Relationship of Motor Mechanisms to Gastroparesis Symptoms: Towards Individualized Treatment

2021 ◽  
Author(s):  
Michael Camilleri
Keyword(s):  
Animal Studies ◽  
Gastrointestinal Symptoms ◽  
Feedback Regulation ◽  
Individualized Treatment ◽  
Control Mechanisms ◽  
Gastric Accommodation ◽  
Billroth I ◽  
Gastric Sensitivity

Following a classical paper by Dr. Keith A. Kelly published in this journal, and over the past 40 years, there has been increased understanding of the functions of different regions of the stomach, specifically the fundus, antrum, and pylorus. Several of the important physiological principles were based on in vivo animal studies that led to the appreciation of regional function and control mechanisms. These include the roles of the extrinsic parasympathetic vagal innervation, the gastric enteric nervous system and electrical syncytium consisting of pacemaker cells and smooth muscle cells, and duodenogastric reflexes providing feedback regulation following the arrival of food and hydrogen ions stimulating the release of hormones and vagal afferent mechanisms that inhibit gastric motility and stimulate pyloric contractility. Further insights on the role of regional motor functions in gastric emptying were obtained from observations in patients following diverse gastric surgeries or bariatric procedures, including fundoplication, Billroth I and sleeve gastrectomy, and sleeve gastroplasty. Antropyloroduodenal manometry as well as measurements of pyloric diameter and distensibility index provided important assessments of the role of antral hypomotility and pylorospasm, and these constitute specific targets for individualized treatment of patients with gastroparesis. Moreover, in patients with upper gastrointestinal symptoms suggestive of gastroparesis, the availability of measurements of gastric accommodation as well as pharmacological agents to reduced gastric sensitivity or enhance gastric accommodation provide additional specific targets for individualized treatment. It is anticipated that, in the future, such physiological measurements will be applied in patients to optimize choice of therapy, possibly including identifying the best candidate for pyloric interventions.

scholarly journals Prolactin and Male Fertility: The Long and Short Feedback Regulation

2009 ◽  
Vol 2009 ◽  
pp. 1-13 ◽  
Author(s):  
M. K. Gill-Sharma
Keyword(s):  
Chromatin Condensation ◽  
Feedback Regulation ◽  
Pituitary Hormones ◽  
Feedback Mechanism ◽  
Reproductive Hormones ◽  
Male Rats ◽  
Normal Men

In the last 20 years, a pituitary-hypothalamus tissue culture system with intact neural and portal connections has been developed in our lab and used to understand the feedback mechanisms that regulate the secretions of adenohypophyseal hormones and fertility of male rats. In the last decade, several in vivo rat models have also been developed in our lab with a view to substantiate the in vitro findings, in order to delineate the role of pituitary hormones in the regulation of fertility of male rats. These studies have relied on both surgical and pharmacological interventions to modulate the secretions of gonadotropins and testosterone. The interrelationship between the circadian release of reproductive hormones has also been ascertained in normal men. Our studies suggest that testosterone regulates the secretion of prolactin through a long feedback mechanism, which appears to have been conserved from rats to humans. These studies have filled in a major lacuna pertaining to the role of prolactin in male reproductive physiology by demonstrating the interdependence between testosterone and prolactin. Systemic levels of prolactin play a deterministic role in the mechanism of chromatin condensation during spermiogenesis.

scholarly journals Subinhibitory Antimicrobial Concentrations: A Review of In Vitro and In Vivo Data

1992 ◽  
Vol 3 (4) ◽  
pp. 193-201 ◽  
Author(s):  
George G Zhanel ◽  
Daryl J Hoban ◽  
Godfrey KM Harding
Keyword(s):  
Antimicrobial Activity ◽  
Animal Studies ◽  
Molecular Level ◽  
Bacterial Virulence ◽  
Antibacterial Effects ◽  
Wide Range ◽  
Immune Defences

Antimicrobial activity is not an ‘all or none’ effect. An increase in the rate and extent of antimicrobial action is usually observed over a wide range of antimicrobial concentrations. Subinhibitory antimicrobial concentrations are well known to produce significant antibacterial effects, and various antimicrobials at subinhibitory concentrations have been reported to inhibit the rate of bacterial growth. Bacterial virulence may be increased or decreased by subinhibitory antimicrobial concentrations by changes in the ability of bacteria to adhere to epithelial cells or by alterations in bacterial susceptibility to host immune defences. Animal studies performed in rats, hamsters and rabbits demonstrate decreased bacterial adherence, reduced infectivity and increased survival of animals treated with subinhibitory antimicrobial concentrations compared to untreated controls. The major future role of investigation of subinhibitory antimicrobial concentrations will be to define more fully, at a molecular level, how antimicrobials exert their antibacterial effects.

scholarly journals Protective Effects of Dietary Antioxidants against Vanadium-Induced Toxicity: A Review

2020 ◽  
Vol 2020 ◽  
pp. 1-14 ◽  
Author(s):  
Iwona Zwolak
Keyword(s):  
Oxidative Stress ◽  
Animal Studies ◽  
Toxic Metal ◽  
Protective Effects ◽  
Dietary Antioxidants ◽  
Vanadium Toxicity ◽  
Preventive Effects

Vanadium (V) in its inorganic forms is a toxic metal and a potent environmental and occupational pollutant and has been reported to induce toxic effects in animals and people. In vivo and in vitro data show that high levels of reactive oxygen species are often implicated in vanadium deleterious effects. Since many dietary (exogenous) antioxidants are known to upregulate the intrinsic antioxidant system and ameliorate oxidative stress-related disorders, this review evaluates their effectiveness in the treatment of vanadium-induced toxicity. Collected data, mostly from animal studies, suggest that dietary antioxidants including ascorbic acid, vitamin E, polyphenols, phytosterols, and extracts from medicinal plants can bring a beneficial effect in vanadium toxicity. These findings show potential preventive effects of dietary antioxidants on vanadium-induced oxidative stress, DNA damage, neurotoxicity, testicular toxicity, and kidney damage. The relevant mechanistic insights of these events are discussed. In summary, the results of studies on the role of dietary antioxidants in vanadium toxicology appear encouraging enough to merit further investigations.

scholarly journals A Review of the Role of Neurotensin and Its Receptors in Colorectal Cancer

2017 ◽  
Vol 2017 ◽  
pp. 1-8 ◽  
Author(s):  
Shengyang Qiu ◽  
Gianluca Pellino ◽  
Francesca Fiorentino ◽  
Shahnawaz Rasheed ◽  
Ara Darzi ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Animal Studies ◽  
In Vivo Studies ◽  
Signalling Pathways ◽  
Diagnostic Biomarker ◽  
Gi Tract ◽  
Cellular Receptors

Neurotensin (NTS) is a physiologically occurring hormone which affects the function of the gastrointestinal (GI) tract. In recent years, NTS, acting through its cellular receptors (NTSR), has been implicated in the carcinogenesis of several cancers. In colorectal cancer (CRC), a significant body of evidence, from in vitro and in vivo studies, is available which elucidates the molecular biology of NTS/NTSR signalling and the resultant growth of CRC cells. There is growing clinical data from human studies which corroborate the role NTS/NTSR plays in the development of human CRC. Furthermore, blockade and modulation of the NTS/NTSR signalling pathways appears to reduce CRC growth in cell cultures and animal studies. Lastly, NTS/NTSR also shows potential of being utilised as a diagnostic biomarker for cancers as well as targets for functional imaging. We summarise the existing evidence and understanding of the role of NTS and its receptors in CRC.

scholarly journals Air pollution and childhood obesity

2020 ◽  
Vol 63 (10) ◽  
pp. 382-388
Author(s):  
Moon Young Seo ◽  
Shin-Hye Kim ◽  
Mi Jung Park
Keyword(s):  
Air Pollution ◽  
Childhood Obesity ◽  
Physical Inactivity ◽  
Animal Studies ◽  
Epidemiologic Studies ◽  
Health Concern ◽  
Postnatal Exposure

Childhood obesity is a global health concern. Air pollution is also a crucial health threat, especially in developing countries. Over the past decade, a number of epidemiologic and animal studies have suggested a possible role of pre- or postnatal exposure to air pollutants on childhood obesity. Although no clear mechanism has been elucidated, physical inactivity, oxidative stress, and epigenetic modifications have been suggested as possible mechanisms by which obesity develops due to air pollution. In this review, we summarize and review previous epidemiologic studies linking air pollution and childhood obesity and discuss the possible mechanisms underlying air pollution-induced obesity based on in vivo and in vitro evidence.

Evidence for the Expression of Urokinase-type Plasminogen Activator by Human Venous Endothelial Cells In Vivo

1998 ◽  
Vol 80 (12) ◽  
pp. 961-967 ◽  
Author(s):  
L. Camoin ◽  
R. Pannell ◽  
F. Anfosso ◽  
J. P. Lefevre ◽  
J. Sampol ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Plasminogen Activator ◽  
Animal Studies ◽  
Normal Subjects ◽  
Immunomagnetic Beads ◽  
Type Plasminogen Activator ◽  
Urokinase Type Plasminogen Activator ◽  
Tissue Plasminogen

SummaryEndothelial cells (ECs) in culture synthesize and secrete urokinase-type plasminogen activator (u-PA), but the normal vascular endothelium is believed to synthesize only tissue plasminogen activator (t-PA), which is thought to be responsible for intravascular fibrinolysis. More recently, animal studies have shown that the biological role of u-PA in fibrinolysis has been underestimated, prompting a re-examination of its synthesis by the endothelium. In this study, we investigated whether u-PA was synthesized by non-atherosclerotic endothelial cells in vivo by testing ECs dislodged by venipuncture from 12 normal volunteers and 17 patients admitted for plasmapheresis. The ECs were isolated with an anti-endothelial monoclonal antibody coupled to immunomagnetic beads and characterized by morphology and by labelling for vWF, CD31, and UEA-1 binding. U-PA antigen was found in 50% of the ECs from the normal subjects and in 60% of those from patients. U-PA enzymatic activity on zymograms was detected in 50% of the normal samples and 60% of the patient samples, with the latter being more frequently and more strongly positive. U-PA mRNA was found in all the normal and patient samples tested. The results indicate that u-PA is synthesized by the venous endothelium in vivo but that its expression is highly variable.

scholarly journals New Evidence on the Role of D-Aspartate Metabolism in Regulating Brain and Endocrine System Physiology: From Preclinical Observations to Clinical Applications

2020 ◽  
Vol 21 (22) ◽  
pp. 8718
Author(s):  
Alessandro Usiello ◽  
Maria Maddalena Di Fiore ◽  
Arianna De Rosa ◽  
Sara Falvo ◽  
Francesco Errico ◽  
...  
Keyword(s):  
Animal Studies ◽  
Endocrine System ◽  
Postnatal Life ◽  
Functional Development ◽  
The Central Nervous System ◽  
High Concentrations ◽  
System Physiology ◽  
Metabolizing Enzyme

The endogenous amino acids serine and aspartate occur at high concentrations in free D-form in mammalian organs, including the central nervous system and endocrine glands. D-serine (D-Ser) is largely localized in the forebrain structures throughout pre and postnatal life. Pharmacologically, D-Ser plays a functional role by acting as an endogenous coagonist at N-methyl-D-aspartate receptors (NMDARs). Less is known about the role of free D-aspartate (D-Asp) in mammals. Notably, D-Asp has a specific temporal pattern of occurrence. In fact, free D-Asp is abundant during prenatal life and decreases greatly after birth in concomitance with the postnatal onset of D-Asp oxidase expression, which is the only enzyme known to control endogenous levels of this molecule. Conversely, in the endocrine system, D-Asp concentrations enhance after birth during its functional development, thereby suggesting an involvement of the amino acid in the regulation of hormone biosynthesis. The substantial binding affinity for the NMDAR glutamate site has led us to investigate the in vivo implications of D-Asp on NMDAR-mediated responses. Herein we review the physiological function of free D-Asp and of its metabolizing enzyme in regulating the functions of the brain and of the neuroendocrine system based on recent genetic and pharmacological human and animal studies.

scholarly journals Aggravated Liver Injury but Attenuated Inflammation in PTPRO-Deficient Mice Following LPS/D-GaIN Induced Fulminant Hepatitis

2015 ◽  
Vol 37 (1) ◽  
pp. 214-224 ◽  
Author(s):  
Xiaochen Wang ◽  
Shushan Yan ◽  
Donghua Xu ◽  
Jun Li ◽  
Yu Xie ◽  
...  
Keyword(s):  
Liver Injury ◽  
Fulminant Hepatitis ◽  
Feedback Regulation ◽  
Adaptive Immune ◽  
Hepatic Cells ◽  
Ifn Γ ◽  
Deficient Mice

Background/Aims: Critical roles of PTPRO and TLR4 have been implicated in hepatocellular carcinoma. However, little is known about their modifying effects on inflammation-related diseases in liver, particularly fulminant hepatitis (FH). We aim to investigate the potential role of PTPRO and its interaction with TLR4 in LPS/D-GaIN induced FH. Methods: A LPS/D-GaIN induced mouse FH model was used. RAW264.7 cells were transfected with PTPRO over-expressed lentiviral plasmids for further investigation. Results: The mortality of PTPRO KO mice is higher than WT mice after LPS/D-GaIN administration. Aggravated liver injury was demonstrated by increased level of serous ALT and AST and numerous hepatic cells death in PTPRO KO mice following LPS/D-GaIN administration. Interestingly, inflammation was attenuated in PTPRO-deficient mice following LPS/D-GaIN administration, which was suggested by decreased inflammatory cytokines (TNF-a, IFN-γ, IL-1ß, IL-6, IL-17A and IL-12) and cells infiltrating into spleen (CD3+IFN-γ+ cells, CD3+TNF-a+ cells, F4/80+/TLR4+ cells). A feedback regulation between PTPRO and TLR4 dependent on NF-γB signaling pathway was demonstrated in vivo and in vitro. Conclusion: PTPRO plays an important role in FH by interacting with TLR4. The crosstalk between PTPRO and TLR4 is a novel bridge linking innate immune and adaptive immune in acute liver injury.

scholarly journals Not merely a protective packing organ? A review of fascia and its force transmission capacity

2018 ◽  
Vol 124 (1) ◽  
pp. 234-244 ◽  
Author(s):  
Jan Wilke ◽  
Robert Schleip ◽  
Can A. Yucesoy ◽  
Winfried Banzer
Keyword(s):  
Animal Studies ◽  
Biomechanical Properties ◽  
Force Transmission ◽  
Locomotor System ◽  
Myofascial Force Transmission ◽  
Transmitted Force ◽  
Muscle Fascia ◽  
The Central Nervous System

Recent research indicates that fascia is capable of changing its biomechanical properties. Moreover, as it links the skeletal muscles, forming a body-wide network of multidirectional myofascial continuity, the classical conception of muscles as independent actuators has been challenged. Hence, the present synthesis review aims to characterize the mechanical relevance of the connective tissue for the locomotor system. Results of cadaveric and animal studies suggest a clinically relevant myofascial force transmission to neighboring structures within one limb (e.g., between synergists) and in the course of muscle-fascia chains (e.g., between leg and trunk). Initial in vivo trials appear to underpin these findings, demonstrating the existence of nonlocal exercise effects. However, the factors influencing the amount of transmitted force (e.g., age and physical activity) remain controversial, as well as the role of the central nervous system within the context of the observed remote exercise effects.

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