Changes in Chemosensitivity and Mechanosensitivity in Aging and Parkinson’s Disease

The risk of aspiration pneumonia in Parkinson’s disease (PD) may be increased by sensory loss in the laryngopharynx and a reduced cough reflex. This study investigated changes in chemo- and mechanosensation with age and in PD and documented cough thresholds and cortical influences over cough. Single-breath citric acid inhalation cough challenge and flexible nasendoscopy were performed in 32 participants with idiopathic PD (mean age = 68.5 years, range = 45.8–82.5) and 16 healthy young adults (8 males, mean age = 25.1 years, range = 21.3–32.4), and 16 healthy elders (8 males, mean age = 72.8 years, range = 61.5–84.7) as controls. Individuals with PD had reduced sensation at the base of the tongue compared to age- and gender-matched counterparts (p < 0.005). All groups demonstrated lower natural cough thresholds than suppressed cough thresholds. No differences in natural cough thresholds were found across groups. Young adults demonstrated greater ability to suppress cough compared to healthy elders (p = 0.021). Tongue-base mechanosensory impairment in PD may account for vallecular residue and complaints of globus sensation. However, decreased cough response was not found to be a characteristic of PD. This study provided evidence for voluntary control of cough and the lack of decline of chemosensitivity with age or disease.     

Crohn’s and colitis in children and adolescents

Crohn’s disease and ulcerative colitis can be grouped as the inflammatory bowel diseases (IBD). These conditions have become increasingly common in recent years, including in children and young people. Although much is known about aspects of the pathogenesis of these diseases, the precise aetiology is not yet understood, and there remains no cure. Recent data has illustrated the importance of a number of genes-several of these are important in the onset of IBD in early life, including in infancy. Pain, diarrhoea and weight loss are typical symptoms of paediatric Crohn’s disease whereas bloody diarrhoea is more typical of colitis in children. However, atypical symptoms may occur in both conditions: these include isolated impairment of linear growth or presentation with extra-intestinal manifestations such as erythema nodosum. Growth and nutrition are commonly compromised at diagnosis in both Crohn’s disease and colitis. Consideration of possible IBD and completion of appropriate investigations are essential to ensure prompt diagnosis, thereby avoiding the consequences of diagnostic delay. Patterns of disease including location and progression of IBD in childhood differ substantially from adult-onset disease. Various treatment options are available for children and adolescents with IBD. Exclusive enteral nutrition plays a central role in the induction of remission of active Crohn’s disease. Medical and surgical therapies need to considered within the context of a growing and developing child. The overall management of these chronic conditions in children should include multi-disciplinary expertise, with focus upon maintaining control of gut inflammation, optimising nutrition, growth and quality of life, whilst preventing disease or treatment-related complications.     

Assessment of resin perfusion in hepatic failure in vitro and in vivo

AIM:To observe the adsorbent effect of resin on endotoxin,cytokine,bilirubin in plasma of patients with hepatic failureand to determine the resin perfusion as an artificial liversupport system in the treatment of hepatic failure.METHODS:One thousand milliliters of discarded plasmawas collected from each of 6 severe hepatitis patients treatedwith plasma exchange.The plasma was passed through aresin perfusion equipment for 1-2 h via extracorporealcirculation,and then absorbent indicators of transaminase,bilirubin,blood ammonia,endotoxin and cytokines wereexamined.In the meantime,study of in vivo resin plasmaperfusion was performed on 7 severe hepatitis patients tocompare the changes of endotoxin and cytokines in bloodbefore and after perfusion.RESULTS:The levels of total bilirubin,endotoxin,interleukin1β and TNF-α in plasma were significantly decreased afterin vitro resin plasma perfusion.The levels of interleukin 1β,TNF-α and endotoxin in blood were also evidently declinedafter in vivo resin plasma perfusion.Nevertheless,no obviouschanges in IL-6,creatinine (Cr) and urea nitrogen (UN),bloodammonia and electrolytes were found both in vitroand in vivo.CONCLUSION:Bilirubin,endotoxin and cytokines in plasmaof patients with hepatic failure can be effectively adsorbedby resin in vitro.Most cytokines and endotoxin in plasma canalso be effectively removed by resin in vivo.It demonstratesthat resin perfusion may have good treatment efficacy onhepatic failure and can be expected to slow down theprogression of hepatic failure.     

Oxidized LDL and anti-oxidized LDL antibodies in atherosclerosis – Novel insights and future directions in diagnosis and therapy,

We provide an up-to-date overview of current topics surrounding oxidized low-density lipoprotein (oxLDL) and its related antibodies in the quest to better identify the individuals at risk of cardiovascular disease and atherosclerotic plaques with unfavorable characteristics. We discuss the potential of oxLDL and anti-oxLDL antibodies as serum biomarkers of cardiovascular disease and emerging studies examining the targeting of arterial oxLDL for imaging and therapeutic delivery.     

P21 and CEA expression and AgNOR counts in DMH induced colon carcinoma in rats

Ｐ２１ａｎｄＣＥＡｅｘｐｒｅｓｓｉｏｎａｎｄＡｇＮＯＲｃｏｕｎｔｓｉｎＤＭＨｉｎｄｕｃｅｄｃｏｌｏｎｃａｒｃｉｎｏｍａｉｎｒａｔｓＺＨＡＮＧＺｈｉＧａｎｇ１，ＷＵＪｉｎｇＹｉｎｇ２，ＦＵＸｉａｎｇＤｏｎｇ２，ＧＵＤａＫｕｎ１ａｎｄＦＡＮＧＦ...     

Hemosuccus pancreaticus： Problems and pitfalls in diagnosis and treatment

Hemosuccus pancreaticus is a rare cause of intermittent upper gastrointestinal bleeding. We report two cases of hemosuccus pancreaticus with multiple episodes of upper gastrointestinal bleeding. The causes of hemorrhage were rupture of pseudoaneurysm of the splenic artery and bleeding from the wall of pancreatic pseudocyst. Interventional radiology is the first modality for early diagnosis and possible treatment of hemosuccus pancreaticus. When angiography shows no abnormal findings or interventional radiological therapy can not be successful, surgery should be considered without delay. Our patients herein underwent surgery without recurrence or sequelae. Intraoperative ultrasonography and pancreatoscopy were helpful modalities for confirming the source of hemorrhage and determining the cutting line of the pancreas. When we encounter intermittent upper gastrointestinal bleeding with an obscure source, hemosuccus pancreaticus should be included in differential diagnoses especially in patients with chronic pancreatitis, which would lead to a prompt and proper treatment.     

Estrogen-related receptor α in normal adrenal cortex and adrenocortical tumors: Involvement in development and oncogenesis

Aims

The nuclear hormone receptor estrogen-related receptor α (ERRα) regulates the activation of mitochondrial genes in various human tissues, but its role in the adrenal gland and its disorders has not been defined. Therefore, we examined ERRα expression in both normal adrenal cortex (NAC) and adrenocortical tumor (ACT) in order to study the possible correlation of ERRα with adrenal development and tumor development.

Methods

Human adrenal specimens (non-pathological fetal n = 7; non-pathological post-birth n = 40; aldosterone producing adenoma (APA) n = 11; cortisol producing adenoma (CPA) n = 11; adrenocortical carcinoma (ACC) n = 8) were immunohistochemically examined in this study. NAC (n = 13) and ACT (n = 28) frozen tissue specimens were also available for studying ERRα mRNA levels.

Key findings

In fetal NAC tissues, ERRα labeling index (LI) in fetal zone (FZ) was significantly higher that that in neocortex (NC), and the differences among age groups for overall mean LI was statistically significant when analyzed according to individual cortical layers. ERRα LI was also significantly higher in ACC than in other types of ACT. ERRα mRNA was detected in NAC and all types of ACT.

Significance

Results of our present study suggest a possible role of ERRα in adrenal development and ACC.     

Maternal Obesity and Cardiac Development in the Offspring: Study in Human Neonates and Minipigs

Objectives

The aim of this study was to investigate the consequences of maternal overweight on cardiac development in offspring in infants (short term) and minipigs (short and longer term).

Expression of NOS and HIF-1αin human colorectal carcinoma and implication in tumor angiogenesis

AIM: To study CD34, CD105, inducible nitric oxide synthase (iNOS), endogenous nitric oxide synthase (eNOS), and hypoxia-inducible factor 1 (HIF-1)αexpression in human colorectal carcinomas. METHODS: The tissue microarrays (TMAs) were made up of 80 cases of colorectal carcinoma and 80 cases of non-neoplasm colorectal mucosa. The expression of CD34, CD105, NOS and HIF-1αwas detected by immunohistochemistry (S-P). RESULTS: iNOS and HIF-1αexpression in colorectal carcinoma was significantly higher than in non-neoplasm colorectal mucosa (X2 = 43.166, P < 0.01; X2 = 10.4278, P < 0.01); eNOS expression in colorectal carcinoma was significantly lower than in non-neoplasm colorectal mucosa (X2 = 11.354, P < 0.01). The expression of iNOS correlated with differentiation (X2 = 18.141, P < 0.01), invasive depth (X2 = 4.748, P < 0.01), and Micro vessel density (MVD) (t = 2.327, P < 0.05). The expression of HIF-1αwas correlated with infiltrating depth (X2 = 4.397, P < 0.05), Duke's staging (X2= 4.255, P < 0.05), and MVD (t = 2.272, P < 0.05). No correlation was found in eNOS expression. CONCLUSION: Over-expression of iNOS and HIF-1αin colorectal carcinoma is correlated with the biological character MVD.     

Assessment and risk analysis of casing and cement impairment in oil and gas wells in Pennsylvania, 2000–2012

Casing and cement impairment in oil and gas wells can lead to methane migration into the atmosphere and/or into underground sources of drinking water. An analysis of 75,505 compliance reports for 41,381 conventional and unconventional oil and gas wells in Pennsylvania drilled from January 1, 2000–December 31, 2012, was performed with the objective of determining complete and accurate statistics of casing and cement impairment. Statewide data show a sixfold higher incidence of cement and/or casing issues for shale gas wells relative to conventional wells. The Cox proportional hazards model was used to estimate risk of impairment based on existing data. The model identified both temporal and geographic differences in risk. For post-2009 drilled wells, risk of a cement/casing impairment is 1.57-fold [95% confidence interval (CI) (1.45, 1.67); P < 0.0001] higher in an unconventional gas well relative to a conventional well drilled within the same time period. Temporal differences between well types were also observed and may reflect more thorough inspections and greater emphasis on finding well leaks, more detailed note taking in the available inspection reports, or real changes in rates of structural integrity loss due to rushed development or other unknown factors. Unconventional gas wells in northeastern (NE) Pennsylvania are at a 2.7-fold higher risk relative to the conventional wells in the same area. The predicted cumulative risk for all wells (unconventional and conventional) in the NE region is 8.5-fold [95% CI (7.16, 10.18); P < 0.0001] greater than that of wells drilled in the rest of the state.Oil and natural gas production has increased substantially in the United States in recent years, predominantly due to innovations such as high-volume hydraulic fracturing and directional drilling in shale formations (1). Concurrent with this increase, concerns have mounted regarding effects of this oil and gas development process on groundwater quality, human health, public safety, and the climate, due, in part, to subsurface migration of methane and other associated hydrocarbon gases and volatile organic compounds. Economic development of gas and oil from shale formations requires a high well density, at least one well per 80 surface acres, over large continuous areas of a play. Osborn et al. (2) and Jackson et al. (3) identified a positive relationship between the concentration of thermogenic methane in private water wells in Pennsylvania and the proximity of those water wells to the nearest unconventional (i.e., Marcellus shale) gas production well. These studies also identified three possible mechanisms for explaining this relationship, and concluded that the most likely of these is subsurface migration from leaking gas wells. Other researchers have observed thermogenic and other subsurface-sourced methane in atmospheric concentrations high above background levels near conventional and unconventional gas development (4–6), suggesting that leaking wells may also contribute to fugitive methane and other associated gas emissions, with clear climatic and air quality consequences (7).Leaking oil and gas wells have long been recognized as a potential mechanism of subsurface migration of thermogenic and biogenic methane, as well as heavier n-alkanes, to the surface (7–11). A leaking well, in this context, is one in which zonal isolation along the wellbore is compromised due to a structural integrity failure of one or more of the cement and/or casing barriers. Such loss of integrity can lead to direct emissions to the atmosphere through one or more leaking annuli and/or subsurface migration of fluids (gas and/or liquid) to groundwater, surface waters, or the atmosphere. Cement barriers may fail at any time over the life of a well for a number of reasons, including hydrostatic imbalances caused by inappropriate cement density, inadequately cleaned bore holes, premature gelation of the cement, excessive fluid loss in the cement, high permeability in the cement slurry, cement shrinkage, radial cracking due to pressure fluctuations in the casings, poor interfacial bonding, and normal deterioration with age (12). Casing may fail due to failed casing joints, casing collapse, and corrosion (13). Loss of zonal isolation creates pressure differentials between the formations intersected by the wellbore and the open barrier(s). The pressure gradient thus created allows for the flow of gases or other formation fluids between geological zones (i.e., interzonal migration) and possibly to the surface (14–16), where it might manifest as sustained casing pressure (SCP) or sustained casing vent flow.Annuli are often vented, as noted in inspection records, and may contribute to fugitive emissions from the well site. Low-pressure leaks may continue to be periodically bled off and monitored, although recent studies warn that bleeding pressure to zero may actually lead to gas migration (17). High-risk (e.g., rapid repressuring of the annulus following bleed down) leaks must be structurally remedied (i.e., cement squeeze, gel squeeze, use of packers, topping off cement). State regulations (Pennsylvania code 25 §78.86) mandate that wells with leaks that cannot be vented or adequately repaired be permanently plugged, which may reduce but not eliminate the interzonal flow of gases and liquids. Leaks that continue undetected or inadequately remedied may lead to the contamination of shallow aquifers, accumulation of explosive gases within and around residences and other structures, and emission of methane and other associated gases to the atmosphere.Although not every instance of loss of zonal isolation will lead to such events, the incidence rate of cement/casing impairments and failures can provide some insight into the scale of current and future problems. However, the structural integrity failure rate of oil and gas well barriers continues to be a subject of debate. The rates most commonly cited (from 2 to >50%) are based upon industry reporting for offshore wells in the Gulf of Mexico (13, 14) and Canadian onshore (mostly conventional) wells (16). Watson and Bachu (16) note that wells drilled during periods of rapid development activity and/or wellbores deviated from vertical (e.g., horizontal wellbores) may be more prone to casing vent flow and/or gas migration away from the wellhead.Due to the lack of publicly available structural integrity monitoring records for onshore wells from industry, more recent studies have used data from state well inspection records to estimate the proportion of unconventional wells drilled that develop cement and/or casing structural integrity issues. For instance, Considine et al. (18) analyzed Pennsylvania Department of Environmental Protection (PADEP) notice of violation (NOV) records for 2008–2011 and found that between 1% and 2% of wells had one or more potential structural integrity issues during that time period. Vidic et al. (19), using the 2008–2013 data from the PADEP database, found that 3.4% of all monitored unconventional wells drilled to date in Pennsylvania might have structural integrity failures based on NOVs related to cement/casing integrity. However, neither study adequately accounts for non-NOV indicators of cement/casing integrity impairment or temporal or spatial dimensions of such impairments.Earlier work found that the NOV count alone does not account for all incidences of cement/casing failure (20). State regulatory agencies and the oil and gas industry monitor many of the wells showing signs of SCP or other indicators of cement and/or casing impairment. Remedial action is often attempted once or many times on a monitored well, but a NOV is not issued by the agency. Additionally, violation codes are sometimes entered incorrectly as non-cement/casing issues and later corrected in violation comments. By not accounting for these, previous assessments based on PADEP inspection records (18, 19) may underestimate the actual proportion of wells with cement and/or casing problems in Pennsylvania.Failure to account for temporal dimensions of the data may also skew results. Previous studies on cement/casing impairment have noted that wells drilled during boom periods may be more susceptible to loss of zonal isolation because operators might cut corners in an attempt to increase the number of wells drilled over a short period (16). The increased risk of zonal isolation problems as wells age and the increased probability of identifying these issues with more inspections may also create a time lag between the date that drilling of the well commences (i.e., the spud date) and the entry of a cement/casing issue in the inspection records. This time lag is due to the fact that wells drilled in recent years have not been subject to the same duration of analysis or number of inspections as older wells. Thus, inspection records on newer wells are incomplete relative to those of older wells.Here, we offer an in-depth analysis of the complete inspection records, including NOVs, observations and corrections noted in the inspector comments, for 32,678 oil and gas production wells drilled in Pennsylvania between 2000 and 2012. We use a time-dependent risk analysis model to assess the cumulative risk of cement/casing problems for wells based on the historical occurrence of cementing/casing impairment events.     

Effects of erythromycin on pressure in pyloric antrum and plasma motilin and somatostatin content in dogs

ＥｆｅｃｔｓｏｆｅｒｙｔｈｒｏｍｙｃｉｎｏｎｐｒｅｓｓｕｒｅｉｎｐｙｌｏｒｉｃａｎｔｒｕｍａｎｄｐｌａｓｍａｍｏｔｉｌｉｎａｎｄｓｏｍａｔｏｓｔａｔｉｎｃｏｎｔｅｎｔｉｎｄｏｇｓＨＵＡＮＧＹｕＸｉｎ１，ＣＨＥＮＹｕｅＸｉａｎｇ１，ＨＵＩＤｅＳ...     

Combinatorial and distinct roles of α₅ and α₄ integrins in stress erythropoiesis in mice

To delineate the role of specific members of β? integrins in stress erythropoiesis in the adult, we compared the response to phenylhydrazine stress in 3 genetically deficient models. The survival of β?-conditionally deficient mice after phenylhydrazine is severely compromised because of their inability to mount a successful life saving splenic erythroid response, a phenotype reproduced in β?(Δ/Δ) reconstituted animals. The response of bone marrow to phenylhydrazine-induced stress was, unlike that of spleen, appropriate in terms of progenitor cell expansion and mobilization to peripheral blood although late differentiation defects qualitatively similar to those in spleen were present in bone marrow. In contrast to β?-deficient mice, α?(Δ/Δ) mice showed only a kinetic delay in recovery and similar to β?(Δ/Δ), terminal maturation defects in both bone marrow and spleen, which were not present in VCAM-1(Δ/Δ) mice. Convergence of information from these comparative studies lends new insight to the distinct in vivo roles of α? and α? integrins in erythroid stress, suggesting that the presence of mainly α?β? integrin in all hematopoietic progenitor cells interacting with splenic microenvironmental ligands/cells is instrumental for their survival and accumulation during hemolytic stress, whereas presence of α? or of both α? and α?, is important for completion of terminal maturation steps.     

Expression of NOS and HIF-1α in human colorectal carcinoma and implication in tumor angiogenesis

AIM: To study CD34, CD105, inducible nitric oxide synthase (iNOS), endogenous nitric oxide synthase (eNOS), and hypoxia-inducible factor 1 (HIF-1) alpha expression in human colorectal carcinomas. METHODS: The tissue microarrays (TMAs) were made up of 80 cases of colorectal carcinoma and 80 cases of non-neoplasm colorectal mucosa. The expression of CD34, CD105, NOS and HIF-1alpha was detected by immunohistochemistry (S-P). RESULTS: iNOS and HIF-1alpha expression in colorectal carcinoma was significantly higher than in non-neoplasm colorectal mucosa (c2 = 43.166, P < 0.01; c2 = 10.4278, P < 0.01); eNOS expression in colorectal carcinoma was significantly lower than in non-neoplasm colorectal mucosa (c2 = 11.354, P < 0.01). The expression of iNOS correlated with differentiation (c2 = 18.141, P < 0.01), invasive depth (c2 = 4.748, P < 0.01), and Micro vessel density (MVD) (t = 2.327, P < 0.05). The expression of HIF-1alpha was correlated with infiltrating depth (c2 = 4.397, P < 0.05), Dukeos staging (c2 = 4.255, P < 0.05), and MVD (t = 2.272, P < 0.05). No correlation was found in eNOS expression. CONCLUSION: Over-expression of iNOS and HIF-1alpha in colorectal carcinoma is correlated with the biological character MVD.     

Nuclear and mitochondrial DNA microsatellite instability in hepatocellular carcinoma in Chinese

AIM:To study the nuclear microsatellite instability (nMSI)at BAT26 and mitochondral microsalellite instability (mtMSI)in the occurrence and development of hepatocellularcarcinoma and the relationship between nMSI and mtMSI.METHODS:nMSI was observed with PCR and mtMSI withPCR-SSCP in 52 cases of hepatocellular carcinoma.RESULTS:mtMSI was detected in 11 out of the 52 cases ofhepatocellular carcinoma (21.2%).Among the 11 cases ofhepatocellular carcinoma with mtMSI,7 occured in one locusand 4 in 2 loci.The frequency of mtMSI in the 52 cases ofhepatocellular carcinoma showed no correlation to sex,age,infection of hepatitis B,liver cirrhosis as well as positive AFPof the patients (P>0.05).In addition,nMSI was detected in3 out of 52 cases of hepatocellular carcinoma (5.8%) andthere was no correlation of the incidence of mtMSI to thatof nMSI(P>0.05).CONCLUSION:mtMSI may be involved in the coccurrenceand development of hepatocellular carcinoma and it isindependent of nMSI.     

Topological and evolutional relationships between HCV core protein and hepatic lipid vesicles： Studies in vitro and in conditionally transgenic mice

AIM： To investigate a specific association between hepatic steatosis and hepatitis C virus （HCV） core.
METHODS： HeLa cells and primary mouse hepatocytes were transfected with HCV core plasmid, and conditional transgenics in which hepatic over-expression of HCV core is regulated by the tetracycline-off system, were developed. The expression of the HCV core was assessed over one to six months after withdrawal of doxycycline （dox） by immunohistochemistry （IHC） and Western blotting and by sequential liver biopsy. Hepatic steatosis was evaluated using oil red stain. 8-hydroxydeoxyguanosine （8-OHdG） stains and caspase levels were conducted to clarify hepatic oxidative stress and apoptosis rate. Serum aminotransferase was checked.
RESULTS： The transfected hepatocytes had globular cores under the lipid vesicles. In transgenic mice on control diet, core expression was robust, localized to the cytoplasmic vesicle membrane and strongly associated with microvesicular steatosis, which was gradually replaced by macrovesicular steatosis. However, both steatosis and core positive hepatocytes diminished with time. Increases in aminotransferase, caspase and 8-OHdG were associated with peak core expression.
CONCLUSION： The core protein was readily detected and morphologically associated with steatosis in individual hepatocytes both in vitro and in vivo. In vivo, oxidative stress caused by the core potentially reduced the number of core positive hepatocytes and in parallel the level of steatosis. To our knowledge, this is the first animal model that directly shows topological relationship between HCV core and hepatic lipid vesicles.