This first-in-human study was designed to evaluate the safety and dosimetry of the progesterone analog 21-18F-fluoro-16α,17α-[(R)-(1′-α-furylmethylidene)dioxy]-19-norpregn-4-ene-3,20-dione (18F-FFNP), as well the feasibility of imaging tumor progesterone receptors (PRs) by PET in breast cancer.
Women with breast cancer underwent PET with 18F-FFNP. Tumor 18F-FFNP uptake was assessed semiquantitatively by determining maximum standardized uptake value and tumor-to-normal breast (T/N) activity ratio and by Logan graphical analysis. The PET results were correlated with estrogen receptor (ER) and PR status, assessed by in vitro assays of the tumor tissue. The biodistribution of 18F-FFNP was measured in patients by whole-body PET, and human dosimetry was estimated.
Twenty patients with 22 primary breast cancers (16 PR-positive [PR+] and 6 PR-negative [PR−]) were evaluated. Tumor maximum standardized uptake value was not significantly different in PR+ and PR− cancers (mean ± SD, 2.5 ± 0.9 vs. 2.0 ± 1.3, P = 0.386), but the T/N ratio was significantly greater in the PR+ cancers (2.6 ± 0.9 vs. 1.5 ± 0.3, P = 0.001). In addition, there was a significant correlation between distribution volume ratio and T/N ratio (r = 0.89; P = 0.001) but not between distribution volume ratio and either PR status or standardized uptake value, likely because of small sample size. On the basis of whole-body PET data in 12 patients, the gallbladder appeared to be the dose-limiting organ, with an average radiation dose of 0.113 mGy/MBq. The whole-body dose was 0.015 mGy/MBq, and the effective dose was 0.020 mSv/MBq. No adverse effects of 18F-FFNP were encountered.
18F-FFNP PET is a safe, noninvasive means for evaluating tumor PRs in vivo in patients with breast cancer. The relatively small absorbed doses to normal organs allow for the safe injection of up to 440 MBq of 18F-FFNP.
PET; progesterone receptor; breast cancer
β-catenin is a unique intracellular protein functioning as an integral component of the cell-cell adherens complex and a principal signaling protein mediating canonical Wnt signaling. Little is known about its function in adult kidneys in the normal physiologic state or after acute kidney injury (AKI). To study this, we generated conditional knockout mice in which the β-catenin gene was specifically disrupted in renal tubules (Ksp-β-cat−/−). These mice were phenotypically normal with no appreciable defects in kidney morphology and function. In the absence of β-catenin, γ-catenin functionally substituted it for E-cadherin binding, thereby sustaining the integrity of epithelial adherens junctions in the kidneys. In AKI induced by ischemia reperfusion or folic acid, the loss of tubular β-catenin substantially aggravated renal lesions. Compared with controls, Ksp-β-cat−/− mice displayed higher mortality, elevated serum creatinine and more severe morphologic injury. Consistently, apoptosis was more prevalent in kidneys of the knockout mice, which was accompanied by increased expression of p53 and Bax, and decreased phosphorylated Akt and survivin. In vitro, activation of β-catenin by Wnt1 or stabilization of β-catenin protected tubular epithelial cells from apoptosis, activated Akt, induced survivin, and repressed p53 and Bax expression. Hence, endogenous β-catenin is pivotal for renal tubular protection after AKI by promoting cell survival through multiple mechanisms.
Wnt; β-catenin; acute kidney injury; apoptosis
Chlamydia spp. are obligate intracellular gram-negative bacteria that cause a wide range of significant diseases in humans and animals worldwide, resulting in significant economic losses. Chlamydial infection in cattle has been reported in many countries including China. However, there has been no survey of chlamydial infection of dairy cattle in Guangzhou, southern China. The objective of the present investigation was to examine the chlamydial seroprevalence in dairy cattle in Guangzhou, subtropical southern China by using an indirect hemagglutination assay (IHA). The overall seroprevalence of chlamydial infection in dairy cattle was 7.25% (29/400). Greater than or equal to eight-yr-old dairy cattle had the highest seroprevalence (10.34%), followed by those that were ≥ 6 years old or < 7 years old dairy cattle (10.20%), although there were no statistically significant differences among different groups (P > 0.05). Dairy cattle with 5 pregnancies had the highest seroprevalence (10.81%). These results indicate that chlamydial infection was present in dairy cattle in Guangzhou, subtropical southern China, and integrated strategies and measures should be executed to control and prevent chlamydial infection and disease outbreak in the study region.
Chlamydia; Dairy cattle; Seroprevalence; Indirect hemagglutination antibody (IHA); Guangzhou; China
Human thelaziosis is an underestimated parasitic disease caused by Thelazia species (Spirurida: Thelaziidae). The oriental eyeworm, Thelazia callipaeda, infects a range of mammalian definitive hosts, including canids, felids and humans. Although this zoonotic parasite is of socio-economic significance in Asian countries, its genetics, epidemiology and biology are poorly understood. Mitochondrial (mt) DNA is known to provide useful genetic markers to underpin fundamental investigations, but no mt genome had been characterized for any members of the family Thelaziidae. In the present study, we sequenced and characterized the mt genome of T. callipaeda. This AT-rich (74.6%) mt genome (13,668 bp) is circular and contains 12 protein-coding genes, 22 transfer RNA genes and two ribosomal RNA genes, but lacks an atp8 gene. All protein-coding genes are transcribed in the same direction; the gene order is the same as those of Dirofilaria immitis and Setaria digitata (Onchocercidae), but distinct from Dracunculus medinensis (Dracunculidae) and Heliconema longissimum (Physalopteridae). Phylogenetic analyses of the concatenated amino acid sequence data for all 12 protein-coding genes by Bayesian inference (BI) showed that T. callipaeda (Thelaziidae) is related to the family Onchocercidae. This is the first mt genome of any member of the family Thelaziidae and should represent a new source of genetic markers for studying the epidemiology, ecology, population genetics and systematics of this parasite of humans and other mammals.
Human thelaziosis is an underestimated parasitic disease caused by the eyeworm Thelazia callipaeda (Spirurida: Thelaziidae). Although this parasite is of significance in humans in many Asian countries, its genetics, epidemiology and biology are poorly understood. Mitochondrial (mt) DNA can provide useful genetic markers for fundamental investigations, but no mt genome had been characterized for any members of the family Thelaziidae. In this study, we sequenced and characterized the mt genome of T. callipaeda. This circular mt genome is 13,668 bp long and contains 12 protein-coding genes, 22 transfer RNA genes and two ribosomal RNA genes, but lacks an atp8 gene. Phylogenetic analyses of the concatenated amino acid sequence data for all 12 protein-coding genes by Bayesian inference showed that T. callipaeda is closely related to the family Onchocercidae, consistent with previous study. This is the first mt genome of any member of the family Thelaziidae, and represents a new source of genetic markers for studies of the epidemiology, ecology, population genetics and systematics of this parasite of human and animal health significance.
The present study aimed to evaluate the early effects of interspinous spacers on lumbar degenerative disease. The clinical outcomes of 23 patients with lumbar degenerative disease, treated using interspinous spacer implantation alone or combined with posterior lumbar fusion, were retrospectively studied and assessed with a visual analogue scale (VAS) and the Oswestry Disability Index (ODI). Pre-operative and post-operative interspinous distance, disc space height, foraminal width and height and segmental lordosis were determined. The early effects and complications associated with the interspinous spacers were recorded. The surgical procedures performed with the in-space treatment were easy and minimally invasive. The VAS scores and ODI were improved post-operatively compared with pre-operatively. Significant changes in the interspinous distance, disc space height, foraminal width and height and segmental lordosis were noted. In-space treatment for degenerative lumbar disease is easy and safe, with good early effects. The in-space system provides an alternative treatment for lumbar degenerative disease.
lumbar degenerative disease; In-space; interspinous dynamic stabilisation
One major challenge in the development of cancer therapeutics is the selective delivery of the drugs to their cellular targets. In the case of pancreatic cancer, the σ-2 receptor is a unique target that triggers apoptosis upon activation. We have previously developed a series of chemical compounds with high affinity for the σ-2 receptor and demonstrated rapid internalization of the ligands. One particular specific ligand of the σ-2 receptor, SV119, binds to pancreatic cancer cells and induces target cell death in vitro and in vivo. In this study, we characterized the ability of SV119 to selectively deliver other death-inducing cargos to augment the cytotoxic properties of SV119 itself. When conjugated to SV119, small molecules that are known to interfere with intracellular pro-survival pathways retained their ability to induce cell death, the efficiency of which was enhanced by the combinatorial effect of SV119 delivered with its small molecule cargo.
Our findings define a simple platform technology to increase the tumor-selective delivery of small molecule therapeutics via sigma-2 ligands, permitting chemotherapeutic synergy that can optimize efficacy and patient benefit.
apoptosis; drug delivery; pancreatic neoplasms; σ-2 receptor; sigma-2 conjugates
Noninvasive imaging methods that can distinguish apoptosis from necrosis may be useful in furthering our understanding of diseases characterized by apoptotic dysregulation as well as aiding drug development targeting apoptotic pathways. We evaluated the ability of radiolabeled isatins to quantify caspase-3 activity induced by the activation of the extrinsic apoptotic pathway by the anti-Fas antibody in mice.
The behavior of three different radiolabeled isatins ([18F]WC-II-89, [18F]WC-IV-3, and [11C]WC-98), was characterized in mice with and without anti-Fas antibody treatment by microPET imaging and biodistribution studies. The activity of [18F]WC-II-89 was also compared with [99mTc]mebrofenin. The effect of pan-caspase inhibition with Q-VD-OPH on [18F]WC-II-89 uptake was studied. Caspase-3 activity was confirmed by a fluorometric enzyme assay.
All three tracers behaved similarly in microPET and biodistribution studies. Increased retention of all tracers was observed in the livers of treated animals and several other organs, all of which demonstrated increased caspase-3 enzyme activity; however, impaired hepatobiliary excretion made attribution of these findings to caspase-3 activity difficult. The isatin [18F]WC-II-89 was retained at statistically significantly higher levels in the organs after anti-Fas antibody treatment while [99mTc]mebrofenin activity cleared, suggesting specific binding to activated caspase-3, but the magnitude of increased binding was still relatively low. Caspase inhibition with Q-VD-OPH partially blocked [18F]WC-II-89 retention but completely blocked caspase-3 enzyme activity in the liver.
The radiolabeled isatins appear to bind specifically to caspase-3 in vivo, but their sensitivity is limited. Further optimization is required for these tracers to be useful for clinical applications.
MicroRNAs (miRNAs) are key regulators of gene expression at the post-transcription level. The present study specifically explored and compared the miRNA expression profiles of F. gigantica and F. hepatica using an integrated sequencing and bioinformatics platform and quantitative real-time PCR. Nineteen and 16 miRNA candidates were identified from F. gigantica and F. hepatica, respectively. The two parasites shared 11 miRNAs, with 8 also showing similarity to miRNAs of Schistosoma japonicum. Another 8 miRNAs were identified as F. gigantica-specific and 5 as F. hepatica-specific, most of which were novel. Predicted target analysis with 11465 mRNA and EST sequences of F. hepatica and F. gigantica revealed that all of the miRNAs had more than one target, ranging from 2 to 398 with an average of 51 targets. Some functions of the predicted targets were only found in F. gigantica, such as “transcription regulator”, while some others were only found in F. hepatica, such as “reproduction” and “response to stimulus”, indicating the different metabolism and gene regulation patterns of the two parasites. The present study represents the first global comparative characterization of miRNA expression profiles of F. gigantica and F. hepatica, which has provided novel valuable resources for a better understanding of the two zoonotic trematodes.
Toxoplasma gondii is a highly prevalent protozoan parasite infecting a wide range of animals and humans. The epidemiological and biological diversity of T. gondii has resulted in a high genetic variation and unusual population structure in this parasite. This study examined sequence diversity in dense granule 5 (GRA5) gene among T. gondii isolates from different hosts and geographical regions.
The entire genome region of the GRA5 gene was amplified and sequenced from 14 T. gondii isolates, and phylogenetic relationship among these T. gondii isolates was reconstructed using Bayesian inference (BI) and maximum parsimony (MP) based on the GRA5 sequences.
The complete sequence of the GRA5 gene was 1614 bp in length for strains TgCatBr5 and MAS, but 1617 bp for the other 12 strains. Sequence analysis identified 41 (0–1.7%) variable nucleotide positions among all isolates, with 18 variations of these being in the coding region. Variable positions in the coding region resulted in 11 amino acid substitutions, and a deletion of 3 bp in the strains TgCatBr5 and MAS leading to the deletion of one amino acid. Sequence variations resulted in the existence of polymorphic restriction sites for endonucleases AatII and MluI, allowing the differentiation of the three major clonal lineage types I, II and III by PCR-RFLP. Phylogenetic analyses using BI and MP supported the clear differentiation of the examined T. gondii strains into their respective genotypes.
This study demonstrated the existence of sequence variability in the GRA5 gene sequence among T. gondii isolates from different hosts and geographical regions, which allowed the differentiation of the examined T. gondii strains into their respective genotypes, suggesting that this highly polymorphic GRA5 locus may provide a new genetic marker for population genetic studies of T. gondii isolates.
Toxoplasma gondii; Toxoplasmosis; GRA5 gene; Genetic diversity; Genotyping
The maintenance of genomic stability requires accurate genome replication, repair of DNA damage, and the precise segregation of chromosomes in mitosis. GEN1 possesses Holliday junction resolvase activity in vitro and presumably functions in homology driven repair of DNA double strand breaks. However, little is currently known about the cellular functions of human GEN1. In the present study we demonstrate that GEN1 is a novel centrosome associated protein and we characterize the various phenotypes associated with GEN1 deficiency. We identify an N-terminal centrosome localization signal in GEN1, which is required and sufficient for centrosome localization. We report that GEN1 depletion results in aberrant centrosome numbers associated with the formation of multiple spindle poles in mitosis, an increased number of cells with multi-nuclei, increased apoptosis and an elevated level of spontaneous DNA damage. We find homologous recombination severely impaired in GEN1 deficient cells, suggesting that GEN1 functions as a Holliday junction resolvase in vivo as well as in vitro. Complementation of GEN1 depleted cells with various GEN1 constructs revealed that centrosome association but not catalytic activity of GEN1 is required for preventing centrosome hyper-amplification, formation of multiple mitotic spindles, and multi-nucleation. Our findings provide novel insight into the biological functions of GEN1 by uncovering an important role of GEN1 in the regulation of centrosome integrity.
The purpose of this study was to assess the value of isocentric C-arm three-dimensional (Iso-C 3D) fluoroscopy for the insertion of an anterior odontoid screw. The results of the Iso-C 3D group were compared with that of an historic control group using conventional fluoroscopy.
Twenty-nine patients diagnosed with type II or rostral-type III odontoid fractures were treated with a single anterior screw fixation in this study. The Iso-C 3D group included 13 patients and the other 16 patients were in the historic control group. All operations were performed by a single surgeon using standard procedure and manner. The clinical and radiographic results were recorded and compared between the two groups.
The fluoroscopy time in the Iso-C 3D group was 42.9 s as compared to 68.1 s in the control group (P < 0.01). The mean operative time was 91.5 min in the Iso-C 3D group when compared with 81.6 min in the control group (P = 0.20). The rate of bony fusion was 96.6% (28/29), the failure rate of reduction or fixation was 13.8% (7.7% in Iso-C 3D group; 18.8% in control group). The Smiley–Webster scale showed that 90% of patients achieved good or better outcomes
In conclusion, this technique can be safely extended to the treatment of technically difficult to treat spinal injuries and at the same time reduce total radiation exposure time both for the patient and the surgeon.
Odontoid fracture; Anterior screw fixation; Isocentric C-arm fluoroscopy; Three-dimensional fluoroscopy
Host cell invasion by Toxoplasma gondii is tightly related to microneme protein 6 (MIC6) and T. gondii perforin-like protein 1 (TgPLP1). In this study, we constructed a DNA vaccine expressing a TgPLP1/MIC6 fusion protein using the pIRESneo vector, and we evaluated the immune response induced by this vaccine in Kunming mice. Levels of IgG antibody, gamma interferon (IFN-γ), interleukin 2 (IL-2), IL-12, IL-4, and IL-10 were examined. Five mice were chosen randomly from every group (vaccinated groups or the nonvaccinated control group) and were challenged intragastrically with 80 cysts of T. gondii strain PRU (genotype II) in order to observe mortality daily. To analyze protection against a less-virulent challenge, eight mice of each group were orally infected with 20 cysts of strain PRU at the 14th day after the last immunization. The brain parasite load was evaluated 6 weeks after infection. The results demonstrated that immunization with pIRESneo/MIC6/PLP1 resulted in the lowest brain cyst count and prolonged the survival time of immunized mice. The levels of Toxoplasma-specific IgG, IFN-γ, IL-2, and IL-12 increased significantly, and the numbers of cysts in brains decreased more obviously, in the group immunized with plasmid pIRESneo/MIC6/PLP1 than in the other groups (P < 0.05). Compared with pIRESneo/MIC6/PLP1, coimmunization with pIRESneo/MIC6/PLP1 and adjuvant murine IL-18 promoted cellular and humoral immune responses but did not contribute significantly to cyst reduction (65.43% versus 61.60%) or the survival of immunized mice (45.0 ± 2.9 days versus 42.8 ± 2.9 days) (P > 0.05). Furthermore, the study also showed that the immune efficacy induced by pIRESneo/MIC6/PLP1 was better than that induced by pVAX/PLP1 or pVAX/MIC6 alone.
The neglected blood flukes Orientobilharzia spp. belonging to the Platyhelminthes, infect animals in a number of countries of the world, and cause cercarial dermatitis in humans, as well as significant diseases and even death in economically-important animals. MicroRNAs (miRNAs) are now considered to be a key mechanism of gene regulation. Herein, we investigated the global miRNA expression profile of adult O. turkestanicum using next-generation sequencing technology and real-time quantitative PCR, to gain further information on the role of these molecules in host invasion and the parasitic lifestyle of this species. A total of 13.48 million high quality reads were obtained out of 13.78 million raw sequencing reads, with 828 expressed miRNAs identified. Phylogenetic analysis showed that the miRNAs of O. turkestanicum were still rapidly evolving and there was a “directed mutation” pattern compared with that of other species. Target mRNAs were successfully predicted to 518 miRNAs. These targets included energy metabolism, transcription initiation factors, signal transduction, growth factor receptors. miRNAs targeting egg proteins, including major egg antigen p40, and heat shock proteins were also found. Enrichment analysis indicated enrichment for mRNAs involved in catalytic, binding, transcription regulators and translation regulators. The present study represented the first large-scale characterization of O. turkestanicum miRNAs, which provides novel resources for better understanding the complex biology of this zoonotic parasite, which, in turn, has implications for the effective control of the disease it causes.
Toxoplasma gondii is an intracellular protozoan parasite infecting almost all warm-blooded animals, including birds, with a worldwide distribution. Surveys of T. gondii infection in wild birds have been reported extensively in the world, but little is known of T. gondii infection in peafowls worldwide. This study was performed to determine the seroprevalence of T. gondii infection in peafowls in Yunnan Province, southwestern China.
Sera from 277 peafowls, including 272 blue peafowls (Pavo cristatus) and 5 green peafowls (Pavo muticus) originated from two geographic areas in Yunnan Province were assayed for T. gondii antibodies using the modified agglutination test (MAT).
Specific T. gondii antibodies were detected in 35 of 277 (12.64%) peafowls (MAT titer ≥ 1:5). Seropositive birds were found in both species, 33 in 272 blue peafowls and 2 in 5 green peafowls. There was no significant difference in T. gondii seroprevalence between the adolescent birds (6.74%) and the adult birds (6.67%) (P > 0.05). The geographical origins of peafowls was found to be highly associated with T. gondii infection in the present study, a statistically significant difference in T. gondii seropositivity was observed between peafowls from Kunming (31.08%) and those from Xishuangbanna Dai Autonomous Prefecture (5.91%) (OR = 10.956, 95% CI = 1.632-73.545, P = 0.014). Statistical analyses showed that there were no significant interactions between ages and geographical origins of peafowls (P > 0.05).
The results of the present survey indicated that infection of peafowls with T. gondii is widespread in Yunnan Province, which has significant public health concerns and implications for prevention and control of toxoplamosis in this province. To our knowledge, this is the first seroprevalence report of T. gondii infection in China’s southwestern Yunnan Province.
Recently, the coexistence of gastrointestinal stromal tumors (GISTs) with other neoplasms has been studied with increasing frequency. Coexistence of pancreatic cancer with GISTs remains a rarity; however, here, we report a very rare case of adenosquamous carcinoma (ASC) of the uncinate process of the pancreas with synchronous GISTs of the stomach in a 62-year-old female. The patient presented with epigastric discomfort and vomiting. Radiographic imaging revealed two masses; one located at the body of the stomach and the other located at the uncinate process of the pancreas. Intraoperatively, a fine needle aspiration biopsy was conducted in the uncinate process of the pancreas, which revealed the malignancy of the masses. A pancreaticoduodenectomy and partial gastrectomy were then conducted, and subsequent pathological examinations identified an ASC of the pancreas and a GIST of the stomach. In our case, contrary to the majority of previous cases of synchronous GISTs and other malignancies, GIST was not an incidental finding. The initial suspicion on the GIST as the underlying cause of clinical symptoms led to the discovery of the ASC of the uncinate process of the pancreas.
adenosquamous carcinoma; gastrointestinal stromal tumor; synchronous cancer; uncinate process of the pancreas
Canine and feline parasitic zoonoses have not been given high priority in China, although the role of companion animals as reservoirs for zoonotic parasitic diseases has been recognized worldwide. With an increasing number of dogs and cats under unregulated conditions in China, the canine and feline parasitic zoonoses are showing a trend towards being gradually uncontrolled. Currently, canine and feline parasitic zoonoses threaten human health, and cause death and serious diseases in China. This article comprehensively reviews the current status of major canine and feline parasitic zoonoses in mainland China, discusses the risks dogs and cats pose with regard to zoonotic transmission of canine and feline parasites, and proposes control strategies and measures.
Parasitic zoonoses; China; Dogs; Cats; Prevalence
Probiotic could be a promising alternative to antibiotics for the prevention of enteric infections; however, further information on the dose effects is required. In this study, weanling piglets were orally administered low- or high-dose Lactobacillus rhamnosus ACTT 7469 (1010 CFU/d or 1012 CFU/d) for 1 week before F4 (K88)-positive Escherichia coli challenge. The compositions of faecal and gastrointestinal microbiota were recorded; gene expression in the intestines was assessed by real-time PCR; serum tumour necrosis factor-α (TNF-α) concentrations and intestinal Toll-like receptor 4 (TLR4) were detected by ELISA and immunohistochemistry, respectively. Unexpectedly, high-dose administration increased the incidence of diarrhoea before F4+ETEC challenge, despite the fact that both doses ameliorated F4+ETEC-induced diarrhoea with increased Lactobacillus and Bifidobacterium counts accompanied by reduced coliform shedding in faeces. Interestingly, L. rhamnosus administration reduced Lactobacillus and Bifidobacterium counts in the colonic contents, and the high-dose piglets also had lower Lactobacillius and Bacteroides counts in the ileal contents. An increase in the concentration of serum TNF-α induced by F4+ETEC was observed, but the increase was delayed by L. rhamnosus. In piglets exposed to F4+ETEC, jejunal TLR4 expression increased at the mRNA and protein levels, while jejunal interleukin (IL)-8 and ileal porcine β-defensins 2 (pBD2) mRNA expression increased; however, these increases were attenuated by administration of L. rhamnosus. Notably, expression of jejunal TLR2, ileal TLR9, Nod-like receptor NOD1 and TNF-α mRNA was upregulated in the low-dose piglets after F4+ETEC challenge, but not in the high-dose piglets. These findings indicate that pretreatment with a low dose of L. rhamnosus might be more effective than a high dose at ameliorating diarrhoea. There is a risk that high-dose L. rhamnosus pretreatment may negate the preventative effects, thus decreasing the prophylactic benefits against potential enteric pathogens. Our data suggest a safe threshold for preventative use of probiotics in clinical practice.
Toxoplasma gondii infection is a global concern, affecting a wide range of warm-blooded animals and humans worldwide, including poultry. Domestic and companion birds are considered to play an important role in the transmission of T. gondii to humans and other animals. However, little information on T. gondii infection in domestic birds in Lanzhou, northwest China was available. Therefore, this study was performed to determine the seroprevalence of T. gondii infection in domestic birds in Lanzhou, northwest China.
In the present study, the seroprevalence of T. gondii antibodies in 413 (305 caged and 108 free-range) adult chickens, 334 (111 caged and 223 free-range) adult ducks and 312 adult pigeons in Lanzhou, northwest China, were examined using the modified agglutination test (MAT).
30 (7.26%) chickens, 38 (11.38%) ducks and 37 (11.86%) pigeons were found to be positive for T. gondii antibodies at the cut-off of 1:5. The prevalences in caged and free-range chickens were 6.23% and 10.19% respectively, however, statistical analysis showed that the difference was not significant (P > 0.05). The seroprevalences in caged and free-range ducks were 6.31% and 13.90% respectively, but the difference was not statistically significant (P > 0.05).
The results of the present survey indicated the presence of T. gondii infection in adult chickens, ducks and pigeons sold for meat in poultry markets in Lanzhou, northwest China, which poses a potential risk for T. gondii infection in humans and other animals in this region. This is the first seroprevalence study of T. gondii infection in domestic birds in this region.
To investigate the clinical applications of coronary CT angiography in patients with suspected coronary artery disease and identify factors that affect CT findings.
Medical records of patients suspected of coronary artery disease over a period of 12 months from a tertiary teaching hospital were retrospectively reviewed. Patient age, sex (male/female), duration of symptoms and abnormal rates of coronary CT angiography scans were analysed to investigate the relationship among these parameters. The patients by age were characterized into five groups: under 36 years, 36–45 years, 46–55 years, 56–65 years and more than 66 years, respectively; while the duration of symptoms was also classified into five groups: less than one week, one week to one month, one to three months, three to six months and more than six months.
Of the 880 patient records reviewed, 800 met the above study criteria. Five hundred and forty nine patients demonstrated abnormal CT findings (68.6%). There was no significant difference in the percentage of abnormal CT findings based on patient sex and the duration of symptoms (P = 0.14). The abnormal rates of coronary CT angiography, however, increased significantly with increasing age (P < 0.001); with patients over 65 years of age 2.5 times more likely to have an abnormal CT scan relative to a patient under 45 years. A significant difference was found between abnormal coronary CT angiography and the duration of symptoms (P = 0.012).
Our results indicate coronary CT angiography findings are significantly related to the patient age group and duration of symptoms. Clinical referral for coronary CT angiography of patients with suspected coronary artery disease needs to be justified with regard to the judicious use of this imaging modality.
Coronary computed tomography; Coronary artery disease; Radiation; Diagnostic indications
Our previous studies demonstrated that simvastatin reduced neuronal death, increased neurogenesis, and promoted functional recovery after TBI. Objective: To investigate the effect of simvastatin on angiogenesis after TBI, and the related signaling pathways.
Saline or simvastatin (1 mg/kg) was administered orally to rats starting at day 1 after TBI or sham surgery and then daily for 14 days. Rats were sacrificed at 3 and 14 days after treatment. Brain sections and tissues were prepared for immunohistochemical staining, ELISA, and Western blot analysis, respectively. Cultured rat brain microvascular endothelial cells (RBMVECs) were subjected to oxygen-glucose deprivation (OGD) followed by immunocytochemical staining with phallotoxins and vascular endothelial growth factor receptor-2 (VEGFR-2). Western blot analysis was carried out to examine the simvastatin-induced activation of the v-akt murine thymoma viral oncogene homolog (Akt) signaling pathway. The expression of VEGFR-2 was detected by ELISA.
Simvastatin significantly increased the length of vascular perimeter, promoted the proliferation of endothelial cells, and improved the sensorimotor function after TBI. Simvastatin stimulated endothelial cell tube formation after OGD in vitro. VEGFR-2 expression in both brain tissues and cultured RBMVECs was enhanced after simvastatin treatment, which may be modulated by activation of Akt. Akt-dependent endothelial nitric oxide synthase (eNOS) phosphorylation was also induced by simvastatin in vivo and in vitro.
Simvastatin augments TBI-induced angiogenesis in the lesion boundary zone and hippocampus and improves functional recovery. Simvastatin also promotes angiogenesis in vitro. These beneficial effects on angiogenesis may be related to simvastatin-induced activation of the VEGFR-2/Akt/eNOS signaling pathway.
Angiogenesis; Simvastatin; Traumatic brain injury; VEGFR-2
A series of isatin analogs containing a hydrophilic group, including a pyridine ring, ethylene glycol group, and a triazole ring, have been synthesized, and their inhibition potency for caspase-3 was measured both in vitro (i.e. recombinant enzyme) and in whole cells (HeLa cells). The analogs having a hydrophilic group, including 12, 13, 16, 38, and 40, have dramatically increased activity in vitro and in HeLa cells compared to the corresponding unsubstituted N-phenyl isatin analogs.
caspase-3; apoptosis; cell death
As an obligate intracellular parasite, Toxoplasma gondii can infect humans and almost all warm-blooded animals. The consumption of raw or undercooked beef and milk is considered a risk for T. gondii infection in humans. However, little is known of T. gondii infection in dairy cattle in metropolitan Guangzhou, southern China. This study was performed to determine the seroprevalence of T. gondii in dairy cattle in Guangzhou, southern China.
Serum samples were collected from 350 dairy cattle on five farms in Guangzhou, China from 2009 to 2010, and all of the 350 serum samples were examined for specific antibodies to T. gondii by indirect hemagglutination antibody test (IHA). The overall seroprevalence of T. gondii in dairy cattle was 5.7% (20/350). Among these examined dairy cattle, dairy cattle which were < 6 year old or ≥ 5 year old had the highest seroprevalence of 12.5% followed by those dairy cattle which were < 5 year old or ≥ 4 year old (8%); dairy cattle with 3 pregnancies had the highest seroprevalence (11.5%), among the examined dairy cattle, although these differences were not statistically significant.
The results of the present survey indicate that T. gondii infection is prevalent in dairy cattle of all age ranges in Guangzhou, southern China, which may be a risk factor for human infection with T. gondii in this region.
Dong-Hui Zhou and Fu-Rong Zhao contributed equally.
Examining the spontaneous activity to understand the neural mechanism of brain disorder is a focus in recent resting-state fMRI. In the current study, to investigate the alteration of brain functional connectivity in partial epilepsy in a systematical way, two levels of analyses (functional connectivity analysis within resting state networks (RSNs) and functional network connectivity (FNC) analysis) were carried out on resting-state fMRI data acquired from the 30 participants including 14 healthy controls(HC) and 16 partial epilepsy patients. According to the etiology, all patients are subdivided into temporal lobe epilepsy group (TLE, included 7 patients) and mixed partial epilepsy group (MPE, 9 patients). Using group independent component analysis, eight RSNs were identified, and selected to evaluate functional connectivity and FNC between groups. Compared with the controls, decreased functional connectivity within all RSNs was found in both TLE and MPE. However, dissociating patterns were observed within the 8 RSNs between two patient groups, i.e, compared with TLE, we found decreased functional connectivity in 5 RSNs increased functional connectivity in 1 RSN, and no difference in the other 2 RSNs in MPE. Furthermore, the hierarchical disconnections of FNC was found in two patient groups, in which the intra-system connections were preserved for all three subsystems while the lost connections were confined to intersystem connections in patients with partial epilepsy. These findings may suggest that decreased resting state functional connectivity and disconnection of FNC are two remarkable characteristics of partial epilepsy. The selective impairment of FNC implicated that it is unsuitable to understand the partial epilepsy only from global or local perspective. We presumed that studying epilepsy in the multi-perspective based on RSNs may be a valuable means to assess the functional changes corresponding to specific RSN and may contribute to the understanding of the neuro-pathophysiological mechanism of epilepsy.
Toxoplasmosis is an important parasitic zoonosis caused by the protozoan Toxoplasma gondii that is distributed world-wide and infects a variety of hosts. However, the prevalence of T. gondii in the environment (such as soil, water and food) is largely unknown. Due to the technical difficulty in oocyst counting directly, an alternative assay using the serologic status of T. gondii in free-living animals, such as stray or free-living dogs, as an indicator, can be used to evaluate environmental contamination indirectly, as they are exposed to the same risk of infection as humans and other animals.
In the present study, 231 stray or free-living dogs across an urban-rural gradient were examined to assess the frequency of T. gondii in the environment. Specific antibodies to T. gondii were found in 93 dogs (40.3%) by enzyme-linked immunosorbent assay (ELISA), and no statistically significant differences were observed in seroprevalences of T. gondii between urban dogs (38.7%) and rural dogs (41%) (p > 0.05).
A high seroprevalence of T. gondii in stray or free-living dogs in the present study indicates that there would be a wide distribution and a constant infection pressure of T. gondii across an urban-rural gradient, and the oocysts of T. gondii in the environment would be an important source of infection for humans and other animals both in urban and rural areas in China.
Prevalence; Toxoplasma gondii; Stray dog; Enzyme-linked immunosorbent assay (ELISA); Environment; Indicator
Sparganosis, caused by the plerocercoid larvae of members of the genus Spirometra, can cause significant public health problem and considerable economic losses. In the present study, the complete mitochondrial DNA (mtDNA) sequence of Spirometra erinaceieuropaei from China was determined, characterized and compared with that of S. erinaceieuropaei from Japan. The gene arrangement in the mt genome sequences of S. erinaceieuropaei from China and Japan is identical. The identity of the mt genomes was 99.1% between S. erinaceieuropaei from China and Japan, and the complete mtDNA sequence of S. erinaceieuropaei from China is slightly shorter (2 bp) than that from Japan. Phylogenetic analysis of S. erinaceieuropaei with other representative cestodes using two different computational algorithms [Bayesian inference (BI) and maximum likelihood (ML)] based on concatenated amino acid sequences of 12 protein-coding genes, revealed that S. erinaceieuropaei is closely related to Diphyllobothrium spp., supporting classification based on morphological features. The present study determined the complete mtDNA sequences of S. erinaceieuropaei from China that provides novel genetic markers for studying the population genetics and molecular epidemiology of S. erinaceieuropaei in humans and animals.
Spirometra erinaceieuropaei; sparganosis; mitochondrial genome; mitochondrial DNA; phylogenetic analyses.