RESUMEN
Although brain scars in adults have been extensively studied, there is less data available regarding scar formation during the neonatal period, and the involvement of peripheral immune cells in this process remains unexplored in neonates. Using a murine model of neonatal hypoxic-ischemic encephalopathy (HIE) and confocal microscopy, we characterized the scarring process and examined the recruitment of peripheral immune cells to cortical and hippocampal scars for up to 1 year post-insult. Regional differences in scar formation were observed, including the presence of reticular fibrotic networks in the cortex and perivascular fibrosis in the hippocampus. We identified chemokines with chronically elevated levels in both regions and demonstrated, through a parabiosis-based strategy, the recruitment of lymphocytes, neutrophils, and monocyte-derived macrophages to the scars several weeks after the neonatal insult. After 1 year, however, neutrophils and lymphocytes were absent from the scars. Our data indicate that peripheral immune cells are transient components of HIE-induced brain scars, opening up new possibilities for late therapeutic interventions.
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Cicatriz , Hipoxia-Isquemia Encefálica , Adulto , Animales , Humanos , Ratones , Cicatriz/patología , Encéfalo/patología , Macrófagos , Hipoxia-Isquemia Encefálica/patologíaRESUMEN
Epilepsy is a neurological disease characterized by spontaneous and recurrent seizures. Epileptic seizures can be initiated and facilitated by inflammatory mechanisms. As the dysregulation of the immune system would be involved in epileptogenesis, it is suggested that anti-inflammatory medications could impact epileptic seizures. These medications could potentially have a side effect by altering the structure and composition of the intestinal microbiota. These changes can disrupt microbial homeostasis, leading to dysbiosis and potentially exacerbating intestinal inflammation. We hypothesize that prednisolone may affect the development of epileptic seizures, potentially influencing the diversity of the intestinal microbiota and the regulation of pro-inflammatory cytokines in intestinal tissue. This study aimed to evaluate the effects of prednisolone treatment on epileptic seizures and investigate the effect of this drug on the bacterial diversity of the intestinal microbiota and markers of inflammatory processes in intestinal tissue. We used Male Wistar rat littermates (n = 31, 90-day-old) divided into four groups: positive control treated with 2 mg/kg of diazepam (n = 6), negative control treated with 0.9 g% sodium chloride (n = 6), and the remaining two groups were subjected to treatment with prednisolone, with one receiving 1 mg/kg (n = 9) and the other 5 mg/kg (n = 10). All administrations were performed intraperitoneally (i.p.) over 14 days. To induce the chronic model of epileptic seizures, we administered pentylenetetrazole (PTZ) 25 mg/kg i.p. on alternate days. Seizure latency (n = 6 - 10) and TNF-α and IL-1ß concentrations from intestinal samples were measured by ELISA (n = 6 per group), and intestinal microbiota was evaluated with intergenic ribosomal RNA (rRNA) spacer (RISA) analysis (n = 6 per group). The prednisolone treatment demonstrated an increase in the latency time of epileptic seizures and TNF-α and IL-1ß concentrations compared to controls. There was no statistically significant difference in intestinal microbiota diversity between the different treatments. However, there was a strong positive correlation between microbial diversity and TNF-α and IL-1ß concentrations. The administration of prednisolone yields comparable results to diazepam on increasing latency between seizures, exhibiting promise for its use in clinical studies. Although there were no changes in intestinal microbial diversity, the increase in the TNF-α and IL-1ß cytokines in intestinal tissue may be linked to immune system signaling pathways involving the intestinal microbiota. Additional research is necessary to unravel the intricacies of these pathways and to understand their implications for clinical practice.
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Citocinas , Modelos Animales de Enfermedad , Epilepsia , Microbioma Gastrointestinal , Excitación Neurológica , Prednisolona , Ratas Wistar , Animales , Prednisolona/farmacología , Prednisolona/uso terapéutico , Masculino , Citocinas/metabolismo , Microbioma Gastrointestinal/efectos de los fármacos , Excitación Neurológica/efectos de los fármacos , Ratas , Epilepsia/tratamiento farmacológico , Epilepsia/microbiología , Antiinflamatorios/farmacologíaRESUMEN
PURPOSE: The EuroPedHp-registry aims to monitor guideline-conform management, antibiotic resistance, and eradication success of 2-week triple therapy tailored to antibiotic susceptibility (TTT) in Helicobacter pylori-infected children. METHODS: From 2017 to 2020, 30 centres from 17 European countries reported anonymized demographic, clinical, antibiotic susceptibility, treatment, and follow-up data. Multivariable logistic regression identified factors associated with treatment failure. RESULTS: Of 1605 patients, 873 had follow-up data (53.2% female, median age 13.0 years, 7.5% with ulcer), thereof 741 (85%) treatment naïve (group A) and 132 (15%) after failed therapy (group B). Resistance to metronidazole was present in 21% (A: 17.7%, B: 40.2%), clarithromycin in 28.8% (A: 25%, B: 51.4%), and both in 7.1% (A: 3.8%, B: 26.5%). The majority received 2-week tailored triple therapy combining proton pump inhibitor (PPI), amoxicillin with clarithromycin (PAC) or metronidazole (PAM). Dosing was lower than recommended for PPI (A: 49%, B: 41%) and amoxicillin (A: 6%, B: 56%). In treatment naïve patients, eradication reached 90% (n = 503, 95% CI 87-93%) and 93% in compliant children (n = 447, 95% CI 90-95%). Tailored triple therapy cured 59% patients after failed therapy (n = 69, 95% CI 48-71%). Treatment failure was associated with PAM in single clarithromycin resistance (OR = 2.47, 95% CI 1.10-5.53), with PAC in single metronidazole resistance (OR = 3.44, 95% CI 1.47-8.08), and with low compliance (OR = 5.89, 95% CI 2.49-13.95). CONCLUSIONS: Guideline-conform 2-weeks therapy with PPI, amoxicillin, clarithromycin or metronidazole tailored to antibiotic susceptibility achieves primary eradication of ≥ 90%. Higher failure rates in single-resistant strains despite tailored treatment indicate missed resistance by sampling error.
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Infecciones por Helicobacter , Helicobacter pylori , Humanos , Niño , Femenino , Adolescente , Masculino , Infecciones por Helicobacter/tratamiento farmacológico , Infecciones por Helicobacter/inducido químicamente , Metronidazol/uso terapéutico , Claritromicina/uso terapéutico , Claritromicina/farmacología , Antibacterianos/farmacología , Quimioterapia Combinada , Amoxicilina/uso terapéutico , Amoxicilina/efectos adversos , Inhibidores de la Bomba de Protones/uso terapéutico , Inhibidores de la Bomba de Protones/efectos adversos , Europa (Continente) , Resultado del TratamientoRESUMEN
Betamethasone (BM) is the drug of choice for antenatal corticosteroid therapy for women at risk of preterm delivery because it induces fetal lung maturation and enhances survival after birth. However, our group reported evidence of fetal programming and impaired reproductive development and function in rats exposed during the critical window of genital system development. Therefore, we aimed to investigate the effects of BM on the sexual development of rats in the period that corresponds to antenatal corticosteroid therapy in humans. Male and female rats were exposed subcutaneously to BM at 0.1 µg/g of pups' body weight or to a NaCl 0.9% solution (control) on postnatal days 1-3. It was observed that neonatal exposure to BM decreased body weight and weight gain in male and female rats during treatment. The estrous cycle was deregulated and LH level was decreased in female rats. In male rats, the sperm concentration in the caput-corpus of the epididymis was decreased, whereas the sperm transit time and sperm concentration in the cauda of the epididymis were increased. Our results demonstrated that neonatal exposure to BM impaired body growth of male and female rats, deregulated the estrous cycle of female rats, and altered sperm quality of male rats. Therefore, BM exposure from postnatal days 1 to 3 corroborated results previously observed after prenatal exposure to this drug. Despite the recognized importance of human antenatal corticosteroid therapy, the findings of this study should encourage further studies in order to minimize possible adverse postnatal effects.
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Betametasona , Semen , Femenino , Masculino , Ratas , Embarazo , Humanos , Animales , Betametasona/toxicidad , Reproducción , Corticoesteroides/farmacología , Peso CorporalRESUMEN
The gut microbiota is a complex community composed by several microorganisms that interact in the maintenance of homeostasis and contribute to physiological processes, including brain function. The relationship of the taxonomic composition of the gut microbiota with neurological diseases such as autism, Parkinson's, Alzheimer's, anxiety, and depression is widely recognized. The immune system is an important intermediary between the gut microbiota and the central nervous system, being one of the communication routes of the gut-brain axis. Although the complexity of the relationship between inflammation and epilepsy has not yet been elucidated, inflammatory processes are similar in many ways to the consequences of dysbiosis and contribute to disease progression. This study aimed to analyze the taxonomic composition of the gut microbiota of rats treated with prednisolone in a kindling model of epilepsy. Male Wistar rats (90 days, n = 24) divided into four experimental groups: sodium chloride solution 0.9 g%, diazepam 2 mg/kg, prednisolone 1 mg/kg, and prednisolone 5 mg/kg administered intraperitoneally (i.p.) for 14 days. The kindling model was induced by pentylenetetrazole (PTZ) 25 mg/kg i.p. on alternate days. The taxonomic profile was established by applying metagenomic DNA sequencing. There was no change in alpha diversity, and the composition of the gut microbiota between prednisolone and diazepam was similar. The significant increase in Verrucomicrobia, Saccharibacteria, and Actinobacteria may be related to the protective activity against seizures and inflammatory processes that cause some cases of epilepsy. Further studies are needed to investigate the functional influence that these species have on epilepsy and the inflammatory processes that trigger it.
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Microbioma Gastrointestinal , Pentilenotetrazol , Animales , Masculino , Prednisolona , Ratas , Ratas Wistar , Convulsiones/inducido químicamenteRESUMEN
Background: Peripheral artery disease (PAD) has high prevalence and is associated with high risk of cardiovascular events. Surgical or endovascular intervention is necessary in chronic limb-threatening ischemia. Objectives: To evaluate the distribution of open and endovascular revascularizations in different regions of Brazil, analyzing the health system costs and mortality related to these procedures. Methods: A descriptive, cross-sectional, observational, epidemiological study was carried out to evaluate open and endovascular surgeries performed on the SUS public healthcare system in Brazil, from 2010 to 2020. Data were collected from the SUS Department of Informatics (Datasus). Results: Over the period analyzed, 83,218 admissions for open and endovascular surgeries were registered, with a total cost of R$ 333,989,523.17. There were more hospital admissions for percutaneous procedures (56,132) than for conventional surgery (27,086). Most of the procedures (83%) were performed in the country's Southeast and South regions, while the North region had the lowest number of procedures. Over the period evaluated, there was a decreasing trend for open procedures and an increasing trend for endovascular procedures. The average hospital stay was shorter for endovascular procedures (5.3 days) than for open surgery (10.2 days). The analysis of mortality related to these procedures revealed a higher rate of in-hospital mortality associated with open revascularization than with endovascular (5.24% vs. 1.56%). Conclusions: Endovascular techniques constituted the primary approach for revascularization treatment in critical limb-threatening ischemia, with a lower in-hospital mortality rate and shorter hospital stay when compared to open surgeries.
RESUMEN
Glutaric acidemia type 1 (GA1) is caused by glutaryl-CoA dehydrogenase deficiency that leads to a blockage in the metabolic route of the amino acids lysine and tryptophan and subsequent accumulation of glutaric acid (GA), 3-hydroxyglutaric acids and glutarylcarnitine (C5DC). Patients predominantly manifest neurological symptoms, associated with acute striatal degeneration, as well as progressive cortical and striatum injury whose pathogenesis is not yet fully established. Current treatment includes protein/lysine restriction and l-carnitine supplementation of (L-car). The aim of this work was to evaluate behavior parameters and pro-inflammatory factors (cytokines IL-1ß, TNF-α and cathepsin-D levels), as well as the anti-inflammatory cytokine IL10 in striatum of knockout mice (Gcdh-/-) and wild type (WT) mice submitted to a normal or a high Lys diet. The potential protective effects of L-car treatment on these parameters were also evaluated. Gcdh-/- mice showed behavioral changes, including lower motor activity (decreased number of crossings) and exploratory activity (reduced number of rearings). Also, Gcdh-/- mice had significantly higher concentrations of glutarylcarnitine (C5DC) in blood and cathepsin-D (CATD), interleukin IL-1ß and tumor factor necrosis alpha (TNF-α) in striatum than WT mice. Noteworthy, L-car treatment prevented most behavioral alterations, normalized CATD levels and attenuated IL-1ß levels in striatum of Gcdh-/- mice. Finally, IL-1ß was positively correlated with CATD and C5DC levels and L-car was negatively correlated with CATD. Our results demonstrate behavioral changes and a pro-inflammatory status in striatum of the animal model of GA1 and, most importantly, L-car showed important protective effects on these alterations.
Asunto(s)
Errores Innatos del Metabolismo de los Aminoácidos/tratamiento farmacológico , Encefalopatías Metabólicas/tratamiento farmacológico , Carnitina/uso terapéutico , Glutaril-CoA Deshidrogenasa/deficiencia , Inflamación/tratamiento farmacológico , Fármacos Neuroprotectores/uso terapéutico , Errores Innatos del Metabolismo de los Aminoácidos/genética , Animales , Encefalopatías Metabólicas/genética , Carnitina/análogos & derivados , Carnitina/metabolismo , Catepsina D/metabolismo , Cuerpo Estriado/efectos de los fármacos , Cuerpo Estriado/metabolismo , Glutaril-CoA Deshidrogenasa/genética , Aseo Animal/efectos de los fármacos , Inflamación/genética , Interleucina-1beta/metabolismo , Locomoción/efectos de los fármacos , Lisina/farmacología , Ratones Noqueados , Prueba de Campo Abierto/efectos de los fármacos , Factor de Crecimiento Transformador beta/metabolismoRESUMEN
OBJECTIVES: Digestive perianastomotic ulcerations (DPAU) resembling Crohn disease lesions are long-term complications of intestinal resections, occurring in children and young adults. They are known to be uncommon, severe and difficult to treat. METHODS: In the absence of recommendations, we performed a large European survey among the members of the ESPGHAN working group on inflammatory bowel disease (IBD) in order to collect the experience of expert pediatric gastroenterologists on DPAU. RESULTS: Fifty-one patients (29 boys and 22 girls) were identified from 19 centers in 8 countries. Most patients were followed after necrotizing enterocolitis (nâ=â20) or Hirschsprung disease (nâ=â11). The anastomosis was performed at a median age (interquartile range) of 6 [1-23] months, and first symptoms occurred 39 [22-106] months after surgery. Anemia was the most prevalent symptom followed by diarrhea, abdominal pain, bloating, and failure to thrive. Hypoalbuminemia, elevated CRP, and fecal calprotectin were common. Deep ulcerations were found in 59% of patients usually proximally to the anastomosis (68%). During a median follow-up of 40 [19-67] months, treatments reported to be the most effective included exclusive enteral nutrition (31/35, 88%), redo anastomosis (18/22, 82%), and alternate antibiotic treatment (37/64, 58%). CONCLUSIONS: Unfortunately, persistence of symptoms, failure to thrive, and abnormal laboratory tests at last follow-up in most of patients show the burden of DPAU lacking optimal therapy and incomplete understanding of the pathophysiology.
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Enfermedad de Crohn , Procedimientos Quirúrgicos del Sistema Digestivo , Enfermedad de Hirschsprung , Anastomosis Quirúrgica , Niño , Enfermedad de Crohn/complicaciones , Enfermedad de Crohn/diagnóstico , Enfermedad de Crohn/terapia , Femenino , Humanos , Lactante , Recién Nacido , Masculino , Úlcera/diagnóstico , Úlcera/etiología , Adulto JovenRESUMEN
A ten-year-old boy presented with a two-year history of iron deficiency anemia (IDA) and occasional vomiting. His medical history included cerebral palsy and chronic pulmonary disease under mechanical cough assistance and nocturnal non-invasive ventilation.
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Anemia Ferropénica , Hernia Hiatal , Úlcera Gástrica , Niño , Hernia Hiatal/complicaciones , Hernia Hiatal/diagnóstico por imagen , Humanos , Masculino , ÚlceraRESUMEN
Chalcones are chemically defined as α,ß-unsaturated ketones with a 1,3-diphenyl-2-propen-1-one nucleus. These compounds occur naturally in plants and are considered precursors of flavonoids. Given that evaluating genetic toxicology tests is essential in investigating the safe use and chemopreventive potential of different natural and synthetic compounds, this study aimed to assess the genotoxic, cytotoxic, antigenotoxic, and anticytotoxic activity of the chalcone 1E,4E-1-(4-chlorophenyl)-5-(2,6,6-trimethylcyclohexen-1-yl)penta-1,4-dien-3-one (CAB7ß). The CAB7ß was synthesized via Claisen-Schmidt reaction. The Ames test was applied using the co-treatment model as well as a micronucleus assay of mouse bone marrow with co-, pre- and post-treatment models. Our results indicate no genotoxic effect for CAB7ß in any of the tests applied. At all the concentrations used, CAB7ß showed a significant DNA protective effect against the mutagenic action of 4-nitroquinoline-1-oxide and sodium azide according to the Ames test, and against doxorubicin in the co-, pre- and post-treatment models of the micronucleus assay. CAB7ß alone displayed cytotoxic activity in the micronucleus test. At concentrations of 12,5 and 50 µg/plate, CAB7ß showed a moderate cytotoxic profile only in Salmonella typhimurium strain TA98. However, an anticytotoxic effect was observed against S. typhimurium strain TA100 for all the concentrations tested and during co-, pre- and post-treatment in the micronucleus assay. It was concluded that CAB7ß exhibited a slightly cytotoxic effect in S. typhimurium strain TA98 and significant antigenotoxic and anticytotoxic effects in cells of mouse, making it a promising candidate in chemoprevention and possibly in the development of new cancer treatments.
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Antimutagênicos/farmacología , Chalconas/farmacología , Daño del ADN/efectos de los fármacos , 4-Nitroquinolina-1-Óxido/toxicidad , Animales , Femenino , Masculino , Ratones , Pruebas de Micronúcleos , Salmonella typhimurium/efectos de los fármacos , Azida Sódica/toxicidadRESUMEN
Urban waste is a complex mixture of different substances, including microplastics and pharmaceuticals and personal care products. Microplastics have a high affinity for hydrophobic substances. One of these substances is triclosan, a bactericide used in a variety of hygiene products. Therefore, microplastics (MPs) may serve as a vector between triclosan and aquatic organisms. The current study sought to evaluate the effects of the interaction between microplastics and triclosan based on a mechanistic approach in which the oyster Crassostrea brasiliana was used as a model. The organisms were exposed to three conditions: the control, microplastic (MP), and microplastic contaminated with triclosan (MPT). The organisms were exposed for 3 or 7 days. After the exposure time, hemolymph was sampled for performing the neutral red retention time assay and, subsequently, the gills, digestive glands, and adductor muscles were dissected for measuring biomarkers responses (EROD, DBF, GST, GPx, GSH, lipid peroxidation, DNA strand breaks, and AChE). Our results demonstrate combined effects of MPs associated with triclosan on oyster physiology and biochemistry, as well as on lysosomal membrane stability. These results contribute to understanding the effects of contaminants of emerging concern and microplastics on aquatic organisms.
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Crassostrea/efectos de los fármacos , Biomarcadores Ambientales/efectos de los fármacos , Microplásticos/toxicidad , Triclosán/toxicidad , Contaminantes Químicos del Agua/toxicidad , Animales , Brasil , Crassostrea/genética , Crassostrea/metabolismo , Daño del ADN , Branquias/efectos de los fármacos , Branquias/metabolismo , Peroxidación de Lípido/efectos de los fármacos , Microplásticos/metabolismo , Modelos Teóricos , Triclosán/metabolismo , Contaminantes Químicos del Agua/metabolismoRESUMEN
OBJECTIVES: Autoimmune gastritis (AIG) is a chronic inflammatory condition of the gastric mucosa, mainly described in adults presenting with pernicious anemia. It results from antibody-mediated destruction of parietal cells, but the precise initiating event is unknown. The pathogenicity of Helicobacter pylori (H pylori) has been suggested but not established. This study aimed to better characterize AIG in pediatric patients and to address the possible role of H pylori infection. METHODS: Descriptive single-center study, retrospectively describing 20 patients with a diagnosis of AIG based on positivity for anti-parietal cell autoantibodies, in addition to analytical and/or histological findings of oxyntic mucosa atrophy. RESULTS: In the majority (18/20), AIG diagnosis was suggested during investigation of refractory iron-deficient anemia. One patient had dyspepsia and none of the others had gastrointestinal symptoms. Fifty-five percent (11/20) were H pylori positive, but there were no significant differences regarding mean hemoglobin values at presentation (10.6â±â2.5 vs 9.5â±â1.0âg/dL, Pâ>â0.05), analytical indicators of gastric atrophy (gastrin, 564.4â±â184 vs 721.2â±â220.6âpg/mL, Pâ>â0.05), or in the presence or the grade of oxyntic mucosa atrophy. CONCLUSIONS: Our findings highlight that AIG may have an age-dependent presentation; thus, we can consider a pediatric phenotype that in contrast to adults, is manifested by refractory iron-deficient anemia and associated with parietal cell autoantibody positivity, but not intrinsic factor autoantibodies. A correlation between H pylori and AIG was not evident in the current study and it is still unclear whether H pylori is a trigger for AIG.
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Enfermedades Autoinmunes/microbiología , Gastritis/microbiología , Infecciones por Helicobacter/inmunología , Helicobacter pylori/inmunología , Adolescente , Autoanticuerpos/sangre , Enfermedades Autoinmunes/inmunología , Niño , Preescolar , Femenino , Gastritis/inmunología , Infecciones por Helicobacter/epidemiología , Humanos , Masculino , Células Parietales Gástricas/inmunología , Células Parietales Gástricas/microbiología , Portugal/epidemiología , Prevalencia , Estudios RetrospectivosRESUMEN
KEY POINTS: Cigarette smoke components directly alter muscle fatigue resistance and intracellular muscle fibre Ca2+ handling independent of a change in lung structure. Changes in muscle vascular structure are associated with a depletion of satellite cells. Sarcoplasmic reticulum Ca2+ uptake is substantially impaired in myofibres during fatiguing contractions in mice treated with cigarette smoke extract. ABSTRACT: Cigarette smokers exhibit exercise intolerance before a decline in respiratory function. In the present study, the direct effects of cigarette smoke on limb muscle function were tested by comparing cigarette smoke delivered to mice by weekly injections of cigarette smoke extract (CSE), or nose-only exposure (CS) 5 days each week, for 8 weeks. Cigarette smoke delivered by either route did not alter pulmonary airspace size. Muscle fatigue measured in situ was 50% lower in the CSE and CS groups than in control. This was accompanied by 34% and 22% decreases in soleus capillary-to-fibre ratio of the CSE and CS groups, respectively, and a trend for fewer skeletal muscle actin-positive arterioles (P = 0.07). In addition, fewer quiescent satellite cells (Nes+Pax7+) were associated with soleus fibres in mice with skeletal myofibre VEGF gene deletion (decreased 47%) and CS exposed (decreased 73%) than with control fibres. Contractile properties of isolated extensor digitorum longus and soleus muscles were impaired. In flexor digitorum brevis myofibres isolated from CSE mice, fatigue resistance was diminished by 43% compared to control and CS myofibres, and this was accompanied by a pronounced slowing in relaxation, an increase in intracellular Ca2+ accumulation, and a slowing in sarcoplasmic reticulum Ca2+ uptake. These data suggest that cigarette smoke components may impair hindlimb muscle vascular structure, fatigue resistance and myofibre calcium handling, and these changes ultimately affect contractile efficiency of locomotor muscles independent of a change in lung function.
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Contracción Muscular , Fibras Musculares Esqueléticas/patología , Músculo Esquelético/patología , Enfermedades Musculares/patología , Retículo Sarcoplasmático/patología , Fumar/efectos adversos , Animales , Capilares , Masculino , Ratones , Ratones Endogámicos C57BL , Músculo Esquelético/irrigación sanguínea , Enfermedades Musculares/etiología , Retículo Sarcoplasmático/metabolismoRESUMEN
BACKGROUND: The increasing prevalence of Helicobacter pylori (H. pylori) antimicrobial resistance, primarily for clarithromycin decreases the success of treatment. The aim of this study is to determine the local pattern of first-line antimicrobials resistance and the eradication rate. MATERIAL AND METHODS: Prospective cohort study of H. pylori infected patients (positive histological or cultural exams) treated at Centro Materno-Infantil do Norte from January of 2013 to October of 2017. Susceptibility to 4 antibiotics: amoxicilin, metronidazole, clarithromycin, and levofloxacin were analyzed by E-test (phenotypic resistance). The E-test was chosen because it is simple and cost-effective for routine susceptibility testing. Point mutations that confer clarithromycin resistance were surveyed (genotypic resistance). Eradication of H. pylori infection was defined by a negative urea breath test or fecal antigen 6-8 weeks after the end of treatment. RESULTS: Of a total of 74 H. pylori infected patients, 16 were excluded because they had previous H. pylori treatment or severe systemic disease. Median age of infection cases was 15 years (3-17 years). Eradication regimen used in all patients combined the use of 3 antibiotics (amoxicillin and metronidazole or clarithromycin) and proton pump inibhitor for 14 days and was tailored according antimicrobial susceptibility. 79.5% of the patients completed the treatment. The resistance rate for metronidazole and clarithromycin was 3.3% and 23.3%, respectively. There was no resistance for amoxicilin and levofloxacin. The rate of genotypic resistance to clarithromycin was 37.2%. The eradication rate was 97.8%. CONCLUSIONS: The authors found a high resistance rate of H. pylori for clarithromycin in this northern portuguese pediatric center. This factor should determine a change in local current treatment, contraindicating the use of clarithromycin as a first-line treatment for H. pylori infection in children. The high eradication rate maybe explained for the eradication treatment tailored according antimicrobial susceptibility.
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Antibacterianos/uso terapéutico , Infecciones por Helicobacter/tratamiento farmacológico , Adolescente , Amoxicilina/uso terapéutico , Niño , Preescolar , Claritromicina/uso terapéutico , Farmacorresistencia Bacteriana , Femenino , Helicobacter pylori , Humanos , Levofloxacino/uso terapéutico , Masculino , Metronidazol/uso terapéutico , Pruebas de Sensibilidad Microbiana , Estudios ProspectivosRESUMEN
SummaryThe aim of this study was to optimize protocols for electroporation (EP) and polyfection (PLF) using polyethyleneimine (PEI) for pig sperm transfection and to determine which method was the most efficient. For EP standardization, different voltages, amounts and times of electric pulses were tested using propidium iodide (PI) as reporter. For PLF standardization, different concentrations of fluorescein isothiocyanate (FITC)-labelled PEI (PEI/FITC) were incubated with sperm for different periods of time. Flow cytometry was performed to evaluate the best protocol in terms of cell viability, including cytoplasmic membrane, acrosome, chromatin integrities and mitochondrial potential using the FITC probe, PI, acridine orange (AO) and JC1. Transfections with the plasmid pmhyGENIE-5 were carried out under optimum conditions for each procedure (EP: 500 volts, 500 µs and two pulses; PLF: PEI 0.5 mg/ml and incubation time 10 min). Transfection efficacy was assessed by fluorescence in situ hybridization (FISH). A lower transfection rate was observed for sperm in the control group (17.8%) compared with EP (36.7%), with PLF (76.8%) being the most efficient. These results suggest that the EP and PEI could be an efficient and low cost transfection method for swine sperm. Notably, treated cells showed higher plasmatic the membrane damage (PMD) and/or acrosome damage (AD) indexes, therefore the combination of this procedure with biotechniques that facilitate fecundation (i.e. in vitro fertilization or intracytoplasmic sperm injection) or even inclusion of antioxidant or anti-apoptotic drugs to improve spermatozoa viability would be important.
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Electroporación/veterinaria , Polietileneimina/química , Preservación de Semen/veterinaria , Espermatozoides/citología , Transfección/veterinaria , Animales , Supervivencia Celular , Fertilización In Vitro , Masculino , Motilidad Espermática , Espermatozoides/fisiología , PorcinosRESUMEN
Dysphagia lusoria (lusus naturae, latin for "freak of nature") describes dysphagia because of vascular compression of the esophagus. Symptoms, when present, occur at the two extremes of life. Owing to the more flexible and compressible nature of the trachea, children usually present with respiratory symptoms, in contrast to adults, who more often present with dysphagia. Here, we report the case of a six-year-old child presenting with a history of progressive dysphagia without respiratory symptoms. A barium esophagogram showed a diagonal impression in the proximal esophagus, while at esophagogastroduodenoscopy there was an extrinsic pulsatile bulging area suggesting an extrinsic compression by an aberrant vessel. Angio-CT (computed tomography) scan confirmed the presence of an aberrant right subclavian artery.
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Anomalías Cardiovasculares , Trastornos de Deglución , Adulto , Aneurisma , Niño , Humanos , Arteria SubclaviaRESUMEN
Bupropion is a dopamine (DA) and norepinephrine (NE) reuptake inhibitor used as smoking cessation and antidepressant drug with a lower incidence of male sexual dysfunction. We showed previously that sibutramine, a norepinephrine/serotonine reuptake inhibitor, reduced male rat fertility. As there are no studies evaluating the impact of bupropion treatment on spermatic parameters and male fertility, we evaluated the effects of bupropion treatment (15 and 30 mg kg(-1), 30 days) on sexual behavior, spermatic parameters and fertility of male Wistar rats and on the epididymal duct in vitro contractility. Bupropion 15 mg kg(-1) increased the serum luteinizing hormone level and the epididymal duct contractility, but the sperm quality was not affected. At 30 mg kg(-1) bupropion impaired sperm quality increasing the incidence of non-progressive sperm. The male sexual behavior and fertility were not modified at both bupropion doses. These results, in rats, suggest the importance of studies evaluating the effects of bupropion on the human male sperm quality.
Asunto(s)
Bupropión/toxicidad , Inhibidores de Captación de Dopamina/toxicidad , Epidídimo/efectos de los fármacos , Contracción Muscular/efectos de los fármacos , Transporte Espermático/efectos de los fármacos , Espermatozoides/efectos de los fármacos , Animales , Epidídimo/fisiopatología , Femenino , Fertilidad/efectos de los fármacos , Hormona Luteinizante/sangre , Masculino , Tamaño de los Órganos/efectos de los fármacos , Ratas Wistar , Conducta Sexual Animal/efectos de los fármacos , Recuento de Espermatozoides , Motilidad Espermática/efectos de los fármacos , Espermatozoides/patologíaRESUMEN
INTRODUCTION: Refractory iron-deficiency anemia with no obvious etiology in pediatric age can be a puzzling problem. Screening of iron malabsorption conditions, including autoimmune atrophic gastritis (AAG), is emerging as a priority in the investigational procedure. MATERIALS AND METHODS: Retrospective analysis of clinical process of children/adolescents with the diagnosis of AAG. RESULTS: Eight patients (aged between 4.7 and 18 years old) were identified. The diagnosis was triggered on the basis of high serum gastrin levels and strong positivity of antiparietal cell antibodies. Upper endoscopy and biopsy revealed atrophic gastritis in all patients, with 2 of them with intestinal metaplasia. Four patients presented with Helicobacter pylori infection object of eradication therapy. After a medium follow-up of 36.6 months, antiparietal cell antibodies and hypergastrinemia did not show evidence of regression. Of the 3 patients who underwent endoscopic reevaluation, a similar anatomo-pathologic pattern was observed in 2 and intestinal metaplasia in 1 patient. Normalization of hematological parameters was achieved, using alternative iron formulas. CONCLUSIONS: AAG must be recognized as a pathology affecting pediatric patients. Gastric autoimmune lesion is a chronic process with potential evolution to malignancy. Management guidelines in childhood are not available. Their elaboration is important considering an important risk factor in these age group: a long life expectancy.