Revisiting astrocyte to neuron conversion with lineage tracing in vivo.

In vivo cell fate conversions have emerged as potential regeneration-based therapeutics for injury and disease. Recent studies reported that ectopic expression or knockdown of certain factors can convert resident astrocytes into functional neurons with high efficiency, region specificity, and precise connectivity. However, using stringent lineage tracing in the mouse brain, we show that the presumed astrocyte-converted neurons are actually endogenous neurons. AAV-mediated co-expression of NEUROD1 and a reporter specifically and efficiently induces reporter-labeled neurons. However, these neurons cannot be traced retrospectively to quiescent or reactive astrocytes using lineage-mapping strategies. Instead, through a retrograde labeling approach, our results reveal that endogenous neurons are the source for these viral-reporter-labeled neurons. Similarly, despite efficient knockdown of PTBP1 in vivo, genetically traced resident astrocytes were not converted into neurons. Together, our results highlight the requirement of lineage-tracing strategies, which should be broadly applied to studies of cell fate conversions in vivo.

Antimicrobial Resistance of Helicobacter pylori Isolated From Latin American Children and Adolescents (2008-2023): A Systematic Review.

BACKGROUND: Latin America has a high prevalence of Helicobacter pylori in children that may lead to peptic ulcer disease and eventually gastric cancer in adulthood. Successful eradication is hindered by rising antimicrobial resistance. We summarize H. pylori resistance rates in Latin American children from 2008 to 2023. MATERIAL AND METHODS: Systematic review following PRISMA guidelines and National Heart, Lung, and Blood Institute checklist to assess risk of bias (PROSPERO CRD42024517108) that included original cross-sectional observational studies reporting resistance to commonly used antibiotics in Latin American children and adolescents. We searched in PubMed, LILACS, and SciELO databases. RESULTS: Of 51 studies, 45 were excluded. The quality of the six analyzed studies (297 H. pylori-positive samples) was satisfactory. Phenotypic methods (N = 3) reported higher resistance rates than genotypic studies (N = 3). Clarithromycin resistance ranged from 8.0% to 26.7% (6 studies; 297 samples), metronidazole from 1.9% to 40.2% (4 studies; 211 samples), amoxicillin from 0% to 10.4% (3 studies; 158 samples), tetracycline resistance was not detected (3 studies; 158 samples), and levofloxacin resistance was 2.8% (1 study; 36 samples). CONCLUSION: Scarce Latin American studies on H. pylori resistance, along with methodological heterogeneity, hinder conclusive findings. Clarithromycin and metronidazole (first-line drugs) resistance is worrisome, likely impacting lower eradication rates. Urgent systematic surveillance or individual testing before treatment is necessary to enhance eradication.

Mounier-Kuhn syndrome in poorly controlled asthma.

INTRODUCTION: Mounier-Kuhn syndrome or tracheobronchomegaly, is a rare condition that consists of abnormal dilation of the trachea and main bronchi due to a pathological arrangement of smooth muscle fibers in this area. CASE REPORT: We present the case of a 46-year-old woman with poorly controlled asthma and recurrent infections, who was diagnosed with Mounier-Kuhn syndrome through a computed tomography scan revealing an unusual enlargement of the trachea with associated bronchiectasis. RESULTS: The diagnosis of Mounier-Kuhn syndrome is radiological, involving measurement of the trachea where a diameter >25 mm in men and >21 mm in women is observed. While diagnosis is sometimes incidental, there is an association with respiratory diseases such as asthma or COPD, hence clinical suspicion is important in patients with poorly controlled underlying conditions who present with recurrent infections, inadequate secretion management, or even hemoptysis. CONCLUSIONS: Despite its rarity, this syndrome significantly impacts patients' quality of life. Diagnosis and management involve comprehensive evaluations including computed tomography, with a multidisciplinary approach including pulmonologists and radiologists. Exploring its clinical features, associations with other respiratory diseases and treatment options is crucial in managing this rare respiratory condition.

Monoclonal antibody treatment for severe uncontrolled asthma in Spain: analytical map.

BACKGROUND: Monoclonal antibodies (mABs) have become available to treat more efficiently patients with severe uncontrolled asthma (SUA). However, the use of mABs is lower than expected given the prevalence of SUA, with significant disparities in the use of these treatments. OBJECTIVE: To evaluate the proportion of patients with SUA treated with mABs in Spain, and to analyze some of the factors that could determine these prescription patterns. METHODS: An analysis was performed on the data provided from the Hospitals National Health System (NHS) 2018 catalogue where Chest Diseases Department and a Hospital Pharmacy were available. Random sampling was performed to determine the sample size, stratifying proportionally by geographic area and hospital level. Characteristics of the participating sites, as well as the prescribing of mABs were collected, which included geographic area, hospital levels, prescribing medical specialities, types of clinics, and mABs prescribed. RESULTS: Data from 90 hospitals were analyzed (Response rate 64.3%). Level 4 hospitals, the Canary Islands geographical area, and the presence of a high complexity Asthma Healthcare Unit (ACU) were associated with a higher probability that the SUA was treated with mABs. CONCLUSION: The map of the prescribing of mABs for SUA in Spain shows a significant variation by geographic area, hospital level, type of clinic, and the accreditation level of the ACUs. At the current time, there appears to be significant under-prescribing of these treatments.

Helicobacter pylori infection and UBT-13C values are associated with changes in body mass index in children and adults.

BACKGROUND: The urea breath test (UBT-13C) is a non-invasive technique that allows the diagnosis and confirmation of eradication of Helicobacter pylori infection. AIM: To evaluate H. pylori positivity and values of UBT-13C among infected Chilean children and adults, and to analyze its variation in relation to sex, nutritional status, and age of the patients. MATERIAL AND METHODS: Retrospective study of 1141 patients aged 6 to 94 years, with an indication for a UBT-13C either for diagnosis or for confirmation of eradication of H. pylori infection. 13C enrichment was measured using an infrared spectrometer calculating the delta 13C values before and after the ingestion of 13C marked urea. The clinical data of the patients were obtained at the time of the examination. RESULTS: We included 241 children and 900 adults. Infected children obtained lower UBT-13C delta values than infected adults (16.1 ± 8.7 and 37 ± 52.9, respectively). The rates of infection were higher in males who were recruited for diagnosis. Significant differences were obtained between positivity for H. pylori in overweight and obese children but not adults. UBT-13C titers were significantly associated with the body mass index (BMI) only in adults. CONCLUSIONS: H. pylori infection rates are similar between sexes and are higher in children probably because of selection bias. In children, H. pylori positivity is associated with higher BMI and excess malnutrition although with similar UBT-13C values. In adults, H. pylori infection is not related with BMI, but a higher BMI impacts UBT-13C titers.

Modulation of glycosyltransferase ST6Gal-I in gastric cancer-derived organoids disrupts homeostatic epithelial cell turnover.

Programmed cell death promotes homeostatic cell turnover in the epithelium but is dysregulated in cancer. The glycosyltransferase ST6Gal-I is known to block homeostatic apoptosis through α2,6-linked sialylation of the death receptor TNFR1 in many cell types. However, its role has not been investigated in gastric epithelial cells or gastric tumorigenesis. We determined that human gastric antral epithelium rarely expressed ST6Gal-I, but the number of ST6Gal-I-expressing epithelial cells increased significantly with advancing premalignancy leading to cancer. The mRNA expression levels of ST6GAL-I and SOX9 in human gastric epithelial cells correlated positively with one another through the premalignancy cascade, indicating that increased epithelial cell expression of ST6Gal-I is associated with premalignant progression. To determine the functional impact of increased ST6Gal-I, we generated human gastric antral organoids from epithelial stem cells and differentiated epithelial monolayers from gastric organoids. Gastric epithelial stem cells strongly expressed ST6Gal-I, suggesting a novel biomarker of stemness. In contrast, organoid-derived epithelial monolayers expressed markedly reduced ST6Gal-I and underwent TNF-induced, caspase-mediated apoptosis, consistent with homeostasis. Conversely, epithelial monolayers generated from gastric cancer stem cells retained high levels of ST6Gal-I and resisted TNF-induced apoptosis, supporting prolonged survival. Protection from TNF-induced apoptosis depended on ST6Gal-I overexpression, because forced ST6Gal-I overexpression in normal gastric stem cell-differentiated monolayers inhibited TNF-induced apoptosis, and cleavage of α2,6-linked sialic acids from gastric cancer organoid-derived monolayers restored susceptibility to TNF-induced apoptosis. These findings implicate up-regulated ST6Gal-I expression in blocking homeostatic epithelial cell apoptosis in gastric cancer pathogenesis, suggesting a mechanism for prolonged epithelioid tumor cell survival.

Compartmentalized Response of IL-6/STAT3 Signaling in the Colonic Mucosa Mediates Colitis Development.

A single layer of polarized epithelial cells lining the colonic mucosa create a semipermeable barrier indispensable for gut homeostasis. The role of intestinal epithelial cell (IEC) polarization in the maintenance of the epithelial homeostasis and in the development of inflammatory bowel diseases is not fully understood. In this review, now we report that IEC polarization plays an essential role in the regulation of IL-6/STAT3 signaling in the colonic mucosa. Our results demonstrate that autocrine STAT3 activation in IECs is mediated by the apical secretion of IL-6 in response to the basolateral stimulation with IFN-γ. This process relies on the presence of functional, IFN-γ-producing CD4+ T cells. In the absence of basolateral IFN-γ, the compartmentalization of the IL-6/STAT3 signaling is disrupted, and STAT3 is activated mainly in macrophages. Thus, in this study, we show that during inflammation, IFN-γ regulates IL-6/STAT3 signaling in IEC in the colonic mucosa.

High Helicobacter pylori Bacterial Load and Low Cytokine Expression Levels Are Associated with Nodular Gastropathy.

BACKGROUND AND AIMS: Nodular gastropathy (NG) is an inflammatory condition of the gastric mucosa characterized by the endoscopic detection of multiple millimeter protrusions. A strong association between NG and Helicobacter pylori and a possible role of NG as a risk factor for undifferentiated gastric cancer have been described. The aim of this study was to characterize the pathogenic and inflammatory profile of patients with NG. METHODS: Adult patients referred for upper gastrointestinal endoscopy were prospectively enrolled in this study. H. pylori infection status was determined by rapid urease test. Biopsies were stained with hematoxylin-eosin. Sydney and OLGA scores were used to assess gastritis characteristics and gastric cancer risk. PCR analysis was performed to determine bacterial load and virulence factors CagA (and its EPIYA motifs) and VacA alleles. Finally, gastric mucosa cytokine gene expression (IL-8, IL-1ß, and TNF-α) was determined by real-time RT-PCR. RESULTS: Forty-eight patients, mean age of 36 years, were recruited. All NG patients were infected by H. pylori. OLGA score was similar in both groups (NG patients and non-NG patients). NG patients had higher bacterial load in the gastric corpus (p = 0.01) and significantly less pro-inflammatory cytokine levels than non-NG infected patients (p = 0.01). CONCLUSIONS: In our study, NG is not associated with preneoplastic lesions. An increase in bacterial load without a concomitant increase in mucosal inflammatory cytokine responses in H. pylori-infected subjects with NG may represent a general dampening of immune responses or an additional mechanism of H. pylori active immune evasion.

Early origins of allergy and asthma (ARIES): study protocol for a prospective prenatal birth cohort in Chile.

BACKGROUND: Growing evidence shows that atopic dermatitis (AD), food allergy (FA), allergic rhinitis, and asthma are largely determined during the first 1000 days (time elapsed from conception to the 2nd birthday). The ARIES birth cohort aims to determine prenatal and perinatal conditions, as well as genetic and epigenetic factors, that participate in the early setting of immune responses, and the role of these in the later determination of the risk of allergic diseases and asthma in the offspring. METHODS: We have designed a birth cohort of 250 families with prenatal recruitment (~ 14 weeks). We will genotype relevant allergy/asthma-associated variants in trios and will perform immunophenotyping and evaluation of allergy biomarkers in cord blood. At 1 and 2 years of age we will assess if infants have developed allergic sensitization, AD, FA, as well as biomarkers of asthma including the asthma predictive index. We will also evaluate how maternal conditions modify immune programming through epigenetic modifications and will then depict newborn epigenetic cues of allergy/asthma risk. Next, we will assess composition/diversity of maternal gut, placenta, breastmilk and infant gut microbiome and their association with immunophenotype and biomarkers at birth, and clinical outcomes at age 1 and 2. Finally, we plan to assess how environmental exposures (perinatal outdoor and indoor pollution, allergens and endotoxin) affect the incidence of allergic sensitization, AD, FA, and risk of asthma. DISCUSSION: The in-depth study of the ARIES birth cohort shall provide crucial information to understand the rising incidence of allergies and asthma in developing countries, and hopefully provide cues on how to prevent and treat these diseases. TRIAL REGISTRATION: clinicaltrials.gov NCT04186949, retrospectively registered on December 5, 2019.

Portal Angiogenesis in Chronic Liver Disease Patients Correlates with Portal Pressure and Collateral Formation.

BACKGROUND/AIMS: One hallmark of chronic liver disease in patients with portal hypertension is the formation of portal-systemic collaterals in which angiogenesis has a fundamental role. We studied patients with chronic liver disease undergoing liver transplantation to correlate levels of circulating angiogenic factors in portal and peripheral circulation with portal pressure and portal-systemic collaterals. METHODS: Sixteen patients who underwent liver transplantation were enrolled. During transplant surgery, we determined portal venous pressure and portal-systemic collateral formation. We determined angiogenics mediator levels in systemic and portal plasma. Peripheral plasma from healthy donors was measured as controls. RESULTS: Vascular endothelial growth factor (VEGF)-R1 and 2, Ang-1 and 2, Tie2, FGF- 1 and 2, CD163, PDGFR-ß, PDGFsRα, PDGF-AB and BB, CD163, TGF-ß VASH-1 levels were significantly different in the controls in comparison to cases. Significantly decreased portal venous levels of Ang-1, FGF-1, PDGF-AB/BB, and CC were observed in patients with higher portal pressure. Peripheral VEGF, Ang-1, pPDGF-AB, BB, and CC were significantly decreased in patients with more severe collateral formation. While peripheral VEGF-R1 was higher in patients with severe collateral formation. For portal circulation, VEGF, Ang-1, -pPDGF-AB, BB, and CC were significantly decreased in patients with more severe collateral formation Conclusions: Angiogenesis factors correlated with portal pressure and collateral formation and different patterns of circulating angiogenesis mediators were found in peripheral and portal blood of patients with chronic liver disease. These results support the importance of angiogenic pathways in cirrhosis and portal hypertension and highlight areas for further study to identify clinically useful noninvasive markers of portal pressure and collateral formation.

pVHL suppresses Akt/ß-catenin-mediated cell proliferation by inhibiting 14-3-3ζ expression.

The mechanisms controlling degradation of cytosolic ß-catenin are important for regulating ß-catenin co-transcriptional activity. Loss of von Hippel-Lindau protein (pVHL) has been shown to stabilize ß-catenin, increasing ß-catenin transactivation and ß-catenin-mediated cell proliferation. However, the role of phosphoinositide 3-kinase (PI3K)/Akt in the regulation of ß-catenin signaling downstream from pVHL has never been addressed. Here, we report that hyperactivation of PI3K/Akt in cells lacking pVHL contributes to the stabilization and nuclear accumulation of active ß-catenin. PI3K/Akt hyperactivation is facilitated by the up-regulation of 14-3-3ζ and the down-regulation of 14-3-3ε, 14-3-3η and 14-3-3θ. Up-regulation of 14-3-3ζ in response to pVHL is important for the recruitment of PI3K to the cell membrane and for stabilization of soluble ß-catenin. In contrast, 14-3-3ε and 14-3-3η enhanced PI3K/Akt signaling by inhibiting PI3K and PDK1, respectively. Thus, our results demonstrated that 14-3-3 family members enhance PI3K/Akt/ß-catenin signaling in order to increase proliferation. Inhibition of Akt activation and/or 14-3-3 function strongly reduces ß-catenin signaling and decreases cell proliferation. Thus, inhibition of Akt and 14-3-3 function efficiently reduces cell proliferation in 786-0 cells characterized by hyperactivation of ß-catenin signaling due to pVHL loss.

Stent-induced tracheal stenosis can be predicted by IL-8 expression in rabbits.

BACKGROUND: Bare metal stents may cause complications like fibrous encapsulation, granulation and tracheal stenosis. We investigated the behaviour of three commercially available stents in vivo (rabbits) and in vitro (coculture of those stents with epithelial and fibroblast cell lines). Also, we investigated whether development of tracheal stenosis could be predicted by any biological marker. MATERIALS AND METHODS: The tracheae of 30 rabbits were implanted with either nitinol stents, with or without paclitaxel elution, or a cobalt-based stent. An additional ten rabbits underwent mock implantation (controls). Serial peripheral venous blood samples were taken throughout the study, and several cytokines measured. Animals were euthanized on day 90, with immediate tracheal endoscopy and lavage performed, then necropsy. RESULTS: Rabbits with cobalt-based stent exhibited more inflammation and the highest stenosis incidence, with reduced survival. Both in vivo and in vitro, this stent induced higher IL-8 levels than nitinol stents. Most important, the presence of stent-induced tracheal stenosis was closely associated to increase in IL-8 expression in blood just 1 day after tracheal stent implantation: a 1·19-fold increase vs. baseline had 83% sensitivity, 83% specificity, 77% positive predictive value, 88% negative predictive value and 83% accuracy to predict development of stenosis. CONCLUSIONS: The cobalt-based stent had the highest incidence of tracheal inflammation and stenosis. On the other hand, the paclitaxel-eluting nitinol stent did not prevent those complications and provoked a marked reaction compared with the bare nitinol stent. Early increase in IL-8 expression in blood after stent implantation could predict development of tracheal stenosis in rabbits.

Helicobacter pylori-Clarithromycin Resistance in Symptomatic Pediatric Patients in a High Prevalence Country.

INTRODUCTION: Failure to eradicate Helicobacter pylori despite antibiotic treatment is generally attributed to increasing clarithromycin resistance conferred by point mutations in the 23S-rRNA gene or metronidazole resistance attributed to rdxA gene (HP0954) deletion in patients. Scarce data for pediatric population are available from developing countries. OBJECTIVES: The aim of the present study was to determine the presence of A2142G/C and A2143G mutations in the 23S-rRNA gene and/or rdxA gene (HP0954) deletion in a group of symptomatic H pylori-infected children recruited from an area with high infection rate and risk of gastric cancer. PATIENTS AND METHODS: We recruited 118 patients referred for upper endoscopy for gastrointestinal symptoms. The presence of H pylori was determined by urease test and histological staining. The rdxA gene (HP0954) deletion, and 2142G/C and A2143G mutations were determined by polymerase chain reaction-restriction fragment length polymorphism. A subgroup of infected patients received a 14-day regimen of omeprazole, amoxicillin, and clarithromycin. The effectiveness of this regime was determined by stool antigen determination 8 weeks after treatment. RESULTS: About 21% of the analyzed infected patients showed mutation in the 23S-rRNA gene, with the A2143G transition as the more frequent mutation, and 2% of the patients showed rdxA gene (HP0954) deletion. After treatment, 25% of the patients continued to harbor the bacteria; of these, 67% carried the A2143G mutation. CONCLUSIONS: H pylori-infected pediatric patients from Chile show high prevalence of the mutation responsible for clarithromycin resistance. The failure to eradicate H pylori can be attributed to the presence of the A2143G mutation.

Caregiver's depressive symptoms and asthma control in children from an underserved community.

Caregiver's or maternal depression has been associated with increased asthma morbidity in children from prosperous nations, but little is known about this link in low and middle-income countries. OBJECTIVE: To examine if caregiver's depressive symptoms are associated with poor asthma control and abnormal immune responses in school-aged children. METHODS: Case-control study of 87 asthmatic children (aged 4-11 years) attending a primary care clinic in an underserved area of Santiago (Chile). Cases were children with poor asthma control (Child Asthma Control Test [cACT] <20 points) and controls were children with adequate asthma control (cACT ≥20 points). The Beck Depression Inventory-II (BDI) and a locally validated family health vulnerability test (SALUFAM) were used to assess caregivers' depression and family health vulnerability. Serum from participating children was assayed for IFN-γ, IL-4, IL-13, TGF-ß, cortisol, and total IgE. RESULTS: The mean (SD) age of study participants was 8.23 (2.15 years), and 55.2% were females. Use of inhaled corticosteroids (ICS), family health vulnerability, and caregiver's depressive symptoms were significantly more common in cases than in controls (65.4% vs. 34.6%, p = 0.003; 41.3% vs. 24.8%, p = 0.07; and 39.1% vs. 19.5%, p = 0.04, respectively). There was no significant difference in the level of any serum biomarkers between groups. In a multivariate analysis, only ICS use was significantly associated with better asthma control (OR = 3.56 [1.34-9.48], p = 0.01). CONCLUSIONS: Presence of caregiver's depressive symptoms is associated with poor asthma control among children from an underserved community, but this association was no longer significant after accounting for ICS use.

Conversion to mycophenolate mofetil monotherapy in liver recipients: Calcineurin inhibitor levels are key.

 The use of calcineurin inhibitors (CNI) after liver transplantation is associated with post-transplant nephrotoxicity. Conversion to mycophenolate mofetil (MMF) monotherapy improves renal function, but is related to graft rejection in some recipients. Our aim was to identify variables associated with rejection after conversion to MMF monotherapy. Conversion was attempted in 40 liver transplant recipients. Clinical variables were determined and peripheral mononuclear blood cells were immunophenotyped during a 12-month follow-up. Conversion was classified as successful (SC) if rejection did not occur during the follow-up. MMF conversion was successful with 28 patients (70%) and was associated with higher glomerular filtration rates at the end of study. It also correlated with increased time elapsed since transplantation, low baseline CNI levels (Tacrolimus ≤ 6.5 ng/mL or Cyclosporine ≤ 635 ng/mL) and lower frequency of tacrolimus use. The only clinical variable independently related to SC in multivariate analysis was low baseline CNI levels (p = 0.02, OR: 6.93, 95%, CI: 1.3-29.7). Mean baseline fluorescent intensity of FOXP3+ T cells was significantly higher among recipients with SC. In conclusion, this study suggests that baseline CNI levels can be used to identify recipients with higher probability of SC to MMF monotherapy. Clinicaltrials.gov identification: NCT01321112.

The pro-inflammatory cytokines IFNγ/TNFα increase chromogranin A-positive neuroendocrine cells in the colonic epithelium.

The gastrointestinal tract is the largest hormone-producing organ in the body due to a specialized cell population called enteroendocrine cells (EECs). The number of EECs increases in the mucosa of inflammatory bowel disease patients; however, the mechanisms responsible for these changes remain unknown. Here, we show that the pro-inflammatory cytokines interferon γ (IFNγ) and tumor necrosis factor α (TNFα) or dextran sulfate sodium (DSS)-induced colitis increase the number of EECs producing chromogranin A (CgA) in the colonic mucosa of C57BL/6J mice. CgA-positive cells were non-proliferating cells enriched with inactive phosphatase and tensin homolog deleted on chromosome 10 (PTEN) and autophagy markers. Moreover, inhibition of Akt and autophagy prevented the increase in CgA-positive cells after IFNγ/TNFα treatment. Similarly, we observed that CgA-positive cells in the colonic mucosa of patients with colitis expressed Akt and autophagy markers. These findings suggest that Akt signaling and autophagy control differentiation of the intestinal EEC lineage during inflammation.

Iron Deficiency and IL1ß Polymorphisms in Helicobacter pylori-infected Children.

BACKGROUND: Helicobacter pylori infection has been associated with an imbalance of iron homeostasis. IL-1ß has been related with iron absorption disturbances through a variety of mechanisms. The aim of this study was to evaluate the presence of polymorphic variants for IL-1ß cluster and gastric IL1ß mRNA expression in H. pylori-infected children and their relationship with hypochlorhydria and iron deficiency (ID). PATIENTS AND METHODS: Prospective study of 123 symptomatic children. At endoscopy, antral biopsies were taken for urease test, pathology and culture and blood for analysis of ferritin, transferrin, serum iron, and total iron-binding capacity. Polymorphisms in the IL-1ß cluster (positions -511, -31, +3954, ILRN) were determined by PCR-RFLP. Gastric mucosal expression of IL-1ß mRNA was determined by RT-PCR. RESULTS: After exclusions, of 105 patients, 33 (31.4%) were H. pylori positive. Nine (8.6%) children were classified as iron deficient (ID). Helicobacter pylori positivity was associated with ID (OR: 5.1; 95% CI: 1.2-21.9) (p = .04). No significant differences were found in allele frequency for IL1ß gene cluster polymorphisms between infected and uninfected children. Helicobacter pylori-infected children with ID had significantly increased gastric IL1ß mRNA in comparison with infected children without ID. In addition, a significant positive correlation was observed between mucosal IL-1ß mRNA and fasting gastric juice pH. Gastric pH values were significantly increased in H. pylori-infected patients with ID compared to uninfected children. CONCLUSIONS: The established association between H. pylori infection and ID in children may be mediated by increased gastric mucosal IL-1ß.

Angiogenesis and portal-systemic collaterals in portal hypertension.

In patients with advanced liver disease with portal hypertension, portal-systemic collaterals contribute to circulatory disturbance, gastrointestinal hemorrhage, hepatic encephalopathy, ascites, hepatopulmonary syndrome and portopulmonary hypertension. Angiogenesis has a pivotal role in the formation of portal-systemic shunts. Recent research has defined many of the mediators and mechanisms involved in this angiogenic process, linking the central roles of hepatic stellate cells and endothelial cells. Studies of animal models have demonstrated the potential therapeutic impact of drugs to inhibit angiogenesis in cirrhosis. For example, inhibition of VEGF reduces portal pressure, hyperdynamic splanchnic circulation, portosystemic collateralization and liver fibrosis. An improved understanding of the role of other angiogenic factors provides hope for a novel targeted therapy for portal hypertension with a tolerable adverse effect profile.

[Maternal infection due to Helicobacter pylori does not increase the risk of the infection in the first trimester of the life of their infants]. / La infección materna por Helicobacter pylori no aumenta el riesgo de contraer la bacteria en el primer trimestre de vida de sus lactantes.

INTRODUCTION: H. pylori infection is acquired early in childhood. However, there is little information available regarding the role of breastfeeding and neonatal acquisition of the infection. OBJECTIVE: To evaluate factors affecting the acquisition of H. pylori in newborns and infants from infected mothers. PATIENTS AND METHOD: Consecutive mothers and their newborns were recruited into the study from the maternity unit, immediately after delivery. After signing informed consent, one stool sample from the mother was obtained before hospital discharge. Three stool samples of the newborns were then collected at home at 15, 60, and 90 days of life, for the detection of H. pylori antigen (Monoclonal HpSAg, sensitivity 94% and specificity 97%). The socio-epidemiological and biomedical variables were also analysed using a questionnaire. RESULTS: A total of 32 mother-child pairs (64 subjects) were enrolled. The mean maternal age was 30.1±5.1 years, with 53% vaginal delivery, and 85% exclusively breastfed. There were 13 (40%) infected mothers. No H. pylori infection was detected in newborns and infants up to 3 months of follow-up. No significant differences were found in socioeconomic level between infected versus non-infected mothers (both groups mostly in the very high socioeconomic category: 28% and 32%, respectively, P=.15) and in the number of family members between infected versus non-infected mothers (3.8±0.8 vs 4.2±1.8 persons, P=.18). CONCLUSION: Despite having a significant percentage of H. pylori-infected mothers, no newborn was infected at the third month of life. The protective role of breastfeeding cannot be ruled out.