme-binding site on the SEA-domain. The heme-binding mode showed heme molecule inserted into a hydrophobic pocket, with heme iron putatively coordinated to two histidine axial ligands. Heme-binding properties were confirmed using biochemical assays and UV-visible absorption spectroscopy, which showed high affinity heme-binding (K D = 1.605×10−6 M) and cognate spectroscopic attributes of hexa-coordinated heme iron. The native proteins were oligomers, antigenic, and are localized on adult worm teguments and gastrodermis; major host-parasite interfaces and site for heme detoxification and acquisition. Conclusions The results suggest potential role, at least in the nucleation step of heme crystallization (hemozoin formation), and as receptors for heme uptake. Survival strategies exploited by parasites, including heme homeostasis mechanism in hemoparasites, are paramount for successful parasitism. Thus, assessing prospects for application in disease intervention is warranted. PMID:24416467

Ultrasonic and x-ray tomographic findings of Schistosomiasis Japonicum

International Nuclear Information System (INIS)

Nagata, Osamu; Uto, Koji; Sugihara, Hisayo; Takii, Masaru; Nohara, Yumiko; Tominaga, Hidetoshi; Kaji, Masaro; Koga, Teruto.

1986-01-01

In the present study, attempts were made to classify the ultrasonic patterns of the liver infected with Schistosoma Japonicum. The calcification and fibrosis of the liver were evaluated by comparative investigation with an ultrasonogram and computed tomography (CT). Schistosomiasis Japonica was examined in 23 patients who were more than 45 years of age. It was diagnosed by liver needle biopsy, an intracutaneous test, or autopsy. The cases with a fish scale and network pattern had attenuation of the liver on ultrasonography and were unspecific on CT. Histological findings demonstrated moderate liver fibrosis. The cases with a sieve pattern had attenuation on ultrasonography, and the CT disclosed a retractive liver and the CT number of that liver was increased. Histological findings demonstrated a severe fibrotic liver. The cases with a mottled pattern had increased reflective spotty echo with an acoustic shadow, and the CT disclosed calcification. The histological findings demonstrated a marked calcification of the eggs. The cases with a mixed pattern, which consisted of mottled and sieve based on fish scale and network, had no retraction with less increase in the CT number. These results suggest that the peculiar reflective echo pattern of Schistosomiasis Japonica was due to not only calcification but also fibrosis of the liver. (author)

The small RNA complement of adult Schistosoma haematobium.

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Andreas J Stroehlein

2018-05-01

Full Text Available Blood flukes of the genus Schistosoma cause schistosomiasis-a neglected tropical disease (NTD that affects more than 200 million people worldwide. Studies of schistosome genomes have improved our understanding of the molecular biology of flatworms, but most of them have focused largely on protein-coding genes. Small non-coding RNAs (sncRNAs have been explored in selected schistosome species and are suggested to play essential roles in the post-transcriptional regulation of genes, and in modulating flatworm-host interactions. However, genome-wide small RNA data are currently lacking for key schistosomes including Schistosoma haematobium-the causative agent of urogenital schistosomiasis of humans.MicroRNAs (miRNAs and other sncRNAs of male and female adults of S. haematobium and small RNA transcription levels were explored by deep sequencing, genome mapping and detailed bioinformatic analyses.In total, 89 transcribed miRNAs were identified in S. haematobium-a similar complement to those reported for the congeners S. mansoni and S. japonicum. Of these miRNAs, 34 were novel, with no homologs in other schistosomes. Most miRNAs (n = 64 exhibited sex-biased transcription, suggestive of roles in sexual differentiation, pairing of adult worms and reproductive processes. Of the sncRNAs that were not miRNAs, some related to the spliceosome (n = 21, biogenesis of other RNAs (n = 3 or ribozyme functions (n = 16, whereas most others (n = 3798 were novel ('orphans' with unknown functions.This study provides the first genome-wide sncRNA resource for S. haematobium, extending earlier studies of schistosomes. The present work should facilitate the future curation and experimental validation of sncRNA functions in schistosomes to enhance our understanding of post-transcriptional gene regulation and of the roles that sncRNAs play in schistosome reproduction, development and parasite-host cross-talk.

The small RNA complement of adult Schistosoma haematobium.

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Stroehlein, Andreas J; Young, Neil D; Korhonen, Pasi K; Hall, Ross S; Jex, Aaron R; Webster, Bonnie L; Rollinson, David; Brindley, Paul J; Gasser, Robin B

2018-05-01

Blood flukes of the genus Schistosoma cause schistosomiasis-a neglected tropical disease (NTD) that affects more than 200 million people worldwide. Studies of schistosome genomes have improved our understanding of the molecular biology of flatworms, but most of them have focused largely on protein-coding genes. Small non-coding RNAs (sncRNAs) have been explored in selected schistosome species and are suggested to play essential roles in the post-transcriptional regulation of genes, and in modulating flatworm-host interactions. However, genome-wide small RNA data are currently lacking for key schistosomes including Schistosoma haematobium-the causative agent of urogenital schistosomiasis of humans. MicroRNAs (miRNAs) and other sncRNAs of male and female adults of S. haematobium and small RNA transcription levels were explored by deep sequencing, genome mapping and detailed bioinformatic analyses. In total, 89 transcribed miRNAs were identified in S. haematobium-a similar complement to those reported for the congeners S. mansoni and S. japonicum. Of these miRNAs, 34 were novel, with no homologs in other schistosomes. Most miRNAs (n = 64) exhibited sex-biased transcription, suggestive of roles in sexual differentiation, pairing of adult worms and reproductive processes. Of the sncRNAs that were not miRNAs, some related to the spliceosome (n = 21), biogenesis of other RNAs (n = 3) or ribozyme functions (n = 16), whereas most others (n = 3798) were novel ('orphans') with unknown functions. This study provides the first genome-wide sncRNA resource for S. haematobium, extending earlier studies of schistosomes. The present work should facilitate the future curation and experimental validation of sncRNA functions in schistosomes to enhance our understanding of post-transcriptional gene regulation and of the roles that sncRNAs play in schistosome reproduction, development and parasite-host cross-talk.

Detection of Schistosoma Antibodies and exploration of associated factors among local residents around Inlay Lake, Southern Shan State, Myanmar.

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Soe, Htin Zaw; Oo, Cho Cho; Myat, Tin Ohn; Maung, Nay Soe

2017-03-01

Schistosomiasis is a chronic parasitic disease caused by blood flukes (trematode worms) of the genus Schistosoma. Its transmission has been reported in 78 countries affecting at least 258 million people world-wide. It was documented that S. japonicum species was prevalent in Shan State, Myanmar, but the serological study was not conducted yet. General objective of the present study was to detect schistosoma antibodies and explore associated factors among local residents living around Inlay Lake, Nyaung Shwe Township, and Southern Shan State, Myanmar. An exploratory and cross-sectional analytic study was conducted among local residents (n = 315) in selected rural health center (RHC) areas from December 2012 through June 2013. The participants were interviewed with pretested semi-structured questionnaires and their blood samples (serum) were tested using Schistosomiasis Serology Microwell ELISA test kits (sensitivity 100% and specificity 85%) which detected IgG antibodies but could not distinguish between a new and past infection. Data collected were analysed by SPSS software 16.0 and associations of variables were determined by Chi-squared test with a significant level set at 0.05. Schistosoma seroprevalence (IgG) in study area was found to be 23.8% (95% CI: 18.8-28.8%). The present study is the first and foremost study producing serological evidence of schistosoma infection-one of the neglected tropical diseases-in local people of Myanmar. The factors significantly associated with seropositivity were being male [OR = 2.6 (95% CI: 1.5-4.49), P Myanmar, and this should be further confirmed parasitologically and kept under surveillance. Proper trainings on diagnosis, treatment, prevention and control of schistosomiasis should be provided to the healthcare providers. ISRCTN ISRCTN73824458 . Registered 28 September 2014, retrospectively registered.

In vivo effect of single oral dose of artemether against early juvenile stages of Schistosoma mansoni Egyptian strain.

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El-Beshbishi, Samar N; Taman, Amira; El-Malky, Mohamed; Azab, Manar S; El-Hawary, Amira K; El-Tantawy, Dina A

2013-10-01

The current treatment and control of schistosomiasis, rely on a single drug, praziquantel, although, it has minor activity against juvenile stages of the parasite. Studies have shown that artemether (ART) exhibits effects against juveniles of Schistosoma mansoni Liberian and Puerto Rican strains, Schistosoma japonicum and Schistosoma haematobium. Aiming to assess the in vivo activity of single oral dose of ART against early juvenile stages of S. mansoni Egyptian strain, this study was established. Mice were treated with ART (400 mg/kg) at two time points evenly spaced over the period of larval development (7 and 21 days post-infection; pi), and a third treatment point (day 49 pi) was included to elucidate when susceptibility decreases. Administration of ART on day 7 pi reduced the total worm burden by 85.94%. The greatest reductions were seen when treatment was given on day 21 pi, with total and female worm burden reductions of 91.52% and 90.57%, respectively, and cessation of oviposition. Similar dose given on day 49 pi reduced total worm burden by 55.17% and female worm burden by 66.51%. Moreover, it induced significant reduction in the tissue egg load and significant alterations in the oogram pattern with decreased immature eggs and increased dead eggs. Antipathological activities were evident in significant reductions in granulomata count and diameter. In conclusion, ART exhibits major in vivo schistosomicidal effects against the early larval migratory stages of S. mansoni Egyptian strain, mainly the 21-day old schistosomula, hence preventing disease progression and morbidity. Copyright © 2013 Elsevier Inc. All rights reserved.

[Seasonal changes and response to stress of total flavonoids content of Farfugium japonicum].

Science.gov (United States)

Cui, Dalian; Ma, Yuxin

2013-05-01

To investigate the seasonal variation of total flavonoid content of Farfugium japonicum and its response to stress. The total flavonoids of Farfugium japonicum were determined by spectrophotometry in different seasons and under various stressful factors. The total flavonoid content in Farfugium japonicum leaves was the highest, followed by the petiole, and rhizomes (Pseasons (Pwater stress, the total flavonoid content in Farfugium japonicum leaves gradually increased, that in petiole first increased and then decreased,while that in rhizomes decreased (Pstress, the total flavonoid content in leaves, petioles and rhizomes of Farfugium japonicum showed a decreasing trend (Pseasons and that in different parts of the plant has different responses to ecological stressful factors.

Ultrastructural alterations in adult Schistosoma mansoni caused by artemether

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Shuhua Xiao

2002-07-01

Full Text Available Progress has been made over the last decade with the development and clinical use of artemether as an agent against major human schistosome parasites. The tegument has been identified as a key target of artemether, implying detailed studies on ultrastructural damage induced by this compound. We performed a temporal examination, employing a transmission electron microscope to assess the pattern and extent of ultrastructural alterations in adult Schistosoma mansoni harboured in mice treated with a single dose of 400 mg/kg artemether. Eight hours post-treatment, damage to the tegument and subtegumental structures was seen. Tegumental alterations reached a peak 3 days after treatment and were characterized by swelling, fusion of distal cytoplasma, focal lysis of the tegumental matrix and vacuolisation. Tubercles and sensory organelles frequently degenerated or collapsed. Typical features of subtegumental alterations, including muscle fibres, syncytium and parenchyma tissues, were focal or extensive lysis, vacuolisation and degeneration of mitochondria. Severe alterations were also observed in gut epithelial cells and vitelline cells of female worms. Our findings of artemether-induced ultrastructural alterations in adult S. mansoni confirm previous results obtained with juvenile S. mansoni and S. japonicum of different ages.

Genetic Evidence of Contemporary Dispersal of the Intermediate Snail Host of Schistosoma japonicum: Movement of an NTD Host Is Facilitated by Land Use and Landscape Connectivity.

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Head, Jennifer R; Chang, Howard; Li, Qunna; Hoover, Christopher M; Wilke, Thomas; Clewing, Catharina; Carlton, Elizabeth J; Liang, Song; Lu, Ding; Zhong, Bo; Remais, Justin V

2016-12-01

While the dispersal of hosts and vectors-through active or passive movement-is known to facilitate the spread and re-emergence of certain infectious diseases, little is known about the movement ecology of Oncomelania spp., intermediate snail host of the parasite Schistosoma japonicum, and its consequences for the spread of schistosomiasis in East and Southeast Asia. In China, despite intense control programs aimed at preventing schistosomiasis transmission, there is evidence in recent years of re-emergence and persistence of infection in some areas, as well as an increase in the spatial extent of the snail host. A quantitative understanding of the dispersal characteristics of the intermediate host can provide new insights into the spatial dynamics of transmission, and can assist public health officials in limiting the geographic spread of infection. Oncomelania hupensis robertsoni snails (n = 833) were sampled from 29 sites in Sichuan, China, genotyped, and analyzed using Bayesian assignment to estimate the rate of recent snail migration across sites. Landscape connectivity between each site pair was estimated using the geographic distance distributions derived from nine environmental models: Euclidean, topography, incline, wetness, land use, watershed, stream use, streams and channels, and stream velocity. Among sites, 14.4% to 32.8% of sampled snails were identified as recent migrants, with 20 sites comprising >20% migrants. Migration rates were generally low between sites, but at 8 sites, over 10% of the overall host population originated from one proximal site. Greater landscape connectivity was significantly associated with increased odds of migration, with the minimum path distance (as opposed to median or first quartile) emerging as the strongest predictor across all environmental models. Models accounting for land use explained the largest proportion of the variance in migration rates between sites. A greater number of irrigation channels leading into a

Genetic Evidence of Contemporary Dispersal of the Intermediate Snail Host of Schistosoma japonicum: Movement of an NTD Host Is Facilitated by Land Use and Landscape Connectivity.

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Jennifer R Head

2016-12-01

Full Text Available While the dispersal of hosts and vectors-through active or passive movement-is known to facilitate the spread and re-emergence of certain infectious diseases, little is known about the movement ecology of Oncomelania spp., intermediate snail host of the parasite Schistosoma japonicum, and its consequences for the spread of schistosomiasis in East and Southeast Asia. In China, despite intense control programs aimed at preventing schistosomiasis transmission, there is evidence in recent years of re-emergence and persistence of infection in some areas, as well as an increase in the spatial extent of the snail host. A quantitative understanding of the dispersal characteristics of the intermediate host can provide new insights into the spatial dynamics of transmission, and can assist public health officials in limiting the geographic spread of infection.Oncomelania hupensis robertsoni snails (n = 833 were sampled from 29 sites in Sichuan, China, genotyped, and analyzed using Bayesian assignment to estimate the rate of recent snail migration across sites. Landscape connectivity between each site pair was estimated using the geographic distance distributions derived from nine environmental models: Euclidean, topography, incline, wetness, land use, watershed, stream use, streams and channels, and stream velocity. Among sites, 14.4% to 32.8% of sampled snails were identified as recent migrants, with 20 sites comprising >20% migrants. Migration rates were generally low between sites, but at 8 sites, over 10% of the overall host population originated from one proximal site. Greater landscape connectivity was significantly associated with increased odds of migration, with the minimum path distance (as opposed to median or first quartile emerging as the strongest predictor across all environmental models. Models accounting for land use explained the largest proportion of the variance in migration rates between sites. A greater number of irrigation channels

Chemical composition and anti-inflammatory effects of essential oil from Farfugium japonicum flower.

Science.gov (United States)

Kim, Ji-Young; Oh, Tae-Heon; Kim, Byeong Jin; Kim, Sang-Suk; Lee, Nam Ho; Hyun, Chang-Gu

2008-01-01

In this study, the chemical composition and anti-inflammatory activities of hydrodistilled essential oil from Farfugium japonicum were investigated for the first time. The chemical constituents of the essential oil were further analyzed by GC-MS and included 1-undecene (22.43%), 1-nonene (19.83%), beta-caryophyllene (12.26%), alpha-copaene (3.70%), gamma-curcumene (2.86%), germacrene D (2.69%), and 1-decene (2.08%). The effects of the essential oil on nitric oxide (NO) and prostaglandin E2 (PGE(2)) production in lipopolysaccharide (LPS)-activated RAW 264.7 macrophages were also examined. The results indicate that the F. japonicum essential oil is an effective inhibitor of LPS-induced NO and PGE(2) production in RAW 264.7 cells. These inhibitory effects of the F. japonicum essential oil were accompanied by dose-dependent decreases in the iNOS and COX-2 mRNA expression. In order to determine whether F. japonicum essential oil can safely be applied to human skin, the cytotoxic effects of F. japonicum essential oil were determined by colorimetric MTT assays in human dermal fibroblast and keratinocyte HaCaT cells. F. japonicum essential oil exhibited low cytotoxicity at 100 mug/mL. Based on these results, we suggest that F. japonicum essential oil may be considered a potential anti-inflammatory candidate for topical application.

Co-inoculation effects of Bradyrhizobium japonicum and ...

African Journals Online (AJOL)

Co-inoculation effects of Bradyrhizobium japonicum and Azospirillum sp. on competitive nodulation and rhizosphere eubacterial community structures of soybean under rhizobia-established soil conditions.

Respon Pertumbunan Tanaman Kedelai terhadap Bradyrhizobium japonicum Toleran Masam dan Pemberian Pupuk di Tanah Masam

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, Triadiati

2013-10-01

Full Text Available The use of acid tolerant rhizobacteria such as Bradyrhizobium japonicum is one effort for increasing soybeanproductivity in acid soil. B. japonicum is a N-fixing bacteria that can promote soybean growth through symbiosis with thehost plants. The objective of this study was to investigate the growth and production of soybean var. Wilis inoculated by B.japonicum and NPK inorganic fertilizer application in acid soil. Two isolates of B. japonicum that were BJ 11(19 and BJ11(wt were used as inoculant for soybean. BJ 11(19 was resulted by transposons mutagenesis, whereas BJ 11(wt is a wild type of bacteria. Both isolates of B. japonicum were acid tolerant. Soybean was inoculated with BJ 11(19 and BJ 11(wtcombined with compost and nitrogen fertilizer (with two rates. The field experiment was conducted at Cikabayan, Darmaga,in a randomized complete block design with 12 treatments and 3 replicates. The results showed that application of the acidtolerant B. japonicum BJ 11(wt, compost, and nitrogen fertilizer (10 g m-2 increased the plant height, dry weight of shootsand roots, nodule number, dry weight of nodules, nitrogenase activity, number of pod and seed, seed weight, and nitrogencontent of seeds in acid soil.Keywords: acid soil, acid tolerant rhizobia, Bradyrhizobium japonicum, compost, nitrogen fertilizer

Chrysosplenium japonicum (Saxifragaceae, Newly Recorded from Taiwan

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Tian-Chuan Hsu

2011-11-01

Full Text Available Chrysosplenium japonicum (Maxim. Makino (Saxifragaceae is newly recorded from northeastern Taiwan. Description, color photos and a key to the Chrysosplenium species in Taiwan are provided.

PENULARAN SCHISTOSOMIASIS DI DESA DODOLO DAN MEKARSARI DATARAN TINGGI NAPU SULAWESI TENGAH

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Rosmini Rosmini

2012-09-01

Full Text Available The transmission of schistosomiasis is still ongoing in Dodolo and Mekarsari Villages ofNapu highland, Poso District. The people who infected with Schistosoma japonicum, intermediate host. Oncomelania hnpensis lindoensis snails that infected by cercaria. infective stage of S. japonicum and reservoir host, rats, which infected by S. japonicum were still (bund. The purpose of this study was to identify the transmission of schistosomiasis at Dodolo and Mekarsari Villages, Napu highland. The epidemiological investigation was analyzed using observational study with cross sectional design. Data collections were conducted, including stool, snail and rat suryeys. Stool samples were examined by the Kato-Katz method and rats were dissected to identify the prevalence rate of schistosomiasis in human and rats. Snails were examined using crushing method to identify the infection rate of the snails. Prevalence rate of schistosomiasis in human, rats (Rattus exulans and infection rate O. hnpensis lindoensis snails in Dodolo were 6,9%, 8,3%, 2,8% and in Mekarsari were 6,1%, 10% 2,6% respectively. Prevalence of schistosomiasis in Dodolo and Mekarsari villages is still high, so we need continuous surveillance.   Keywords: Schistosomiasis, Schistosoma japonicum, O. hupensis lindoensis, Dodolo, Mekarsari

Soybean Lectin Enhances Biofilm Formation by Bradyrhizobium japonicum in the Absence of Plants

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Julieta Pérez-Giménez

2009-01-01

Full Text Available Soybean lectin (SBL purified from soybean seeds by affinity chromatography strongly bound to Bradyrhizobium japonicum USDA 110 cell surface. This lectin enhanced biofilm formation by B. japonicum in a concentration-dependent manner. Presence of galactose during biofilm formation had different effects in the presence or absence of SBL. Biofilms were completely inhibited in the presence of both SBL and galactose, while in the absence of SBL, galactose was less inhibitory. SBL was very stable, since its agglutinating activity of B. japonicum cells as well as of human group A+ erythrocytes was resistant to preincubation for one week at 60°C. Hence, we propose that plant remnants might constitute a source of this lectin, which might remain active in soil and thus favor B. japonicum biofilm formation in the interval between soybean crop seasons.

Co-inoculation effects of Bradyrhizobium japonicum and ...

African Journals Online (AJOL)

Corporate Edition

2013-05-15

. 2851. MATERIALS AND METHODS. Bacterial strains, media and growth conditions. Two B. japonicum strains of CB 1809 and USDA 110 those currently used in rhizobial inoculants production for soybean at the. Department ...

Dicty_cDB: Contig-U10248-1 [Dicty_cDB

Lifescience Database Archive (English)

Full Text Available stosoma japonicum SJCHGC02833 ... 130 3e-34 AB241242_1( AB241242 |pid:none) Symbiotic protist of Reticuliter...FN320591 |pid:none) Schistosoma japonicum isolate Anhu... 130 7e-34 AB241243_1( AB241243 |pid:none) Symbiotic... 115 2e-32 CR932686_1( CR932686 |pid:none) Paramecium tetraurelia, Small GTPa... 124 2e-32 AB241241_1( AB241241 |pid:none) Symbiotic

Pectolinarigenin - A Flavonoid Compound from Cirsium Japonicum ...

African Journals Online (AJOL)

HP

/tjpr.v13i2.9. Original Research Article. Pectolinarigenin - A Flavonoid Compound from Cirsium. Japonicum with Potential Anti-proliferation Activity in MCF-. 7 Breast Cancer Cell. Mingqian Lu. 1,2,3. , Qingzhi Kong. 1,4. *, Xinhua Xu. 2,3.

Produtividade da soja em resposta à aplicação de Molibdênio e inoculação com Bradyrhizobium japonicum Soybean yield in response to Molybdenum and Bradyrhizobium japonicum inoculation

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Eloir Paulo Gris

2005-02-01

Full Text Available A soja em simbiose com Bradyrhizobium japonicum é capaz de ter a sua exigência de N satisfeita com a fixação biológica de N2 (FBN. Entretanto, a FBN é afetada pela deficiência Mo, visto que este nutriente faz parte da enzima nitrogenase responsável pelo processo. Foi realizado um experimento, em condição de campo, em Latossolo Vermelho eutroférrico, no município de Palotina, PR, com o objetivo de avaliar o tratamento de sementes com Mo, inoculação de B. japonicum e adubação foliar de Mo na produtividade da soja. Os tratamentos foram quatro doses de Mo (0, 40, 80 e 160 g ha-1 aplicadas em adubação foliar e tratamento com aplicação nas sementes de 40 g ha-1 de Mo, combinados com e sem inoculação com B. japonicum. Não foram observados efeitos estatísticos significativos do tratamento de sementes com Mo, inoculação de B. japonicum e adubação foliar de Mo na produtividade da soja. Não foram obtidas diferenças significativas entre os tratamentos, obtendo-se tendência apra ganho de produtividade apenas com aplicação foliar de 80 g ha-1 de Mo e tratamento de sementes com 40 g ha-1.Soybean in symbiosis with Bradyrhizobium japonicum is able to satisfy its nitrogen (N2 demand with biological nitrogen fixation (BNF. However, BNF can be affected by molybdenium deficiency because this micronutrient is part of the nitrogenase enzyme responsible for the process. An experiment was conducted under field conditions on a Red Latosol (Oxisol in Palotina, state of Paraná, Brazil. The effects of seed treatments with Mo, B. japonicum inoculation as well as foliar Mo fertilization on soybean yield were evaluated. Four Mo rates (0, 40, 80 and 160 g ha-1 were applied as foliar fertilizer in two Mo application forms (without Mo, seed treatment with Mo 40 g ha-1 combined with and without B. japonicum inoculation. There were no significant effects of the seed treatments with Mo, inoculation with B. japonicum and foliar Mo fertilization on

Growth and nitrogen dynamics of glycine max inoculated with bradyrhizobium japonicum and exposed to elevated atmospheric carbon dioxide

International Nuclear Information System (INIS)

Rehman, A.; Hamid, N.; Jawaid, F.

2010-01-01

Seeds of Glycine max (soybean) were inoculated with N-fixing bacterium Bradyrhizobium japonicum and grown in growth chamber to investigate interactive effects of atmospheric CO/sub 2/ and plants Nitrogen status on root and shoot length and biomass, nodule formation and Nitrogen concentration. Plants were grown with CO/sub 2/ at 3500 and 1000 ppm with or without Bradyrhizobium japonicum inoculation. Root and shoot length and dry mass of Glycine max increased significantly with CO/sub 2/ enrichment provided with Bradyrhizobium japonicum as compared to deficient Nitrogen fixing bacterium. While ambient and enriched CO/sub 2/ levels resulted in increased Nitrogen concentration of Glycine max shoot and root which is inoculated with N-fixing bacterium. Nodule formation was also enhanced in plants supplied with Bradyrhizobium japonicum as compared to plants which is Bradyrhizobium japonicum deficient at both CO/sub 2/ concentrations. (author)

KONTRIBUSI HEWAN MAMALIA SAPI, KERBAU, KUDA, BABI DAN ANJING DALAM PENULARAN SCHISTOSOMIASIS DI KECAMATAN LINDU KABUPATEN SIGI PROPINSI SULAWESI TENGAH TAHUN 2013

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Gunawan Gunawan

2015-01-01

Full Text Available AbstrakSchistosomiasis merupakan penyakit parasitik jaringan yang terabaikan. Schistosomiasis adalah penyakit parasitik yang bersifat zoonosis, selain menginfeksi manusia juga menginfeksi hewan mamalia lainnya. Ada 13 mamalia yang diketahui dapat terinfeksi oleh schistosomiasis antara lain sapi(Bos sundaicus, kerbau (Bubalus bubalis, kuda (Equus cabalus, anjing (Canis familiaris, babi (Sus sp, musang (Vivera tangalunga, rusa (Carvus timorensis, dan berbagai jenis tikus (Rattus exulans, R. hoffmani, R. chysomomusrallus, R. marmosurus, R norvegicus, R palallae. Di Indonesia schistosomiasis disebabkan oleh cacing Schistosoma japonicum dan hanya ditemukan endemik di Sulawesi Tengah yaitu di dataran tinggi Lindu, Napu dan Bada.Penelitian ini bertujuan untuk mengetahui kontribusi reservoir dalam penularan schistosomiasis di Kecamatan Lindu, Kabupaten Sigi, Propinsi Sulawesi Tengah. Metode penelitian ini adalah deskriptif observational dengan pendekatan cross sectional. Pengumpulan data primer dilakukan dengan mengobservasi mamalia yang berisiko,dengan pengambilan dan pemeriksaan sampel tinja hewan mamali tersebut. Sejumlah 219 sampel tinja hewan mamalia yang terdiri dari sapi, kerbau, anjing, babi dan kuda diperiksa dengan menggunakan metode sentrifugasi formalin-eter. Dari hasil pemeriksaan tinja yang dilakukan dilaboratorium Parasitologi Balai Litbang P2B2 Donggala sebanyak 54 sampel tinja hewan mamalia (sapi, kerbau, anjing, babi dan kuda positif terinfeksi S.japonicum.Kata kunci : Schistosomiasis, hewan mamalia, Schistosoma japonicumAbstractSchistosomiasis is one of neglected parasitic diseaseds and also a zoonosic disease, in addition to humans it also infect mammals. There were 13 known mammals that can be infected by schistosomiasis, i.e. cattle (Bos sundaicus, buffalo (Bubalus bubalis, horse (Equus Cabalus, dog (Canis familiaris, pig(Sus sp, civet cat(Vivera tangalunga, deer (Cervus timorensis, and various types of rat (Rattus exulans, R

Application of representational difference analysis to identify genomic differences between Bradyrhizobium elkanii and B. Japonicum species.

Science.gov (United States)

Soares, René Arderius; Passaglia, Luciane Maria Pereira

2010-10-01

Bradyrhizobium elkanii is successfully used in the formulation of commercial inoculants and, together with B. japonicum, it fully supplies the plant nitrogen demands. Despite the similarity between B. japonicum and B. elkanii species, several works demonstrated genetic and physiological differences between them. In this work Representational Difference Analysis (RDA) was used for genomic comparison between B. elkanii SEMIA 587, a crop inoculant strain, and B. japonicum USDA 110, a reference strain. Two hundred sequences were obtained. From these, 46 sequences belonged exclusively to the genome of B. elkanii strain, and 154 showed similarity to sequences from B. japonicum genome. From the 46 sequences with no similarity to sequences from B. japonicum, 39 showed no similarity to sequences in public databases and seven showed similarity to sequences of genes coding for known proteins. These seven sequences were divided in three groups: similar to sequences from other Bradyrhizobium strains, similar to sequences from other nitrogen-fixing bacteria, and similar to sequences from non nitrogen-fixing bacteria. These new sequences could be used as DNA markers in order to investigate the rates of genetic material gain and loss in natural Bradyrhizobium strains.

Functional characterization of the Bradyrhizobium japonicum modA and modB genes involved in molybdenum transport.

Science.gov (United States)

Delgado, María J; Tresierra-Ayala, Alvaro; Talbi, Chouhra; Bedmar, Eulogio J

2006-01-01

A modABC gene cluster that encodes an ABC-type, high-affinity molybdate transporter from Bradyrhizobium japonicum has been isolated and characterized. B. japonicum modA and modB mutant strains were unable to grow aerobically or anaerobically with nitrate as nitrogen source or as respiratory substrate, respectively, and lacked nitrate reductase activity. The nitrogen-fixing ability of the mod mutants in symbiotic association with soybean plants grown in a Mo-deficient mineral solution was severely impaired. Addition of molybdate to the bacterial growth medium or to the plant mineral solution fully restored the wild-type phenotype. Because the amount of molybdate required for suppression of the mutant phenotype either under free-living or under symbiotic conditions was dependent on sulphate concentration, it is likely that a sulphate transporter is also involved in Mo uptake in B. japonicum. The promoter region of the modABC genes has been characterized by primer extension. Reverse transcription and expression of a transcriptional fusion, P(modA)-lacZ, was detected only in a B. japonicum modA mutant grown in a medium without molybdate supplementation. These findings indicate that transcription of the B. japonicum modABC genes is repressed by molybdate.

Role of Bradyrhizobium japonicum and Trichoderma spp. in the control of root rot disease of soybean

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Syed Ehteshamul-Haque

2014-08-01

Full Text Available Seed treatment of soybean with Bndyrhizobium japonicum, Trichoderma harzianum, T. viride, T. hamatum, T. koningii and T. pseudokoningii significantly controlled the infection of 30-day-old seedlingsby Maerophomina phaseolina, Rhizoctonia solani and Fusarium spp. In 60-day-old plants Trichoderma spp.. and B. japonicum inhibited the grouth of R. solani and Fusarium spp., whereas the use of B. japonicum (TAL-102 with T. harzianum. T. viride, T. koningii and T. pseudokoningii controlled the infection by M. phaseolina. Greater grain yield was recorded when B. japonium (TAI-102 was used with T. hamatum.

Ganoderma neo-japonicum Imazeki revisited: Domestication study and antioxidant properties of its basidiocarps and mycelia

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Tan, Wee-Cheat; Kuppusamy, Umah Rani; Phan, Chia-Wei; Tan, Yee-Shin; Raman, Jegadeesh; Anuar, Azliza Mad; Sabaratnam, Vikineswary

2015-01-01

Mushroom cultivation benefits humankind as it deliberately encourages wild mushrooms to be commercially propagated while recycling agricultural wastes. Ganoderma neo-japonicum is a rare polypore mushroom found growing on decaying Schizostachyum brachycladium (a tropical bamboo) clumps in Malaysia. The Malaysian indigenous tribes including the Temuans and Temiars use the basidiocarps of G. neo-japonicum to treat various ailments including diabetes. In this study, the domestication of G. neo-japonicum in artificial logs of different agricultural residues was investigated. Sawdust promoted the mycelia spawn colonisation in the shortest period of 38 ± 0.5 days. However, only sawdust and bamboo dust supported the primodia formation. Complex medium supported mycelium growth in submerged cultures and 27.11 ± 0.43 g/L of mycelia was obtained after 2 weeks of cultivation at 28 °C and 200 rpm. Antioxidant potential in mushroom may be influenced by different cultivation and extraction methods. The different extracts from the wild and cultivated basidiocarps as well as mycelia were then tested for their antioxidant properties. Aqueous and ethanol extracts of mycelia and basidiocarps tested had varying levels of antioxidant activities. To conclude, domestication of wild G. neo-japonicum using agroresidues may ensure a continuous supply of G. neo-japonicum for its medicinal use while ensuring the conservation of this rare species. PMID:26213331

Pectolinarigenin - A Flavonoid Compound from Cirsium Japonicum ...

African Journals Online (AJOL)

Protein expression of Bcl2 was almost completely inhibited upon the treatment with 25 μM pectolinarigenin. Conclusion: A rapid method to isolate high purity pectolinarigenin from C. japonicum and as well as evaluate its anti-proliferative potential and induction of apoptosis in MCF-7 breast cancer cells is presented for the ...

Cerebral Schistosomiasis Caused by Schistosoma mansoni: a Case Report with Clinical Analysis

Directory of Open Access Journals (Sweden)

M Li

2009-05-01

Full Text Available "nCentral nervous system involvement arising from schistosomiasis is uncommon. It may be produced most fre­quently by Schistosoma japonicum infection, but reports of S. mansoni presenting as an intracerebral mass lesion are particularly rare. The authors describe the case of a 35-year-old woman with a 3-month history of partial epilep­tic seizures and head­aches. She immigrated to Egypt 4 years ago and had worked in Iraq for 2 years after the immigration. The patient's gen­eral physical and neurological examinations were unremarkable. Magnetic resonance (MR imaging revealed an enhanc­ing lesion with surrounding edema and mild mass effect in the left frontal lobe. A stereotactic brain biopsy demonstrated intraparenchymal granulomas surrounding S. mansoni eggs. S. mansoni was identified by stool examination. Prednisone (1 mg/kg per day for 1 week, with gradual with­drawal during the following 3 weeks and praziquantel (2 doses at 20 mg/kg per day therapy was initiated. The patient's symptoms resolved following medical treatment and the follow-up MR imaging yielded normal findings. This case is the rare imported case of cerebral schistosomiasis in China and the neuroschistosomiasis should be considered as the patient lived in a region in which this disease is endemic.

Resistance against Schistosoma mansoni induced by highly irradiated infections: studies on species specificity of immunization and attempts to transfer resistance

International Nuclear Information System (INIS)

Bickle, Q.D.; Andrews, B.J.; Doenhoff, M.J.; Ford, M.J.; Taylor, M.G.

1985-01-01

Significant levels of resistance against Schistosoma mansoni challenge were developed by mice exposed to highly irradiated (20 krad.) cercariae of the homologous species (53-67%), whereas vaccination with S. bovis, S. haematobium or S. japonicum failed to confer significant levels of resistance (-5-12%), thus confirming the specificity of the immunizing procedure. Attempts to transfer resistance to naive recipients by injection of serum and of spleen or lymph node cells from donor mice vaccinated with highly irradiated cercariae were largely unsuccessful. However, significant levels of resistance could be transferred to mice by injection of serum from rabbits exposed to irradiated cercariae. Comparable levels of resistance were conferred by injection of serum at the time of challenge (34-69%) or 5-6 days later (31-56%). In contrast, sera from rabbits injected with soluble egg antigen or homogenized cercariae failed to confer protection upon recipient mice. Sera from vaccinated mice, vaccinated rabbits and antigen-injected rabbits all caused cell adherence to skin-transformed schistosomula but neither the level of adherence nor the serum titre correlated with the ability to confer protection to mice. (author)

Lack of glyphosate resistance gene transfer from Roundup Ready soybean to Bradyrhizobium japonicum under field and laboratory conditions.

Science.gov (United States)

Isaza, Laura Arango; Opelt, Katja; Wagner, Tobias; Mattes, Elke; Bieber, Evi; Hatley, Elwood O; Roth, Greg; Sanjuán, Juan; Fischer, Hans-Martin; Sandermann, Heinrich; Hartmann, Anton; Ernst, Dieter

2011-01-01

A field study was conducted at the Russell E. Larson Agricultural Research Center to determine the effect of transgenic glyphosate-resistant soybean in combination with herbicide (Roundup) application on its endosymbiont Bradyrhizobium japonicum. DNA of bacteroids from isolated nodules was analysed for the presence of the transgenic 5-enolpyruvylshikimate-3-phosphate synthase (CP4-EPSPS) DNA sequence using polymerase chain reaction (PCR). To further assess the likelihood that the EPSPS gene may be transferred from the Roundup Ready (RR) soybean to B. japonicum, we have examined the natural transformation efficiency of B. japonicum strain 110spc4. Analyses of nodules showed the presence of the transgenic EPSPS DNA sequence. In bacteroids that were isolated from nodules of transgenic soybean plants and then cultivated in the presence of glyphosate this sequence could not be detected. This indicates that no stable horizontal gene transfer (HGT) of the EPSPS gene had occurred under field conditions. Under laboratory conditions, no natural transformation was detected in B. japonicum strain 110spc4 in the presence of various amounts of recombinant plasmid DNA. Our results indicate that no natural competence state exists in B. japonicum 110spc4. Results from field and laboratory studies indicate the lack of functional transfer of the CP4-EPSPS gene from glyphosate-tolerant soybean treated with glyphosate to root-associated B. japonicum.

SmCL3, a gastrodermal cysteine protease of the human blood fluke Schistosoma mansoni.

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Jan Dvorák

2009-06-01

Full Text Available Blood flukes of the genus Schistosoma are platyhelminth parasites that infect 200 million people worldwide. Digestion of nutrients from the host bloodstream is essential for parasite development and reproduction. A network of proteolytic enzymes (proteases facilitates hydrolysis of host hemoglobin and serum proteins.We identified a new cathepsin L termed SmCL3 using PCR strategies based on S. mansoni EST sequence data. An ortholog is present in Schistosoma japonicum. SmCL3 was heterologously expressed as an active enzyme in the yeast, Pichia pastoris. Recombinant SmCL3 has a broad pH activity range against peptidyl substrates and is inhibited by Clan CA protease inhibitors. Consistent with a function in degrading host proteins, SmCL3 hydrolyzes serum albumin and hemoglobin, is localized to the adult gastrodermis, and is expressed mainly in those life stages infecting the mammalian host. The predominant form of SmCL3 in the parasite exists as a zymogen, which is unusual for proteases. This zymogen includes an unusually long prodomain with alpha helical secondary structure motifs. The striking specificity of SmCL3 for amino acids with large aromatic side chains (Trp and Tyr at the P2 substrate position, as determined with positional scanning-synthetic combinatorial library, is consistent with a molecular model that shows a large and deep S2 pocket. A sequence similarity network (SSN view clusters SmCL3 and other cathepsins L in accordance with previous large-scale phylogenetic analyses that identify six super kingdoms.SmCL3 is a gut-associated cathepsin L that may contribute to the network of proteases involved in degrading host blood proteins as nutrients. Furthermore, this enzyme exhibits some unusual sequence and biophysical features that may result in additional functions. The visualization of network inter-relationships among cathepsins L suggests that these enzymes are suitable 'marker sequences' for inclusion in future phylogenetic analyses.

Assessment of Trichogramma japonicum and T. chilonis as Potential Biological Control Agents of Yellow Stem Borer in Rice

Science.gov (United States)

Tang, Rui; Babendreier, Dirk; Zhang, Feng; Kang, Min; Song, Kai; Hou, Mao-Lin

2017-01-01

Two species of Trichogramma wasps were assessed for their effectiveness against yellow stem borer Scirpophaga incertulas. A laboratory cage test with T. japonicum and T. chilonis showed that both species parasitized yellow stem borer egg masses at 60.0% ± 9.13% and 40.7% ± 7.11%, respectively, with egg parasitism rates of 15.8% ± 22.2% for T. japonicum and 2.8% ± 5.0% for T. chilonis. Once the host eggs were parasitized, emergence rates were high for both species (95.7% ± 0.12% for T. japonicum and 100% for T. chilonis). In paddy field trials, the two Trichogramma species were released at three densities (50,000/ha, 100,000/ha and 200,000/ha) in Southwestern China. Egg mass parasitism was 9% ± 7.7% for T. japonicum and 15% ± 14.1% for T. chilonis, and again only a relatively small fraction of eggs was successfully parasitized. No clear conclusion could be drawn on the most efficient release rate as no significant differences were found among the three release rates. A comparison of field-collected T. japonicum with T. japonicum and T. chilonis mass reared on Corcyra cephalonica showed significantly larger body size and ovipositor length in field-collected wasps, suggesting potentially higher effectiveness on yellow stem borer eggs after at least one generation on the target host. Factors contributing to the low field parasitism rates are discussed. PMID:28208706

Molecular characterization of thyroid hormone receptor beta from Schistosoma japonicum and assessment of its potential as a vaccine candidate antigen against schistosomiasis in BALB/c mice

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Qiu Chunhui

2012-08-01

Full Text Available Abstract Background Thyroid hormones (TH modulate growth, development and differentiation and metabolic processes by interacting with thyroid hormone receptors (THRs. The purpose of this study was to identify a novel thyroid hormone receptor beta encoding gene of Schistosoma japonicum (SjTHRβ and to investigate its potential as a vaccine candidate antigen against schistosomiasis in BALB/c mice. Methods The full-length cDNA sequence of SjTHRβ, its gene organization, and its transcript levels were characterized, and the phylogenetic relationship between THR, RAR and RXR from other organisms were analysis, the ability of this protein binding to a conserved DNA core motif, and its potential as a vaccine candidate antigen against schistosomiasis in BALB/c mice were evaluated. Results The SjTHRβ cDNA was cloned, verified by 5’ and 3’ Rapid Amplification of cDNA Ends and shown to be polyadenylated at the 3’end, suggesting the transcript is full-length. SjTHRβ is homologous to THRs from other species and has a predicted conservative DNA binding domain and ligand binding domain that normally characterizes these receptors. A comparative quantitative PCR analysis showed that SjTHRβ was the highest expressed in 21d worms and the lowest in 7 d and 13 d schistosomula. The cDNA corresponding to DNA binding domain (SjTHRβ-DBD and ligand binding domain (SjTHRβ-LBD were cloned and subsequently expressed in E coli. The expressed proteins were used to immunize mice and generate specific serum against recombinant SjTHRβ (rSjTHRβ. Western blotting revealed that anti-rSjTHRβ-LBD serum recognized two protein bands in extracts from 21 d worm with molecular sizes of approximately 95 kDa and 72 kDa. Electrophoretic mobility shift assay (EMSA analysis showed that rSjTHRβ-DBD could bind to a conserved DNA core motif. Immunization of BALB/c mice with rSjTHRβ-LBD could induce partial protective efficacy(27.52% worm reduction and 29.50% liver eggs

Aspartic protease activities of schistosomes cleave mammalian hemoglobins in a host-specific manner

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Jeffrey W Koehler

2007-02-01

Full Text Available We examined the efficiency of digestion of hemoglobin from four mammalian species, human, cow, sheep, and horse by acidic extracts of mixed sex adults of Schistosoma japonicum and S. mansoni. Activity ascribable to aspartic protease(s from S. japonicum and S. mansoni cleaved human hemoglobin. In addition, aspartic protease activities from S. japonicum cleaved hemoglobin from bovine, sheep, and horse blood more efficiently than did the activity from extracts of S. mansoni. These findings support the hypothesis that substrate specificity of hemoglobin-degrading proteases employed by blood feeding helminth parasites influences parasite host species range; differences in amino acid sequences in key sites of the parasite proteases interact less or more efficiently with the hemoglobins of permissive or non-permissive hosts.

Towards the Elimination of Schistosomiasis japonica through Control of the Disease in Domestic Animals in The People's Republic of China: A Tale of over 60Years.

Science.gov (United States)

Cao, Z-G; Zhao, Y-E; Lee Willingham, A; Wang, T-P

2016-01-01

Schistosomiasis japonica, an endemic, zoonotic tropical parasitic disease caused by Schistosoma japonicum, remains an important public health concern in The People's Republic of China. Unlike other species of Schistosoma, over 40 species of wild and domestic animals can act as reservoir hosts of S. japonicum, which increases the difficulty for the control of this tropical disease. It is widely recognized that domestic animals, particularly water buffaloes and cattle, play an important role in the transmission of S. japonicum. Hence, since the 1950s when The People's Republic of China commenced fight against the disease, the control of animal schistosomiasis has been carried out almost synchronously with that of human schistosomiasis, such that great strides have been made over the past six decades. In this chapter, we review the history and current status of schistosomiasis control in domestic animals in The People's Republic of China. We thoroughly analyse the prevalence of domestic animal schistosomiasis at different stages of schistosomiasis control and the role of different species of domestic animals in transmission of the disease, summarize the control strategies and assess their effectiveness. Furthermore, the challenges ahead are discussed and recommendations for future direction are provided. Copyright © 2016 Elsevier Ltd. All rights reserved.

Diagnostic performance of Schistosoma real-time PCR in urine samples from Kenyan children infected with Schistosoma haematobium

DEFF Research Database (Denmark)

Vinkeles Melchers, Natalie V. S.; van Dam, Govert J.; Shaproski, David

2014-01-01

treatment. METHODOLOGY: Previously collected urine samples (N = 390) from 114 preselected proven parasitological and/or clinical S. haematobium positive Kenyan schoolchildren were analyzed by a Schistosoma internal transcribed spacer-based real-time PCR after 14 years of storage. Pre-treatment day......, respectively. Based on the 'gold standard', PCR showed high sensitivity (>92%) as compared to >31% sensitivity for microscopy, both pre- and post-treatment. CONCLUSIONS/SIGNIFICANCE: Detection and quantification of Schistosoma DNA in urine by real-time PCR was shown to be a powerful and specific diagnostic...

In vitro propagation of katsura tree (Cercidiphyllum japonicum Sieb ...

African Journals Online (AJOL)

ajl5

Katsura tree (Cercidiphyllum japonicum Sieb. Et Zucc) is a long-lived, deciduous, wind-pollinated tree with dimorphic leaves. It is valued as an ornamental or a shade tree for landscape and a commercially valuable tree. Conventional propagation through seeds and cutting is not sufficient to satisfy the progressive demand.

Determinants of Schistosoma mansoni in Sanja health center, north West Ethiopia.

Science.gov (United States)

Andargie, Asrat Atsedeweyn; Abera, Agmas Sisay

2018-05-11

In developing countries, Schistosoma mansoni is one of the chronic but neglected tropical diseases. In sub-Saharan Africa, the disease affects over 250 million people with nearly 800 million are at risk. In Ethiopia, Schistosoma mansoni is one of the most prevalent parasitic diseases. The aim of this study was to determine the prevalence and identify the determinant factors of Schistosoma mansoni, in terms of some socio-demographic variables and risk factors. A cross-sectional parasitological survey was conducted at Sanja health center, northwest Ethiopia from June 1 to June 30, 2015. A total of 228 study participants were included in the study. The participants were selected using systematic random sampling technique. Stool specimens were collected and examined using Kato-Katz methods. Structural questionnaires were used to collect data on socio-demographic variables and risk factors by face to face interviews. The major risk factors and demographic determinants of the infection status of Schistosoma mansoni were identified by using descriptive and ordinal logistic regression techniques. The overall prevalence of Schistosoma mansoni was 16.67% (95%CI: 11.83-21.51%). Covariates such as no habit of swimming in rivers has lower risk (AOR = 0.022: 95%CI: 0.011-0.764), no frequency of swimming in rivers (AOR = 0.022: 95%CI: 0.0024-0.207), and 1 to 2 frequency of swimming (OR = 0.302: 95%CI: 0.097-0.941), washing clothes in rivers (AOR = 0.194: 95%CI: 0.046-0.0.811) and bathing in the river (AOR = 0.09: 95%CI: 0.010-0.815) were the most important determinant factors (P-value < 0.5) of Schistosoma mansoni in Sanja health center. In this study, the prevalence of Schistosoma mansoni was found to be high. Swimming habits, frequency of swimming, washing clothes, and bathing in rivers were found to be significant predictors of Schistosoma mansoni. Provisions of a safe water supply in the area and health education about the transmission of the Schistosoma

Schistosome serine protease inhibitors: parasite defense or homeostasis?

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Landys A. Lopez Quezada

2011-06-01

Full Text Available Serpins are a structurally conserved family of macromolecular inhibitors found in numerous biological systems. The completion and annotation of the genomes of Schistosoma mansoni and Schistosoma japonicum has enabled the identification by phylogenetic analysis of two major serpin clades. S. mansoni shows a greater multiplicity of serpin genes, perhaps reflecting adaptation to infection of a human host. Putative targets of schistosome serpins can be predicted from the sequence of the reactive center loop (RCL. Schistosome serpins may play important roles in both post-translational regulation of schistosome-derived proteases, as well as parasite defense mechanisms against the action of host proteases.Serpinas são uma família de inibidores macromoleculares estruturalmente conservados encontrados em inúmeros sistemas biológicos. O término e a anotação dos genomas de Schistosoma mansoni e de Schistosoma japonicum permitiram a identificação por análise filogenética de dois principais clados de serpinas. S. mansoni mostra uma multiplicidade maior de genes de serpinas, talvez refletindo uma adaptação à infecção de um hospedeiro humano. Alvos putativos das serpinas de esquistossomos podem ser preditos a partir da sequência do "loop" do centro reativo. Serpinas de esquistossomos podem ter importantes papeis tanto na regulação pós-traducional de proteases derivadas do esquistossoma, quanto nos mecanismos de defesa contra a ação de proteases do hospedeiro.

Floral organ MADS-box genes in Cercidiphyllum japonicum (Cercidiphyllaceae: Implications for systematic evolution and bracts definition.

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Yupei Jin

Full Text Available The dioecious relic Cercidiphyllum japonicum is one of two species of the sole genus Cercidiphyllum, with a tight inflorescence lacking an apparent perianth structure. In addition, its systematic place has been much debated and, so far researches have mainly focused on its morphology and chloroplast genes. In our investigation, we identified 10 floral organ identity genes, including four A-class, three B-class, two C-class and one D-class. Phylogenetic analyses showed that all ten genes are grouped with Saxifragales plants, which confirmed the phylogenetic place of C. japonicum. Expression patterns of those genes were examined by quantitative reverse transcriptase PCR, with some variations that did not completely coincide with the ABCDE model, suggesting some subfunctionalization. As well, our research supported the idea that thebract actually is perianth according to our morphological and molecular analyses in Cercidiphyllum japonicum.

Floral organ MADS-box genes in Cercidiphyllum japonicum (Cercidiphyllaceae): Implications for systematic evolution and bracts definition.

Science.gov (United States)

Jin, Yupei; Wang, Yubing; Zhang, Dechun; Shen, Xiangling; Liu, Wen; Chen, Faju

2017-01-01

The dioecious relic Cercidiphyllum japonicum is one of two species of the sole genus Cercidiphyllum, with a tight inflorescence lacking an apparent perianth structure. In addition, its systematic place has been much debated and, so far researches have mainly focused on its morphology and chloroplast genes. In our investigation, we identified 10 floral organ identity genes, including four A-class, three B-class, two C-class and one D-class. Phylogenetic analyses showed that all ten genes are grouped with Saxifragales plants, which confirmed the phylogenetic place of C. japonicum. Expression patterns of those genes were examined by quantitative reverse transcriptase PCR, with some variations that did not completely coincide with the ABCDE model, suggesting some subfunctionalization. As well, our research supported the idea that thebract actually is perianth according to our morphological and molecular analyses in Cercidiphyllum japonicum.

Dicty_cDB: VHI203 [Dicty_cDB

Lifescience Database Archive (English)

Full Text Available s producing significant alignments: (bits) Value AF325215_2( AF325215 |pid:none) Lymphocytic choriomeningitis...5090 |pid:none) Schistosoma japonicum SJCHGC03255 ... 36 2.8 EU480452_2( EU480452 |pid:none) Lymphocytic choriomeningitis...325214_2( AF325214 |pid:none) Lymphocytic choriomeningitis virus... 35 8.2 BX2941

[Impact of new trend of ecological environment changes on growth, reproduction and diffusion of Oncomelania hupensis].

Science.gov (United States)

Juan, Xie; Li-Yong, Wen

2016-03-07

Oncomelania hupensis is the only intermediate host of Schistosoma japonicum , and the growth, reproduction and distribution of O.hupensis play an important role in schistosomiasis prevalence and transmission. This article reviews the influence of the new trend of ecological environment changes on the growth, reproduction and diffusion of the snails.

CT manifestation of schistosoma haematobium cystitis

International Nuclear Information System (INIS)

Wang Yujun; Hu Lirong; Cheng Yougen; Mao Guoqun; Yang Guangzhao; Modya Camara; Mohamed Traore

2014-01-01

Objective: To analyze CT manifestation of Schistosoma haematobium cystitis. Methods: Retrospective analysis 32 patients, who were tested for Schistosoma haematobium cystitis using the urine filtration method. CT scan was performed for each patient with contrast enhancement. Results: The vast majority of urinary tract schistomiasis lesions were in the urinary bladder. Calcification of the bladder wall was observed in all patients and mild enhancement in non calcified zone was found after intravenous contrast. Except for 5 patients of bladder cancer, the rest were no abnormality in size of bladder when bladder was filling or emptying. Ureteral wall annular calcification could also be identified in 25 patients. Twenty two patients were companied with ureteric hydronephrosis. Seminal vesicle calcification was seen in 4 patients among 11 male patients, while both uterine and ovarian in female and prostate in men had non calcification. Serious illness can be combined with bladder cancer. In 5 patients of patients with bladder cancer, bladder showed irregular soft tissue mass which was enhanced moderately after post-contrast scan, with vesical calcification in mass medially. Conclusion: Bladder calcification is the most prominent CT feature of Schistosoma haematobium cystitis, which is useful in diagnosis the disease. (authors)

Identification of Potential High-Risk Habitats within the Transmission Reach of Oncomelania hupensis after Floods Based on SAR Techniques in a Plane Region in China.

Science.gov (United States)

Shi, Yuanyuan; Qiu, Juan; Li, Rendong; Shen, Qiang; Huang, Duan

2017-08-30

Schistosomiasis japonica is an infectious disease caused by Schistosoma japonicum , and it remains endemic in China. Flooding is the main hazard factor, as it causes the spread of Oncomelania hupensis , the only intermediate host of Schistosoma japonicum , thereby triggering schistosomiasis outbreaks. Based on multi-source real-time remote sensing data, we used remote sensing (RS) technology, especially synthetic aperture radar (SAR), and geographic information system (GIS) techniques to carry out warning research on potential snail habitats within the snail dispersal range following flooding. Our research result demonstrated: (1) SAR data from Sentinel-1A before and during a flood were used to identify submerged areas rapidly and effectively; (2) the likelihood of snail survival was positively correlated with the clay proportion, core area standard deviation, and ditch length but negatively correlated with the wetness index, NDVI (normalized difference vegetation index), elevation, woodland area, and construction land area; (3) the snail habitats were most abundant near rivers and ditches in paddy fields; (4) the rivers and paddy irrigation ditches in the submerged areas must be the focused of mitigation efforts following future floods.

Uptake and metabolism of carbohydrates by Bradyrhizobium japonicum bacteroids

International Nuclear Information System (INIS)

Salminen, S.O.; Streeter, J.G.

1987-01-01

Bradyrhizobium japonicum bacteroids were isolated anaerobically and were supplied with 14 C-labeled trehalose, sucrose, UDP-glucose, glucose, or fructose under low O 2 (2% in the gas phase). Uptake and conversion of 14 C to CO 2 were measured at intervals up to 90 minutes. Of the five compounds studied, UDP-glucose was most rapidly absorbed but it was very slowly metabolized. Trehalose was the sugar most rapidly converted to CO 2 , and fructose was respired at a rate of at least double that of glucose. Sucrose and glucose were converted to CO 2 at a very low but measurable rate ( 2 at a rate 30 times greater than the conversion of carbon Number 6 to CO 2 , indicating high activity of the pentose phosphate pathway. Enzymes of the Entner-Doudoroff pathway were not detected in bacteroids, but very low activities of sucrose synthase and phosphofructokinase were demonstrated. Although metabolism of sugars by B. japonicum bacteroids was clearly demonstrated, the rate of sugar uptake was only 1/30 to 1/50 the rate of succinate uptake. The overall results support the view that, although bacteroids metabolize sugars, the rates are very low and are inadequate to support nitrogenase

Detection of Extracellular Enzyme Activities in Ganoderma neo-japonicum

OpenAIRE

Jo, Woo-Sik; Park, Ha-Na; Cho, Doo-Hyun; Yoo, Young-Bok; Park, Seung-Chun

2011-01-01

The ability of Ganoderma to produce extracellular enzymes, including β-glucosidase, cellulase, avicelase, pectinase, xylanase, protease, amylase, and ligninase was tested in chromogenic media. β-glucosidase showed the highest activity, among the eight tested enzymes. In particular, Ganoderma neo-japonicum showed significantly stronger activity for β-glucosidase than that of the other enzymes. Two Ganoderma lucidum isolates showed moderate activity for avicelase; however, Ganoderma neo-japonic...

[Spatio-temporal variations of origin, distribution and diffusion of Oncomelania hupensis in Yangtze River Basin].

Science.gov (United States)

Deng, Chen; Li-Yong, Wen

2017-10-24

As the only intermediate host of Schistosoma japonicum, Oncomelania hupensis in China is mainly distributed in the Yangtze River Basin. The origin of the O. hupensis and the spatio-temporal variations of its distribution and diffusion in the Yangtze River Basin and the influencing factors, as well as significances in schistosomiasis elimination in China are reviewed in this paper.

Proteomic analysis of human skin treated with larval schistosome peptidases reveals distinct invasion strategies among species of blood flukes.

Directory of Open Access Journals (Sweden)

Jessica Ingram

2011-09-01

Full Text Available Skin invasion is the initial step in infection of the human host by schistosome blood flukes. Schistosome larvae have the remarkable ability to overcome the physical and biochemical barriers present in skin in the absence of any mechanical trauma. While a serine peptidase with activity against insoluble elastin appears to be essential for this process in one species of schistosomes, Schistosoma mansoni, it is unknown whether other schistosome species use the same peptidase to facilitate entry into their hosts.Recent genome sequencing projects, together with a number of biochemical studies, identified alternative peptidases that Schistosoma japonicum or Trichobilharzia regenti could use to facilitate migration through skin. In this study, we used comparative proteomic analysis of human skin treated with purified cercarial elastase, the known invasive peptidase of S. mansoni, or S. mansoni cathespin B2, a close homolog of the putative invasive peptidase of S. japonicum, to identify substrates of either peptidase. Select skin proteins were then confirmed as substrates by in vitro digestion assays.This study demonstrates that an S. mansoni ortholog of the candidate invasive peptidase of S. japonicum and T. regenti, cathepsin B2, is capable of efficiently cleaving many of the same host skin substrates as the invasive serine peptidase of S. mansoni, cercarial elastase. At the same time, identification of unique substrates and the broader species specificity of cathepsin B2 suggest that the cercarial elastase gene family amplified as an adaptation of schistosomes to human hosts.

Identification of the Schistosoma mansoni Molecular Target for the Antimalarial Drug Artemether

KAUST Repository

Lepore, Rosalba

2011-11-28

Plasmodium falciparum and Schistosoma mansonii are the parasites responsible for most of the malaria and schistosomiasis cases in the world. Notwithstanding their many differences, the two agents have striking similarities in that they both are blood feeders and are targets of an overlapping set of drugs, including the well-known artemether molecule. Here we explore the possibility of using the known information about the mode of action of artemether in Plasmodium to identify the molecular target of the drug in Schistosoma and provide evidence that artemether binds to SmSERCA, a putative Ca2+-ATPase of Schistosoma. We also predict the putative binding mode of the molecule for both its Plasmodium and Schistosoma targets. Our analysis of the mode of binding of artemether to Ca2+-ATPases also provides an explanation for the apparent paradox that, although the molecule has no side effect in humans, it has been shown to possess antitumoral activity. © 2011 American Chemical Society.

Structural characterization of the thermostable Bradyrhizobium japonicumD-sorbitol dehydrogenase.

Science.gov (United States)

Fredslund, Folmer; Otten, Harm; Gemperlein, Sabrina; Poulsen, Jens Christian N; Carius, Yvonne; Kohring, Gert Wieland; Lo Leggio, Leila

2016-11-01

Bradyrhizobium japonicum sorbitol dehydrogenase is NADH-dependent and is active at elevated temperatures. The best substrate is D-glucitol (a synonym for D-sorbitol), although L-glucitol is also accepted, giving it particular potential in industrial applications. Crystallization led to a hexagonal crystal form, with crystals diffracting to 2.9 Å resolution. In attempts to phase the data, a molecular-replacement solution based upon PDB entry 4nbu (33% identical in sequence to the target) was found. The solution contained one molecule in the asymmetric unit, but a tetramer similar to that found in other short-chain dehydrogenases, including the search model, could be reconstructed by applying crystallographic symmetry operations. The active site contains electron density consistent with D-glucitol and phosphate, but there was not clear evidence for the binding of NADH. In a search for the features that determine the thermostability of the enzyme, the T m for the orthologue from Rhodobacter sphaeroides, for which the structure was already known, was also determined, and this enzyme proved to be considerably less thermostable. A continuous β-sheet is formed between two monomers in the tetramer of the B. japonicum enzyme, a feature not generally shared by short-chain dehydrogenases, and which may contribute to thermostability, as may an increased Pro/Gly ratio.

Dicty_cDB: Contig-U12039-1 [Dicty_cDB

Lifescience Database Archive (English)

Full Text Available 9 |pid:none) Mougeotia scalaris neochrome gene,... 101 7e-20 AB206962_1( AB206962 |pid:none) Mougeotia scala...AB206961_1( AB206961 |pid:none) Mougeotia scalaris NEO1 mRNA for n... 97 2e-18 ( ...01 7e-20 AY813860_1( AY813860 |pid:none) Schistosoma japonicum SJCHGC06050 ... 101 7e-20 AY878549_1( AY87854

[Cloning and expressing of cyclophilin B gene from Schistosoma japonnicum and the analysis of immunoprotective effect].

Science.gov (United States)

Peng, Jinbiao; Han, Hongxiao; Hong, Yang; Wang, Yan; Guo, Fanji; Shi, Yaojun; Fu, Zhiqiang; Liu, Jinming; Cheng, Guofeng; Lin, Jiaojiao

2010-03-01

The present study was intend to clone and express the cDNA encoding Cyclophilin B (CyPB) of Schistosoma japonicum, its preliminary biological function and further immunoprotective effect against schistosome infection in mice. RT-PCR technique was applied to amplify a full-length cDNA encoding protein Cyclophilin B (Sj CyPB) from schistosomula cDNA. The expression profiles of Sj CyPB were determined by Real-time PCR using the template cDNAs isolated from 7, 13, 18, 23, 32 and 42 days parasites. The cDNA containing the Open Reading Frame of CyPB was then subcloned into a pGEX-6P-1 vector and transformed into competent Escherichia coli BL21 for expressing. The recombinant protein was renaturated, purified and its antigenicity were detected by Western blotting, and the immunoprotective effect induced by recombinant Sj CyPB was evaluated in Balb/C mice. The cDNA containing the ORF of Sj CyPB was cloned with the length of 672 base pairs, encoding 223 amino acids. Real-time PCR analysis revealed that the gene had the highest expression in 18-day schistosomula, suggesting that Sj CyPB was schistosomula differentially expressed gene. The recombinant protein showed a good antigenicity detected by Western blotting. Animal experiment indicated that the vaccination of recombinant CyPB protein in mice led to 31.5% worm and 41.01% liver egg burden reduction, respectively, compared with those of the control. A full-length cDNA differentially expressed in schistosomula was obtained. The recombinant Sj CyPB protein could induce partial protection against schistosome infection.

Detection of Schistosoma mansoni and Schistosoma haematobium by Real-Time PCR with High Resolution Melting Analysis

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Hany Sady

2015-07-01

Full Text Available The present study describes a real-time PCR approach with high resolution melting-curve (HRM assay developed for the detection and differentiation of Schistosoma mansoni and S. haematobium in fecal and urine samples collected from rural Yemen. The samples were screened by microscopy and PCR for the Schistosoma species infection. A pair of degenerate primers were designed targeting partial regions in the cytochrome oxidase subunit I (cox1 gene of S. mansoni and S. haematobium using real-time PCR-HRM assay. The overall prevalence of schistosomiasis was 31.8%; 23.8% of the participants were infected with S. haematobium and 9.3% were infected with S. mansoni. With regards to the intensity of infections, 22.1% and 77.9% of S. haematobium infections were of heavy and light intensities, respectively. Likewise, 8.1%, 40.5% and 51.4% of S. mansoni infections were of heavy, moderate and light intensities, respectively. The melting points were distinctive for S. mansoni and S. haematobium, categorized by peaks of 76.49 ± 0.25 °C and 75.43 ± 0.26 °C, respectively. HRM analysis showed high detection capability through the amplification of Schistosoma DNA with as low as 0.0001 ng/µL. Significant negative correlations were reported between the real-time PCR-HRM cycle threshold (Ct values and microscopic egg counts for both S. mansoni in stool and S. haematobium in urine (p < 0.01. In conclusion, this closed-tube HRM protocol provides a potentially powerful screening molecular tool for the detection of S. mansoni and S. haematobium. It is a simple, rapid, accurate, and cost-effective method. Hence, this method is a good alternative approach to probe-based PCR assays.

Gynecological manifestations, histopathological findings, and schistosoma-specific polymerase chain reaction results among women with Schistosoma haematobium infection

DEFF Research Database (Denmark)

Randrianasolo, Bodo Sahondra; Jourdan, Peter Mark; Ravoniarimbinina, Pascaline

2015-01-01

BACKGROUND: The pathophysiology of female genital schistosomiasis (FGS) is only partially understood. This study aims to describe the histopathological findings, polymerase chain reaction (PCR) results, and gynecological manifestations of FGS in women with different intensities of Schistosoma hae...

Evolution of sarcoma 180 (ascitic tumor in mice infected with Schistosoma mansoni

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Fausto Edmundo Lima Pereira

1986-03-01

Full Text Available Mice infected with 60 cercariae of Schistosoma mansoni were more resistant to the sarcoma 180 ascites tumor. Tumor inoculation was performed 50 days after schistosoma infection and the animals were observed and weighed at 48 hours intervals for development and progression of malignancy. In infected mice the weight gain (ascites formation started later and was shorter than in uninfected Controls. Also, the number of tumor cells into the peritoneal cavity 72h after tumor implantation was shorter in infected group than incontrols. This in creased resistance against a transplantable tumor probably is related to the effect of endotoxin on tumoricidal activity of macrophages activated by the infection. The immunodepression induced by Schistosoma mansoni infection enhances the proliferation of endogenous bacteria increasing the amount of endotoxin absorbed from the gut.

Inoculation with Bradyrhizobium japonicum enhances the organic and fatty acids content of soybean (Glycine max (L.) Merrill) seeds.

Science.gov (United States)

Silva, Luís R; Pereira, Maria J; Azevedo, Jessica; Mulas, Rebeca; Velazquez, Encarna; González-Andrés, Fernando; Valentão, Patrícia; Andrade, Paula B

2013-12-15

Soybean (Glycine max (L.) Merrill) is one of the most important food crops for human and animal consumption, providing oil and protein at relatively low cost. The least expensive source of nitrogen for soybean is the biological fixation of atmospheric nitrogen by the symbiotic association with soil bacteria, belonging mainly to the genus Bradyrhizobium. This study was conducted to assess the effect of the inoculation of G. max with Bradyrhizobium japonicum on the metabolite profile and antioxidant potential of its seeds. Phenolic compounds, sterols, triterpenes, organic acids, fatty acids and volatiles profiles were characterised by different chromatographic techniques. The antioxidant activity was evaluated against DPPH, superoxide and nitric oxide radicals. Inoculation with B. japonicum induced changes in the profiles of primary and secondary metabolites of G. max seeds, without affecting their antioxidant capacity. The increase of organic and fatty acids and volatiles suggest a positive effect of the inoculation process. These findings indicate that the inoculation with nodulating B. japonicum is a beneficial agricultural practice, increasing the content of bioactive metabolites in G. max seeds owing to the establishment of symbiosis between plant and microorganism, with direct effects on seed quality. Copyright © 2013 Elsevier Ltd. All rights reserved.

Dicty_cDB: Contig-U08887-1 [Dicty_cDB

Lifescience Database Archive (English)

Full Text Available 1 FN317772_1( FN317772 |pid:none) Schistosoma japonicum isolate Anhu... 72 6e-11 X98769_1( X98769 |pid:none) Megaselia scala...ris mRNA for Sex-lethal... 71 1e-10 AJ000546_1( AJ000546 |pid:none) Megaselia scala...a cruzi RNA-binding prot... 67 2e-09 AF110846_1( AF110846 |pid:none) Megaselia scalaris sex-lethal homo... 6

Schistosoma real-time PCR as diagnostic tool for international travellers and migrants.

Science.gov (United States)

Cnops, Lieselotte; Tannich, Egbert; Polman, Katja; Clerinx, Jan; Van Esbroeck, Marjan

2012-10-01

To evaluate the use of a genus-specific PCR that combines high sensitivity with the detection of different Schistosoma species for diagnosis in international travellers and migrants in comparison to standard microscopy. The genus-specific real-time PCR was developed to target the 28S ribosomal RNA gene of the major human Schistosoma species. It was validated for analytical specificity and reproducibility and demonstrated an analytical sensitivity of 0.2 eggs per gram of faeces. Its diagnostic performance was further evaluated on 152 faecal, 32 urine and 38 serum samples from patients presenting at the outpatient clinic of the Institute of Tropical Medicine in Antwerp (Belgium). We detected Schistosoma DNA in 76 faecal (50.0%) and five urine (15.6%) samples of which, respectively, nine and one were not detected by standard microscopy. Only two of the 38 serum samples of patients with confirmed schistosomiasis were positive with the presently developed PCR. Sequence analysis on positive faecal samples allowed identification of the Schistosoma species complex. The real-time PCR is highly sensitive and may offer added value in diagnosing imported schistosomiasis. The genus-specific PCR can detect all schistosome species that are infectious to humans and performs very well with faeces and urine, but not in serum. © 2012 Blackwell Publishing Ltd.

Complete Genome Sequence of the Soybean Symbiont Bradyrhizobium japonicum Strain USDA6T

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Nobukazu Uchiike

2011-10-01

Full Text Available The complete nucleotide sequence of the genome of the soybean symbiont Bradyrhizobium japonicum strain USDA6T was determined. The genome of USDA6T is a single circular chromosome of 9,207,384 bp. The genome size is similar to that of the genome of another soybean symbiont, B. japonicum USDA110 (9,105,828 bp. Comparison of the whole-genome sequences of USDA6T and USDA110 showed colinearity of major regions in the two genomes, although a large inversion exists between them. A significantly high level of sequence conservation was detected in three regions on each genome. The gene constitution and nucleotide sequence features in these three regions indicate that they may have been derived from a symbiosis island. An ancestral, large symbiosis island, approximately 860 kb in total size, appears to have been split into these three regions by unknown large-scale genome rearrangements. The two integration events responsible for this appear to have taken place independently, but through comparable mechanisms, in both genomes.

Effect of schistosoma infection on malaria immune response: A systematic review.

Science.gov (United States)

Yesuf, Elias Ali; Dejene, Tariku

2011-01-01

Background Worldwide an estimated 225 million cases and about 800, 000 deaths due to malaria were documented in 2009. Malaria vaccines have been developed as a malaria control strategy. Immune response to these vaccines might be affected by the blood fluke schistosoma which is often co-endemic with malaria in Sub-Saharan Africa where most of phase II and Phase III malaria vaccine trials were conducted.Objectives To systematically search, appraise and synthesize the best available evidence on the effect of schistosoma infection on the immune response to malaria antigens and provide direction to future malaria vaccination trials.Types of participants The review considered studies with above 5 year old individuals as participants.Phenomenon of interest The phenomenon of interest was the presence of schistosoma infectionTypes of outcomes Blood serum levels of Th1 and Th2 specific to Merozoite Surface Proteins 1, 2, and 3 of malaria were considered as primary outcomes. While blood serum levels of IgG1, IgG2, IgG3, IFN-γ, IL-10 and TGF-β directed against Merozoite Surface Proteins were considered as secondary outcomes.Types of studies Studies with any quantitative study designs were considered for inclusion.Search Strategy Any quantitative English language articles published between 1994 and April 2011 were sought using a comprehensive search strategy.Assessment of methodological quality It was done using Joanna Briggs Institutes' Meta Analysis of Statistical Assessment and Review Instrument critical appraisal tools.Data extraction Data extraction was carried out using the Joanna Briggs Institute Meta Analysis of Statistical Assessment and Review Instrument data extraction tool.Data synthesis Meta- analysis was conducted using random effects model with an inverse variance method with RevMan5 software. Heterogeneity between the studies was assessed using ξ test at a p-value of SMD (95% CI), 0.15 (-2.00, 2.31), p=0.89.Similarly a small and statistically not significant

case report endomyocardial fibrosis associated with schistosoma

African Journals Online (AJOL)

2014-12-01

Dec 1, 2014 ... stored in containers and subsequently used for bathing. Both patients were ... His urine was amber and of adequate vol- ume. He had been ... schistosome specific antibody test for Schistosoma haematobium ... health problem, with the highest prevalence seen in communities ... newer drug targets.13,14.

Improved Soybean Root Association of N-Starved Bradyrhizobium japonicum

OpenAIRE

López-García, Silvina L.; Vázquez, Tirso E. E.; Favelukes, Gabriel; Lodeiro, Aníbal R.

2001-01-01

In this study, we addressed the effects of N limitation in Bradyrhizobium japonicum for its association with soybean roots. The wild-type strain LP 3001 grew for six generations with a growth rate of 1.2 day−1 in a minimal medium with 28 mM mannitol as the carbon source and with the N source [(NH4)2SO4] limited to only 20 μM. Under these conditions, the glutamine synthetase (GS) activity was five to six times higher than in similar cultures grown with 1 or 0.1 mM (NH4)2SO4. The NtrBC-inducibl...

Discovery and molecular characterization of a Bcl-2–regulated cell death pathway in schistosomes

OpenAIRE

Lee, Erinna F.; Clarke, Oliver B.; Evangelista, Marco; Feng, Zhiping; Speed, Terence P.; Tchoubrieva, Elissaveta B.; Strasser, Andreas; Kalinna, Bernd H.; Colman, Peter M.; Fairlie, W. Douglas

2011-01-01

Schistosomiasis is an infectious disease caused by parasites of the phylum platyhelminthe. Here, we describe the identification and characterization of a Bcl-2–regulated apoptosis pathway in Schistosoma japonicum and S. mansoni. Genomic, biochemical, and cell-based mechanistic studies provide evidence for a tripartite pathway, similar to that in humans including BH3-only proteins that are inhibited by prosurvival Bcl-2–like molecules, and Bax/Bak-like proteins that facilitate mitochondrial ou...

Mutagenicity of nicotine in Schistosoma mansoni - infected mice ...

African Journals Online (AJOL)

Analysis of meiotic chromosomes showed significant elevation in the Schistosoma-infected mice. Administration of nicotine to infected mice substantially increased the percentages of micronucleated cells and total CAs. The percentage of chromosomal abnormalities in spermatocyte metaphase-I cells increased significantly ...

Clinical Effects of Formulated Food of Peucedanum japonicum Extract and Saw Palmetto Extract in Male Patients with Lower Urinary Tract Symptoms.

Science.gov (United States)

Kageyama, Shinji; Beppu, Masanori; Ohnogi, Hiromu; Miyazaki, Sayaka; Haruno, Akihiro; Ito, Yoshihiko; Yamada, Shizuo

2018-05-01

To evaluate changes over time in subjective symptom scores and urination parameters before and after oral administration of formulated food containing a combination of Peucedanum japonicum (P. japonicum) extract and saw palmetto extract (SPE) in male patients with lower urinary tract symptoms (LUTS). This study was conducted in an open label manner on male patients with untreated LUTS. The urination state of patients was evaluated before and after administration of food formulated with P. japonicum extract and SPE for 4 weeks, based on urodynamic parameters and subjective symptom scores (International Prostate Symptom Score [IPSS and IPSS-QOL], Overactive Bladder Symptom Score [OABSS], Overactive Bladder Questionnaire [OAB-q], and International Index of Erectile Function [IIEF]). After the administration of food formulated with these extracts, the following results were obtained: (i) Subjective findings: The IPSS-QOL score improved significantly; both parameters related to nocturia, i.e., frequency of nighttime urination and OABSS-2, improved significantly; other ratings for subjective symptoms slightly improved. (ii) Objective findings: Residual urine volume decreased significantly, and blood prostate specific antigen (PSA) and urinary 8-OHdG levels decreased slightly after the treatment. (iii) Other findings: Blood pressure decreased slightly. No adverse drug reactions were reported. (iv) Patient impressions: 75% of patients gave a rating of "Good" or higher, with 15 out of 20 patients wanting to continue treatment after the end of 4-week administration period. Food formulated with P. japonicum extract and SPE may be useful to decrease frequency of nighttime urination and residual urine volume in male patients with LUTS. © 2017 John Wiley & Sons Australia, Ltd.

Decision-model estimation of the age-specific disability weight for schistosomiasis japonica: a systematic review of the literature.

Science.gov (United States)

Finkelstein, Julia L; Schleinitz, Mark D; Carabin, Hélène; McGarvey, Stephen T

2008-03-05

Schistosomiasis is among the most prevalent parasitic infections worldwide. However, current Global Burden of Disease (GBD) disability-adjusted life year estimates indicate that its population-level impact is negligible. Recent studies suggest that GBD methodologies may significantly underestimate the burden of parasitic diseases, including schistosomiasis. Furthermore, strain-specific disability weights have not been established for schistosomiasis, and the magnitude of human disease burden due to Schistosoma japonicum remains controversial. We used a decision model to quantify an alternative disability weight estimate of the burden of human disease due to S. japonicum. We reviewed S. japonicum morbidity data, and constructed decision trees for all infected persons and two age-specific strata, or =15 y. We conducted stochastic and probabilistic sensitivity analyses for each model. Infection with S. japonicum was associated with an average disability weight of 0.132, with age-specific disability weights of 0.098 ( or =15 y). Re-estimated disability weights were seven to 46 times greater than current GBD measures; no simulations produced disability weight estimates lower than 0.009. Nutritional morbidities had the greatest contribution to the S. japonicum disability weight in the disability weights for schistosomiasis urgently need to be revised, and species-specific disability weights should be established. Even a marginal increase in current estimates would result in a substantial rise in the estimated global burden of schistosomiasis, and have considerable implications for public health prioritization and resource allocation for schistosomiasis research, monitoring, and control.

The synergistic effect of concomitant schistosomiasis, hookworm, and trichuris infections on children's anemia burden.

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Amara E Ezeamama

2008-06-01

Full Text Available To estimate the degree of synergism between helminth species in their combined effects on anemia.Quantitative egg counts using the Kato-Katz method were determined for Ascaris lumbricoides, hookworm, Trichuris trichiura, and Schistosoma japonicum in 507 school-age children from helminth-endemic villages in The Philippines. Infection intensity was defined in three categories: uninfected, low, or moderate/high (M+. Anemia was defined as hemoglobin <11 g/dL. Logistic regression models were used to estimate odds ratios (OR, 95% confidence intervals (CI, and synergy index for pairs of concurrent infections.M+ co-infection of hookworm and S. japonicum (OR = 13.2, 95% CI: 3.82-45.5 and of hookworm and T. trichiura (OR = 5.34, 95% CI: 1.76-16.2 were associated with higher odds of anemia relative to children without respective M+ co-infections. For co-infections of hookworm and S. japonicum and of T. trichiura and hookworm, the estimated indices of synergy were 2.9 (95% CI: 1.1-4.6 and 1.4 (95% CI: 0.9-2.0, respectively.Co-infections of hookworm and either S. japonicum or T. trichiura were associated with higher levels of anemia than would be expected if the effects of these species had only independent effects on anemia. This suggests that integrated anti-helminthic treatment programs with simultaneous deworming for S. japonicum and some geohelminths could yield a greater than additive benefit for reducing anemia in helminth-endemic regions.

A Genome Wide Comparison to Identify Markers to Differentiate the Sex of Larval Stages of Schistosoma haematobium, Schistosoma bovis and their Respective Hybrids.

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Julien Kincaid-Smith

2016-11-01

Full Text Available For scientists working on gonochoric organisms, determining sex can be crucial for many biological questions and experimental studies, such as crossbreeding, but it can also be a challenging task, particularly when no sexual dimorphism is visible or cannot be directly observed. In metazoan parasites of the genus Schistosoma responsible for schistosomiasis, sex is genetically determined in the zygote with a female heterogametic ZW/ZZ system. Adult flukes have a pronounced sexual dimorphism, whereas the sexes of the larval stages are morphologically indistinguishable but can be distinguished uniquely by using molecular methods. Therefore, reliable methods are needed to identify the sex of larvae individuals. Here, we present an endpoint PCR-based assay using female-specific sequences identified using a genome-wide comparative analysis between males and females. This work allowed us to identify sex-markers for Schistosoma haematobium and Schistosoma bovis but also the hybrid between both species that has recently emerged in Corsica (France. Five molecular sex-markers were identified and are female-specific in S. haematobium and the hybrid parasite, whereas three of them are also female-specific in S. bovis. These molecular markers will be useful to conduct studies, such as experimental crosses on these disease-causing blood flukes, which are still largely neglected but no longer restricted to tropical areas.

Spatial analysis of Schistosomiasis in Hubei Province, China: a GIS-based analysis of Schistosomiasis from 2009 to 2013.

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Yan-Yan Chen

Full Text Available Schistosomiasis remains a major public health problem in China. The major endemic areas are located in the lake and marshland regions of southern China, particularly in areas along the middle and low reach of the Yangtze River. Spatial analytical techniques are often used in epidemiology to identify spatial clusters in disease regions. This study assesses the spatial distribution of schistosomiasis and explores high-risk regions in Hubei Province, China to provide guidance on schistosomiasis control in marshland regions.In this study, spatial autocorrelation methodologies, including global Moran's I and local Getis-Ord statistics, were utilized to describe and map spatial clusters and areas where human Schistosoma japonicum infection is prevalent at the county level in Hubei province. In addition, linear logistic regression model was used to determine the characteristics of spatial autocorrelation with time.The infection rates of S. japonicum decreased from 2009 to 2013. The global autocorrelation analysis results on the infection rate of S. japonicum for five years showed statistical significance (Moran's I > 0, P < 0.01, which suggested that spatial clusters were present in the distribution of S. japonicum infection from 2009 to 2013. Local autocorrelation analysis results showed that the number of highly aggregated areas ranged from eight to eleven within the five-year analysis period. The highly aggregated areas were mainly distributed in eight counties.The spatial distribution of human S. japonicum infections did not exhibit a temporal change at the county level in Hubei Province. The risk factors that influence human S. japonicum transmission may not have changed after achieving the national criterion of infection control. The findings indicated that spatial-temporal surveillance of S. japonicum transmission plays a significant role on schistosomiasis control. Timely and integrated prevention should be continued, especially in the Yangtze

Photosensory transduction in unicellular eukaryotes: a comparison between related ciliates Blepharisma japonicum and Stentor coeruleus and photoreceptor cells of higher organisms.

Science.gov (United States)

Sobierajska, Katarzyna; Fabczak, Hanna; Fabczak, Stanisław

2006-06-01

Blepharisma japonicum and Stentor coeruleus are related ciliates, conspicuous by their photosensitivity. They are capable of avoiding illuminated areas in the surrounding medium, gathering exclusively in most shaded places (photodispersal). Such behaviour results mainly from motile photophobic response occurring in ciliates. This light-avoiding response is observed during a relatively rapid increase in illumination intensity (light stimulus) and consists of cessation of cell movement, a period of backward movement (ciliary reversal), followed by a forward swimming, usually in a new direction. The photosensitivity of ciliates is ascribed to their photoreceptor system, composed of pigment granules, containing the endogenous photoreceptor -- blepharismin in Blepharisma japonicum, and stentorin in Stentor coeruleus. A light stimulus, applied to both ciliates activates specific stimulus transduction processes leading to the electrical changes at the plasma membrane, correlated with a ciliary reversal during photophobic response. These data indicate that both ciliates Blepharisma japonicum and Stentor coeruleus, the lower eukaryotes, are capable of transducing the perceived light stimuli in a manner taking place in some photoreceptor cells of higher eukaryotes. Similarities and differences concerning particular stages of light transduction in eukaryotes at different evolutional levels are discussed in this article.

Mitigation of nitrous oxide emissions from soils by Bradyrhizobium japonicum inoculation

Science.gov (United States)

Itakura, Manabu; Uchida, Yoshitaka; Akiyama, Hiroko; Hoshino, Yuko Takada; Shimomura, Yumi; Morimoto, Sho; Tago, Kanako; Wang, Yong; Hayakawa, Chihiro; Uetake, Yusuke; Sánchez, Cristina; Eda, Shima; Hayatsu, Masahito; Minamisawa, Kiwamu

2013-03-01

Nitrous oxide (N2O) is a greenhouse gas that is also capable of destroying the ozone layer. Agricultural soil is the largest source of N2O (ref. ). Soybean is a globally important leguminous crop, and hosts symbiotic nitrogen-fixing soil bacteria (rhizobia) that can also produce N2O (ref. ). In agricultural soil, N2O is emitted from fertilizer and soil nitrogen. In soybean ecosystems, N2O is also emitted from the degradation of the root nodules. Organic nitrogen inside the nodules is mineralized to NH4+, followed by nitrification and denitrification that produce N2O. N2O is then emitted into the atmosphere or is further reduced to N2 by N2O reductase (N2OR), which is encoded by the nosZ gene. Pure culture and vermiculite pot experiments showed lower N2O emission by nosZ+ strains and nosZ++ strains (mutants with increased N2OR activity) of Bradyrhizobium japonicum than by nosZ- strains. A pot experiment using soil confirmed these results. Although enhancing N2OR activity has been suggested as a N2O mitigation option, this has never been tested in the field. Here, we show that post-harvest N2O emission from soybean ecosystems due to degradation of nodules can be mitigated by inoculation of nosZ+ and non-genetically modified organism nosZ++ strains of B. japonicum at a field scale.

Evaluation of Schistosoma mansoni morbidity one year after ...

African Journals Online (AJOL)

The design was a Prospective cohorts study; and the setting was a busy canoe landing sites along Albert Nile in Schistosoma (S) mansoni hyperendemic areas of Rhino Camp and Obongi fishing village were selected for the study. Previously in 2005, 1562 people including fishermen and women, school pupils, teachers, ...

Decision-model estimation of the age-specific disability weight for schistosomiasis japonica: a systematic review of the literature.

Directory of Open Access Journals (Sweden)

Julia L Finkelstein

2008-03-01

Full Text Available Schistosomiasis is among the most prevalent parasitic infections worldwide. However, current Global Burden of Disease (GBD disability-adjusted life year estimates indicate that its population-level impact is negligible. Recent studies suggest that GBD methodologies may significantly underestimate the burden of parasitic diseases, including schistosomiasis. Furthermore, strain-specific disability weights have not been established for schistosomiasis, and the magnitude of human disease burden due to Schistosoma japonicum remains controversial. We used a decision model to quantify an alternative disability weight estimate of the burden of human disease due to S. japonicum. We reviewed S. japonicum morbidity data, and constructed decision trees for all infected persons and two age-specific strata, or =15 y. We conducted stochastic and probabilistic sensitivity analyses for each model. Infection with S. japonicum was associated with an average disability weight of 0.132, with age-specific disability weights of 0.098 ( or =15 y. Re-estimated disability weights were seven to 46 times greater than current GBD measures; no simulations produced disability weight estimates lower than 0.009. Nutritional morbidities had the greatest contribution to the S. japonicum disability weight in the <15 y model, whereas major organ pathologies were the most critical variables in the older age group. GBD disability weights for schistosomiasis urgently need to be revised, and species-specific disability weights should be established. Even a marginal increase in current estimates would result in a substantial rise in the estimated global burden of schistosomiasis, and have considerable implications for public health prioritization and resource allocation for schistosomiasis research, monitoring, and control.

Genetic Variation between Biomphalaria alexandrina Snails Susceptible and Resistant to Schistosoma mansoni Infection

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Suzanne M. F. El-Nassery

2013-01-01

Full Text Available Much effort has been made to control schistosomiasis infection in Egypt. However, enduring effects from such strategies have not yet been achieved. In this study, we sought to determine the genetic variability related to the interaction between Biomphalaria alexandrina snails and Schistosoma mansoni. Using RAPD-PCR with eight (10 mers random primers, we were able to determine the polymorphic markers that differed between snails susceptible and resistant to Schistosoma mansoni infection using five primers out of the eight. Our results suggest that the RAPD-PCR technique is an efficient means by which to compare genomes and to detect genetic variations between schistosomiasis intermediate hosts. The RAPD technique with the above-noted primers can identify genomic markers that are specifically related to the Biomphalaria alexandrina/Schistosoma mansoni relationship in the absence of specific nucleotide sequence information. This approach could be used in epidemiologic surveys to investigate genetic diversity among Biomphalaria alexandrina snails. The ability to determine resistant markers in Biomphalaria alexandrina snails could potentially lead to further studies that use refractory snails as agents to control the spread of schistosomiasis.

Survival and Competitiveness of Bradyrhizobium japonicum Strains 20 Years after Introduction into Field Locations in Poland.

Science.gov (United States)

Narożna, Dorota; Pudełko, Krzysztof; Króliczak, Joanna; Golińska, Barbara; Sugawara, Masayuki; Mądrzak, Cezary J; Sadowsky, Michael J

2015-08-15

It was previously demonstrated that there are no indigenous strains of Bradyrhizobium japonicum forming nitrogen-fixing root nodule symbioses with soybean plants in arable field soils in Poland. However, bacteria currently classified within this species are present (together with Bradyrhizobium canariense) as indigenous populations of strains specific for nodulation of legumes in the Genisteae tribe. These rhizobia, infecting legumes such as lupins, are well established in Polish soils. The studies described here were based on soybean nodulation field experiments, established at the Poznań University of Life Sciences Experiment Station in Gorzyń, Poland, and initiated in the spring of 1994. Long-term research was then conducted in order to study the relation between B. japonicum USDA 110 and USDA 123, introduced together into the same location, where no soybean rhizobia were earlier detected, and nodulation and competitive success were followed over time. Here we report the extra-long-term saprophytic survival of B. japonicum strains nodulating soybeans that were introduced as inoculants 20 years earlier and where soybeans were not grown for the next 17 years. The strains remained viable and symbiotically competent, and molecular and immunochemical methods showed that the strains were undistinguishable from the original inoculum strains USDA 110 and USDA 123. We also show that the strains had balanced numbers and their mobility in soil was low. To our knowledge, this is the first report showing the extra-long-term persistence of soybean-nodulating strains introduced into Polish soils and the first analyzing the long-term competitive relations of USDA 110 and USDA 123 after the two strains, neither of which was native, were introduced into the environment almost 2 decades ago. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

Catabolism of indole-3-acetic acid and 4- and 5-chloroindole-3-acetic acid in Bradyrhizobium japonicum

DEFF Research Database (Denmark)

Jensen, J B; Egsgaard, H; Van Onckelen, H

1995-01-01

Some strains of Bradyrhizobium japonicum have the ability to catabolize indole-3-acetic acid. Indoleacetic acid (IAA), 4-chloro-IAA (4-Cl-IAA), and 5-Cl-IAA were metabolized to different extents by strains 61A24 and 110. Metabolites were isolated and analyzed by high-performance liquid chromatogr...

Hubungan Perilaku Anak Sekolah Dasar dengan Kejadian Schistosomiasis di Kecamatan Lindu Kabupaten Sigi, Sulawesi Tengah

Directory of Open Access Journals (Sweden)

Octaviani Octaviani

2017-12-01

Full Text Available ABSTRAK Schistosomiasis merupakan penyakit parasitik yang disebabkan infeksi cacing Schistosoma japonicum, S. haematobium, S. mansoni, S. mekongi, dan S. intercalatum. Penyakit ini ditularkan melalui air tercemar cercaria ke hospes. Di Indonesia, schistosomiasis disebabkan oleh  S. japonicum ditemukan endemis di dataran tinggi Lindu, dataran tinggi Napu, dan dataran tinggi Bada. Penyakit schistosomiasis bisa menyerang semua orang termasuk anak-anak. Apabila tidak diberikan pengobatan bisa menjadi kronis. Anak yang terinfeksi akan mengalami gangguan pertumbuhan, gangguan kognitif, bahkan dapat menimbulkan kematian. Secara epidemiologi penularan schistosomiasis tidak terpisahkan dari faktor perilaku atau kebiasaan manusia. Penelitian bertujuan mengidentifikasi hubungan perilaku anak sekolah dasar dengan kejadian schistosomiasis. Penelitian dilakukan di Kecamatan Lindu Kabupaten Sigi Provinsi Sulawesi Tengah, selama 8 bulan mulai bulan Maret sampai Oktober 2014. Penelitian observasional ini menggunakan desain cross sectional. Pengumpulan data dilakukan dengan pengambilan sampel tinja dan wawancara pada anak sekolah. Sampel tinja diperiksa dengan menggunakan metode Kato-Katz. Hasil uji chi-square menunjukkan bahwa tidak ada hubungan antara kebiasaan mandi, kebiasaan buang air besar, kebiasaan ke daerah fokus dan kebiasaan penggunaan sepatu boot dengan kejadian schistosomiasis. Kata kunci: schistosomiasis, perilaku, anak sekolah dasar ABSTRACT Schistosomiasis is a parasitic disease caused by infection of Schistosoma japonicum, S. haematobium, S. mansoni, S. mekongi, and S. intercalatum. It is transmitted to definitive host through cercaria contaminated water. In Indonesia, schistosomiasis was caused by S. japonicum which can be found in endemic areas at Lindu, Napu, and Bada highland. Schistosomiasis can infect all people regardless their age. If untreated, it leads to a chronic condition. Children who are infected will have a growth and cognitive

Glucose Uptake in the Human Pathogen Schistosoma mansoni Is Regulated Through Akt/Protein Kinase B Signaling.

Science.gov (United States)

McKenzie, Maxine; Kirk, Ruth S; Walker, Anthony J

2018-06-05

In Schistosoma mansoni, the facilitated glucose transporter SGTP4, which is expressed uniquely in the apical surface tegumental membranes of the parasite, imports glucose from host blood to support its growth, development, and reproduction. However, the molecular mechanisms that underpin glucose uptake in this blood fluke are not understood. In this study we employed techniques including Western blotting, immunolocalization, confocal laser scanning microscopy, pharmacological assays, and RNA interference to functionally characterize and map activated Akt in S mansoni. We find that Akt, which could be activated by host insulin and l-arginine, was active in the tegument layer of both schistosomules and adult worms. Blockade of Akt attenuated the expression and evolution of SGTP4 at the surface of the host-invading larval parasite life-stage, and suppressed SGTP4 expression at the tegument in adults; concomitant glucose uptake by the parasite was also attenuated in both scenarios. These findings shed light on crucial mechanistic signaling processes that underpin the energetics of glucose uptake in schistosomes, which may open up novel avenues for antischistosome drug development.

Blockade of PD-1 Signaling Enhances Th2 Cell Responses and Aggravates Liver Immunopathology in Mice with Schistosomiasis japonica.

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Sha Zhou

2016-10-01

Full Text Available More than 220 million people worldwide are chronically infected with schistosomes, causing severe disease or even death. The major pathological damage occurring in schistosomiasis is attributable to the granulomatous inflammatory response and liver fibrosis induced by schistosome eggs. The inflammatory response is tightly controlled and parallels immunosuppressive regulation, constantly maintaining immune homeostasis and limiting excessive immunopathologic damage in important host organs. It is well known that the activation of programmed death 1 (PD-1 signaling causes a significant suppression of T cell function. However, the roles of PD-1 signaling in modulating CD4+ T cell responses and immunopathology during schistosome infection, have yet to be defined.Here, we show that PD-1 is upregulated in CD4+ T cells in Schistosoma japonicum (S. japonicum-infected patients. We also show the upregulation of PD-1 expression in CD4+ T cells in the spleens, mesenteric lymph nodes, and livers of mice with S. japonicum infection. Finally, we found that the blockade of PD-1 signaling enhanced CD4+ T helper 2 (Th2 cell responses and led to more severe liver immunopathology in mice with S. japonicum infection, without a reduction of egg production or deposition in the host liver.Overall, our study suggests that PD-1 signaling is specifically induced to control Th2-associated inflammatory responses during schistosome infection and is beneficial to the development of PD-1-based control of liver immunopathology.

Molecular identification and genetic variation of varieties of Styphnolobium japonicum (Fabaceae) using SRAP markers.

Science.gov (United States)

Sun, R X; Zhang, C H; Zheng, Y Q; Zong, Y C; Yu, X D; Huang, P

2016-05-06

Thirty-four Styphnolobium japonicum varieties were analyzed using sequence-related amplified polymorphism (SRAP) markers, to investigate genetic variation and test the effectiveness of SRAP markers in DNA fingerprint establishment. Twelve primer pairs were selected from 120 primer combinations for their reproducibility and high polymorphism. We found a total of 430 amplified fragments, of which 415 fragments were considered polymorphic with an average of 34.58 polymorphic fragments for each primer combination. The percentage of polymorphic fragments was 96.60%, and four primer pairs showed 100% polymorphism. Moreover, simple matched coefficients ranged between 0.68 and 0.89, with an average of 0.785, indicating that the genetic variation among varieties was relatively low. This could be because of the narrow genetic basis of the selected breeding material. Based on the similarity coefficient value of 0.76, the varieties were divided into four major groups. In addition, abundant and clear SRAP fingerprints were obtained and could be used to establish DNA fingerprints. In the DNA fingerprints, each variety had its unique pattern that could be easily distinguished from others. The results demonstrated that 34 varieties of S. japonicum had a relatively narrow genetic variation. Hence, a broadening of the genetic basis of breeding material is necessary. We conclude that establishment of DNA fingerprint is feasible by means of SRAP markers.

Assessment of the molluscicidal activities of Tribromosalan, Cartap and Chlorothalonil against Oncomelania hupensis.

Science.gov (United States)

Xia, Q; Tan, P; Feng, X; Chen, M; Kajihara, N; Minai, M; Hosaka, Y

1992-04-01

Molluscicidal activities of Tribromosalan, Cartap and Chlorothalonil were evaluated in the laboratory and the field against Oncomelania hupensis, the intermediate host of Schistosoma japonicum in China. The three chemicals were very effective against O. hupensis in the laboratory. The molluscicidal activities found in the field trials suggest that Tribromosalan and Cartap may be used as practical molluscicides. Dosage of 10 g/m2 of Tribromosalan in spring only and 20 g/m2 of Cartap in both spring and autumn would be recommendable as practical mollusciciding doses for the control of O. hupensis.

Evolution of sarcoma 180 (ascitic tumor in mice infected with Schistosoma mansoni

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Fausto Edmundo Lima Pereira

1986-03-01

Full Text Available Mice infected with 60 cercariae of Schistosoma mansoni were more resistant to the sarcoma 180 ascites tumor. Tumor inoculation was performed 50 days after schistosoma infection and the animals were observed and weighed at 48 hours intervals for development and progression of malignancy. In infected mice the weight gain (ascites formation started later and was shorter than in uninfected Controls. Also, the number of tumor cells into the peritoneal cavity 72h after tumor implantation was shorter in infected group than incontrols. This in creased resistance against a transplantable tumor probably is related to the effect of endotoxin on tumoricidal activity of macrophages activated by the infection. The immunodepression induced by Schistosoma mansoni infection enhances the proliferation of endogenous bacteria increasing the amount of endotoxin absorbed from the gut.Camundongos infectados com 60 cercárias de Schistosoma mansoni tomaram-se mais resistentes ao sarcoma 180 na forma de tumor ascítico. A inoculação das células tumorais foi feita no 50º dia de infecção e a evolução do tumor foi acompanhada através dapesagem dos animais com intervalos de 48 horas. Nos camundongos infectados o ganho de peso (formação da ascite começou mais tarde e foi menor do que nos controles não infectados. Também o número de células tumorais na cavidade peritoneal 72 horas após a implantação do tumor foi menor no grupo infectado. Este aumento de resistência a um tumor transplantávelpossivelmente está relacionado ao efeito de endotoxinas sobre a atividade tumoricida dos macrofagos ativados pela infecção. A imunossupressão induzida pela infecção favorece a proliferação de bactérias da flora endógena aumentando a quantidade de endotoxinas absorvidas pelo intestino.

Effects of Mirazid Treatment and Vaccination with Irradiated Cercariae in Experimentally Schistosoma mansoni Infected Mice

International Nuclear Information System (INIS)

Fayad, M.E.; Moawad, M.A.; Abd El-Fattah, N.Se.

2006-01-01

Schistosomiasis Tops all the endemic parasitic diseases particularly in Egypt. This study was performed on 4 groups of mice, each group formed of 25 mice. Group 1 (control group) infected with Schistosoma mansoni cercariae, group 2 (vaccinated group) vaccinated with irradiated cercariae, group 3 (treated group) infected with living cercariae of Schistosoma mansoni, then treated with Mirazid in the day post infection and group 4 (vaccinated and treated group) vaccinated with irradiated cercariae of Schistosoma mansoni then challenged and treated with Mirazid in the day post infection. By comparing the results of group 4 (vaccinated and treated group) with respective control there was a highly significant difference in all parameters. The worm burden reduction was 100 % and the percentage reduction of the eggs in the liver was 96.6 % and in the intestine was 89.76 %. Also, there were marked reduction in the size and number of granulomas with preservation of the liver architecture and absence of areas of degeneration and necrosis. So, this study shown that resistance to schistosomiasis can be consistently induced in mice by combining drug therapy with vaccination

The schistosoma-specific antibody response after treatment in non-immune travellers

DEFF Research Database (Denmark)

Duus, Liv Marie; Christensen, Anders Vittrup; Navntoft, Dorte

2009-01-01

Egg detection is the gold standard in diagnosing and controlling treatment in schistosomiasis, but sensitivity is poor in lightly infected individuals, whereas Schistosoma-specific antibodies are more sensitive. The purpose of the study was to evaluate use of Gut Associated Antigen (GAA...

Schistosoma mansoni c-AMP-dependent Protein Kinase (PKA): A Potential New Drug Target

Science.gov (United States)

2009-12-07

subunits from other eukaryotic organisms (Aplysia californica, S. japonicum, Caenorhabditis 143 elegans Mus musculus, Onchocerca volvulus , and Homo...Caenorhabditis elegans PKA-R (J05220); OvR, Onchocerca volvulus PKA-R (AY159364). 156 157 Figure 19: RNAi of Sm04765 in...PKA cancer chemotherapeutics [12]. Interestingly, the PKA-R subunit homologue in Onchocerca volvulus , causative agent of river blindness, is being

Morfologia e desenvolvimento de Schistosoma mansoni Sambon, 1907 em infecções unissexuais experimentalmente produzidas no camundongo Morphology and development of Schistosoma mansoni Sambon, 1907 in unisexual infections produced experimentally in mice

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Eliana Maria Zanotti

1982-04-01

Full Text Available Estudou-se o desenvolvimento de Schistosoma mansoni em infecções unissexuais no camundongo. Os esquistossomos fêmeos apresentaram-se menos desenvolvidos do que os machos. Houve correlação entre o comprimento dos machos e o número de testículos. Verificou-se que o isolamento sexual é prejudicial aos dois sexos, principalmente à fêmea.The Schistosoma mansoni development in mice submitted to unisexual infections was studied. The single female worms developed less than the single males. There was correlation between the male's length and the number of his tests. It was verified that sexual isolation of the schistosomes is prejudicial to both sexes, mainly for the female.

Bioakumulasi Logam Berat oleh Beberapa Galur Bradyrhizobium japonicum

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ADE NOOR SYAMSUDIN

2005-09-01

Full Text Available Heavy metal utilization in industry and agriculture have caused an environmental problem to existing life. Bioaccumulation is made up by a concentration of certain chemical compounds in living tissues. The objective of this research was to reveal the ability of lipopolysaccharides (LPSs of heavy metal Bradyrhizobium japonicum tolerant strains in accumulating heavy metals. The strains used were BDG 10, KDR 10, and KDR 15. The ability of each strains on heavy metal accumulation of Cu, Pb, Zn, Ni, and Cd were quantitatively determined using atomic absorption spectrophotometry. The result showed that each strains has its own capacity to accumulate heavy metals. Accumulation of Cu (0.100, Pb (0.320, and Cd (0.048 ppm/mg dry weight by KDR 10 seem higher than BDG 10 and KDR 15. The highest accumulation of Zn and Ni was shown by KDR 15 in which the value were 0.360 and 0.165 ppm/mg dry weight, respectively and the least accumulation of all heavy metal studied was shown by BDG 10.

State-space forecasting of Schistosoma haematobium time-series in Niono, Mali.

Science.gov (United States)

Medina, Daniel C; Findley, Sally E; Doumbia, Seydou

2008-08-13

Much of the developing world, particularly sub-Saharan Africa, exhibits high levels of morbidity and mortality associated with infectious diseases. The incidence of Schistosoma sp.-which are neglected tropical diseases exposing and infecting more than 500 and 200 million individuals in 77 countries, respectively-is rising because of 1) numerous irrigation and hydro-electric projects, 2) steady shifts from nomadic to sedentary existence, and 3) ineffective control programs. Notwithstanding the colossal scope of these parasitic infections, less than 0.5% of Schistosoma sp. investigations have attempted to predict their spatial and or temporal distributions. Undoubtedly, public health programs in developing countries could benefit from parsimonious forecasting and early warning systems to enhance management of these parasitic diseases. In this longitudinal retrospective (01/1996-06/2004) investigation, the Schistosoma haematobium time-series for the district of Niono, Mali, was fitted with general-purpose exponential smoothing methods to generate contemporaneous on-line forecasts. These methods, which are encapsulated within a state-space framework, accommodate seasonal and inter-annual time-series fluctuations. Mean absolute percentage error values were circa 25% for 1- to 5-month horizon forecasts. The exponential smoothing state-space framework employed herein produced reasonably accurate forecasts for this time-series, which reflects the incidence of S. haematobium-induced terminal hematuria. It obliquely captured prior non-linear interactions between disease dynamics and exogenous covariates (e.g., climate, irrigation, and public health interventions), thus obviating the need for more complex forecasting methods in the district of Niono, Mali. Therefore, this framework could assist with managing and assessing S. haematobium transmission and intervention impact, respectively, in this district and potentially elsewhere in the Sahel.

Engineering metabolic pathways in Amycolatopsis japonicum for the optimization of the precursor supply for heterologous brasilicardin congeners production

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Paul N. Schwarz

2018-03-01

Full Text Available The isoprenoid brasilicardin A is a promising immunosuppressant compound with a unique mode of action, high potency and reduced toxicity compared to today's standard drugs. However, production of brasilicardin has been hampered since the producer strain Nocardia terpenica IFM0406 synthesizes brasilicardin in only low amounts and is a biosafety level 2 organism. Previously, we were able to heterologously express the brasilicardin gene cluster in the nocardioform actinomycete Amycolatopsis japonicum. Four brasilicardin congeners, intermediates of the BraA biosynthesis, were produced. Since chemical synthesis of the brasilicardin core structure has remained elusive we intended to produce high amounts of the brasilicardin backbone for semi synthesis and derivatization. Therefore, we used a metabolic engineering approach to increase heterologous production of brasilicardin in A. japonicum. Simultaneous heterologous expression of genes encoding the MVA pathway and expression of diterpenoid specific prenyltransferases were used to increase the provision of the isoprenoid precursor isopentenyl diphosphate (IPP and to channel the precursor into the direction of diterpenoid biosynthesis. Both approaches contributed to an elevated heterologous production of the brasilicardin backbone, which can now be used as a starting point for semi synthesis of new brasilicardin congeners with better properties.

Novel carbazole aminoalcohols as inhibitors of β-hematin formation: Antiplasmodial and antischistosomal activities

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Weisi Wang

2017-08-01

Full Text Available Malaria and schistosomiasis are two of the most socioeconomically devastating parasitic diseases in tropical and subtropical countries. Since current chemotherapeutic options are limited and defective, there is an urgent need to develop novel antiplasmodials and antischistosomals. Hemozoin is a disposal product formed from the hemoglobin digestion by some blood-feeding parasites. Hemozoin formation is an essential process for the parasites to detoxify free heme, which is a reliable therapeutic target for identifying novel antiparasitic agents. A series of novel carbazole aminoalcohols were designed and synthesized as potential antiplasmodial and antischistosomal agents, and several compounds showed potent in vitro activities against Plasmodium falciparum 3D7 and Dd2 strains and adult and juvenile Schistosoma japonicum. Investigations on the dual antiparasitic mechanisms showed the correlation between inhibitory activity of β-hematin formation and antiparasitic activity. Inhibiting hemozoin formation was identified as one of the mechanisms of action of carbazole aminoalcohols. Compound 7 displayed potent antiplasmodial (Pf3D7 IC50 = 0.248 μM, PfDd2 IC50 = 0.091 μM and antischistosomal activities (100% mortality of adult and juvenile schistosomes at 5 and 10 μg/mL, respectively and exhibited low cytotoxicity (CC50 = 7.931 μM, which could be considered as a promising lead for further investigation. Stoichiometry determination and molecular docking studies were also performed to explain the mode of action of compound 7. Keywords: Carbazole aminoalcohols, Plasmodium falciparum, Schistosoma japonicum, Antiplasmodials, Antischistosomals, Hematin

Glycogen metabolism in Schistosoma mansoni worms after their isolation from the host

NARCIS (Netherlands)

Tiolens, A.G.M.; Bergh, S.G. van den

Adult Schistosoma mansoni worms rapidly degrade their endogenous glycogen stores immediately after isolation from the host. In NCTC 109 or in a diphasic culture medium the glycogen levels slowly recovered again after the initial decrease. The rapid degradation of glycogen could be prevented, even in

Activation route of the Schistosoma mansoni cathepsin B1 drug target

Czech Academy of Sciences Publication Activity Database

Jílková, Adéla; Horn, Martin; Řezáčová, Pavlína; Marešová, Lucie; Fajtová, Pavla; Brynda, Jiří; Vondrášek, Jiří; McKerrow, J. H.; Caffrey, C. R.; Mareš, Michael

2015-01-01

Roč. 22, č. 1 (2015), s. 39 ISSN 1211-5894. [Discussions in Structural Molecular Biology. Annual Meeting of the Czech Society for Structural Biology /13./. 19.03.2015-21.03.2015, Nové Hrady] Institutional support: RVO:61388963 ; RVO:68378050 Keywords : Schistosoma mansoni * cathepsin B1 * sulfated polysaccharides Subject RIV: CE - Biochemistry

An L-glucitol oxidizing dehydrogenase from Bradyrhizobium japonicum USDA 110 for production of D-sorbose with enzymatic or electrochemical cofactor regeneration

DEFF Research Database (Denmark)

Gauer, Sabrina; Wang, Zhijie; Otten, Harm

2014-01-01

A gene in Bradyrhizobium japonicum USDA 110, annotated as a ribitol dehydrogenase (RDH), had 87 % sequence identity (97 % positives) to the N-terminal 31 amino acids of an L-glucitol dehydrogenase from Stenotrophomonas maltophilia DSMZ 14322. The 729-bp long RDH gene coded for a protein consistin...

Dicty_cDB: Contig-U15443-1 [Dicty_cDB

Lifescience Database Archive (English)

Full Text Available lic Acid Glyc... 42 7e-04 2 ( EL475659 ) CHUL3619.b1_F17.ab1 CHU(LMS) puzzle sunf...Schistosoma japonicum cDNA similar ... 42 0.12 2 ( EL482406 ) CHUM4387.b1_F17.ab1 CHU(LMS) puzzle sunflower ...200.b1_O04.ab1 CHU(LMS) puzzle sunflower Hel... 42 5e-04 3 ( CD414213 ) Gm_ck46258 Soybean induced by Salicy.... 58 2e-04 2 ( EH303465 ) UAHYP_14C_F_G04 UaHyphae_ARS Uromyces appendicula... 46 3e-04 2 ( EL483290 ) CHUM5

Effects of Endosulfan on Predator–Prey Interactions Between Catfish and Schistosoma Host Snails

NARCIS (Netherlands)

Monde, Concillia; Syampungani, Stephen; Brink, van den Paul J.

2016-01-01

The effect of the pesticide endosulfan on predator–prey interactions between catfish and Schistosoma host snails was assessed in static tank experiments. Hybrid catfish (Clarias gariepinus × C. ngamensis) and Bulinus globosus were subjected to various endosulfan concentrations including an

Schistosome syntenin partially protects vaccinated mice against Schistosoma mansoni infection.

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Barbara C Figueiredo

2014-08-01

Full Text Available Schistosomiasis is a neglected tropical disease caused by several species of trematode of the genus Schistosoma. The disease affects more than 200 million people in the world and causes up to 280,000 deaths per year, besides having high morbidity due to chronic illness that damages internal organs. Current schistosomiasis control strategies are mainly based on chemotherapy, but many researchers believe that the best long-term strategy to control disease is a combination of drug treatment and immunization with an anti-schistosome vaccine. Among the most promising molecules as vaccine candidates are the proteins present in the tegument and digestive tract of the parasite.In this study, we describe for the first time Schistosoma mansoni syntenin (SmSynt and we evaluate its potential as a recombinant vaccine. We demonstrate by real-time PCR that syntenin is mainly expressed in intravascular life stages (schistosomula and adult worms of the parasite life cycle and, by confocal microscopy, we localize it in digestive epithelia in adult worms and schistosomula. Administration of siRNAs targeting SmSynt leads to the knock-down of syntenin gene and protein levels, but this has no demonstrable impact on parasite morphology or viability, suggesting that high SmSynt gene expression is not essential for the parasites in vitro. Mice immunization with rSmSynt, formulated with Freund's adjuvant, induces a Th1-type response, as suggested by the production of IFN-γ and TNF-α by rSmSynt-stimulated cultured splenocytes. The protective effect conferred by vaccination with rSmSynt was demonstrated by 30-37% reduction of worm burden, 38-43% reduction in the number, and 35-37% reduction in the area, of liver granulomas.Our report is the first characterization of syntenin in Schistosoma mansoni and our data suggest that this protein is a potential candidate for the development of a multi-antigen vaccine to control schistosomiasis.

Effect of gamma-radiation on cercariae of Schistosoma incognitum and S. spindale

Energy Technology Data Exchange (ETDEWEB)

Bhaskara Rao, T; Rao, B V; Hafeez, Md [College of Veterinary Sciences, Tirupati (India). Dept. of Parasitology

1989-06-01

In the present study an attempt has been made to study the effect of gamma radiation on cercariae of Schistosoma incognitum and S. spindale in mice at different dose levels of radiation, so as to note differences in their developmental patterns, compared with non-irradiated controls. (author). 10 refs.

PhaP phasins play a principal role in poly-β-hydroxybutyrate accumulation in free-living Bradyrhizobium japonicum

OpenAIRE

Yoshida, Ken-ichi; Takemoto, Yuki; Sotsuka, Takayuki; Tanaka, Kosei; Takenaka, Shinji

2013-01-01

Background Bradyrhizobium japonicum USDA110, a soybean symbiont, is capable of accumulating a large amount of poly-β-hydroxybutyrate (PHB) as an intracellular carbon storage polymer during free-living growth. Within the genome of USDA110, there are a number of genes annotated as paralogs of proteins involved in PHB metabolism, including its biosynthesis, degradation, and stabilization of its granules. They include two phbA paralogs encoding 3-ketoacyl-CoA thiolase, two phbB paralogs encoding ...

Isojacareubin from the Chinese Herb Hypericum japonicum: Potent Antibacterial and Synergistic Effects on Clinical Methicillin-Resistant Staphylococcus aureus (MRSA)

OpenAIRE

Zuo, Guo-Ying; An, Jing; Han, Jun; Zhang, Yun-Ling; Wang, Gen-Chun; Hao, Xiao-Yan; Bian, Zhong-Qi

2012-01-01

Through bioassay-guided fractionation of the extracts from the aerial parts of the Chinese herb Hypericum japonicum Thunb. Murray, Isojacareubin (ISJ) was characterized as a potent antibacterial compound against the clinical methicillin-resistant Staphylococcus aureus (MRSA). The broth microdilution assay was used to determine the minimal inhibitory concentrations (MICs) and minimal bactericidal concentrations (MBCs) of ISJ alone. The results showed t...

Human infections and co-infections with helminths in a rural population in Guichi, Anhui Province, China

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Yi Hu

2015-11-01

Full Text Available Helminth infections are believed to be common in tropical and subtropical countries. A cross-sectional study was carried out in two villages located in Guichi District in Anhui Province, the People’s Republic of China, where multiparasitism was investigated using parasitological tests. The data collected were fitted to Bayesian multi-level models to profile risk factors for helminth infections. The prevalence of Schistosoma (S. japonicum, Ascaris (A. lumbricoides and Trichuris (T. trichiura were 0.43% (range: 0-0.87% at the village level, 2.28% (range: 1.69-2.88%, and 0.21% (range: 0-0.42%, respectively. No hookworm infection was found. With regard to multiparasitism, only a 33-year-old female was found to be co-infected with S. japonicum and A. lumbricoides. Multiparasitism was unexpectedly rare in the study area, which contrasts with results from other studies carried out elsewhere in the country. The long-term usage of albendazole for individuals serologically positive for schistosomiasis may be the main reason, but this needs to be confirmed by future studies.

Acer japonicum Thunb.

OpenAIRE

2010-01-01

В статье приведены результаты работы за 2007 год, когда после аномально теплой зимы, впервые за 110 лет интродукции Acer japonicum (клён японский, входит в Красную книгу России) в ботаническом саду Санкт-Петербургской лесотехнической академии были получены его семена, и из них выращено семенное потомство. На фоне потепления климата в начале XXI века клён японский стал меньше обмерзать, отдельные экземпляры из жизненной формы кустарника стали расти деревом. Этот вид достиг здесь рекордных разм...

Organomegaly in Mali before and after praziquantel treatment. A possible association with Schistosoma haematobium

DEFF Research Database (Denmark)

Stecher, Chalotte Willemann; Madsen, Henry; Wilson, Shona

2017-01-01

Continuous exposure to schistosome-infested water results in acute and chronic morbidity in all ages. We analysed occurence of organomegaly via ultrasonography and investigated a possible additive effect of dual-dose drug administration in 401 Schistosoma haematobium infected individuals from...

Prolyl Oligopeptidase from the Blood Fluke Schistosoma mansoni: From Functional Analysis to Anti-schistosomal Inhibitors

Czech Academy of Sciences Publication Activity Database

Fajtová, P.; Štefanić, S.; Hradilek, M.; Dvořák, Jan; Vondrášek, J.; Jílková, A.; Ulrychová, L.; McKerrow, J.H.; Caffrey, C.R.; Mareš, M.; Horn, M.

2015-01-01

Roč. 9, č. 6 (2015), e0003827 ISSN 1935-2735 Institutional support: RVO:60077344 Keywords : Schistosoma mansoni * schistosomiasis * prolyl oligopeptidase * blood fluke Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 3.948, year: 2015

Inhibition of hydrogenase synthesis by DNA gyrase inhibitors in Bradyrhizobium japonicum

International Nuclear Information System (INIS)

Novak, P.D.; Maier, R.J.

1987-01-01

Derepression of an uptake hydrogenase in Bradyrhizobium japonicum is dependent on a microaerophilic environment. Addition of DNA gyrase inhibitors during derepression of hydrogenase specifically prevented expression of the hydrogenase enzyme. Antibodies to individual hydrogenase subunits failed to detect the protein after derepression in the presence of inhibitors, although there was no general inhibition of protein synthesis. The general pattern of proteins synthesized from 14 C-labeled amino acids during derepression was no significantly different whether proteins were labeled in the presence or in the absence of gyrase inhibitors. In contrast, if transcription or translation was inhibited by addition of inhibitors of those functions, virtually no proteins were labeled during derepression. This indicated that most of the 14 C-labeled proteins were synthesized de novo during derepression, synthesis of most proteins was unaffected by gyrase inhibitors, and the dependence of hydrogenase synthesis on gyrase activity was a specific one

Evolutionary Instability of Symbiotic Function in Bradyrhizobium japonicum

Science.gov (United States)

Sachs, Joel L.; Russell, James E.; Hollowell, Amanda C.

2011-01-01

Bacterial mutualists are often acquired from the environment by eukaryotic hosts. However, both theory and empirical work suggest that this bacterial lifestyle is evolutionarily unstable. Bacterial evolution outside of the host is predicted to favor traits that promote an independent lifestyle in the environment at a cost to symbiotic function. Consistent with these predictions, environmentally-acquired bacterial mutualists often lose symbiotic function over evolutionary time. Here, we investigate the evolutionary erosion of symbiotic traits in Bradyrhizobium japonicum, a nodulating root symbiont of legumes. Building on a previous published phylogeny we infer loss events of nodulation capability in a natural population of Bradyrhizobium, potentially driven by mutation or deletion of symbiosis loci. Subsequently, we experimentally evolved representative strains from the symbiont population under host-free in vitro conditions to examine potential drivers of these loss events. Among Bradyrhizobium genotypes that evolved significant increases in fitness in vitro, two exhibited reduced symbiotic quality, but no experimentally evolved strain lost nodulation capability or evolved any fixed changes at six sequenced loci. Our results are consistent with trade-offs between symbiotic quality and fitness in a host free environment. However, the drivers of loss-of-nodulation events in natural Bradyrhizobium populations remain unknown. PMID:22073160

High prevalence of enteroparasites in children from Ribeirão Preto, São Paulo, Brazil

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Renata Elizabete Pagotti da Fonseca

Full Text Available ABSTRACT Objective: To determine the prevalence of intestinal parasites and possible associated factors. Method: Cross-sectional epidemiological study of 962 children (3-12-years from an area within the scope of a basic health unit in Ribeirão Preto, São Paulo, Brazil. Data were collected by home interviews and three-sample stool analysis and evaluated with the chi-square and Fisher's exact tests (p<0.05. Results: The prevalence of intestinal parasites was significantly high (57.5%. Giardia lamblia was the most prevalent (50.8%, followed by Ascaris lumbricoides (17.8%, Entamoeba histolytica, Hymenolepis nana, Entamoeba coli and Enterobius vermiculares (5.6-7.3% and other parasites of lower prevalence, such as Schistosoma japonicum (1% and Schistosoma mansoni (0.5%. No statistically significant associations were detected between prevalence and the risk factors analyzed. Conclusion: Since the area presents good conditions of environmental sanitation, health education programs should be implemented that emphasize hygiene procedures for the hands and for food and water to be consumed by the population.

Cistitis por schistosoma haematobium, presentación de un caso

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Ramón Zaragoza Durañona

2014-08-01

Full Text Available No es frecuente en nuestro medio la infección por Schistosoma. haematobium, pero existen todos los elementos de la triada ecológica para su transmisión. Se presenta el caso de un paciente masculino, de raza mestiza, con 46 años de edad y procedencia rural, que refiere dolores lumbares al orinar, disuria, tenesmo vesical y polaquiuria durante el último año. Al examen físico se encontró el abdomen discretamente doloroso a la palpación superficial y profunda en hipogastrio y fosas lumbares. Se trató como una infección urinaria sin mejoría. Los complementarios arrojaron discreta eosinofilia y reflujo vesicoureteral grado IV en la uretrocistografía retrógrada y miccional. La cistoscopia videoasistida reportó, a nivel del trígono, la mucosa vesical enrojecida con estructuras en forma de granos de arroz de aspecto puntiforme; la biopsia informó huevos de esquistosomas y cambios metaplásicos en el epitelio vesical. Se trató con praziquantel y desaparecieron los síntomas. A los seis meses los complementarios resultaron normales y el paciente está asintomático. Se concluye en la importancia de considerar la infección por Schistosoma haematobium entre los diagnósticos de la infección urinaria refractaria al tratamiento

The feasibility of MS and advanced data processing for monitoring Schistosoma mansoni infection

DEFF Research Database (Denmark)

Balog, Crina I.A.; Alexandrov, Theodore; Derks, Rico J.

2010-01-01

Sensitive diagnosis, monitoring of disease progression and the evaluation of chemotherapeutic interventions are of prime importance for the improvement of control and prevention strategies for Schistosomiasis. The aim of the present study was to identify novel markers of Schistosoma mansoni...

Schistosomiasis research in the dongting lake region and its impact on local and national treatment and control in China.

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Donald P McManus

2011-08-01

Full Text Available Schistosomiasis is a chronic and debilitating parasitic disease that has often been neglected because it is a disease of poverty, affecting poor rural communities in the developing world. This is not the case in the People's Republic of China (PRC, where the disease, caused by Schistosoma japonicum, has long captured the attention of the Chinese authorities who have, over the past 50-60 years, undertaken remarkably successful control programs that have substantially reduced the schistosomiasis disease burden. The Dongting Lake region in Hunan province is one of the major schistosome-endemic areas in the PRC due to its vast marshland habitats for the Oncomelania snail intermediate hosts of S. japonicum. Along with social, demographic, and other environmental factors, the recent completion and closure of the Three Gorges dam will most likely increase the range of these snail habitats, with the potential for re-emergence of schistosomiasis and increased transmission in Hunan and other schistosome-endemic provinces being a particular concern. In this paper, we review the history and the current status of schistosomiasis control in the Dongting Lake region. We explore the epidemiological factors contributing to S. japonicum transmission there, and summarise some of the key research findings from studies undertaken on schistosomiasis in Hunan province over the past 10 years. The impact of this research on current and future approaches for sustainable integrated control of schistosomiasis in this and other endemic areas in the PRC is emphasised.

Nickel accumulation and storage in bradyrhizobium japonicum

International Nuclear Information System (INIS)

Maier, R.J.; Pihl, T.D.; Stults, L.; Sray, W.

1990-01-01

Hydrogenase-depressed (chemolithotrophic growth conditions) and heterotrophically grown cultures of Bradyrhizobium japonicum accumulated nickel about equally over a 3-h period. Both types of cultures accumulated nickel primarily in a form that was not exchangeable with NiCl 2 , and they accumulated much more Ni than would be needed for the Ni-containing hydrogenase. The nickel accumulated by heterotrophically incubated cultures could later be mobilized to allow active hydrogenase synthesis during derepression in the absence of nickel, while cells both grown with Ni and the derepressed without nickel had low hydrogenase activities. The level of activity in cells grown with Ni and then derepressed without nickel was about the same as that in cultures derepressed in the presence of nickel. The Ni accumulated by heterotrophically grown cultures was associated principally with soluble proteins rather than particulate material, and this Ni was not lost upon dialyzing an extract containing the soluble proteins against either Ni-containing or EDTA-containing buffer. However, this Ni was lost upon pronase or low pH treatments. The soluble Ni-binding proteins were partially purified by gel filtration and DEAE chromatography. They were not antigenically related to hydrogenase peptides. Much of the 63 Ni eluted as a single peak of 48 kilodaltons. Experiments involving immunuprecipitation of 63 Ni-containing hydrogenase suggested that the stored source of Ni in heterotrophic cultures that could later be mobilized into hydrogenase resided in the nonexchangeable Ni-containing fraction rather than in loosely bound or ionic forms

System analysis of salt and osmotic stress induced proteins in Nostoc muscorum and Bradyrhizobium japonicum

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Vipin Kaithwas

2017-06-01

Full Text Available In this study the proteome response of the two diazotrophic organism’s viz. Nostoc muscorum and Bradyrhizobium japonicum exposed to salt (NaCl and osmotic (sucrose stresses was compared. Out of the total over expressed proteins; we have selected only three over expressed proteins viz. GroEL chaperonin, nitrogenase Mo-Fe protein and argininosuccinate synthase for further analysis, and then we analyzed the amino acid frequencies of all the three over expressed proteins. That led to the conclusion that amino acids e.g. alanine, glycine and valine that were energetically cheaper to produce were showing higher frequencies. This study would help in tracing the phylogenetic relationship between protein families.

Schistosoma mansoni infection along the coast of Lake Victoria in Mwanza region, Tanzania

DEFF Research Database (Denmark)

Olsen, Annette; Kinung'hi, Safari; Magnussen, Pascal

2015-01-01

Prevalence and intensity of Schistosoma mansoni infection according to age, sex, and occupation were investigated in 100 first-year students (aged 7-8 years), 100 schoolchildren (aged 9-12 years), and 50 adults (aged 20-55 years) from 149 villages. The schoolchildren provided three stool specimen...

Increased prevalence of leukocytes and elevated cytokine levels in semen from Schistosoma haematobium-infected individuals

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Leutscher, Peter D C; Pedersen, Mette; Raharisolo, Clairette

2005-01-01

In this study, we investigated the seminal inflammatory response to egg infestation of the urogenital organs in 240 semen-donating men aged 15-49 years living in a Schistosoma haematobium-endemic area of Madagascar. In 29 subjects (12%) with excretion of > or =5 ova/ejaculate, leukocytospermia (>10...

Improving the management of imported schistosomiasis haematobia in China: lessons from a case with multiple misdiagnoses.

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Hua, Hai-Yong; Wang, Wei; Cao, Guo-Qun; Tang, Feng; Liang, You-Sheng

2013-09-11

Human Schistosoma haematobium infection that causes urinary schistosomiasis occurs in Africa and the eastern Mediterranean, and China is only endemic for S. japonicum. In this report, we reported an imported case with S. haematobium infection returning from Angola to Shaanxi Province, northwestern China, where S. japonicum is not endemic. The case was misdiagnosed as ureteral calculus, invasive urothelial carcinoma and eosinophilic cystitis in several hospitals, and was finally diagnosed by means of serological assay followed by microscopic examination of the urine sediment. The patient was then treated with praziquantel, and a satisfactory outcome was obtained. As S. haematobium is not indigenous to China, most Chinese doctors and medical technicians are unfamiliar with this introduced parasitic disease, therefore, they need to increase the awareness of its existence when they encounter persons who have visited or resided in endemic areas, and the techniques for detection of the parasite, so as to reduce the misdiagnosis. In addition, health education should be given to those who will go to the endemic areas to improve their knowledge and awareness on prevention and control of schistosomiasis haematobia, thereby reducing the risk of exposure to the infested freshwater.

High burden of Schistosoma mansoni infection in school-aged children in Marolambo District, Madagascar.

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Spencer, Stephen A; Penney, James M St John; Russell, Hannah J; Howe, Anthony P; Linder, Cortland; Rakotomampianina, Andriamahitsisambatra L D; Nandimbiniaina, Anjara M; Squire, S Bertel; Stothard, J Russell; Bustinduy, Amaya L; Rahetilahy, Alain M

2017-06-24

A school-based survey was undertaken to assess prevalence and infection intensity of schistosomiasis in school-aged children in the Marolambo District of Madagascar. School-aged children from six purposively selected schools were tested for Schistosoma haematobium by urine filtration and Schistosoma mansoni using circulating cathodic antigen (CCA) and Kato-Katz stool analysis. The investigators did not address soil-transmitted helminths (STH) in this study. Of 399 school-aged children screened, 93.7% were infected with S. mansoni based on CCA analysis. Kato-Katz analysis of stool revealed S. mansoni infection in 73.6% (215/ 292). Heavy infections (> 400 eggs per gram) were common (32.1%; 69/ 215), with a mean of 482 eggs per gram of stool. Moderate infection intensities were detected in 31.2% (67/ 215) and light infection intensities in 36.7% (79/ 215) of infected participants. No infection with S. haematobium was detected by urine filtration. Intestinal schistosomiasis appears a considerable public health issue in this remote area of Madagascar where there is a pressing need for mass drug administration.

Schistosoma mansoni infection in a fishermen community, the Lake Manzala region-Egypt

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Amira Taman

2014-12-01

Full Text Available Objective: To determine the prevalence of schistosomiasis in the fishermen community in Egypt. Methods: A cross-sectional survey for schistosomiasis mansoni was conducted among 150 fishermen and their families from January to November 2013. Faecal samples were examined by Kato Katz method and formalin-ether concentration technique. Malacological survey was conducted to identify infection of the snail intermediate host by larval stage of Schistosoma mansoni. Snails were collected and checked for shedding of cercariae after light exposure. Results: Overall prevalence of infection was 26.6% with an intensity of (42.7依7.2 ova/g of stool. Infection was common in male and significantly increased in the age of 20-40 years. Praziquanteltreated individuals had a high significant decrease in intensity (27.2依2.4 ova/g of stool than those with no treatment history. Biomphalaria alexandrina snail was infected with Schistosoma mansoni particularly in warm seasons and mice infection was established successfully from the shed cercariae, moreover adult worms were obtained via portal perfusion of the infected mice. Conclusions: Findings indicated the endemicity of schistosomiasis mansoni in Lake Manzala region, therefore, appropriate integrated control measures are needed among fishermen including health education, environmental sanitation, periodic screening and mass treatment with praziquantel.

Fast evolutionary rates associated with functional loss in class I glucose transporters of Schistosoma mansoni

Czech Academy of Sciences Publication Activity Database

Cabezas-Cruz, A.; Valdés, James J.; Lancelot, J.; Pierce, R.J.

2015-01-01

Roč. 16, NOV 19 2015 (2015), s. 980 ISSN 1471-2164 R&D Projects: GA MŠk(CZ) EE2.3.30.0032 Institutional support: RVO:60077344 Keywords : Schistosoma mansoni * glucose transporters * transcriptional regulation * phylogen * biophysics Subject RIV: EI - Biotechnology ; Bionics Impact factor: 3.867, year: 2015

Concentrated insulins: the new basal insulins

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Lamos EM

2016-03-01

Full Text Available Elizabeth M Lamos,1 Lisa M Younk,2 Stephen N Davis3 1Division of Endocrinology, Diabetes and Nutrition, 2Department of Medicine, University of Maryland School of Medicine, 3Department of Medicine, University of Maryland Medical Center, Baltimore, MD, USA Introduction: Insulin therapy plays a critical role in the treatment of type 1 and type 2 diabetes mellitus. However, there is still a need to find basal insulins with 24-hour coverage and reduced risk of hypoglycemia. Additionally, with increasing obesity and insulin resistance, the ability to provide clinically necessary high doses of insulin at low volume is also needed. Areas covered: This review highlights the published reports of the pharmacokinetic (PK and glucodynamic properties of concentrated insulins: Humulin-R U500, insulin degludec U200, and insulin glargine U300, describes the clinical efficacy, risk of hypoglycemic, and metabolic changes observed, and finally, discusses observations about the complexity of introducing a new generation of concentrated insulins to the therapeutic market. Conclusion: Humulin-R U500 has a similar onset but longer duration of action compared with U100 regular insulin. Insulin glargine U300 has differential PK/pharmacodynamic effects when compared with insulin glargine U100. In noninferiority studies, glycemic control with degludec U200 and glargine U300 is similar to insulin glargine U100 and nocturnal hypoglycemia is reduced. Concentrated formulations appear to behave as separate molecular entities when compared with earlier U100 insulin analog compounds. In the review of available published data, newer concentrated basal insulins may offer an advantage in terms of reduced intraindividual variability as well as reducing the injection burden in individuals requiring high-dose and large volume insulin therapy. Understanding the PK and pharmacodynamic properties of this new generation of insulins is critical to safe dosing, dispensing, and administration

Tolerance of Oncomelania hupensis quadrasi to varying concentrations of dissolved oxygen and organic pollution*

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Garcia, Rolando G.

1972-01-01

Ecological investigations were made of habitats containing natural populations of the snail Oncomelania hupensis quadrasi and of habitats free from the snail in the island of Leyte, Philippines. This species of snail is a vector of Schistosoma japonicum in the Philippines. Snail-infested habitats had dissolved oxygen levels of 3.8-9.85 ppm but snail-free habitats had levels of only 0.08-3.6 ppm. Snail-infested habitats were less polluted by organic matter than habitats that were snail-free. Larger numbers of chlorophyll-bearing algae were present in both the water and the soil of snail-infested habitats. Other factors, including temperature, pH, hydrogen carbonate alkalinity, and relative humidity, were also investigated. PMID:4538906

Schistosoma mansoni and HIV infection in a Ugandan population with high HIV and helminth prevalence.

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Sanya, Richard E; Muhangi, Lawrence; Nampijja, Margaret; Nannozi, Victoria; Nakawungu, Prossy Kabuubi; Abayo, Elson; Webb, Emily L; Elliott, Alison M

2015-09-01

Recent reports suggest that Schistosoma infection may increase the risk of acquiring human immunodeficiency virus (HIV). We used data from a large cross-sectional study to investigate whether Schistosoma mansoni infection is associated with increased HIV prevalence. We conducted a household survey of residents in island fishing communities in Mukono district, Uganda, between October 2012 and July 2013. HIV status was assessed using rapid test kits. Kato-Katz (KK) stool tests and urine-circulating cathodic antigen (CCA) were used to test for Schistosoma infection. Multivariable logistic regression, allowing for the survey design, was used to investigate the association between S. mansoni infection and HIV infection. Data from 1412 participants aged 13 years and older were analysed (mean age 30.3 years, 45% female). The prevalence of HIV was 17.3%. Using the stool Kato-Katz technique on a single sample, S. mansoni infection was detected in 57.2% (719/1257) of participants; urine CCA was positive in 73.8% (478/650) of those tested. S. mansoni infection was not associated with HIV infection. [KK (aOR = 1.04; 95% CI: 0.74-1.47, P = 0.81), CCA (aOR = 1.53; 95% CI: 0.78-3.00, P = 0.19)]. The median S. mansoni egg count per gram was lower in the HIV-positive participants (P = 0.005). These results add to the evidence that S. mansoni has little effect on HIV transmission, but may influence egg excretion. © 2015 The Authors. Tropical Medicine & International Health Published by John Wiley & Sons Ltd.

Immunolocalization of Schistosoma mansoni and Schistosoma haematobium antigens reacting with their Egyptian snail vectors.

Science.gov (United States)

El-Dafrawy, Shadia M; Mohamed, Amira H; Hammam, Olfat A; Rabia, Ibrahim

2007-12-01

The reaction of the haemolymph and the tissue of infected intermediate hosts, Biomphalaria alexandrina and Bulinus truncatus to Schistosoma mansoni and S. haematobium antigens were investigated using the indirect immunoperoxidase technique. A new technique, Agarose cell block was used in collection of haemolymph which helped in collecting plenty of well formed cells in comparison to the ordinary one using the cytospin. Collected haemolymph and prepared tissues of uninfected and infected B. alexandria and B. truncatus were fixed and then reacted with anti-S. mansoni and anti-S. haematobium IgG polyclonal antibodies. The haemolymph and tissue of infected B. alexandrina and B. truncatus gave a positive peroxidase reaction represented by a brown colour. In haemolymph, the positive peroxidase reaction was detected mainly in the cytoplasm of the amoebocytes. In the tissue, it was detected in epithelial cells lining the tubules, male cells in the lumen of the tubules and in female oogonia cells along the periphery of the tubules. The similarity in the strength and distribution of positive reaction in B. alexandrina and B. truncates was observed as compared to control. Thus, the immunoperoxidase technique proved to be an effective indicator for the schistosome-antigen in the snails.

An Atlas for Schistosoma mansoni Organs and Life-Cycle Stages Using Cell Type-Specific Markers and Confocal Microscopy

Science.gov (United States)

Cogswell, Alexis; Williams, David L.; Newmark, Phillip A.

2011-01-01

Schistosomiasis (bilharzia) is a tropical disease caused by trematode parasites (Schistosoma) that affects hundreds of millions of people in the developing world. Currently only a single drug (praziquantel) is available to treat this disease, highlighting the importance of developing new techniques to study Schistosoma. While molecular advances, including RNA interference and the availability of complete genome sequences for two Schistosoma species, will help to revolutionize studies of these animals, an array of tools for visualizing the consequences of experimental perturbations on tissue integrity and development needs to be made widely available. To this end, we screened a battery of commercially available stains, antibodies and fluorescently labeled lectins, many of which have not been described previously for analyzing schistosomes, for their ability to label various cell and tissue types in the cercarial stage of S. mansoni. This analysis uncovered more than 20 new markers that label most cercarial tissues, including the tegument, the musculature, the protonephridia, the secretory system and the nervous system. Using these markers we present a high-resolution visual depiction of cercarial anatomy. Examining the effectiveness of a subset of these markers in S. mansoni adults and miracidia, we demonstrate the value of these tools for labeling tissues in a variety of life-cycle stages. The methodologies described here will facilitate functional analyses aimed at understanding fundamental biological processes in these parasites. PMID:21408085

Projecting the long-term impact of school- or community-based mass-treatment interventions for control of Schistosoma infection.

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Xiaoxia Wang

Full Text Available Schistosomiasis remains a significant health burden in many areas of the world. Morbidity control, focused on limiting infection intensity through periodic delivery of anti-schistosomal medicines, is the thrust of current World Health Organization guidelines (2006 for reduction of Schistosoma-related disease. A new appreciation of the lifetime impact of repeated Schistosoma infection has directed attention toward strategies for greater suppression of parasite infection per se, with the goal of transmission interruption. Variations in drug schedules involving increased population coverage and/or treatment frequency are now undergoing field trials. However, their relative effectiveness in long-term infection suppression is presently unknown.Our study used available field data to calibrate advanced network models of village-level Schistosoma transmission to project outcomes of six different community- or school age-based programs, as compared to the impact of current 2006 W.H.O. recommended control strategies. We then scored the number of years each of 10 typical villages would remain below 10% infection prevalence (a practicable level associated with minimal prevalence of disease. All strategies that included four annual treatments effectively reduced community prevalence to less than 10%, while programs having yearly gaps ('holidays' failed to reach this objective in half of the communities. Effective post-program suppression of infection prevalence persisted in half of the 10 villages for 7-10 years, whereas in five high-risk villages, program effects on prevalence lasted zero to four years only.At typical levels of treatment adherence (60 to 70%, current WHO recommendations will likely not achieve effective suppression of Schistosoma prevalence unless implemented for ≥6 years. Following more aggressive 4 year annual intervention, some communities may be able to continue without further intervention for 8-10 years, while in higher

Structural bioinformatics study of PNP from Schistosoma mansoni

International Nuclear Information System (INIS)

Silveira, Nelson Jose Freitas da; Uchoa, Hugo Brandao; Canduri, Fernanda; Pereira, Jose Henrique; Camera, Joao Carlos; Basso, Luiz Augusto; Palma, Mario Sergio; Santos, Diogenes Santiago; Filgueira de Azevedo, Walter

2004-01-01

The parasite Schistosoma mansoni lacks the de novo pathway for purine biosynthesis and depends on salvage pathways for its purine requirements. Schistosomiasis is endemic in 76 countries and territories and amongst the parasitic diseases ranks second after malaria in terms of social and economic impact and public health importance. The PNP is an attractive target for drug design and it has been submitted to extensive structure-based design. The atomic coordinates of the complex of human PNP with inosine were used as template for starting the modeling of PNP from S. mansoni complexed with inosine. Here we describe the model for the complex SmPNP-inosine and correlate the structure with differences in the affinity for inosine presented by human and S. mansoni PNPs

Biolistic transformation of Schistosoma mansoni: Studies with modified reporter-gene constructs containing regulatory regions of protease genes

Czech Academy of Sciences Publication Activity Database

Dvořák, Jan; Beckmann, S.; Lim, K.-C.; Engel, J. C.; Grevelding, C. G.; McKerrow, J. H.; Caffrey, C. R.

2010-01-01

Roč. 170, č. 1 (2010), s. 37-40 ISSN 0166-6851 Institutional research plan: CEZ:AV0Z60220518 Keywords : Schistosoma * Protease * Transgene * Gene promoter * Biolistics * Electroporation Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 2.875, year: 2010

Helminths and Cancers From the Evolutionary Perspective.

Science.gov (United States)

Scholte, Larissa L S; Pascoal-Xavier, Marcelo A; Nahum, Laila A

2018-01-01

Helminths include free-living and parasitic Platyhelminthes and Nematoda which infect millions of people worldwide. Some Platyhelminthes species of blood flukes ( Schistosoma haematobium, Schistosoma japonicum , and Schistosoma mansoni ) and liver flukes ( Clonorchis sinensis and Opisthorchis viverrini ) are known to be involved in human cancers. Other helminths are likely to be carcinogenic. Our main goals are to summarize the current knowledge of human cancers caused by Platyhelminthes, point out some helminth and human biomarkers identified so far, and highlight the potential contributions of phylogenetics and molecular evolution to cancer research. Human cancers caused by helminth infection include cholangiocarcinoma, colorectal hepatocellular carcinoma, squamous cell carcinoma, and urinary bladder cancer. Chronic inflammation is proposed as a common pathway for cancer initiation and development. Furthermore, different bacteria present in gastric, colorectal, and urogenital microbiomes might be responsible for enlarging inflammatory and fibrotic responses in cancers. Studies have suggested that different biomarkers are involved in helminth infection and human cancer development; although, the detailed mechanisms remain under debate. Different helminth proteins have been studied by different approaches. However, their evolutionary relationships remain unsolved. Here, we illustrate the strengths of homology identification and function prediction of uncharacterized proteins from genome sequencing projects based on an evolutionary framework. Together, these approaches may help identifying new biomarkers for disease diagnostics and intervention measures. This work has potential applications in the field of phylomedicine (evolutionary medicine) and may contribute to parasite and cancer research.

Helminths and Cancers From the Evolutionary Perspective

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Larissa L. S. Scholte

2018-04-01

Full Text Available Helminths include free-living and parasitic Platyhelminthes and Nematoda which infect millions of people worldwide. Some Platyhelminthes species of blood flukes (Schistosoma haematobium, Schistosoma japonicum, and Schistosoma mansoni and liver flukes (Clonorchis sinensis and Opisthorchis viverrini are known to be involved in human cancers. Other helminths are likely to be carcinogenic. Our main goals are to summarize the current knowledge of human cancers caused by Platyhelminthes, point out some helminth and human biomarkers identified so far, and highlight the potential contributions of phylogenetics and molecular evolution to cancer research. Human cancers caused by helminth infection include cholangiocarcinoma, colorectal hepatocellular carcinoma, squamous cell carcinoma, and urinary bladder cancer. Chronic inflammation is proposed as a common pathway for cancer initiation and development. Furthermore, different bacteria present in gastric, colorectal, and urogenital microbiomes might be responsible for enlarging inflammatory and fibrotic responses in cancers. Studies have suggested that different biomarkers are involved in helminth infection and human cancer development; although, the detailed mechanisms remain under debate. Different helminth proteins have been studied by different approaches. However, their evolutionary relationships remain unsolved. Here, we illustrate the strengths of homology identification and function prediction of uncharacterized proteins from genome sequencing projects based on an evolutionary framework. Together, these approaches may help identifying new biomarkers for disease diagnostics and intervention measures. This work has potential applications in the field of phylomedicine (evolutionary medicine and may contribute to parasite and cancer research.

Frequency and mitotic heritability of epimutations in Schistosoma mansoni.

Science.gov (United States)

Roquis, David; Rognon, Anne; Chaparro, Cristian; Boissier, Jerome; Arancibia, Nathalie; Cosseau, Celine; Parrinello, Hugues; Grunau, Christoph

2016-04-01

Schistosoma mansoni is a parasitic platyhelminth responsible for intestinal bilharzia. It has a complex life cycle, infecting a freshwater snail of the Biomphalaria genus, and then a mammalian host. Schistosoma mansoni adapts rapidly to new (allopatric) strains of its intermediate host. To study the importance of epimutations in this process, we infected sympatric and allopatric mollusc strains with parasite clones. ChIP-Seq was carried out on four histone modifications (H3K4me3, H3K27me3, H3K27ac and H4K20me1) in parallel with genomewide DNA resequencing (i) on parasite larvae shed by the infected snails and (ii) on adult worms that had developed from the larvae. No change in single nucleotide polymorphisms and no mobilization of transposable elements were observed, but 58-105 copy number variations (CNVs) within the parasite clones in different molluscs were detected. We also observed that the allopatric environment induces three types of chromatin structure changes: (i) host-induced changes on larvae epigenomes in 51 regions of the genome that are independent of the parasites' genetic background, (ii) spontaneous changes (not related to experimental condition or genotype of the parasite) at 64 locations and (iii) 64 chromatin structure differences dependent on the parasite genotype. Up to 45% of the spontaneous, but none of the host-induced chromatin structure changes were transmitted to adults. In our model, the environment induces epigenetic changes at specific loci but only spontaneous epimutations are mitotically heritable and have therefore the potential to contribute to transgenerational inheritance. We also show that CNVs are the only source of genetic variation and occur at the same order of magnitude as epimutations. © 2016 John Wiley & Sons Ltd.

Changes in the expression of Hepatic Cytochrome P450 Isoenzymes 2E1, 2B1/2, 4A, and 2C6 in mice infected with different levels of Schistosoma Mansoni Cercariae

International Nuclear Information System (INIS)

Sheweita, Salah A.

2005-01-01

Most xenobiotic agents are metabolized by cytochrome P450 system. In the present study, Western blotting was used to investigate the effect of different levels of Schistosoma Mansoni infection on the expression of somr cytochrome P450 isozymes (CYP 2E1, 2B1/2, 2C6, 4A) and to enzyme assay their related metabolic functions in mouse liver microsomes. Male mice were infected with 60, 120, 180, 300 and 600 Schistosoma Mansoni cercariae per mouse for 33 days and 60, 120, 180 and 300 cercariae/mouse with no change at the last level of Schistosoma Mansoni infection. Also the expression of CYP 4A was potentially induced at all levels of Schistosoma Mansoni infection. A significant induction of CYP 2B1/2 expression was observed at all levels of Schistosoma Mansoni infection with loss of signal at 180 cercariaea/mouse. In contrast, CYP 2C6 expression was induced at the first two levels and such expression was decreased at the last three levels. In addition, the infection of the mouse with 60, 120 and 180 cercariae/mouse decreased; [1] 7-methoxycoumarin O-demethylase activity by 36, 54 and 58% respectively; [2] 7-ethoxycoumarin O-deethylase activity by 33, 40 and 57% respectively; [3] coumarin hydroxlase activity by 33, 45 and 55% respectively. However, 300 and 600 cercariae/mouse induced: [1] 7-methoxycoumarin O-demethylase activity by 45 and 97% respectively: [2] 7-ethoxycoumarin O-deethylase activity by 26 and 90% respectively; [3] coumarin hydroxylase activity by 100 and 200% respectively. In addition, all levels of Schistosoma Mansoni infection decreased the sleeping time caused by hexobarital. It is concluded that different levels of Schistosoma Mansoni infection change the expression of different CYPisozymes and that these alterations could enhance the carcinogenicity of N-nitrosamines which is mainly dependent on CYP 2E1. The alterations in the expression of CYP 2E1, 4A and 2B1/2 isozymes as a result of Schistosoma Mansoni infection may change the therapeutic actions

An artemisinin derivative of praziquantel as an orally active antischistosomal agent.

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Lanlan Dong

Full Text Available Schistosomiasis is a major health problem in tropical and sub-tropical areas caused by species of trematode belonging to the genus Schistosoma. The treatment and control of this disease has been relying on the use of a single drug praziquantel. However, the drug resistance concern urged the development of new drugs against schistosoma. Here, we report our systematic biological evaluation of DW-3-15, a new lead compound developed based on our conjugation design rationale as an effective anti-schistosomal agent.The antischistosomal activity of DW-3-15 was systematically evaluated in S. japonicum infected mouse model for its stage-sensitivity and dose response. The results revealed that DW-3-15 exhibited 60-85% worm reduction rate against different development stage of worm. Scanning electron microscopy (SEM observation indicated that DW-3-15 may damage to the tegument of male schistosomes.Our results demonstrated that DW-3-15 showed potent anti-schistosomal activities in vivo. The results strongly support our conjugation design strategy of artemisinin analogs and further development of DW-3-15 as a new lead compound as anti-schistosomal agent.

Of monkeys and men: immunomic profiling of sera from humans and non-human primates resistant to schistosomiasis reveals novel potential vaccine candidates

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Mark ePearson

2015-05-01

Full Text Available Schistosoma haematobium affects more than 100 million people throughout Africa and is the causative agent of urogenital schistosomiasis. The parasite is strongly associated with urothelial cancer in infected individuals and as such is designated a group I carcinogen by the International Agency for Research on Cancer. Using a protein microarray containing schistosome proteins, we sought to identify antigens that were the targets of protective IgG1 immune responses in S. haematobium-exposed individuals that acquire drug-induced resistance (DIR to schistosomiasis after praziquantel treatment. Numerous antigens with known vaccine potential were identified, including calpain (Smp80, tetraspanins, glutathione-S-transferases and glucose transporters (SGTP1, as well as previously uncharacterized proteins. Reactive IgG1 responses were not elevated in exposed individuals who did not acquire DIR. To complement our human subjects study, we screened for antigen targets of rhesus macaques rendered resistant to Schistosoma japonicum by experimental infection followed by self-cure, and discovered a number of new and known vaccine targets, including major targets recognised by our human subjects. This study has further validated the immunomics-based approach to schistosomiasis vaccine antigen discovery and identified numerous novel potential vaccine antigens.

Identification, immunolocalization, and characterization analyses of an exopeptidase of papain superfamily, (cathepsin C) from Clonorchis sinensis.

Science.gov (United States)

Liang, Pei; He, Lei; Xu, Yanquan; Chen, Xueqing; Huang, Yan; Ren, Mengyu; Liang, Chi; Li, Xuerong; Xu, Jin; Lu, Gang; Yu, Xinbing

2014-10-01

Cathepsin C is an important exopeptidase of papain superfamily and plays a number of great important roles during the parasitic life cycle. The amino acid sequence of cathepsin C from Clonorchis sinensis (C. sinensis) showed 54, 53, and 49% identities to that of Schistosoma japonicum, Schistosoma mansoni, and Homo sapiens, respectively. Phylogenetic analysis utilizing the sequences of papain superfamily of C. sinensis demonstrated that cathepsin C and cathepsin Bs came from a common ancestry. Cathepsin C of C. sinensis (Cscathepsin C) was identified as an excretory/secretory product by Western blot analysis. The results of transcriptional level and translational level of Cscathepsin C at metacercaria stage were higher than that at adult worms. Immunolocalization analysis indicated that Cscathepsin C was specifically distributed in the suckers (oral sucker and ventral sucker), eggs, vitellarium, intestines, and testis of adult worms. In the metacercaria, it was mainly detected on the cyst wall and excretory bladder. Combining with the results mentioned above, it implies that Cscathepsin C may be an essential proteolytic enzyme for proteins digestion of hosts, nutrition assimilation, and immune invasion of C. sinensis. Furthermore, it may be a potential diagnostic antigen and drug target against C. sinensis infection.

An overview of the metabolic differences between Bradyrhizobium japonicum 110 bacteria and differentiated bacteroids from soybean (Glycine max) root nodules: an in vitro 13C- and 31P-nuclear magnetic resonance spectroscopy study

International Nuclear Information System (INIS)

Vauclare, Pierre; Bligny, Richard; Gout, Elisabeth; Widmer, Francois

2013-01-01

Bradyrhizobium japonicum is a symbiotic nitrogen-fixing soil bacteria that induce root nodules formation in legume soybean (Glycine max.). Using 13 C- and 31 P-nuclear magnetic resonance (NMR) spectroscopy, we have analysed the metabolite profiles of cultivated B. japonicum cells and bacteroids isolated from soybean nodules. Our results revealed some quantitative and qualitative differences between the metabolite profiles of bacteroids and their vegetative state. This includes in bacteroids a huge accumulation of soluble carbohydrates such as trehalose, glutamate, myo-inositol and homo-spermidine as well as Pi, nucleotide pools and intermediates of the primary carbon metabolism. Using this novel approach, these data show that most of the compounds detected in bacteroids reflect the metabolic adaptation of rhizobia to the surrounding microenvironment with its host plant cells. (authors)

Insulin and insulin signaling play a critical role in fat induction of insulin resistance in mouse

Science.gov (United States)

Ning, Jie; Hong, Tao; Yang, Xuefeng; Mei, Shuang; Liu, Zhenqi; Liu, Hui-Yu

2011-01-01

The primary player that induces insulin resistance has not been established. Here, we studied whether or not fat can cause insulin resistance in the presence of insulin deficiency. Our results showed that high-fat diet (HFD) induced insulin resistance in C57BL/6 (B6) mice. The HFD-induced insulin resistance was prevented largely by the streptozotocin (STZ)-induced moderate insulin deficiency. The STZ-induced insulin deficiency prevented the HFD-induced ectopic fat accumulation and oxidative stress in liver and gastrocnemius. The STZ-induced insulin deficiency prevented the HFD- or insulin-induced increase in hepatic expression of long-chain acyl-CoA synthetases (ACSL), which are necessary for fatty acid activation. HFD increased mitochondrial contents of long-chain acyl-CoAs, whereas it decreased mitochondrial ADP/ATP ratio, and these HFD-induced changes were prevented by the STZ-induced insulin deficiency. In cultured hepatocytes, we observed that expressions of ACSL1 and -5 were stimulated by insulin signaling. Results in cultured cells also showed that blunting insulin signaling by the PI3K inhibitor LY-294002 prevented fat accumulation, oxidative stress, and insulin resistance induced by the prolonged exposure to either insulin or oleate plus sera that normally contain insulin. Finally, knockdown of the insulin receptor prevented the oxidative stress and insulin resistance induced by the prolonged exposure to insulin or oleate plus sera. Together, our results show that insulin and insulin signaling are required for fat induction of insulin resistance in mice and cultured mouse hepatocytes. PMID:21586696

Studies on insulin secretion and insulin resistance in non-insulin-dependent diabetes in young Indians

International Nuclear Information System (INIS)

Naidoo, C.

1986-01-01

Patients with Non-insulin-dependent diabetes mellitus (NIDDM) have defects in insulin secretion and insulin action. In the discrete genetic syndrome of NIDDY (non-insulin-dependent diabetes in the young), the situation is less clear and these aspects is the subject of this thesis. This study included Indian pasients with three generation transmission of NIDDM via one parent. The insulin and C-peptide responses to oral and intravenous glucose in patients with NIDDY were studied. The insulin and glucose responses to non-glucose secretogogues glucagon, tolbutamide and arginine, in NIDDY were also investigated. The following aspects with regard to insulin resistance in NIDDY were examined: glucose and free fatty acid response to intravenous insulin administration, insulin binding to circulating erythrocytes and monocytes, 125 I-insulin binding to the solubilized erythrocyte membrane receptor and 125 I-insulin binding to fibroblasts in culture

Studies on insulin secretion and insulin resistance in non-insulin-dependent diabetes in young Indians

Energy Technology Data Exchange (ETDEWEB)

Naidoo, C

1986-01-01

Patients with Non-insulin-dependent diabetes mellitus (NIDDM) have defects in insulin secretion and insulin action. In the discrete genetic syndrome of NIDDY (non-insulin-dependent diabetes in the young), the situation is less clear and these aspects is the subject of this thesis. This study included Indian pasients with three generation transmission of NIDDM via one parent. The insulin and C-peptide responses to oral and intravenous glucose in patients with NIDDY were studied. The insulin and glucose responses to non-glucose secretogogues glucagon, tolbutamide and arginine, in NIDDY were also investigated. The following aspects with regard to insulin resistance in NIDDY were examined: glucose and free fatty acid response to intravenous insulin administration, insulin binding to circulating erythrocytes and monocytes, /sup 125/I-insulin binding to the solubilized erythrocyte membrane receptor and /sup 125/I-insulin binding to fibroblasts in culture.

Synthesis of silver nanoparticles on the basis of low and high molar mass exopolysaccharides of Bradyrhizobium japonicum 36 and its antimicrobial activity against some pathogens.

Science.gov (United States)

Rasulov, Bakhtiyor; Rustamova, Nigora; Yili, Abulimiti; Zhao, Hai-Qing; Aisa, Haji A

2016-07-01

Silver nanoparticles (SNPs) were synthesized on the basis of exopolysaccharides (low and high molar mass) of diazotrophic Bradyrhizobium japonicum 36 strain. The synthesis of SNPs was carried out by direct reduction of silver nitrate with ethanol-insoluble (high molar mass, HMW) and ethanol-soluble (low molar mass, LMW) fractions of exopolysaccharides (EPS), produced by diazotrophic strain B. japonicum 36. SNPs were characterized using UV-vis spectroscopy, transmission electron microscopy (TEM), X-ray diffraction (XRD), and Fourier transform infrared spectroscopy (FTIR). SNPs synthesized on the basis of LMW EPS absorbed radiation in the visible regions of 420 nm, whereas SNPs based on the HMW EPS have a wavelength maximum at 450 nm because of the strong SPR transition. Moreover, the antibacterial and antifungal activities of the SNPs were examined in vitro against Escherichia coli, Staphylococcus aureus, and Candida albicans. SNPs synthesized on the basis of LMW EPS were active than those synthesized on the basis of HMW EPS. Besides, UV-visible spectroscopic evaluation confirmed that SNPs synthesized on the basis of LMW EPS were far more stable than those obtained on the basis of HMW EPS.

Defense response of susceptible and resistant Biomphalaria alexandrina snails against Schistosoma mansoni infection

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Iman F. Abou-El-Naga

2012-09-01

Full Text Available In Egypt, Biomphalaria alexandrina is the intermediate host for Schistosoma mansoni. The fates of Schistosoma miracidia in the snails varies between different species of Biomphalaria. The internal defense system is one of the factors that influence the susceptibility pattern of the snails. The interaction between Biomphalaria snails and S. mansoni needs to be identified for each species, and even between the members of the same species with different degrees of susceptibility. In the present study, the first generation of susceptible and resistant parents of B. alexandrina was examined histologically at the 30th day post exposure. The study includes the characterization of the immune response, as expressed by tissue reactions, of susceptible and resistant B. alexandrina snails against S. mansoni. It was also designed to determine the impact of the resistance increase in parent snails, on the mechanisms of interaction of their offspring against infection. The results showed that the infection rate of the offspring from the susceptible parents was 92%. No susceptible offspring was produced from the resistant parents. When the parents were of equal number of susceptible and resistant snails, they gave an offspring with an infection rate of 20%. Susceptible snails that had susceptible parents showed a higher degree of susceptibility than those that had both susceptible and resistant parents. A common feature of the resistant snails was the absence of any viable parasites. The tissue reactions of the resistant snails having only resistant parents occurred at the site of miracidial penetration. In resistant snails for which susceptible ones were included in their parents, the reactions occurred in the deep tissues. These results characterized the immune response of B. alexandrina snails against Schistosoma infection which was found to occur by two different mechanisms. One type of defense occurs in highly resistant snails, and employs direct

Dicty_cDB: Contig-U03730-1 [Dicty_cDB

Lifescience Database Archive (English)

Full Text Available us... 38 0.002 3 ( DC237378 ) Hodotermopsis sjoestedti cDNA clone: MY0684BHsMg_... 38 0.002 2 ( FD625418 ) s... 40 0.007 2 ( EJ329051 ) 1092963417437 Global-Ocean-Sampling_GS-28-01-01-1... 42 0.007 2 ( DA728805 ) Homo sapie... AGENCOURT_13629201 NIH_MGC_148 Homo sapiens cDNA ... 40 0.007 2 ( EK209959 ) 1095460095251 Global-Ocean-Sampli...8746 ) ox66e02.s1 Soares_NhHMPu_S1 Homo sapiens cDNA clo... 40 0.007 2 ( EJ828039 ) 1093017568475 Global-Ocean-Sampli...136358 ) 1092343604888 Global-Ocean-Sampling_GS-27-01-01-1... 54 0.008 1 ( BU801459 ) SJF2DDD09 SJF Schistosoma japonicum cDNA sim

Degludec insulin: A novel basal insulin

OpenAIRE

Kalra, Sanjay; Unnikrishnan, Ambika Gopalakrishnan; Baruah, Manash; Kalra, Bharti

2011-01-01

This paper reviews a novel insulin analogue, degludec, which has the potential to emerge as an ideal basal insulin. It reviews the limitations of existing basal insulin and analogues, and highlights the need for a newer molecule. The paper discusses the potential advantages of degludec, while reviewing its pharmacologic and clinical studies done so far. The paper assesses the potential role of insulin degludec and degludec plus in clinical diabetes practice.

Insulin secretion and insulin action in non-insulin-dependent diabetes mellitus: which defect is primary?

Science.gov (United States)

Reaven, G M

1984-01-01

Defects in both insulin secretion and insulin action exist in patients with non-insulin-dependent diabetes mellitus (NIDDM). The loss of the acute plasma insulin response to intravenous glucose is seen in patients with relatively mild degrees of fasting hyperglycemia, but patients with severe fasting hyperglycemia also demonstrate absolute hypoinsulinemia in response to an oral glucose challenge. In contrast, day-long circulating insulin levels are within normal limits even in severely hyperglycemic patients with NIDDM. The relationship between NIDDM and insulin action in NIDDM is less complex, and is a characteristic feature of the syndrome. This metabolic defect is independent of obesity, and the severity of the resistance to insulin-stimulated glucose uptake increases with magnitude of hyperglycemia. Control of hyperglycemia with exogenous insulin ameliorates the degree of insulin resistance, and reduction of insulin resistance with weight loss in obese patients with NIDDM leads to an enhanced insulin response. Since neither therapeutic intervention is capable of restoring all metabolic abnormalities to normal, these observations do not tell us which of these two defects is primarily responsible for the development of NIDDM. Similarly, the observation that most patients with impaired glucose tolerance are hyperinsulinemic and insulin resistant does not prove that insulin resistance is the primary defect in NIDDM. In conclusion, reduction in both insulin secretion and action is seen in patients with NIDDM, and the relationship between these two metabolic abnormalities is very complex.(ABSTRACT TRUNCATED AT 250 WORDS)

A multidisciplinary, integrated approach for the elimination of schistosomiasis: a longitudinal study in a historically hyper-endemic region in the lower reaches of the Yangtze River, China from 2005 to 2014.

Science.gov (United States)

Sun, Le-Ping; Wang, Wei; Zuo, Yin-Ping; Hong, Qing-Biao; Du, Guang-Lin; Ma, Yu-Cai; Wang, Jian; Yang, Guo-Jing; Zhu, Dao-Jian; Liang, You-Sheng

2017-03-14

Although great success has been achieved, schistosomiasis remains a major public health concern in China, and the remaining core endemic regions are concentrated along the middle and lower reaches of the Yangtze River. In this longitudinal study, we evaluated the effectiveness of a multidisciplinary, integrated approach for schistosomiasis elimination in a historically hyper-endemic region in the lower reaches of the Yangtze River, China over the 10-year period from 2005 through 2014. A three-step roadmap for schistosomiasis elimination was designed in the study site, and multidisciplinary, integrated interventions were implemented by the health, agriculture, water resources development, land and resources, and forestry sectors from 2005 to 2014, including chemotherapy for infected individuals, health education, management of the source of Schistosoma japonicum infection, and intermediate host snail control. The annual number of schistosomiasis patients, S. japonicum infection in humans, bovines and Oncomelania hupensis snails, and water infectivity were observed to assess the effectiveness of the multidisciplinary, integrated approach for the elimination of schistosomiasis. There was a tendency towards a gradual decline in both the number of schistosomiasis cases and the prevalence of S. japonicum human infection across the study period from 2005 through 2014. No S. japonicum human infection was detected since 2012, and no acute infection was seen since 2006. During the study period, no infection was found in bovines, and a 0.03% overall infection rate was observed in O. hupensis snails. Since 2009, no infected snails were identified, and the area of both snail habitats and infected snail habitats appeared a reduction over the study period. Following the 3-year multidisciplinary, integrated control, infection control was achieved, and transmission control was achieved after 6-year implementation, with all infected snails and water infectivity eliminated; in

A 5-year longitudinal study of schistosomiasis transmission in Shian village, the Anning River Valley, Sichuan Province, the Peoples' Republic of China

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Li Yue-Sheng

2011-03-01

Full Text Available Abstract Background Schistosoma japonicum is a major public health concern in the Peoples' Republic of China (PRC, with over one million people infected and another 50 million living in areas at risk of infection. Based on ecological, environmental, population genetic and molecular factors, schistosomiasis transmission in PRC can be categorised into four discrete ecosystems or transmission modes. It is predicted that the Three Gorges Dam (TGD will impact upon the transmission of schistosomiasis in the PRC, with varying degree across the four transmission modes. We undertook longitudinal surveillance from 2002 to 2006 in sentinel villages both above and below the TGD across five provinces (Hunan, Jiangxi, Hubei, Anhui and Sichuan to determine whether there was any impact of the TGD on schistosomiasis transmission during its construction. Here we present the results from a schistosomiasis-endemic village located above the dam in Sichuan Province. Results Baseline results showed a human S. japonicum prevalence of 42.0% (95% CI: 36.6-47.5. At follow-up, results showed that the incidence of S. japonicum infection in the selected human cohort in Shian decreased by three quarters from 46% in 2003 to 11.3% in 2006. A significant (P S. japonicum infection in bovines declined from 11.8% in the first year to zero in the final year of follow-up. Conclusions The substantial decrease in human (75% and bovine (100% incidence observed in Shian village can probably be attributed to the annual human and bovine PZQ treatment of positives; as seen in drug (PZQ intervention studies in other parts of PRC. If an increase in schistosome transmission had occurred as a result of the TGD, it would be of negligible size compared to the treatment induced decline seen here. It appears therefore that the construction of the TGD had virtually no impact on schistosomiasis transmission in Shian village over the period of study. Furthermore, contrary to previous reports from

Genomes and geography: genomic insights into the evolution and phylogeography of the genus Schistosoma

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Ironside Joe E

2011-07-01

Full Text Available Abstract Blood flukes within the genus Schistosoma still remain a major cause of disease in the tropics and subtropics and the study of their evolution has been an area of major debate and research. With the advent of modern molecular and genomic approaches deeper insights have been attained not only into the divergence and speciation of these worms, but also into the historic movement of these parasites from Asia into Africa, via migration and dispersal of definitive and snail intermediate hosts. This movement was subsequently followed by a radiation of Schistosoma species giving rise to the S. mansoni and S. haematobium groups, as well as the S. indicum group that reinvaded Asia. Each of these major evolutionary events has been marked by distinct changes in genomic structure evident in differences in mitochondrial gene order and nuclear chromosomal architecture between the species associated with Asia and Africa. Data from DNA sequencing, comparative molecular genomics and karyotyping are indicative of major constitutional genomic events which would have become fixed in the ancestral populations of these worms. Here we examine how modern genomic techniques may give a more in depth understanding of the evolution of schistosomes and highlight the complexity of speciation and divergence in this group.

Development of Schistosoma incognitum in mice upon intraperitoneal inoculation with irradiated schistosomula

International Nuclear Information System (INIS)

Bhilegaonkar, N.G.; Sahasrabudhe, V.K.

1987-01-01

As a prelude to the study of the immunizing potential of gamma-irradiated Schistosoma incognitum schistosomula, experiments were conducted to study the effect of different doses of gamma irradiation (1,3,5 and 10 kr) on the development and survival of S. incognitum in mice, and its attendant pathology. The present experiments suggested that 3 and 5 kr irradiation doses can be safely used for irradiating schistosomula for immunization experiments in mice as the worms will not mature and therefore no harm will be caused which is mainly due to the eggs. (author). 7 refs

Trypsin- and Chymotrypsin-Like Serine Proteases in Schistosoma mansoni - 'The Undiscovered Country'

Czech Academy of Sciences Publication Activity Database

Horn, Martin; Fajtová, Pavla; Arreola, L. R.; Ulrychová, Lenka; Bartošová-Sojková, Pavla; Franta, Zdeněk; Protasio, A. V.; Opavský, David; Vondrášek, Jiří; McKerrow, J. H.; Mareš, Michael; Caffrey, C. R.; Dvořák, Jan

2014-01-01

Roč. 8, č. 3 (2014), e2766/1-e2766/13 ISSN 1935-2735 R&D Projects: GA ČR(CZ) GAP302/11/1481; GA MŠk(CZ) ME10011 EU Projects: European Commission(XE) 248642 - SCHISTOSOMA PROTEASE Institutional support: RVO:61388963 ; RVO:68378050 ; RVO:60077344 Keywords : schistosomiasis * blood fluke * serine protease Subject RIV: CE - Biochemistry; EB - Genetics ; Molecular Biology (UMG-J); FN - Epidemiology, Contagious Diseases ; Clinical Immunology (BC-A) Impact factor: 4.446, year: 2014 http://www.plosntds.org/article/info%3Adoi%2F10.1371%2Fjournal.pntd.0002766

Insulin degludec versus insulin glargine in insulin-naive patients with type 2 diabetes

DEFF Research Database (Denmark)

Zinman, Bernard; Philis-Tsimikas, Athena; Cariou, Bertrand

2012-01-01

To compare ultra-long-acting insulin degludec with glargine for efficacy and safety in insulin-naive patients with type 2 diabetes inadequately controlled with oral antidiabetic drugs (OADs).......To compare ultra-long-acting insulin degludec with glargine for efficacy and safety in insulin-naive patients with type 2 diabetes inadequately controlled with oral antidiabetic drugs (OADs)....

Estudios inmunologicos en hamsters (Cricetus auratus infectados con Schistosoma mansoni

Directory of Open Access Journals (Sweden)

Eduardo Monge

1986-08-01

Full Text Available Los resultados de este trabajo muestran que el hamster (Cricetus auratus puede ser utilizado como un modelo experimental para estudios inmunológicos en la infección por Schistosoma mansoni. Los datos obtenidos, relativos a inmunidad concomitante, producción de anticuerpo letal e inmunosupresión se asemejan a los conseguidos en otros modelos experimentales ya establecidos. Estas observaciones indican que el hámster, además de ser un hospedero satisfactorio para el mantenimiento del parásito en el laboratorio, puede ser considerado como un modelo experimental alterno cuyo crecimiento y mantenimiento son relativamente simples y además es un animal de fácil manejo.

The Role of Insulin, Insulin Growth Factor, and Insulin-Degrading Enzyme in Brain Aging and Alzheimer's Disease

OpenAIRE

Messier, Claude; Teutenberg, Kevin

2005-01-01

Most brain insulin comes from the pancreas and is taken up by the brain by what appears to be a receptor-based carrier. Type 2 diabetes animal models associated with insulin resistance show reduced insulin brain uptake and content. Recent data point to changes in the insulin receptor cascade in obesity-related insulin resistance, suggesting that brain insulin receptors also become less sensitive to insulin, which could reduce synaptic plasticity. Insulin transport to the brain is reduced in a...

Analysis of Poly-β-Hydroxybutyrate in Rhizobium japonicum Bacteroids by Ion-Exclusion High-Pressure Liquid Chromatography and UV Detection †

Science.gov (United States)

Karr, Dale B.; Waters, James K.; Emerich, David W.

1983-01-01

Ion-exclusion high-pressure liquid chromatography (HPLC) was used to measure poly-β-hydroxybutyrate (PHB) in Rhizobium japonicum bacteroids. The products in the acid digest of PHB-containing material were fractionated by HPLC on Aminex HPX-87H ion-exclusion resin for organic acid analysis. Crotonic acid formed from PHB during acid digestion was detected by its intense absorbance at 210 nm. The Aminex-HPLC method provides a rapid and simple chromatographic technique for routine analysis of organic acids. Results of PHB analysis by Aminex-HPLC were confirmed by gas chromatography and spectrophotometric analysis. PMID:16346443

A rapid and simple method of detection of Blepharisma japonicum using PCR and immobilisation on FTA paper

Science.gov (United States)

Hide, Geoff; Hughes, Jacqueline M; McNuff, Robert

2003-01-01

Background The rapid expansion in the availability of genome and DNA sequence information has opened up new possibilities for the development of methods for detecting free-living protozoa in environmental samples. The protozoan Blepharisma japonicum was used to investigate a rapid and simple detection system based on polymerase chain reaction amplification (PCR) from organisms immobilised on FTA paper. Results Using primers designed from the α-tubulin genes of Blepharisma, specific and sensitive detection to the equivalent of a single Blepharisma cell could be achieved. Similar detection levels were found using water samples, containing Blepharisma, which were dried onto Whatman FTA paper. Conclusion This system has potential as a sensitive convenient detection system for Blepharisma and could be applied to other protozoan organisms. PMID:14516472

Schistosoma mansoni infection suppresses the growth of Plasmodium yoelii parasites in the liver and reduces gametocyte infectivity to mosquitoes.

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Taeko Moriyasu

2018-01-01

Full Text Available Malaria and schistosomiasis are major parasitic diseases causing morbidity and mortality in the tropics. Epidemiological surveys have revealed coinfection rates of up to 30% among children in Sub-Saharan Africa. To investigate the impact of coinfection of these two parasites on disease epidemiology and pathology, we carried out coinfection studies using Plasmodium yoelii and Schistosoma mansoni in mice. Malaria parasite growth in the liver following sporozoite inoculation is significantly inhibited in mice infected with S. mansoni, so that when low numbers of sporozoites are inoculated, there is a large reduction in the percentage of mice that go on to develop blood stage malaria. Furthermore, gametocyte infectivity is much reduced in mice with S. mansoni infections. These results have profound implications for understanding the interactions between Plasmodium and Schistosoma species, and have implications for the control of malaria in schistosome endemic areas.

Oogram studies in mice infected with Schistosoma mansoni and treated with dexamethasone Oograma em camundongos infectados com Schistosoma mansoni e tratados com dexametasona

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Marco Victor Hermeto

1994-04-01

Full Text Available Mice infected with about 90 cercariae of Schistosoma mansoni (LE strain were treated during five consecutive days with dexamethasone (50 mg/Kg, subcutaneously, starting on the 42th day of infection. Groups of five mice were then daily sacrificed from the first day after onset of treatment until the first day after. The perfusion of the portal system was performed and a piece of the intestine was processed for qualitative and quantitative oograms. This treatment carries to larger numbers of eggs in the tissues of treated mice, when compared with untreated groups. No changes were observed in the kinetics of oviposition, as all stages of viable eggs were observed in the tissues of treated and control mice. These data reinforce the hypothesis of a partial blockade of the egg excretion in immunossupressed mice.Camundongos infectados com cerca de 90 cercárias da cepa LE de Schistosoma mansoni foram tratados durante 5 dias consecutivos com dexametasona (50mg/ Kg, subcutaneamente a partir do 42º dia de infecção. Grupos de cinco camundongos foram sacrificados diariamente após o primeiro dia do início do tratamento até o primeiro dia após o término. A perfusão do sistema porta foi feita e fragmentos do intestino foram processados para a realização de oogramas qualitativos e quantitativos. O tratamento leva a um maior número de ovos nos tecidos dos camundongos tratados, se comparado com os grupos não tratados. Nenhuma mudança foi observada na cinética de oviposição, e ovos viáveis em todos os estádios evolutivos foram observados nos tecidos de camundongos tratados e controles. Estes dados reforçam a hipótese de um bloqueio parcial na saída de ovos dos tecidos do intestino para o lúmem intestinal em camundongos imunossuprimidos.

Defense response of susceptible and resistant Biomphalaria alexandrina snails against Schistosoma mansoni infection

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Iman F. Abou-El-Naga

2012-09-01

Full Text Available In Egypt, Biomphalaria alexandrina is the intermediate host for Schistosoma mansoni. The fates of Schistosoma miracidia in the snails varies between different species of Biomphalaria. The internal defense system is one of the factors that influence the susceptibility pattern of the snails. The interaction between Biomphalaria snails and S. mansoni needs to be identified for each species, and even between the members of the same species with different degrees of susceptibility. In the present study, the first generation of susceptible and resistant parents of B. alexandrina was examined histologically at the 30th day post exposure. The study includes the characterization of the immune response, as expressed by tissue reactions, of susceptible and resistant B. alexandrina snails against S. mansoni. It was also designed to determine the impact of the resistance increase in parent snails, on the mechanisms of interaction of their offspring against infection. The results showed that the infection rate of the offspring from the susceptible parents was 92%. No susceptible offspring was produced from the resistant parents. When the parents were of equal number of susceptible and resistant snails, they gave an offspring with an infection rate of 20%. Susceptible snails that had susceptible parents showed a higher degree of susceptibility than those that had both susceptible and resistant parents. A common feature of the resistant snails was the absence of any viable parasites. The tissue reactions of the resistant snails having only resistant parents occurred at the site of miracidial penetration. In resistant snails for which susceptible ones were included in their parents, the reactions occurred in the deep tissues. These results characterized the immune response of B. alexandrina snails against Schistosoma infection which was found to occur by two different mechanisms. One type of defense occurs in highly resistant snails, and employs direct

Epidemiological studies of Schistosoma mattheei infections in cattle in the highveld and lowveld communal grazing areas of Zimbabwe

DEFF Research Database (Denmark)

Pfukenyi, D.M.; Mukaratirwa, S.; Willingham, Arve Lee

2006-01-01

there were peaks between March / May and September / November. The mean num ber of snails collected was positively correlated with the water plants Nymphaea caerulea and Typha species. Overall, 2.5 % of B. globosus were shedding Schistosoma cercariae. In the highveld, 2.8 % of B. globosus were infected...

DNA barcoding of schistosome cercariae reveals a novel sub-lineage within Schistosoma rodhaini from Ngamba Island Chimpanzee Sanctuary, Lake Victoria.

Science.gov (United States)

Standley, C J; Stothard, J R

2012-10-01

While Schistosoma rodhaini is typically considered a parasite of small mammals and is very scantly distributed in the Lake Victoria basin, it is known to hybridize with the more widespread Schistosoma mansoni, the causative agent of intestinal schistosomiasis. As part of broader parasitological and malacological surveys for S. mansoni across Lake Victoria, schistosome cercariae were harvested from a field-caught Biomphalaria choanomphala taken on Ngamba Island Chimpanzee Sanctuary, Uganda. Upon DNA barcoding, these cercariae were found to be a mixture of both S. rodhaini and S. mansoni, with further phylogenetic analysis revealing a hitherto unknown sub-lineage within S. rodhaini. Despite repeated sampling for eggs and miracidia from both chimpanzees and staff on Ngamba Island Sanctuary, detection of S. rodhaini within local definitive hosts awaits additional efforts, which should be mindful of a potential host role of spotted-necked otters.

Anemia and growth retardation associated with Schistosoma haematobium infection in Mali

DEFF Research Database (Denmark)

Stecher, Chalotte W; Sacko, Moussa; Madsen, Henry

2017-01-01

BackgroundThe aim of this cross-sectional study was to investigate a possible association of Schistosoma haematobium with child growth development and describe a plausible schistosomiasis-related anemia in children and adults in a highly schistosomiasis endemic area of Mali. MethodsUrine, feces...... associated with anemia; i.e., odds of having anemia in the highest and the next highest category was 3.25 (95% CL 1.61–6.55; p... factors. Anemia was most pronounced in the 2–5 year olds males (55.5%, n=98). P. falciparum infection was not significantly associated with anemia. Stunting (body mass index [BMI] for age z-score

Schistosoma haematobium infection and asymptomatic bacteriuria in young South African females

DEFF Research Database (Denmark)

Kildemoes, Anna M. O.; Kjetland, Eyrun Floerecke; Zulu, Siphosenkosi Gift

2015-01-01

Schistosoma haematobium eggs can induce lesions in the urinary and genital tract epithelia, as eggs pass through or get trapped in the tissue. Local inflammatory reactions induced by S. haematobium eggs might affect the ability of bacteria to establish mucosal super-infection foci. S. haematobium...... school students from a schistosomiasis endemic area in KwaZulu-Natal, South Africa. Furthermore, it was demonstrated that asymptomatic bacteriuria is not a bias for use of micro-haematuria as a proxy diagnostic measure for S. haematobium infection in this population....

The potential for using red claw crayfish and hybrid African catfish as biological control agents for Schistosoma host snails

NARCIS (Netherlands)

Monde, C.; Syampungani, S.; Rico, A.; Brink, van den P.J.

2017-01-01

The potential of red claw crayfish and hybrid African catfish (Clarias gariepinus and Clarias ngamensis) as predators for Schistosoma host snails was evaluated in 2014 by monitoring the consumption of snails by crayfish and catfish in experimental tanks over time under laboratory conditions. After

Insulin receptors

International Nuclear Information System (INIS)

Kahn, C.R.; Harrison, L.C.

1988-01-01

This book contains the proceedings on insulin receptors. Part A: Methods for the study of structure and function. Topics covered include: Method for purification and labeling of insulin receptors, the insulin receptor kinase, and insulin receptors on special tissues

Clinical efficacy and tolerability of praziquantel for intestinal and urinary schistosomiasis-a meta-analysis of comparative and non-comparative clinical trials.

Directory of Open Access Journals (Sweden)

Julien Zwang

Full Text Available Extensive use of praziquantel for treatment and control of schistosomiasis requires a comprehensive understanding of efficacy and safety of various doses for different Schistosoma species.A systematic review and meta-analysis of comparative and non-comparative trials of praziquantel at any dose for any Schistosoma species assessed within two months post-treatment. Of 273 studies identified, 55 were eligible (19,499 subjects treated with praziquantel, control treatment or placebo. Most studied were in school-aged children (64%, S. mansoni (58%, and the 40 mg/kg dose (56%; 68% of subjects were in Africa. Efficacy was assessed as cure rate (CR, n=17,017 and egg reduction rate (ERR, n=13,007; safety as adverse events (AE incidence. The WHO-recommended dose of praziquantel 40 mg/kg achieved CRs of 94.7% (95%CI 92.2-98.0 for S. japonicum, 77.1% (68.4-85.1 for S. haematobium, 76.7% (95%CI 71.9-81.2 for S. mansoni, and 63.5% (95%CI 48.2-77.0 for mixed S. haematobium/S. mansoni infections. Using a random-effect meta-analysis regression model, a dose-effect for CR was found up to 40 mg/kg for S. mansoni and 30 mg/kg for S. haematobium. The mean ERR was 95% for S. japonicum, 94.1% for S. haematobium, and 86.3% for S. mansoni. No significant relationship between dose and ERR was detected. Tolerability was assessed in 40 studies (12,435 subjects. On average, 56.9% (95%CI 47.4-67.9 of the subjects receiving praziquantel 40 mg/kg experienced an AE. The incidence of AEs ranged from 2.3% for urticaria to 31.1% for abdominal pain.The large number of subjects allows generalizable conclusions despite the inherent limitations of aggregated-data meta-analyses. The choice of praziquantel dose of 40 mg/kg is justified as a reasonable compromise for all species and ages, although in a proportion of sites efficacy may be lower than expected and age effects could not be fully explored.

New insights into the genetic diversity of Schistosoma mansoni and S. haematobiumin Yemen.

Science.gov (United States)

Sady, Hany; Al-Mekhlafi, Hesham M; Webster, Bonnie L; Ngui, Romano; Atroosh, Wahib M; Al-Delaimy, Ahmed K; Nasr, Nabil A; Chua, Kek Heng; Lim, Yvonne A L; Surin, Johari

2015-10-20

Human schistosomiasis is a neglected tropical disease of great importance that remains highly prevalent in Yemen, especially amongst rural communities. In order to investigate the genetic diversity of human Schistosoma species, a DNA barcoding study was conducted on S. mansoni and S. haematobium in Yemen. A cross-sectional study was conducted to collect urine and faecal samples from 400 children from five provinces in Yemen. The samples were examined for the presence of Schistosoma eggs. A partial fragment of the schistosome cox1 mitochondrial gene was analysed from each individual sample to evaluate the genetic diversity of the S. mansoni and S. haematobium infections. The data was also analysed together with previous published cox1 data for S. mansoni and S. haematobium from Africa and the Indian Ocean Islands. Overall, 31.8 % of participants were found to be excreting schistosome eggs in either the urine or faeces (8.0 % S. mansoni and 22.5 % S. haematobium). Nineteen unique haplotypes of S. mansoni were detected and split into four lineages. Furthermore, nine unique haplotypes of S. haematobium were identified that could be split into two distinct groups. This study provides novel and interesting insights into the population diversity and structure of S. mansoni and S. haematobium in Yemen. The data adds to our understanding of the evolutionary history and phylogeography of these devastating parasites whilst the genetic information could support the control and monitoring of urogenital and intestinal schistosomiasis in these endemic areas.

Comparative Evaluation of Anthelmintic Activity of Edible and Ornamental Pomegranate Ethanolic Extracts against Schistosoma mansoni

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Doaa A. Yones

2016-01-01

Full Text Available Due to the development of praziquantel (PZQ schistosomes resistant strains, the discovery of new antischistosomal agents is of high priority in research. This work reported the in vitro and in vivo effects of the edible and ornamental pomegranate extracts against Schistosoma mansoni. Leaves and stem bark ethanolic extracts of both dried pomegranates were prepared at 100, 300, and 500 μg/mL for in vitro and 600 and 800 mg/kg for in vivo. Adult worms Schistosoma mansoni in RPMI-1640 medium for in vitro and S. mansoni infected mice for in vivo tests were obtained from Theodor Bilharz Research Institute, Cairo, Egypt. In vitro activity was manifested by significant coupled worms separation, reduction of motor activity, lethality, and ultrastructural tegumental alterations in adult worms. In vivo activity was manifested revealed by significant reduction of hepatic granulomas number and diameter, decreased number of bilharzial eggs in liver tissues, lowered liver inflammatory infiltration, decreased hepatic fibrosis, and inducible nitric oxide synthase (iNOS expression. Ethanolic stem bark extract of edible pomegranate exhibited highest antischistosomal activities both in vitro and in vivo. Therefore, pomegranate showed a good potential to be used as a promising new candidate for the development of new schistosomicidal agents.

Improved insulin sensitivity after exercise: focus on insulin signaling

DEFF Research Database (Denmark)

Frøsig, Christian; Richter, Erik

2009-01-01

After a single bout of exercise, the ability of insulin to stimulate glucose uptake is markedly improved locally in the previously active muscles. This makes exercise a potent stimulus counteracting insulin resistance characterizing type 2 diabetes (T2D). It is believed that at least part...... of the mechanism relates to an improved ability of insulin to stimulate translocation of glucose transporters (GLUT4) to the muscle membrane after exercise. How this is accomplished is still unclear; however, an obvious possibility is that exercise interacts with the insulin signaling pathway to GLUT4...... translocation allowing for a more potent insulin response. Parallel to unraveling of the insulin signaling cascade, this has been investigated within the past 25 years. Reviewing existing studies clearly indicates that improved insulin action can occur independent of interactions with proximal insulin signaling...

Structural Basis for Inhibition of Cathepsin B Drug Target from the Human Blood Fluke, Schistosoma mansoni

Czech Academy of Sciences Publication Activity Database

Jílková, Adéla; Řezáčová, Pavlína; Lepšík, Martin; Horn, Martin; Váchová, Jana; Fanfrlík, Jindřich; Brynda, Jiří; McKerrow, J. H.; Caffrey, C. R.; Mareš, Michael

2011-01-01

Roč. 286, č. 41 (2011), s. 35770-35881 ISSN 0021-9258 R&D Projects: GA ČR GA203/09/1585; GA ČR GAP208/11/0295; GA MŠk OC09007 Institutional research plan: CEZ:AV0Z40550506; CEZ:AV0Z50520514 Keywords : cathepsin B * schistosoma * crystal structure Subject RIV: CC - Organic Chemistry Impact factor: 4.773, year: 2011

Angiogenesis in Schistosoma haematobium-associated urinary bladder cancer.

Science.gov (United States)

Dematei, Anderson; Fernandes, Rúben; Soares, Raquel; Alves, Helena; Richter, Joachim; Botelho, Monica C

2017-12-01

Schistosoma haematobium, a parasitic flatworm that infects more than 100 million people, mostly in the developing world, is the causative agent of urogenital schistosomiasis, and is associated with a high incidence of squamous cell carcinoma (SCC) of the bladder. During infection, eggs are deposited in the bladder causing an intense inflammatory reaction. Angiogenesis is defined as the formation of new blood vessels from preexisting ones and is recognized as a key event in cell proliferation and carcinogenesis and spread of malignant lesions. A growing amount of evidence points to angiogenesis playing a key role in schistosomiasis-associated bladder cancer. Thus, identifying biomarkers of this process plays an important role in the study of cancer. Here, we review recent findings on the role of angiogenesis in bladder cancer and the growth factors that induce and assist in their development, particularly SCC of the bladder associated to urogenital schistosomiasis. © 2017 APMIS. Published by John Wiley & Sons Ltd.

Prolyl Oligopeptidase from the Blood Fluke Schistosoma mansoni: From Functional Analysis to Anti-schistosomal Inhibitors

Czech Academy of Sciences Publication Activity Database

Fajtová, Pavla; Štefanic, S.; Hradilek, Martin; Dvořák, Jan; Vondrášek, Jiří; Jílková, Adéla; Ulrychová, Lenka; McKerrow, J. H.; Caffrey, C. R.; Mareš, Michael; Horn, Martin

2015-01-01

Roč. 9, č. 6 (2015), e0003827/1-e0003827/24 ISSN 1935-2735 R&D Projects: GA ČR(CZ) GAP302/11/1481; GA MŠk LO1302 Institutional support: RVO:61388963 ; RVO:68378050 Keywords : Schistosoma mansoni * schistosomiasis * prolyl oligopeptidase * blood fluke Subject RIV: CE - Biochemistry; EB - Genetics ; Molecular Biology (UMG-J) Impact factor: 3.948, year: 2015 http://journals.plos.org/plosntds/article?id=10.1371/journal.pntd.0003827

Innate scavenger receptor-A regulates adaptive T helper cell responses to pathogen infection

Science.gov (United States)

Xu, Zhipeng; Xu, Lei; Li, Wei; Jin, Xin; Song, Xian; Chen, Xiaojun; Zhu, Jifeng; Zhou, Sha; Li, Yong; Zhang, Weiwei; Dong, Xiaoxiao; Yang, Xiaowei; Liu, Feng; Bai, Hui; Chen, Qi; Su, Chuan

2017-01-01

The pattern recognition receptor (PRR) scavenger receptor class A (SR-A) has an important function in the pathogenesis of non-infectious diseases and in innate immune responses to pathogen infections. However, little is known about the role of SR-A in the host adaptive immune responses to pathogen infection. Here we show with mouse models of helminth Schistosoma japonicum infection and heat-inactivated Mycobacterium tuberculosis stimulation that SR-A is regulated by pathogens and suppresses IRF5 nuclear translocation by direct interaction. Reduced abundance of nuclear IRF5 shifts macrophage polarization from M1 towards M2, which subsequently switches T-helper responses from type 1 to type 2. Our study identifies a role for SR-A as an innate PRR in regulating adaptive immune responses. PMID:28695899

The use of ionizing radiation in the control of Oncomelania quadrasi snails

International Nuclear Information System (INIS)

Cruz, B. de la; Asis, A.V.; Pagulayan, P.; Payongayong, A.; Pineda, R.

1983-01-01

Schistosomiasis is still an endemic disease affecting mostly farmers. One way of checking the spread of the disease is to eradicate the intermediate host of parasite. Previous reports indicate that application of nuclear techniques could be a viable tool in the control of parasites of medical importance. To determine whether ionizing radiation could be a useful tool in the control of Oncomelania quadrasi, which is the vector host of Schistosoma japonicum. Attempts have been made to determine whether genetic effects on irradiated male snails can be transmitted to their progenies. These deleterious effects could be either short life span or defective reproductive capacity of the progenies. Attemps were also made to determine whether introduction of irradiated male snails in a given population could reduce the snail density. (author)

Massa tumoral secundária a infecção por Schistosoma mansoni simulando neoplasia de pulmão: relato de caso Tumoral pulmonary mass secondary to Schistosoma mansoni infection resembling neoplasia: case report

Directory of Open Access Journals (Sweden)

Cláudio Dornas de Oliveira

2009-12-01

Full Text Available Indivíduos infectados com Schistosoma mansoni na fase crônica da doença podem apresentar comprometimento pulmonar com sintomatologia e alterações radiológicas variáveis. Os pulmões podem ser acometidos pela migração anômala de ovos do sistema porta para o sistema arterial pulmonar (através de anastomoses porto-sistêmicas e menos comumente por migrações ectópicas de vermes adultos. Há casos com extenso comprometimento parenquimatoso e outros com predomínio de arterites, com hipertensão pulmonar e cor pulmonale. Paciente jovem, residente em área endêmica de esquistossomose, com massa pulmonar sugestiva de neoplasia foi submetida a toracotomia exploradora sem possibilidade de ressecção da massa. Exame histopatológico mostrou vários granulomas esquistossomóticos e hiperplasia do tecido conjuntivo, sem sinais de neoplasia. Evoluiu com insuficiência respiratória e instabilidade hemodinâmica no pós-operatório imediato. Recebeu tratamento específico (praziquantel associado a prednisona. A paciente cursou com infecção pulmonar e choque séptico. Recebeu antibioticoterapia, aminas vasoativas, suporte ventilatório e tratamento hemodiálitico sem melhora. Evoluiu para óbito 28 dias após cirurgia.Patients with chronic Schistosoma mansoni infection may feature a range of pulmonary symptoms and radiological findings. Eggs, and rarely adult worms, may passively enter the pulmonary circulation, usually via the portal system, where they may cause pulmonary inflammation, fibrosis, hypertension and cor pulmonale. A 25-year-old patient who lived in a schistosomiasis endemic area with a pulmonary mass suggestive of malignancy underwent exploratory thoracotomy. The mass was adherent, with no resection possibility. The lung-biopsy specimen evaluation showed several granulomas with Schistosoma mansoni eggs and hyperplasic connective tissue with no sign of malignancy. The patient had respiratory failure and hypotension immediately

Human Schistosoma haematobium antifecundity immunity is dependent on transmission intensity and associated with immunoglobulin G1 to worm-derived antigens

DEFF Research Database (Denmark)

Wilson, Shona; Jones, Frances M.; van Dam, Govert J.

2014-01-01

BACKGROUND: Immunity that reduces worm fecundity and, in turn, reduces morbidity is proposed for Schistosoma haematobium, a parasite of major public health importance. Mathematical models of epidemiological trends suggest that antifecundity immunity is dependent on antibody responses to adult......-worm-derived antigen. METHODS: For a Malian cohort (age, 5-29 years) residing in high-transmission fishing villages or a moderate-transmission village, worm fecundity was assessed using the ratio of urinary egg excretion to levels of circulating anodic antigen, a Schistosoma-specific antigen that is steadily secreted......, host age and transmission were negatively associated with worm fecundity. A significant interaction term between host age and transmission indicates that antifecundity immunity develops earlier in high-transmission areas. SWA immunoglobulin G1 (IgG1) levels explained the effect of transmission...

PCR-based detection of Schistosoma bovis in cattle in Maiduguri Metropolis and Jere Local Government Areas in Borno State, Nigeria

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Idris Umar Hambali

2016-06-01

Results: The overall prevalence of Schistosoma infection was 2% (n=200. Jere LGA had 3% (n=100 while MMC had 1% (n=100. There was no statistical significant association in prevalence rate in the two LGAs studied (P=0.621 (P>0.05. At the ward levels, Custom Area in Jere LGA had 15%, Jiddari ward in MMC had 5%, and the remaining ward levels had no cases. Of the 103 female and 97 male cattle screened, the prevalence in female was 1(0.97% and 3(3.09% in the male. Of the 177 serum samples from above 1year (adult examined, 4 (2.26% were positive and none in the young. There was no statistical significant association in prevalence rate among ward levels, sex groups and age groups in the study areas (P=0.621 (P>0.05, (P=0.356 (P>0.05 and (P=1.000 (P>0.05 respectively. Of the eight (8 breeds screened, Kuri had 2.7%, Sokoto Gudali (1.82%, Abore (2%, Red Bororo (2.63%, White Fulani, Porland, Mbala and Wafara recorded no cases. The difference in prevalence rates among the breeds based on the trend of occurrence of Schistosoma infection were not significantly associated statistically (P=1.000 (P>0.05. Conclusion: There is a prevalence of Schistosoma infection in cattle in the two LGAs of Borno state. It is recommended that a system be established to maintain preventive and control programs. [J Adv Vet Anim Res 2016; 3(2.000: 92-98

Long-term frozen storage of urine samples: a trouble to get PCR results in Schistosoma spp. DNA detection?

Science.gov (United States)

Fernández-Soto, Pedro; Velasco Tirado, Virginia; Carranza Rodríguez, Cristina; Pérez-Arellano, José Luis; Muro, Antonio

2013-01-01

Human schistosomiasis remains a serious worldwide public health problem. At present, a sensitive and specific assay for routine diagnosis of schistosome infection is not yet available. The potential for detecting schistosome-derived DNA by PCR-based methods in human clinical samples is currently being investigated as a diagnostic tool with potential application in routine schistosomiasis diagnosis. Collection of diagnostic samples such as stool or blood is usually difficult in some populations. However, urine is a biological sample that can be collected in a non-invasive method, easy to get from people of all ages and easy in management, but as a sample for PCR diagnosis is still not widely used. This could be due to the high variability in the reported efficiency of detection as a result of the high variation in urine samples' storage or conditions for handling and DNA preservation and extraction methods. We evaluate different commercial DNA extraction methods from a series of long-term frozen storage human urine samples from patients with parasitological confirmed schistosomiasis in order to assess the PCR effectiveness for Schistosoma spp. detection. Patients urine samples were frozen for 18 months up to 7 years until use. Results were compared with those obtained in PCR assays using fresh healthy human urine artificially contaminated with Schistosoma mansoni DNA and urine samples from mice experimentally infected with S. mansoni cercariae stored frozen for at least 12 months before use. PCR results in fresh human artificial urine samples using different DNA based extraction methods were much more effective than those obtained when long-term frozen human urine samples were used as the source of DNA template. Long-term frozen human urine samples are probably not a good source for DNA extraction for use as a template in PCR detection of Schistosoma spp., regardless of the DNA method of extraction used.

Micro-geographical heterogeneity in Schistosoma mansoni and S. haematobium infection and morbidity in a co-endemic community in northern Senegal.

NARCIS (Netherlands)

Meurs, L.; Mbow, M.; Boon, N.; Van den Broeck, F.; Vereecken, K.; Dieye, T.N.; Abatih, E.; Huyse, T.; Mboup, S.; Polman, K.

2013-01-01

Background:Schistosoma mansoni and S. haematobium are co-endemic in many areas in Africa. Yet, little is known about the micro-geographical distribution of these two infections or associated disease within such foci. Such knowledge could give important insights into the drivers of infection and

The effect of treatment on the age-antibody relationship in children infected with Schistosoma mansoni and Schistosoma haematobium

Directory of Open Access Journals (Sweden)

Mutapi Francisca

2002-01-01

Full Text Available The effect of praziquantel treatment on the age-antibody relationship was studied in 174 children aged between 6 and 17 years from a schistosome endemic area in Zimbabwe. The children were co-infected with Schistosoma mansoni and S. haematobium with infection prevalences of 74% and 53% respectively. Antibody levels for the isotypes IgA, IgE, IgM, IgG1, IgG2, IgG3 and IgG4, directed against soluble egg antigen were measured using an indirect ELISA assay. Treatment resulted in a significant increase in levels of IgG2 and IgG3 while levels of IgA decreased significantly. In untreated children there were significant decreases in levels of IgG4. Treatment also resulted in significant alteration in the age-antibody profiles for the isotypes IgE, IgM, IgG1 and IgG2 in treated children but not in untreated children. The results are discussed in the context of factors believed to give rise to the age-antibody relationship; i.e. age-related exposure patterns, age-related development of acquired immunity, age-related hormonal changes and age-related changes in innate susceptibility to infection.

Anti-inflammatory effects and corresponding mechanisms of cirsimaritin extracted from Cirsium japonicum var. maackii Maxim.

Science.gov (United States)

Shin, Myoung-Sook; Park, Jun Yeon; Lee, Jaemin; Yoo, Hye Hyun; Hahm, Dae-Hyun; Lee, Sang Cheon; Lee, Sanghyun; Hwang, Gwi Seo; Jung, Kiwon; Kang, Ki Sung

2017-07-15

In this study, we investigated the anti-inflammatory effects and mechanisms of cirsimaritin isolated from an ethanol extract of the aerial parts of Cirsium japonicum var. maackii Maxim. using RAW264.7 cells. The extract and its flavonoid cirsimaritin inhibited nitric oxide (NO) production and inducible nitric oxide synthase expression in RAW264.7 cells. Cirsimaritin inhibited interleukin-6, tumor necrosis factor-α, and NO production in a concentration-dependent manner in lipopolysaccharide (LPS)-stimulated RAW264.7 cells. From a western blot study, pretreatment with cirsimaritin inhibited phosphorylation/degradation of IκBα and phosphorylation of Akt in LPS-stimulated RAW264.7 cells. Moreover, cirsimaritin suppressed activation of LPS-induced transcription factors, such as c-fos and signal transducer and activator of transcription 3 (STAT3), in RAW264.7 cells. Collectively, these results show that cirsimaritin possesses anti-inflammatory activity, which is regulated by inhibition of c-fos and STAT3 phosphorylation in RAW264.7 cells. Copyright © 2017 Elsevier Ltd. All rights reserved.

[Comparison between basal insulin glargine and NPH insulin in patients with diabetes type 1 on conventional intensive insulin therapy].

Science.gov (United States)

Pesić, Milica; Zivić, Sasa; Radenković, Sasa; Velojić, Milena; Dimić, Dragan; Antić, Slobodan

2007-04-01

Insulin glargine is a long-acting insulin analog that mimics normal basal insulin secretion without pronounced peaks. The aim of this study was to compare insulin glargine with isophane insulin (NPH insulin) for basal insulin supply in patients with type 1 diabetes. A total of 48 type 1 diabetics on long term conventional intensive insulin therapy (IT) were randomized to three different regimens of basal insulin substitution: 1. continuation of NPH insulin once daily at bedtime with more intensive selfmonitoring (n = 15); 2. NPH insulin twice daily (n = 15); 3. insulin glargine once daily (n = 18). Meal time insulin aspart was continued in all groups. Fasting blood glucose (FBG) was lower in the glargine group (7.30+/-0.98 mmol/1) than in the twice daily NPH group (7.47+/-1.06 mmol/1), but without significant difference. FBG was significantly higher in the once daily NPH group (8.44+/-0.85 mmol/l; p < 0.05). HbAlc after 3 months did not change in the once daily NPH group, but decreased in the glargine group (from 7.72+/-0.86% to 6.87+/-0.50%), as well as in the twice daily NPH group (from 7.80+/-0.83% to 7.01+/-0.63%). Total daily insulin doses were similar in all groups but only in the glargine group there was an increase of basal and decrease of meal related insulin doses. The frequency of mild hypoglycemia was significantly lower in the glargine group (6.56+/-2.09) than in both NPH groups (9.0+/-1.65 in twice daily NPH group and 8.13+/-1.30 in other NPH group) (episodes/patients-month, p < 0.05). Basal insulin supplementation in type 1 diabetes mellitus with either twice daily NPH insulin or glargine can result in similar glycemic control when combined with meal time insulin aspart. However, with glargine regimen FBG, HbAlc and frequency of hypoglycemic event are lower. These facts contribute to better patients satisfaction with insulin glargine versus NPH insulin in IIT in type 1 diabetics.

Subcutaneous insulin absorption explained by insulin's physicochemical properties. Evidence from absorption studies of soluble human insulin and insulin analogues in humans.

Science.gov (United States)

Kang, S; Brange, J; Burch, A; Vølund, A; Owens, D R

1991-11-01

To study the influence of molecular aggregation on rates of subcutaneous insulin absorption and to attempt to elucidate the mechanism of absorption of conventional soluble human insulin in humans. Seven healthy male volunteers aged 22-43 yr and not receiving any drugs comprised the study. This study consisted of a single-blind randomized comparison of equimolar dosages of 125I-labeled forms of soluble hexameric 2 Zn2+ human insulin and human insulin analogues with differing association states at pharmaceutical concentrations (AspB10, dimeric; AspB28, mixture of monomers and dimers; AspB9, GluB27, monomeric). After an overnight fast and a basal period of 1 h, 0.6 nmol/kg of either 125I-labeled human soluble insulin (Actrapid HM U-100) or 125I-labeled analogue was injected subcutaneously on 4 separate days 1 wk apart. Absorption was assessed by measurement of residual radioactivity at the injection site by external gamma-counting. The mean +/- SE initial fractional disappearance rates for the four preparations were 20.7 +/- 1.9 (hexameric soluble human insulin), 44.4 +/- 2.5 (dimeric analogue AspB10), 50.6 +/- 3.9 (analogue AspB28), and 67.4 +/- 7.4%/h (monomeric analogue AspB9, GluB27). Absorption of the dimeric analogue was significantly faster than that of hexameric human insulin (P less than 0.001); absorption of monomeric insulin analogue AspB9, GluB27 was significantly faster than that of dimeric analogue AspB10 (P less than 0.01). There was an inverse linear correlation between association state and the initial fractional disappearance rates (r = -0.98, P less than 0.02). Analysis of the disappearance data on a log linear scale showed that only the monomeric analogue had a monoexponential course throughout. Two phases in the rates of absorption were identified for the dimer and three for hexameric human insulin. The fractional disappearance rates (%/h) calculated by log linear regression analysis were monomer 73.3 +/- 6.8; dimer 44.4 +/- 2.5 from 0 to 2 h and

Insulin receptor internalization defect in an insulin-resistant mouse melanoma cell line

International Nuclear Information System (INIS)

Androlewicz, M.J.; Straus, D.S.; Brandenburg, D.F.

1989-01-01

Previous studies from this laboratory demonstrated that the PG19 mouse melanoma cell line does not exhibit a biological response to insulin, whereas melanoma x mouse embryo fibroblast hybrids do respond to insulin. To investigate the molecular basis of the insulin resistance of the PG19 melanoma cells, insulin receptors from the insulin-resistant melanoma cells and insulin-sensitive fibroblast x melanoma hybrid cells were analyzed by the technique of photoaffinity labeling using the photoprobe 125 I-NAPA-DP-insulin. Photolabeled insulin receptors from the two cell types have identical molecular weights as determined by SDS gel electrophoresis under reducing and nonreducing conditions, indicating that the receptors on the two cell lines are structurally similar. Insulin receptor internalization studies revealed that the hybrid cells internalize receptors to a high degree at 37 degree C, whereas the melanoma cells internalize receptors to a very low degree or not at all. The correlation between ability to internalize insulin receptors and sensitivity to insulin action in this system suggests that uptake of the insulin-receptor complex may be required for insulin action in these cells. Insulin receptors from the two cell lines autophosphorylate in a similar insulin-dependent manner both in vitro and in intact cells, indicating that insulin receptors on the melanoma and hybrid cells have functional tyrosine protein kinase activity. Therefore, the block in insulin action in the PG19 melanoma cells appears to reside at a step beyond insulin-stimulated receptor autophosphorylation

Reduced Circulating Insulin Enhances Insulin Sensitivity in Old Mice and Extends Lifespan

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Nicole M. Templeman

2017-07-01

Full Text Available The causal relationships between insulin levels, insulin resistance, and longevity are not fully elucidated. Genetic downregulation of insulin/insulin-like growth factor 1 (Igf1 signaling components can extend invertebrate and mammalian lifespan, but insulin resistance, a natural form of decreased insulin signaling, is associated with greater risk of age-related disease in mammals. We compared Ins2+/− mice to Ins2+/+ littermate controls, on a genetically stable Ins1 null background. Proteomic and transcriptomic analyses of livers from 25-week-old mice suggested potential for healthier aging and altered insulin sensitivity in Ins2+/− mice. Halving Ins2 lowered circulating insulin by 25%–34% in aged female mice, without altering Igf1 or circulating Igf1. Remarkably, decreased insulin led to lower fasting glucose and improved insulin sensitivity in aged mice. Moreover, lowered insulin caused significant lifespan extension, observed across two diverse diets. Our study indicates that elevated insulin contributes to age-dependent insulin resistance and that limiting basal insulin levels can extend lifespan.

Reduced Circulating Insulin Enhances Insulin Sensitivity in Old Mice and Extends Lifespan.

Science.gov (United States)

Templeman, Nicole M; Flibotte, Stephane; Chik, Jenny H L; Sinha, Sunita; Lim, Gareth E; Foster, Leonard J; Nislow, Corey; Johnson, James D

2017-07-11

The causal relationships between insulin levels, insulin resistance, and longevity are not fully elucidated. Genetic downregulation of insulin/insulin-like growth factor 1 (Igf1) signaling components can extend invertebrate and mammalian lifespan, but insulin resistance, a natural form of decreased insulin signaling, is associated with greater risk of age-related disease in mammals. We compared Ins2 +/- mice to Ins2 +/+ littermate controls, on a genetically stable Ins1 null background. Proteomic and transcriptomic analyses of livers from 25-week-old mice suggested potential for healthier aging and altered insulin sensitivity in Ins2 +/- mice. Halving Ins2 lowered circulating insulin by 25%-34% in aged female mice, without altering Igf1 or circulating Igf1. Remarkably, decreased insulin led to lower fasting glucose and improved insulin sensitivity in aged mice. Moreover, lowered insulin caused significant lifespan extension, observed across two diverse diets. Our study indicates that elevated insulin contributes to age-dependent insulin resistance and that limiting basal insulin levels can extend lifespan. Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.

Hyperinsulinemic hypoglycemia associated with insulin antibodies caused by exogenous insulin analog

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Chih-Ting Su

2016-11-01

Full Text Available Insulin antibodies (IA associated with exogenous insulin administration seldom caused hypoglycemia and had different characteristics from insulin autoantibodies (IAA found in insulin autoimmune syndrome (IAS, which was first described by Dr Hirata in 1970. The characteristic of IAS is the presence of insulin-binding autoantibodies and related fasting or late postprandial hypoglycemia. Here, we report a patient with type 1 diabetes mellitus under insulin glargine and insulin aspart treatment who developed recurrent spontaneous post-absorptive hyperinsulinemic hypoglycemia with the cause probably being insulin antibodies induced by exogenous injected insulin. Examinations of serial sera disclosed a high titre of insulin antibodies (33%, normal <5%, high insulin concentration (111.9 IU/mL and undetectable C-peptide when hypoglycemia occurred. An oral glucose tolerance test revealed persistent high serum levels of total insulin and undetectable C-peptide. Image studies of the pancreas were unremarkable, which excluded the diagnosis of insulinoma. The patient does not take any of the medications containing sulfhydryl compounds, which had been reported to cause IAS. After administering oral prednisolone for 3 weeks, hypoglycemic episodes markedly improved, and he was discharged smoothly.

Five-year longitudinal assessment of the downstream impact on schistosomiasis transmission following closure of the Three Gorges Dam.

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Darren J Gray

Full Text Available Schistosoma japonicum is a major public health concern in the Peoples' Republic of China (PRC, with about 800,000 people infected and another 50 million living in areas at risk of infection. Based on ecological, environmental, population genetic and molecular factors, schistosomiasis transmission in PRC can be categorised into four discrete ecosystems or transmission modes. It is predicted that, long-term, the Three Gorges Dam (TGD will impact upon the transmission of schistosomiasis in the PRC, with varying degree across the four transmission modes.We undertook longitudinal surveillance from 2002 to 2006 in sentinel villages of the three transmission modes below the TGD across four provinces (Hunan, Jiangxi, Hubei and Anhui to determine whether there was any immediate impact of the TGD on schistosomiasis transmission. Eight sentinel villages were selected to represent both province and transmission mode. The primary end point measured was human incidence. Here we present the results of this five-year longitudinal cohort study. Results showed that the incidence of human S. japonicum infection declined considerably within individual villages and overall mode over the course of the study. This is also reflected in the yearly odds ratios (adjusted for infection risk that showed significant (P<0.01 downward trends in all modes over the follow-up period.The decrease in human S. japonicum incidence observed across all transmission modes in this study can probably be attributed to the annual human and bovine PZQ chemotherapy. If an increase in schistosome transmission had occurred as a result of the TGD, it would be of negligible size compared to the treatment induced decline seen here. It appears therefore that there has been virtually no immediate impact of the TGD on schistosomiasis transmission downstream of the dam.

Comparison between basal insulin glargine and NPH insulin in patients with diabetes type 1 on conventional intensive insulin therapy

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Pešić Milica

2007-01-01

Full Text Available Background/Aim. Insulin glargine is a long-acting insulin analog that mimics normal basal insulin secretion without pronounced peaks. The aim of this study was to compare insulin glargine with isophane insulin (NPH insulin for basal insulin supply in patients with type 1 diabetes. Methods. A total of 48 type 1 diabetics on long term conventional intensive insulin therapy (IIT were randomized to three different regimens of basal insulin substitution: 1. continuation of NPH insulin once daily at bedtime with more intensive selfmonitoring (n = 15; 2. NPH insulin twice daily (n = 15; 3. insulin glargine once daily (n = 18. Meal time insulin aspart was continued in all groups. Results. Fasting blood glucose (FBG was lower in the glargine group (7.30±0.98 mmol/l than in the twice daily NPH group (7.47±1.06 mmol/l, but without significant difference. FBG was significantly higher in the once daily NPH group (8.44±0.85 mmol/l; p < 0.05. HbA1c after 3 months did not change in the once daily NPH group, but decreased in the glargine group (from 7.72±0.86% to 6.87±0.50%, as well as in the twice daily NPH group (from 7.80±0.83% to 7.01±0.63%. Total daily insulin doses were similar in all groups but only in the glargine group there was an increase of basal and decrease of meal related insulin doses. The frequency of mild hypoglycemia was significantly lower in the glargine group (6.56±2.09 than in both NPH groups (9.0±1.65 in twice daily NPH group and 8.13±1.30 in other NPH group (episodes/patients-month, p < 0.05. Conclusion. Basal insulin supplementation in type 1 diabetes mellitus with either twice daily NPH insulin or glargine can result in similar glycemic control when combined with meal time insulin aspart. However, with glargine regimen FBG, HbA1c and frequency of hypoglycemic event are lower. These facts contribute to better patients satisfaction with insulin glargine versus NPH insulin in IIT in type 1 diabetics.

Epidemiological studies of Schistosoma mattheei infections in cattle in the highveld and lowveld communal grazing areas of Zimbabwe

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D.M. Pfukenyi

2006-09-01

Full Text Available During the period between January 1999 and December 2000, the distribution and seasonal patterns of Schistosoma mattheei infections in cattle in the highveld and lowveld communal grazing areas of Zimbabwe were determined through monthly coprological examination. Faecal samples of cattle were collected from 12 and nine dipping sites in the highveld and lowveld communal grazing areas, respectively. Patterns of distribution and seasonal fluctuations of the intermediate host-snail populations and the climatic factors influencing the distribution were also determined at monthly intervals from November 1998 to October 2000, a period of 24 months, in six dams and six streams in the highveld and nine dams in the lowveld communal grazing areas. Monthly, each site was sampled for relative snail density, the vegetation cover and type, and physical and chemical properties of the water. Mean monthly rainfall and temperature were recorded. Snails collected at the same time were individually examined for shedding of cercariae of S. mattheei and Schistosoma haematobium. A total of 16 264 (5 418 calves, 5 461 weaners and 5 385 adults faecal samples were collected during the entire period of study and 734 (4.5 % were positive for S. mattheei eggs. Significantly higher prevalences were found in the highveld compared to the lowveld (P < 0.001, calves compared to adult cattle (P < 0.01 and the wet season compared to the dry season (P < 0.01. Faecal egg output peaked from October/ November to March / April for both years of the study. Bulinus globosus, the snail intermediate host of S. mattheei was recorded from the study sites with the highveld having a significantly higher abundance of the snails than the lowveld (P < 0.01. Monthly densities of B. globosus did not show a clearcut pattern although there were peaks between March / May and September / November. The mean num ber of snails collected was positively correlated with the water plants Nymphaea caerulea and

A model of insulin fibrils derived from the x-ray crystal structure of a monomeric insulin (despentapeptide insulin).

Science.gov (United States)

Brange, J; Dodson, G G; Edwards, D J; Holden, P H; Whittingham, J L

1997-04-01

The crystal structure of despentapeptide insulin, a monomeric insulin, has been refined at 1.3 A spacing and subsequently used to predict and model the organization in the insulin fibril. The model makes use of the contacts in the densely packed despentapeptide insulin crystal, and takes into account other experimental evidence, including binding studies with Congo red. The dimensions of this model fibril correspond well with those measured experimentally, and the monomer-monomer contacts within the fibril are in accordance with the known physical chemistry of insulin fibrils. Using this model, it may be possible to predict mutations in insulin that might alleviate problems associated with fibril formation during insulin therapy.

Tau hyperphosphorylation induces oligomeric insulin accumulation and insulin resistance in neurons.

Science.gov (United States)

Rodriguez-Rodriguez, Patricia; Sandebring-Matton, Anna; Merino-Serrais, Paula; Parrado-Fernandez, Cristina; Rabano, Alberto; Winblad, Bengt; Ávila, Jesús; Ferrer, Isidre; Cedazo-Minguez, Angel

2017-12-01

Insulin signalling deficiencies and insulin resistance have been directly linked to the progression of neurodegenerative disorders like Alzheimer's disease. However, to date little is known about the underlying molecular mechanisms or insulin state and distribution in the brain under pathological conditions. Here, we report that insulin is accumulated and retained as oligomers in hyperphosphorylated tau-bearing neurons in Alzheimer's disease and in several of the most prevalent human tauopathies. The intraneuronal accumulation of insulin is directly dependent on tau hyperphosphorylation, and follows the tauopathy progression. Furthermore, cells accumulating insulin show signs of insulin resistance and decreased insulin receptor levels. These results suggest that insulin retention in hyperphosphorylated tau-bearing neurons is a causative factor for the insulin resistance observed in tauopathies, and describe a novel neuropathological concept with important therapeutic implications. © The Author (2017). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Effect of metal stress on photosynthetic pigments in the Cu-hyperaccumulating lichens Cladonia humilis and Stereocaulon japonicum growing in Cu-polluted sites in Japan.

Science.gov (United States)

Nakajima, Hiromitsu; Yamamoto, Yoshikazu; Yoshitani, Azusa; Itoh, Kiminori

2013-11-01

To understand the ecology and physiology of metal-accumulating lichens growing in Cu-polluted sites, we investigated lichens near temple and shrine buildings with Cu roofs in Japan and found that Stereocaulon japonicum Th. Fr. and Cladonia humilis (With.) J. R. Laundon grow in Cu-polluted sites. Metal concentrations in the lichen samples collected at some of these sites were determined by inductively coupled plasma mass spectroscopy (ICP-MS). UV-vis absorption spectra of pigments extracted from the lichen samples were measured, and the pigment concentrations were estimated from the spectral data using equations from the literature. Secondary metabolites extracted from the lichen samples were analyzed by high-performance liquid chromatography (HPLC) with a photodiode array detector. We found that S. japonicum and C. humilis are Cu-hyperaccumulating lichens. Differences in pigment concentrations and their absorption spectra were observed between the Cu-polluted and control samples of the 2 lichens. However, no correlation was found between Cu and pigment concentrations. We observed a positive correlation between Al and Fe concentrations and unexpectedly found high negative correlations between Al and pigment concentrations. This suggests that Al stress reduces pigment concentrations. The concentrations of secondary metabolites in C. humilis growing in the Cu-polluted sites agreed with those in C. humilis growing in the control sites. This indicates that the metabolite concentrations are independent of Cu stress. Copyright © 2013 Elsevier Inc. All rights reserved.

Anti-insulin antibody test

Science.gov (United States)

Insulin antibodies - serum; Insulin Ab test; Insulin resistance - insulin antibodies; Diabetes - insulin antibodies ... Normally, there are no antibodies against insulin in your blood. ... different laboratories. Some labs use different measurements or ...

Cerebral insulin, insulin signaling pathway, and brain angiogenesis.

Science.gov (United States)

Zeng, Yi; Zhang, Le; Hu, Zhiping

2016-01-01

Insulin performs unique non-metabolic functions within the brain. Broadly speaking, two major areas of these functions are those related to brain endothelial cells and the blood-brain barrier (BBB) function, and those related to behavioral effects, like cognition in disease states (Alzheimer's disease, AD) and in health. Recent studies showed that both these functions are associated with brain angiogenesis. These findings raise interesting questions such as how they are linked to each other and whether modifying brain angiogenesis by targeting certain insulin signaling pathways could be an effective strategy to treat dementia as in AD, or even to help secure healthy longevity. The two canonical downstream pathways involved in mediating the insulin signaling pathway, the phosphoinositide-3 kinase (PI3K), and mitogen-activated protein kinase (MAPK) cascades, in the brain are supposed to be similar to those in the periphery. PI3K and MAPK pathways play important roles in angiogenesis. Both are involved in stimulating hypoxia inducible factor (HIF) in angiogenesis and could be activated by the insulin signaling pathway. This suggests that PI3K and MAPK pathways might act as cross-talk between the insulin signaling pathway and the angiogenesis pathway in brain. But the cerebral insulin, insulin signaling pathway, and the detailed mechanism in the connection of insulin signaling pathway, brain angiogenesis pathway, and healthy aging or dementias are still mostly not clear and need further studies.

Glycomic Analysis of Life Stages of the Human Parasite Schistosoma mansoni Reveals Developmental Expression Profiles of Functional and Antigenic Glycan Motifs

NARCIS (Netherlands)

Smit, C.H.; van Diepen, A.; Nguyen, D.L.; Wuhrer, M.; Hoffmann, K.F.; Deelder, A.M.; Hokke, C.H.

2015-01-01

Glycans present on glycoproteins and glycolipids of the major human parasite Schistosoma mansoni induce innate as well as adaptive immune responses in the host. To be able to study the molecular characteristics of schistosome infections it is therefore required to determine the expression profiles

Insulin resistance in obesity can be reliably identified from fasting plasma insulin.

Science.gov (United States)

ter Horst, K W; Gilijamse, P W; Koopman, K E; de Weijer, B A; Brands, M; Kootte, R S; Romijn, J A; Ackermans, M T; Nieuwdorp, M; Soeters, M R; Serlie, M J

2015-12-01

Insulin resistance is the major contributor to cardiometabolic complications of obesity. We aimed to (1) establish cutoff points for insulin resistance from euglycemic hyperinsulinemic clamps (EHCs), (2) identify insulin-resistant obese subjects and (3) predict insulin resistance from routinely measured variables. We assembled data from non-obese (n=112) and obese (n=100) men who underwent two-step EHCs using [6,6-(2)H2]glucose as tracer (insulin infusion dose 20 and 60 mU m(-2) min(-1), respectively). Reference ranges for hepatic and peripheral insulin sensitivity were calculated from healthy non-obese men. Based on these reference values, obese men with preserved insulin sensitivity or insulin resistance were identified. Cutoff points for insulin-mediated suppression of endogenous glucose production (EGP) and insulin-stimulated glucose disappearance rate (Rd) were 46.5% and 37.3 μmol kg(-)(1) min(-)(1), respectively. Most obese men (78%) had EGP suppression within the reference range, whereas only 12% of obese men had Rd within the reference range. Obese men with Rd obese men in age, body mass index (BMI), body composition, fasting glucose or cholesterol, but did have higher fasting insulin (110±49 vs 63±29 pmol l(-1), Pobese men could be identified with good sensitivity (80%) and specificity (75%) from fasting insulin >74 pmol l(-1). Most obese men have hepatic insulin sensitivity within the range of non-obese controls, but below-normal peripheral insulin sensitivity, that is, insulin resistance. Fasting insulin (>74 pmol l(-1) with current insulin immunoassay) may be used for identification of insulin-resistant (or metabolically unhealthy) obese men in research and clinical settings.

Schistosoma mansoni: effects of anesthetics and antimonial drugs on worm shift in the mouse

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José Renan da Cunha-Melo

1986-08-01

Full Text Available Mice experimentally infected with Schistosoma mansoni were injected with sodium thiopental or sodium antimonyl gluconate (Triostib R, or submitted to halothane inhalation, with or without a previous injection of thiopental. Data obtained showed that halothane and thiopental induce worm shift to the liver (99 and 76%, respectively. Sodium gluconate and antimonium (Triostib R shifted 52% of worms towards the liver. These results seem to indicate that the use of antimonium would be unnecessary, when surgical removal of schistosomules is carried out through the extracorporeal filtration technique, in patients with portal hypertension.

Absence of down-regulation of the insulin receptor by insulin. A possible mechanism of insulin resistance in the rat.

OpenAIRE

Walker, A P; Flint, D J

1983-01-01

Insulin resistance occurs in rat adipocytes during pregnancy and lactation despite increased or normal insulin binding respectively; this suggests that a post-receptor defect exists. The possibility has been examined that, although insulin binding occurs normally, internalization of insulin or its receptor may be impaired in these states. Insulin produced a dose-dependent reduction in the number of insulin receptors on adipocytes from virgin rats maintained in culture medium, probably due to ...

Influence of the nontarget mollusc Marisa cornuarietis on the hourly cercarial production of Schistosoma mansoni from Biomphalaria glabrata.

Science.gov (United States)

Ferrer, J R; Pointier, J P; Théron, A; Moné, H

1991-10-01

A comparative study of hourly cercarial productivities of Schistosoma mansoni from infected Biomphalaria glabrata was carried out in the presence of either healthy B. glabrata (control) or healthy Marisa cornuarietis (experimental). The results showed that, with M. cornuarietis, almost all the hourly cercarial productivities increased by a factor varying from 1.3 to 2.5 without modification of the shedding period.

Clinical use of the co-formulation of insulin degludec and insulin aspart

DEFF Research Database (Denmark)

Kumar, A; Awata, T; Bain, S C

2016-01-01

(HbA1c ) to current modern insulins, but with lower risk of nocturnal hypoglycaemia. In prior insulin users, glycaemic control was achieved with lower or equal insulin doses vs. other basal+meal-time or premix insulin regimens. In insulin-naïve patients with T2DM, IDegAsp can be started once or twice...... a simpler insulin regimen than other available basal-bolus or premix-based insulin regimens, with stable daytime basal coverage, a lower rate of hypoglycaemia and some flexibility in injection timing compared with premix insulins....

Effects of intranasal insulin on endogenous glucose production in insulin-resistant men.

Science.gov (United States)

Xiao, Changting; Dash, Satya; Stahel, Priska; Lewis, Gary F

2018-03-14

The effects of intranasal insulin on the regulation of endogenous glucose production (EGP) in individuals with insulin resistance were assessed in a single-blind, crossover study. Overweight or obese insulin-resistant men (n = 7; body mass index 35.4 ± 4.4 kg/m 2 , homeostatic model assessment of insulin resistance 5.6 ± 1.6) received intranasal spray of either 40 IU insulin lispro or placebo in 2 randomized visits. Acute systemic spillover of intranasal insulin into the circulation was matched with a 30-minute intravenous infusion of insulin lispro in the nasal placebo arm. EGP was assessed under conditions of a pancreatic clamp with a primed, constant infusion of glucose tracer. Under these experimental conditions, compared with placebo, intranasal administration of insulin did not significantly affect plasma glucose concentrations, EGP or glucose disposal in overweight/obese, insulin-resistant men, in contrast to our previous study, in which an equivalent dose of intranasal insulin significantly suppressed EGP in lean, insulin-sensitive men. Insulin resistance is probably associated with impairment in centrally mediated insulin suppression of EGP. © 2018 John Wiley & Sons Ltd.

Metabolism and insulin signaling in common metabolic disorders and inherited insulin resistance

DEFF Research Database (Denmark)

Højlund, Kurt

2014-01-01

. These metabolic disorders are all characterized by reduced plasma adiponectin and insulin resistance in peripheral tissues. Quantitatively skeletal muscle is the major site of insulin resistance. Both low plasma adiponectin and insulin resistance contribute to an increased risk of type 2 diabetes...... described a novel syndrome characterized by postprandial hyperinsulinemic hypoglycemia and insulin resistance. This syndrome is caused by a mutation in the tyrosine kinase domain of the insulin receptor gene (INSR). We have studied individuals with this mutation as a model of inherited insulin resistance....... Type 2 diabetes, obesity and PCOS are characterized by pronounced defects in the insulin-stimulated glucose uptake, in particular glycogen synthesis and to a lesser extent glucose oxidation, and the ability of insulin to suppress lipid oxidation. In inherited insulin resistance, however, only insulin...

Analysis of the primary structure and post-translational modifications of the Schistosoma mansoni antigen Smp28 by electrospray mass spectrometry

NARCIS (Netherlands)

Bouchon, B.; Jaquinod, M.; Klarskov, K.; Trottein, F.; Klein, Michele; Van Dorsselaer, A.; Bischoff, Rainer; Roitsch, C.

1994-01-01

The Schistosoma mansoni glutathione-S-transferase with an apparent molecular mass of 28 kDa, Smp28, has a blocked N-terminus which has been elucidated with the aid of the cDNA sequence combined with mass spectrometry and amino acid composition analysis of the N-terminal tryptic peptide. The blocked

Psychological insulin resistance in type 2 diabetes patients regarding oral antidiabetes treatment, subcutaneous insulin injections, or inhaled insulin.

Science.gov (United States)

Petrak, Frank; Herpertz, Stephan; Stridde, Elmar; Pfützner, Andreas

2013-08-01

"Psychological insulin resistance" (PIR) is an obstacle to insulin treatment in type 2 diabetes, and patients' expectations regarding alternative ways of insulin delivery are poorly understood. PIR and beliefs regarding treatment alternatives were analyzed in patients with type 2 diabetes (n=532; mean glycated hemoglobin, 68±12 mmol/mol [8.34±1.5%]) comparing oral antidiabetes treatment, subcutaneous insulin injections, or inhaled insulin. Questionnaires were used to assess barriers to insulin treatment (BIT), generic and diabetes-specific quality of life (Short Form 36 and Problem Areas in Diabetes, German version), diabetes knowledge, locus of control (Questionnaire for the Assessment of Diabetes-Specific Locus of Control, in German), coping styles (Freiburg Questionnaire of Illness Coping, 15-Items Short Form), self-esteem (Rosenberg Self-Esteem Scale, German version), and mental disorders (Patient Health Questionnaire, German version). Patients discussed treatment optimization options with a physician and were asked to make a choice about future diabetes therapy options in a two-step treatment choice scenario. Step 1 included oral antidiabetes drugs or subcutaneous insulin injection (SCI). Step 2 included an additional treatment alternative of inhaled insulin (INH). Subgroups were analyzed according to their treatment choice. Most patients perceived their own diabetes-related behavior as active, problem-focused, internally controlled, and oriented toward their doctors' recommendations, although their diabetes knowledge was limited. In Step 1, rejection of the recommended insulin was 82%, and in Step 2, it was 57%. Fear of hypoglycemia was the most important barrier to insulin treatment. Patients choosing INH (versus SCI) scored higher regarding fear of injection, expected hardship from insulin therapy, and BIT-Sumscore. The acceptance of insulin is very low in type 2 diabetes patients. The option to inhale insulin increases the acceptability for some but

Estudo quantitativo de metais presentes na hemolinfa de Biomphalaria glabrata (Gastropoda, infectadas e não infectadas com Schistosoma mansoni Quantitative study of metal present in the hemolymph of Biomphalaria glabrata (Gastropoda, infected and uninfected with Schistosoma mansoni

Directory of Open Access Journals (Sweden)

Marco Antonio Vasconcelos Santos

2005-04-01

Full Text Available Inicialmente, desenvolveu-se um estudo para quantificar e comparar as concentrações de alguns metais presentes em duas amostras de hemolinfa do caramujo Biomphalaria glabrata (infectados e não-infectados com Schistosoma mansoni. A espectrometria de emissão óptica com fonte de plasma induzido (ICP-OES, foi utilizada para analisar os metais nas duas amostras. Os metais estudados foram: alumínio, cálcio, cádmio, cobalto, cromo, cobre, ferro, potássio, magnésio, manganês, chumbo e zinco. Os resultados mostram que, a princípio, os metais não são fatores determinantes no processo de defesa desses organismos contra este parasita, quando presente nos seus tecidos.We conducted a preliminary study to quantify and compare two concentrations of the same metals present in the hemolymph of snail Biomphalaria glabrata. In this context, we used Induction Coupled Plasma Optical Emission Spectroscopy technique (ICP-OES, to analyze the metals in the two samples (snails infected and not infected with Schistosoma mansoni. The metals studied were: aluminum, calcium, cadmium, cobalt, chromium, copper, iron, potassium, magnesium, manganese, lead and zinc. Preliminary results showed that such metals are not involved in the defense of these organisms against the parasite, when present in their tissues.

Sonographic screening for urinary tract abnormalities in patients with Schistosoma haematobium infection: pitfalls in examining pregnant women.

OpenAIRE

Richter, J.; Wagatsuma, Y.; Aryeetey, M.; Feldmeier, H.

1996-01-01

In areas where Schistosoma haematobium is endemic, urinary schistosomiasis and pregnancy are frequently concomitant; however, both these conditions may produce similar urinary tract changes in ultrasound scans and hence their differential diagnosis may be difficult. In patients with urinary schistosomiasis, focal and/or diffuse urinary bladder wall changes are frequently detected ultrasonically. Dilatation of one or both ureters and progressive hydronephrosis may be observed in more severe ca...

Postreceptor defects causing insulin resistance in normoinsulinemic non-insulin-dependent diabetes mellitus

International Nuclear Information System (INIS)

Bolinder, J.; Ostman, J.; Arner, P.

1982-01-01

The mechanisms of the diminished hypoglycemic response to insulin in non-insulin-dependent diabetes mellitus (NIDDM) with normal levels of circulating plasma insulin were investigated. Specific binding of mono- 125 I (Tyr A14)-insulin to isolated adipocytes and effects of insulin (5--10,000 microunits/ml) on glucose oxidation and lipolysis were determined simultaneously in subcutaneous adipose tissue of seven healthy subjects of normal weight and seven untreated NIDDM patients with normal plasma insulin levels. The two groups were matched for age, sex, and body weight. Insulin binding, measured in terms of receptor number and affinity, was normal in NIDDM, the total number of receptors averaging 350,000 per cell. Neither sensitivity nor the maximum antilipolytic effect of insulin was altered in NIDDM patients as compared with control subjects; the insulin concentration producing half the maximum effect (ED50) was 10 microunits/ml. As regards the effect of insulin on glucose oxidation, for the control subjects ED50 was 30 microunits/ml, whereas in NIDDM patients, insulin exerted no stimulatory effect. The results obtained suggest that the effect of insulin on glucose utilization in normoinsulinemic NIDDM may be diminished in spite of normal insulin binding to receptors. The resistance may be due solely to postreceptor defects, and does not involve antilipolysis

Serum Insulin, Glucose, Indices of Insulin Resistance, and Risk of Lung Cancer.

Science.gov (United States)

Argirion, Ilona; Weinstein, Stephanie J; Männistö, Satu; Albanes, Demetrius; Mondul, Alison M

2017-10-01

Background: Although insulin may increase the risk of some cancers, few studies have examined fasting serum insulin and lung cancer risk. Methods: We examined serum insulin, glucose, and indices of insulin resistance [insulin:glucose molar ratio and homeostasis model assessment of insulin resistance (HOMA-IR)] and lung cancer risk using a case-cohort study within the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study of Finnish men. A total of 196 cases and 395 subcohort members were included. Insulin and glucose were measured in fasting serum collected 5 to 12 years before diagnosis. Cox proportional hazards models were utilized to estimate the relative risk of lung cancer. Results: The average time between blood collection and lung cancer was 9.6 years. Fasting serum insulin levels were 8.7% higher in subcohort members than cases. After multivariable adjustment, men in the fourth quartile of insulin had a significantly higher risk of lung cancer than those in the first quartile [HR = 2.10; 95% confidence interval (CI), 1.12-3.94]. A similar relationship was seen with HOMA-IR (HR = 1.83; 95% CI, 0.99-3.38). Risk was not strongly associated with glucose or the insulin:glucose molar ratio ( P trend = 0.55 and P trend = 0.27, respectively). Conclusions: Higher fasting serum insulin concentrations, as well as the presence of insulin resistance, appear to be associated with an elevated risk of lung cancer development. Impact: Although insulin is hypothesized to increase risk of some cancers, insulin and lung cancer remain understudied. Higher insulin levels and insulin resistance were associated with increased lung cancer risk. Although smoking cessation is the best method of lung cancer prevention, other lifestyle changes that affect insulin concentrations and sensitivity may reduce lung cancer risk. Cancer Epidemiol Biomarkers Prev; 26(10); 1519-24. ©2017 AACR . ©2017 American Association for Cancer Research.

Differential effects of insulin injections and insulin infusions on levels ...

African Journals Online (AJOL)

Studies have shown that while injections of insulin cause an increase in fat mass, infusions of insulin increase fat mass. The aim of this paper was to test the hypothesis that if an increase in glycogen is an indicator of an impending increase in adipose mass, then insulin infusions should not increase glycogen, while insulin ...

The Schistosoma Granuloma: Friend or Foe?

Science.gov (United States)

Hams, Emily; Aviello, Gabriella; Fallon, Padraic G.

2013-01-01

Infection of man with Schistosoma species of trematode parasite causes marked chronic morbidity. Individuals that become infected with Schistosomes may develop a spectrum of pathology ranging from mild cercarial dermatitis to severe tissue inflammation, in particular within the liver and intestines, which can lead to life threatening hepatosplenomegaly. It is well established that the etiopathology during schistosomiasis is primarily due to an excessive or unregulated inflammatory response to the parasite, in particular to eggs that become trapped in various tissue. The eggs forms the foci of a classical type 2 granulomatous inflammation, characterized by an eosinophil-rich, CD4+ T helper (Th) 2 cell dominated infiltrate with additional infiltration of alternatively activated macrophages (M2). Indeed the sequela of the type 2 perioval granuloma is marked fibroblast infiltration and development of fibrosis. Paradoxically, while the granuloma is the cause of pathology it also can afford some protection, whereby the granuloma minimizes collateral tissue damage in the liver and intestines. Furthermore, the parasite is exquisitely reliant on the host to mount a granulomatous reaction to the eggs as this inflammatory response facilitates the successful excretion of the eggs from the host. In this focused review we will address the conundrum of the S. mansoni granuloma acting as both friend and foe in inflammation during infection. PMID:23596444

Schistosoma mansoni: host cell adhesion to the different stages of the parasite, in vivo Schistosoma mansoni: adesão de células do hospedeiro aos diferentes estádios do parasito, in vivo

Directory of Open Access Journals (Sweden)

Alan L. Melo

1992-06-01

Full Text Available The peritoneal cavity of laboratory mice was used to study the phenomenon of host cell adhesion to different evolutive stages of the Schistosoma mansoni (cercaria, adult worm, developing and mature eggs, miracidium, young and mature daughter sporocysts. Material recovered from the peritoneal cavity 30 and 180 min after the inoculation of each evolutive form was examined with the help of a stereomicroscope. The free swimming larvae (cercaria and miracidium, and the evolutive forms producing such larvae (mature egg and mature daughter sporocyst elicited the host cell adhesion phenomenon. In all forms but cercariae the adherent cells remained as so till 180 minutes after inoculationA cavidade peritoneal de camundongos foi utilizada para estudos de adesão celular a diferentes estádios evolutivos do Schistosoma mansoni (cercária, verme adulto, ovos imaturos e maduros, miracídio, esporocisto jovem e esporocisto maduro. O material recuperado da cavidade peritoneal 30 e 180 min após o inóculo, foi examinado com auxílio de estereomicroscópio. As formas livres (cercária e miracídio e as formas evolutivas que produzem tais larvas (ovo maduro e esporocisto maduro apresentam células do hospedeiro aderidas à superfície. Em todas as formas, exceto cercária, as células permanecem aderidas pelo menos até 180 min após o inóculo

Economic benefits of improved insulin stability in insulin pumps.

Science.gov (United States)

Weiss, Richard C; van Amerongen, Derek; Bazalo, Gary; Aagren, Mark; Bouchard, Jonathan R

2011-05-01

Insulin pump users discard unused medication and infusion sets according to labeling and manufacturer's instructions. The stability labeling for insulin aspart (rDNA origin] (Novolog) was increased from two days to six. The associated savings was modeled from the perspective of a hypothetical one-million member health plan and the total United States population. The discarded insulin volume and the number of infusion sets used under a two-day stability scenario versus six were modeled. A mix of insulin pumps of various reservoir capacities with a range of daily insulin dosages was used. Average daily insulin dose was 65 units ranging from 10 to 150 units. Costs of discarded insulin aspart [rDNA origin] were calculated using WAC (Average Wholesale Price minus 16.67%). The cost of pump supplies was computed for the two-day scenario assuming a complete infusion set change, including reservoirs, every two days. Under the six-day scenario complete infusion sets were discarded every six days while cannulas at the insertion site were changed midway between complete changes. AWP of least expensive supplies was used to compute their costs. For the hypothetical health plan (1,182 pump users) the annual reduction in discarded insulin volume between scenarios was 19.8 million units. The corresponding cost reduction for the plan due to drug and supply savings was $3.4 million. From the U.S. population perspective, savings of over $1 billion were estimated. Using insulin that is stable for six days in pump reservoirs can yield substantial savings to health plans and other payers, including patients.

Metabolism and insulin signaling in common metabolic disorders and inherited insulin resistance.

Science.gov (United States)

Højlund, Kurt

2014-07-01

Type 2 diabetes, obesity and polycystic ovary syndrome (PCOS) are common metabolic disorders which are observed with increasing prevalences, and which are caused by a complex interplay between genetic and environmental factors, including increased calorie intake and physical inactivity. These metabolic disorders are all characterized by reduced plasma adiponectin and insulin resistance in peripheral tissues. Quantitatively skeletal muscle is the major site of insulin resistance. Both low plasma adiponectin and insulin resistance contribute to an increased risk of type 2 diabetes and cardiovascular disease. In several studies, we have investigated insulin action on glucose and lipid metabolism, and at the molecular level, insulin signaling to glucose transport and glycogen synthesis in skeletal muscle from healthy individuals and in obesity, PCOS and type 2 diabetes. Moreover, we have described a novel syndrome characterized by postprandial hyperinsulinemic hypoglycemia and insulin resistance. This syndrome is caused by a mutation in the tyrosine kinase domain of the insulin receptor gene (INSR). We have studied individuals with this mutation as a model of inherited insulin resistance. Type 2 diabetes, obesity and PCOS are characterized by pronounced defects in the insulin-stimulated glucose uptake, in particular glycogen synthesis and to a lesser extent glucose oxidation, and the ability of insulin to suppress lipid oxidation. In inherited insulin resistance, however, only insulin action on glucose uptake and glycogen synthesis is impaired. This suggests that the defects in glucose and lipid oxidation in the common metabolic disorders are secondary to other factors. In young women with PCOS, the degree of insulin resistance was similar to that seen in middle-aged patients with type 2 diabetes. This supports the hypothesis of an unique pathogenesis of insulin resistance in PCOS. Insulin in physiological concentrations stimulates glucose uptake in human skeletal

Analysis of recombinant Schistosoma mansoni antigen rSmp28 by on-line liquid chromatography-mass spectrometry combined with sodium dodecyl sulfate polyacrylamide gel electrophoresis

NARCIS (Netherlands)

Klarskov, K.; Roecklin, D.; Bouchon, B.; Sabatie, J.; Van Dorsselaer, A.; Bischoff, Rainer

1994-01-01

A recombinant Schistosoma mansoni antigen produced in Saccharomyces cerevisiae and purified by glutathione-Sepharose affinity chromatography was analyzed by tryptic peptide mapping using on-line reversed-phase high-performance liquid chromatography pneumatically assisted electrospray mass

Pregestational diabetes with extreme insulin resistance: use of U-500 insulin in pregnancy.

Science.gov (United States)

Zuckerwise, Lisa C; Werner, Erika F; Pettker, Christian M; McMahon-Brown, Erin K; Thung, Stephen F; Han, Christina S

2012-08-01

Increased insulin requirements in pregnancy can hinder attainment of glycemic control in diabetic patients. U-500 insulin is a concentrated form of regular insulin that can be a valuable tool in the treatment of patients with severe insulin resistance. A 24-year-old woman with pregestational diabetes mellitus experienced increasing insulin requirements during pregnancy, peaking at 650 units daily. The frequent, large-volume injections of standard-concentration insulin were poorly tolerated by the patient and resulted in nonadherence. She subsequently achieved glycemic control on thrice-daily U-500 insulin. Pregnancy exacerbates insulin resistance in diabetic patients, and these patients may require high doses of insulin. U-500 insulin is an effective alternative for patients with severe insulin resistance and should be considered for pregnant women with difficulty achieving glycemic control.

Sex differences in the malnourished status of Chinese children due to schistosomiasis infections and inadequate dietary intake.

Science.gov (United States)

Zhou, Huan; He, Yongkang; Ohtsuka, Ryutaro

2005-01-01

Based on nutritional and parasitological examinations of 389 children aged 10-13 years in five primary schools in the schistosomiasis endemic Dongting Lake region of China, the causal factors of their retarded growth, represented by height, weight, mid-upper arm circumference and body mass index, were investigated. Among the four parasites, schistosomiasis infection due to Schistosoma japonicum played a significant role, with higher rates in girls than in boys. Praziquantel treatment of schistosomiasis decreased the infection rate and improved the children's growth. For dietary intake factors, the contribution of protein to total energy intake, which was lower in girls than in boys, had the greatest effect on the growth patterns. The sex difference in growth retardation is judged to be attributable to the traditional norms, such as girls spending more time in infested environments and gender discrimination in food distribution.

Dicty_cDB: Contig-U02520-1 [Dicty_cDB

Lifescience Database Archive (English)

Full Text Available ) KBrH001K21F KBrH, Brassica rapa HindIII BAC libra... 46 3.3 1 ( CT538104 ) A BAC library has been constructed from culti...1 ( DR026249 ) Osmo00116 F. cylindrus osmotic stress library Fra... 46 3.3 1 ( DN805411 ) 76947238 Sea Urchi...( CV793140 ) c-030216-1w_E04.abd cDNA library of Tamarix andro... 46 3.3 1 ( CV672849 ) RET7SJ_07D06.T7 Schistosoma japonicum re...012 2 ( CK416159 ) AUF_IpPit_34_o05 Pituitary cDNA library Ictalurus... 54 0.013 1 ( FE840166 ) CCAG48972.g1...99 ) NF075H11EC1F1095 Elicited cell culture Medicago t... 48 0.20 2 ( BF647354 ) NF075A06EC1F1040 Elicited cell culture Medic

Evaluation of Lethal Giant Larvae as a Schistosomiasis Vaccine Candidate

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Yufan Cao

2016-01-01

Full Text Available Schistosomiasis is a neglected tropical disease of humans, and it is considered to be the second most devastating parasitic disease after malaria. Eggs produced by normally developed female worms are important in the transmission of the parasite, and they responsible for the pathogenesis of schistosomiasis. The tumor suppressor gene lethal giant larvae (lgl has an essential function in establishing apical-basal cell polarity, cell proliferation, differentiation, and tissue organization. In our earlier study, downregulation of the lgl gene induced a significant reduction in the egg hatching rate of Schistosoma japonicum (Sj eggs. In this study, the Sjlgl gene was used as a vaccine candidate against schistosomiasis, and vaccination achieved and maintained a stable reduction of the egg hatching rate, which is consistent with previous studies, in addition to reducing the worm burden and liver egg burden in some trials.

Lipid-induced insulin resistance does not impair insulin access to skeletal muscle

Science.gov (United States)

Richey, Joyce M.; Castro, Ana Valeria B.; Broussard, Josiane L.; Ionut, Viorica; Bergman, Richard N.

2015-01-01

Elevated plasma free fatty acids (FFA) induce insulin resistance in skeletal muscle. Previously, we have shown that experimental insulin resistance induced by lipid infusion prevents the dispersion of insulin through the muscle, and we hypothesized that this would lead to an impairment of insulin moving from the plasma to the muscle interstitium. Thus, we infused lipid into our anesthetized canine model and measured the appearance of insulin in the lymph as a means to sample muscle interstitium under hyperinsulinemic euglycemic clamp conditions. Although lipid infusion lowered the glucose infusion rate and induced both peripheral and hepatic insulin resistance, we were unable to detect an impairment of insulin access to the lymph. Interestingly, despite a significant, 10-fold increase in plasma FFA, we detected little to no increase in free fatty acids or triglycerides in the lymph after lipid infusion. Thus, we conclude that experimental insulin resistance induced by lipid infusion does not reduce insulin access to skeletal muscle under clamp conditions. This would suggest that the peripheral insulin resistance is likely due to reduced cellular sensitivity to insulin in this model, and yet we did not detect a change in the tissue microenvironment that could contribute to cellular insulin resistance. PMID:25852002

Long-term frozen storage of urine samples: a trouble to get PCR results in Schistosoma spp. DNA detection?

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Pedro Fernández-Soto

Full Text Available BACKGROUND: Human schistosomiasis remains a serious worldwide public health problem. At present, a sensitive and specific assay for routine diagnosis of schistosome infection is not yet available. The potential for detecting schistosome-derived DNA by PCR-based methods in human clinical samples is currently being investigated as a diagnostic tool with potential application in routine schistosomiasis diagnosis. Collection of diagnostic samples such as stool or blood is usually difficult in some populations. However, urine is a biological sample that can be collected in a non-invasive method, easy to get from people of all ages and easy in management, but as a sample for PCR diagnosis is still not widely used. This could be due to the high variability in the reported efficiency of detection as a result of the high variation in urine samples' storage or conditions for handling and DNA preservation and extraction methods. METHODOLOGY/PRINCIPAL FINDINGS: We evaluate different commercial DNA extraction methods from a series of long-term frozen storage human urine samples from patients with parasitological confirmed schistosomiasis in order to assess the PCR effectiveness for Schistosoma spp. detection. Patients urine samples were frozen for 18 months up to 7 years until use. Results were compared with those obtained in PCR assays using fresh healthy human urine artificially contaminated with Schistosoma mansoni DNA and urine samples from mice experimentally infected with S. mansoni cercariae stored frozen for at least 12 months before use. PCR results in fresh human artificial urine samples using different DNA based extraction methods were much more effective than those obtained when long-term frozen human urine samples were used as the source of DNA template. CONCLUSIONS/SIGNIFICANCE: Long-term frozen human urine samples are probably not a good source for DNA extraction for use as a template in PCR detection of Schistosoma spp., regardless of the DNA

Alternative translation initiation of Caveolin-2 desensitizes insulin signaling through dephosphorylation of insulin receptor by PTP1B and causes insulin resistance.

Science.gov (United States)

Kwon, Hayeong; Jang, Donghwan; Choi, Moonjeong; Lee, Jaewoong; Jeong, Kyuho; Pak, Yunbae

2018-06-01

Insulin resistance, defined as attenuated sensitivity responding to insulin, impairs insulin action. Direct causes and molecular mechanisms of insulin resistance have thus far remained elusive. Here we show that alternative translation initiation (ATI) of Caveolin-2 (Cav-2) regulates insulin sensitivity. Cav-2β isoform yielded by ATI desensitizes insulin receptor (IR) via dephosphorylation by protein-tyrosine phosphatase 1B (PTP1B), and subsequent endocytosis and lysosomal degradation of IR, causing insulin resistance. Blockage of Cav-2 ATI protects against insulin resistance by preventing Cav-2β-PTP1B-directed IR desensitization, thereby normalizing insulin sensitivity and glucose uptake. Our findings show that Cav-2β is a negative regulator of IR signaling, and identify a mechanism causing insulin resistance through control of insulin sensitivity via Cav-2 ATI. Copyright © 2018 Elsevier B.V. All rights reserved.

Development of a Schistosoma mansoni shotgun O-glycan microarray and application to the discovery of new antigenic schistosome glycan motifs.

Science.gov (United States)

van Diepen, Angela; van der Plas, Arend-Jan; Kozak, Radoslaw P; Royle, Louise; Dunne, David W; Hokke, Cornelis H

2015-06-01

Upon infection with Schistosoma, antibody responses are mounted that are largely directed against glycans. Over the last few years significant progress has been made in characterising the antigenic properties of N-glycans of Schistosoma mansoni. Despite also being abundantly expressed by schistosomes, much less is understood about O-glycans and antibody responses to these have not yet been systematically analysed. Antibody binding to schistosome glycans can be analysed efficiently and quantitatively using glycan microarrays, but O-glycan array construction and exploration is lagging behind because no universal O-glycanase is available, and release of O-glycans has been dependent on chemical methods. Recently, a modified hydrazinolysis method has been developed that allows the release of O-glycans with free reducing termini and limited degradation, and we applied this method to obtain O-glycans from different S. mansoni life stages. Two-dimensional HPLC separation of 2-aminobenzoic acid-labelled O-glycans generated 362 O-glycan-containing fractions that were printed on an epoxide-modified glass slide, thereby generating the first shotgun O-glycan microarray containing naturally occurring schistosome O-glycans. Monoclonal antibodies and mass spectrometry showed that the O-glycan microarray contains well-known antigenic glycan motifs as well as numerous other, potentially novel, antibody targets. Incubations of the microarrays with sera from Schistosoma-infected humans showed substantial antibody responses to O-glycans in addition to those observed to the previously investigated N- and glycosphingolipid glycans. This underlines the importance of the inclusion of these often schistosome-specific O-glycans in glycan antigen studies and indicates that O-glycans contain novel antigenic motifs that have potential for use in diagnostic methods and studies aiming at the discovery of vaccine targets. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights

Conversion from insulin glargine U-100 to insulin glargine U-300 or insulin degludec and the impact on dosage requirements.

Science.gov (United States)

Pearson, Scott M; Trujillo, Jennifer M

2018-04-01

We wanted to determine whether basal insulin requirements change when patients transition from insulin glargine U-100 (Gla-100) to insulin glargine U-300 (Gla-300) or insulin degludec. This study involved subjects seen in the University of Colorado Health Endocrine Clinic who were transitioned from Gla-100 to either Gla-300 ( n = 95) or insulin degludec ( n = 39). The primary outcome was the difference between baseline Gla-100 dose and dose of Gla-300 or insulin degludec prescribed after first follow-up visit within 1-12 months. Secondary outcomes included changes in glycemic control and empiric dose conversion from Gla-100 to Gla-300 or insulin degludec on the day of transition. Wilcoxon rank sum tests evaluated changes in insulin doses, and paired t tests assessed changes in glycemic control using GraphPad statistical software. Median daily basal insulin dose increased for individuals transitioned from Gla-100 to Gla-300 from 30 [19-60 interquartile range (IQR)] units at baseline to 34.5 (19-70 IQR) units after follow up ( p = 0.01). For patients transitioned to insulin degludec, dose changes from baseline to follow up were not significantly different ( p = 0.56). At the time of transition, the prescribed dose of Gla-300 or insulin degludec did not significantly differ from the previous dose of Gla-100 ( p = 0.73 and 0.28, respectively), indicating that empiric dose adjustments were not routinely prescribed. Patients who transitioned from Gla-100 to Gla-300 had increased basal insulin requirements between visits, while basal insulin requirements for those transitioned from Gla-100 to insulin degludec were not significantly different.

Secreted serine protease SmSP2 of the blood fluke Schistosoma mansoni: Biochemical characterization, localization and host protein processing

Czech Academy of Sciences Publication Activity Database

Leontovyč, Adrian; Ulrychová, Lenka; O'Donoghue, A.J.; Marešová, Lucie; Vondrášek, Jiří; Caffrey, C. R.; Mareš, Michael; Horn, Martin; Dvořák, Jan

2017-01-01

Roč. 15, č. 1 (2017), s. 18 ISSN 2336-7202. [Mezioborové setkání mladých biologů, biochemiků a chemiků /17./. 30.05.2017-01.06.2017, Milovy] R&D Projects: GA MŠk LD15101; GA MŠk LO1302 Institutional support: RVO:61388963 Keywords : Schistosoma mansoni * SmSP2 Subject RIV: CE - Biochemistry

Avaliação terapêutica do artesunato na infecção experimental pelo Schistosoma mansoni Therapeutical evaluation of the artesunate in experimental Schistosoma mansoni infection

Directory of Open Access Journals (Sweden)

Neusa Araújo

1999-02-01

Full Text Available Camundongos infectados experimentalmente com Schistosoma mansoni foram tratados, em dose oral única, com artesunato (LACTAB®, 300 ou 500mg/kg ou durante cinco dias consecutivos. Os animais foram sacrificados 7, 30, 60 ou 90 dias após o tratamento. Diferenças estatisticamente significativas foram encontradas na distribuição e mortalidade dos vermes e na alteração do oograma nos grupos tratados quando comparados ao controle, em todos os esquemas testados quando os animais foram sacrificados 30 dias após o tratamento. A análise morfológica dos vermes mostrou alterações no aparelho reprodutor feminino com diminuição do volume ovariano, rarefação dos folículos vitelínicos, alterações estas mais acentuadas nas dosagens mais altas, justificando o encontro na alteração do oograma que chegou a 100%. Entretanto, quando os animais foram sacrificados 60 ou 90 dias após o tratamento, as diferenças e alterações foram menores, mostrando que os vermes sobreviventes se recuperaram e reiniciaram a postura.Mice experimentally infected with Schistosoma mansoni were treated orally with artesunate (Lactab® in a single dose of 300 or 500mg/kg or over a period of five consecutive days. The animals were sacrificed 7, 30, 60 or 90 days after treatment. Statistically significant differences were found in the distribution and mortality of the worms and in the alterations of the oogram in the treated group when compared to control in all of the tested schemes when the animals were sacrificed 30 days after treatment. Morphological analysis of female worms showed a reduction of ovarian volume and rarefaction of the vitelline follicles. These modifications were more marked after treatment with the higher dose, explaining the alteration of the oogram which reached 100%. However, when the animals were sacrificed 60 or 90 days after treatment, the differences and alterations were smaller, showing that the surviving worms recovered and restarted

Update on insulin treatment for dogs and cats: insulin dosing pens and more

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Thompson A

2015-04-01

Full Text Available Ann Thompson,1 Patty Lathan,2 Linda Fleeman3 1School of Veterinary Science, The University of Queensland, Gatton, QLD, Australia; 2College of Veterinary Medicine Mississippi State University, Starkville, MS, USA; 3Animal Diabetes Australia, Melbourne, VIC, Australia Abstract: Insulin therapy is still the primary therapy for all diabetic dogs and cats. Several insulin options are available for each species, including veterinary registered products and human insulin preparations. The insulin chosen depends on the individual patient's requirements. Intermediate-acting insulin is usually the first choice for dogs, and longer-acting insulin is the first choice for cats. Once the insulin type is chosen, the best method of insulin administration should be considered. Traditionally, insulin vials and syringes have been used, but insulin pen devices have recently entered the veterinary market. Pens have different handling requirements when compared with standard insulin vials including: storage out of the refrigerator for some insulin preparations once pen cartridges are in use; priming of the pen to ensure a full dose of insulin is administered; and holding the pen device in place for several seconds during the injection. Many different types of pen devices are available, with features such as half-unit dosing, large dials for visually impaired people, and memory that can display the last time and dose of insulin administered. Insulin pens come in both reusable and disposable options. Pens have several benefits over syringes, including improved dose accuracy, especially for low insulin doses. Keywords: diabetes, mellitus, canine, feline, NPH, glargine, porcine lente

Estudo morfológico do Schistosoma mansoni Sambon, 1907 encontrado na espécie humana

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M. R. Q. de Kastner

1975-10-01

Full Text Available O presente trabalho estuda; a morfologia do Schistosoma mansoni Sambon, 1907, obtido por filtração extra-corpórea de 5 (cinco pacientes do Hospital São Vicente de Paula em Minas Gerais. Foram elucidados detalhes morfológicos até então controvertidos na literatura, tendo sido, inclusive, correlacionados com os estudados pela microscopia eletrônica por outros autores. Não foram observadas diferenças morfológicas entre os vermes humanos e os descritos em animais de pequeno porte.

Novel covalently linked insulin dimer engineered to investigate the function of insulin dimerization

DEFF Research Database (Denmark)

Vinther, Tine N.; Norrman, Mathias; Strauss, Holger M.

2012-01-01

An ingenious system evolved to facilitate insulin binding to the insulin receptor as a monomer and at the same time ensure sufficient stability of insulin during storage. Insulin dimer is the cornerstone of this system. Insulin dimer is relatively weak, which ensures dissociation into monomers...... in the circulation, and it is stabilized by hexamer formation in the presence of zinc ions during storage in the pancreatic ß-cell. Due to the transient nature of insulin dimer, direct investigation of this important form is inherently difficult. To address the relationship between insulin oligomerization...... and insulin stability and function, we engineered a covalently linked insulin dimer in which two monomers were linked by a disulfide bond. The structure of this covalent dimer was identical to the self-association dimer of human insulin. Importantly, this covalent dimer was capable of further oligomerization...

Insulin analogues: have they changed insulin treatment and improved glycaemic control?

DEFF Research Database (Denmark)

Madsbad, Sten

2002-01-01

To improve insulin therapy, new insulin analogues have been developed. Two fast-acting analogues with a more rapid onset of effect and a shorter duration of action combined with a low day-to-day variation in absorption rate are now available. Despite this favourable time-action profile most studies....... This is probably the main explanation for the absence of improvement in overall glycaemic control when compared with regular human insulin. A tendency to a reduction in hypoglycaemic events during treatment with fast-acting analogues has been observed in most studies. Recent studies have indicated that NPH insulin...... administered several times daily at mealtimes can improve glycaemic control without increasing the risk of hypoglycaemia. The fast-acting analogues are now also available as insulin mixed with NPH. Insulin glargine is a new long-acting insulin which is soluble and precipitates after injection, resulting...

Cerebral vasculitis associated with Schistosoma mansoni infection

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Camuset Guillaume

2012-09-01

Full Text Available Abstract Background Cerebral involvement in schistosomiasis is not rare, but it is underdiagnosed because of the lack of clinical suspicion and the frequency of asymptomatic forms. Neurologic complications are generally supported by granuloma formation around ectopic eggs which have migrated to the brain. Moreover, vascular lesions and cerebral arteritis have been well documented in histopathological studies. Nevertheless, cerebral vasculitis in later stages of the Schistosoma mansoni infection have not yet been described in living subjects. Case presentation A 28-year-old french woman had a stroke linked with cerebral vasculitis, 6 monthes after returning from Burkina-Faso. At the same time, a S. mansoni disseminated infection was diagnosed. She suffered from a new stroke after undertaking praziquantel therapy, which lead us to associate the S. mansoni infection and cerebral vasculitis. Conclusion This is the first report of such association, since cerebral vasculitis has never been described in later stages of the S. mansoni infection. Although the causal link between the two pathologies could not be proved, we suggest that S. mansoni is able to cause severe vascular damage in cerebral vessels. Schistosomiasis must be investigated in the event of a brain infarct in young people, particularly in patients originating or returning from an endemic area.

Insulin structure and stability.

Science.gov (United States)

Brange, J; Langkjoer, L

1993-01-01

Insulin is composed of 51 amino acids in two peptide chains (A and B) linked by two disulfide bonds. The three-dimensional structure of the insulin molecule (insulin monomer), essentially the same in solution and in solid phase, exists in two main conformations. These differ in the extent of helix in the B chain which is governed by the presence of phenol or its derivatives. In acid and neutral solutions, in concentrations relevant for pharmaceutical formulation, the insulin monomer assembles to dimers and at neutral pH, in the presence of zinc ions, further to hexamers. Many crystalline modifications of insulin have been identified but only those with the hexamer as the basic unit are utilized in preparations for therapy. The insulin hexamer forms a relatively stable unit but some flexibility remains within the individual molecules. The intrinsic flexibility at the ends of the B chain plays an important role in governing the physical and chemical stability of insulin. A variety of chemical changes of the primary structure (yielding insulin derivatives), and physical modifications of the secondary to quaternary structures (resulting in "denaturation," aggregation, and precipitation) are known to affect insulin and insulin preparations during storage and use (Fig. 8). The tendency of insulin to undergo structural transformation resulting in aggregation and formation of insoluble insulin fibrils has been one of the most intriguing and widely studied phenomena in relation to insulin stability. Although the exact mechanism of fibril formation is still obscure, it is now clear that the initial step is an exposure of certain hydrophobic residues, normally buried in the three-dimensional structure, to the surface of the insulin monomer. This requires displacement of the COOH-terminal B-chain residues from their normal position which can only be accomplished via monomerization of the insulin. Therefore, most methods stabilizing insulin against fibrillation share the

Alteration in insulin action

DEFF Research Database (Denmark)

Tanti, J F; Gual, P; Grémeaux, T

2004-01-01

Insulin resistance, when combined with impaired insulin secretion, contributes to the development of type 2 diabetes. Insulin resistance is characterised by a decrease in insulin effect on glucose transport in muscle and adipose tIssue. Tyrosine phosphorylation of insulin receptor substrate 1 (IRS......-1) and its binding to phosphatidylinositol 3-kinase (PI 3-kinase) are critical events in the insulin signalling cascade leading to insulin-stimulated glucose transport. Modification of IRS-1 by serine phosphorylation could be one of the mechanisms leading to a decrease in IRS-1 tyrosine...... to phosphorylate these serine residues have been identified. These exciting results suggest that serine phosphorylation of IRS-1 is a possible hallmark of insulin resistance in biologically insulin responsive cells or tIssues. Identifying the pathways by which "diabetogenic" factors activate IRS-1 kinases...

In nondiabetic, human immunodeficiency virus-infected patients with lipodystrophy, hepatic insulin extraction and posthepatic insulin clearance rate are decreased in proportion to insulin resistance

DEFF Research Database (Denmark)

Haugaard, Steen B; Andersen, Ove; Hansen, Birgitte R

2005-01-01

In healthy, nondiabetic individuals with insulin resistance, fasting insulin is inversely correlated to the posthepatic insulin clearance rate (MCRi) and the hepatic insulin extraction (HEXi). We investigated whether similar early mechanisms to facilitate glucose homeostasis exist in nondiabetic...... endogenous insulin secretion, which was estimated by deconvolution of C-peptide concentrations. Hepatic extraction of insulin was calculated as 1 minus the ratio of fasting posthepatic insulin delivery rate to fasting endogenous insulin secretion rate. Compared with controls, LIPO displayed increased fasting...... insulin (130%, P Hepatic extraction of insulin was similar between groups (LIPO, 55%; controls, 57%; P > .8). In LIPO, HEXi and MCRi correlated inversely with fasting insulin (r = -0.56, P

Schistosoma japonicum transmission risk maps at present and under climate change in mainland China.

Science.gov (United States)

Zhu, Gengping; Fan, Jingyu; Peterson, A Townsend

2017-10-01

The South-to-North Water Diversion (SNWD) project is designed to channel fresh water from the Yangtze River north to more industrialized parts of China. An important question is whether future climate change and dispersal via the SNWD may synergistically favor a northward expansion of species involved in hosting and transmitting schistosomiasis in China, specifically the intermediate host, Oncomelania hupensis. In this study, climate spaces occupied by the four subspecies of O. hupensis (O. h. hupensis, O. h. robertsoni, O. h. guangxiensis and O. h. tangi) were estimated, and niche conservatism tested among each pair of subspecies. Fine-tuned Maxent (fMaxent) and ensemble models were used to anticipate potential distributions of O. hupensis under future climate change scenarios. We were largely unable to reject the null hypothesis that climatic niches are conserved among the four subspecies, so factors other than climate appear to account for the divergence of O. hupensis populations across mainland China. Both model approaches indicated increased suitability and range expansion in O. h. hupensis in the future; an eastward and northward shift in O. h. robertsioni and O. h. guangxiensis, respectively; and relative distributional stability in O. h. gangi. The southern parts of the Central Route of SNWD will coincide with suitable areas for O. h. hupensis in 2050-2060; its suitable areas will also expand northward along the southern parts of the Eastern Route by 2080-2090. Our results call for rigorous monitoring and surveillance of schistosomiasis along the southern Central Route and Eastern Route of the SNWD in a future, warmer China.

Novel covalently linked insulin dimer engineered to investigate the function of insulin dimerization.

Directory of Open Access Journals (Sweden)

Tine N Vinther

Full Text Available An ingenious system evolved to facilitate insulin binding to the insulin receptor as a monomer and at the same time ensure sufficient stability of insulin during storage. Insulin dimer is the cornerstone of this system. Insulin dimer is relatively weak, which ensures dissociation into monomers in the circulation, and it is stabilized by hexamer formation in the presence of zinc ions during storage in the pancreatic β-cell. Due to the transient nature of insulin dimer, direct investigation of this important form is inherently difficult. To address the relationship between insulin oligomerization and insulin stability and function, we engineered a covalently linked insulin dimer in which two monomers were linked by a disulfide bond. The structure of this covalent dimer was identical to the self-association dimer of human insulin. Importantly, this covalent dimer was capable of further oligomerization to form the structural equivalent of the classical hexamer. The covalently linked dimer neither bound to the insulin receptor, nor induced a metabolic response in vitro. However, it was extremely thermodynamically stable and did not form amyloid fibrils when subjected to mechanical stress, underlining the importance of oligomerization for insulin stability.

MicroR-146 blocks the activation of M1 macrophage by targeting signal transducer and activator of transcription 1 in hepatic schistosomiasis

Directory of Open Access Journals (Sweden)

Xing He

2016-11-01

Full Text Available Schistosomiasis is a chronic disease caused by the parasite of the Schistosoma genus and is characterized by egg-induced hepatic granulomas and fibrosis. Macrophages play a central role in schistosomiasis with several studies highlighting their differentiation into M2 cells involved in the survival of infected mice through limitation of immunopathology. However, little is known regarding the mechanisms of regulating macrophage differentiation. Here, we showed that the early stage of infection by Schistosoma japonicum induced expression of type 1 T-helper-cell (Th1 cytokine, interferon-γ (IFN-γ, leading to increase in M1 cells. However, the presence of liver-trapped eggs induced the expression of Th2 cytokines including interleukin-4 (IL-4, IL-10, and IL-13 that upregulated the transcription of miR-146b by activating signal transducer and activator of transcription 3/6 (STAT3/6 that bind to the promoter of the pre-miR-146b gene. We found that the miR-146a/b was significantly upregulated in macrophages during the progression of hepatic schistosomiasis. The elevated miR-146a/b inhibited the IFN-γ-induced differentiation of macrophages to M1 cells through targeting STAT1. Our data indicate the protective roles of miR-146a/b in hepatic schistosomiasis through regulating the differentiation of macrophages into M2 cells.

Insulin resistance in obesity can be reliably identified from fasting plasma insulin

NARCIS (Netherlands)

ter Horst, K. W.; Gilijamse, P. W.; Koopman, K. E.; de Weijer, B. A.; Brands, M.; Kootte, R. S.; Romijn, J. A.; Ackermans, M. T.; Nieuwdorp, M.; Soeters, M. R.; Serlie, M. J.

2015-01-01

Insulin resistance is the major contributor to cardiometabolic complications of obesity. We aimed to (1) establish cutoff points for insulin resistance from euglycemic hyperinsulinemic clamps (EHCs), (2) identify insulin-resistant obese subjects and (3) predict insulin resistance from routinely

Evidence for altered transport of insulin across the blood-brain barrier in insulin-resistant humans.

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Heni, Martin; Schöpfer, Patricia; Peter, Andreas; Sartorius, Tina; Fritsche, Andreas; Synofzik, Matthis; Häring, Hans-Ulrich; Maetzler, Walter; Hennige, Anita M

2014-08-01

Eating behavior, body weight regulation, peripheral glucose metabolism, and cognitive function depend on adequate insulin action in the brain, and recent studies in humans suggested that impaired insulin action in the brain emerges upon fat intake, obesity, and genetic variants. As insulin enters into the brain in a receptor-mediated fashion, we hypothesized that whole-body insulin sensitivity might affect the transport of insulin into the brain and contribute to the aversive effect of insulin resistance in the central nervous system. In this study, we aimed to determine the ratio of insulin in the cerebrospinal fluid and serum to whole-body insulin sensitivity. Healthy human subjects participated in an oral glucose tolerance test to determine whole-body insulin sensitivity and underwent lumbar puncture. Blood and CSF concentrations of insulin were significantly correlated. The CSF/serum ratio for insulin was significantly associated with whole body insulin sensitivity with reduced insulin transported into the CSF in insulin-resistant subjects. Together, our data suggest that transport of insulin into the CSF relates to peripheral insulin sensitivity and impairs insulin action in the brain. This underlines the need for sensitizing measures in insulin-resistant subjects.

Comparison of a soluble co-formulation of insulin degludec/insulin aspart vs biphasic insulin aspart 30 in type 2 diabetes

DEFF Research Database (Denmark)

Niskanen, Leo; Leiter, Lawrence A; Franek, Edward

2012-01-01

Insulin degludec/insulin aspart (IDegAsp) is a soluble co-formulation of insulin degludec (70%) and insulin aspart (IAsp: 30%). Here, we compare the efficacy and safety of IDegAsp, an alternative IDegAsp formulation (AF: containing 45% IAsp), and biphasic IAsp 30 (BIAsp 30)....

Molecular Mechanisms of Insulin Secretion and Insulin Action.

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Flatt, Peter R.; Bailey, Clifford J.

1991-01-01

Information and current ideas on the factors regulating insulin secretion, the mechanisms underlying the secretion and biological actions of insulin, and the main characteristics of diabetes mellitus are presented. (Author)

Synthesis and conjugation of oligosaccharide fragments related to the immunologically reactive part of the circulating anodic antigen of the parasite Schistosoma mansoni

NARCIS (Netherlands)

Vliegenthart, J.F.G.; Vermeer, H.J.; Halkes, K.M.; Kuik, J.A. van; Kamerling, J.P.

2000-01-01

The immunoreactive part of the circulating anodic antigen (CAA) from the parasite Schistosoma mansoni is a threonine-linked polysaccharide consisting of ->6)-[beta-D-GlcpA-(1->3)]-beta-D-GalpNAc-(1-> repeating disaccharides. In the framework of an immunochemical project, as a follow-up of earlier

Insulin Biosynthetic Interaction Network Component, TMEM24, Facilitates Insulin Reserve Pool Release

Directory of Open Access Journals (Sweden)

Anita Pottekat

2013-09-01

Full Text Available Insulin homeostasis in pancreatic β cells is now recognized as a critical element in the progression of obesity and type II diabetes (T2D. Proteins that interact with insulin to direct its sequential synthesis, folding, trafficking, and packaging into reserve granules in order to manage release in response to elevated glucose remain largely unknown. Using a conformation-based approach combined with mass spectrometry, we have generated the insulin biosynthetic interaction network (insulin BIN, a proteomic roadmap in the β cell that describes the sequential interacting partners of insulin along the secretory axis. The insulin BIN revealed an abundant C2 domain-containing transmembrane protein 24 (TMEM24 that manages glucose-stimulated insulin secretion from a reserve pool of granules, a critical event impaired in patients with T2D. The identification of TMEM24 in the context of a comprehensive set of sequential insulin-binding partners provides a molecular description of the insulin secretory pathway in β cells.

Identification of residues in the insulin molecule important for binding to insulin-degrading enzyme

Energy Technology Data Exchange (ETDEWEB)

Affholter, J.A.; Roth, R.A. (Stanford Univ. School of Medicine, CA (USA)); Cascieri, M.A.; Bayne, M.L. (Merck Sharp and Dohme Research Labs., Rahway, NJ (USA)); Brange, J. (Novo Research Institute, Bagsvaerd (Denmark)); Casaretto, M. (Deutsches Wollforschungsinstitut an der Technischen, Aachen (West Germany))

1990-08-21

Insulin-degrading enzyme (IDE) hydrolyzes insulin at a limited number of sites. Although the positions of these cleavages are known, the residues of insulin important in its binding to IDE have not been defined. To this end, the authors have studied the binding of a variety of insulin analogues to the protease in a solid-phase binding assay using immunoimmobilized IDE. Since IDE binds insulin with 600-fold greater affinity than it does insulin-like growth factor, the first set of analogues studied were hybrid molecules of insulin and IGF I. Removal of the eight amino acid D-chain region of IGF I (which has been predicted to interfere with binding to the 23-25 region) results in a 25-fold increase in affinity for IDE, confirming the importance of residues 23-25 in the high-affinity recognition of IDE. A similar role for the corresponding (B24-26) residues of insulin is supported by the use of site-directed mutant and semisynthetic insulin analogues. Insulin mutants (B25-Asp)insulin and (B25-His)insulin display 16- and 20-fold decreases in IDE affinity versus wild-type insulin. Similar decreases in affinity are observed with the C-terminal truncation mutants (B1-24-His{sup 25}-NH{sub 2})insulin and (B1-24-Leu{sup 25}-NH{sub 2})insulin, but not (B1-24-Trp{sup 25}-NH{sub 2})insulin and (B1-24-Tyr{sup 25}-NH{sub 2})insulin. The truncated analogue with the lowest affinity for IDE ((B1-24-His{sup 25}-NH{sub 2})insulin) has one of the highest affinities for the insulin receptor. Therefore, they have identified a region of the insulin molecule responsible for its high-affinity interaction with IDE. Although the same region has been implicated in the binding of insulin to its receptor, the data suggest that the structural determinants required for binding to receptor and IDE differ.

Identification of residues in the insulin molecule important for binding to insulin-degrading enzyme

International Nuclear Information System (INIS)

Affholter, J.A.; Roth, R.A.; Cascieri, M.A.; Bayne, M.L.; Brange, J.; Casaretto, M.

1990-01-01

Insulin-degrading enzyme (IDE) hydrolyzes insulin at a limited number of sites. Although the positions of these cleavages are known, the residues of insulin important in its binding to IDE have not been defined. To this end, the authors have studied the binding of a variety of insulin analogues to the protease in a solid-phase binding assay using immunoimmobilized IDE. Since IDE binds insulin with 600-fold greater affinity than it does insulin-like growth factor, the first set of analogues studied were hybrid molecules of insulin and IGF I. Removal of the eight amino acid D-chain region of IGF I (which has been predicted to interfere with binding to the 23-25 region) results in a 25-fold increase in affinity for IDE, confirming the importance of residues 23-25 in the high-affinity recognition of IDE. A similar role for the corresponding (B24-26) residues of insulin is supported by the use of site-directed mutant and semisynthetic insulin analogues. Insulin mutants [B25-Asp]insulin and [B25-His]insulin display 16- and 20-fold decreases in IDE affinity versus wild-type insulin. Similar decreases in affinity are observed with the C-terminal truncation mutants [B1-24-His 25 -NH 2 ]insulin and [B1-24-Leu 25 -NH 2 ]insulin, but not [B1-24-Trp 25 -NH 2 ]insulin and [B1-24-Tyr 25 -NH 2 ]insulin. The truncated analogue with the lowest affinity for IDE ([B1-24-His 25 -NH 2 ]insulin) has one of the highest affinities for the insulin receptor. Therefore, they have identified a region of the insulin molecule responsible for its high-affinity interaction with IDE. Although the same region has been implicated in the binding of insulin to its receptor, the data suggest that the structural determinants required for binding to receptor and IDE differ

Continuation versus discontinuation of insulin secretagogues when initiating insulin in type 2 diabetes

NARCIS (Netherlands)

Swinnen, S. G.; Dain, M.-P.; Mauricio, D.; DeVries, J. H.; Hoekstra, J. B.; Holleman, F.

2010-01-01

We compared the combined use of basal insulin, metformin and insulin secretagogues with a combination of basal insulin and metformin in patients with type 2 diabetes starting basal insulin analogue therapy. This analysis was part of a 24-week trial, in which 964 insulin-naive patients with type 2

Exogenous insulin antibody syndrome (EIAS): a clinical syndrome associated with insulin antibodies induced by exogenous insulin in diabetic patients.

Science.gov (United States)

Hu, Xiaolei; Chen, Fengling

2018-01-01

Insulin has been used for diabetes therapy and has achieved significant therapeutic effect. In recent years, the use of purified and recombinant human insulin preparations has markedly reduced, but not completely suppressed, the incidence of insulin antibodies (IAs). IAs induced by exogenous insulin in diabetic patients is associated with clinical events, which is named exogenous insulin antibody syndrome (EIAS). The present review is based on our research and summarizes the characterization of IAs, the factors affecting IA development, the clinical significance of IAs and the treatments for EIAS. © 2018 The authors.

The effect of tubing dwell time on insulin adsorption during intravenous insulin infusions.

Science.gov (United States)

Thompson, Cecilia D; Vital-Carona, Jessica; Faustino, E Vincent S

2012-10-01

Insulin adsorbs to plastic tubing, which decreases the concentration of an insulin solution delivered from an intravenous infusion set. Dwelling insulin within tubing before starting the infusion decreases adsorption but delays treatment initiation and wastes time in infusion preparation. The lack of data on dwell time effects results in wide variability in practice. We aim to determine the effect of dwell time on insulin concentration from intravenous infusion tubing. In this in vitro study, we used insulin solutions with concentrations of 0.1 unit/mL, 1 unit/mL, and 10 units/mL. Each solution dwelled in intravenous infusion sets for 0, 15, 30, or 60 min. After the dwell, we measured insulin concentrations from the solution bags and tubing. We repeated each insulin concentration-dwell time combination five times. Comparisons were performed using analyses of variance. For each of the three insulin concentrations, the mean insulin concentrations from the tubing were not significantly different between dwell times. Duration of dwell time did not affect insulin adsorption in polypropylene intravenous infusion sets. We recommend that following a 20-mL flush, insulin infusions can be started without any dwell time. Removal of dwell times may improve clinical practice by minimizing preparation time and will allow faster initiation of insulin infusion therapy.

Intensive insulin therapy improves insulin sensitivity and mitochondrial function in severely burned children.

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Fram, Ricki Y; Cree, Melanie G; Wolfe, Robert R; Mlcak, Ronald P; Qian, Ting; Chinkes, David L; Herndon, David N

2010-06-01

To institute intensive insulin therapy protocol in an acute pediatric burn unit and study the mechanisms underlying its benefits. Prospective, randomized study. An acute pediatric burn unit in a tertiary teaching hospital. Children, 4-18 yrs old, with total body surface area burned > or =40% and who arrived within 1 wk after injury were enrolled in the study. Patients were randomized to one of two groups. Intensive insulin therapy maintained blood glucose levels between 80 and 110 mg/dL. Conventional insulin therapy maintained blood glucose patients were included in the data analysis consisting of resting energy expenditure, whole body and liver insulin sensitivity, and skeletal muscle mitochondrial function. Studies were performed at 7 days postburn (pretreatment) and at 21 days postburn (posttreatment). Resting energy expenditure significantly increased posttreatment (1476 +/- 124 to 1925 +/- 291 kcal/m(2) x day; p = .02) in conventional insulin therapy as compared with a decline in intensive insulin therapy. Glucose infusion rate was identical between groups before treatment (6.0 +/- 0.8 conventional insulin therapy vs. 6.8 +/- 0.9 mg/kg x min intensive insulin therapy; p = .5). Intensive insulin therapy displayed a significantly higher glucose clamp infusion rate posttreatment (9.1 +/- 1.3 intensive insulin therapy versus 4.8 +/- 0.6 mg/kg x min conventional insulin therapy, p = .005). Suppression of hepatic glucose release was significantly greater in the intensive insulin therapy after treatment compared with conventional insulin therapy (5.0 +/- 0.9 vs. 2.5 +/- 0.6 mg/kg x min; intensive insulin therapy vs. conventional insulin therapy; p = .03). States 3 and 4 mitochondrial oxidation of palmitate significantly improved in intensive insulin therapy (0.9 +/- 0.1 to 1.7 +/- 0.1 microm O(2)/CS/mg protein/min for state 3, p = .004; and 0.7 +/- 0.1 to 1.3 +/- 0.1 microm O(2)/CS/mg protein/min for state 4, p protocol improves insulin sensitivity and mitochondrial

Green synthesis of silver nanoparticles using Ganoderma neo-japonicum Imazeki: a potential cytotoxic agent against breast cancer cells

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Gurunathan, Sangiliyandi; Raman, Jegadeesh; Malek, Sri Nurestri Abd; John, Priscilla A; Vikineswary, Sabaratnam

2013-01-01

Background Silver nanoparticles (AgNPs) are an important class of nanomaterial for a wide range of industrial and biomedical applications. AgNPs have been used as antimicrobial and disinfectant agents due their detrimental effect on target cells. The aim of our study was to determine the cytotoxic effects of biologically synthesized AgNPs using hot aqueous extracts of the mycelia of Ganoderma neo-japonicum Imazeki on MDA-MB-231 human breast cancer cells. Methods We developed a green method for the synthesis of water-soluble AgNPs by treating silver ions with hot aqueous extract of the mycelia of G. neo-japonicum. The formation of AgNPs was characterized by ultraviolet-visible absorption spectroscopy, X-ray diffraction, dynamic light scattering, and transmission electron microscopy. Furthermore, the toxicity of synthesized AgNPs was evaluated using a series of assays: such as cell viability, lactate dehydrogenase leakage, reactive oxygen species generation, caspase 3, DNA laddering, and terminal deoxynucleotidyl transferase deoxyuridine triphosphate nick-end labeling in human breast cancer cells (MDA-MB-231). Results The ultraviolet-visible absorption spectroscopy results showed a strong resonance centered on the surface of AgNPs at 420 nm. The X-ray diffraction analysis confirmed that the synthesized AgNPs were single-crystalline, corresponding with the result of transmission electron microscopy. Treatment of MDA-MB-231 breast cancer cells with various concentrations of AgNPs (1–10 μg/mL) for 24 hours revealed that AgNPs could inhibit cell viability and induce membrane leakage in a dose-dependent manner. Cells exposed to AgNPs showed increased reactive oxygen species and hydroxyl radical production. Furthermore, the apoptotic effects of AgNPs were confirmed by activation of caspase 3 and DNA nuclear fragmentation. Conclusion The results indicate that AgNPs possess cytotoxic effects with apoptotic features and suggest that the reactive oxygen species generated by

Insulin-loaded poly(epsilon-caprolactone) nanoparticles: efficient, sustained and safe insulin delivery system.

Science.gov (United States)

de Araújo, Thiago M; Teixeira, Zaine; Barbosa-Sampaio, Helena C; Rezende, Luiz F; Boschero, Antonio C; Durán, Nelson; Höehr, Nelci F

2013-06-01

The aim of this work was to develop an efficient, biodegradable, biocompatible and safe controlled release system using insulin-loaded poly(epsilon-caprolactone) (PCL) nanoparticles. The insulin-loaded PCL nanoparticles were prepared by double emulsion method (water-in-oil-in-water) using Pluronic F68 as emulsifier. Using the double emulsion method a high insulin encapsulation efficiency (90.6 +/-1.6%) with a zeta potential of -29 +/-2.7 mV and average particle size of 796 +/-10.5 nm was obtained. Insulin-loaded PCL nanoparticles showed no toxicity to MIN6 cells. Insulin nanoparticles administered subcutaneously and intraperitoneally in rats reduced glycaemia of basal levels after 15 minutes, and presented a sustainable hypoglycemic effect on insulin-dependent type 1 diabetic rats, showing to be more efficient than unencapsulated insulin. Furthermore, these nanoparticles were not hepatotoxic, as evaluated by the effect over liver cell-death and oxidative stress scavenger system in rats. These results suggest that insulin-loaded PCL nanoparticles prepared by water-in-oil-in-water emulsion method are biocompatible, efficient and safe insulin-delivering system with controlled insulin release, which indicates that it may be a powerful tool for insulin-dependent patients care.

Point-of-care mobile digital microscopy and deep learning for the detection of soil-transmitted helminths and Schistosoma haematobium.

Science.gov (United States)

Holmström, Oscar; Linder, Nina; Ngasala, Billy; Mårtensson, Andreas; Linder, Ewert; Lundin, Mikael; Moilanen, Hannu; Suutala, Antti; Diwan, Vinod; Lundin, Johan

2017-06-01

Microscopy remains the gold standard in the diagnosis of neglected tropical diseases. As resource limited, rural areas often lack laboratory equipment and trained personnel, new diagnostic techniques are needed. Low-cost, point-of-care imaging devices show potential in the diagnosis of these diseases. Novel, digital image analysis algorithms can be utilized to automate sample analysis. Evaluation of the imaging performance of a miniature digital microscopy scanner for the diagnosis of soil-transmitted helminths and Schistosoma haematobium, and training of a deep learning-based image analysis algorithm for automated detection of soil-transmitted helminths in the captured images. A total of 13 iodine-stained stool samples containing Ascaris lumbricoides, Trichuris trichiura and hookworm eggs and 4 urine samples containing Schistosoma haematobium were digitized using a reference whole slide-scanner and the mobile microscopy scanner. Parasites in the images were identified by visual examination and by analysis with a deep learning-based image analysis algorithm in the stool samples. Results were compared between the digital and visual analysis of the images showing helminth eggs. Parasite identification by visual analysis of digital slides captured with the mobile microscope was feasible for all analyzed parasites. Although the spatial resolution of the reference slide-scanner is higher, the resolution of the mobile microscope is sufficient for reliable identification and classification of all parasites studied. Digital image analysis of stool sample images captured with the mobile microscope showed high sensitivity for detection of all helminths studied (range of sensitivity = 83.3-100%) in the test set (n = 217) of manually labeled helminth eggs. In this proof-of-concept study, the imaging performance of a mobile, digital microscope was sufficient for visual detection of soil-transmitted helminths and Schistosoma haematobium. Furthermore, we show that deep

Insulin pumps and insulin quality--requirements and problems.

Science.gov (United States)

Brange, J; Havelund, S

1983-01-01

In developing insulin solution suitable for delivery devices the chemical and biological stability, as well as the physical stability, must be taken into consideration. Addition of certain mono- and disaccharides increases the physical stability of neutral insulin solutions, but concurrently the chemical and biological stability decrease to an unacceptable degree. Addition of Ca-ions in low concentrations offers a physiologically acceptable method for stabilizing neutral insulin solutions against heat precipitation without affecting the quality, including the chemical and biological stability.

Insulin-stimulated glucose uptake in healthy and insulin-resistant skeletal muscle

DEFF Research Database (Denmark)

Deshmukh, Atul S

2016-01-01

transporter protein 4 (GLUT4) to the plasma membrane which leads to facilitated diffusion of glucose into the cell. Understanding the precise signaling events guiding insulin-stimulated glucose uptake is pivotal, because impairment in these signaling events leads to development of insulin resistance and type...... 2 diabetes. This review summarizes current understanding of insulin signaling pathways mediating glucose uptake in healthy and insulin-resistant skeletal muscle....

Toward understanding insulin fibrillation.

Science.gov (United States)

Brange, J; Andersen, L; Laursen, E D; Meyn, G; Rasmussen, E

1997-05-01

Formation of insulin fibrils is a physical process by which partially unfolded insulin molecules interact with each other to form linear aggregates. Shielding of hydrophobic domains is the main driving force for this process, but formation of intermolecular beta-sheet may further stabilize the fibrillar structure. Conformational displacement of the B-chain C-terminal with exposure of nonpolar, aliphatic core residues, including A2, A3, B11, and B15, plays a crucial role in the fibrillation process. Recent crystal analyses and molecular modeling studies have suggested that when insulin fibrillates this exposed domain interacts with a hydrophobic surface domain formed by the aliphatic residues A13, B6, B14, B17, and B18, normally buried when three insulin dimers form a hexamer. In rabbit immunization experiments, insulin fibrils did not elicit an increased immune response with respect to formation of IgG insulin antibodies when compared with native insulin. In contrast, the IgE response increased with increasing content of insulin in fibrillar form. Strategies and practical approaches to prevent insulin from forming fibrils are reviewed. Stabilization of the insulin hexameric structure and blockage of hydrophobic interfaces by addition of surfactants are the most effective means of counteracting insulin fibrillation.

Reductive methylation of insulin. Production of a biologically active tritiated insulin

Energy Technology Data Exchange (ETDEWEB)

Marsh, J W; Nahum, A; Steiner, D F [Department of Biochemistry, University of Chicago, Illinois, USA

1983-01-01

Reductive methylation of the three amino groups of porcine insulin was accomplished by incubation with formaldehyde and sodium cyanoborohydride. The two amino termini and the epsilon amino group of B29 lysine were each dimethylated within 1 h of incubation. The fully methylated insulin bound more tightly to a reverse phase column than did native insulin, had a slightly more acid isoelectric point, and maintained approximately 50% biological activity when examined with an insulin sensitive cultured cell line. Reductive methylation with sodium cyanoboro (/sup 3/H) hydride resulted in a (/sup 3/H) methylated insulin with a specific activity of 6 Ci/mmol.

Depressive symptoms, insulin sensitivity and insulin secretion in the RISC cohort study

DEFF Research Database (Denmark)

Bot, M; Pouwer, F; De Jonge, P

2013-01-01

Sensitivity and Cardiovascular Disease Risk (RISC) study. Presence of significant depressive symptoms was defined as a Center for Epidemiologic Studies Depression Scale (CES-D) score ≥ 16. Standard oral glucose tolerance tests were performed. Insulin sensitivity was assessed with the oral glucose insulin......AIM: This study explored the association of depressive symptoms with indices of insulin sensitivity and insulin secretion in a cohort of non-diabetic men and women aged 30 to 64 years. METHODS: The study population was derived from the 3-year follow-up of the Relationship between Insulin...... sensitivity (OGIS) index. Insulin secretion was estimated using three model-based parameters of insulin secretion (beta-cell glucose sensitivity, the potentiation factor ratio, and beta-cell rate sensitivity). RESULTS: A total of 162 out of 1027 participants (16%) had significant depressive symptoms. Having...

Insulin aspart in diabetic pregnancy

DEFF Research Database (Denmark)

Mathiesen, Elisabeth R

2008-01-01

in insulin requirements during pregnancy necessitate short-acting insulins for postprandial control of hyperglycemia. The fast-acting insulin analogue insulin aspart has been tested in a large, randomized trial of pregnant women with Type 1 diabetes and offers benefits in control of postprandial...... hyperglycemia with a tendency towards fewer episodes of severe hypoglycemia compared with human insulin. Treatment with insulin aspart was associated with a tendency toward fewer fetal losses and preterm deliveries than treatment with human insulin. Insulin aspart could not be detected in the fetal circulation...... and no increase in insulin antibodies was found. Thus, the use of insulin aspart in pregnancy is regarded safe....

Evaluation of symbiotic performance of some mutant lines of soybean inoculated with two bradyrhizobium japonicum strains using 15N technique

International Nuclear Information System (INIS)

Kurdali, F.; Mir-Ali, N.; Al-Nabulsi, I.

2002-11-01

A pot experiment was conducted to study the symbiotic performance of two soybean varieties and some of their mutants (that were obtained as a result of a previous mutation breeding program) with two bradyrhizobium japonicum strains (RG and FA3) using 15 N isotopic dilution method. Random amplified polymorphic DNA technique (RAPD) was used to study the genetic relationships among the soybean genotypes and to make sure that the two rhizobial strains are different. The 25 random primers used discriminated the different soybean genotypes and the dendrogram resultants from shared polymorphic fragments put each variety and its mutants in two separate clusters asserting that the mutants and their mother lines are different. Both strains of B. japonicum were able to form effective nodules on all soybean plants. However, number of nodules, dry matter yield and N-uptake from the available sources by soybeans were affected by both plant genotype and rhizobial strains. N 2 -fixation was affected to a large extent by different strain and plant genotype combinations. Percentage of fixed N 2 (N dfa) ranged between 35 and 49%; whereas, the actual amounts of fixed N 2 were between 105 and 210 mg N/pot. Amounts of N 2 -fixed by FA3 strain were higher than of RG in both soybean varieties, whereas, the latter strain showed higher performance in the mutant lines. The results showed that total plant N estimation may not be a sufficient indicator for high N 2 -fixation. the results also showed that it is very important to determine both the amount of nitrogen derived from N 2 -fixation and N derived from soil for evaluating the symbiotic performance ability. Moreover, the performance of symbiotic N 2 -fixation in soybean was shown to depend on both plant genotype and rhizobial strain and the amount of N 2 -fixation can be increased by combining the best plant genotypes and the most adapted strain. (author)

Comparison of metformin and insulin versus insulin alone for type 2 diabetes

DEFF Research Database (Denmark)

Hemmingsen, Bianca; Christensen, Louise Lundby; Wetterslev, Jørn

2012-01-01

To compare the benefits and harms of metformin and insulin versus insulin alone as reported in randomised clinical trials of patients with type 2 diabetes.......To compare the benefits and harms of metformin and insulin versus insulin alone as reported in randomised clinical trials of patients with type 2 diabetes....

In nondiabetic, human immunodeficiency virus-infected patients with lipodystrophy, hepatic insulin extraction and posthepatic insulin clearance rate are decreased in proportion to insulin resistance

DEFF Research Database (Denmark)

Haugaard, Steen B; Andersen, Ove; Hansen, Birgitte R

2005-01-01

In healthy, nondiabetic individuals with insulin resistance, fasting insulin is inversely correlated to the posthepatic insulin clearance rate (MCRi) and the hepatic insulin extraction (HEXi). We investigated whether similar early mechanisms to facilitate glucose homeostasis exist in nondiabetic...... > .1). Our data suggest that HEXi and MCRi are decreased in proportion to the degree of insulin resistance in nondiabetic HIV-infected patients with lipodystrophy....... insulin clearance rate was estimated as the ratio of posthepatic insulin appearance rate to steady-state plasma insulin concentration during a euglycemic hyperinsulinemic clamp (40 mU.m-2 .min-1). Posthepatic insulin appearance rate during the clamp was calculated, taking into account the remnant...

Insulin glulisine compared to insulin aspart and to insulin lispro administered by continuous subcutaneous insulin infusion in patients with type 1 diabetes: a randomized controlled trial

NARCIS (Netherlands)

van Bon, Arianne C.; Bode, Bruce W.; Sert-Langeron, Caroline; DeVries, J. Hans; Charpentier, Guillaume

2011-01-01

In a previous pilot study comparing insulin glulisine (GLU) with insulin aspart (ASP) administered by continuous subcutaneous insulin infusion (CSII), GLU-treated patients did show a trend toward fewer catheter occlusions compared with ASP-treated patients. Here we performed a randomized open-label,

Comparison of insulin analogue B9AspB27Glu and soluble human insulin in insulin-treated diabetes.

Science.gov (United States)

Kang, S; Owens, D R; Vora, J P; Brange, J

1990-02-10

Postprandial plasma glucose excursions and plasma levels of free insulin after subcutaneous bolus injection of a rapidly absorbed monomeric insulin analogue (B9AspB27Glu) or soluble human insulin ('Actrapid HM' U100) were studied in six insulin-treated diabetic subjects. 10 U actrapid or an equimolar amount of the analogue were injected, in random order with an interval of 1 week, immediately before a 500 kcal test meal. Basal insulin levels were similar on the 2 study days (mean 74.1 [SE 5.1] pmol/l, actrapid; 79.7 [13.0] pmol/l, analogue). After injection of actrapid plasma free insulin levels rose slowly, reaching a plateau by 105 min at 222 (19) pmol/l. Injection of the analogue resulted in a rapid early peak at 30 min (798 [112] pmol/l), and levels were significantly higher than those after actrapid between 15 and 210 min. The more physiological plasma insulin levels achieved with the analogue were accompanied by a substantial reduction in postprandial plasma glucose excursions; the integrated area under the incremental plasma glucose curve was 45% lower after the analogue than after actrapid.

Mechanical stress regulates insulin sensitivity through integrin-dependent control of insulin receptor localization.

Science.gov (United States)

Kim, Jung; Bilder, David; Neufeld, Thomas P

2018-01-15

Insulin resistance, the failure to activate insulin signaling in the presence of ligand, leads to metabolic diseases, including type 2 diabetes. Physical activity and mechanical stress have been shown to protect against insulin resistance, but the molecular mechanisms remain unclear. Here, we address this relationship in the Drosophila larval fat body, an insulin-sensitive organ analogous to vertebrate adipose tissue and livers. We found that insulin signaling in Drosophila fat body cells is abolished in the absence of physical activity and mechanical stress even when excess insulin is present. Physical movement is required for insulin sensitivity in both intact larvae and fat bodies cultured ex vivo. Interestingly, the insulin receptor and other downstream components are recruited to the plasma membrane in response to mechanical stress, and this membrane localization is rapidly lost upon disruption of larval or tissue movement. Sensing of mechanical stimuli is mediated in part by integrins, whose activation is necessary and sufficient for mechanical stress-dependent insulin signaling. Insulin resistance develops naturally during the transition from the active larval stage to the immotile pupal stage, suggesting that regulation of insulin sensitivity by mechanical stress may help coordinate developmental programming with metabolism. © 2018 Kim et al.; Published by Cold Spring Harbor Laboratory Press.

Therapeutic effect of Arctium lappa in Schistosoma haematobium associated kidney disturbance: biochemical and molecular effects.

Science.gov (United States)

Koriem, Khaled M M; Idris, Zulzamri H; Haron, Hasniza F; Omar, Nurulhuda A; Lazain, Halita S

2016-12-01

Schistosoma haematobium ( S. haematobium ) infection has been found to be strongly associated with bladder cancer, which necessitates for discover of a natural new therapeutic agent. The aim of this study was to evaluate the therapeutic effect of Arctium lappa seed extract in S. haematobium associated kidney disturbance. Forty male albino mice were used and divided into four equal groups; group 1 control includes non-infected healthy mice, groups 2, 3 and 4 subcutaneous infected with S. haematobium cercariae. Groups 3 co-treated daily with oral dose of A. lappa seed extract (300 mg/kg, bwt) for 15 days in the same time of S. haematobium infection. Groups 4 post-treated daily for 15 days with oral dose of A. lappa seed extract (300 mg/kg, bwt) after 15 days of S. haematobium infection. The results obtained revealed that S. haematobium significantly decreased kidney weight and serum sodium, potassium and chloride, but increased urinary volume, urinary excretion of sodium, potassium and chloride, serum urea, creatinine and uric acid. Schistosoma haematobium also significantly decreased kidney superoxide dismutase, glutathione peroxidase and reduced glutathione levels while increased kidney lipid peroxidation level. Co- and post-treatment with A. lappa seed extract restore all the above parameters to approach the normal values. These results were supported with histopathological examinations. In conclusion, A. lappa seed extract has therapeutic effect in kidney disturbance caused by S. haematobium where co-treatment of A. lappa seed extract was more effective than post-treatment of the extract.

Inheritance of Schistosoma mansoni infection incompatibility in Biomphalaria alexandrina snails

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Iman F Abou El Naga

2010-03-01

Full Text Available In this study, we looked at the inheritance of susceptibility and resistance to Schistosoma mansoni infection in the first generation of crossbred Biomphalaria alexandrina snails. Our ultimate goal is to use such information to develop a biological method of controlling schistosomiasis. We infected laboratory-bred snails with S. mansoni miracidia and examined cercarial shedding to determine susceptibility and resistance. Five parental groups were used: Group I contained 30 susceptible snails, Group II contained 30 resistant snails, Group III contained 15 susceptible and 15 resistant snails, Group IV contained 27 susceptible and three resistant snails and Group V contained three susceptible and 27 resistant snails. The percentage of resistant snails in the resulting progeny varied according to the ratio of susceptible and resistant parents per group; they are 7%, 100%, 68%, 45% and 97% from Groups I, II, III, IV and V, respectively. On increasing the percentage of resistant parent snails, the percentage of resistant progeny increased, while cercarial production in their susceptible progeny decreased.

Insulin and Insulin-Sensitizing Drugs in Neurodegeneration: Mitochondria as Therapeutic Targets

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Paula I. Moreira

2009-12-01

Full Text Available Insulin, besides its glucose lowering effects, is involved in the modulation of lifespan, aging and memory and learning processes. As the population ages, neurodegenerative disorders become epidemic and a connection between insulin signaling dysregulation, cognitive decline and dementia has been established. Mitochondria are intracellular organelles that despite playing a critical role in cellular metabolism are also one of the major sources of reactive oxygen species. Mitochondrial dysfunction, oxidative stress and neuroinflammation, hallmarks of neurodegeneration, can result from impaired insulin signaling. Insulin-sensitizing drugs such as the thiazolidinediones are a new class of synthetic compounds that potentiate insulin action in the target tissues and act as specific agonists of the peroxisome proliferator-activated receptor gamma (PPAR-γ. Recently, several PPAR agonists have been proposed as novel and possible therapeutic agents for neurodegenerative disorders. Indeed, the literature shows that these agents are able to protect against mitochondrial dysfunction, oxidative damage, inflammation and apoptosis. This review discusses the role of mitochondria and insulin signaling in normal brain function and in neurodegeneration. Furthermore, the potential protective role of insulin and insulin sensitizers in Alzheimer´s, Parkinson´s and Huntington´s diseases and amyotrophic lateral sclerosis will be also discussed.

Cytosine methylation is a conserved epigenetic feature found throughout the phylum Platyhelminthes

Science.gov (United States)

2013-01-01

Background The phylum Platyhelminthes (flatworms) contains an important group of bilaterian organisms responsible for many debilitating and chronic infectious diseases of human and animal populations inhabiting the planet today. In addition to their biomedical and veterinary relevance, some platyhelminths are also frequently used models for understanding tissue regeneration and stem cell biology. Therefore, the molecular (genetic and epigenetic) characteristics that underlie trophic specialism, pathogenicity or developmental maturation are likely to be pivotal in our continued studies of this important metazoan group. Indeed, in contrast to earlier studies that failed to detect evidence of cytosine or adenine methylation in parasitic flatworm taxa, our laboratory has recently defined a critical role for cytosine methylation in Schistosoma mansoni oviposition, egg maturation and ovarian development. Thus, in order to identify whether this epigenetic modification features in other platyhelminth species or is a novelty of S. mansoni, we conducted a study simultaneously surveying for DNA methylation machinery components and DNA methylation marks throughout the phylum using both parasitic and non-parasitic representatives. Results Firstly, using both S. mansoni DNA methyltransferase 2 (SmDNMT2) and methyl-CpG binding domain protein (SmMBD) as query sequences, we illustrate that essential DNA methylation machinery components are well conserved throughout the phylum. Secondly, using both molecular (methylation specific amplification polymorphism, MSAP) and immunological (enzyme-linked immunoabsorbent assay, ELISA) methodologies, we demonstrate that representative species (Echinococcus multilocularis, Protopolystoma xenopodis, Schistosoma haematobium, Schistosoma japonicum, Fasciola hepatica and Polycelis nigra) within all four platyhelminth classes (Cestoda, Monogenea, Trematoda and ‘Turbellaria’) contain methylated cytosines within their genome compartments

Classifying insulin regimens

DEFF Research Database (Denmark)

Neu, A; Lange, K; Barrett, T

2015-01-01

Modern insulin regimens for the treatment of type 1 diabetes are highly individualized. The concept of an individually tailored medicine accounts for a broad variety of different insulin regimens applied. Despite clear recommendations for insulin management in children and adolescents with type 1...

Globular adiponectin ameliorates metabolic insulin resistance via AMPK-mediated restoration of microvascular insulin responses

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Zhao, Lina; Fu, Zhuo; Wu, Jing; Aylor, Kevin W; Barrett, Eugene J; Cao, Wenhong; Liu, Zhenqi

2015-01-01

Abstract Hypoadiponectinaemia is closely associated with endothelial dysfunction and insulin resistance, and microvasculature plays a critical role in the regulation of insulin action in muscle. Here we tested whether adiponectin replenishment could improve metabolic insulin sensitivity in male rats fed a high-fat diet (HFD) via the modulation of microvascular insulin responses. Male Sprague–Dawley rats were fed either a HFD or low-fat diet (LFD) for 4 weeks. Small resistance artery myograph changes in tension, muscle microvascular recruitment and metabolic response to insulin were determined. Compared with rats fed a LFD, HFD feeding abolished the vasodilatory actions of globular adiponectin (gAd) and insulin on pre-constricted distal saphenous arteries. Pretreatment with gAd improved insulin responses in arterioles isolated from HFD rats, which was blocked by AMP-activated protein kinase (AMPK) inhibition. Similarly, HFD abolished microvascular responses to either gAd or insulin and decreased insulin-stimulated glucose disposal by ∼60%. However, supplementing gAd fully rescued insulin’s microvascular action and significantly improved the metabolic responses to insulin in HFD male rats and these actions were abolished by inhibition of either AMPK or nitric oxide production. We conclude that HFD induces vascular adiponectin and insulin resistance but gAd administration can restore vascular insulin responses and improve insulin’s metabolic action via an AMPK- and nitric oxide-dependent mechanism in male rats. Key points Adiponectin is an adipokine with anti-inflammatory and anti-diabetic properties. Hypoadiponectinaemia is closely associated with endothelial dysfunction and insulin resistance in obesity and diabetes. Insulin resistance is present in muscle microvasculature and this may contribute to decreased insulin delivery to, and action in, muscle. In this study we examined whether adiponectin ameliorates metabolic insulin resistance by affecting muscle

Estudos preliminares com bromoacetamida, um novo moluscicida

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Naftale Katz

1985-09-01

Full Text Available A bromoacetamida tem sido testada como moluscicida na República Popular da China, para tratamento de criadouros de Oncomelania, hospedeiro do Schistosoma japonicum, com bons resultados. O produto é solúvel em água, o que simplifica seu uso. Foram feitos ensaios biológicos preliminares deste produto em caramujos adultos (Biomphalaria glabrata, B. tenagophila e B. straminea, recém-eclodidos e desovas. Paralelamente foram feitos ensaios com o pentaclorofenol para avaliar a suscetibilidade dos caramujos. O produto foi testado também sobre peixes, Lebistes reticulatus. Os moluscos testados mediam 8-10 mm de diâmetro; os recém-eclodidos tinham 1-3 dias de idade e as desovas 0-1 dia de idade. A temperatura da água durante os experimentos variou de 24,3 a 27,0°C. O produto foi ativo para caramujos adultos, recém-eclodidos e desovas, em concentrações em tomo de 1 a 4 ppm. Para os peixes o produto foi menos tóxico do que para os caramujos (CLço 7,5 ppm. Estes resultados indicam que a bromoacetamida apresenta propriedades moluscicidas promissoras para o controle da Biomphalaria spp.Bromocetamide has been tested as molluscicide, with good results, in the People's Republic of China, on Oncomelania, host of Schistosoma japonicum. We have conducted preliminary assays with bromoacetamide on adult snails (B. glabrata, B. tenagophila and B. straminea, newly hatched smails and egg-masses. This product has been also tested on fishes (Lebistes reticulatus. Comparative assays have been made with pentaclorophenol to evaluate the suceptibility of the snails. Snails tested had a diameter of 8-10 mm; the newly hatched were 1-3 days old and the eggs-masses. 0-1 day old. The temperature of the water varied from 24.3 to 27.5° C. Bromoacetamide was active on adult and newly hatched snails and egg-masses, in concentrations from 1-4ppm. The product was less toxic for jish (LC90 = 7,5 ppm. These results indicate that bromoacetamide has promising molluscicide

A Rapid Monitoring and Evaluation Method of Schistosomiasis Based on Spatial Information Technology.

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Wang, Yong; Zhuang, Dafang

2015-12-12

Thanks to Spatial Information Technologies (SITs) such as Remote Sensing (RS) and Geographical Information System (GIS) that are being quickly developed and updated, SITs are being used more widely in the public health field. The use of SITs to study the characteristics of the temporal and spatial distribution of Schistosoma japonicum and to assess the risk of infection provides methods for the control and prevention of schistosomiasis japonica has gradually become a hot topic in the field. The purpose of the present paper was to use RS and GIS technology to develop an efficient method of prediction and assessment of the risk of schistosomiasis japonica. We choose the Yueyang region, close to the east DongTing Lake (Hunan Province, China), as the study area, where a recent serious outbreak of schistosomiasis japonica took place. We monitored and evaluated the transmission risk of schistosomiasis japonica in the region using SITs. Water distribution data were extracted from RS images. The ground temperature, ground humidity and vegetation index were calculated based on RS images. Additionally, the density of oncomelania snails, which are the Schistosoma japonicum intermediate host, was calculated on the base of RS data and field measurements. The spatial distribution of oncomelania snails was explored using SITs in order to estimate the area surrounding the residents with transmission risk of schistosomiasis japonica. Our research result demonstrated: (1) the risk factors for the transmission of schistosomiasis japonica were closely related to the living environment of oncomelania snails. Key factors such as water distribution, ground temperature, ground humidity and vegetation index can be quickly obtained and calculated from RS images; (2) using GIS technology and a RS deduction technique along with statistical regression models, the density distribution model of oncomelania snails could be quickly built; (3) using SITs and analysis with overlaying population

Insulin aspart pharmacokinetics

DEFF Research Database (Denmark)

Rasmussen, Christian Hove; Roge, Rikke Meldgaard; Ma, Zhulin

2014-01-01

Background: Insulin aspart (IAsp) is used by many diabetics as a meal-time insulin to control postprandial glucose levels. As is the case with many other insulin types, the pharmacokinetics (PK), and consequently the pharmacodynamics (PD), is associated with clinical variability, both between...... to investigate and quantify the properties of the subcutaneous depot. Data from Brange et al. (1990) are used to determine the effects of insulin chemistry in subcutis on the absorption rate. Intravenous (i.v.) bolus and infusion PK data for human insulin are used to understand and quantify the systemic...... distribution and elimination (Porksen et al., 1997; Sjostrand et al., 2002). PK and PD profiles for type 1 diabetics from Chen et al. (2005) are analyzed to demonstrate the effects of IAsp antibodies in terms of bound and unbound insulin. PK profiles from Thorisdottir et al. (2009) and Ma et al. (2012b...

Exogenous insulin antibody syndrome (EIAS: a clinical syndrome associated with insulin antibodies induced by exogenous insulin in diabetic patients

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Xiaolei Hu

2018-01-01

Full Text Available Insulin has been used for diabetes therapy and has achieved significant therapeutic effect. In recent years, the use of purified and recombinant human insulin preparations has markedly reduced, but not completely suppressed, the incidence of insulin antibodies (IAs. IAs induced by exogenous insulin in diabetic patients is associated with clinical events, which is named exogenous insulin antibody syndrome (EIAS. The present review is based on our research and summarizes the characterization of IAs, the factors affecting IA development, the clinical significance of IAs and the treatments for EIAS.

Intranasal Insulin Restores Metabolic Parameters and Insulin Sensitivity in Rats with Metabolic Syndrome.

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Derkach, K V; Ivantsov, A O; Chistyakova, O V; Sukhov, I B; Buzanakov, D M; Kulikova, A A; Shpakov, A O

2017-06-01

We studied the effect of 10-week treatment with intranasal insulin (0.5 IU/day) on glucose tolerance, glucose utilization, lipid metabolism, functions of pancreatic β cells, and insulin system in the liver of rats with cafeteria diet-induced metabolic syndrome. The therapy reduced body weight and blood levels of insulin, triglycerides, and atherogenic cholesterol that are typically increased in metabolic syndrome, normalized glucose tolerance and its utilization, and increased activity of insulin signaling system in the liver, thus reducing insulin resistance. The therapy did not affect the number of pancreatic islets and β cells. The study demonstrates prospects of using intranasal insulin for correction of metabolic parameters and reduction of insulin resistance in metabolic syndrome.

Remote sensing for predicting potential habitats of Oncomelania hupensis in Hongze, Baima and Gaoyou lakes in Jiangsu province, China

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Guo-Jing Yang

2006-11-01

Full Text Available Political and health sector reforms, along with demographic, environmental and socio-economic transformations in the face of global warming, could cause the re-emergence of schistosomiasis in areas where transmission has been successfully interrupted and its emergence in previously non-endemic areas in China. In the present study, we used geographic information systems and remote sensing techniques to predict potential habitats of Oncomelania hupensis, the intermediate host snail of Schistosoma japonicum. Focussing on the Hongze, Baima and Gaoyou lakes in Jiangsu province in eastern China, we developed a model using the normalized difference vegetation index, a tasseled-cap transformed wetness index, and flooding areas to predict snail habitats at a small scale. Data were extracted from two Landsat images, one taken during a typical dry year and the other obtained three years later during a flooding event. An area of approximately 163.6 km2 was predicted as potential O. hupensis habitats around the three lakes, which accounts for 4.3% of the estimated snail habitats in China. In turn, these predicted snail habitats are risk areas for transmission of schistosomiasis, and hence illustrate the scale of the possible impact of climate change and other ecological transformations. The generated risk map can be used by health policy makers to guide mitigation policies targetting the possible spread of O. hupensis, and with the aim of containing the transmission of S. japonicum.

Highlights on the World Bank Loan Schistosomiasis Control Program in China (1991-1998): a special focus on Hunan Province.

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Dongbao, Y; Ross, A G; Musheng, X; Yuesheng, L; Yan, C

1999-12-01

A region-wide sampling survey was conducted in 1995 in order to evaluate the current epidemiological status of schistosomiasis japonica in Hunan Province, China. A total of 45,590 humans and 3,726 domestic animals, from 52 villages, were examined parasitologically and/or serologically for current Schistosoma japonicum infections. In uncontrolled endemic areas (43 villages) the overall human prevalence of S. japonicum was 7.81% across the different geographical subtypes. The geometric mean intensity of infection was 17.71 eggs per gram (epg) among infected individuals and only 1.25 epg in the general population. The bovine prevalence, as determined by the hatching test, was 9.63% in the uncontrolled endemic villages. Only one sero-positive (by indirect hemagglutination assay) child was found among 1,072 children tested aged 10-14 years in the 9 endemic villages under effective control. No infection was confirmed by the Kato-Katz thick smear stool examination. When the results of this survey were compared to those seen at baseline (1989) an overall reduction of 45.65% was seen in the human prevalence but no significant change was apparent in the lake-beach ecotype. Additionally, there was more than a 60% reduction in the prevalence among bovines over the same sampling period. The results demonstrate that the World Bank Loan Schistosomiasis Program was successful in achieving its most basic objectives for this province - to reduce human and bovine infections by 40%.

Insulin production rate in normal man as an estimate for calibration of continuous intravenous insulin infusion in insulin-dependent diabetic patients.

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Waldhäusl, W K; Bratusch-Marrain, P R; Francesconi, M; Nowotny, P; Kiss, A

1982-01-01

This study examines the feasibility of deriving the 24-h insulin requirement of insulin-dependent diabetic patients who were devoid of any endogenous insulin release (IDD) from the insulin-production rate (IPR) of healthy man (basal, 17 mU/min; stimulated 1.35 U/12.5 g glucose). To this end, continuous intravenous insulin infusion (CIVII) was initiated at a precalculated rate of 41.2 +/- 4.6 (SD) U/24 h in IDD (N - 12). Blood glucose profiles were compared with those obtained during intermittent subcutaneous (s.c.) insulin therapy (IIT) and those of healthy controls (N = 7). Regular insulin (Hoechst CS) was infused with an adapted Mill Hill Infuser at a basal infusion rate of 1.6 U/h (6:00 a.m. to 8:00 p.m.), and of 0.8 U/h from 8:00 p.m. to 6:00 a.m. Preprandial insulin (3.2-6.4 U) was added for breakfast, lunch, and dinner. Daily individual food intake totaled 7688 +/- 784 kJ (1836 +/- 187 kcal)/24 h including 184 +/- 37 g of glucose. Proper control of blood glucose (BG) (mean BG 105 +/- 10 mg/dl; mean amplitude of glycemic excursions 54 +/- 18 mg/dl; and 1 h postprandial BG levels not exceeding 160 mg/dl) and of plasma concentrations of beta-hydroxybutyrate and lactate was maintained by 41.4 +/- 4.4 U insulin/24 h. Although BG values only approximated the upper normal range as seen in healthy controls, they were well within the range reported by others during CIVII. Therefore, we conclude that in adult IDD completely devoid of endogenous insulin (1) the IPR of normal man can be used during CIVII as an estimate for the patient's minimal insulin requirement per 24 h, and (2) this approach allows for a blood glucose profile close to the upper range of a normal control group. Thus, deriving a patient's daily insulin dose from the insulin production rate of healthy man may add an additional experimental protocol which aids in making general calculations of a necessary insulin dose instead of using trial and error or a closed-loop insulin infusion system.

Insulin resistance in dairy cows.

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De Koster, Jenne D; Opsomer, Geert

2013-07-01

Glucose is the molecule that drives milk production, and insulin plays a pivotal role in the glucose metabolism of dairy cows. The effect of insulin on the glucose metabolism is regulated by the secretion of insulin by the pancreas and the insulin sensitivity of the skeletal muscles, the adipose tissue, and the liver. Insulin resistance may develop as part of physiologic (pregnancy and lactation) and pathologic processes, which may manifest as decreased insulin sensitivity or decreased insulin responsiveness. A good knowledge of the normal physiology of insulin is needed to measure the in vivo insulin resistance of dairy cows. Copyright © 2013 Elsevier Inc. All rights reserved.

Cognitively impaired elderly exhibit insulin resistance and no memory improvement with infused insulin.

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Morris, Jill K; Vidoni, Eric D; Mahnken, Jonathan D; Montgomery, Robert N; Johnson, David K; Thyfault, John P; Burns, Jeffrey M

2016-03-01

Insulin resistance is a risk factor for Alzheimer's disease (AD), although its role in AD etiology is unclear. We assessed insulin resistance using fasting and insulin-stimulated measures in 51 elderly subjects with no dementia (ND; n = 37) and with cognitive impairment (CI; n = 14). CI subjects exhibited either mild CI or AD. Fasting insulin resistance was measured using the homeostatic model assessment of insulin resistance (HOMA-IR). Insulin-stimulated glucose disposal was assessed using the hyperinsulinemic-euglycemic clamp to calculate glucose disposal rate into lean mass, the primary site of insulin-stimulated glucose disposal. Because insulin crosses the blood-brain barrier, we also assessed whether insulin infusion would improve verbal episodic memory compared to baseline. Different but equivalent versions of cognitive tests were administered in counterbalanced order in the basal and insulin-stimulated state. Groups did not differ in age or body mass index. Cognitively impaired subjects exhibited greater insulin resistance as measured at fasting (HOMA-IR; ND: 1.09 [1.1] vs. CI: 2.01 [2.3], p = 0.028) and during the hyperinsulinemic clamp (glucose disposal rate into lean mass; ND: 9.9 (4.5) vs. AD 7.2 (3.2), p = 0.040). Cognitively impaired subjects also exhibited higher fasting insulin compared to ND subjects, (CI: 8.7 [7.8] vs. ND: 4.2 [3.8] μU/mL; p = 0.023) and higher fasting amylin (CI: 24.1 [39.1] vs. 8.37 [14.2]; p = 0.050) with no difference in fasting glucose. Insulin infusion elicited a detrimental effect on one test of verbal episodic memory (Free and Cued Selective Reminding Test) in both groups (p insulin resistance was observed in cognitively impaired subjects compared to ND controls, insulin infusion did not improve memory. Furthermore, a significant correlation between HOMA-IR and glucose disposal rate was present only in ND (p = 0.0002) but not in cognitively impaired (p = 0.884) subjects, indicating potentially important

Aminoacid polymorphisms of insulin receptor substrate-1 in non-insulin-dependent diabetes mellitus

DEFF Research Database (Denmark)

Almind, K; Bjørbaek, C; Vestergaard, H

1993-01-01

Since relative or absolute insulin deficiency and insulin insensitivity are involved in the aetiology of non-insulin-dependent diabetes mellitus (NIDDM), we examined whether patients with NIDDM exhibit genetic variability in the coding region of insulin receptor substrate-1 (IRS-1), a candidate...

Metformin and insulin receptors

International Nuclear Information System (INIS)

Vigneri, R.; Gullo, D.; Pezzino, V.

1984-01-01

The authors evaluated the effect of metformin (N,N-dimethylbiguanide), a biguanide known to be less toxic than phenformin, on insulin binding to its receptors, both in vitro and in vivo. Specific 125 I-insulin binding to cultured IM-9 human lymphocytes and MCF-7 human breast cancer cells was determined after preincubation with metformin. Specific 125 I-insulin binding to circulating monocytes was also evaluated in six controls, eight obese subjects, and six obese type II diabetic patients before and after a short-term treatment with metformin. Plasma insulin levels and blood glucose were also measured on both occasions. Metformin significantly increased insulin binding in vitro to both IM-9 lymphocytes and MCF-7 cells; the maximum increment was 47.1% and 38.0%, respectively. Metformin treatment significantly increased insulin binding in vivo to monocytes of obese subjects and diabetic patients. Scatchard analysis indicated that the increased binding was mainly due to an increase in receptor capacity. Insulin binding to monocytes of normal controls was unchanged after metformin as were insulin levels in all groups; blood glucose was significantly reduced after metformin only in diabetic patients. These data indicate that metformin increases insulin binding to its receptors in vitro and in vivo. The effect in vivo is observed in obese subjects and in obese type II diabetic patients, paralleling the clinical effectiveness of this antidiabetic agent, and is not due to receptor regulation by circulating insulin, since no variation in insulin levels was recorded

Bulinus nyassanus is an intermediate host for Schistosoma haematobium in Lake Malawi

DEFF Research Database (Denmark)

Madsen, H.; Bloch, P.; Phiri, H.

2001-01-01

At Cape Maclear on the Nankumba Peninsula, close to the southern end of Lake Malawi, Schistosoma haematobium is highly prevalent in the local people and many tourists become infected with this parasite each year. A 'Bilharzia Control Programme' was initiated in this area in August 1998......, field-collected B. nyassanus. These are remarkable observations since, although there are very few reports of diploid members of this species group being experimentally infected with S. haematobium, B. nyassanus is a diploid member (2n = 36) of the truncatus/tropicus group. Bulinus nyassanus is probably......, schistosome-infected B. nyassanus were discovered in surveys to identify transmission sites on the peninsula. Experimental infections of wild-caught B. nyassanus with S. haematobium proved successful and S. haematobium eggs were found in hamsters experimentally exposed to cercariae retrieved from schistosome-infected...

Recombinant DNA derived monomeric insulin analogue: comparison with soluble human insulin in normal subjects.

Science.gov (United States)

Vora, J P; Owens, D R; Dolben, J; Atiea, J A; Dean, J D; Kang, S; Burch, A; Brange, J

1988-11-12

To compare the rate of absorption from subcutaneous tissue and the resulting hypoglycaemic effect of iodine-125 labelled soluble human insulin and a monomeric insulin analogue derived by recombinant DNA technology. Single blind randomised comparison of equimolar doses of 125I labelled soluble human insulin and insulin analogue. Study in normal people at a diabetes research unit and a university department of medical physics. Seven healthy male volunteers aged 20-39 not receiving any other drugs. After an overnight fast and a basal period of one hour two doses (0.05 and 0.1 U/kg) of 125I labelled soluble human insulin and insulin analogue were injected subcutaneously into the anterior abdominal wall on four separate days. To find a fast acting insulin for meal related requirements in insulin dependent diabetics. MEASUREMENTS and main results--Residual radioactivity at the injection site was measured continuously for the first two hours after injection of the 125I labelled preparations and thereafter for five minutes simultaneously with blood sampling. Frequent venous blood samples were obtained over six hours for determination of plasma immunoreactive insulin, insulin analogue, glucose, and glucagon values. Time to 50% of initial radioactivity at the injection site for the insulin analogue compared with soluble insulin was 61 v 135 minutes (p less than 0.05) with 0.05 U/kg and 67 v 145 minutes (p less than 0.001) with 0.1 U/kg. Concentrations in plasma increased faster after the insulin analogue compared with soluble insulin, resulting in higher plasma concentrations between 10 and 150 minutes (0.001 less than p less than 0.05) after 0.05 U/kg and between 40 and 360 minutes (0.001 less than p less than 0.05) after 0.1 U/kg. The hypoglycaemic response to insulin analogue was a plasma glucose nadir at 60 minutes with both doses compared with 90 and 120 minutes with soluble insulin at 0.5 and 0.1 U/kg respectively. The response of glucagon substantiated the earlier and

Efficient expression and purification of a protease from the common cold virus, human rhinovirus type 14

Science.gov (United States)

Leong, L. E.-C.; Walker, P. A.; Porter, A. G.

1992-08-01

The protease (3C pro) from human rhinovirus serotype-14 (HRV-14) has been cloned and efficiently expressed in E. coli. A straightforward single-step purification of the recombinant 3C pro has been achieved by fusing the protein to the car☐y-terminus of the glutathione-S-transferase from Schistosoma japonicum. Modifications made to the 5' end of the PCR fragment coding for the 3C pro have allowed the specific cleavage of the fusion protein using thrombin to yield mature 3C pro with the correct amino-terminal amino acid. This protease has been shown to be active when assayed using synthetic peptides corresponding to the natural cleavage recognition sequences within the polyprotein. Other substrates are being developed for this protease for possible use in the screening of inhibitors of 3C pro. Sufficient protease 3C pro has been purified for initial attempts at crystallization.

SCHISTOSOMIASIS: GEOSPATIAL SURVEILLANCE AND RESPONSE SYSTEMS IN SOUTHEAST ASIA

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J. Malone

2016-10-01

Full Text Available Geographic information system (GIS and remote sensing (RS from Earth-observing satellites offer opportunities for rapid assessment of areas endemic for vector-borne diseases including estimates of populations at risk and guidance to intervention strategies. This presentation deals with GIS and RS applications for the control of schistosomiasis in China and the Philippines. It includes large-scale risk mapping including identification of suitable habitats for Oncomelania hupensis, the intermediate host snail of Schistosoma japonicum. Predictions of infection risk are discussed with reference to ecological transformations and the potential impact of climate change and the potential for long-term temperature increases in the North as well as the impact on rivers, lakes and water resource developments. Potential integration of geospatial mapping and modeling in schistosomiasis surveillance and response systems in Asia within Global Earth Observation System of Systems (GEOSS guidelines in the health societal benefit area is discussed.

Calcium phosphate-PEG-insulin-casein (CAPIC) particles as oral delivery systems for insulin.

Science.gov (United States)

Morçöl, T; Nagappan, P; Nerenbaum, L; Mitchell, A; Bell, S J D

2004-06-11

An oral delivery system for insulin was developed and functional activity was tested in a non-obese diabetic (NOD) mice model. Calcium phosphate particles containing insulin was synthesized in the presence of PEG-3350 and modified by aggregating the particles with caseins to obtain the calcium phosphate-PEG-insulin-casein (CAPIC) oral insulin delivery system. Single doses of CAPIC formulation were tested in NOD mice under fasting or fed conditions to evaluate the glycemic activity. The blood glucose levels were monitored every 1-2h for 12h following the treatments using an ACCU CHECK blood glucose monitoring system. Orally administered and subcutaneously injected free insulin solution served as controls in the study. Based on the results obtained we propose that: (1). the biological activity of insulin is preserved in CAPIC formulation; (2). insulin in CAPIC formulations, but not the free insulin, displays a prolonged hypoglycemic effect after oral administration to diabetic mice; (3). CAPIC formulation protects insulin from degradation while passing through the acidic environment of the GI track until it is released in the less acidic environment of the intestines where it can be absorbed in its biologically active form; (4). CAPIC formulation represents a new and unique oral delivery system for insulin and other macromolecules.

Insulin and the Brain

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Grosu Cristina

2017-12-01

Full Text Available The brain represents an important site for the action of insulin. Besides the traditionally known importance in glucoregulation, insulin has significant neurotrophic properties and influences the brain activity: insulin influences eating behavior, regulates the storage of energy and several aspects concerning memory and knowledge. Insulin resistance and hyperinsulinism could be associated with brain aging, vascular and metabolic pathologies. Elucidating the pathways and metabolism of brain insulin could have a major impact on future targeted therapies.

Insulin Secretagogues

Science.gov (United States)

... than sulfonylureas. What are the side effects and disadvantages of insulin secretagogues? Both types of insulin-releasing ... help find the cause. Questions to ask your doctor What else can I do to keep my ...

Conservation Genetics of an Endangered Lady’s Slipper Orchid: Cypripedium japonicum in China

Science.gov (United States)

Qian, Xin; Li, Quan-Jian; Liu, Fen; Gong, Mao-Jiang; Wang, Cai-Xia; Tian, Min

2014-01-01

Knowledge about the population genetic variation of the endangered orchid, Cypripedium japonicum, is conducive to the development of conservation strategies. Here, we examined the levels and partitioning of inter-simple sequence repeat (ISSR) diversity (109 loci) in five populations of this orchid to gain insight into its genetic variation and population structure in Eastern and Central China. It harbored considerably lower levels of genetic diversity both at the population (percentage of polymorphic loci (PPL) = 11.19%, Nei’s gene diversity (H) = 0.0416 and Shannon’s information index (I) = 0.0613) and species level (PPL = 38.53%, H = 0.1273 and I = 0.1928) and a significantly higher degree of differentiation among populations (the proportion of the total variance among populations (Φpt) = 0.698) than those typical of ISSR-based studies in other orchid species. Furthermore, the Nei’s genetic distances between populations were independent of the corresponding geographical distances. Two main clusters are shown in an arithmetic average (UPGMA) dendrogram, which is in agreement with the results of principal coordinate analysis (PCoA) analysis and the STRUCTURE program. In addition, individuals within a population were more similar to each other than to those in other populations. Based on the genetic data and our field survey, the development of conservation management for this threatened orchid should include habitat protection, artificial gene flow and ex situ measures. PMID:24983476

Conservation Genetics of an Endangered Lady’s Slipper Orchid: Cypripedium japonicum in China

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Xin Qian

2014-06-01

Full Text Available Knowledge about the population genetic variation of the endangered orchid, Cypripedium japonicum, is conducive to the development of conservation strategies. Here, we examined the levels and partitioning of inter-simple sequence repeat (ISSR diversity (109 loci in five populations of this orchid to gain insight into its genetic variation and population structure in Eastern and Central China. It harbored considerably lower levels of genetic diversity both at the population (percentage of polymorphic loci (PPL = 11.19%, Nei’s gene diversity (H = 0.0416 and Shannon’s information index (I = 0.0613 and species level (PPL = 38.53%, H = 0.1273 and I = 0.1928 and a significantly higher degree of differentiation among populations (the proportion of the total variance among populations (Φpt = 0.698 than those typical of ISSR-based studies in other orchid species. Furthermore, the Nei’s genetic distances between populations were independent of the corresponding geographical distances. Two main clusters are shown in an arithmetic average (UPGMA dendrogram, which is in agreement with the results of principal coordinate analysis (PCoA analysis and the STRUCTURE program. In addition, individuals within a population were more similar to each other than to those in other populations. Based on the genetic data and our field survey, the development of conservation management for this threatened orchid should include habitat protection, artificial gene flow and ex situ measures.

Micro-geographical heterogeneity in Schistosoma mansoni and S. haematobium infection and morbidity in a co-endemic community in northern Senegal.

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Lynn Meurs

Full Text Available BACKGROUND: Schistosoma mansoni and S. haematobium are co-endemic in many areas in Africa. Yet, little is known about the micro-geographical distribution of these two infections or associated disease within such foci. Such knowledge could give important insights into the drivers of infection and disease and as such better tailor schistosomiasis control and elimination efforts. METHODOLOGY: In a co-endemic farming community in northern Senegal (346 children (0-19 y and 253 adults (20-85 y; n = 599 in total, we studied the spatial distribution of S. mansoni and S. haematobium single and mixed infections (by microscopy, S. mansoni-specific hepatic fibrosis, S. haematobium-specific urinary tract morbidity (by ultrasound and water contact behavior (by questionnaire. The Kulldorff's scan statistic was used to detect spatial clusters of infection and morbidity, adjusted for the spatial distribution of gender and age. PRINCIPAL FINDINGS: Schistosoma mansoni and S. haematobium infection densities clustered in different sections of the community (p = 0.002 and p = 0.023, respectively, possibly related to heterogeneities in the use of different water contact sites. While the distribution of urinary tract morbidity was homogeneous, a strong geospatial cluster was found for severe hepatic fibrosis (p = 0.001. Particularly those people living adjacent to the most frequently used water contact site were more at risk for more advanced morbidity (RR = 6.3; p = 0.043. CONCLUSIONS/SIGNIFICANCE: Schistosoma infection and associated disease showed important micro-geographical heterogeneities with divergent patterns for S. mansoni and S. haematobium in this Senegalese community. Further in depth investigations are needed to confirm and explain our observations. The present study indicates that local geospatial patterns should be taken into account in both research and control of schistosomiasis. The observed extreme focality of schistosomiasis even at community level

Identification of residues in the insulin molecule important for binding to insulin-degrading enzyme.

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Affholter, J A; Cascieri, M A; Bayne, M L; Brange, J; Casaretto, M; Roth, R A

1990-08-21

Insulin-degrading enzyme (IDE) hydrolyzes insulin at a limited number of sites. Although the positions of these cleavages are known, the residues of insulin important in its binding to IDE have not been defined. To this end, we have studied the binding of a variety of insulin analogues to the protease in a solid-phase binding assay using immunoimmobilized IDE. Since IDE binds insulin with 600-fold greater affinity than it does insulin-like growth factor I (25 nM and approximately 16,000 nM, respectively), the first set of analogues studied were hybrid molecules of insulin and IGF I. IGF I mutants [insB1-17,17-70]IGF I, [Tyr55,Gln56]IGF I, and [Phe23,Phe24,Tyr25]IGF I have been synthesized and share the property of having insulin-like amino acids at positions corresponding to primary sites of cleavage of insulin by IDE. Whereas the first two exhibit affinities for IDE similar to that of wild type IGF I, the [Phe23,Phe24,Tyr25]IGF I analogue has a 32-fold greater affinity for the immobilized enzyme. Replacement of Phe-23 by Ser eliminates this increase. Removal of the eight amino acid D-chain region of IGF I (which has been predicted to interfere with binding to the 23-25 region) results in a 25-fold increase in affinity for IDE, confirming the importance of residues 23-25 in the high-affinity recognition of IDE. A similar role for the corresponding (B24-26) residues of insulin is supported by the use of site-directed mutant and semisynthetic insulin analogues. Insulin mutants [B25-Asp]insulin and [B25-His]insulin display 16- and 20-fold decreases in IDE affinity versus wild-type insulin.(ABSTRACT TRUNCATED AT 250 WORDS)

Altered insulin distribution and metabolism in type I diabetics assessed by [123I]insulin scanning

International Nuclear Information System (INIS)

Hachiya, H.L.; Treves, S.T.; Kahn, C.R.; Sodoyez, J.C.; Sodoyez-Goffaux, F.

1987-01-01

Scintigraphic scanning with [ 123 I]insulin provides a direct and quantitative assessment of insulin uptake and disappearance at specific organ sites. Using this technique, the biodistribution and metabolism of insulin were studied in type 1 diabetic patients and normal subjects. The major organ of [ 123 I]insulin uptake in both diabetic and normal subjects was the liver. After iv injection in normal subjects, the uptake of [ 123 I]insulin by the liver was rapid, with peak activity at 7 min. Activity declined rapidly thereafter, consistent with rapid insulin degradation and clearance. Rapid uptake of [ 123 I]insulin also occurred in the kidneys, although the uptake of insulin by the kidneys was about 80% of that by liver. In type 1 diabetic patients, uptake of [ 123 I]insulin in these organ sites was lower than that in normal subjects; peak insulin uptakes in liver and kidneys were 21% and 40% lower than those in normal subjects, respectively. The kinetics of insulin clearance from the liver was comparable in diabetic and normal subjects, whereas clearance from the kidneys was decreased in diabetics. The plasma clearance of [ 123 I]insulin was decreased in diabetic patients, as was insulin degradation, assessed by trichloroacetic acid precipitability. Thirty minutes after injection, 70.9 +/- 3.8% (+/- SEM) of [ 123 I]insulin in the plasma of diabetics was trichloroacetic acid precipitable vs. only 53.9 +/- 4.0% in normal subjects. A positive correlation was present between the organ uptake of [123I]insulin in the liver or kidneys and insulin degradation (r = 0.74; P less than 0.001)

Treatment of severe insulin resistance in pregnancy with 500 units per milliliter of concentrated insulin.

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Mendez-Figueroa, Hector; Maggio, Lindsay; Dahlke, Joshua D; Daley, Julie; Lopes, Vrishali V; Coustan, Donald R; Rouse, Dwight J

2013-07-01

To evaluate glycemic control and pregnancy outcomes among pregnant women with severe insulin resistance treated with 500 units/mL concentrated insulin. Retrospective analysis of gravid women with severe insulin resistance (need for greater than 100 units of insulin per injection or greater than 200 units/d) treated with either 500 units/mL concentrated insulin or conventional insulin therapy. We performed a two-part analysis: 1) between gravid women treated with and without 500 units/mL concentrated insulin; and 2) among gravid women treated with 500 units/mL concentrated insulin, comparing glycemic control before and after its initiation. Seventy-three pregnant women with severe insulin resistance were treated with 500 units/mL concentrated insulin and 78 with conventional insulin regimens. Patients treated with 500 units/mL concentrated insulin were older and more likely to have type 2 diabetes mellitus. Average body mass index was comparable between both groups (38.6 compared with 40.4, P=.11) as were obstetric and perinatal outcomes and glycemic control during the last week of gestation. Within the 500 units/mL concentrated insulin cohort, after initiation of this medication, fasting and postprandial blood glucose concentrations improved. However, the rates of blood glucose values less than 60 mg/dL and less than 50 mg/dL were higher in the 500 units/mL concentrated insulin group after initiation than before, 4.8% compared with 2.0% (Pinsulin in severely obese insulin-resistant pregnant women confers similar glycemic control compared with traditional insulin regimens but may increase the risk of hypoglycemia. II.

Role of sialic acid in insulin action and the insulin resistance of diabetes mellitus

International Nuclear Information System (INIS)

Salhanick, A.I.; Amatruda, J.M.

1988-01-01

Adipocytes treated with neuraminidase show markedly reduced responsiveness to insulin without any alteration in insulin binding. In addition, several studies have separately demonstrated both insulin resistance and decreases in membrane sialic acid content and associated biosynthetic enzymes in diabetes mellitus. In the present study, the authors investigated the role that sialic acid residues may play in insulin action and in the hepatic insulin resistance associated with nonketotic diabetes. Primary cultures of hepatocytes from normal rats treated with neuraminidase demonstrated a dose-dependent decrease in insulin-stimulated lipogenesis. At a concentration of neuraminidase that decreases insulin action by 50%, 23% of total cellular sialic acid content was released. Neuraminidase-releasable sialic acid was significantly decreased in hepatocytes from diabetic rats and this was associated with significant insulin resistance. Treatment of hepatocytes from diabetic rats with cytidine 5'-monophospho-N-acetylneuraminic acid (CMP-NANA) enhanced insulin responsiveness 39%. The enhanced insulin responsiveness induced by CMP-NANA was blocked by cytidine 5'-monophosphate (CMP) suggesting that the CMP-NANA effect was catalyzed by a cell surface sialyl-transferase. CMP reduced neuraminidase-releasable [ 14 C]sialic acid incorporation into hepatocytes by 43%. The data demonstrate a role for cell surface sialic acid residues in hepatic insulin action and support a role for decreased cell surface sialic acid residues in the insulin resistance of diabetes mellitus

Insulin resistance, insulin sensitization and inflammation in polycystic ovarian syndrome

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Dhindsa G

2004-04-01

Full Text Available It is estimated that 5-10% of women of reproductive age have polycystic ovarian syndrome (PCOS. While insulin resistance is not part of the diagnostic criteria for PCOS, its importance in the pathogenesis of PCOS cannot be denied. PCOS is associated with insulin resistance independent of total or fat-free body mass. Post-receptor defects in the action of insulin have been described in PCOS which are similar to those found in obesity and type 2 diabetes. Treatment with insulin sensitizers, metformin and thiazolidinediones, improve both metabolic and hormonal patterns and also improve ovulation in PCOS. Recent studies have shown that PCOS women have higher circulating levels of inflammatory mediators like C-reactive protein, tumour necrosis factor- , tissue plasminogen activator and plasminogen activator inhibitor-1 (PAI-1 . It is possible that the beneficial effect of insulin sensitizers in PCOS may be partly due to a decrease in inflammation.

Protection of sheep against Schistosoma bovis using cryopreserved radiation-attenuated schistosomula

International Nuclear Information System (INIS)

James, E.R.; Dobinson, A.R.; Andrews, B.J.; Bickle, Q.D.; Taylor, M.G.; Ham, P.J.

1985-01-01

Three sheep were vaccinated with two doses of 3 krad-irradiated cryopreserved Schistosoma bovis schistosomula containing 20,000 and 17,000 organisms respectively, injected intramuscularly 23 days apart after storage in liquid nitrogen for between 9 and 46 days. A challenge of 5360 S. bovis cercariae was administered percutaneously approximately four weeks after the last vaccine dose to these animals and to three controls. Post-challenge the vaccinated animals gained significantly more weight (27% v. 9%), produced fewer eggs in their faeces, showed a smaller reduction in PCV values (-18% v. -27%) and were over-all in better condition than control animals. At perfusion 49.1% fewer adult worms were found in the vaccinated sheep than in controls. The tissue egg burdens were similar in both groups. Histopathologically both groups were similar except that fewer and smaller egg lesions were observed in the livers of vaccinated animals. (author)

Treatment of Type 1 and Type 2 Diabetes Mellitus with Insulin Detemir, a Long-Acting Insulin Analog

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Jason R. Young

2010-01-01

Full Text Available Insulin detemir is a long-acting basal insulin approved for use in patients with type 1 (T1DM or type 2 diabetes (T2DM. Insulin detemir has demonstrated equivalent glycemic control and hypoglycemic risk when compared to insulin glargine, and insulin detemir has generally but not consistently demonstrated less weight gain than insulin glargine in T2DM. The benefits of basal insulin analogs relative to NPH insulin are well recognized, including less FBG variability, lower risk of hypoglycemia, and less weight gain specifically with insulin detemir. However, NPH insulin continues to be widely prescribed, which may be due in part to economic considerations. While NPH insulin generally costs less per prescription, insulin detemir has been shown to be cost effective compared to NPH insulin as well as insulin glargine. Therefore, insulin detemir is an effective option from both clinical and economic perspectives for patients with T1DM or T2DM who require basal insulin to achieve glycemic control.

Immunohistochemical expression of insulin, glucagon, and somatostatin in pancreatic islets of horses with and without insulin resistance.

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Newkirk, Kim M; Ehrensing, Gordon; Odoi, Agricola; Boston, Raymond C; Frank, Nicholas

2018-02-01

OBJECTIVE To assess insulin, glucagon, and somatostatin expression within pancreatic islets of horses with and without insulin resistance. ANIMALS 10 insulin-resistant horses and 13 insulin-sensitive horses. PROCEDURES For each horse, food was withheld for at least 10 hours before a blood sample was collected for determination of serum insulin concentration. Horses with a serum insulin concentration horses with a serum insulin concentration > 20 μU/mL underwent a frequently sampled IV glucose tolerance test to determine sensitivity to insulin by minimal model analysis. Horses with a sensitivity to insulin horses were euthanized with a barbiturate overdose, and pancreatic specimens were harvested and immunohistochemically stained for determination of insulin, glucagon, and somatostatin expression in pancreatic islets. Islet hormone expression was compared between insulin-resistant and insulin-sensitive horses. RESULTS Cells expressing insulin, glucagon, and somatostatin made up approximately 62%, 12%, and 7%, respectively, of pancreatic islet cells in insulin-resistant horses and 64%, 18%, and 9%, respectively, of pancreatic islet cells in insulin-sensitive horses. Expression of insulin and somatostatin did not differ between insulin-resistant and insulin-sensitive horses, but the median percentage of glucagon-expressing cells in the islets of insulin-resistant horses was significantly less than that in insulin-sensitive horses. CONCLUSIONS AND CLINICAL RELEVANCE Results suggested that, in insulin-resistant horses, insulin secretion was not increased but glucagon production might be downregulated as a compensatory response to hyperinsulinemia.

Changing the insulin receptor to possess insulin-like growth factor I ligand specificity

International Nuclear Information System (INIS)

Andersen, A.S.; Kjeldsen, T.; Wiberg, F.C.; Christensen, P.M.; Rasmussen, J.S.; Norris, K.; Moeller, K.B.; Moeller, N.P.H.

1990-01-01

To examine the role of the N-terminal part of the insulin-like growth factor I (IGF-I) receptor and insulin receptor in determining ligand specificity, the authors prepared an expression vector encoding a hybrid receptor where exon 1 (encoding the signal peptide and seven amino acids of the α-subunit), exon 2, and exon 3 of the insulin receptor were replaced with the corresponding IGF-I receptor cDNA (938 nucleotides). To allow direct quantitative comparison of the binding capabilities of this hybrid receptor with those of the human IGF-I receptor and the insulin receptor, all three receptors were expressed in baby hamster kidney (BHK) cells as soluble molecules and partially purified before characterization. The hybrid IGF-I/insulin receptor bound IGF-I with an affinity comparable to that of the wild-type IGF-I receptor. In contrast, the hybrid receptor no longer displayed high-affinity binding of insulin. These results directly demonstrate that it is possible to change the specificity of the insulin receptor to that of the IGF-I receptor and, furthermore, that the binding specificity for IGF-I is encoded within the nucleotide sequence from 135 to 938 of the IGF-I receptor cDNA. Since the hybrid receptor only bound insulin with low affinity, the insulin binding region is likely to be located within exons 2 and 3 of the insulin receptor

Insulin and the Lung

DEFF Research Database (Denmark)

Singh, Suchita; Prakash, Y S; Linneberg, Allan

2013-01-01

, molecular understanding is necessary. Insulin resistance is a strong, independent risk factor for asthma development, but it is unknown whether a direct effect of insulin on the lung is involved. This review summarizes current knowledge regarding the effect of insulin on cellular components of the lung...... and highlights the molecular consequences of insulin-related metabolic signaling cascades that could adversely affect lung structure and function. Examples include airway smooth muscle proliferation and contractility and regulatory signaling networks that are associated with asthma. These aspects of insulin...

Prevalence of Schistosoma mansoni Infection in Four Health Areas of Kisantu Health Zone, Democratic Republic of the Congo

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R. Khonde Kumbu

2016-01-01

Full Text Available Background. Schistosomiasis is a public health problem in Democratic Republic of the Congo but estimates of its prevalence vary widely. The aim of this study was to determine prevalence of Schistosoma mansoni infection and associated risk factors among children in 4 health areas of Kisantu health zone. Methods. A cross-sectional study was carried out in 4 health areas of Kisantu health zone. 388 children randomly selected were screened for S. mansoni using Kato Katz technique and the sociodemographic data was collected. Data were entered and encoded using software EpiData version 3.1. Analysis was performed using SPSS version 21 software. Results. The prevalence of S. mansoni was 26.5% (103; almost two-thirds (63 (61.2% had light infection intensity. A significant association was found between S. mansoni infection and age (p=0.005, educational level (p=0.001, and practices of swimming/bathing (p<0.001 and using water from river/lake/stream for domestic use (p<0.001. Kipasa health area had high prevalence of schistosomiasis (64.6% (64/99; 95% CI 54.4–74.0 compared to other health areas. Conclusion. Schistosoma mansoni infection still remains a public health problem in these areas. There is a need to promote health education and promote behavioral changes in children towards schistosomiasis.

In silico repositioning-chemogenomics strategy identifies new drugs with potential activity against multiple life stages of Schistosoma mansoni.

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Bruno J Neves

2015-01-01

Full Text Available Morbidity and mortality caused by schistosomiasis are serious public health problems in developing countries. Because praziquantel is the only drug in therapeutic use, the risk of drug resistance is a concern. In the search for new schistosomicidal drugs, we performed a target-based chemogenomics screen of a dataset of 2,114 proteins to identify drugs that are approved for clinical use in humans that may be active against multiple life stages of Schistosoma mansoni. Each of these proteins was treated as a potential drug target, and its amino acid sequence was used to interrogate three databases: Therapeutic Target Database (TTD, DrugBank and STITCH. Predicted drug-target interactions were refined using a combination of approaches, including pairwise alignment, conservation state of functional regions and chemical space analysis. To validate our strategy, several drugs previously shown to be active against Schistosoma species were correctly predicted, such as clonazepam, auranofin, nifedipine, and artesunate. We were also able to identify 115 drugs that have not yet been experimentally tested against schistosomes and that require further assessment. Some examples are aprindine, gentamicin, clotrimazole, tetrabenazine, griseofulvin, and cinnarizine. In conclusion, we have developed a systematic and focused computer-aided approach to propose approved drugs that may warrant testing and/or serve as lead compounds for the design of new drugs against schistosomes.

Comparison of Subcutaneous Regular Insulin and Lispro Insulin in Diabetics Receiving Continuous Nutrition

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Stull, Mamie C.; Strilka, Richard J.; Clemens, Michael S.; Armen, Scott B.

2015-01-01

Background: Optimal management of non–critically ill patients with diabetes maintained on continuous enteral feeding (CEN) is poorly defined. Subcutaneous (SQ) lispro and SQ regular insulin were compared in a simulated type 1 and type 2 diabetic patient receiving CEN. Method: A glucose-insulin feedback mathematical model was employed to simulate type 1 and type 2 diabetic patients on CEN. Each patient received 25 SQ injections of regular insulin or insulin lispro, ranging from 0-6 U. Primary endpoints were the change in mean glucose concentration (MGC) and change in glucose variability (GV); hypoglycemic episodes were also reported. The model was first validated against patient data. Results: Both SQ insulin preparations linearly decreased MGC, however, SQ regular insulin decreased GV whereas SQ lispro tended to increase GV. Hourly glucose concentration measurements were needed to capture the increase in GV. In the type 2 diabetic patient, “rebound hyperglycemia” occurred after SQ lispro was rapidly metabolized. Although neither SQ insulin preparation caused hypoglycemia, SQ lispro significantly lowered MGC compared to SQ regular insulin. Thus, it may be more likely to cause hypoglycemia. Analyses of the detailed glucose concentration versus time data suggest that the inferior performance of lispro resulted from its shorter duration of action. Finally, the effects of both insulin preparations persisted beyond their duration of actions in the type 2 diabetic patient. Conclusions: Subcutaneous regular insulin may be the short-acting insulin preparation of choice for this subset of diabetic patients. Clinical trial is required before a definitive recommendation can be made. PMID:26134836

Blood Glucose and Insulin Concentrations after Octreotide Administration in Horses With Insulin Dysregulation.

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Frank, N; Hermida, P; Sanchez-Londoño, A; Singh, R; Gradil, C M; Uricchio, C K

2017-07-01

Octreotide is a somatostatin analog that suppresses insulin secretion. We hypothesized that octreotide would suppress insulin concentrations in horses and that normal (N) horses and those with insulin dysregulation (ID) would differ significantly in their plasma glucose and insulin responses to administration of octreotide. Twelve horses, N = 5, ID = 7. Prospective study. An oral sugar test was performed to assign horses to N and ID groups. Octreotide (1.0 μg/kg IV) was then administered, and blood was collected at 0, 5, 10, 15, 20, 25, 30, 45, 60, 75, and 90 minute, and 2, 3, 4, 6, 8, 12, and 24 hour for measurement of glucose and insulin concentrations. Area under the curve (AUC) values were calculated. Mean AUC values for glucose and insulin did not differ between normal (n = 5) and ID (n = 7) groups after octreotide injection. Significant time (P glucose and insulin concentrations. A group × time interaction (P = .091) was detected for insulin concentrations after administration of octreotide, but the group (P = .33) effect was not significant. Octreotide suppresses insulin secretion, resulting in hyperglycemia, and then concentrations increase above baseline as glycemic control is restored. Our hypothesis that octreotide causes insulin concentrations to decrease in horses was supported, but differences between N and ID groups did not reach statistical significance when blood glucose and insulin responses were compared. The utility of an octreotide response test remains to be determined. Copyright © 2017 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals, Inc. on behalf of the American College of Veterinary Internal Medicine.

Aerosolized liposomes with dipalmitoyl phosphatidylcholine enhance pulmonary absorption of encapsulated insulin compared with co-administered insulin.

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Chono, Sumio; Togami, Kohei; Itagaki, Shirou

2017-11-01

We have previously shown that aerosolized liposomes with dipalmitoyl phosphatidylcholine (DPPC) enhance the pulmonary absorption of encapsulated insulin. In this study, we aimed to compare insulin encapsulated into the liposomes versus co-administration of empty liposomes and unencapsulated free insulin, where the DPCC liposomes would serve as absorption enhancer. The present study provides the useful information for development of noninvasive treatment of diabetes. Co-administration of empty DPPC liposomes and unencapsulated free insulin was investigated in vivo to assess the potential enhancement in protein pulmonary absorption. Co-administration was compared to DPPC liposomes encapsulating insulin, and free insulin. DPPC liposomes enhanced the pulmonary absorption of unencapsulated free insulin; however, the enhancing effect was lower than that of the DPPC liposomes encapsulating insulin. The mechanism of the pulmonary absorption of unencapsulated free insulin by DPPC liposomes involved the opening of epithelial cell space in alveolar mucosa, and not mucosal cell damage, similar to that of the DPPC liposomes encapsulating insulin. In an in vitro stability test, insulin in the alveolar mucus layer that covers epithelial cells was stable. These findings suggest that, although unencapsulated free insulin spreads throughout the alveolar mucus layer, the concentration of insulin released near the absorption surface is increased by the encapsulation of insulin into DPPC liposomes and the absorption efficiency is also increased. We revealed that the encapsulation of insulin into DPPC liposomes is more effective for pulmonary insulin absorption than co-administration of DPPC liposomes and unencapsulated free insulin.

Glucose-lowering effect and glycaemic variability of insulin glargine, insulin detemir and insulin lispro protamine in people with type 1 diabetes.

Science.gov (United States)

Derosa, G; Franzetti, I; Querci, F; Romano, D; D'Angelo, A; Maffioli, P

2015-06-01

To compare, using a continuous glucose monitoring (CGM) system, the effect on glycaemic variability of insulin glargine, detemir and lispro protamine. A total of 49 white people with type 1 diabetes, not well controlled by three times daily insulin lispro, taken for at least 2 months before study and on a stable dose, were enrolled. The study participants were randomized to add insulin glargine, detemir or lispro protamine, once daily, in the evening. We used a CGM system, the iPro Digital Recorder (Medtronic MiniMed, Northridge, CA, USA) for 1 week. Glycaemic control was assessed according to mean blood glucose values, the area under the glucose curve above 3.9 mmol/l (AUC(>3.9)) or above 10.0 mmol/l (AUC(>10.0)), and the percentage of time spent with glucose values >3.9 or >10.0 mmol/l. Intraday glycaemic variability was assessed using standard deviation (s.d.) values, the mean amplitude of glycaemic excursions and continuous overlapping of net glycaemic action. Day-to-day glycaemic variability was assessed using the mean of daily differences. The s.d. was found to be significantly lower with insulin lispro protamine and glargine compared with insulin detemir. AUC(>3.9) was higher and AUC(>10.0) was lower with insulin lispro protamine and glargine compared with detemir. The mean amplitude of glycaemic excursions and continuous overlapping net glycaemic action values were lower with insulin lispro protamine and glargine compared with detemir. In addition, the mean of daily differences was significantly lower with insulin lispro protamine and glargine compared with detemir. Fewer hypoglycaemic events were recorded during the night-time with insulin lispro protamine compared with glargine and detemir. The results suggest that insulin lispro protamine and glargine are more effective than detemir in reducing glycaemic variability and improving glycaemic control in people with type 1 diabetes. Insulin lispro protamine seems to lead to fewer hypoglycaemic

Schistosoma mansoni: assessment of effects of oleic acid, cercarial age and water temperature on parasite-host attraction.

Science.gov (United States)

Lee, Vivien S T; Burgess, Jefferey L; Sterling, Charles R; Lutz, Eric A

2013-09-01

Although the lifecycle of Schistosoma spp. and pathophysiology of schistosomiasis have been established, the mechanism by which cercariae find their host is not well understood. Speculatively, host infection by random and accidental host contact is not as biologically plausible as a biochemical mechanism of mammalian attraction. A few studies have indicated that biochemical cues and temperature gradients may play a role in host identification, attraction and attachment triggers. This study aimed to elucidate these mechanisms more specifically through evaluation of biochemical, age and temperature influences leading to Schistosoma mansoni cercariae attraction and attachment behaviors. Oleic acid, a common unsaturated free fatty acid in the outer layer of human skin, was tested for cercariae attraction across biologically relevant concentrations. Influence of media type (beeswax, nail varnish and agar), age-dependent behavior variability and environmentally appropriate temperatures (22 and 30 °C) were also evaluated. Results indicated that oleic acid at concentrations of 0.3, 0.9 and 1.8 g/mL in beeswax significantly increased median attachment to media (median attachment of 7.50%, 4.20% and 3.71%, respectively, P0.05). Biochemical, age and environmental factors influencing cercarial host attraction and attachment behavior have been elucidated by this study. This information will inform further development of devices for environmental surveillance and potentially improve cercarial exposure prevention strategies. Copyright © 2013 Australian Society for Parasitology Inc. Published by Elsevier Ltd. All rights reserved.

Flexibility in insulin prescription

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Sanjay Kalra

2016-01-01

Full Text Available This communication explores the concept of flexibility, a propos insulin preparations and insulin regimes used in the management of type 2 diabetes. The flexibility of an insulin regime or preparation is defined as their ability to be injected at variable times, with variable injection-meal time gaps, in a dose frequency and quantum determined by shared decision making, with a minimal requirement of glucose monitoring and health professional consultation, with no compromise on safety, efficiency and tolerability. The relative flexibility of various basal, prandial and dual action insulins, as well as intensive regimes, is compared. The biopsychosocial model of health is used to assess the utility of different insulins while encouraging a philosophy of flexible insulin usage.

Glucose tolerance, insulin release, and insulin binding to monocytes in kidney transplant recipients

International Nuclear Information System (INIS)

Briggs, W.A.; Wielechowski, K.S.; Mahajan, S.K.; Migdal, S.D.; McDonald, F.D.

1982-01-01

In order to evaluate glucose tolerance following renal transplantation, intravenous glucose tolerance tests (IVGTT), with evaluation of hormonal responses to the intravenous glucose load and percent specific 125 I-insulin binding to peripheral blood monocytes, were studied in eight clinically stable kidney transplant recipients. For comparison purposes, identical studies were done in eight control subjects and seven clinically stable hemodialysis patients. One transplant recipient was glucose intolerant, with fasting hyperglycemia, elevated HbA1C, and abnormal glucose decay constant. Impaired pancreatic insulin release appeared to be the major factor accounting for his glucose intolerance. The seven glucose-tolerant transplant recipients had significantly increased insulin release during IVGTT compared to control subjects, and significant correlations were found among insulin release, glucose decay constant, and fasting blood sugar in those patients. Insulin binding to monocytes was significantly greater in transplant recipients than control subjects due to an increase in insulin binding capacity per cell. A significant correlation was found between percent specific 125 I-insulin binding and steroid dose, expressed as mg/kg body weight/day, in those patients. Thus, chronic steroid administration does not cause glucose intolerance in transplant recipients who manifest steroid-associated increases in pancreatic insulin release and cellular insulin binding capacity

Effect of oxamniquine on cell adhesion to Schistosoma mansoni larvae in the peritoneal cavity of naive mice Efeito da oxamniquina sobre a adesão celular da larva do S. mansoni na cavidade peritoneal de camundongos

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Alan Lane de Melo

1993-06-01

Full Text Available The treatment of naive mice with high closes of oxamniquine, 1 hour before the intraperitoneal inoculation of Schistosoma mansoni cercariae, induces a delay in the transformation process resulting in a longer host cell adhesion.O tratamento de camundongos sem infecção prévia com altas doses de oxamniquina, 1 hora antes do inóculo intraperitoneal com cercárias de Schistosoma mansoni, induz a um atraso no processo de transformação, resultando conseqüentemente em larvas com adesão celular mais duradoura.

Insulin Resistance Induced by Hyperinsulinemia Coincides with a Persistent Alteration at the Insulin Receptor Tyrosine Kinase Domain

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Catalano, Karyn J.; Maddux, Betty A.; Szary, Jaroslaw; Youngren, Jack F.; Goldfine, Ira D.; Schaufele, Fred

2014-01-01

Insulin resistance, the diminished response of target tissues to insulin, is associated with the metabolic syndrome and a predisposition towards diabetes in a growing proportion of the worldwide population. Under insulin resistant states, the cellular response of the insulin signaling pathway is diminished and the body typically responds by increasing serum insulin concentrations to maintain insulin signaling. Some evidence indicates that the increased insulin concentration may itself further dampen insulin response. If so, insulin resistance would worsen as the level of circulating insulin increases during compensation, which could contribute to the transition of insulin resistance to more severe disease. Here, we investigated the consequences of excess insulin exposure to insulin receptor (IR) activity. Cells chronically exposed to insulin show a diminished the level of IR tyrosine and serine autophosphorylation below that observed after short-term insulin exposure. The diminished IR response did not originate with IR internalization since IR amounts at the cell membrane were similar after short- and long-term insulin incubation. Förster resonance energy transfer between fluorophores attached to the IR tyrosine kinase (TK) domain showed that a change in the TK domain occurred upon prolonged, but not short-term, insulin exposure. Even though the altered ‘insulin refractory’ IR TK FRET and IR autophosphorylation levels returned to baseline (non-stimulated) levels after wash-out of the original insulin stimulus, subsequent short-term exposure to insulin caused immediate re-establishment of the insulin-refractory levels. This suggests that some cell-based ‘memory’ of chronic hyperinsulinemic exposure acts directly at the IR. An improved understanding of that memory may help define interventions to reset the IR to full insulin responsiveness and impede the progression of insulin resistance to more severe disease states. PMID:25259572

Insulin resistance induced by hyperinsulinemia coincides with a persistent alteration at the insulin receptor tyrosine kinase domain.

Directory of Open Access Journals (Sweden)

Karyn J Catalano

Full Text Available Insulin resistance, the diminished response of target tissues to insulin, is associated with the metabolic syndrome and a predisposition towards diabetes in a growing proportion of the worldwide population. Under insulin resistant states, the cellular response of the insulin signaling pathway is diminished and the body typically responds by increasing serum insulin concentrations to maintain insulin signaling. Some evidence indicates that the increased insulin concentration may itself further dampen insulin response. If so, insulin resistance would worsen as the level of circulating insulin increases during compensation, which could contribute to the transition of insulin resistance to more severe disease. Here, we investigated the consequences of excess insulin exposure to insulin receptor (IR activity. Cells chronically exposed to insulin show a diminished the level of IR tyrosine and serine autophosphorylation below that observed after short-term insulin exposure. The diminished IR response did not originate with IR internalization since IR amounts at the cell membrane were similar after short- and long-term insulin incubation. Förster resonance energy transfer between fluorophores attached to the IR tyrosine kinase (TK domain showed that a change in the TK domain occurred upon prolonged, but not short-term, insulin exposure. Even though the altered 'insulin refractory' IR TK FRET and IR autophosphorylation levels returned to baseline (non-stimulated levels after wash-out of the original insulin stimulus, subsequent short-term exposure to insulin caused immediate re-establishment of the insulin-refractory levels. This suggests that some cell-based 'memory' of chronic hyperinsulinemic exposure acts directly at the IR. An improved understanding of that memory may help define interventions to reset the IR to full insulin responsiveness and impede the progression of insulin resistance to more severe disease states.

Patient safety and minimizing risk with insulin administration - role of insulin degludec.

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Aye, Myint M; Atkin, Stephen L

2014-01-01

Diabetes is a lifelong condition requiring ongoing medical care and patient self-management. Exogenous insulin therapy is essential in type 1 diabetes and becomes a necessity in patients with longstanding type 2 diabetes who fail to achieve optimal control with lifestyle modification, oral agents, and glucagon-like peptide 1-based therapy. One of the risks that hinders insulin use is hypoglycemia. Optimal insulin therapy should therefore minimize the risk of hypoglycemia while improving glycemic control. Insulin degludec (IDeg) is a novel basal insulin that, following subcutaneous injection, assembles into a depot of soluble multihexamer chains. These subsequently release IDeg monomers that are absorbed at a slow and steady rate into the circulation, with the terminal half-life of IDeg being ~25 hours. Thus, it requires only once-daily dosing unlike other basal insulin preparations that often require twice-daily dosing. Despite its long half-life, once-daily IDeg does not cause accumulation of insulin in the circulation after reaching steady state. IDeg once a day will produce a steady-state profile with a lower peak:trough ratio than other basal insulins. In clinical trials, this profile translates into a lower frequency of nocturnal hypoglycemia compared with insulin glargine, as well as an ability to allow some flexibility in dose timing without compromising efficacy and safety. Indeed, a study that tested the extremes of dosing intervals of 8 and 40 hours showed no detriment in either glycemic control or hypoglycemic frequency versus insulin glargine given at the same time each day. While extreme flexibility in dose timing is not recommended, these findings are reassuring. This may be particularly beneficial to elderly patients, patients with learning difficulties, or others who have to rely on health-care professionals for their daily insulin injections. Further studies are required to confirm whether this might benefit adherence to treatment, reduce long

Insulin, cognition, and dementia

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Cholerton, Brenna; Baker, Laura D.; Craft, Suzanne

2015-01-01

Cognitive disorders of aging represent a serious threat to the social and economic welfare of current society. It is now widely recognized that pathology related to such conditions, particularly Alzheimer’s disease, likely begins years or decades prior to the onset of clinical dementia symptoms. This revelation has led researchers to consider candidate mechanisms precipitating the cascade of neuropathological events that eventually lead to clinical Alzheimer’s disease. Insulin, a hormone with potent effects in the brain, has recently received a great deal of attention for its potential beneficial and protective role in cognitive function. Insulin resistance, which refers to the reduced sensitivity of target tissues to the favorable effects of insulin, is related to multiple chronic conditions known to impact cognition and increase dementia risk. With insulin resistance-associated conditions reaching epidemic proportions, the prevalence of Alzheimer’s disease and other cognitive disorders will continue to rise exponentially. Fortunately, these chronic insulin-related conditions are amenable to pharmacological intervention. As a result, novel therapeutic strategies that focus on increasing insulin sensitivity in the brain may be an important target for protecting or treating cognitive decline. The following review will highlight our current understanding of the role of insulin in brain, potential mechanisms underlying the link between insulin resistance and dementia, and current experimental therapeutic strategies aimed at improving cognitive function via modifying the brain’s insulin sensitivity. PMID:24070815

Insulin and the brain.

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Derakhshan, Fatemeh; Toth, Cory

2013-03-01

Mainly known for its role in peripheral glucose homeostasis, insulin has also significant impact within the brain, functioning as a key neuromodulator in behavioral, cellular, biochemical and molecular studies. The brain is now regarded as an insulin-sensitive organ with widespread, yet selective, expression of the insulin receptor in the olfactory bulb, hypothalamus, hippocampus, cerebellum, amygdala and cerebral cortex. Insulin receptor signaling in the brain is important for neuronal development, glucoregulation, feeding behavior, body weight, and cognitive processes such as with attention, executive functioning, learning and memory. Emerging evidence has demonstrated insulin receptor signaling to be impaired in several neurological disorders. Moreover, insulin receptor signaling is recognized as important for dendritic outgrowth, neuronal survival, circuit development, synaptic plasticity and postsynaptic neurotransmitter receptor trafficking. We review the multiple roles of insulin in the brain, as well as its endogenous trafficking to the brain or its exogenous intervention. Although insulin can be directly targeted to the brain via intracerebroventricular (ICV) or intraparenchymal delivery, these invasive techniques are with significant risk, necessitating repeated surgical intervention and providing potential for systemic hypoglycemia. Another method, intranasal delivery, is a non-invasive, safe, and alternative approach which rapidly targets delivery of molecules to the brain while minimizing systemic exposure. Over the last decades, the delivery of intranasal insulin in animal models and human patients has evolved and expanded, permitting new hope for associated neurodegenerative and neurovascular disorders.

Insulin sensitivity and insulin secretion at birth in intrauterine growth retarded infants.

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Setia, Sajita; Sridhar, M G; Bhat, Vishnu; Chaturvedula, Lata; Vinayagamoorti, R; John, Mathew

2006-06-01

To study insulin sensitivity, secretion and relation of insulin levels with birth weight and ponderal index in intrauterine growth retarded (IUGR) infants at birth. We studied 30 IUGR and 30 healthy newborns born at term by vaginal delivery in Jipmer, Pondicherry, India. Cord blood was collected at the time of delivery for measurement of plasma glucose and insulin. When compared with healthy newborns, IUGR newborns had lower plasma glucose levels (mean 2.3+/-0.98 versus 4.1+/-0.51 mmol/L, p<0.001); lower plasma insulin levels (mean 4.5+/-2.64 versus 11.03+/-1.68 microU/L, p<0.001); higher insulin sensitivity calculated using G/I ratio (mean 11.6+/-5.1 versus 6.7+/-0.31, p<0.001), HOMA IS (mean 5.5+/-6.0 versus 0.53+/-0.15, p<0.001), and QUICKI (mean 0.47+/-0.12 versus 0.34+/-0.02, p<0.001); and decreased pancreatic beta-cell function test measured as I/G (mean 0.10+/-0.037 versus 0.15+/-0.006, p<0.001). A positive correlation was identified between insulin levels and birth weight in both the healthy control group (r2 = 0.17, p = 0.024) and IUGR group (r2 = 0.13, p = 0.048). However correlation of insulin levels with ponderal index was much more confident in both healthy control (r2 = 0.90, p<0.001) and IUGR groups (r2 = 0.28, p = 0.003). Insulin status correlated both with birth weight and ponderal index more confidently in control group than in IUGR group. At birth, IUGR infants are hypoglycaemic, hypoinsulinaemic and display increased insulin sensitivity and decreased pancreatic beta-cell function. Insulin levels correlate with ponderal index much more confidently than with birth weight.

Fasting and feeding variations of insulin requirements and insulin binding to erythrocytes at different times of the day in insulin dependent diabetics--assessed under the condition of glucose-controlled insulin infusion.

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Hung, C T; Beyer, J; Schulz, G

1986-07-01

Nine insulin-dependent diabetic patients were examined for insulin requirement, counterregulatory hormones, and receptor binding during their connection to glucose-controlled insulin infusion system. They were of 103% ideal body weight. A diet of 45% carbohydrate, 20% protein and 35% fat was divided into three meals and three snacks averaging the daily calorie intake of 1859 kcal. Following an equilibrating phase of 14 hours after the connection to the glucose-controlled insulin infusion system the blood samples were taken at 0800, 1200 and 1800. The insulin infusion rate increased at 0300 in the early morning from 0.128 mU/kg/min to 0.221 mU/kg/min (P less than 0.02). The postprandial insulin infusion rate jumped from 0.7 U/h (0700-0800) to 7.5 U/h (0800-0900). The calorie related and carbohydrate related insulin demands after breakfast were also highest and declined after lunch respectively (1.16 uU/kg/min kj vs. 0.61 uU/kg/min kj, P less than 0.05 and 236 mU/g CHO vs. 129 mU/g CHO and 143 mU/g CHO). Of the counterregulatory hormones the cortisol showed a significant diurnal rhythm to insulin demands. The insulin tracer binding was higher at 0800 before breakfast than that at 1200 before lunch (P less than 0.05). The increased binding could be better attributed to receptor concentration change than to affinity change. The cause of insulin relative insensitivity in the morning could be due to altered liver response to the cortisol peak in type 1 diabetics. The preserved variation of insulin binding in our patients might be referred to feeding.

Insulin sensitivity and albuminuria

DEFF Research Database (Denmark)

Pilz, Stefan; Rutters, Femke; Nijpels, Giel

2014-01-01

OBJECTIVE: Accumulating evidence suggests an association between insulin sensitivity and albuminuria, which, even in the normal range, is a risk factor for cardiovascular diseases. We evaluated whether insulin sensitivity is associated with albuminuria in healthy subjects. RESEARCH DESIGN...... AND METHODS: We investigated 1,415 healthy, nondiabetic participants (mean age 43.9 ± 8.3 years; 54.3% women) from the RISC (Relationship between Insulin Sensitivity and Cardiovascular Disease) study, of whom 852 participated in a follow-up examination after 3 years. At baseline, insulin sensitivity...... was assessed by hyperinsulinemic-euglycemic clamps, expressed as the M/I value. Oral glucose tolerance test-based insulin sensitivity (OGIS), homeostasis model assessment of insulin resistance (HOMA-IR), and urinary albumin-to-creatinine ratio (UACR) were determined at baseline and follow-up. RESULTS...

Insulin Resistance and Mitochondrial Dysfunction.

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Gonzalez-Franquesa, Alba; Patti, Mary-Elizabeth

2017-01-01

Insulin resistance precedes and predicts the onset of type 2 diabetes (T2D) in susceptible humans, underscoring its important role in the complex pathogenesis of this disease. Insulin resistance contributes to multiple tissue defects characteristic of T2D, including reduced insulin-stimulated glucose uptake in insulin-sensitive tissues, increased hepatic glucose production, increased lipolysis in adipose tissue, and altered insulin secretion. Studies of individuals with insulin resistance, both with established T2D and high-risk individuals, have consistently demonstrated a diverse array of defects in mitochondrial function (i.e., bioenergetics, biogenesis and dynamics). However, it remains uncertain whether mitochondrial dysfunction is primary (critical initiating defect) or secondary to the subtle derangements in glucose metabolism, insulin resistance, and defective insulin secretion present early in the course of disease development. In this chapter, we will present the evidence linking mitochondrial dysfunction and insulin resistance, and review the potential for mitochondrial targets as a therapeutic approach for T2D.

Selective Insulin Resistance in Adipocytes*

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Tan, Shi-Xiong; Fisher-Wellman, Kelsey H.; Fazakerley, Daniel J.; Ng, Yvonne; Pant, Himani; Li, Jia; Meoli, Christopher C.; Coster, Adelle C. F.; Stöckli, Jacqueline; James, David E.

2015-01-01

Aside from glucose metabolism, insulin regulates a variety of pathways in peripheral tissues. Under insulin-resistant conditions, it is well known that insulin-stimulated glucose uptake is impaired, and many studies attribute this to a defect in Akt signaling. Here we make use of several insulin resistance models, including insulin-resistant 3T3-L1 adipocytes and fat explants prepared from high fat-fed C57BL/6J and ob/ob mice, to comprehensively distinguish defective from unaffected aspects of insulin signaling and its downstream consequences in adipocytes. Defective regulation of glucose uptake was observed in all models of insulin resistance, whereas other major actions of insulin such as protein synthesis and anti-lipolysis were normal. This defect corresponded to a reduction in the maximum response to insulin. The pattern of change observed for phosphorylation in the Akt pathway was inconsistent with a simple defect at the level of Akt. The only Akt substrate that showed consistently reduced phosphorylation was the RabGAP AS160 that regulates GLUT4 translocation. We conclude that insulin resistance in adipose tissue is highly selective for glucose metabolism and likely involves a defect in one of the components regulating GLUT4 translocation to the cell surface in response to insulin. PMID:25720492

Insulin resistance: definition and consequences.

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Lebovitz, H E

2001-01-01

Insulin resistance is defined clinically as the inability of a known quantity of exogenous or endogenous insulin to increase glucose uptake and utilization in an individual as much as it does in a normal population. Insulin action is the consequence of insulin binding to its plasma membrane receptor and is transmitted through the cell by a series of protein-protein interactions. Two major cascades of protein-protein interactions mediate intracellular insulin action: one pathway is involved in regulating intermediary metabolism and the other plays a role in controlling growth processes and mitoses. The regulation of these two distinct pathways can be dissociated. Indeed, some data suggest that the pathway regulating intermediary metabolism is diminished in type 2 diabetes while that regulating growth processes and mitoses is normal.--Several mechanisms have been proposed as possible causes underlying the development of insulin resistance and the insulin resistance syndrome. These include: (1) genetic abnormalities of one or more proteins of the insulin action cascade (2) fetal malnutrition (3) increases in visceral adiposity. Insulin resistance occurs as part of a cluster of cardiovascular-metabolic abnormalities commonly referred to as "The Insulin Resistance Syndrome" or "The Metabolic Syndrome". This cluster of abnormalities may lead to the development of type 2 diabetes, accelerated atherosclerosis, hypertension or polycystic ovarian syndrome depending on the genetic background of the individual developing the insulin resistance.--In this context, we need to consider whether insulin resistance should be defined as a disease entity which needs to be diagnosed and treated with specific drugs to improve insulin action.

Interaction between exogenous insulin, endogenous insulin, and glucose in type 2 diabetes patients.

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Janukonyté, Jurgita; Parkner, Tina; Bruun, Niels Henrik; Lauritzen, Torsten; Christiansen, Jens Sandahl; Laursen, Torben

2015-05-01

Little is known about the influence of exogenous insulin and actual glucose levels on the release of endogenous insulin in insulin-treated type 2 diabetes mellitus (T2DM) patients. This study investigated the interaction among serum endogenous insulin (s-EI), serum exogenous insulin aspart (s-IAsp), and blood glucose levels in an experimental short-term crossover design. Eight T2DM patients (63.52 years old; range, 49-69 years; mean body mass index, 28.8±3.8 kg/m(2)) were randomized to treatment with individual fixed doses of insulin aspart (0.5-1.5 IU/h) as a continuous subcutaneous insulin infusion (CSII) during a 10-h period on two occasions with different duration of hyperglycemia: (1) transient hyperglycemia for 2 h (visit TH) and (2) continuous hyperglycemia for 12 h (visit CH). During steady state the variances of plasma glucose (p-glucose), s-IAsp, and s-EI were equal within visit TH and within visit CH, but variances were significantly higher during visit CH compared with visit TH. The s-IAsp reached lower levels at visit CH compared with visit TH (test for slope=1, P=0.005). The s-EI depended on p-glucose in a nonlinear fashion during the first 100 min of both visits when s-IAsp was undetectable (adjusted R(2)=0.9). A complex but statistically significant interaction among s-IAsp, s-EI, p-glucose, and patients was observed during measurable s-IAsp levels (adjusted R(2)=0.70). Endogenous and exogenous insulin showed higher variation during continuous hyperglycemia. Significantly lower levels of exogenous insulin were observed following CSII during continuous hyperglycemia compared with transient hyperglycemia. Endogenous insulin levels could in a complex way be explained by an individual interaction among p-glucose and serum exogenous insulin, if present.

Studies on interaction of insulin and insulin receptor in rat liver cell membranes

Energy Technology Data Exchange (ETDEWEB)

Sakai, Y; Hara, H; Kawate, R; Kawasaki, T [Hiroshima Univ. (Japan). School of Medicine

1975-07-01

Rat liver was homogenized with a Polytron PT 20 ST and fractionated by differential centrifugation. Prepared plasma membranes (100 ..mu..g protein) were incubated with enzymatically iodinated /sup 125/I-insulin (0.3 ng, specific activity 107 ..mu..Ci/..mu..g) in 25 mM Tris-HCl buffer, pH 7.5, containing 0.9% NaCl and 1% bovine serum albumin. The 12,000xg- and 17,000xg-sediments obtained after subfractionation of liver homogenates showed almost equally high specific binding activity with /sup 125/I-insulin and less activity was detected in the 600 g-, 5,000 g- and 40,000 g- sediments and the 40,000 g- supernatant. Specific binding of insulin with the membrane fraction was time-, temperature- and ionic strength-dependent. The highest binding was obtained under conditions in which the membrane fraction was incubated with insulin for 24 hours at 4/sup 0/C in the buffer containing 1 M NaCl. Under these conditions, specific binding of /sup 125/I-insulin was 26.8% of the total radioactivity. The effect of native insulin on the binding of /sup 125/I-insulin with the membrane fraction was studied in the range of 0--6.4 x 10/sup 5/ ..mu..U/ml of unlabeled insulin and a distinct competitive displacement of /sup 125/I-insulin with native insulin was observed between 10 and 10/sup 4/ ..mu..U/ml. Kinetic studies by Scatchard plot analysis of the above results revealed heterogeneity in insulin receptors or receptor sites, one with a high affinity of 10/sup 9/ M/sup -1/ order and the other with a low affinity of 10/sup 8/ M/sup -1/ order. Both affinities were also affected by temperature and ionic strength.

Clinical experience with insulin detemir, biphasic insulin aspart and insulin aspart in people with type 2 diabetes: Results from the Casablanca cohort of the A 1 chieve study

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Ahmed Farouqi

2013-01-01

Full Text Available Background: The A 1 chieve, a multicentric (28 countries, 24-week, non-interventional study evaluated the safety and effectiveness of insulin detemir, biphasic insulin aspart and insulin aspart in people with T2DM (n = 66,726 in routine clinical care across four continents. Materials and Methods: Data was collected at baseline, at 12 weeks and at 24 weeks. This short communication presents the results for patients enrolled from Casablanca, Morocco. Results: A total of 495 patients were enrolled in the study. Four different insulin analogue regimens were used in the study. Study patients had started on or were switched to biphasic insulin aspart (n = 231, insulin detemir (n = 151, insulin aspart (n = 19, basal insulin plus insulin aspart (n = 53 and other insulin combinations (n = 41. At baseline glycaemic control was poor for both insulin naïve (mean HbA 1 c: 10.2% and insulin user (mean HbA 1 c: 9.4% groups. After 24 weeks of treatment, both groups showed improvement in HbA 1 c (insulin naïve: −2.3%, insulin users: −1.8%. Major hypoglycaemia was observed in the insulin naïve group after 24 weeks. SADRs were reported in 1.2% of insulin naïve and 2.1% of insulin user groups. Conclusion: Starting or switching to insulin analogues was associated with improvement in glycaemic control with a low rate of hypoglycaemia.

Insulin Resistance in Alzheimer's Disease

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Dineley, Kelly T; Jahrling, Jordan B; Denner, Larry

2014-01-01

Insulin is a key hormone regulating metabolism. Insulin binding to cell surface insulin receptors engages many signaling intermediates operating in parallel and in series to control glucose, energy, and lipids while also regulating mitogenesis and development. Perturbations in the function of any of these intermediates, which occur in a variety of diseases, cause reduced sensitivity to insulin and insulin resistance with consequent metabolic dysfunction. Chronic inflammation ensues which exacerbates compromised metabolic homeostasis. Since insulin has a key role in learning and memory as well as directly regulating ERK, a kinase required for the type of learning and memory compromised in early Alzheimer's disease (AD), insulin resistance has been identified as a major risk factor for the onset of AD. Animal models of AD or insulin resistance or both demonstrate that AD pathology and impaired insulin signaling form a reciprocal relationship. Of note are human and animal model studies geared toward improving insulin resistance that have led to the identification of the nuclear receptor and transcription factor, peroxisome proliferator-activated receptor gamma (PPARγ) as an intervention tool for early AD. Strategic targeting of alternate nodes within the insulin signaling network has revealed disease-stage therapeutic windows in animal models that coalesce with previous and ongoing clinical trial approaches. Thus, exploiting the connection between insulin resistance and AD provides powerful opportunities to delineate therapeutic interventions that slow or block the pathogenesis of AD. PMID:25237037

Identification of Schistosoma mansoni candidate antigens for diagnosis of schistosomiasis

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Gardenia Braz Figueiredo Carvalho

2011-11-01

Full Text Available The development of a more sensitive diagnostic test for schistosomiasis is needed to overcome the limitations of the use of stool examination in low endemic areas. Using parasite antigens in enzyme linked immunosorbent assay is a promising strategy, however a more rational selection of parasite antigens is necessary. In this study we performed in silico analysis of the Schistosoma mansoni genome, using SchistoDB database and bioinformatic tools for screening immunogenic antigens. Based on evidence of expression in all parasite life stage within the definitive host, extracellular or plasmatic membrane localization, low similarity to human and other helminthic proteins and presence of predicted B cell epitopes, six candidates were selected: a glycosylphosphatidylinositol-anchored 200 kDa protein, two putative cytochrome oxidase subunits, two expressed proteins and one hypothetical protein. The recognition in unidimensional and bidimensional Western blot of protein with similar molecular weight and isoelectric point to the selected antigens by sera from S. mansoni infected mice indicate a good correlation between these two approaches in selecting immunogenic proteins.

Activity of praziquantel on in vitro transformed Schistosoma mansoni sporocysts

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ACA Mattos

2006-10-01

Full Text Available Praziquantel (PZQ is effective against all the evolutive phases of Schistosoma mansoni. Infected Biomphalaria glabrata snails have their cercarial shedding interrupted when exposed to PZQ. Using primary in vitro transformed sporocysts, labeled with the probe Hoechst 33258 (indicator of membrane integrity, and lectin of Glycine max (specific for carbohydrate of N-acetylgalactosamine membrane, we evaluated the presence of lysosomes at this evolutive phase of S. mansoni, as well as the influence of PZQ on these acidic organelles and on the tegument of the sporocyst. Although the sporocyst remained alive, it was observed that there was a marked contraction of its musculature, and there occurred a change in the parasite's structure. Also, the acidic vesicles found in the sporocysts showed a larger delimited area after contact of the parasites with PZQ. Damages to the tegument was also observed, as show a well-marked labeling either with Hoechst 33258 or with lectin of Glycine max after contact of sporocysts with the drug. These results could partially explain the interruption/reduction mechanism of cercarial shedding in snails exposed to PZQ.

Radiation-resistant acquired immunity of vaccinated mice to Schistosoma mansoni

International Nuclear Information System (INIS)

Aitken, R.; Coulson, P.S.; Dixon, B.; Wilson, R.A.

1987-01-01

Vaccination of mice with attenuated cercariae of Schistosoma mansoni induces specific acquired resistance to challenge infection. This resistance is immunologically-mediated, possibly via a delayed-type hypersensitivity. Studies of parasite migration have shown that the protective mechanism operates most effectively in the lungs of vaccinated mice. We have probed the mechanism by exposing mice to 500 rads of gamma radiation before challenge infection. Our results show that the effector mechanism operative against challenge larvae is resistant to radiation. In contrast, classical immune responses are markedly suppressed by the same treatment. While leukocyte populations in the blood fall dramatically after irradiation, numbers of cells recoverable by bronchoalveolar lavage are unaffected. We suggest that vaccination with attenuated cercariae establishes populations of sensitized cells in the lungs which trigger the mechanism of resistance when challenge schistosomula migrate through pulmonary capillary beds. Although the cells may be partially disabled by irradiation, they remain responsive to worm antigens and thereby capable of initiating the elimination mechanism. This hypothesis would explain the radiation resistance of vaccine-induced immunity to S. mansoni

Hormone-sensitive lipase null mice exhibit signs of impaired insulin sensitivity whereas insulin secretion is intact

DEFF Research Database (Denmark)

Mulder, Hindrik; Sörhede-Winzell, Maria; Contreras, Juan Antonio

2003-01-01

of increased amounts of insulin. Impaired insulin sensitivity was further indicated by retarded glucose disposal during an insulin tolerance test. A euglycemic hyperinsulinemic clamp revealed that hepatic glucose production was insufficiently blocked by insulin in HSL null mice. In vitro, insulin......-stimulated glucose uptake into soleus muscle, and lipogenesis in adipocytes were moderately reduced, suggesting additional sites of insulin resistance. Morphometric analysis of pancreatic islets revealed a doubling of beta-cell mass in HSL null mice, which is consistent with an adaptation to insulin resistance....... Insulin secretion in vitro, examined by perifusion of isolated islets, was not impacted by HSL deficiency. Thus, HSL deficiency results in a moderate impairment of insulin sensitivity in multiple target tissues of the hormone but is compensated by hyperinsulinemia....

Depressive symptoms, insulin sensitivity and insulin secretion in the RISC cohort study

NARCIS (Netherlands)

Bot, M.; Pouwer, F.; de Jonge, P.; Nolan, J.J.; Mari, A.; Højlund, K.; Golay, A.; Balkau, B.; Dekker, J.M.

2013-01-01

Aim This study explored the association of depressive symptoms with indices of insulin sensitivity and insulin secretion in a cohort of non-diabetic men and women aged 30 to 64 years. Methods The study population was derived from the 3-year follow-up of the Relationship between Insulin Sensitivity

Depressive symptoms, insulin sensitivity and insulin secretion in the RISC cohort study

NARCIS (Netherlands)

Bot, M.; Pouwer, F.; De Jonge, P.; Nolan, J. J.; Mari, A.; Hojlund, K.; Golay, A.; Balkau, B.; Dekker, J. M.

Aim. This study explored the association of depressive symptoms with indices of insulin sensitivity and insulin secretion in a cohort of non-diabetic men and women aged 30 to 64 years. Methods. The study population was derived from the 3-year follow-up of the Relationship between Insulin Sensitivity

Diabetes, insulin and exercise

DEFF Research Database (Denmark)

Richter, Erik; Galbo, H

1986-01-01

The metabolic and hormonal adaptations to single exercise sessions and to exercise training in normal man and in patients with insulin-dependent as well as non-insulin-dependent diabetes mellitus are reviewed. In insulin-dependent (type I) diabetes good metabolic control is best obtained...... by a regular pattern of life which will lead to a fairly constant demand for insulin from day to day. Exercise is by nature a perturbation that makes treatment of diabetes difficult: Muscle contractions per se tend to decrease the plasma glucose concentration whereas the exercise-induced response of the so......-called counter-regulatory hormones tend to increase plasma glucose by increasing hepatic glucose production and adipose tissue lipolysis. If the pre-exercise plasma insulin level is high, hypoglycaemia may develop during exercise whereas hyperglycaemia and ketosis may develop if pre-exercise plasma insulin...

Tegumental Ca-stimulated adenosine triphosphatase activity in adult Schistosoma mansoni worms Atividade da adenosina trifosfatase estimulada pelo Ca no tegumento de vermes adultos de Schistosoma mansoni

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Italo M. Cesari

1989-09-01

Full Text Available A Ca-stimulated ATPase activity (pH 9.5 associated with the tegumental membrane enriched (TME fraction of Schistosoma mansoni adults was partially inhibited by NAP-taurine or by increasing concentrations of chlorpromazine; endogenous calmodulin was found associated with the TME fraction. A similar activity (pH 8.6 was histochemically visualized whithin the tegument of fixed worms on the cytoplasmic leaflet of both the doubel surface membrane and the basement membrane; this reaction was inhibited by 1 µM chloropromazine and it was also observed on the inner side of double membrane vesicles present in the TME fraction. No ATPase activity could be seen at alkaline pH with added Mg or Na/K ions. Without ATP, the addition of external Ca to the fixed worms induced the appearance of lead precipitates on the tegumental discoid bodies; this reaction was inhibited by molybdate and not by chlorpromazine. The intrategumentary regulation of calcium by the systems described and the possible use of phenothiazines against schistosimes are discussed.A atividade ATPse (pH 9.5 estimulada por ions de Ca associados a uma fração enriquecida de membranas do tegumento (fração EMT de vermes adultos de Schistosoma mansoni, foi inibida pro NAP-taurina ou por concentrações crescentes de clorpromacina. Foi encontrada calmodulina enfogena associada principlamente a esta fração. Em vermes adultos fixados com glutaraldeido se detectou histoquimicamente uma atividade ATPase similar (pH 8.6 na face citoplasmática da dupla membrana de superfície e da membrana por 1 µM de clorpromacina e foi também observada na face interna de vesículas de dupla membrana presentes na fração EMT. Não se pôde detectar atividade ATpase em pH alcalino na presença de ions de Mg ou Na/K. A adição externa de Ca, sem ATP, aos vermes fixados induz ao aparecimento de precipitados nos corpos discóides do tegumento; esta reação foi inibida. Os resultados são discutidos em relação a

[News and perspectives in insulin treatment].

Science.gov (United States)

Haluzík, Martin

2014-09-01

Insulin therapy is a therapeutic cornerstone in patients with type 1 diabetes and also in numerous patients with type 2 diabetes especially with longer history of diabetes. The initiation of insulin therapy in type 2 diabetes patients is often delayed which is at least partially due to suboptimal pharmacokinetic characteristics of available insulins. The development of novel insulins with more favorable characteristics than those of current insulins is therefore still ongoing. The aim of this paper is to review current knowledge of novel insulins that have been recently introduced to the market or are getting close to routine clinical use. We will also focus on the perspectives of insulin therapy in the long-term run including the alternative routes of insulin administration beyond its classical subcutaneous injection treatment.Key words: alternative routes of insulin administration - diabetes mellitus - hypoglycemia - insulin - insulin analogues.

[Continuous insulin therapy versus multiple insulin injections in the management of type 1 diabetes: a longitutinal study].

Science.gov (United States)

Ribeiro, Maria Estela Bellini; Del Roio Liberatore Junior, Raphael; Custodio, Rodrigo; Martinelli Junior, Carlos Eduardo

2016-01-01

To compare multiple doses of insulin and continuous insulin infusion therapy as treatment for type 1 diabetes melito. 40 patients with type 1 diabetes melito (21 female) with ages between 10 and 20 years (mean=14.2) and mean duration of diabetes of 7 years used multiple doses of insulin for at least 6 months and after that, continuous insulin infusion therapy for at least 6 months. Each one of the patients has used multiple doses of insulin and continuous insulin infusion therapy. For analysis of HbA1c, mean glycated hemoglobin levels (mHbA1c) were obtained during each treatment period (multiple doses of insulin and continuous insulin infusion therapy period). Although mHbA1c levels were lower during continuous insulin infusion therapy the difference was not statistically significant. During multiple doses of insulin, 14.2% had mHbA1c values below 7.5% vs. 35.71% while on continuous insulin infusion therapy; demonstrating better glycemic control with the use of continuous insulin infusion therapy. During multiple doses of insulin, 15-40 patients have severe hypoglycemic events versus 5-40 continuous insulin infusion therapy. No episodes of ketoacidosis events were recorded. This is the first study with this design comparing multiple doses of insulin and continuous insulin infusion therapy in Brazil showing no significant difference in HbA1c; hypoglycemic events were less frequent during continuous insulin infusion therapy than during multiple doses of insulin and the percentage of patients who achieved a HbA1c less than 7.5% was greater during continuous insulin infusion therapy than multiple doses of insulin therapy. Copyright © 2015 Sociedade de Pediatria de São Paulo. Publicado por Elsevier Editora Ltda. All rights reserved.

Pitfalls of Insulin Pump Clocks

Science.gov (United States)

Reed, Amy J.

2014-01-01

The objective was to raise awareness about the importance of ensuring that insulin pumps internal clocks are set up correctly at all times. This is a very important safety issue because all commercially available insulin pumps are not GPS-enabled (though this is controversial), nor equipped with automatically adjusting internal clocks. Special attention is paid to how basal and bolus dose errors can be introduced by daylight savings time changes, travel across time zones, and am-pm clock errors. Correct setting of insulin pump internal clock is crucial for appropriate insulin delivery. A comprehensive literature review is provided, as are illustrative cases. Incorrect setting can potentially result in incorrect insulin delivery, with potential harmful consequences, if too much or too little insulin is delivered. Daylight saving time changes may not significantly affect basal insulin delivery, given the triviality of the time difference. However, bolus insulin doses can be dramatically affected. Such problems may occur when pump wearers have large variations in their insulin to carb ratio, especially if they forget to change their pump clock in the spring. More worrisome than daylight saving time change is the am-pm clock setting. If this setting is set up incorrectly, both basal rates and bolus doses will be affected. Appropriate insulin delivery through insulin pumps requires correct correlation between dose settings and internal clock time settings. Because insulin pumps are not GPS-enabled or automatically time-adjusting, extra caution should be practiced by patients to ensure correct time settings at all times. Clinicians and diabetes educators should verify the date/time of insulin pumps during patients’ visits, and should remind their patients to always verify these settings. PMID:25355713

Cyclodextrin-insulin complex encapsulated polymethacrylic acid based nanoparticles for oral insulin delivery.

Science.gov (United States)

Sajeesh, S; Sharma, Chandra P

2006-11-15

Present investigation was aimed at developing an oral insulin delivery system based on hydroxypropyl beta cyclodextrin-insulin (HPbetaCD-I) complex encapsulated polymethacrylic acid-chitosan-polyether (polyethylene glycol-polypropylene glycol copolymer) (PMCP) nanoparticles. Nanoparticles were prepared by the free radical polymerization of methacrylic acid in presence of chitosan and polyether in a solvent/surfactant free medium. Dynamic light scattering (DLS) experiment was conducted with particles dispersed in phosphate buffer (pH 7.4) and size distribution curve was observed in the range of 500-800 nm. HPbetaCD was used to prepare non-covalent inclusion complex with insulin and complex was analyzed by Fourier transform infrared (FTIR) and fluorescence spectroscopic studies. HPbetaCD complexed insulin was encapsulated into PMCP nanoparticles by diffusion filling method and their in vitro release profile was evaluated at acidic/alkaline pH. PMCP nanoparticles displayed good insulin encapsulation efficiency and release profile was largely dependent on the pH of the medium. Enzyme linked immunosorbent assay (ELISA) study demonstrated that insulin encapsulated inside the particles was biologically active. Trypsin inhibitory effect of PMCP nanoparticles was evaluated using N-alpha-benzoyl-L-arginine ethyl ester (BAEE) and casein as substrates. Mucoadhesive studies of PMCP nanoparticles were conducted using freshly excised rat intestinal mucosa and the particles were found fairly adhesive. From the preliminary studies, cyclodextrin complexed insulin encapsulated mucoadhesive nanoparticles appear to be a good candidate for oral insulin delivery.

TLR4 and Insulin Resistance

Directory of Open Access Journals (Sweden)

Jane J. Kim

2010-01-01

Full Text Available Chronic inflammation is a key feature of insulin resistance and obesity. Toll-Like Receptor 4 (TLR4, involved in modulating innate immunity, is an important mediator of insulin resistance and its comorbidities. TLR4 contributes to the development of insulin resistance and inflammation through its activation by elevated exogenous ligands (e.g., dietary fatty acids and enteric lipopolysaccharide and endogenous ligands (e.g., free fatty acids which are elevated in obese states. TLR4, expressed in insulin target tissues, activates proinflammatory kinases JNK, IKK, and p38 that impair insulin signal transduction directly through inhibitory phosphorylation of insulin receptor substrate (IRS on serine residues. TLR4 activation also leads to increased transcription of pro-inflammatory genes, resulting in elevation of cytokine, chemokine, reactive oxygen species, and eicosanoid levels that promote further insulin-desensitization within the target cell itself and in other cells via paracrine and systemic effects. Increased understanding of cell type-specific TLR4-mediated effects on insulin action present the opportunity and challenge of developing related therapeutic approaches for improving insulin sensitivity while preserving innate immunity.

Clinical experience with insulin detemir, biphasic insulin aspart and insulin aspart in people with type 2 diabetes: Results from the Mumbai cohort of the A1chieve study.

Science.gov (United States)

Talwalkar, P G; Gupta, Vishal; Kovil, Rajiv

2013-11-01

The A1chieve, a multicentric (28 countries), 24-week, non-interventional study evaluated the safety and effectiveness of insulin detemir, biphasic insulin aspart and insulin aspart in people with T2DM (n = 66,726) in routine clinical care across four continents. Data was collected at baseline, at 12 weeks and at 24 weeks. This short communication presents the results for patients enrolled from Mumbai, India. A total of 2112 patients were enrolled in the study. Four different insulin analogue regimens were used in the study. Patients had started on or were switched to biphasic insulin aspart (n = 1561), insulin detemir (n = 313), insulin aspart (n = 144), basal insulin plus insulin aspart (n = 53) and other insulin combinations (n = 41). At baseline glycaemic control was poor for both insulin naïve (mean HbA1c: 8.7%) and insulin user (mean HbA1c: 9.2%) groups. After 24 weeks of treatment, both the groups showed improvement in HbA1c (insulin naïve: -1.4%, insulin users: -1.8%). SADRs including major hypoglycaemic events or episodes did not occur in any of the study patients. Starting or switching to insulin analogues was associated with improvement in glycaemic control with a low rate of hypoglycaemia.

Sodium retention and insulin treatment in insulin-dependent diabetes mellitus

DEFF Research Database (Denmark)

Nørgaard, K; Feldt-Rasmussen, B

1994-01-01

subcutaneously, contributes to the increased ENa. Three studies were performed. Study 1 was a cross-sectional study comprising 28 type 1 diabetic men (aged 18-35 years) with short-duration diabetes (diabetic complications, and 22 control subjects. Study 2 was a prospective study of 17...... subcutaneous insulin infusion for improvement of glycaemic control or to remain on conventional insulin treatment. In study 1, ENa was higher in short-duration type 1 diabetic men than in controls (3003 +/- 325 vs 2849 +/- 207 mEq/1.73 m2, P ...The hypothesis that total body exchangeable sodium (ENa) is elevated in type 1 (insulin-dependent) diabetic patients with short-duration diabetes and no signs of microangiopathy was tested. Also tested was whether peripheral hyperinsulinaemia, in terms of the amounts of insulin injected...

The interaction of insulin, glucose, and insulin-glucose mixtures with a phospholipid monolayer.

Science.gov (United States)

Shigenobu, Hayato; McNamee, Cathy E

2012-12-15

We determined how glucose or insulin interacts with a phospholipid monolayer at the air/water interface and explained these mechanisms from a physico-chemical point of view. The 1,2-dipalmitoyl-2-sn-glycero-3-phosphatidylcholine (DPPC) monolayer at an air/water interface acted as a model membrane, which allowed the effect of the molecular packing density in the monolayer on the interactions to be determined. The interaction of glucose, insulin, and a mixture of glucose and insulin to the DPPC monolayer were investigated via surface pressure-area per molecule Langmuir isotherms and fluorescence microscopy. Glucose adsorbed to the underside of the DPPC monolayer, while insulin was able to penetrate through the monolayer when the phospholipid molecules were not densely packed. The presence of a mixture of insulin and glucose affected the molecular packing in the DPPC monolayer differently than the pure insulin or glucose solutions, and the glucose-insulin mixture was seen to be able to penetrate through the monolayer. These results indicated that glucose and insulin interact with one another, giving a material that may then transported through a pore in the monolayer or through the spaces between the molecules of the monolayer. Copyright © 2012 Elsevier Inc. All rights reserved.

Effect of aldicarb on growth and radio-carbon (14C) and radio-phosphorus (32P) assimilation by Rhizobium japonicum

International Nuclear Information System (INIS)

Balasubramanian, A.; Nilakantan, Gita

1976-01-01

In vitro studies on the effect of aldicarb (2-methyl-2-(methyl thio) propionaldehde-o-methyl carbamoyl oxime), a soil applied systemic insecticide, on Rhizobium japonicum revealed that the chemical (at 1,2 and 5 ppm levels) stimulated the growth of the organism initially upto 48 hr which declined thereafter upto 72 hr. The incorporation of 14 C-glucose by the cells considerably reduced due to the insecticide treatment. The production of extracellular, water-soluble slime (polysacchardes) was also reduced considerably with increased concentrations of the chemical. However, the incorporation of 14 C-radio-activity in the extracellular slime generally enhanced due to the treatment, upto 6 hr after injection of the radioactivity, which declined significantly later at 15 hr, indicating a qualitative difference in the extracellular polysaccharides produced by the insecticide treated cells. The insecticide treatment drastically reduced the incorporation of 32 P-disodium hydrogen phosphate into Rhizobium cells, but enhanced the specific activity of the extracellular polysacchrides. (author)

Insulin resistance and chronic inflammation

Directory of Open Access Journals (Sweden)

Natalia Matulewicz

2016-12-01

Full Text Available Insulin resistance is a condition of reduced biological response to insulin. Growing evidence indicates the role of the chronic low-grade inflammatory response in the pathogenesis of insulin resistance. Adipose tissue in obesity is characterized by increased lipolysis with the excessive release of free fatty acids, and is also a source of proinflammatory cytokines. Both these factors may inhibit insulin action. Proinflammatory cytokines exert their effect by stimulating major inflammatory NFκB and JNK pathways within the cells. Inflammatory processes in other insulin responsive tissues may also play a role in inducing insulin resistance. This paper is an overview of the chronic low-grade inflammation in adipose tissue, skeletal muscle, liver and endothelial cells during the development of insulin resistance.

Bariatric surgery in morbidly obese insulin resistant humans normalises insulin signalling but not insulin-stimulated glucose disposal.

Directory of Open Access Journals (Sweden)

Mimi Z Chen

Full Text Available Weight-loss after bariatric surgery improves insulin sensitivity, but the underlying molecular mechanism is not clear. To ascertain the effect of bariatric surgery on insulin signalling, we examined glucose disposal and Akt activation in morbidly obese volunteers before and after Roux-en-Y gastric bypass surgery (RYGB, and compared this to lean volunteers.The hyperinsulinaemic euglycaemic clamp, at five infusion rates, was used to determine glucose disposal rates (GDR in eight morbidly obese (body mass index, BMI=47.3 ± 2.2 kg/m(2 patients, before and after RYGB, and in eight lean volunteers (BMI=20.7 ± 0.7 kg/m2. Biopsies of brachioradialis muscle, taken at fasting and insulin concentrations that induced half-maximal (GDR50 and maximal (GDR100 GDR in each subject, were used to examine the phosphorylation of Akt-Thr308, Akt-473, and pras40, in vivo biomarkers for Akt activity.Pre-operatively, insulin-stimulated GDR was lower in the obese compared to the lean individuals (P<0.001. Weight-loss of 29.9 ± 4 kg after surgery significantly improved GDR50 (P=0.004 but not GDR100 (P=0.3. These subjects still remained significantly more insulin resistant than the lean individuals (p<0.001. Weight loss increased insulin-stimulated skeletal muscle Akt-Thr308 and Akt-Ser473 phosphorylation, P=0.02 and P=0.03 respectively (MANCOVA, and Akt activity towards the substrate PRAS40 (P=0.003, MANCOVA, and in contrast to GDR, were fully normalised after the surgery (obese vs lean, P=0.6, P=0.35, P=0.46, respectively.Our data show that although Akt activity substantially improved after surgery, it did not lead to a full restoration of insulin-stimulated glucose disposal. This suggests that a major defect downstream of, or parallel to, Akt signalling remains after significant weight-loss.

Glycosphingolipids and insulin resistance

NARCIS (Netherlands)

Langeveld, Mirjam; Aerts, Johannes M. F. G.

2009-01-01

Obesity is associated with an increased risk for insulin resistance, a state characterized by impaired responsiveness of liver, muscle and adipose tissue to insulin. One class of lipids involved in the development of insulin resistance are the (glyco)sphingolipids. Ceramide, the most simple

Changes in insulin and insulin signaling in Alzheimer’s disease: cause or consequence?

Science.gov (United States)

Stanley, Molly; Macauley, Shannon L.

2016-01-01

Individuals with type 2 diabetes have an increased risk for developing Alzheimer’s disease (AD), although the causal relationship remains poorly understood. Alterations in insulin signaling (IS) are reported in the AD brain. Moreover, oligomers/fibrils of amyloid-β (Aβ) can lead to neuronal insulin resistance and intranasal insulin is being explored as a potential therapy for AD. Conversely, elevated insulin levels (ins) are found in AD patients and high insulin has been reported to increase Aβ levels and tau phosphorylation, which could exacerbate AD pathology. Herein, we explore whether changes in ins and IS are a cause or consequence of AD. PMID:27432942

Insulin receptors in the mammary gland

International Nuclear Information System (INIS)

Smith, D.H.

1986-01-01

Insulin binding studies were conducted using mammary membrane preparations to further the authors understanding of insulin's role in regulating mammary metabolism, particularly ruminant mammary metabolism. Specific objectives were to: (1) characterize insulin binding to bovine mammary microsomes and determine if the specificity and kinetics of binding indicate the presence of insulin receptors in bovine mammary gland; (2) examine and compare insulin binding by liver and mammary microsomes of the pig and dairy cow; (3) examine insulin binding to bovine milk fat globule membranes (MFGM) and evaluate this model's usefulness in assessing insulin receptor regulation in the mammary gland of the cow; (4) examine the effect of dietary fat in insulin binding by rat mammary and liver microsomes. The specificity and kinetics of 125 I-insulin binding of bovine mammary microsomes indicated the presence of insulin receptors in bovine mammary gland. Bovine liver and mammary microsomes specifically bound less 125 I-insulin than did the corresponding porcine microsomes, and mammary microsomes, regardless of species, specifically bound less 125 I-insulin than did liver microsomes. These differences in binding suggest differences in insulin responsiveness between pigs and cattle, as well as between the liver and mammary glands

Genetic diversity of Schistosoma haematobium parasite IS NOT associated with severity of disease in an endemic area in Sudan.

Science.gov (United States)

Gasmelseed, Nagla; Karamino, Nhashal E; Abdelwahed, Mohammed O; Hamdoun, Anas O; Elmadani, Ahmed E

2014-08-27

Over 650 million people globally are at risk of schistosomiasis infection, while more than 200 million people are infected of which the higher disease rates occur in children. Eighty three students between 6-20 years (mean 12.45 ± 3.2) from Quran School for boys in Radwan village, Gezira state were recruited to investigate for the relationship between the genetic diversity of Schistosoma haematobium strains and the severity of the disease. Schistosoma haematobium infection was detected by filtration of urine. Ultrasonography was done on each study subject, while PCR technique was used for genotyping via random amplified polymorphic DNA (RAPD) with A01, A02, A12, Y20 and A13 primers. A01 primer gave three different genotypes (A01-1, A01-2 and A01-3). About 54.2% (45/83) were S. haematobium egg positive by urine filtration. On assessment of the upper and lower urinary tract by ultrasound technique, 61.4% (51/83) were positiveand73.3% (60/83) samples were PCR positive. No significant difference was found when comparing the three different genotypes with severity of the disease. This study concludes that no association was found between the different genotypes of S.haemtobium and the severity of the disease. Examination of more samples from different areas to identify any possible differences between the parasites genes and disease severity was recommended.

Blood Glucose and Insulin Concentrations after Octreotide Administration in Horses With Insulin Dysregulation

OpenAIRE

Frank, N.; Hermida, P.; Sanchez?Londo?o, A.; Singh, R.; Gradil, C.M.; Uricchio, C.K.

2017-01-01

Background Octreotide is a somatostatin analog that suppresses insulin secretion. Hypothesis We hypothesized that octreotide would suppress insulin concentrations in horses and that normal (N) horses and those with insulin dysregulation (ID) would differ significantly in their plasma glucose and insulin responses to administration of octreotide. Animals Twelve horses, N = 5, ID = 7. Methods Prospective study. An oral sugar test was performed to assign horses to N and ID groups. Octreotide (1....

Clinical experience with insulin detemir, biphasic insulin aspart and insulin aspart in people with type 2 diabetes: Results from the Rajasthan cohort of the A 1 chieve study

Directory of Open Access Journals (Sweden)

Akhil Joshi

2013-01-01

Full Text Available Background: The A 1 chieve, a multicentric (28 countries, 24-week, non-interventional study evaluated the safety and effectiveness of insulin detemir, biphasic insulin aspart and insulin aspart in people with T2DM (n = 66,726 in routine clinical care across four continents. Materials and Methods: Data was collected at baseline, at 12 weeks and at 24 weeks. This short communication presents the results for patients enrolled from Rajasthan, India. Results: A total of 477 patients were enrolled in the study. Four different insulin analogue regimens were used in the study. Patients had started on or were switched to biphasic insulin aspart (n = 340, insulin detemir (n = 90, insulin aspart (n = 37, basal insulin plus insulin aspart (n = 7 and other insulin combinations (n = 2. At baseline glycaemic control was poor for both insulin naïve (mean HbA 1 c: 8.3% and insulin user (mean HbA 1 c: 8.4% groups. After 24 weeks of treatment, both the groups showed improvement in HbA 1 c (insulin naïve: −0.9%, insulin users: −1.2%. Major hypoglycaemic events decreased from 0.5 events/patient-year to 0.0 events/patient-year in insulin naïve group while no change from baseline (1.3 events/patients-year was observed for insulin users. SADRs were not reported in any of the study patients. Conclusion: Starting or switching to insulin analogues was associated with improvement in glycaemic control with a low rate of hypoglycaemia.

Iontophoresis of monomeric insulin analogues in vitro: effects of insulin charge and skin pretreatment.

Science.gov (United States)

Langkjaer, L; Brange, J; Grodsky, G M; Guy, R H

1998-01-23

The aim of this study was to investigate the influence of association state and net charge of human insulin analogues on the rate of iontophoretic transport across hairless mouse skin, and the effect of different skin pretreatments on said transport. No insulin flux was observed with anodal delivery probably because of degradation at the Ag/AgCl anode. The flux during cathodal iontophoresis through intact skin was insignificant for human hexameric insulin, and only low and variable fluxes were observed for monomeric insulins. Using stripped skin on the other hand, the fluxes of monomeric insulins with two extra negative charges were 50-100 times higher than that of hexameric human insulin. Introducing three additional charges led to a further 2-3-fold increase in flux. Wiping the skin gently with absolute alcohol prior to iontophoresis resulted in a 1000-fold increase in transdermal transport of insulin relative to that across untreated skin, i.e. to almost the same level as stripping the skin. The alcohol pretreatment reduced the electrical resistance of the skin, presumably by lipid extraction. In conclusion, monomeric insulin analogues with at least two extra negative charges can be iontophoretically delivered across hairless mouse skin, whereas insignificant flux is observed with human, hexameric insulin. Wiping the skin with absolute alcohol prior to iontophoresis gave substantially improved transdermal transport of monomeric insulins resulting in clinically relevant delivery rates for basal treatment.

Insulin resistance, insulin response, and obesity as indicators of metabolic risk

DEFF Research Database (Denmark)

Ferrannini, Ele; Balkau, Beverley; Coppack, Simon W

2007-01-01

CONTEXT: Insulin resistance (IR) and obesity, especially abdominal obesity, are regarded as central pathophysiological features of a cluster of cardiovascular risk factors (CVRFs), but their relative roles remain undefined. Moreover, the differential impact of IR viz. insulin response has not been...... evaluated. OBJECTIVE: The objective of this study was to dissect out the impact of obesity, abdominal obesity, and IR/insulin response on CVRF. DESIGN: This was a cross-sectional study. SETTING: The study was conducted at 21 research centers in Europe. SUBJECTS: The study included a cohort of 1308......-cholesterol, and lower high-density lipoprotein-cholesterol, and insulin response to higher heart rate, blood pressure and fasting glucose, and the same dyslipidemic profile as IR (P

Clinical experience with insulin detemir, biphasic insulin aspart and insulin aspart in people with type 2 diabetes: Results from the Kolkata cohort of the A 1 chieve study

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Anirban Majumder

2013-01-01

Full Text Available Background: The A 1 chieve, a multicentric (28 countries, 24-week, non-interventional study evaluated the safety and effectiveness of insulin detemir, biphasic insulin aspart and insulin aspart in people with T2DM (n = 66,726 in routine clinical care across four continents. Materials and Methods: Data was collected at baseline, at 12 weeks and at 24 weeks. This short communication presents the results for patients enrolled from Kolkata, India. Results: A total of 576 patients were enrolled in the study. Four different insulin analogue regimens were used in the study. Patients had started on or were switched to biphasic insulin aspart (n = 417, insulin detemir (n = 70, insulin aspart (n = 55, basal insulin plus insulin aspart (n = 19 and other insulin combinations (n = 15. At baseline, glycaemic control was poor for both insulin naïve (mean HbA 1 c: 8.3% and insulin user (mean HbA 1 c: 8.6% groups. After 24 weeks of treatment, both the groups showed improvement in HbA 1 c (insulin naïve: −1.3%, insulin users: −1.4%. SADRs including major hypoglycaemic events or episodes did not occur in any of the study patients. Conclusion: Starting or switching to insulin analogues was associated with improvement in glycaemic control with a low rate of hypoglycaemia.

[Role of goat in transmission of schistosomiasis japonica III Environmental contamination by goat feces and prediction of environments at high risk of S. japonicum infection].

Science.gov (United States)

You-Sheng, Liang; Yi-An, Wang; Xue-Hui, Shen; Wei, Wang; Guo-Li, Qu; Yun-Tian, Xing; Jian-Rong, Dai

2016-10-18

To quantitatively estimate the range and area of environmental contamination by the feces of Schistosoma japonicum -infected that were freely grazed, so as to provide the theoretical evidence for the scientific assessment of the role of the freely grazed goat in the transmission of schistosomiasis japonica and development of control strategy. All the fecal samples excreted by the infected goat at daytime (12 h) were collected by using a self-made goat fecal collector, weighed and counted. The quantity and dispersal of the feces excreted by the freely grazed goat at daytime under a natural condition were investigated, and the walking route and speed of the freely grazed goat at daytime were recorded with a multifunction GPS data logger. The maximum range and area of the environment contaminated by the feces of the freely grazed goat at daytime were estimated, and the maximum range and area of the Oncomelania hupensis snails that may be infected by the schistosome miracidium released from the eggs in the fecal samples of the freely graze goat at daytime were calculated. During the walking along the marshland at daytime (12 h), the quantity of the feces execrated by the freely grazed infected goat was (232.8 ± 39.8) g per goat, and the fecal samples were composed of (819.2 ± 152.1) pellets. The goat had a mean walking speed of (0.522 7 ± 0.099 7) km/h, and the longest distance, largest radius and largest range of walking activity were (6.272 4 ± 1.195 8) km, 3.136 2 km and (3 191.113 0 ± 1 189.709 4) hm 2 at daytime, respectively. The area of the snails that may be infected by the miracidium released from the eggs in the fecal samples of the freely graze goat (range of key regions for infected snails detection and control) at daytime was estimated to be (3 210.717 5 ± 1 190.907 3) hm 2 . The intensity of environmental contamination by the eggs in the fecal samples of the freely grazed goat is linked to the number of infected goat. The contamination range caused

Effects of insulin-free plasma on the charcoal-separation method for radioimmunoassay of insulin

Energy Technology Data Exchange (ETDEWEB)

Frayn, K N [Medical Research Council, Carshalton (UK). Toxicology Unit

1976-03-01

Radioimmunoassay of insulin in rat plasma using a popular method involving charcoal-separation of free and antibody-bound insulin was found to be unsatisfactory despite inclusion in standard tubes of insulin-free plasma prepared in either of two ways. Insulin-free plasma and untreated plasma had different effects on adsorption of free insulin to the charcoal. It was concluded that separation with charcoal is very sensitive to any prior treatment of the plasma. Particular care must be taken to ensure that hormone-free plasma is identical in all other respects to untreated plasma.

Fluoxetine increases insulin action in obese type II (non-insulin dependent) diabetic patients

NARCIS (Netherlands)

Potter van Loon, B. J.; Radder, J. K.; Froelich, M.; Krans, H. Michiel J.; Zwinderman, A. H.; Meinders, A. E.

1992-01-01

Insulin resistance contributes to the metabolic defects in non-insulin dependent diabetes mellitus (NIDDM). Anorectic agents have been shown to improve insulin action in NIDDM, irrespective of weight reduction. In a double-blind placebo-controlled cross-over study, we examined hepatic and peripheral

Pulmonary leukocytic responses are linked to the acquired immunity of mice vaccinated with irradiated cercariae of Schistosoma mansoni

International Nuclear Information System (INIS)

Aitken, R.; Coulson, P.S.; Wilson, R.A.

1988-01-01

Pulmonary cellular responses in C57BL/6 mice exposed to Schistosoma mansoni have been investigated by sampling cells from the respiratory airways with bronchoalveolar lavage. Mice exposed to cercariae attenuated with 20 krad gamma-radiation developed stronger and more persistent pulmonary leukocytic responses than animals exposed to equal numbers of normal parasites. Although vaccination with irradiated cercariae also stimulated T cell responses of greater magnitude and duration than normal infection, the lymphocytic infiltrate elicited by each regimen did not differ substantially in its composition, 5 wk after exposure. Studies with cercariae attenuated by different treatments established that a link exists between the recruitment of leukocytes to the lungs of vaccinated mice and resistance to reinfection. There was a strong association between pulmonary leukocytic responses and the elimination of challenge infections by vaccinated mice. Animals exposed to irradiated cercariae of S. mansoni were resistant to homologous challenge infection but were not protected against Schistosoma margrebowiei. Homologous challenge of vaccinated mice stimulated anamnestic leukocytic and T lymphocytic responses in the lungs, 2 wk postinfection, but exposure of immunized animals to the heterologous species failed to trigger an expansion in these populations of cells. Our studies indicate that pulmonary leukocytes and T lymphocytes are intimately involved in the mechanism of vaccine-induced resistance to S. mansoni. It remains unclear whether these populations of cells initiate protective inflammatory reactions against challenge parasites in the lungs, or accumulate in response to the activation of the protective mechanism by other means

Studies on insulin receptor, 1

International Nuclear Information System (INIS)

Sakai, Yukio

1979-01-01

The present study was designed for the purpose of establishing a method of insulin radioreceptor assay using plasma membranes of guinea pigs as receptor sites. The results obtained are as follows: 1) Insulin receptor in the renal plasma membranes of guinea pigs showed a significantly high affinity to porcine insulin compared with that in the plasma membranes of guinea pig liver or rat kidney and liver. 2) In the insulin radioreceptor assay, an optimum condition was observed by the incubation at 4 0 C for 24 - 48 hours with 100 μg membrane protein of guinea pig kidney and 0.08 ng of 125 I-insulin. This assay method was specific for insulin and showed an accurate biological activity of insulin. 3) The recovery rate of insulin radioreceptor assay was 98.4% and dilution check up to 16 times did not influence on the result. An average of coefficient variation was 3.92% within assay. All of these results indicated the method to be satisfactory. 4) Glucose induced insulin release by perfusion method in isolated Langerhans islets of rats showed an identical pattern of reaction curves between radioreceptor assay and radioimmunoassay, although the values of radioreceptor assay was slightly low. 5) Insulin free serum produced by ultra filtration method was added to the standard assay medium. By this procedure, direct measurement of human serum by radioreceptor assay became possible. 6) The value of human serum insulin receptor binding activity by the radioreceptor assay showed a high correlation with that of insulin radioimmunoassay in sera of normal, borderline or diabetic type defined by glucose tolerance test. (author)

Intranasal insulin therapy: the clinical realities

DEFF Research Database (Denmark)

Hilsted, J; Madsbad, Sten; Hvidberg, A

1995-01-01

To evaluate metabolic control and safety parameters (hypoglycaemia frequency and nasal mucosa physiology), 31 insulin-dependent diabetic patients were treated with intranasal insulin at mealtimes for 1 month and with subcutaneous fast-acting insulin at meals for another month in an open, crossover...... randomized trial. During both treatment periods the patients were treated with intermediate-acting insulin at bedtime. Six of the patients were withdrawn from the study during intranasal insulin therapy due to metabolic dysregulation. Serum insulin concentrations increased more rapidly and decreased more...... quickly during intranasal as compared with subcutaneous insulin administration. Metabolic control deteriorated, as assessed by haemoglobin A1c concentrations, slightly but significantly after intranasal as compared with subcutaneous insulin therapy. The bioavailability of intranasally applied insulin...

Effect of iodination site on binding of radiolabeled ligand by insulin antibodies and insulin autoantibodies

International Nuclear Information System (INIS)

Diaz, J.L.; Wilkin, T.J.

1988-01-01

Four human insulins and four porcine insulins, each monoiodinated to the same specific activity at one of the four tyrosine residues (A14, A19, B16, B26) and purified by reversed-phase liquid chromatography, were tested in a radiobinding assay against a panel of insulin-antibody (IA)-positive sera from 10 insulin-treated diabetics and insulin-autoantibody-positive (IAA) sera from 10 nondiabetics. Of the 10 IAA-positive sera, five were fully cross reactive with both insulin species, and five were specific for human insulin. The rank order of binding of sera with the four ligands from each species was random for IA (mean rank values of 1.9 for A14, 2.0 for A19, 2.5 for B16, and 3.6 for B26 from a possible ranking range of 1 to 4), but more consistent for non-human-insulin-specific IAA (mean rank values 1.3 for A14, 3.8 for A19, 1.7 for B16, and 3.2 for B26 for labeled human insulins; 1.2 for A14, 4.0 for A19, 1.8 for B16, and 3.0 for B26 for labeled porcine insulins). The rank order of binding was virtually uniform for human-insulin-specific IAA (mean values 1.2 for A14, 3.0 for A19, 1.8 for B16, and 4.0 for B26). The influence of iodination site on the binding of labeled insulin appears to be dependent on the proximity of the labeled tyrosine to the antibody binding site and the clonal diversity, or restriction, of insulin-binding antibodies in the test serum. When IA and IAA are measured, the implications of this study regarding the choice of assay ligand may be important

The Establishment and Function of Schistosomiasis Surveillance System Towards Elimination in The People's Republic of China.

Science.gov (United States)

Zhang, L-J; Li, S-Z; Wen, L-Y; Lin, D-D; Abe, E M; Zhu, R; Du, Y; Lv, S; Xu, J; Webster, B L; Rollinson, D; Zhou, X-N

2016-01-01

Schistosoma japonicum is the main schistosome species in The People's Republic of China, causing intestinal schistosomiasis, a debilitating disease of public health importance. The People's Republic of China used to be heavily endemic with schistosomiasis, but great progress has been made through the vigorous efforts of the national control programmes in the last six decades. Presently, efforts are geared towards eliminating schistosomiasis from The People's Republic of China by the end of 2025 through effective schistosomiasis surveillance, an important component in the drive towards schistosomiasis elimination. Therefore, this article explicitly outlines the development and progress made in schistosomiasis surveillance since 1990 with a special focus on the new surveillance system in use. Although the surveillance system has steadily improved over the years, it is faced with many challenges. Hence, more efforts are needed to establish an effective and sensitive evaluation system for the national schistosomiasis elimination programme in The People's Republic of China. Copyright © 2016 Elsevier Ltd. All rights reserved.

Studies concerning the photoreceptor pigments of stentor coeruleus and blepharisma japonicum

International Nuclear Information System (INIS)

Dax, T.G.

2000-05-01

In the presence of 1,8-bis-(dimethylamino)-naphthalene, solutions of 3-O-benzyl hypericin and 3,4-di-O-benzyl hypericin in aromatic solvents like benzene or toluene have shown to be photoreactive, whereas in the dark no reactions occurred. 3-O-benzyl hypericin was found to enter a photorearrangement reaction leading to a product species, whose structural details could be elicited by UV/VIS, NMR, and mass spectroscopy together with spectrophotometric titrations. Investigation results led to a 11-phenyl-11H-benz{4,10}anthra{2,1,9,8-nopqa}pleiadene skeleton forming the backbone of the photoproduct. This fundamental system is the more of interest since it highly resembles the parent compound of the blepharismins, the photoreceptor pigments of Blepharisma japonicum. In analogy to blepharismin C, which can be converted photochemically into oxyblepharismin C and further on into stentorin by treatment with acid, the photoproduct could be transformed into hypericin upon irradiation and additional acidic work up. As the photoproduct incorporates several equilibrium systems, computer aided calculations were executed to achieve an idea about the relative stability of the photoproduct's various isomeric forms. The described photoreaction represents a possible route for the total synthesis of blepharismins and oxyblepharismins. Furthermore, it could shed some light on the biogenesis of these photosensing pigments. Irradiation of 3,4-di-O-benzyl hypericin in benzene solution together with a large excess of 1,8-bis-(dimethylamino)-naphthalene produced a species exhibiting a tremendous absorption band in the near IR. By means of EPR spectroscopy it could be stated that this primary photoproduct was of radical nature. The product was examined by means of UV/VIS, NMR, IR and mass spectroscopy. (author)

Acceptance of insulin therapy: a long shot? Psychological insulin resistance in primary care

NARCIS (Netherlands)

Woudenberg, Y. J. C.; Lucas, C.; Latour, C.; Scholte Op Reimer, W. J. M.

2012-01-01

Diabet. Med. 29, 796802 (2012) Abstract Aim To explore which factors are associated with psychological insulin resistance in insulin-naive patients with Type 2 diabetes in primary care. Methods A sample of 101 insulin-naive patients with Type 2 diabetes completed self-administered questionnaires

Effect of Avocado Soybean Unsaponifiables on Insulin Secretion and Insulin Sensitivity in Patients with Obesity

Directory of Open Access Journals (Sweden)

Esperanza Martínez-Abundis

2013-10-01

Full Text Available Aim: To evaluate the effect of avocado soybean unsaponifiables (ASU on insulin secretion and insulin sensitivity in patients with obesity. Methods: A randomized, double-blind, placebo-controlled, clinical trial was carried out in 14 obese adult volunteers. After random allocation of the intervention, 7 patients received 300 mg of ASU or placebo during a fasting state for 3 months. A metabolic profile including IL-6 and high-sensitivity C-reactive protein (hs-CRP levels was carried out prior to the intervention. A hyperglycemic-hyperinsulinemic clamp technique was used to assess insulin secretion and insulin sensitivity phases. Mann-Whitney U test and Wilcoxon test were performed for statistical analyses. The study was approved by the local ethics committee of our institution. Results: At baseline, both groups were similar according to clinical and laboratory characteristics. There was no significant difference in insulin secretion and insulin sensitivity with ASU. Conclusions: ASU administration for 3 months did not modify insulin secretion and insulin sensitivity in patients with obesity.