A novel abdominal aortic aneurysm model produced by periarterial application of hydrochloric acid.

Previous abdominal aortic aneurysm (AAA) animal modeling methodologies were either expensive or complicated. Here, we developed a novel AAA model which was simple to set up and generated minimal calcification. Twenty-four rats were divided randomly into four groups. Groups 1, 2 and 3 underwent surgery in which 15% hydrochloric acid (HCl) was applied periarterially to the abdominal aorta for 5 min, followed by sacrifice 1 week (group 1), 2 weeks (group 2), and 4 weeks (group 3) after surgery. The maximum aortic diameter (MAD) was measured at surgery and before animal sacrifice. Rats in group 4 were sham-treated. The MADs in group 1, 2 and 3 showed significant dilation compared with group 4, with a mean dilation rate of 33.8% in the first week after surgery. Histopathological examination revealed infiltration of macrophages into the adventitia, obvious apoptosis of smooth muscle cells, and rupture and collapse of the elastic fibers. Furthermore, no calcification was observed in the dilated aorta. The mRNA expression levels of inflammatory factors were at least two-fold higher in group 1 than in group 4, indicating significant inflammatory response in the progression of AAA information. In conclusion, periarterial application of 15% HCl is a convenient and reliable model to create an abdominal aortic aneurysm in rats, and the potential development mechanism may be related to the proinflammatory effects of HCl.

Effect of hydrochloric acid commercial presentation for microabrasion technique on loss of enamel structure and surface / Efeito da apresentação comercial de ácido clorídrico para técnica de microabrasão na perda de estrutura e superfície do esmalte

Introdução: A técnica de microabrasão pode ser realizada através de pasta pronta para uso, disponível comercialmente, ou o profissional pode manipulá-la no consultório. Objetivo: Verificar o efeito da apresentação comercial do ácido clorídrico a 10% na manipulação de pasta para microabrasão sobre a superfície do esmalte. Metodologia: Foram selecionados incisivos bovinos e divididos em dois grupos, de acordo com a apresentação comercial do ácido clorídrico (líquido ou em gel). O tratamento foi realizado através de dez aplicações com 10s de duração cada, intercaladas por lavagem de 10s. Vinte incisivos (n=10) foram utilizados para se determinar a perda de estrutura do esmalte. Cada amostra foi pesada, em balança analítica, antes e após submissão à microabrasão. Outras 20 amostras (n=10) foram utilizadas para determinação da rugosidade superficial média (Ra) utilizando-se um rugosímetro. Três amostras de cada grupo do experimento anterior foram selecionadas, aleatoriamente, e outras três amostras adicionais foram preparadas como controle (baseline) para análise em MEV. Resultados: Verificou-se diferença estatística significativa entre a massa final e a inicial e rugosidade superficial das amostras, independente da apresentação comercial do ácido. Nas imagens de MEV observou-se presença de superfície regular para o grupo controle (baseline). Nas demais imagens verificou-se superfície com considerável irregularidade e dissolução discreta do esmalte. Conclusões: O tratamento realizado causou perda significativa de estrutura e aumentou a rugosidade superficial dos espécimes, independente da apresentação comercial do ácido e sem apresentar diferença entre os grupos ao final. A apresentação comercial do ácido não parece ser um fator a interferir no tratamento. (AU)

Introduction: The microabrasion technique can be performed using a commercially available paste, or the dentist can prepare it in his office. Objective: To verify the effect of hydrochloric acid commercial presentation in the handling of microabrasion paste on the enamel surface. Methodology: Bovine incisors were divided into two groups, according to the commercial presentation of 10% hydrochloric acid (liquid or gel). The treatment was carried out through ten applications of 10 s duration each, intercalated with a 10s wash. Twenty teeth (n=10) were used to determine the loss of enamel structure. Each sample was weighed on an analytical balance before and after submission to microabrasion. Another 20 teeth (n=10) were used to determine the average surface roughness (Ra) using a rugosimeter. Three samples from each group of the previous experiment were selected, randomly, and another three additional samples were repared as a control (baseline) for SEM analysis. Results: There was a statistically significant difference between the final and initial mass and the surface roughness of the samples, regardless of the acid commercial presentation. In the SEM images, a regular surface was observed for the control group (baseline). In the other images, there was a surface with considerable irregularity and a slight dissolution of the enamel. Conclusions: The treatment carried out. (AU)

Impact of the dialysate acid component on haemodialysis mortality rates.

BACKGROUND: No prospective study has evaluated the long-term effect on mortality of the new acid concentrates added to bicarbonate dialysate. The aim of this pharmacoepidemiological study was to evaluate the association between hydrochloric or citric acid-based dialysate and mortality on haemodialysis (HD). METHODS: This study included 117 796 patients with 3 723 887 months on HD recorded in the national French Renal Epidemiology and Information Network registry. Dialysate acid components were retrospectively reconstructed for each facility. All patients on HD were associated each month with an exposure based on that at their facility of treatment. We took each patient's time-varying exposure into account to calculate the monthly mortality rates for each exposure. Incidence rate ratios (IRRs) for mortality were calculated with a Poisson regression, with acetic acid as the reference. Regressions were adjusted for initial clinical characteristics (age, gender, previous cardiovascular events, active malignancy, diabetes, pulmonary disease, mobility), dialysis technique and location (in-centre, outpatient centre, self-care unit) and ESRD vintage, updated monthly. RESULTS: The crude mortality rate per 1000 patient-months with citric acid {11.5 [95% confidence interval (CI) 11.1-12.0]} was lower than with either acetic acid [12.9 (95% CI 12.8-13.1)] or hydrochloric acid [12.8 (95% CI 12.2-13.5)]. For the 2014-17 period, the IRR for mortality with citric acid [adjusted IRR 0.94 (95% CI 0.90-0.99)] and with hydrochloric acid [adjusted IRR 0.86 (95% CI 0.79-0.94)] were significantly lower than with acetic acid. CONCLUSION: This post-marketing study of long-term exposure to dialysate acidifiers at the patient level found the use of citric and hydrochloric acid-based dialysates, compared with acetic acid, was associated with lower mortality.

Antimicrobial effects of fentanyl and bupivacaine: an in vitro study / Efeitos antimicrobianos do fentanil e da bupivacaína: estudo in vitro

Abstract Study objective: In this study, we aimed to compare the antimicrobial effects of bupivacaine and fentanyl citrate and to reveal the impact on antimicrobial effect potential in the case of combined use. Design: In vitro prospective study. Setting: University Clinical Microbiology Laboratory. Measurements: In our study, in vitro antimicrobial effect of 0.05 mg.mL-1 fentanyl citrate, 5 mg.mL-1 bupivacaine were tested against Staphylococcus aureus American Type Culture Collection (ATCC) 29213, Pseudomonas aeruginosa ATCC 27853, Klebsiella pneumoniae ATCC 13883, Escherichia coli ATCC 25922 and Candida albicans ATCC 10231 as Group F (Fentanyl Citrate) and Group B (Bupivacaine), respectively. S. aureus ATCC 29213, P. aeruginosa ATCC 27853, Klebsiella pneumoniae ATCC 13883 and Escherichia coli ATCC 25922 were cultured onto Mueller Hinton agar (Oxoid, UK) plates and Candida albicans ATCC 10231 were cultured onto Sabouraud dextrose agar (Oxoid, UK) plates for 18-24 hours at 37 °C. Main results: In terms of inhibition zone diameters, S. Aureus ATCC 29213, P. aeruginosa ATCC 27853, and C. albicans ATCC10231 values obtained after 12 and 24 hours of incubation ​​were significantly higher in Group F than Group B (p < 0.001). In terms of inhibition zone diameters, E. coli ATCC 25922, and K. pneumomiae ATCC 13883 values obtained after 12 and 24 hours of incubation ​​were significantly higher in Group B than Group F (p < 0.001, E. coli 12ª hour p = 0.005). Conclusions: Addition of fentanyl to Local Anesthetics (LAs) is often preferred in regional anesthesia applications in today's practice owing especially to its effect on decreasing the local anesthetic dose and increasing analgesia quality and patient satisfaction. However, when the fact that fentanyl antagonized the antimicrobial effects of LAs in the studies is taken into account, it might be though that it contributes to an increase in infection complications. When the fact that fentanyl citrate which was used in our study and included hydrochloric acid and sodium hydroxide as protective agents, broadened the antimicrobial effect spectrum of LAs, had no antagonistic effect and showed a synergistic antimicrobial effect against E. Coli is considered, we are of the opinion that the addition of fentanyl to LAs would contribute significantly in preventing the increasing regional anesthesia infection complications.

Resumo Objetivo: O objetivo do presente estudo foi comparar os efeitos antimicrobianos da bupivacaína e citrato de fentanil e revelar o impacto no potencial do efeito antimicrobiano no caso de uso combinado. Desenho: Estudo prospectivo in vitro. Local: Laboratório de Microbiologia Clínica da Universidade. Medidas: Em nosso estudo, os efeitos antimicrobianos in vitro do citrato de fentanil na concentração de 0,05 mg.mL-1 - Grupo F e da bupivacaína na concentração de 5 mg.mL-1 - Grupo B foram testados em culturas de Staphylococcus aureus ATCC 29213 (do inglês American Type Culture Collection 29213), Pseudomonas aeruginosa ATCC 27853, Klebsiella pneumoniae ATCC 13883, Escherichia coli ATCC 25922 e Candida albicans ATCC 10231. As culturas de S. aureus ATCC 29213, P. aeruginosa ATCC 27853, Klebsiella pneumoniae ATCC 13883 e Escherichia coli ATCC 25922 foram semeadas em placas de ágar Mueller Hinton (Oxoid, Reino Unido), e a cultura de Candida albicans ATCC 10231 foi realizada em placa de ágar Sabouraud dextrose (Oxoid, Reino Unido) durante 18-24 horas a 37 °C. Principais resultados: Com relação ao diâmetro da zona de inibição, os valores de S. aureus ATCC 29213, P. aeruginosa ATCC 27853 e C. albicans ATCC10231 obtidos após 12 e 24 horas de incubação foram significantemente maiores no Grupo F do que no Grupo B (p < 0,001). Os valores do diâmetro da zona de inibição das culturas de E. coli ATCC 25922 e K. pneumomiae ATCC 13883 obtidos após 12 e 24 horas de incubação foram significantemente maiores no Grupo B do que no Grupo F (p < 0,001, E. coli na 12ª hora p = 0,005) Conclusões: A preferência atual e frequente pela adição de fentanil aos Anestésicos Locais (AL) para a realização de anestesia regional se deve sobretudo à possibilidade de redução da dose do anestésico local, a melhora na qualidade da analgesia e a satisfação do paciente. No entanto, ao considerar estudos em que o fentanil antagonizou o efeito antimicrobiano dos AL, pode-se pensar que esse fato contribua para aumento de complicação infecciosa. O citrato de fentanil usado em nosso estudo, contendo ácido clorídrico e hidróxido de sódio como agentes conservantes, ampliou o espectro de efeitos antimicrobianos dos AL, não teve efeito antagônico e demonstrou efeito antimicrobiano sinérgico contra a E. coli. Acreditamos que a adição de fentanil aos anestésicos locais traria importante contribuição na prevenção das crescentes complicações por infecção da anestesia regional.

Post-treatment with a heat shock protein 90 inhibitor prevents chronic lung injury and pulmonary fibrosis, following acute exposure of mice to HCl.

Aim/Purpose: Exposure to high levels of hydrochloric acid (HCl) is associated with severe lung injury including both acute inflammation and chronic lung disease, which leads to the development of pulmonary fibrosis. Currently, there are no specific therapeutic agents for HCl-induced lung injury. Heat shock protein 90 (HSP90) has been implicated in the pathogenesis of pulmonary fibrosis. Thus, we have used a murine model of intra-tracheal acid instillation to investigate the antidotal effects of AUY-922, a small molecule HSP90 inhibitor, already in clinical trials for various types of cancer, against HCl-induced chronic lung injury and pulmonary fibrosis.Methods: HCl (0.1 N, 2 µl/g body weight) was instilled into male C57Bl/6J mice at day 0. After 24 h, mice began receiving 1 mg/kg AUY-922, 2x/week for 15 or 30 days.Results: AUY-922 suppressed the HCl-induced sustained inflammation, as reflected in the reduction of leukocyte and protein concentrations in bronchoalveolar lavage fluid, and inhibited the activation of pro-fibrotic biomarkers, ERK and HSP90. Furthermore, AUY-922 improved lung function, decreased the overexpression and accumulation of extracellular matrix proteins and dramatically reduced histologic evidence of fibrosis in the lungs of mice exposed to HCl.Conclusions: We conclude that AUY-922, and possibly other HSP90 inhibitors, successfully block the adverse effects associated with acute exposures to HCl and may represent an effective antidote against HCl-induced chronic lung injury and fibrosis.

Enhancement of transduction efficiency using Adeno-associated viral vectors by chemical pretreatment to mice bladder urothelium.

Adeno-associated virus (AAV) vectors have been recognized as promising tools for gene delivery. The bladder is a seemingly ideal organ for virus transfer, with easy access through the urethra enabling organ-specific delivery. However, achieving adequate transduction efficiency in the urothelium has been a major challenge because of the barrier function of the glycosaminoglycan (GAG) layer. We investigated optimal pretreatments of the bladder urothelium to maximize transduction efficiency by AAV vectors in vivo. Murine bladders were pretreated with five different chemical agents followed by transurethral instillation with an AAV2 vector encoding a tdTOMATO reporter. After 7 days, transduction efficiency of the urothelium was evaluated. Bladder urothelia pretreated with HCl showed clear evidence of AAV infection and gene delivery. Mice treated with 0.1 N HCl for 4 min showed significantly higher survival rates (nearly 80 %) compared with mice receiving other pretreatment regimens. AAV vector transduction in the urothelium was observed in seven of 20 mice (35 %), and the mean transduction efficiency in these mice was 14.5 %. Thus, HCl pretreatment enhanced transduction efficiency of the mice bladder urothelium by an AAV vector in vivo. Pretreatment with 0.1 N HCl for 4 min was the optimal condition to maximize survival and transduction efficiency of the urothelium.

Acid/bile exposure triggers TRAIL-mediated apoptosis in esophageal cancer cells by suppressing the decoy receptors and c-FLIPR.

Esophageal adenocarcinoma essentially develops from esophageal inflammation caused by chronic GERD. During GERD episodes, the lower esophageal epithelium is repeatedly exposed to stomach acid, which often contains duodenal bile salts that prompt malignant transformation. TRAIL is one of the cytokines produced in response to such insults and targets the transformed cells exclusively. In this study, we simulated GERD episodes in vitro by exposing the cancer cells to acid or acid/bile combination and found that the cancer cells lived through acid attacks by expression of the decoy receptors and c-FLIPR but died of TRAIL-mediated apoptosis when bile salts were present. Further investigation revealed that acid/bile exposure downregulated the decoy receptors and thereby facilitated TRAIL signaling; meantime, it inhibited protein kinase C activity and thus expedited c-FLIPR degradation, allowing apoptosis to take place.

Lubiprostone protects esophageal mucosa from acid injury in porcine esophagus.

Esophageal injury from acid exposure related to gastroesophageal reflux disease is a common problem and a risk factor for development of Barrett's esophagus and esophageal adenocarcinoma. Our previous work highlights the benefits of using porcine esophagus to study human esophageal disease because of the similarities between porcine and human esophagus. In particular, esophageal submucosal glands (ESMGs) are present in human esophagus and proximal porcine esophagus but not in rodent esophagus. Although CFTR is expressed in the ducts of ESMGs, very little is known about CFTR and alternate anion channels, including ClC-2, in the setting of acid-related esophageal injury. After finding evidence of CFTR and ClC-2 in the basal layers of the squamous epithelium, and in the ducts of the ESMGs, we developed an ex vivo porcine model of esophageal acid injury. In this model, esophageal tissue was placed in Ussing chambers to determine the effect of pretreatment with the ClC-2 agonist lubiprostone on tissue damage related to acid exposure. Pretreatment with lubiprostone significantly reduced the level of acid injury and significantly augmented the recovery of the injured tissue (P < 0.05). Evaluation of the interepithelial tight junctions showed well-defined membrane localization of occludin in lubiprostone-treated injured tissues. Pretreatment of tissues with the Na+-K+-2Cl- cotransporter inhibitor bumetanide blocked lubiprostone-induced increases in short-circuit current and inhibited the reparative effect of lubiprostone. Furthermore, inhibition of ClC-2 with ZnCl2 blocked the effects of lubiprostone. We conclude that ClC-2 contributes to esophageal protection from acid exposure, potentially offering a new therapeutic target.NEW & NOTEWORTHY This research is the first to describe the presence of anion channels ClC-2 and CFTR localized to the basal epithelia of porcine esophageal mucosa and the esophageal submucosal glands. In the setting of ex vivo acid exposure, the ClC-2 agonist lubiprostone reduced acid-related injury and enhanced recovery of the epithelial barrier. This work may ultimately provide an alternate mechanism for treating gastroesophageal reflux disease.

Increased expression of CART, nNOS, VIP, PACAP, SP and GAL in enteric neurons of the porcine stomach prepyloric region following hydrochloric acid infusion.

INTRODUCTION: Stomach hyperacidity leads to damage of the mucus/bicarbonate barrier, ulcerations and the development of stomach cancer. Key regulators of the mucosal barrier/luminal acid balance are neurotransmitters secreted by intramural neurons. The aim of the current study was to determine the expression of gastric neuropeptides and nNOS in the porcine stomach following hydrochloric acid instillation. We report on increased expression of enteric neurotransmitters involved in adaptive reaction to an experimentally-induced hyperacidity state. MATERIAL AND METHODS: The investigation was conducted on eight 12-18 kg pigs. The influence of intragastric infusion of hydrochloric acid on the expression of cocaine- and amphetamine-regulated transcript peptide (CART), neuronal nitric oxide synthase (nNOS), vasoactive intestinal polypeptide (VIP), pituitary adenylate cyclase-activating peptide (PACAP), substance P (SP) and galanin (GAL) in the submucous and myenteric gastric neurons of the pig has been studied with double immunofluorescence. RESULTS: A mimicked hyperacidity state significantly increased the proportion of enteric neurons immunoreactive to CART, nNOS, VIP, PACAP, SP and GAL in the submucous gastric neurons. In the myenteric plexus, a significant increase of the number of VIP-, CART- and GAL-immunoreactive (IR) neurons was found. Similarly, the percentage of myenteric nNOS-IR and PACAP-IR neurons tended to increase, while the fraction of SP-IR cells did not change. CONCLUSIONS: Stomach hyperacidity modifies the expression of the studied neurotransmitters in a specific way depending on the location of the neurons in particular plexuses of the stomach. Increased numbers of neurons expressing CART, nNOS, VIP, PACAP, SP and GAL clearly indicate their regulatory engagement in the restoration of the physiological gastric balance following hyperacidity.

New One-Pot Synthesis of 1,3,5-Triazines: Three-Component Condensation, Dimroth Rearrangement, and Dehydrogenative Aromatization.

A new, effective one-pot synthesis of the 6, N2-diaryl-1,3,5-triazine-2,4-diamines under microwave irradiation was developed. The method involved an initial three-component condensation of cyanoguanidine, aromatic aldehydes, and arylamines in the presence of hydrochloric acid. Without isolation, the resulting 1,6-diaryl-1,6-dihydro-1,3,5-triazine-2,4-diamines were treated with a base to initiate Dimroth rearrangement and spontaneous dehydrogenative aromatization, affording the desired compounds. The developed method was found to be sufficiently general in scope, tolerating various aromatic aldehydes and amines; by using their combinations in the first step, a representative library of 110 compounds was successfully prepared and screened for anticancer properties.

Hydrochloric acid prolongs the lifetime of central venous catheters in haematologic patients with bacteraemia.

INTRODUCTION: Bacteraemia in adult patients undergoing treatment for leukaemia is common and associated with profound morbidity and mortality. Infections related to the use of a central venous catheter (CVC) are difficult to eliminate with systemic antibiotics. Premature catheter removal is often due to retained biofilm infection. This study investigated if the additional use of hydrochloric acid (HCl) as an intraluminal lock solution may prolong the lifetime of the CVC. METHODS: The study was performed retrospectively based on a database including patients with a tunnelled Leonard 10 F dual or triple lumen CVC implanted who received HCl instillation due to bacteraemia during a five-year period. RESULTS: In a total of 71 cases of bacteraemia, HCl instil-lation was performed. Following HCI instillation, the CVC was not removed due to infection in 49 out of 71 patients (69%). Furthermore, 22 patients (31%) retained their CVC until the end of treatment. Non-infectious mortality (19/71), accidental pull (2/71) or mechanical CVC dysfunction (6/71) were other reasons for premature removal. Twenty-two catheters (31%) had to be removed due to ongoing infection. The median time from CVC placement until HCl instillation was 39 days. The median time from HCl instillation until removal of CVC was 58 days. The most common bacteriological findings were coagulase-negative staphylococci 34%, Enterococcus spp 14% and Escherichia coli 14%. CONCLUSIONS: The study's findings indicate that a prolonged use of CVC is possible following HCl instillation in adult haematologic patients with bacteraemia. FUNDING: none. TRIAL REGISTRATION: not relevant.

Acidosis enhances the self-renewal and mitochondrial respiration of stem cell-like glioma cells through CYP24A1-mediated reduction of vitamin D.

Acidosis is a significant feature of the tumor microenvironment in glioma, and it is closely related to multiple biological functions of cancer stem cells. Here, we found that the self-renewal ability, the mitochondrial activity and ATP production were elevated in stem cell-like glioma cells (SLCs) under acidic microenvironment, which promoted and maintained the stemness of SLCs. Under acidosis, 25-hydroxy vitamin D3-24-hydroxylase (CYP24A1) was upregulated and catalyzed the fast degradation of 1α,25(OH)2D3. We further revealed that the active form of vitamin D (1α,25(OH)2D3) could inhibit the expression of stemness markers, attenuate acidosis-induced increase of self-renewal ability and mitochondrial respiration in stem cell-like glioma cells. Our study indicates that the acidosis-CYP24A1-vitamin D pathway may be a key regulator of the cancer stem cell phenotype in malignant glioma and point out the potential value for the utilization of vitamin D to target cancer stem cells and to restrain the growth of malignant glioma in the future.

Effects of hydrochloric acid washing on the microstructure and pyrolysis bio-oil components of sweet sorghum bagasse.

Acid washing is an alternative and promising approach for biomass to produce high-quality bio-oil. The hydrochloric acid washing pretreatment of sweet sorghum bagasse was performed in this study. The effects of acid washing on the ultrastructure of sweet sorghum bagasse were investigated using scanning electron microscope and Fourier transform infrared, and the effects on pyrolysis using thermogravimetric analyzer and a fast pyrolysis device. The results indicated acid treatment obviously changed the surface morphology of the cell walls of sweet sorghum bagasse, effectively removed most metals from sweet sorghum bagasse, and increased the volatiles and bio-oil yields. The results showed that bio-oil produced from pretreated sweet sorghum bagasse contained less components categories, lower contents of phenols, aldehydes, furans and alcohols, while much higher contents of d-allose and ketones than that from the original sample. Hydrochloric acid-washing pretreatment of sweet sorghum bagasse can increase the contents of some high-value chemicals in bio-oil.

Treatment of corn with lactic acid or hydrochloric acid modulates the rumen and plasma metabolic profiles as well as inflammatory responses in beef steers.

BACKGROUND: High-grain diets that meet the energy requirements of high-producing ruminants are associated with a high risk of rumen disorders. Mild acid treatment with lactic acid (LA) has been used to modify the degradable characteristics of grains to improve the negative effects of high-grain diets. However, the related studies mainly focused on dairy cows and explored the effects on rumen fermentation, production performance, ruminal pH and so forth. And up to date, no studies have reported the hydrochloric acid (HA) treatment of grains for ruminant animals. Therefore, based on metabolomics analysis, the aim of this study was to evaluate the effects of treatment of corn by steeping in 1% LA or 1% HA for 48 h on the rumen and plasma metabolic profiles in beef steers fed a high corn (48.76%) diet with a 60:40 ratio of concentrate to roughage. The inflammatory responses of beef cattle fed LA- and HA-treated corn were also investigated. RESULTS: Based on ultra-high-performance liquid tandem chromatography-quadrupole time-of-flight mass spectrometry (UHPLC-QTOF/MS) metabolomics and multivariate analyses, this study showed that steeping corn in 1% LA or 1% HA modulated the metabolic profiles of the rumen. Feeding beef steers corn steeped in 1% LA or 1% HA was associated with lower relative abundance of carbohydrate metabolites, amino acid metabolites, xanthine, uracil and DL-lactate in the rumen; with higher ruminal pH; with lower concentrations of acetate, iso-butyrate and iso-valerate; and with a tendency for lower ruminal lipopolysaccharide (LPS) concentrations. Moreover, the data showed lower concentrations of plasma C-reactive protein, serum amyloid A, haptoglobin, interleukin (IL)-1ß and IL-8 in beef steers fed 1% LA- or HA-treated corn. The 1% LA treatment decreased the concentrations of plasma LPS, LPS-binding protein and tumour necrosis factor-alpha and the relative abundance of L-phenylalanine, DL-3-phenyllactic acid and tyramine in plasma. The 1% HA treatment decreased the relative abundance of urea in plasma and increased the relative abundance of all amino acids in the plasma. CONCLUSIONS: These findings indicated that LA or HA treatment of corn modulated the degradation characteristics of starch, which contributed to improving the rumen and plasma metabolic profiles and to decreasing inflammatory responses in beef steers fed a high-concentrate diet.

Early life esophageal acid exposure reduces expression of NMDAR1 in the adult rat dorsal hippocampus and medial prefrontal cortex: Potential relationship with hyperlocomotion.

OBJECTIVE: Early life esophageal acid exposure causes long-term molecular alterations in the rostral cingulate cortex; however, whether it induces behavioral changes remains unverified. Little is known about the molecular changes resulting from this event in the developing hippocampus and medial prefrontal cortex (mPFC). This study aimed to investigate the influence of early life esophageal acid exposure on spontaneous locomotor behavior and N-methyl-D-aspartate receptor (NMDAR), expression in these brain regions of adult rats. METHODS: Male Sprague-Dawley rats were administered with an esophageal acid or saline infusion once per day (postnatal days 7-14). Some of these rats were given acute esophageal acid rechallenge in adulthood (postnatal day 60). The spontaneous locomotor behavior and expressions of esophageal epithelial caludin-1 and NMDAR subunits in the dorsal hippocampus (DH), ventral hippocampus (VH) and mPFC of the adult rats were recorded. RESULTS: Neonatal esophageal acid stimulation caused long-term impairment of the tight junctions in the adult esophagus. Simultaneously, hyperlocomotion and reduced expression of NMDAR1 subunits in both the DH and mPFC were observed, but not in the VH regions. Adult acute acid rechallenge reversed the decreased NMDAR1 expression in the DH and mPFC. The glycine ligand to NMDAR1 subunits was also changed. CONCLUSIONS: Peripheral visceral stimulation such as esophageal acid exposure during cerebral development induces increased locomotor activity, which may be related to the alteration of central sensitivity via NMDAR1 subunit reduction in the DH and mPFC. The impairment of tight junctions in the esophageal epithelium may contribute to the formation of central neuroplasticity.

Two hit induced acute lung injury impairs cognitive function in mice: A potential model to study cross talk between lung and brain.

Acute lung injury (ALI), a pulmonary inflammatory disorder, is associated with high morbidity and mortality rates. Interestingly, ALI survivors have been reported for some neurocognitive deterioration at/after discharge. However, the molecular factors behind such extra pulmonary manifestation are not clearly known. The present work was designed to investigate lung-brain cross talk in experimental mice for deciphering primary molecular factors that may be involved in ALI-mediated cognitive impairment. ALI was induced in Balb/c mice by intra-tracheal administration of either 0.1 N HCl (2 ml/kg) or LPS (1 mg/kg) as single hits or both agents were administered successively to mimic the 'two hit' model. Interestingly two hit-mediated ALI resulted in exaggerated inflammatory response as reflected by increased pulmonary neutrophils and inflammatory factors (TNF-α/IL-1ß/IL-6). Additionally, two hits resulted in delayed resolution of lung inflammation and was coupled with persistent decline in memory, as assessed by Morris water maze test. Further, two hits elevate serum levels of TNF-α/IL-1ß which was associated with compromised blood brain barrier (BBB), as evident by decreased expression of occludin/claudin-5 and consequent Evans-blue extravasation in hippocampus 1 week post injury. Finally, dexamethasone protects against the two hit mediated cognitive impairment by lowering the pro-inflammatory factors (TNF-α/IL-1ß) both in lungs and blood. Overall, we report for the first time that 'two hit' mediated ALI cause persistent cognitive impairment in mice partly via up-regulating systemic expression of TNF-α/IL-1ß that may disrupt BBB and hence the model may be a useful tool to examine the lung-brain cross-talk at the molecular level for exploring newer therapeutics.

Characteristics of hydrogen-producing enrichment cultures from marine sediment using macroalgae Laminaria japonica as a feedstock.

This study aimed to investigate the characteristics of hydrogen production by mixed cultures using Laminaria japonica hydrolysates. The hydrolysates of L. japonica were prepared by pretreatment methods, including heat (100°C or 121°C) and acid (HCl or H2SO4) pretreatments. The mixed cultures could produce hydrogen using L. japonica as a substrate, with the highest cumulative hydrogen production of 825 ± 14 mL/L from HCl-pretreated L. japonica. High-throughput sequencing of the 16S rRNA gene revealed that the microbial community in the hydrolysate of HCl-pretreated L. japonica was the most diverse among all the samples, with a Shannon diversity index of 5.253. The mixed culture from HCl-pretreated L. japonica and those from heat-pretreated (100°C and 121°C) L. japonica occupied different regions in a principal component analysis (PCA) plot. The dominant population in the hydrolysate of HCl-pretreated L. japonica was represented by hydrogen-producing bacteria, Clostridium spp. and Bacillus spp. The results suggested that L. japonica was an optimal feedstock for hydrogen production. The acid (HCl) pretreatment method could effectively enhance the hydrogen production from L. japonica.

Increasing radiofrequency ablation volumes with the use of internally cooled electrodes and injected hydrochloric acid in ex vivo bovine livers.

PURPOSE: We used an impedance-controlled generator with an internally cooled electrode to perform radiofrequency ablation (RFA) in ex vivo bovine livers, with a single injection of either 38.5% sodium chloride (NaCl) or 10% hydrochloric acid (HCl), to determine the relative effects of these two solutions on tissue impedance, temperature and ablation volume. MATERIALS AND METHODS: We performed 10 ablations each with injections of NaCl (NaCl-RFA), HCl (HCl-RFA) or nothing (RFA-alone), with a power setting of 200 W for 15 minutes. We recorded tissue impedance before and after injection. We logged temperatures obtained from thermocouple probes positioned 5, 10, 15 and 20 mm from the internally cooled RF electrode. After ablation, we measured ablation zone longitudinal and transverse diameters, and we calculated a spherical ratio (SR) for each ablation. RESULTS: Mean post-injection impedance of 30.3 (standard deviation [SD] 2.5) ohms for HCl was significantly lower than that of 55.4 (SD 3.5) ohms for NaCl (p < .001). Mean maximum temperatures recorded at each respective distance from the RFA electrode were all highest for HCl-RFA and lowest for RFA-alone (p < .001). Mean longitudinal and transverse diameters after HCl-RFA (5.50 [SD 0.25] cm and 5.28 [SD 0.22] cm, respectively) were significantly larger than those after NaCl-RFA (4.24 [SD 0.35] cm and 3.55 [SD 0.43] cm, respectively) and after RFA-alone (3.60 [SD 0.10] cm and 2.70 [SD 0.13] cm, respectively) (p < .001). Mean SR after HCl-RFA (0.93, SD 0.02) was significantly higher than mean SR after NaCl-RFA (0.76, SD 0.06) and RFA-alone (0.72, SD 0.04) (p < .001). CONCLUSION: Monopolar, impedance-controlled RFA, with an internally cooled electrode and a single 10% HCl injection may allow larger tumors to be treated, potentially resulting in improved patient outcomes.

Safety and effect on ablation size of hydrochloric acid-perfused radiofrequency ablation in animal livers.

PURPOSE: Our objective was to determine the safety and ablation size of hydrochloric acid-perfused radiofrequency ablation (HCl-RFA) in liver tissues, prospectively using in vivo rabbit and ex vivo porcine liver models. MATERIALS AND METHODS: The livers in 30 rabbits were treated in vivo with perfusions of normal saline (controls) and HCl concentrations of 5%, 10%, 15%, and 20%, during RFA at 103 °C and 30 W for 3 min. For each experimental setting, six ablations were created. Safety was assessed by comparing baseline weight and selected laboratory values with those at 2, 7, and 14 days' post-ablation, and by histopathological analysis. The livers in 25 pigs were treated ex vivo with the same five perfusions during RFA at 103 °C, at both 30 W and 60 W, for 30 min. Ablation diameters and volumes were measured by two examiners. RESULTS: Rabbit weights and selected laboratory values did not differ significantly from baseline to 7 and 14 days' post-ablation, liver tissues outside the ablation zones were normal histologically, and adjacent organs showed no macroscopic damage. The mean ablation volumes in the porcine livers treated with HCl-RFA were all larger than those treated with normal saline perfusion during RFA (NS-RFA), at both 30 W and 60 W (p < 0.001). The largest ablation volume and transverse diameter were observed in the porcine livers during 10% HCl-RFA at 60 W, measuring 179.22 (SD = 24.79) cm3 and 6.84 (SD = 0.36) cm, respectively. CONCLUSIONS: Based on our experiments, HCl-RFA in the liver appears to be as safe as NS-RFA while also resulting in larger ablation zones.

Effect of matrix metalloproteinase inhibitor on disrupted E-cadherin after acid exposure in the human nasal epithelium.

OBJECTIVE: Laryngopharyngeal reflux disease (LPRD) is one of potential factors in recalcitrant chronic rhinosinusitis with or without polyps. An increase in junctional permeability in the nasal mucosa in LPRD may be due to disrupted protein bridge formation with cell-to-cell adhesion molecules such as E-cadherin. Despite the relationship between nasal mucosal inflammation and LPRD, the clear mechanism by which acid reflux affects the nasal epithelium remains unclear. METHODS: The expression levels and distribution patterns of E-cadherin in primary culture of nasal epithelial cells after acid exposure with or without dexamethasone and matrix metalloproteinase (MMP) inhibitor were determined using Western blot and immunocytochemistry. The functional roles of MMP inhibitor in maintaining junctional permeability in the nasal epithelium were elucidated by transepithelial permeability test. RESULTS: By acid exposure to nasal epithelial cells, mature E-cadherin was decreased and cleaved E-cadherin was increased. This was thought to be caused by cleavage of mature E-cadherin between cells and was confirmed by the increment of E-cadherin inside a cell in immunocytochemical evaluation. Whereas disruption of E-cadherin was not recovered by steroid medication with various treatments of dexamethasone, disrupted E-cadherin was restored to normal by inhibition of MMPs with actinonin, a broad MMP inhibitor. This recovery was functionally demonstrated by transepithelial permeability test. CONCLUSION: Our results suggest that altered expression of E-cadherin in the nasal epithelium by acid exposure may be a possible mechanism for nasal tissue injury in chronic nasal inflammation with LPRD, and that MMP inhibition is a potential treatment. LEVEL OF EVIDENCE: NA. Laryngoscope, 128:E1-E7, 2018.