Animal Models to Study the Role of Long-Term Hypergastrinemia in Gastric Carcinogenesis

Patients with chronic hypergastrinemia due to chronic atrophic gastritis or gastrinomas have an increased risk of developing gastric malignancy, and it has been questioned whether also patients with hypergastrinemia caused by long-term use of acid inhibiting drugs are at risk. Gastric carcinogenesis in humans is affected by numerous factors and progresses slowly over years. When using animal models with the possibility of intervention, a complex process can be dissected by studying the role of hypergastrinemia in carcinogenesis within a relatively short period of time. We have reviewed findings from relevant models where gastric changes in animal models of long-term hypergastrinemia have been investigated. In all species where long-term hypergastrinemia has been induced, there is an increased risk of gastric malignancy. There is evidence that hypergastrinemia is a common causative factor in carcinogenesis in the oxyntic mucosa, while other cofactors may vary in the different models.

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Role of diuretics on long-term mortality may differ in volume status in patients with acute myocardial infarction

European Heart Journal ◽

10.1093/ehjci/ehaa946.1598 ◽

2020 ◽

Vol 41 (Supplement_2) ◽

Author(s):

T Kawai ◽

D Nakatani ◽

T Yamada ◽

T Watanabe ◽

T Morita ◽

...

Keyword(s):

Myocardial Infarction ◽

Acute Myocardial Infarction ◽

Propensity Score ◽

Plasma Volume ◽

Cox Regression ◽

Volume Status ◽

Increased Risk ◽

Long Term Mortality

Abstract Background Diuretics has been reported to have a potential for an activation of the renin-angiotensin-aldosterone system and the sympathetic nervous system, leading to a possibility of poor clinical outcome in patients with cardiovascular disease. However, few data are available on clinical impact of diuretics on long-term outcome in patients with acute myocardial infarction (AMI) based on plasma volume status. Methods To address the issue, a total of 3,416 survived patients with AMI who were registered to a large database of the Osaka Acute Coronary Insufficiency Study (OACIS) were studied. Plasma volume status was assessed with the estimated plasma volume status (ePVS) that was calculated at discharge as follows: actual PV = (1 − hematocrit) × [a + (b × body weight)] (a=1530 in males and a=864 in females, b=41.0 in males and b=47.9 in females); ideal PV = c × body weight (c=39 in males and c=40 in females), and ePVS = [(actual PV − ideal PV)/ideal PV] × 100 (%). Multivariable Cox regression analysis and propensity score matching were performed to account for imbalances in covariates. The endpoint was all-cause of death (ACD) within 5 years. Results During a median follow-up period of 855±656 days, 193 patients had ACD. In whole population, there was no significant difference in long-term mortality risk between patients with and without diuretics in both multivariate cox regression model and propensity score matching population. When patients were divided into 2 groups according to ePVS with a median value of 4.2%, 46 and 147 patients had ACD in groups with low ePVS and high ePVS, respectively. Multivariate Cox analysis showed that use of diuretics was independently associated with an increased risk of ACD in low ePVS group, (HR: 2.63, 95% confidence interval [CI]: 1.22–5.63, p=0.01), but not in high ePVS group (HR: 0.70, 95% CI: 0.44–1.10, p=0.12). These observations were consistent in the propensity-score matched cohorts; the 5-year mortality rate was significantly higher in patients with diuretics than those without among low ePVS group (4.7% vs 1.7%, p=0.041), but not among high ePVS group (8.0% vs 10.3%, p=0.247). Conclusion Prescription of diuretics at discharge was associated with increased risk of 5-year mortality in patients with AMI without PV expansion, but not with PV expansion. The role of diuretics on long-term mortality may differ in plasma volume status. Therefore, prescription of diuretics after AMI may be considered based on plasma volume status. Funding Acknowledgement Type of funding source: None

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Prognostic role of neoplastic markers in Takotsubo syndrome

Scientific Reports ◽

10.1038/s41598-021-95990-9 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Francesco Santoro ◽

Tecla Zimotti ◽

Adriana Mallardi ◽

Alessandra Leopizzi ◽

Enrica Vitale ◽

...

Keyword(s):

Serum Levels ◽

Takotsubo Syndrome ◽

Ca 15.3 ◽

Risk Of Death ◽

Increased Risk ◽

Ca 19.9 ◽

Long Term Follow Up

AbstractTakotsubo syndrome (TTS) is an acute heart failure syndrome with significant rates of in and out-of-hospital mayor cardiac adverse events (MACE). To evaluate the possible role of neoplastic biomarkers [CA-15.3, CA-19.9 and Carcinoembryonic Antigen (CEA)] as prognostic marker at short- and long-term follow-up in subjects with TTS. Ninety consecutive subjects with TTS were enrolled and followed for a median of 3 years. Circulating levels of CA-15.3, CA-19.9 and CEA were evaluated at admission, after 72 h and at discharge. Incidence of MACE during hospitalization and follow-up were recorded. Forty-three (46%) patients experienced MACE during hospitalization. These patients had increased admission levels of CEA (4.3 ± 6.2 vs. 2.2 ± 1.5 ng/mL, p = 0.03). CEA levels were higher in subjects with in-hospital MACE. At long term follow-up, CEA and CA-19.9 levels were associated with increased risk of death (log rank p < 0.01, HR = 5.3, 95% CI 1.9–14.8, HR = 7.8 95% CI 2.4–25.1, respectively, p < 0.01). At multivariable analysis levels higher than median of CEA, CA-19.9 or both were independent predictors of death at long term (Log-Rank p < 0.01). Having both CEA and CA-19.9 levels above median (> 2 ng/mL, > 8 UI/mL respectively) was associated with an increased risk of mortality of 11.8 (95% CI 2.6–52.5, p = 0.001) at follow up. Increased CEA and CA-19.9 serum levels are associated with higher risk of death at long-term follow up in patients with TTS. CEA serum levels are correlated with in-hospital MACE.

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Incidence of Delirium in Hospitalized Children with Cancer

Journal of Pediatrics & Neonatal Biology ◽

10.33140/jpnb.04.02.07 ◽

2019 ◽

Vol 4 (2) ◽

Keyword(s):

Cognitive Deficits ◽

Pediatric Intensive Care ◽

Limited Data ◽

Statistical Manual ◽

Diagnostic And Statistical Manual ◽

Dsm V ◽

Increased Risk ◽

Short Period ◽

Fluctuating Course

Delirium is defined in the Diagnostic and Statistical Manual of Mental Disorders: Fifth edition (DSM-V) as a “disturbance and change in attention and awareness from baseline that develops over a short period of time, with fluctuating course” [1]. Delirium occurs as a result of factors related to primary illness, the treatment of that illness, and stressful and disorientating environment of the hospital [2]. There are limited data to describe the incidence of delirium in children hospitalized with cancer [3]. Delirium occurs frequently in adults and is an independent predictor of mortality, increased length of stay, and increased risk for long-term cognitive deficits [3]. The prevalence of delirium in hospitalized adults ages 18-56 with cancer ranges from 18%-44% [4]. Most pediatric studies on delirium focus on the critically ill child in the pediatric intensive care unit (PICU). It is estimated that the incidence of delirium in this population is as high as 29% [5].

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Nutritional Contributions to the CNS Pathophysiology of HIV-1 Infection and Implications for Treatment

CNS Spectrums ◽

10.1017/s1092852900013122 ◽

2000 ◽

Vol 5 (4) ◽

pp. 61-72 ◽

Cited By ~ 5

Author(s):

Teri T. Baldewicz ◽

Pim Brouwers ◽

Karl Goodkin ◽

Adarsh M. Kumar ◽

Mahendra Kumar

Keyword(s):

Disease Progression ◽

Causative Factor ◽

Nutritional Deficiencies ◽

Micronutrient Deficiencies ◽

Increased Risk ◽

Immunodeficiency Virus ◽

Nutritional Deficits ◽

Hiv 1

AbstractNutritional deficiencies are commonplace in patients with human immunodeficiency virus type 1 (HIV-1) infection, and recent research has indicated that nutritional factors may play an important role in the pathogenesis of HIV-1 disease. Although nutritional deficiencies are unlikely to be the primary causative factor in disease progression, they may contribute to cognitive dysfunction, neurologic abnormalities, mood disturbance, and immune dysregulation associated with HIV-1 infection. Furthermore, deficiencies of specific micronutrients have been associated with increased risk of HIV-1–associated mortality. This article will briefly summarize the role of macronutrient deficiency, the interactions of specific micronutrient deficiencies with neuropsychiatrie functioning, and the role of these factors in HIV-1 disease progression. Since recent research has shown that normalization of many nutritional deficits and supplementation beyond normal levels are associated with improvements in neuropsychiatrie functioning, potential treatment implications will also be discussed.

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Skin Immunology and Rejection in VCA and Organ Transplantation

Current Transplantation Reports ◽

10.1007/s40472-020-00310-1 ◽

2020 ◽

Vol 7 (4) ◽

pp. 251-259

Author(s):

D. A. Leonard ◽

K. R. Amin ◽

H. Giele ◽

J. E. Fildes ◽

Jason K. F. Wong

Keyword(s):

Animal Models ◽

Lymph Nodes ◽

Clinical Studies ◽

Small Animal ◽

Immune Protection ◽

Small Animal Models ◽

Skin Immunology ◽

Discrete Populations

Abstract Purpose of Review Skin provides a window into the health of an individual. Using transplanted skin as a monitor can provide a powerful tool for surveillance of rejection in a transplant. The purpose of this review is to provide relevant background to the role of skin in vascularized transplantation medicine. Recent Findings Discrete populations of T memory cells provide distributed immune protection in skin, and cycle between skin, lymph nodes, and blood. Skin-resident TREG cells proliferate in response to inflammation and contribute to long-term VCA survival in small animal models. Early clinical studies show sentinel flap rejection to correlate well with facial VCA skin rejection, and abdominal wall rejection demonstrates concordance with visceral rejection, but further studies are required. Summary This review focuses on the immunology of skin, skin rejection in vascularized composite allografts, and the recent advances in monitoring the health of transplanted tissues using distant “sentinel” flaps.

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Postnatal Role of the Cytoskeleton in Adult Epileptogenesis

Cerebral Cortex Communications ◽

10.1093/texcom/tgaa024 ◽

2020 ◽

Vol 1 (1) ◽

Author(s):

Cezar Gavrilovici ◽

Yulan Jiang ◽

Ivana Kiroski ◽

G Campbell Teskey ◽

Jong M Rho ◽

...

Keyword(s):

Animal Models ◽

Neuronal Activity ◽

Causative Factor ◽

Cytoskeletal Proteins ◽

Human Studies ◽

Pathogenic Mechanism ◽

Neuronal Connectivity ◽

Cytoskeletal Disruption

Abstract Mutations in cytoskeletal proteins can cause early infantile and childhood epilepsies by misplacing newly born neurons and altering neuronal connectivity. In the adult epileptic brain, cytoskeletal disruption is often viewed as being secondary to aberrant neuronal activity and/or death, and hence simply represents an epiphenomenon. Here, we review the emerging evidence collected in animal models and human studies implicating the cytoskeleton as a potential causative factor in adult epileptogenesis. Based on the emerging evidence, we propose that cytoskeletal disruption may be an important pathogenic mechanism in the mature epileptic brain.

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The evolving role of endoscopy in the diagnosis of premalignant gastric lesions

F1000Research ◽

10.12688/f1000research.12087.1 ◽

2018 ◽

Vol 7 ◽

pp. 715 ◽

Cited By ~ 5

Author(s):

William Waddingham ◽

David Graham ◽

Matthew Banks ◽

Marnix Jansen

Keyword(s):

Risk Assessment ◽

Intestinal Metaplasia ◽

Narrow Band Imaging ◽

Sampling Error ◽

Evolutionary Model ◽

Chronic Atrophic Gastritis ◽

Recent Advances ◽

Increased Risk ◽

High Degree

Gastric adenocarcinoma is a disease that is often detected late, at a stage when curative treatment is unachievable. This must be addressed through changes in our approach to the identification of patients at increased risk by improving the detection and risk assessment of premalignant changes in the stomach, including chronic atrophic gastritis and intestinal metaplasia. Current guidelines recommend utilising random biopsies in a pathology-led approach in order to stage the extent and severity of gastritis and intestinal metaplasia. This random method is poorly reproducible and prone to sampling error and fails to acknowledge recent advances in our understanding of the progression to gastric cancer as a non-linear, branching evolutionary model. Data suggest that recent advances in endoscopic imaging modalities, such as narrow band imaging, can achieve a high degree of accuracy in the stomach for the diagnosis of these premalignant changes. In this review, we outline recent data to support a paradigm shift towards an endoscopy-led approach to diagnosis and staging of premalignant changes in the stomach. High-quality endoscopic interrogation of the chronically inflamed stomach mucosa, supported by targeted biopsies, will lead to more accurate risk assessment, with reduced rates of under or missed diagnoses.

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Long-term changes in muddy fine sand community of the Rance Basin: role of recruitment

Journal of the Marine Biological Association of the United Kingdom ◽

10.1017/s0025315401004234 ◽

2001 ◽

Vol 81 (4) ◽

pp. 553-564 ◽

Cited By ~ 13

Author(s):

Nicolas Desroy ◽

Christian Retière

Keyword(s):

Dominant Species ◽

General Rule ◽

Fine Sand ◽

Mean Value ◽

English Channel ◽

Power Station ◽

Tidal Power ◽

Short Period

Dynamics of the Abra alba muddy fine sand community of the Rance Basin (western English Channel), initially sampled in one station by Retière at the beginning of the 1970s after the tidal power station built at the mouth of the estuary went into service, was reassessed from 1995 to 1997. Results showed a more ‘mature’ community in 1995–1997 with an increase in the number of species. After a short period, in spring 1995, during which the structure of the community was comparable to those described in 1972–1973, the assemblage was characterized by a great interannual structural stability. Densities of dominant species seem to fluctuate around a mean value comparable to the carrying capacity of the biota for these species. The recruitment of the dominant species with a long life span appears low compared to the densities of adults but seems sufficient to assure the replacement of individuals. Our results suggest that the pattern of massive recruitment followed by high mortality rates could not be the general rule and that a pattern of moderate recruitment followed by low post-settlement mortality of recruits should be more frequent.

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The Long and Short of It: The Role of Telomeres in Fetal Origins of Adult Disease

Journal of Pregnancy ◽

10.1155/2012/638476 ◽

2012 ◽

Vol 2012 ◽

pp. 1-8 ◽

Cited By ~ 24

Author(s):

Stephanie E. Hallows ◽

Timothy R. H. Regnault ◽

Dean H. Betts

Keyword(s):

Intrauterine Growth Restriction ◽

The Body ◽

Premature Aging ◽

Fetal Origins ◽

Maternal Malnutrition ◽

Adult Disease ◽

Increased Risk

Placental insufficiency, maternal malnutrition, and other causes of intrauterine growth restriction (IUGR) can significantly affect short-term growth and long-term health. Following IUGR, there is an increased risk for cardiovascular disease and Type 2 Diabetes. The etiology of these diseases is beginning to be elucidated, and premature aging or cellular senescence through increased oxidative stress and DNA damage to telomeric ends may be initiators of these disease processes. This paper will explore the areas where telomere and telomerase biology can have significant effects on various tissues in the body in IUGR outcomes.

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A Translational Perspective of Maternal Immune Activation by SARS-CoV-2 on the Potential Prenatal Origin of Neurodevelopmental Disorders: The Role of the Cholinergic Anti-inflammatory Pathway

Frontiers in Psychology ◽

10.3389/fpsyg.2021.614451 ◽

2021 ◽

Vol 12 ◽

Author(s):

José Javier Reyes-Lagos ◽

Eric Alonso Abarca-Castro ◽

Juan Carlos Echeverría ◽

Hugo Mendieta-Zerón ◽

Alejandra Vargas-Caraveo ◽

...

Keyword(s):

Immune Activation ◽

Neurodevelopmental Disorders ◽

Inflammatory Pathway ◽

Maternal Immune Activation ◽

Increased Risk ◽

Anti Inflammatory ◽

Psychophysiological Data

The emergent Coronavirus Disease 2019 (COVID-19) caused by the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) could produce a maternal immune activation (MIA) via the inflammatory response during gestation that may impair fetal neurodevelopment and lead to postnatal and adulthood mental illness and behavioral dysfunctions. However, so far, limited evidence exists regarding long-term physiological, immunological, and neurodevelopmental modifications produced by the SARS-CoV-2 in the human maternal-fetal binomial and, particularly, in the offspring. Relevant findings derived from epidemiological and preclinical models show that a MIA is indeed linked to an increased risk of neurodevelopmental disorders in the offspring. We hypothesize that a gestational infection triggered by SARS-CoV-2 increases the risks leading to neurodevelopmental disorders of the newborn, which can affect childhood and the long-term quality of life. In particular, disruption of either the maternal or the fetal cholinergic anti-inflammatory pathway (CAP) could cause or exacerbate the severity of COVID-19 in the maternal-fetal binomial. From a translational perspective, in this paper, we discuss the possible manifestation of a MIA by SARS-CoV-2 and the subsequent neurodevelopmental disorders considering the role of the fetal-maternal cytokine cross-talk and the CAP. Specifically, we highlight the urgent need of preclinical studies as well as multicenter and international databanks of maternal-fetal psychophysiological data obtained pre-, during, and post-infection by SARS-CoV-2 from pregnant women and their offspring.

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