Applicability of the Barcelona scale to assess the quality of cleanliness of mucosa at esophagogastroduodenoscopy.

BACKGROUND AND OBJECTIVES: There are few scales with prospective validation for the assessment of the upper gastrointestinal mucosal cleanliness during an esophagogastroduodenoscopy (EGD). The aim of this study was to develop a valid and reproducible cleanliness scale for use during an EGD. METHODS: We developed a cleanliness scale (Barcelona scale) with a score (0-2 points) of five segments of the upper gastrointestinal tract with thorough cleaning techniques (esophagus, fundus, body, antrum, and duodenum). First, 125 photos (25 of each area) were assessed, and a score was assigned to each image by consensus among 7 experts endoscopists. Subsequently, 100 of the 125 images were selected and the inter- and intra-observer variability of 15 previously trained endoscopists was evaluated using the same images at two different times. RESULTS: In total, 1500 assessments were performed. In 1336/1500 observations (89%) there was agreement with the consensus score, with a mean kappa value of 0.83 (0.45-0.96). In the second evaluation, in 1330/1500 observations (89%) there was agreement with the consensus score, with a mean kappa value of 0.82 (0.45-0.93). The intra-observer variability was 0.89 (0.76-0.99). CONCLUSIONS: The Barcelona cleanliness scale is a valid measure and reproducible with minimal training. Its application in clinical practice is a significant step to standardize the quality of the EGD.

Impact of time-restricted feeding on kidney injury in male rats with experimental metabolic syndrome.

Disruptions to circadian rhythm may be implicated in the pathogenesis of metabolic syndrome (Met-S). For example, eating during an extended period of the day may negatively impact the circadian rhythms governing metabolic control, contributing, therefore, to Met-S and associated end-organ damage. Accordingly, time-restricted eating (TRE)/feeding (TRF) is gaining popularity as a dietary intervention for the treatment and prevention of Met-S. To date, no studies have specifically examined the impact of TRE/TRF on the renal consequences of Met-S. The proposed study seeks to use a model of experimental Met-S-associated kidney disease to address this knowledge gap, disambiguating therein the effects of calorie restriction from the timing of food intake. Spontaneously hypertensive rats will consume a high-fat diet (HFD) for 8 weeks and then be allocated by stratified randomisation according to albuminuria to one of three groups. Rats will have free 24-h access to HFD (Group A), access to HFD during the scheduled hours of darkness (Group B) or access to HFD provided in the form of two rations, one provided during the light phase and one provided during the dark phase, equivalent overall in quantity to that consumed by rats in Group B (Group C). The primary outcome measure will be a change in albuminuria. Changes in food intake, body weight, blood pressure, glucose tolerance, fasting plasma insulin, urinary excretion of C-peptide and renal injury biomarkers, liver and kidney histopathology and inflammation, and fibrosis-related renal gene expression will be assessed as secondary outcomes.

Age-associated polyamines in peripheral blood cells and plasma in 20 to 70 years of age subjects.

Dietary polyamines have been associated with slowing ageing processes and various pathologies, raising the importance of establishing reference values at different ages throughout life. This study aimed to analyse age-dependent variations in polyamine content using peripheral blood cells and plasma in a healthy and homogeneous population. Peripheral blood of 193 volunteers of both sexes (20-70 years), selected by convenience, was processed to separate cells and plasma. A pre-column derivatization method was used to determine the amines by HPLC (nmol or pmol/mg protein or nmol/ml) to analyse their association with the age (continuous or ordinal in decades) of the subjects. Putrescine and spermine weakly declined significantly in mononuclear cells with age. In erythrocytes and plasma, putrescine showed an evident decrease in the 60-70-year-old group compared to the rest. The ratios between polyamines, mainly in erythrocytes, decreased in the 60-70 years age group and increased the ratio of putrescine in mononuclear cells/erythrocytes. The ratio of putrescine in mononuclear cells/erythrocytes was higher in the 60-70-year-old age group than in the rest. In a sample of subjects (20-29 vs. 60-70 years), whole blood polyamines were not significantly different when differences existed in erythrocytes. Polyamine homeostasis in blood cells and plasma changed with age. Putrescine declined in mononuclear cells and decreased in erythrocytes and plasma in the decade of the 60 s. Further studies should establish an age-dependent phenotype and whether polyamines' supplementation could restore the decreased values and be associated with long-term overall biological benefits.

Expression of MMP-2, MMP-7, MMP-9, and TIMP-1 by Inflamed Mucosa in the Initial Diagnosis of Ulcerative Colitis as a Response Marker for Conventional Medical Treatment.

INTRODUCTION: Experimental and clinical data involve matrix metalloproteases (MMPs) and their tissue inhibitors (TIMPs) in the pathogenesis of inflammatory bowel diseases. However, the impact of MMPs/TIMPs expression by inflamed mucosa on medical response therapy has scarcely been investigated. METHODS: The expression of MMP-2, MMP-7, MMP-9, and TIMP-1 was determined by immunohistochemical analysis in inflamed mucosa samples at diagnosis in 82 patients with ulcerative colitis (UC; 22 never-treated with corticosteroids, 28 nonresponders, and 32 responders to corticosteroid therapy) and 15 patients with acute diverticulitis (AD). The global expression (score value) of each factor was analyzed by computer-generated image analysis. RESULTS: UC samples showed higher MMP-2 and MMP-9 expression but lower TIMP-1 expression than the AD samples (p < 0.0001, for all). High MMP-9 and TIMP-1 scores were significantly associated with no need for corticosteroid treatment (p < 0.001 and p = 0.017, respectively); whereas higher score in the MMP-7 expression was significantly associated with nonresponse to corticosteroid therapy (p = 0.037). In addition, in this latter UC subgroup, MMP-7 correlated positively with the younger age of the patients and with the extension of the disease (p = 0.030 and p = 0.010, respectively). CONCLUSION: Our results suggest the relevance of MMPs and TIMPs for predicting treatment response to both 5-aminosalicylates and corticosteroids in UC.

A Q fever outbreak among visitors to a natural cave, Bizkaia, Spain, December 2020 to October 2021.

We describe a large Q fever outbreak reported in Spain, including 108 cases, 53 with pneumonia and 27 requiring hospitalisations. The first cases were detected in February 2021 among rock climbers visiting a cave in Bizkaia, and the last case was detected in October 2021. Most cases were notified after the Easter holiday (April-May 2021). More males (63.9%) than females (36.1%) were infected (median ages: 42 (1-68) and 39 years (6-61), respectively). We detected Coxiella burnetii by PCR in faecal, dust and/or aerosol samples taken inside the cave in March 2021, and in dust and aerosol samples collected between March 2021 and February 2023. Coxiella burnetii from dust samples were cultured on Vero cells, showing viability for 24 months. Based on serological and genotyping data, goats sheltering in the cave were the most likely source of infection. The cave was closed on 29 April 2021, movements of goats and sheep in the area were restricted (March-July 2021), and the animals were vaccinated in October 2021. Investigation of Q fever outbreaks requires a multidisciplinary One Health approach as these outbreaks can occur in unexpected places like natural sites where animals are present.

Comments on "Sigmoid volvulus management, only endoscopic devolvulation?"

We are grateful our case has aroused such interest from our Turkish colleagues, and we thank them for their kind reply. Sigmoid volvulus (SV) is the third leading cause of colonic obstruction in the world. Is it widely known there is a progressive aging of the population. Prevention with lifestyle habits and early treatment of cardiovascular risk factors has led to an increase of pluripatologic chronic conditions. A higher incidence of neurodegenerative diseases is also a proven fact. Their intestinalinvolvementcan be ina direct form, withneuronal destruction in myenteric plexus leading to chronic constipation, and alsodue to secondary drug effects (laxatives causing fecal overloading, increased intracolonic pressure, dolichocolon…), all favouringweakness in colonic wall, and therefore the appearance of sigmoid volvulus. We don´t have specific data about SV incidence and recurrence in our centre.However, literature reviews show recurrence is the norm in the majority of cases after colonic decompression. Data reported from our colleagues in Turkey represents a single centre cohort and a broad spectrum over time (from 1960s until now), so recurrence rate should not be generalized to global population. The continuous improvement in endoscopic procedures since their beginning might have despair results of colonic decompression and need of surgery among years. Nowadays we have more sophisticated and high-resolution endoscopes, as well as better trained endoscopists with more advanced therapeutic techniques. This might overlap with surgical development of less invasive techniques, lower rates of complication and shorter postoperative recovery. We suggest the authors to examin in their database the different outcomes through decades in their cohort since we believe medical/endoscopic/surgical approach has changed from 1960s until now. Finally, we agree elective surgery must be the final treatment in SV cases with American Society of Anesthesiologists (ASA) scores 1-3. Endoscopic or laparoscopic colopexychoice for ASA > 3 patients should be made based on each centre´s experience. We believe endoscopic approach with endoscopic colostomy or sigmoidopexy might be the first approach for fragile patients since it is an easily performed technique, with low rate of complications and acceptable long-term results preventing a recurrence of SV. Further studies are needed to compare minimally invasive surgery to endoscopic approach.

Sigmoid volvulus management, only endoscopic devolvulation?

Intestinal obstruction due to sigmoid volvulus (SV) represents a relevant percentage of abdominal diseases presenting at the emergency department. Treatment is based on early endoscopic devolvulation (ED), followed by elective surgery as definitive treatment. A 78-year-old man institutionalized with Lewy body dementia presents with abdominal pain, distention, and absence of stool in 72 hours. Coffee bean sign was seen in abdominal x-ray. Previously, he had been admitted three times last year with recurrent SV, managed with ED succesfully. Despite the recurrence, no surgical treatment was indicated after resolution of the acute situation and recovery of intestinal transit. This time, urgent colonoscopy was performed and a 20 cm length of purplish-black (isquemic) sigmoid mucosa was observed. With these findings of stablished intestinal ischemia urgent surgical intervention was performed (sigmoidectomy and terminal "Hartmann" colostomy). Histologically, necrosis, severe ulceration and mixed inflammation was noticed in the surgical piece. The patient develops favorably during a postoperative period without incidents. Therefore, he is discharged to his center. At the moment he is asymptomatic one year after the intervention with no new episodes. Recurrency of SV after ED is up to 86% of cases. In every episode, the incidence of complications such as intestinal ischemia or perforation increases significantly, as well as urgent surgery and mortality. Definitive treatment must be surgical, sigmoidectomy and terminal anastomosis is the choice technique.

Endoscopy-Related Bleeding and Thromboembolic Events in Patients on Direct Oral Anticoagulants or Vitamin K Antagonists.

BACKGROUND & AIMS: Few prospective studies have assessed the safety of direct oral anticoagulants (DOACs) in elective endoscopy. Our primary aim was to compare the risks of endoscopy-related gastrointestinal bleeding and thromboembolic events in patients on DOACs or vitamin K antagonists (VKAs) in this setting. Secondarily, we examined the impact of the timing of anticoagulant resumption on the risk of delayed bleeding in high-risk therapeutic procedures. METHODS: We conducted a multicenter, prospective, observational study from January 2018 to March 2020 of 1602 patients on oral anticoagulants (1004 on VKAs and 598 on DOACs) undergoing 1874 elective endoscopic procedures. Our primary outcomes were 90-day thromboembolic events and 30-day endoscopy-related gastrointestinal bleeding. The inverse probability of treatment weighting propensity score method was used for baseline covariate adjustment. RESULTS: The 2 groups had similar risks of endoscopy-related gastrointestinal bleeding (VKAs vs DOACs, 6.2% vs 6.7%; adjusted odds ratio [OR], 1.05; 95% CI, 0.67-1.65) and thromboembolic events (VKAs vs DOACs, 1.3% vs 1.5%; adjusted OR, 0.90; 95% CI, 0.34-2.38). In high bleeding risk procedures (n = 747), delayed anticoagulant resumption (> 48 hours or 24-48 hours vs < 24 hours) did not reduce the risk of postprocedural bleeding (10.3%, 9%, and 5.8%, respectively; adjusted P = .43). Hot and cold snare polypectomy were the most frequent high-risk interventions (41.8% and 39.8%, respectively). CONCLUSION: In a prospective study of patients on DOACs or VKAs undergoing elective endoscopy, endoscopy-related bleeding and thromboembolic events showed similar risk. Our study suggests that early anticoagulant resumption is safe in most patients, but more data are needed for advanced high-risk therapeutic procedures.

Quality of Colonoscopy Is Associated With Adenoma Detection and Postcolonoscopy Colorectal Cancer Prevention in Lynch Syndrome.

BACKGROUND & AIMS: Colonoscopy reduces colorectal cancer (CRC) incidence and mortality in Lynch syndrome (LS) carriers. However, a high incidence of postcolonoscopy CRC (PCCRC) has been reported. Colonoscopy is highly dependent on endoscopist skill and is subject to quality variability. We aimed to evaluate the impact of key colonoscopy quality indicators on adenoma detection and prevention of PCCRC in LS. METHODS: We conducted a multicenter study focused on LS carriers without previous CRC undergoing colonoscopy surveillance (n = 893). Incident colorectal neoplasia during surveillance and quality indicators of all colonoscopies were analyzed. We performed an emulated target trial comparing the results from the first and second surveillance colonoscopies to assess the effect of colonoscopy quality indicators on adenoma detection and PCCRC incidence. Risk analyses were conducted using a multivariable logistic regression model. RESULTS: The 10-year cumulative incidence of adenoma and PCCRC was 60.6% (95% CI, 55.5%-65.2%) and 7.9% (95% CI, 5.2%-10.6%), respectively. Adequate bowel preparation (odds ratio [OR], 2.07; 95% CI, 1.06-4.3), complete colonoscopies (20% vs 0%; P = .01), and pan-chromoendoscopy use (OR, 2.14; 95% CI, 1.15-3.95) were associated with significant improvement in adenoma detection. PCCRC risk was significantly lower when colonoscopies were performed during a time interval of less than every 3 years (OR, 0.35; 95% CI, 0.14-0.97). We observed a consistent but not significant reduction in PCCRC risk for a previous complete examination (OR, 0.16; 95% CI, 0.03-1.28), adequate bowel preparation (OR, 0.64; 95% CI, 0.17-3.24), or previous use of high-definition colonoscopy (OR, 0.37; 95% CI, 0.02-2.33). CONCLUSIONS: Complete colonoscopies with adequate bowel preparation and chromoendoscopy use are associated with improved adenoma detection, while surveillance intervals of less than 3 years are associated with a reduction of PCCRC incidence. In LS, high-quality colonoscopy surveillance is of utmost importance for CRC prevention.

Crosstalk between cyclophilins and T lymphocytes in coronary artery disease.

Cardiovascular diseases and atherosclerosis are currently some of the most widespread diseases of our time. Within cardiovascular disease, coronary artery disease and underlying atherosclerosis were recently linked with systemic and local inflammation. Cyclophilins participate in the initiation and progression of these inflammatory-related diseases. Cyclophilins are released into the extracellular space upon inflammatory stimuli and participate in the pathology of cardiovascular diseases. The cell surface receptor for extracellular cyclophilins, the CD147 receptor, also contributes to coronary artery disease pathogenesis. Nevertheless, the physiological relevance of cyclophilin's family and their receptor in cardiovascular diseases remains unclear. The present study aimed to better understand the role of cyclophilins in cardiovascular artery disease and their relationship with inflammation. Hence, cyclophilins and pro-inflammatory interleukins were measured in the serum of 30 subjects (divided into three groups according to coronary artery disease status: 10 patients with acute coronary syndrome, 10 patients with chronic coronary artery disease, and 10 control volunteers). In addition, cyclophilin levels and CD147 receptor expression were measured in T lymphocytes purified from these subjects. Cyclophilin A, B, and C, pro-inflammatory interleukins, and CD147 membrane expression were significantly elevated in patients with coronary artery disease.

Cytotoxic Mechanism of Sphaerodactylomelol, an Uncommon Bromoditerpene Isolated from Sphaerococcus coronopifolius.

Marine natural products have exhibited uncommon chemical structures with relevant antitumor properties highlighting their potential to inspire the development of new anticancer agents. The goal of this work was to study the antitumor activities of the brominated diterpene sphaerodactylomelol, a rare example of the dactylomelane family. Cytotoxicity (10-100 µM; 24 h) was evaluated on tumor cells (A549, CACO-2, HCT-15, MCF-7, NCI-H226, PC-3, SH-SY5Y, SK-ML-28) and the effects estimated by MTT assay. Hydrogen peroxide (H2O2) levels and apoptosis biomarkers (membrane translocation of phosphatidylserine, depolarization of mitochondrial membrane potential, Caspase-9 activity, and DNA condensation and/or fragmentation) were studied in the breast adenocarcinoma cellular model (MCF-7) and its genotoxicity on mouse fibroblasts (L929). Sphaerodactylomelol displayed an IC50 range between 33.04 and 89.41 µM without selective activity for a specific tumor tissue. The cells' viability decrease was accompanied by an increase on H2O2 production, a depolarization of mitochondrial membrane potential and an increase of Caspase-9 activity and DNA fragmentation. However, the DNA damage studies in L929 non-malignant cell line suggested that this compound is not genotoxic for normal fibroblasts. Overall, the results suggest that the cytotoxicity of sphaerodactylomelol seems to be mediated by an increase of H2O2 levels and downstream apoptosis.

Gracilin-Derivatives as Lead Compounds for Anti-inflammatory Effects.

Gracilins are diterpenes derivative, isolated from the marine sponge Spongionella gracilis. Natural gracilins and synthetic derivatives have shown antioxidant, immunosuppressive, and neuroprotective capacities related to the affinity for cyclophilins. The aim of this work was to study anti-inflammatory and immunosuppressive pathways modulated by gracilin L and two synthetic analogues, compound 1 and 2, on a cellular model of inflammation. In this way, the murine BV2 microglia cell line was used. To carry out the experiments, microglia cells were pre-treated with compounds for 1 h and then stimulated with lipopolysaccharide for 24 h to determine reactive oxygen species production, mitochondrial membrane potential, the release of nitric oxide, interleukin-6 and tumor necrosis factor-α and the expression of Nuclear factor-erythroid 2-related factor 2, Nuclear Factor-κB, the inducible nitric oxide synthase, and the cyclophilin A. Finally, a co-culture of neuron SH-SY5Y and microglia BV2 cells was used to check the neuroprotective effect of these compounds. Cyclosporine A was used as a control of effect. The compounds were able to decrease inflammatory mediators, the expression of inflammatory target proteins as well as they activated anti-oxidative mechanism upon inflammatory conditions. For this reason, natural and synthetic gracilins could be interesting for developing anti-inflammatory drugs.

Biological Activities of Cyclic and Acyclic B-Type Laxaphycins in SH-SY5Y Human Neuroblastoma Cells.

Laxaphycins are a family of non-ribosomal lipopeptides that have been isolated from several cyanobacteria. Some of these compounds have presented cytotoxic activities, but their mechanism of action is poorly understood. In this work, the already described laxaphycins B and B3, and acyclolaxaphycins B and B3 were isolated from the marine cyanobacteria Anabaena torulosa. Moreover, two new acyclic compounds, [des-(Ala4-Hle5)] acyclolaxaphycins B and B3, were purified from the herviborous gastropod Stylocheilus striatus, with this being the first description of biotransformed laxaphycins. The structure of these new compounds was elucidated, together with the absolute configuration of acyclolaxaphycins B and B3. The bioactivities of the six peptides were determined in SH-SY5Y human neuroblastoma cells. Laxaphycins B and B3 were cytotoxic (IC50: 1.8 and 0.8 µM, respectively) through the induction of apoptosis. In comparison, acyclic laxaphycins did not show cytotoxicity but affected mitochondrial functioning, so their effect on autophagy-related protein expression was analyzed, finding that acyclic peptides affected this process by increasing AMPK phosphorylation and inhibiting mTOR. This work confirms the pro-apoptotic properties of cyclic laxaphycins B and is the first report indicating the effects on autophagy of their acyclic analogs. Moreover, gastropod-derived compounds presented ring opening and amino-acids deletion, a biotransformation that had not been previously described.

Caniferolide A, a Macrolide from Streptomyces caniferus, Attenuates Neuroinflammation, Oxidative Stress, Amyloid-Beta, and Tau Pathology in Vitro.

The macrolide caniferolide A was isolated from extracts of a culture of the marine-derived actinomycete Streptomyces caniferus, and its ability to ameliorate Alzheimer's disease (AD) hallmarks was determined. The compound reduced neuroinflammatory markers in BV2 microglial cells activated with lipopolysaccharide (LPS), being able to block NFκB-p65 translocation to the nucleus and to activate the Nrf2 pathway. It also produced a decrease in pro-inflammatory cytokines (IL-1ß, IL-6, and TNF-α), reactive oxygen species (ROS) and nitric oxide release and inhibited iNOS, JNK, and p38 activities. Moreover, the compound blocked BACE1 activity and attenuated Aß-activation of microglia by drastically diminishing ROS levels. The phosphorylated state of the tau protein was evaluated in SH-SY5Y tau441 cells. Caniferolide A reduced Thr212 and Ser214 phosphorylation by targeting p38 and JNK MAPK kinases. On the other side, the antioxidant properties of the macrolide were determined in an oxidative stress model with SH-SY5Y cells treated with H2O2. The compound diminished ROS levels and increased cell viability and GSH content by activating the nuclear factor Nrf2. Finally, the neuroprotective ability of the compound was confirmed in two trans-well coculture systems with activated BV2 cells (both with LPS and Aß) and wild type and transfected SH-SY5Y cells. The addition of caniferolide A to microglial cells produced a significant increase in the survival of neuroblastoma in both cases. These results indicate that the compound is able to target many pathological markers of AD, suggesting that caniferolide A could be an interesting drug lead for a polypharmacological approach to the illness.

Structure and biological evaluation of new cyclic and acyclic laxaphycin-A type peptides.

Five new laxaphycins were isolated and fully characterised from the bloom forming cyanobacteria Anabaena torulosa sampled from Moorea, French Polynesia: three acyclic laxaphycin A-type peptides, acyclolaxaphycin A (1), [des-Gly11]acyclolaxaphycin A (2) and [des-(Leu10-Gly11)]acyclolaxaphycin A (3), as well as two cyclic ones, [l-Val8]laxaphycin A (4) and [d-Val9]laxaphycin A (5). The absolute configuration of the amino acids, established using advanced Marfey's analysis for compounds 2-5, highlights a conserved stereochemistry at the Cα carbons of the peptide ring that is characteristic of this family. To the best of our knowledge, this is the first report of acyclic analogues within the laxaphycin A-type peptides. Whether these linear laxaphycins with the aliphatic ß-amino acid on the N-terminal are biosynthetic precursors or compounds obtained after enzymatic hydrolysis of the macrocycle is discussed. Biological evaluation of the new compounds together with the already known laxaphycin A shows that [l-Val8]laxaphycin A, [d-Val9]laxaphycin A and [des-Gly11]acyclolaxaphycin induce cellular toxicity whereas laxaphycin A and des-[(Leu10-Gly11)]acyclolaxaphycin A do not affect the cellular viability. An analysis of cellular death shows that the active peptides do not induce apoptosis or necrosis but instead, involve the autophagy pathway.

A multicentric Spanish study on the characteristics and survival of gastric adenocarcinoma under the age of 60.

INTRODUCTION: In Europe, gastric adenocarcinoma (GADC) is commonly regarded as a disease of the elderly. This study aims to assess the proportion, characteristics, and survival of patients diagnosed with GADC under the age of 60. MATERIALS AND METHODS: This is a retrospective, multicentric, and analytical study conducted at four tertiary Spanish hospitals. All patients diagnosed with GADC between 2008 and 2015 were included. Demographic, clinical, endoscopic, histologic, and survival data were retrieved. A multivariate analysis was performed to compare GADC in young (age≤60 years) and elderly patients. RESULTS: A total of 1374 patients with GADC were included. The mean age was 74 years (SD:11.1); 62.2% were males. There were 177 patients under the age of 60 (12.9%, 95% CI: 11.2-14.8%). GADC was frequently encountered as a metastatic disease in both young and elderly patients (Stage IV: 45.7% and 41%, respectively). In the multivariate analysis, alcohol abuse, ASA functional status I-II, diffuse subtype, neoadjuvant, and palliative therapy were independently associated (P<0.05) with age ≤60 years. No differences were found in 2-year survival (GADC ≤60: 39% vs. 35%, P=0.45). Curative-intent surgery, TNM stage I-II, body mass index<30kg/m2, and better functional status at diagnosis were independent predictors of survival in GADC under the age of 60. CONCLUSIONS: One out of eight cases of GADC were diagnosed under the age of 60. Metastatic disease was frequent at diagnosis and overall survival was poor regardless of age. Factors associated with localized disease correlated with improved survival in younger patients. Our results underline the need for early diagnosis strategies in our country.

Structures and Activities of Tiahuramides A-C, Cyclic Depsipeptides from a Tahitian Collection of the Marine Cyanobacterium Lyngbya majuscula.

The structures of three new cyclic depsipeptides, tiahuramides A (1), B (2), and C (3), from a French Polynesian collection of the marine cyanobacterium Lyngbya majuscula are described. The planar structures of these compounds were established by a combination of mass spectrometry and 1D and 2D NMR experiments. Absolute configurations of natural and nonproteinogenic amino acids were determined through a combination of acid hydrolysis, derivitization with Marfey's reagent, and HPLC. The absolute configuration of hydroxy acids was confirmed by Mosher's method. The antibacterial activities of tiahuramides against three marine bacteria were evaluated. Compound 3 was the most active compound of the series, with an MIC of 6.7 µM on one of the three tested bacteria. The three peptides inhibit the first cell division of sea urchin fertilized eggs with IC50 values in the range from 3.9 to 11 µM. Tiahuramide B (2), the most potent compound, causes cellular alteration characteristics of apoptotic cells, blebbing, DNA condensation, and fragmentation, already at the first egg cleavage. The cytotoxic activity of compounds 1-3 was tested in SH-SY5Y human neuroblastoma cells. Compounds 2 and 3 showed an IC50 of 14 and 6.0 µM, respectively, whereas compound 1 displayed no toxicity in this cell line at 100 µM. To determine the type of cell death induced by tiahuramide C (3), SH-SY5Y cells were costained with annexin V-FITC and propidium iodide and analyzed by flow cytometry. The double staining indicated that the cytotoxicity of compound 3 in this cell line is produced by necrosis.

Zoanthamine Alkaloids from the Zoantharian Zoanthus cf. pulchellus and Their Effects in Neuroinflammation.

Two new zoanthamine alkaloids, namely 3-acetoxynorzoanthamine (1) and 3-acetoxyzoanthamine (2), have been isolated from the zoantharian Zoanthus cf. pulchellus collected off the coast of the Santa Elena Peninsula, Ecuador, together with three known derivatives: zoanthamine, norzoanthamine, and 3-hydroxynorzoanthamine. The chemical structures of 1 and 2 were determined by interpretation of their 1D and 2D NMR data and comparison with literature data. This is the first report of zoanthamine-type alkaloids from Zoanthus cf. pulchellus collected in the Tropical Eastern Pacific. The neuroinflammatory activity of all the isolated compounds was evaluated in microglia BV-2 cells and high inhibitory effects were observed in reactive oxygen species (ROS) and nitric oxide (NO) generation.

Obstructive jaundice secondary to a hepatic hydatid cyst.

The rupture of a hepatic hydatid cyst into the intrahepatic bile ducts is one the most common and serious complication of hepatic hydatidosis and occurs in 5-25% of cases. (1, 2, 3). Endoscopic retrograde cholangiopancreatography (ERCP) plays an indisputable role in the diagnosis and treatment of this condition.

Listeriosis during the period 2003-2016.

Listeria monocytogenes can cause invasive disease in immunocompromised patients. We have retrospectively reviewed the clinical characteristics, treatment and evolution of the cases of listeriosis registered at our center during a long period of 14 years. Listeria monocytogenes infection is potentially serious with high mortality. Therefore, a high index of suspicion and early directed antibiotic treatment are needed, especially for immunocompromised patients.