The Gastric and Intestinal Microbiome: Role of Proton Pump Inhibitors

Abstract

Purpose of review

The discovery of Helicobacter pylori and other organisms colonizing the stomach and the intestines has shed some light on the importance of microbiome in maintaining overall health and developing pathological conditions when alterations in biodiversity are present. The gastric acidity plays a crucial role in filtering out bacteria and preventing development of enteric infections. In this article, we discuss the physiology of gastric acid secretion and bacterial contribution to the composition of gastric and intestinal barriers and review the current literature on the role of proton pump inhibitors (PPIs) in the microbial biodiversity of the gastrointestinal tract.

Recent findings

Culture-independent techniques, such as 16S rRNA sequencing, have revolutionized our understanding of the microbial biodiversity in the gastrointestinal tract. Luminal and mucosa-associated microbial populations are not identical. Streptococcus is overrepresented in the biopsies of patients with antral gastritis and may also be responsible for the development of peptic ulcer disease. The use of PPIs favors relative streptococcal abundance irrespective of H. pylori status and may explain the persistence of dyspeptic symptoms in patients on PPI therapy. Increased risk of enteric infections has also been seen in patients taking PPIs. The overuse of PPIs leads to significant shift of the gastrointestinal microbiome towards a less healthy state.

Summary

With the advent of PPIs, many studies have demonstrated the significant changes in the microbial composition of both gastric and intestinal microbiota. Although they are considered relatively safe over-the-counter medications, PPIs in many cases are over- and even inappropriately used. Future studies assessing the safety of PPIs and their role in the development of microbiome changes should be encouraged.

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Obesity as predictor of postoperative outcomes in liver transplant candidates: review of the literature and future perspectives

Current American and European guidelines consider a pre-transplant BMI ≥40kg/m2 as a relative contraindication for liver transplantation but this recommendation is graded as uncertain and requires further research. Moreover, conflicting results are reported on the predictive value of BMI 30-39.9kg/m2 on post-transplant complication and mortality risk.

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THE USE OF ORAL CORTICOSTEROIDS IN INFLAMMATORY BOWEL DISEASES IN ITALY: AN IG-IBD SURVEY

to evaluate how Italian gastroenterologists use corticosteroids in clinical practice for the treatment of Crohn's disease (CD) and ulcerative colitis (UC).

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Family History of Gastric Cancer is Associated with the Risk of Colorectal Neoplasia in Korean Population

Family history of cancers at different sites except for colorectum has not been evaluated as a risk factor for colorectal neoplasia (CRN).

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Obesity as predictor of postoperative outcomes in liver transplant candidates: review of the literature and future perspectives

Current American and European guidelines consider a pre-transplant BMI ≥40kg/m2 as a relative contraindication for liver transplantation but this recommendation is graded as uncertain and requires further research. Moreover, conflicting results are reported on the predictive value of BMI 30-39.9kg/m2 on post-transplant complication and mortality risk.

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THE USE OF ORAL CORTICOSTEROIDS IN INFLAMMATORY BOWEL DISEASES IN ITALY: AN IG-IBD SURVEY

to evaluate how Italian gastroenterologists use corticosteroids in clinical practice for the treatment of Crohn's disease (CD) and ulcerative colitis (UC).

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Family History of Gastric Cancer is Associated with the Risk of Colorectal Neoplasia in Korean Population

Family history of cancers at different sites except for colorectum has not been evaluated as a risk factor for colorectal neoplasia (CRN).

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Statistical Data Analyses for Clinical Neurophysiology

Appropriate statistical data analyses and presentation of these results are critically important to many of the papers submitted to Clinical Neurophysiology. A well designed statistical approach allows readers to more clearly understand the significance of group differences in neurophysiological measures and, hence, the clinical and scientific implications of that data.

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ATP and astrocytes play a prominent role in the control of the respiratory pattern generator in the lamprey

Abstract

The role of ATP and astrocytes in respiratory rhythm modulation has been recently investigated in neonatal rodents. However, no information on the role of ATP and astrocytes within the respiratory network of the lamprey is available, particularly within the paratrigeminal respiratory group (pTRG), the proposed respiratory central pattern generator. To address these issues, the present study was carried out on isolated brainstems of the adult lamprey. Bath application of ATP caused marked increases in respiratory frequency followed by decreases in the respiratory motor output, mediated by the ATP metabolite adenosine at the level of the pTRG. Bath applications and microinjections of agonists and antagonists of purinergic receptors showed that ATP increased respiratory activity through an action on pTRG P2X receptors. To disclose the respiratory role of astrocytes, we used bath application of the gliotoxin aminoadipic acid which dramatically depressed the respiratory motor output that, however, promptly recovered following glutamine application. Furthermore, the excitatory responses to ATP-γ-S (a non-hydrolyzable ATP analog), but not to substance P, microinjected into the pTRG, were abolished. Finally, we also demonstrated that acidification-induced increases in respiratory activity were ATP-independent, but mediated by astrocytes glutamate-glutamine cycle. The results show for the first time that ATP and especially astrocytes strongly contribute to the modulation of the lamprey respiratory pattern. Their role in the modulation or maintenance of rhythmic neuronal activities appears to be phylogenetically conserved.

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Differential calcium sensitivity in NaV1.5 mixed syndrome mutants

Abstract

Introduction

Inherited arrhythmias may arise from mutations in the SCN5a gene, which encodes the cardiac voltage-gated sodium channel, Na_V1.5. Mutants in Na_V1.5 result in Brugada Syndrome (BrS1), Long-QT Syndrome (LQT3), or mixed syndromes (an overlap of BrS1/LQT3). Exercise is a potential arrhythmogenic trigger in mixed syndromes. We sought to determine the effects of elevated cytosolic calcium, common during exercise, in mixed syndrome Na_V1.5 mutants.

Methods

We used whole-cell patch-clamp to assess the biophysical properties of Na_V1.5 wild-type (WT), ∆KPQ, E1784K, 1795insD, and Q1909R mutants in Human Embryonic Kidney (HEK293) cells transiently transfected with the Na_V1.5 α subunit (WT or mutants), β1 subunit, and eGFP. Voltage-dependence and kinetics were measured at approximately 0 nm, 500 nm, and 2500 nm cytosolic calciumlevels. In silico, action potential (AP) model simulations were performed using a modified O'Hara Rudy model.

Results

Elevated cytosolic calciumattenuates the late sodium current in ∆KPQ, 1795insD, and Q1909R but not in E1784K. Elevated cytosolic calcium restores steady-state slow inactivation (SSSI) to the WT-form in Q1909R, but depolarized SSSI in E1784K. Our AP simulations showed a frequency-dependent reduction of action potential duration (APD) in ∆KPQ, 1795insD, and Q1909R carriers. In E1784K, APD is relatively prolonged at both low and high heart rates, resulting in a sodium overload.

Conclusions

Cellular perturbations during exercise may affect BrS1/LQT3 patients differently depending on their individual genetic signature. Thus, exercise may be therapeutic or may be an arrhythmogenic trigger in some SCN5a patients.

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Post-translational palmitoylation controls the voltage gating and lipid raft association of CALHM1 channel

Abstract

Emerging roles of CALHM1, a recently discovered voltage-gated ion channel, include purinergic neurotransmission of tastes in taste buds and memory formation in the brain, highlighting its physiological importance. However, the regulatory mechanisms of the CALHM1 channel remain entirely unexplored, hindering full understanding of its contribution in vivo. In fact, the different gating properties of CALHM1 in vivo and in vitro suggest undiscovered regulatory mechanisms. Here, in searching for post-translational regulatory mechanisms, we discovered the regulation of CALHM1 gating and association with lipid microdomains via protein S-palmitoylation, the only reversible lipid modification of proteins on cysteine residues. CALHM1 is palmitoylated at two intracellular cysteines located in the juxtamembrane regions of the third and forth transmembrane domains. Enzymes that catalyze CALHM1 palmitoylation are identified by screening 23 members of the DHHC protein acyltransferase family. Epitope-tagging of endogenous CALHM1 proteins in mice reveals that CALHM1 is basally palmitoylated in taste buds in vivo. Functionally, palmitoylation downregulates CALHM1 without effects on its synthesis, degradation, and cell surface expression. Mutation of the palmitoylation sites has profound impact on CALHM1 gating, shifting the conductance-voltage relationship to more negative voltages and accelerating the activation kinetics. The same mutation also reduces CALHM1 association with detergent-resistant membranes. Our results comprehensively uncover a post-translational regulation of the voltage-dependent gating of CALHM1 by palmitoylation.

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Brain responses to 40-Hz binaural beat and effects on emotion and memory

Publication date: Available online 21 July 2017
Source:International Journal of Psychophysiology
Author(s): Nantawachara Jirakittayakorn, Yodchanan Wongsawat
Gamma oscillation plays a role in binding process or sensory integration, a process by which several brain areas beside primary cortex are activated for higher perception of the received stimulus. Beta oscillation is also involved in interpreting received stimulus and occurs following gamma oscillation, and this process is known as gamma-to-beta transition, a process for neglecting unnecessary stimuli in surrounding environment. Gamma oscillation also associates with cognitive functions, memory and emotion. Therefore, modulation of the brain activity can lead to manipulation of cognitive functions. The stimulus used in this study was 40-Hz binaural beat because binaural beat induces frequency following response. This study aimed to investigate the neural oscillation responding to the 40-Hz binaural beat and to evaluate working memory function and emotional states after listening to that stimulus. Two experiments were developed based on the study aims. In the first experiment, electroencephalograms were recorded while participants listened to the stimulus for 30min. The results suggested that frontal, temporal, and central regions were activated within 15min. In the second experiment, word list recall task was conducted before and after listening to the stimulus for 20min. The results showed that, after listening, the recalled words were increase in the working memory portion of the list. Brunel Mood Scale, a questionnaire to evaluate emotional states, revealed changes in emotional states after listening to the stimulus. The emotional results suggested that these changes were consistent with the induced neural oscillations.



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Importance of the skeletal muscle carnitine stores in fuel selection

Abstract

L-Carnitine (3-hydroxy-4-N,N,N- trimethylaminobutyrate) is a small molecule needed for the transport of long-chain fatty acids into the mitochondrial matrix for β-oxidation (Fritz & Mc, 1959).

This article is protected by copyright. All rights reserved

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A Silent Killer: Insights Into Venous Thromboembolism Formation and Prevention

No abstract available

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Perioperative Venous Thromboembolism: A Review

Venous thromboembolism (VTE) is a significant problem in the perioperative period, increasing patient morbidity, mortality, and health care costs. It is also considered the most preventable of the major postoperative complications. Despite widespread adoption of prophylaxis guidelines, it appears that morbidity from the disease has not substantially changed within the past 2 decades. It is becoming clear that current prophylaxis efforts are not sufficient. Using more potent anticoagulants may decrease the incidence of VTE, but increase the risk for bleeding and infection. Much has been learned about the pathophysiology of venous thrombogenesis in recent years. Beyond the "traditional coagulation cascade," which anticoagulants modulate, there is a growing appreciation for the roles of tissue factor, monocytes, neutrophils, neutrophil extracellular traps, microvesicles, and platelets in thrombus initiation and propagation. These recent studies explain to some degree why aspirin appears to be remarkably effective in preventing thrombus propagation. Endothelial dysfunction, traditionally thought of as a risk factor for arterial thrombosis, plays an important role within the cusps of venous valves, a unique environment where the majority of venous thrombi originate. This suggests a role for newer treatment modalities such as statins. Not all patients have an equal likelihood of experiencing a VTE, even when undergoing high-risk procedures, and better tools are required to accurately predict VTE risk. Only then will we be able to effectively individualize prophylaxis by balancing the risks for VTE against the risks associated with treatment. Given the different cell types and pathways involved in thrombogenesis, it is likely that multimodal treatment regimens will be more effective, enabling the use of lower and safer doses of hemostatic modulating therapies such as anticoagulants, antithrombotics, and antiplatelet medications.

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Ischemic Leg, Perfused Lung: A Trial of Remote Ischemic Preconditioning

No abstract available

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Remote Ischemic Preconditioning Decreases Oxidative Lung Damage After Pulmonary Lobectomy: A Single-Center Randomized, Double-Blind, Controlled Trial

BACKGROUND: During lobectomy in patients with lung cancer, the operated lung is often collapsed and hypoperfused. Ischemia/reperfusion injury may then occur when the lung is re-expanded. We hypothesized that remote ischemic preconditioning (RIPC) would decrease oxidative lung damage and improve gas exchange in the postoperative period. METHODS: We conducted a single-center, randomized, double-blind trial in patients with nonsmall cell lung cancer undergoing elective lung lobectomy. Fifty-three patients were randomized to receive limb RIPC immediately after anesthesia induction (3 cycles: 5 minutes ischemia/5 minutes reperfusion induced by an ischemia cuff applied on the thigh) and/or control therapy without RIPC. Oxidative stress markers were measured in exhaled breath condensate (EBC) and arterial blood immediately after anesthesia induction and before RIPC and surgery (T0, baseline); during operated lung collapse, immediately before resuming two-lung ventilation (TLV) (T1); immediately after resuming TLV (T2); and 120 minutes after resuming TLV (T3). The primary outcome was 8-isoprostane levels in EBC at T1, T2, and T3. Secondary outcomes included the following: NO2−+NO3−, H2O2 levels, and pH in EBC and in blood (8-isoprostane, NO2−+NO3−) and pulmonary gas exchange variables (PaO2/FiO2, A-aDO2, a/A ratio, and respiratory index). RESULTS: Patients subjected to RIPC had lower EBC 8-isoprostane levels when compared with controls at T1, T2, and T3 (differences between means and 95% confidence intervals): −15.3 (5.8–24.8), P = .002; −20.0 (5.5–34.5), P = .008; and −10.4 (2.5–18.3), P = .011, respectively. In the RIPC group, EBC NO2−+NO3− and H2O2 levels were also lower than in controls at T2 and T1–T3, respectively (all P

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Recommendations for Procedural Sedation Clinical Trials

No abstract available

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Induction

No abstract available

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Ischemic Leg, Perfused Lung: A Trial of Remote Ischemic Preconditioning

No abstract available

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Electric Nerve Stimulation Does Not Correctly Predict Needle-Nerve Distance and Potential Local Anesthetic Spread for Interscalene Brachial Plexus Blockade

This study evaluated electric nerve stimulation as a nerve location tool. After eliciting motor response in 43 patients undergoing shoulder surgery, the needle tip's position, distance from the closest nerve, and spread of saline were evaluated using ultrasound imaging. The needle's tip resided 1 to 4 mm from the closest nerve in 21, in direct contact with it in 7, and 6 to 18 mm away in 15 patients. In 21 patients, subsequent saline dissection did not reach the brachial plexus. Thus, the success rate of electric nerve stimulation for correct needle-nerve distance identification was 48.8%, with correct fluid spread reached in only 51.2% of patients.

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Fasting Before Anesthesia: An Unsettled Dilemma

No abstract available

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In Response

No abstract available

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Time Is Money

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In Response

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Inhaled Pulmonary Vasodilators in Cardiac Surgery Patients: Correct Answer Is “NO”

No abstract available

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Role of Sigma-1 Receptor/p38 MAPK Inhibition in Acupoint Catgut Embedding–Mediated Analgesic Effects in Complete Freund’s Adjuvant-Induced Inflammatory Pain

BACKGROUND: The endoplasmic reticulum chaperone protein Sigma-1 receptor (Sig-1 R) and mitogen-activated protein kinases (MAPKs) are involved in the mechanism of pain. Acupoint stimulation exerts an exact antihyperalgesic effect in inflammatory pain. However, whether Sig-1 R and MAPKs are associated with the acupoint stimulation-induced analgesic effects is not clear. This study investigated the analgesic effect of acupoint catgut embedding (ACE) and the inhibition of Sig-1 R and MAPKs in ACE analgesia. METHODS: Rats were prepared with intrathecal catheter implantation. ACE was applied to bilateral "Kunlun" (BL60), "Zusanli" (ST36), and "Sanyinjiao" (SP6) acupoints in the rat model of inflammatory pain (complete Freund's adjuvant [CFA] intraplantar injection). Then, Sig-1R agonist PRE084 or saline was intrathecally given daily. The paw withdrawal thresholds and paw edema were measured before CFA injection and at 1, 3, and 5 day after CFA injection. Western bolt was used to evaluate the protein expression of spinal Sig-1R, p38MAPK, and extracellular signal-regulated kinase (ERK), and immunohistochemistry of Sig-1R was detected at 1, 3, and 5 days after CFA injection. RESULTS: ACE exhibited specific analgesic effects. ACE increased paw withdrawal thresholds and markedly decreased CFA-induced paw edema at 1, 3, and 5 days. ACE downregulated the protein expression of Sig-1R, which was increased significantly at 1, 3, and 5 days after CFA injection. ACE decreased the expression of p38 MAPK and ERK at 1 and 3 days but not at 5 days. However, an injection of Sig-1R agonist PRE084 markedly reversed these alterations, except ERK expression. CONCLUSIONS: The present study demonstrated that ACE exhibited antihyperalgesic effects via the inhibition of the Sig-1R that modulated p38 MAPK, but not ERK, expression in the CFA-induced inflammatory pain model in rats.

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Professionalism: The “Forgotten” Core Competency

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An Institution-Wide Rule-Based Protocol for Early Detection of Esophageal Intubation

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Two Minutes to Improve Cardiac Surgery Outcomes

No abstract available

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In Response

No abstract available

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The Consensus Bundle on Hypertension in Pregnancy and the Anesthesiologist: Doing All the Right Things for All the Patients All of the Time

No abstract available

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In Response

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Surveying the Literature: Synopsis of Recent Key Publications

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A Silent Killer: Insights Into Venous Thromboembolism Formation and Prevention

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Aerosolized Vasodilators for the Treatment of Pulmonary Hypertension in Cardiac Surgical Patients: A Systematic Review and Meta-analysis

BACKGROUND: In cardiac surgery, pulmonary hypertension is an important prognostic factor for which several treatments have been suggested over time. In this systematic review and meta-analysis, we compared the efficacy of inhaled aerosolized vasodilators to intravenously administered agents and to placebo in the treatment of pulmonary hypertension during cardiac surgery. We searched MEDLINE, CENTRAL, EMBASE, Web of Science, and clinicaltrials.gov databases from inception to October 2015. The incidence of mortality was assessed as the primary outcome. Secondary outcomes included length of stay in hospital and in the intensive care unit, and evaluation of the hemodynamic profile. METHODS: Of the 2897 citations identified, 10 studies were included comprising a total of 434 patients. RESULTS: Inhaled aerosolized agents were associated with a significant decrease in pulmonary vascular resistance (−41.36 dyne·s/cm5, P= .03) and a significant increase in mean arterial pressure (8.24 mm Hg, P= .02) and right ventricular ejection fraction (7.29%, P

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Interventions for Neuropathic Pain: An Overview of Systematic Reviews

Numerous interventions for neuropathic pain (NeuP) are available, but its treatment remains unsatisfactory. We systematically summarized evidence from systematic reviews (SRs) of randomized controlled trials on interventions for NeuP. Five electronic databases were searched up to March 2015. Study quality was analyzed using A Measurement Tool to Assess Systematic Reviews. The most common interventions in 97 included SRs were pharmacologic (59%) and surgical (15%). The majority of analyzed SRs were of medium quality. More than 50% of conclusions from abstracts on efficacy and approximately 80% on safety were inconclusive. Effective interventions were described for painful diabetic neuropathy (pregabalin, gabapentin, certain tricyclic antidepressants [TCAs], opioids, antidepressants, and anticonvulsants), postherpetic neuralgia (gabapentin, pregabalin, certain TCAs, antidepressants and anticonvulsants, opioids, sodium valproate, topical capsaicin, and lidocaine), lumbar radicular pain (epidural corticosteroids, repetitive transcranial magnetic stimulation [rTMS], and discectomy), cervical radicular pain (rTMS), carpal tunnel syndrome (carpal tunnel release), cubital tunnel syndrome (simple decompression and ulnar nerve transposition), trigeminal neuralgia (carbamazepine, lamotrigine, and pimozide for refractory cases, rTMS), HIV-related neuropathy (topical capsaicin), and central NeuP (certain TCAs, pregabalin, cannabinoids, and rTMS). Evidence about interventions for NeuP is frequently inconclusive or completely lacking. New randomized controlled trials about interventions for NeuP are necessary; they should address safety and use clear diagnostic criteria.

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