Background: Prematurely-born individuals tend to exhibit higher resting oxidative stress, although evidence suggests they may be more resistant to acute hypoxia-induced redox balance alterations. We aimed to investiga...Background: Prematurely-born individuals tend to exhibit higher resting oxidative stress, although evidence suggests they may be more resistant to acute hypoxia-induced redox balance alterations. We aimed to investigate the redox balance changes across a 3-day hypobaric hypoxic exposure at 3375 m in healthy adults born preterm(gestational age ≤ 32 weeks) and their term-born(gestational age ≥ 38 weeks)counterparts.Methods: Resting venous blood was obtained in normoxia(prior to altitude exposure), immediately upon arrival to altitude, and the following 3mornings. Antioxidant(superoxide dismutase(SOD), catalase, glutathione peroxidase(GPx), and ferric reducing antioxidant power(FRAP)),pro-oxidant(xanthine oxidase(XO) and myeloperoxidase(MPO)) enzyme activity, oxidative stress markers(advanced oxidation protein product(AOPP) and malondialdehyde(MDA)), nitric oxide(NO) metabolites(nitrites, nitrates, and total nitrite and nitrate(NOx)), and nitrotyrosine were measured in plasma.Results: SOD increased only in the preterm group(p < 0.05). Catalase increased at arrival in preterm group(p < 0.05). XO activity increased at Day 3 for the preterm group, while it increased acutely(arrival and Day 1) in control group. MPO increased in both groups throughout the3 days(p < 0.05). AOPP only increased at arrival in the preterm(p < 0.05) whereas it decreased at arrival up to Day 3(p < 0.05) for control.MDA decreased in control group from arrival onward. Nitrotyrosine decreased in both groups(p < 0.05). Nitrites increased on Day 3(p < 0.05)in control group and decreased on Day 1(p < 0.05) in preterm group.Conclusion: These data indicate that antioxidant enzymes seem to increase immediately upon hypoxic exposure in preterm adults. Conversely, the blunted pro-oxidant enzyme response to prolonged hypoxia exposure suggests that these enzymes may be less sensitive in preterm individuals.These findings lend further support to the potential hypoxic preconditioning effect of preterm birth.展开更多
According to epidemiological studies,twice as many women as men are affected by irritable bowel syndrome(IBS)in western countries,suggesting a role for sex hormones in IBS pathophysiology.Despite growing evidence abou...According to epidemiological studies,twice as many women as men are affected by irritable bowel syndrome(IBS)in western countries,suggesting a role for sex hormones in IBS pathophysiology.Despite growing evidence about the implications of sex hormones in IBS symptom modulation,data on mechanisms by which they influence disease development are sparse.This review aims to determine the state of knowledge about the role of sex hormones in sensorimotor dysfunctions and to address the possible interplay of sex hormones with common risk factors associated with IBS.The scientific bibliography was searched using the following keywords:irritable bowel syndrome,sex,gender,ovarian hormone,estradiol,progesterone,testosterone,symptoms,pain,sensitivity,motility,permeability,stress,immune system,brain activity,spinal,supraspinal,imaging.Ovarian hormones variations along themenstrual cycle affect sensorimotor gastrointestinal function in both healthy and IBS populations.They can modulate pain processing by interacting with neuromodulator systems and the emotional system responsible for visceral pain perception.These hormones can also modulate the susceptibility to stress,which is a pivotal factor in IBS occurrence and symptom severity.For instance,estrogen-dependent hyper-responsiveness to stress can promote immune activation or impairments of gut barrier function.In conclusion,whereas it is important to keep in mind that ovarian hormones cannot be considered as a causal factor of IBS,they arguably modulate IBS onset and symptomatology.However,our understanding of the underlying mechanisms remains limited and studies assessing the link between IBS symptoms and ovarian hormone levels are needed to improve our knowledge of the disease evolution with regard to gender.Further studies assessing the role of male hormones are also needed to understand fully the role of sex hormones in IBS.Finally,investigation of brain-gut interactions is critical to decipher how stress,ovarian hormones,and female brain processing of pain can translate into gut dysfunctions.展开更多
The features of JAK-STAT signaling in liver cells are discussed in the current review. The role of this signaling cascade in carcinogenesis is accentuated. The possible involvement of this pathway and alteration of it...The features of JAK-STAT signaling in liver cells are discussed in the current review. The role of this signaling cascade in carcinogenesis is accentuated. The possible involvement of this pathway and alteration of its elements are compared for normal cholangiocytes, cholangiocarcinoma predisposition and development. Prolactin and interleukin-6 are described in detail as the best studied examples. In addition, the non-classical nuclear translocation of cytokine receptors is discussed in terms of its possible implication to cholangiocarcinoma development.展开更多
Hepatocyte nuclear factor 4-alpha (HNF4-α) is a nuclear receptor regulating metabolism, cell junctions, differentiation and proliferation in liver and intestinal epithelial cells. Mutations within the HNF4...Hepatocyte nuclear factor 4-alpha (HNF4-α) is a nuclear receptor regulating metabolism, cell junctions, differentiation and proliferation in liver and intestinal epithelial cells. Mutations within the HNF4A gene are associated with human diseases such as maturity-onset diabetes of the young. Recently, HNF4A has also been described as a susceptibility gene for ulcerative colitis in genome-wide association studies. In addition, specific HNF4A genetic variants have been identified in pediatric cohorts of Crohn’s disease. Results obtained from knockout mice supported that HNF4-α can protect the intestinal mucosae against inflammation. However, the exact molecular links behind HNF4-α and inflammatory bowel diseases remains elusive. In this review, we will summarize the current knowledge about the role of HNF4-α and its isoforms in inflammation. Specific nature of HNF4-α P1 and P2 classes of isoforms will be summarized. HNF4-α role as a hepatocyte mediator for cytokines relays during liver inflammation will be integrated based on documented examples of the literature. Conclusions that can be made from these earlier liver studies will serve as a basis to extrapolate correlations and divergences applicable to intestinal inflammation. Finally, potential functional roles for HNF4-α isoforms in protecting the intestinal mucosae from chronic and pathological inflammation will be presented.展开更多
Angiogenesis consists of the sprouting of capillaries from pre-existing vessels. It is well-known that tumor growth is angiogenesis-dependent. Vascular endothelial growth factor （VEGF） and basic fibroblast growth fa...Angiogenesis consists of the sprouting of capillaries from pre-existing vessels. It is well-known that tumor growth is angiogenesis-dependent. Vascular endothelial growth factor （VEGF） and basic fibroblast growth factor （bFGF） stimulated vascular endothelial cell proliferation and are involved in the neoplastic angiogenesis of several types of tumors including those of the intestinal tract. Authors usually investigated VEGF and using immunohistochemistry bFGF protein expressions or Western blotting and VEGF and bFGF transcripts using reverse transcriptase Dolymerase chain reaction （RT-PCR）.展开更多
AIM： To evaluate the results of sub total colectomy withI cecorectal anastomosis （STC-CRA） for isolated colonicinertia （CI）. METHODS： Fourteen patients （mean age 57.5±16.5 year） underwent surgery for isol...AIM： To evaluate the results of sub total colectomy withI cecorectal anastomosis （STC-CRA） for isolated colonicinertia （CI）. METHODS： Fourteen patients （mean age 57.5±16.5 year） underwent surgery for isolated CI between January 1986 and December 2002. The mean frequency of bowel motions with the aid of laxatives was 1.2±0.6 per week. All subjects underwent colonoscopy, anorectal manometry, cinedefaecography and colonic transit time （CTF）. CI was defined as diffuse markers delay on CTF without evidence of pelvic floor dysfunction. All patients underwent STC-CRA. Long-term follow-up was obtained prospectively by clinical visits between October 2005 and February 2006 at a mean of 10.5 ＋ 3.6 years （range 5-16 years） during which we considered the number of stool emissions, the presence of abdominal pain or digitations, the use of pain killers, laxatives and/or fibers. Patients were also asked if they were satisfied with the surgery. RESULTS： There was no postoperative mortality Postoperative complications occurred in 21.4% （3/14）. At the end of follow-up, bowel frequency was significantly （P〈0.05）increased to a mean of 4.8±7.5 per day （range 1-30）. One patient reported disabling diarrhea. Two patients used laxatives less than three times per month without complaining of what they called constipation Overall, 78.5% of patients would have chosen surgery again if necessary. CONCLUSION： STC-CRA is feasible and safe in patients with CI achieving 79% of success at a mean follow-up of 10.5 years. A prospective controlled evaluation is warranted to verify the advantages of this surgical approach in patients with CI.展开更多
Development of the spine and thoracic cage consists of a complex series of events involving multiple metabolic processes, genes and signaling pathways. During growth, complex phenomena occur in rapid succession. This ...Development of the spine and thoracic cage consists of a complex series of events involving multiple metabolic processes, genes and signaling pathways. During growth, complex phenomena occur in rapid succession. This succession of events, this establishment of elements, is programmed according to a hierarchy. These events are well synchronized to maintain harmonious limb, spine and thoracic cage relationships, as growth in the various body segments does not occur simultaneously at the same magnitude or rate. In most severe cases of untreated progressive earlyonset spinal deformities, respiratory insufficiency and pulmonary and cardiac hypertension(cor pulmonale), which characterize thoracic insufficiency syndrome(TIS), can develop, sometimes leading to death. TIS is the inability of the thorax to ensure normal breathing. This clinical condition can be linked to costo-vertebral malformations(e.g., fused ribs, hemivertebrae, congenital bars), neuromuscular diseases(e.g., expiratory congenital hypotonia), Jeune or Jarcho-Levin syndromes or to 50% to 75% fusion of the thoracic spine before seven years of age. Complex spinal deformities alter normal growth plate development, and vertebral bodies become progressively distorted, perpetuating the disorder. Therefore, many scoliotic deformities can become growth plate disorders over time. This review aims to provide a comprehensive review of how spinal deformities can affect normal spine and thoracic cage growth. Previous conceptualizations are integrated with more recent scientific data to provide a better understanding of both normal and abnormal spine and thoracic cage growth.展开更多
Cell therapy has the potential to improve healing of ischemic heart, repopulate injured myocardium and restore cardiac function. The tremendous hope and potential of stem cell therapy is well understood, yet recent tr...Cell therapy has the potential to improve healing of ischemic heart, repopulate injured myocardium and restore cardiac function. The tremendous hope and potential of stem cell therapy is well understood, yet recent trials involving cell therapy for cardiovascular diseases have yielded mixed results with inconsistent data thereby readdressing controversies and unresolved questions regarding stem cell efficacy for ischemic cardiac disease treatment. These controversies are believed to arise by the lack of uniformity of the clinical trial methodologies, uncertainty regarding the underlying reparative mechanisms of stem cells, questions concerning the most appropriate cell population to use, the proper delivery method and timing in relation to the moment of infarction, as well as the poor stem cell survival and engraftment especially in a diseased microenvironment which is collectively acknowledged as a major hindrance to any form of cell therapy. Indeed, the microenvironment of the failing heart exhibits pathological hypoxic, oxidative and inflammatory stressors impairing the survival of transplanted cells. Therefore, in order to observe any significant therapeutic benefit there is a need to increase resilience of stem cells to death in the transplant microenvironment while preserving or better yet improving their reparative functionality. Although stem cell differentiation into cardiomyocytes has been observed in some instance, the prevailing reparative benefits are afforded through paracrine mechanisms that promote angiogenesis, cell survival, transdifferentiate host cells and modulate immune responses. Therefore, to maximize their reparative functionality, ex vivo manipulation of stem cells through physical, genetic and pharmacological means have shown promise to enable cells to thrive in the postischemic transplant microenvironment. In the present work, we will overview the current status of stem cell therapy for ischemic heart disease, discuss the most recurring cell populations employed, the mechanisms by which stem cells deliver a therapeutic benefit andstrategies that have been used to optimize and increase survival and functionality of stem cells including ex vivo preconditioning with drugs and a novel "pharmacooptimizer" as well as genetic modifications.展开更多
Hepatitis C virus （HCV） is a major cause of chronic liver disease, cirrhosis and hepatocellular carcinoma （HCC）. In man, the pathobiological changes associated with HCV infection have been attributed to both the i...Hepatitis C virus （HCV） is a major cause of chronic liver disease, cirrhosis and hepatocellular carcinoma （HCC）. In man, the pathobiological changes associated with HCV infection have been attributed to both the immune system and direct viral cytopathic effects. Until now, the lack of simple culture systems to infect and propagate the virus has hampered progress in understanding the viral life cycle and pathogenesis of HCV infection, including the molecular mechanisms implicated in HCV-induced HCC. This clearly demonstrates the need to develop small animal models for the study of HCV-associated pathogenesis. This review describes and discusses the development of new HCV animal models to study viral infection and investigate the direct effects of viral protein expression on liver disease.展开更多
AIM： To investigate the effect of stable c-Fos over- expression on immortalized human hepatocyte （IHH） proliferation. METHODS： IHHs stably transfected with c-Fos （IHH- Fos） or an empty vector （IHH-C） were grow...AIM： To investigate the effect of stable c-Fos over- expression on immortalized human hepatocyte （IHH） proliferation. METHODS： IHHs stably transfected with c-Fos （IHH- Fos） or an empty vector （IHH-C） were grown in me- dium supplemented with 1% serum or stimulated with 10% serum. Cell proliferation was assessed by cell counts, 3H-thymidine uptake and flow cytometry analyses. The levels of cell cycle regulatory proteins （Cyclin DI, E, A） cyclin dependent kinases （cdk） cdk2, cdk4, cdk6, and their inhibitors p15, p16, p21, p27, total and phosphorylated GSK-3β and epidermal growth factor receptor （EGF-R） were assayed by Western blotting. Analysis of O/c/in D1 mRNA levels was performed by reverse transcription-polymerase chain reaction and real-time polymerase chain reaction （PCR） analysis. Stability of Cyclin DI was studied by cycloheximide blockade experiments. RESULTS： Stable c-Fos overexpression increased cell proliferation under low serum conditions and resulted in a two-fold increase in [3H]-thymidine incorpora- tion following serum addition. Cell cycle analysis by flow cytometry showed that c-Fos accelerated the cell cycle kinetics. Following serum stimulation, Cyclin D1 was more abundantly expressed in c-Fos overexpress- ing cells. Cyclin D1 accumulation did not result from increased transcriptional activation, but from nuclear stabilization. Overexpression of c-Fos correlated with higher nuclear levels of inactive phosphorylated GSK- 3β, a kinase involved in Cyclin D1 degradation and higher levels of EGF-R mRNA, and EGF-R protein com- pared to IHH-C both in serum starved, and in serum stimulated cells. Abrogation of EGF-R signalling in IHH- Fos by treatment with AG1478, a specific EGF-R tyro- sine kinase inhibitor, prevented the phosphorylation of GSK-3β induced by serum stimulation and decreased Cyclin D1 stability in the nucleus. CONCLUSION： Our results clearly indicate a positive role for c-Fos in cell cycle regulation in hepatocytes. Importantly, we delineate a new mechanism by which c-Fos could contribute to hepatocarcinogenesis through stabilization of Cyclin D1 within the nucleus, evoking a new feature to c-Fos implication in hepatocellular carcinoma.展开更多
Until recently, ovarian cancer research has mainly focused on the tumor cells themselves ignoring for the most part the surrounding tumor environment which includes malignant peritoneal effusions. However, one of the ...Until recently, ovarian cancer research has mainly focused on the tumor cells themselves ignoring for the most part the surrounding tumor environment which includes malignant peritoneal effusions. However, one of the major conceptual advances in oncology over the last few years has been the appreciation that cancer progression cannot be explained by aberrations in cancer cells themselves and is strongly influenced by the surrounding tumor environment. The mechanisms of ovarian cancer progression differ from that of other solid tumors because ovarian cancer cells primarily disseminate within the peritoneal cavity.Malignant peritoneal effusion accumulates in the peritoneal cavity during ovarian cancer progression. These exudative fluids act as a unique tumor environment providing a framework that orchestrates cellular and molecular changes contributing to aggressiveness and disease progression. The composition of ascites, which includes cellular and acellular components, constantly adapts during the course of the disease in response to various cellular cues originating from both tumor and stromal cells. The tumor environment that represents peritoneal effusions closely constitute an ecosystem, with specific cell types and signaling molecules increasing and decreasing during the course of the disease progression creating a single complex network. Although recent advances aiming to understand the ovarian tumor environment have focused one at a time on components, the net impact of the whole environment cannot be understood simply from its parts or outside is environmental context.展开更多
The incidence of obesity is steadily rising, and it has been estimated that 40% of the US population will be obese by the year 2025 if the current trend continues. In recent years there has been renewed interest in th...The incidence of obesity is steadily rising, and it has been estimated that 40% of the US population will be obese by the year 2025 if the current trend continues. In recent years there has been renewed interest in the surgical treatment of morbid obesity in concomitance with the epidemic of obesity. Bariatric surgery proved effective in providing weight loss of large magnitude, correction of comorbidities and excellent short-term and long-term outcomes, decreasing overall mortality and providing a marked survival advantage. The Laparoscopic Sleeve Gastrectomy (LSG) has increased in popularity and is currently very "trendy" among laparoscopic surgeons involved in bariatric surgery. As LSG proved to be effective in achieving considerable weight loss in the short-term, it has been proposed by some as a sole bariatric procedure. This editorial focuses on the particular advantages of LSG in the treatment of morbid obesity.展开更多
AIM： Platelet-activating factor （PAF） is a pro-inflammatory and angiogenic lipid mediator. Here we aimed to investigate levels of PAF, lyso-PAF （the PAF precursor）, phospholipase A2 （PLA2, the enzymatic activity...AIM： Platelet-activating factor （PAF） is a pro-inflammatory and angiogenic lipid mediator. Here we aimed to investigate levels of PAF, lyso-PAF （the PAF precursor）, phospholipase A2 （PLA2, the enzymatic activity generating lyso-PAF）, acetylhydrolase activity （AHA, the PAF degrading enzyme） and PAF receptor （PAF-R） transcripts in cirrhotic liver and hepatocellular carcinoma （HCC）. METHODS： Twenty-nine patients with HCC were enrolled in this study. Cirrhosis was present in fourteen patients and seven had no liver disease. Tissue PAF levels were investigated by a platelet-aggregation assay. Lyso- PAF was assessed after its chemical acetylation into PAR AHA was determined by degradation of [^3H]-PAE PLA2 levels were assessed by EIA. PAF-R transcripts were investigated using RT-PCR. RESULTS： Elevated amounts of PAF and PAF-R transcripts 1 （leukocyte-type） were found in cirrhotic tissues as compared with non-cirrhotic ones. Higher amounts of PAF and PAF-R transcripts 1 and 2 （tissue-type） were found in HCC tissues as compared with non-tumor tissues. PLA2, lyso-PAF and AHA levels were not changed in cirrhotic tissues and HCC. CONCLUSION： While the role of PAF is currently unknown in liver physiology, this study suggests its potential involvement in the inflammatory network found in the cirrhotic liver and in the angiogenic response during HCC.展开更多
Laparoscopic cholecystectomy is the most commonlyperformed abdominal intervention in Western countries. In an attempt to reduce the invasiveness of the procedure, surgeons have developed single-incision laparoscopic c...Laparoscopic cholecystectomy is the most commonlyperformed abdominal intervention in Western countries. In an attempt to reduce the invasiveness of the procedure, surgeons have developed single-incision laparoscopic cholecystectomy(SILC), minilaparoscopic cholecystectomy(MLC) and natural orifice transluminal endoscopic surgery(NOTES). The aim of this review was to determine the role of these new minimally invasive approaches for elective laparoscopic cholecystectomy in the treatment of gallstone related disease. Current literature remains insufficient for the correct assessment of emerging techniques for laparoscopic cholecystectomy. None of these procedures has demonstrated clear benefits over conventional laparoscopic cholecystectomy. SILC cannot be currently recommended as it can be associated with an increased risk of bile duct injury and incisional hernia incidence. NOTES cholecystectomy is still experimental, although hybrid transvaginal cholecystectomy is gaining popularity in clinical practice. As it is standardized and almost identical to the standard laparoscopic technique, MLC could lead to limited benefits without exposing patients to increased postoperative complications, being therefore adoptable for routine elective cholecystectomy. Technical challenges of SILC and NOTES cholecystectomy could be addressed with the evolution of new surgical tools that need to catch up with the innovative minds of surgeons. Regardless the place of these approaches in the future, robotization may be necessary to impose them as standard treatment.展开更多
Objective: The aim was to determine if endothelial VCAM-1 (eVCAM-1) expression in the common carotid artery (CCA) would correlate with predictive markers of atherosclerotic disease, would precede reduction of markers ...Objective: The aim was to determine if endothelial VCAM-1 (eVCAM-1) expression in the common carotid artery (CCA) would correlate with predictive markers of atherosclerotic disease, would precede reduction of markers of endothelial cell function and would predict coronary artery disease (CAD). Methods and results: Carotid arterial segments (bifurcation, proximal and distal CCA) were harvested from 14 and 24 month-old male castrated familial hypercholesterolemic (FH) swine, a model of spontaneous atherosclerosis. Quantification of local expression of eVCAM-1, intimal macrophage accumulation, oxidative stress, intima-media (I/M) ratio, intima-media thickness (IMT), endothelial nitric oxide synthase (eNOS) and phosphorylated eNOS (p-eNOS) in selected regions of the carotids revealed a relationship between local inflammation and atherosclerotic plaque progression. Importantly, inflammation was not uniform throughout the CCA. Endothelial VCAM-1 expression was the greatest at the bifurcation and increased with age. Finally, eVCAM-1 best estimated the severity of CAD compared to blood levels of glucose, hypercholesterolemia, carotid IMT, and p-eNOS. Conclusion: Our data suggested that eVCAM-1 was closely associated with atherosclerotic plaque progression and preceded impairment of EDD. Thus, this study supported the use of carotid VCAM-1 targeting agents to estimate the severity of CAD.展开更多
We read with a great interest the recent work of Deli and colleagues. in the World Journal of Gastroenterology reporting vascular endothelial growth factor （VEGF） expression in hepatocellular carcinoma （HCC） and c...We read with a great interest the recent work of Deli and colleagues. in the World Journal of Gastroenterology reporting vascular endothelial growth factor （VEGF） expression in hepatocellular carcinoma （HCC） and cirrhotic liver tissues. This well-documented work shows that VEGF was significantly higher in surrounding cirrhotic liver tissues than in HCC. Authors assessed VEGF expression using immunohistochemistry. The immunohistochemical staining is an efficient tool to assess the percentage of cells stained positively for VEGF but is not really efficient to estimate their true VEGF content. Evaluation of the VEGF protein by an enzyme-linked immunosorbent assay 0ELISA） has been reported, by us and others, to be an efficient tool in order to assess tissue VEGF expression. We have, thus, tested whether the ELISA method might be an efficient tool in order to confirm data reporting higher amounts of VEGF in surrounding cirrhotic liver tissues than in HCC. Deli and colleagues. also correctly pointed out that basic fibroblast growth factor （bFGF） has been reported to act cooperatively on VEGF expression. We have, thus, also assessed bFGF tissue levels in order to search for a putative link between VEGF and bFGF levels in cirrhotic tissues.展开更多
Livestock is traditionally managed in mixed crop-livestock production systems in Sud-Kivu, D. R. Congo. Currently, livestock production is facing numerous constraints due to wars and insecurity in the country, with lo...Livestock is traditionally managed in mixed crop-livestock production systems in Sud-Kivu, D. R. Congo. Currently, livestock production is facing numerous constraints due to wars and insecurity in the country, with looting of animals, demographic pressure on natural resources, and lack of extension services. Multipurpose trees and shrubs with adequate forage quality could help overcome dry-season feed shortage. The objective of this research was to assess the agro-ecological adaptability of selected forage tree and shrub legumes combined with farmer participatory evaluation. The study was carried out at two distinct mid-altitude sites in Sud-Kivu. Trees and shrubs were planted randomly in eleven lines, with each species/accession consisting of nine plants split into three replications. Following a standardization cut after one year of growth, regular biomass harvests were performed every eight weeks during one year;Desmodium and Flemingia were cut at 0.5 m above soil surface, while Leucaena and Calliandra at 1 m. Before every harvest, plant height was measured and number of stems counted. Fresh leaf and stem biomass were weighted, sub samples dried and leaves analyzed for nutritive value. Results from agronomic evaluation show that Leucaena diversifolia ILRI 15551 and Leucaena leucocephala had the highest yield in the rainy season on fertile soil;during dry season, Leucaena diversifolia ILRI 15551 was superior. On poor soil, Flemingia macrophylla CIAT 17403 performed best in both seasons, however, its forage quality was relatively low. Forage tree and shrub legumes chosen by farmers were, in general, the same as those superior ones in agronomic evaluation.展开更多
Neuromuscular disorders are a group of diseases affecting the neuro-musculo-skeletal system. Children with neuromuscular disorders frequently develop progressive spinal deformities with cardio-respiratory compromise i...Neuromuscular disorders are a group of diseases affecting the neuro-musculo-skeletal system. Children with neuromuscular disorders frequently develop progressive spinal deformities with cardio-respiratory compromise in the most severe cases. The incidence of neuromuscular scoliosis is variable, inversely correlated with ambulatory abilities and with a reported risk ranging from 80% to 100% in non-ambulatory patients. As surgical and peri-operative techniques have improved, more severely affected children with complex neuromuscular deformities and considerable co-morbidities are now believed to be candidates for extensive surgery for spinal deformity. This article aimed to provide a comprehensive review of how neuromuscular spinal deformities can affect normal spine balance and how these deformities can be treated with segmental instrumentation and sub-laminar devices. Older concepts have been integrated with newer scientific data to provide the reader with a basis for better understanding of how treatment of neuromuscular scoliosis has evolvedover the past few decades. Recent advances, as well as challenges that remain to be overcome, in the surgical treatment of neuromuscular curves with sub-laminar devices and in the management of post-operative infections are outlined.展开更多
基金funded by the Swiss National Science Foundation(SNSF Grant No.320030L_192073 to GM)the Slovenian Research Agency(ARRS Grant No.N5-0152 to TD).
文摘Background: Prematurely-born individuals tend to exhibit higher resting oxidative stress, although evidence suggests they may be more resistant to acute hypoxia-induced redox balance alterations. We aimed to investigate the redox balance changes across a 3-day hypobaric hypoxic exposure at 3375 m in healthy adults born preterm(gestational age ≤ 32 weeks) and their term-born(gestational age ≥ 38 weeks)counterparts.Methods: Resting venous blood was obtained in normoxia(prior to altitude exposure), immediately upon arrival to altitude, and the following 3mornings. Antioxidant(superoxide dismutase(SOD), catalase, glutathione peroxidase(GPx), and ferric reducing antioxidant power(FRAP)),pro-oxidant(xanthine oxidase(XO) and myeloperoxidase(MPO)) enzyme activity, oxidative stress markers(advanced oxidation protein product(AOPP) and malondialdehyde(MDA)), nitric oxide(NO) metabolites(nitrites, nitrates, and total nitrite and nitrate(NOx)), and nitrotyrosine were measured in plasma.Results: SOD increased only in the preterm group(p < 0.05). Catalase increased at arrival in preterm group(p < 0.05). XO activity increased at Day 3 for the preterm group, while it increased acutely(arrival and Day 1) in control group. MPO increased in both groups throughout the3 days(p < 0.05). AOPP only increased at arrival in the preterm(p < 0.05) whereas it decreased at arrival up to Day 3(p < 0.05) for control.MDA decreased in control group from arrival onward. Nitrotyrosine decreased in both groups(p < 0.05). Nitrites increased on Day 3(p < 0.05)in control group and decreased on Day 1(p < 0.05) in preterm group.Conclusion: These data indicate that antioxidant enzymes seem to increase immediately upon hypoxic exposure in preterm adults. Conversely, the blunted pro-oxidant enzyme response to prolonged hypoxia exposure suggests that these enzymes may be less sensitive in preterm individuals.These findings lend further support to the potential hypoxic preconditioning effect of preterm birth.
文摘According to epidemiological studies,twice as many women as men are affected by irritable bowel syndrome(IBS)in western countries,suggesting a role for sex hormones in IBS pathophysiology.Despite growing evidence about the implications of sex hormones in IBS symptom modulation,data on mechanisms by which they influence disease development are sparse.This review aims to determine the state of knowledge about the role of sex hormones in sensorimotor dysfunctions and to address the possible interplay of sex hormones with common risk factors associated with IBS.The scientific bibliography was searched using the following keywords:irritable bowel syndrome,sex,gender,ovarian hormone,estradiol,progesterone,testosterone,symptoms,pain,sensitivity,motility,permeability,stress,immune system,brain activity,spinal,supraspinal,imaging.Ovarian hormones variations along themenstrual cycle affect sensorimotor gastrointestinal function in both healthy and IBS populations.They can modulate pain processing by interacting with neuromodulator systems and the emotional system responsible for visceral pain perception.These hormones can also modulate the susceptibility to stress,which is a pivotal factor in IBS occurrence and symptom severity.For instance,estrogen-dependent hyper-responsiveness to stress can promote immune activation or impairments of gut barrier function.In conclusion,whereas it is important to keep in mind that ovarian hormones cannot be considered as a causal factor of IBS,they arguably modulate IBS onset and symptomatology.However,our understanding of the underlying mechanisms remains limited and studies assessing the link between IBS symptoms and ovarian hormone levels are needed to improve our knowledge of the disease evolution with regard to gender.Further studies assessing the role of male hormones are also needed to understand fully the role of sex hormones in IBS.Finally,investigation of brain-gut interactions is critical to decipher how stress,ovarian hormones,and female brain processing of pain can translate into gut dysfunctions.
文摘The features of JAK-STAT signaling in liver cells are discussed in the current review. The role of this signaling cascade in carcinogenesis is accentuated. The possible involvement of this pathway and alteration of its elements are compared for normal cholangiocytes, cholangiocarcinoma predisposition and development. Prolactin and interleukin-6 are described in detail as the best studied examples. In addition, the non-classical nuclear translocation of cytokine receptors is discussed in terms of its possible implication to cholangiocarcinoma development.
文摘Hepatocyte nuclear factor 4-alpha (HNF4-α) is a nuclear receptor regulating metabolism, cell junctions, differentiation and proliferation in liver and intestinal epithelial cells. Mutations within the HNF4A gene are associated with human diseases such as maturity-onset diabetes of the young. Recently, HNF4A has also been described as a susceptibility gene for ulcerative colitis in genome-wide association studies. In addition, specific HNF4A genetic variants have been identified in pediatric cohorts of Crohn’s disease. Results obtained from knockout mice supported that HNF4-α can protect the intestinal mucosae against inflammation. However, the exact molecular links behind HNF4-α and inflammatory bowel diseases remains elusive. In this review, we will summarize the current knowledge about the role of HNF4-α and its isoforms in inflammation. Specific nature of HNF4-α P1 and P2 classes of isoforms will be summarized. HNF4-α role as a hepatocyte mediator for cytokines relays during liver inflammation will be integrated based on documented examples of the literature. Conclusions that can be made from these earlier liver studies will serve as a basis to extrapolate correlations and divergences applicable to intestinal inflammation. Finally, potential functional roles for HNF4-α isoforms in protecting the intestinal mucosae from chronic and pathological inflammation will be presented.
基金Supported by La Ligue Nationale Francaise Contre le Cancer (Comitéde la Corrèze et de la Haute Vienne)
文摘Angiogenesis consists of the sprouting of capillaries from pre-existing vessels. It is well-known that tumor growth is angiogenesis-dependent. Vascular endothelial growth factor （VEGF） and basic fibroblast growth factor （bFGF） stimulated vascular endothelial cell proliferation and are involved in the neoplastic angiogenesis of several types of tumors including those of the intestinal tract. Authors usually investigated VEGF and using immunohistochemistry bFGF protein expressions or Western blotting and VEGF and bFGF transcripts using reverse transcriptase Dolymerase chain reaction （RT-PCR）.
文摘AIM： To evaluate the results of sub total colectomy withI cecorectal anastomosis （STC-CRA） for isolated colonicinertia （CI）. METHODS： Fourteen patients （mean age 57.5±16.5 year） underwent surgery for isolated CI between January 1986 and December 2002. The mean frequency of bowel motions with the aid of laxatives was 1.2±0.6 per week. All subjects underwent colonoscopy, anorectal manometry, cinedefaecography and colonic transit time （CTF）. CI was defined as diffuse markers delay on CTF without evidence of pelvic floor dysfunction. All patients underwent STC-CRA. Long-term follow-up was obtained prospectively by clinical visits between October 2005 and February 2006 at a mean of 10.5 ＋ 3.6 years （range 5-16 years） during which we considered the number of stool emissions, the presence of abdominal pain or digitations, the use of pain killers, laxatives and/or fibers. Patients were also asked if they were satisfied with the surgery. RESULTS： There was no postoperative mortality Postoperative complications occurred in 21.4% （3/14）. At the end of follow-up, bowel frequency was significantly （P〈0.05）increased to a mean of 4.8±7.5 per day （range 1-30）. One patient reported disabling diarrhea. Two patients used laxatives less than three times per month without complaining of what they called constipation Overall, 78.5% of patients would have chosen surgery again if necessary. CONCLUSION： STC-CRA is feasible and safe in patients with CI achieving 79% of success at a mean follow-up of 10.5 years. A prospective controlled evaluation is warranted to verify the advantages of this surgical approach in patients with CI.
文摘Development of the spine and thoracic cage consists of a complex series of events involving multiple metabolic processes, genes and signaling pathways. During growth, complex phenomena occur in rapid succession. This succession of events, this establishment of elements, is programmed according to a hierarchy. These events are well synchronized to maintain harmonious limb, spine and thoracic cage relationships, as growth in the various body segments does not occur simultaneously at the same magnitude or rate. In most severe cases of untreated progressive earlyonset spinal deformities, respiratory insufficiency and pulmonary and cardiac hypertension(cor pulmonale), which characterize thoracic insufficiency syndrome(TIS), can develop, sometimes leading to death. TIS is the inability of the thorax to ensure normal breathing. This clinical condition can be linked to costo-vertebral malformations(e.g., fused ribs, hemivertebrae, congenital bars), neuromuscular diseases(e.g., expiratory congenital hypotonia), Jeune or Jarcho-Levin syndromes or to 50% to 75% fusion of the thoracic spine before seven years of age. Complex spinal deformities alter normal growth plate development, and vertebral bodies become progressively distorted, perpetuating the disorder. Therefore, many scoliotic deformities can become growth plate disorders over time. This review aims to provide a comprehensive review of how spinal deformities can affect normal spine and thoracic cage growth. Previous conceptualizations are integrated with more recent scientific data to provide a better understanding of both normal and abnormal spine and thoracic cage growth.
文摘Cell therapy has the potential to improve healing of ischemic heart, repopulate injured myocardium and restore cardiac function. The tremendous hope and potential of stem cell therapy is well understood, yet recent trials involving cell therapy for cardiovascular diseases have yielded mixed results with inconsistent data thereby readdressing controversies and unresolved questions regarding stem cell efficacy for ischemic cardiac disease treatment. These controversies are believed to arise by the lack of uniformity of the clinical trial methodologies, uncertainty regarding the underlying reparative mechanisms of stem cells, questions concerning the most appropriate cell population to use, the proper delivery method and timing in relation to the moment of infarction, as well as the poor stem cell survival and engraftment especially in a diseased microenvironment which is collectively acknowledged as a major hindrance to any form of cell therapy. Indeed, the microenvironment of the failing heart exhibits pathological hypoxic, oxidative and inflammatory stressors impairing the survival of transplanted cells. Therefore, in order to observe any significant therapeutic benefit there is a need to increase resilience of stem cells to death in the transplant microenvironment while preserving or better yet improving their reparative functionality. Although stem cell differentiation into cardiomyocytes has been observed in some instance, the prevailing reparative benefits are afforded through paracrine mechanisms that promote angiogenesis, cell survival, transdifferentiate host cells and modulate immune responses. Therefore, to maximize their reparative functionality, ex vivo manipulation of stem cells through physical, genetic and pharmacological means have shown promise to enable cells to thrive in the postischemic transplant microenvironment. In the present work, we will overview the current status of stem cell therapy for ischemic heart disease, discuss the most recurring cell populations employed, the mechanisms by which stem cells deliver a therapeutic benefit andstrategies that have been used to optimize and increase survival and functionality of stem cells including ex vivo preconditioning with drugs and a novel "pharmacooptimizer" as well as genetic modifications.
文摘Hepatitis C virus （HCV） is a major cause of chronic liver disease, cirrhosis and hepatocellular carcinoma （HCC）. In man, the pathobiological changes associated with HCV infection have been attributed to both the immune system and direct viral cytopathic effects. Until now, the lack of simple culture systems to infect and propagate the virus has hampered progress in understanding the viral life cycle and pathogenesis of HCV infection, including the molecular mechanisms implicated in HCV-induced HCC. This clearly demonstrates the need to develop small animal models for the study of HCV-associated pathogenesis. This review describes and discusses the development of new HCV animal models to study viral infection and investigate the direct effects of viral protein expression on liver disease.
文摘AIM： To investigate the effect of stable c-Fos over- expression on immortalized human hepatocyte （IHH） proliferation. METHODS： IHHs stably transfected with c-Fos （IHH- Fos） or an empty vector （IHH-C） were grown in me- dium supplemented with 1% serum or stimulated with 10% serum. Cell proliferation was assessed by cell counts, 3H-thymidine uptake and flow cytometry analyses. The levels of cell cycle regulatory proteins （Cyclin DI, E, A） cyclin dependent kinases （cdk） cdk2, cdk4, cdk6, and their inhibitors p15, p16, p21, p27, total and phosphorylated GSK-3β and epidermal growth factor receptor （EGF-R） were assayed by Western blotting. Analysis of O/c/in D1 mRNA levels was performed by reverse transcription-polymerase chain reaction and real-time polymerase chain reaction （PCR） analysis. Stability of Cyclin DI was studied by cycloheximide blockade experiments. RESULTS： Stable c-Fos overexpression increased cell proliferation under low serum conditions and resulted in a two-fold increase in [3H]-thymidine incorpora- tion following serum addition. Cell cycle analysis by flow cytometry showed that c-Fos accelerated the cell cycle kinetics. Following serum stimulation, Cyclin D1 was more abundantly expressed in c-Fos overexpress- ing cells. Cyclin D1 accumulation did not result from increased transcriptional activation, but from nuclear stabilization. Overexpression of c-Fos correlated with higher nuclear levels of inactive phosphorylated GSK- 3β, a kinase involved in Cyclin D1 degradation and higher levels of EGF-R mRNA, and EGF-R protein com- pared to IHH-C both in serum starved, and in serum stimulated cells. Abrogation of EGF-R signalling in IHH- Fos by treatment with AG1478, a specific EGF-R tyro- sine kinase inhibitor, prevented the phosphorylation of GSK-3β induced by serum stimulation and decreased Cyclin D1 stability in the nucleus. CONCLUSION： Our results clearly indicate a positive role for c-Fos in cell cycle regulation in hepatocytes. Importantly, we delineate a new mechanism by which c-Fos could contribute to hepatocarcinogenesis through stabilization of Cyclin D1 within the nucleus, evoking a new feature to c-Fos implication in hepatocellular carcinoma.
文摘Until recently, ovarian cancer research has mainly focused on the tumor cells themselves ignoring for the most part the surrounding tumor environment which includes malignant peritoneal effusions. However, one of the major conceptual advances in oncology over the last few years has been the appreciation that cancer progression cannot be explained by aberrations in cancer cells themselves and is strongly influenced by the surrounding tumor environment. The mechanisms of ovarian cancer progression differ from that of other solid tumors because ovarian cancer cells primarily disseminate within the peritoneal cavity.Malignant peritoneal effusion accumulates in the peritoneal cavity during ovarian cancer progression. These exudative fluids act as a unique tumor environment providing a framework that orchestrates cellular and molecular changes contributing to aggressiveness and disease progression. The composition of ascites, which includes cellular and acellular components, constantly adapts during the course of the disease in response to various cellular cues originating from both tumor and stromal cells. The tumor environment that represents peritoneal effusions closely constitute an ecosystem, with specific cell types and signaling molecules increasing and decreasing during the course of the disease progression creating a single complex network. Although recent advances aiming to understand the ovarian tumor environment have focused one at a time on components, the net impact of the whole environment cannot be understood simply from its parts or outside is environmental context.
文摘The incidence of obesity is steadily rising, and it has been estimated that 40% of the US population will be obese by the year 2025 if the current trend continues. In recent years there has been renewed interest in the surgical treatment of morbid obesity in concomitance with the epidemic of obesity. Bariatric surgery proved effective in providing weight loss of large magnitude, correction of comorbidities and excellent short-term and long-term outcomes, decreasing overall mortality and providing a marked survival advantage. The Laparoscopic Sleeve Gastrectomy (LSG) has increased in popularity and is currently very "trendy" among laparoscopic surgeons involved in bariatric surgery. As LSG proved to be effective in achieving considerable weight loss in the short-term, it has been proposed by some as a sole bariatric procedure. This editorial focuses on the particular advantages of LSG in the treatment of morbid obesity.
文摘AIM： Platelet-activating factor （PAF） is a pro-inflammatory and angiogenic lipid mediator. Here we aimed to investigate levels of PAF, lyso-PAF （the PAF precursor）, phospholipase A2 （PLA2, the enzymatic activity generating lyso-PAF）, acetylhydrolase activity （AHA, the PAF degrading enzyme） and PAF receptor （PAF-R） transcripts in cirrhotic liver and hepatocellular carcinoma （HCC）. METHODS： Twenty-nine patients with HCC were enrolled in this study. Cirrhosis was present in fourteen patients and seven had no liver disease. Tissue PAF levels were investigated by a platelet-aggregation assay. Lyso- PAF was assessed after its chemical acetylation into PAR AHA was determined by degradation of [^3H]-PAE PLA2 levels were assessed by EIA. PAF-R transcripts were investigated using RT-PCR. RESULTS： Elevated amounts of PAF and PAF-R transcripts 1 （leukocyte-type） were found in cirrhotic tissues as compared with non-cirrhotic ones. Higher amounts of PAF and PAF-R transcripts 1 and 2 （tissue-type） were found in HCC tissues as compared with non-tumor tissues. PLA2, lyso-PAF and AHA levels were not changed in cirrhotic tissues and HCC. CONCLUSION： While the role of PAF is currently unknown in liver physiology, this study suggests its potential involvement in the inflammatory network found in the cirrhotic liver and in the angiogenic response during HCC.
文摘Laparoscopic cholecystectomy is the most commonlyperformed abdominal intervention in Western countries. In an attempt to reduce the invasiveness of the procedure, surgeons have developed single-incision laparoscopic cholecystectomy(SILC), minilaparoscopic cholecystectomy(MLC) and natural orifice transluminal endoscopic surgery(NOTES). The aim of this review was to determine the role of these new minimally invasive approaches for elective laparoscopic cholecystectomy in the treatment of gallstone related disease. Current literature remains insufficient for the correct assessment of emerging techniques for laparoscopic cholecystectomy. None of these procedures has demonstrated clear benefits over conventional laparoscopic cholecystectomy. SILC cannot be currently recommended as it can be associated with an increased risk of bile duct injury and incisional hernia incidence. NOTES cholecystectomy is still experimental, although hybrid transvaginal cholecystectomy is gaining popularity in clinical practice. As it is standardized and almost identical to the standard laparoscopic technique, MLC could lead to limited benefits without exposing patients to increased postoperative complications, being therefore adoptable for routine elective cholecystectomy. Technical challenges of SILC and NOTES cholecystectomy could be addressed with the evolution of new surgical tools that need to catch up with the innovative minds of surgeons. Regardless the place of these approaches in the future, robotization may be necessary to impose them as standard treatment.
文摘Objective: The aim was to determine if endothelial VCAM-1 (eVCAM-1) expression in the common carotid artery (CCA) would correlate with predictive markers of atherosclerotic disease, would precede reduction of markers of endothelial cell function and would predict coronary artery disease (CAD). Methods and results: Carotid arterial segments (bifurcation, proximal and distal CCA) were harvested from 14 and 24 month-old male castrated familial hypercholesterolemic (FH) swine, a model of spontaneous atherosclerosis. Quantification of local expression of eVCAM-1, intimal macrophage accumulation, oxidative stress, intima-media (I/M) ratio, intima-media thickness (IMT), endothelial nitric oxide synthase (eNOS) and phosphorylated eNOS (p-eNOS) in selected regions of the carotids revealed a relationship between local inflammation and atherosclerotic plaque progression. Importantly, inflammation was not uniform throughout the CCA. Endothelial VCAM-1 expression was the greatest at the bifurcation and increased with age. Finally, eVCAM-1 best estimated the severity of CAD compared to blood levels of glucose, hypercholesterolemia, carotid IMT, and p-eNOS. Conclusion: Our data suggested that eVCAM-1 was closely associated with atherosclerotic plaque progression and preceded impairment of EDD. Thus, this study supported the use of carotid VCAM-1 targeting agents to estimate the severity of CAD.
文摘We read with a great interest the recent work of Deli and colleagues. in the World Journal of Gastroenterology reporting vascular endothelial growth factor （VEGF） expression in hepatocellular carcinoma （HCC） and cirrhotic liver tissues. This well-documented work shows that VEGF was significantly higher in surrounding cirrhotic liver tissues than in HCC. Authors assessed VEGF expression using immunohistochemistry. The immunohistochemical staining is an efficient tool to assess the percentage of cells stained positively for VEGF but is not really efficient to estimate their true VEGF content. Evaluation of the VEGF protein by an enzyme-linked immunosorbent assay 0ELISA） has been reported, by us and others, to be an efficient tool in order to assess tissue VEGF expression. We have, thus, tested whether the ELISA method might be an efficient tool in order to confirm data reporting higher amounts of VEGF in surrounding cirrhotic liver tissues than in HCC. Deli and colleagues. also correctly pointed out that basic fibroblast growth factor （bFGF） has been reported to act cooperatively on VEGF expression. We have, thus, also assessed bFGF tissue levels in order to search for a putative link between VEGF and bFGF levels in cirrhotic tissues.
文摘Livestock is traditionally managed in mixed crop-livestock production systems in Sud-Kivu, D. R. Congo. Currently, livestock production is facing numerous constraints due to wars and insecurity in the country, with looting of animals, demographic pressure on natural resources, and lack of extension services. Multipurpose trees and shrubs with adequate forage quality could help overcome dry-season feed shortage. The objective of this research was to assess the agro-ecological adaptability of selected forage tree and shrub legumes combined with farmer participatory evaluation. The study was carried out at two distinct mid-altitude sites in Sud-Kivu. Trees and shrubs were planted randomly in eleven lines, with each species/accession consisting of nine plants split into three replications. Following a standardization cut after one year of growth, regular biomass harvests were performed every eight weeks during one year;Desmodium and Flemingia were cut at 0.5 m above soil surface, while Leucaena and Calliandra at 1 m. Before every harvest, plant height was measured and number of stems counted. Fresh leaf and stem biomass were weighted, sub samples dried and leaves analyzed for nutritive value. Results from agronomic evaluation show that Leucaena diversifolia ILRI 15551 and Leucaena leucocephala had the highest yield in the rainy season on fertile soil;during dry season, Leucaena diversifolia ILRI 15551 was superior. On poor soil, Flemingia macrophylla CIAT 17403 performed best in both seasons, however, its forage quality was relatively low. Forage tree and shrub legumes chosen by farmers were, in general, the same as those superior ones in agronomic evaluation.
文摘Neuromuscular disorders are a group of diseases affecting the neuro-musculo-skeletal system. Children with neuromuscular disorders frequently develop progressive spinal deformities with cardio-respiratory compromise in the most severe cases. The incidence of neuromuscular scoliosis is variable, inversely correlated with ambulatory abilities and with a reported risk ranging from 80% to 100% in non-ambulatory patients. As surgical and peri-operative techniques have improved, more severely affected children with complex neuromuscular deformities and considerable co-morbidities are now believed to be candidates for extensive surgery for spinal deformity. This article aimed to provide a comprehensive review of how neuromuscular spinal deformities can affect normal spine balance and how these deformities can be treated with segmental instrumentation and sub-laminar devices. Older concepts have been integrated with newer scientific data to provide the reader with a basis for better understanding of how treatment of neuromuscular scoliosis has evolvedover the past few decades. Recent advances, as well as challenges that remain to be overcome, in the surgical treatment of neuromuscular curves with sub-laminar devices and in the management of post-operative infections are outlined.
