Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 70
Filtrar
Mais filtros

Intervalo de ano de publicação
1.
Proc Natl Acad Sci U S A ; 121(10): e2321910121, 2024 Mar 05.
Artigo em Inglês | MEDLINE | ID: mdl-38422018

RESUMO

Bacteroidota are abundant members of the human gut microbiota that shape the enteric landscape by modulating host immunity and degrading dietary- and host-derived glycans. These processes are mediated in part by Outer Membrane Vesicles (OMVs). Here, we developed a high-throughput screen to identify genes required for OMV biogenesis and its regulation in Bacteroides thetaiotaomicron (Bt). We identified a family of Dual membrane-spanning anti-sigma factors (Dma) that control OMV biogenesis. We conducted molecular and multiomic analyses to demonstrate that deletion of Dma1, the founding member of the Dma family, modulates OMV production by controlling the activity of the ECF21 family sigma factor, Das1, and its downstream regulon. Dma1 has a previously uncharacterized domain organization that enables Dma1 to span both the inner and outer membrane of Bt. Phylogenetic analyses reveal that this common feature of the Dma family is restricted to the phylum Bacteroidota. This study provides mechanistic insights into the regulation of OMV biogenesis in human gut bacteria.


Assuntos
Bacteroides thetaiotaomicron , Humanos , Bacteroides thetaiotaomicron/genética , Fator sigma , Filogenia
2.
Hum Genet ; 143(5): 667-681, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38578438

RESUMO

CLCN4-related disorder is a rare X-linked neurodevelopmental condition with a pathogenic mechanism yet to be elucidated. CLCN4 encodes the vesicular 2Cl-/H+ exchanger ClC-4, and CLCN4 pathogenic variants frequently result in altered ClC-4 transport activity. The precise cellular and molecular function of ClC-4 remains unknown; however, together with ClC-3, ClC-4 is thought to have a role in the ion homeostasis of endosomes and intracellular trafficking. We reviewed our research database for patients with CLCN4 variants and epilepsy, and performed thorough phenotyping. We examined the functional properties of the variants in mammalian cells using patch-clamp electrophysiology, protein biochemistry, and confocal fluorescence microscopy. Three male patients with developmental and epileptic encephalopathy were identified, with differing phenotypes. Patients #1 and #2 had normal growth parameters and normal-appearing brains on MRI, while patient #3 had microcephaly, microsomia, complete agenesis of the corpus callosum and cerebellar and brainstem hypoplasia. The p.(Gly342Arg) variant of patient #1 significantly impaired ClC-4's heterodimerization capability with ClC-3 and suppressed anion currents. The p.(Ile549Leu) variant of patient #2 and p.(Asp89Asn) variant of patient #3 both shift the voltage dependency of transport activation by 20 mV to more hyperpolarizing potentials, relative to the wild-type, with p.(Asp89Asn) favouring higher transport activity. We concluded that p.(Gly342Arg) carried by patient #1 and the p.(Ile549Leu) expressed by patient #2 impair ClC-4 transport function, while the p.(Asp89Asn) variant results in a gain-of-transport function; all three variants result in epilepsy and global developmental impairment, but with differences in epilepsy presentation, growth parameters, and presence or absence of brain malformations.


Assuntos
Canais de Cloreto , Epilepsia , Estudos de Associação Genética , Humanos , Canais de Cloreto/genética , Canais de Cloreto/metabolismo , Masculino , Epilepsia/genética , Pré-Escolar , Criança , Fenótipo , Lactente , Mutação
3.
Brain Behav Immun ; 120: 121-140, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38777288

RESUMO

BACKGROUND: The purinergic ATP-gated P2X7 receptor (P2X7R) is increasingly recognized to contribute to pathological neuroinflammation and brain hyperexcitability. P2X7R expression has been shown to be increased in the brain, including both microglia and neurons, in experimental models of epilepsy and patients. To date, the cell type-specific downstream effects of P2X7Rs during seizures remain, however, incompletely understood. METHODS: Effects of P2X7R signaling on seizures and epilepsy were analyzed in induced seizure models using male mice including the kainic acid model of status epilepticus and pentylenetetrazole model and in male and female mice in a genetic model of Dravet syndrome. RNA sequencing was used to analyze P2X7R downstream signaling during seizures. To investigate the cell type-specific role of the P2X7R during seizures and epilepsy, we generated mice lacking exon 2 of the P2rx7 gene in either microglia (P2rx7:Cx3cr1-Cre) or neurons (P2rx7:Thy-1-Cre). To investigate the protective potential of overexpressing P2X7R in GABAergic interneurons, P2X7Rs were overexpressed using adeno-associated virus transduction under the mDlx promoter. RESULTS: RNA sequencing of hippocampal tissue from wild-type and P2X7R knock-out mice identified both glial and neuronal genes, in particular genes involved in GABAergic signaling, under the control of the P2X7R following seizures. Mice with deleted P2rx7 in microglia displayed less severe acute seizures and developed a milder form of epilepsy, and microglia displayed an anti-inflammatory molecular profile. In contrast, mice lacking P2rx7 in neurons showed a more severe seizure phenotype when compared to epileptic wild-type mice. Analysis of single-cell expression data revealed that human P2RX7 expression is elevated in the hippocampus of patients with temporal lobe epilepsy in excitatory and inhibitory neurons. Functional studies determined that GABAergic interneurons display increased responses to P2X7R activation in experimental epilepsy. Finally, we show that viral transduction of P2X7R in GABAergic interneurons protects against evoked and spontaneous seizures in experimental temporal lobe epilepsy and in mice lacking Scn1a, a model of Dravet syndrome. CONCLUSIONS: Our results suggest a dual and opposing action of P2X7R in epilepsy and suggest P2X7R overexpression in GABAergic interneurons as a novel therapeutic strategy for acquired and, possibly, genetic forms of epilepsy.


Assuntos
Modelos Animais de Doenças , Microglia , Neurônios , Receptores Purinérgicos P2X7 , Convulsões , Animais , Microglia/metabolismo , Receptores Purinérgicos P2X7/metabolismo , Receptores Purinérgicos P2X7/genética , Masculino , Camundongos , Convulsões/metabolismo , Convulsões/genética , Neurônios/metabolismo , Feminino , Camundongos Endogâmicos C57BL , Ácido Caínico , Epilepsias Mioclônicas/metabolismo , Epilepsias Mioclônicas/genética , Hipocampo/metabolismo , Estado Epiléptico/metabolismo , Estado Epiléptico/genética , Camundongos Knockout , Pentilenotetrazol , Transdução de Sinais , Neurônios GABAérgicos/metabolismo , Epilepsia/metabolismo , Epilepsia/genética , Encéfalo/metabolismo
4.
Soft Matter ; 2024 Aug 06.
Artigo em Inglês | MEDLINE | ID: mdl-39105348

RESUMO

Mechanically bonded membranes of interlocked ring polymers are a significant generalization of conventional elastic sheets, where connectivity is provided by covalent bonding, and represent a promising class of topological meta-materials. In this context, two open questions regard the large-scale reverberations of the heterogeneous composition of the rings and the inequivalent modes of interlocking neighboring rings. We address these questions with Langevin dynamics simulations of chainmails with honeycomb-lattice connectivity, where the rings are block copolymers with two segments of different rigidity. We considered various combinations of the relative lengths of the two segments and the patterns of the over- and under-passes linking neighboring rings. We find that varying ring composition and linking patterns have independent and complementary effects. While the former sets the overall size of the chainmail, the latter defines the shape, enabling the selection of starkly different conformation types. Notably, one of the considered linking patterns favors saddle-shaped membranes, providing a first example of spontaneous negative Gaussian curvature in mechanically bonded sheets. The results help establish the extent to which mechanically bonded membranes can differ from conventional elastic ones, particularly for the achievable shape and size tunability.

5.
Anaerobe ; 85: 102816, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38145709

RESUMO

The aim of this study was to describe the in vitro activity of delafloxacin against 230 anaerobic isolates and compare it with the activity of other antimicrobials used against infections caused by anaerobic microorganisms. Minimal inhibitory concentrations (MICs) were lower for delafloxacin than for all other antibiotics tested with the exception of piperacillin-tazobactam and meropenem against Gram-positive anaerobic cocci. Only two (0.8 %) isolates of Bacteroides spp. showed a MIC ≥4 µg/mL. With some exceptions, the present results show lower MICs for delafloxacin in comparison to the other antibiotics used against anaerobes.


Assuntos
Anti-Infecciosos , Infecções Bacterianas , Fluoroquinolonas , Cocos Gram-Positivos , Humanos , Antibacterianos/farmacologia , Infecções Bacterianas/microbiologia , Bactérias Anaeróbias , Testes de Sensibilidade Microbiana
6.
Artigo em Inglês, Espanhol | MEDLINE | ID: mdl-38311006

RESUMO

BACKGROUND: Real-world studies about the effectiveness and safety of vedolizumab (VDZ) in the treatment of inflammatory bowel disease (IBD) in Latin America are scarce. Our study describes the effectiveness and safety of VDZ in Colombian patients with IBD. METHODS: EXVEDOCOL (EXperience of VEDOlizumab in COLombia) was a retrospective, multicenter, observational study. Adults with IBD receiving a first dose of VDZ between July 2016 and October 2018 were included. The co-primary outcomes clinical response, and remission, were determined at week 14 and last visit during the maintenance phase (LVMP). The secondary outcomes, deep remission and loss of response were recorded at LVMP. RESULTS: Thirty-one patients (25 ulcerative colitis (UC), 6 Crohn's disease (CD)) were included. At week 14, clinical response was achieved by 87.1% (27/31) of the patients treated with VDZ, while loss of response was reported in 6.7% (2/30). The remission rate at week 14 was 65.5% (19/29) and 75.9% (22/29) at LVMP. Prior anti-TNF exposure was reported in 61.3% (19 patients) of whom 84.2% (16/19) achieved clinical response at week 14 and 89.5% (17/19) at LVMP. For anti-TNF naïve patients, clinical response was recorded in 91.7% (11/12) at week 14 and 100% (12/12) at LVMP. CONCLUSIONS: High clinical remission rates and safety profile highlight VDZ as a valuable treatment option for IBD patients. Anti-TNF naïve patients may derive greater benefit from therapy. Studies with larger cohorts could confirm these findings.

7.
Parasitol Res ; 123(1): 53, 2023 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-38100003

RESUMO

The reproductive mode of viviparity has independently evolved in various animal taxa. It refers to the condition in which the embryos or young develop inside the female's body during gestation, providing advantages such as protection, nutrition, and improved survival chances. However, parasites and diseases can be an evolutionary force that limit the host's resources, leading to physiological, morphological, and behavioral changes that impose additional costs on both the pregnant female and her offspring. This review integrates the primary literature published between 1980 and 2021 on the parasitism of viviparous hosts. We describe aspects such as reproductive investment in females, offspring sex ratios, lactation investment in mammals, alterations in birth intervals, current reproductive investment, variations between environments, immune system activity in response to immunological challenges, and other factors that can influence the interaction between viviparous females and parasites. Maintaining pregnancy incurs costs in managing the mother's resources and regulating the immune system's responses to the offspring, while simultaneously maintaining an adequate defense against parasites and pathogens. Parasites can significantly influence this reproductive mode: parasitized females adjust their investment in survival and reproduction based on their life history, environmental factors, and the diversity of encountered parasites.


Assuntos
Evolução Biológica , Vertebrados , Feminino , Animais , Gravidez , Lactação , Estado Nutricional , Reprodução , Mamíferos
8.
Exp Clin Transplant ; 22(Suppl 1): 345-347, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38385424

RESUMO

Patients with chronic kidney disease who are candidates for transplant may experience changes in capillary permeability, coagulation, and the endocrine system; alterations in the pulmonary vasculature; and cardiac structural and functional changes. Patients with renal replacement by hemodialysis have a mortality rate 30 times higher than those who do not have uremia. According to the onset, duration, and severity of chronic kidney disease, cardiovascular disease will be reflected in baseline function and response to stress. For this reason, it is important to establish the functional condition so that preoperative management can be started and factors inherent to the patient and the surgical procedure can be modified. Here, we report a 29-year-old male patient with chronic kidney disease secondary to renal hypoplasia, with no family history. The patient had renal replacement therapy with peritoneal dialysis and had progressive deterioration of general status, decreased functional capacity, decreased tolerance to physical activity, presence of fatigue and pulmonary congestion, and retention of liquids, with a diagnosis of moderate to severe mitral regurgitation.


Assuntos
Anestésicos , Falência Renal Crônica , Transplante de Rim , Insuficiência da Valva Mitral , Insuficiência Renal Crônica , Masculino , Humanos , Adulto , Transplante de Rim/efeitos adversos , Insuficiência da Valva Mitral/diagnóstico por imagem , Insuficiência da Valva Mitral/etiologia , Insuficiência da Valva Mitral/cirurgia , Diálise Renal , Insuficiência Renal Crônica/complicações , Falência Renal Crônica/complicações
9.
J Chem Theory Comput ; 20(5): 2261-2272, 2024 Mar 12.
Artigo em Inglês | MEDLINE | ID: mdl-38411091

RESUMO

The response of double-stranded DNA to external mechanical stress plays a central role in its interactions with the protein machinery in the cell. Modern atomistic force fields have been shown to provide highly accurate predictions for the fine structural features of the duplex. In contrast, and despite their pivotal function, less attention has been devoted to the accuracy of the prediction of the elastic parameters. Several reports have addressed the flexibility of double-stranded DNA via all-atom molecular dynamics, yet the collected information is insufficient to have a clear understanding of the relative performance of the various force fields. In this work, we fill this gap by performing a systematic study in which several systems, characterized by different sequence contexts, are simulated with the most popular force fields within the AMBER family, bcs1 and OL15, as well as with CHARMM36. Analysis of our results, together with their comparison with previous work focused on bsc0, allows us to unveil the differences in the predicted rigidity between the newest force fields and suggests a roadmap to test their performance against experiments. In the case of the stretch modulus, we reconcile these differences, showing that a single mapping between sequence-dependent conformation and elasticity via the crookedness parameter captures simultaneously the results of all force fields, supporting the key role of crookedness in the mechanical response of double-stranded DNA.


Assuntos
DNA , Simulação de Dinâmica Molecular , DNA/química , Conformação Molecular , Elasticidade , Estresse Mecânico , Conformação de Ácido Nucleico
10.
Front Sports Act Living ; 6: 1372664, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38596641

RESUMO

Objective: To determine if the active methodology for improving sports initiation (M.A.M.I.deporte®) shared between children and parents successfully promotes children in sports activities, maintains their activity and improves long-term adherence. Participants: The study involved 118 participants aged between 2 and 11 years (6.3 ± 2.3). In the first season, 34 participated (16 girls; 18 boys); in the second season, 46 participated (22 girls; 24 boys) and in the third season, 38 participated (19 girls; 19 boys). Methodology: It was carried out from October to June over three academic years for two hours a week. Every 4 sessions a different sporting activity was carried out, planned so that parents and children could practise them, simultaneously. Analysis: At the beginning and end of each period, a survey was carried out on the sports activities in which the participants had started. If participants remained in the activity, the survey was face-to-face and if participants no longer attended the activity, they were contacted by telephone. Descriptive values were obtained for the variables in absolute and percentage form and a repeated measures anova was performed. Results: Vigorous physical activity performed was 3.82 ± 1.16 h/week in the first year, 3.38 ± 1.59 in the second year and 2.99 ± 1.46 in the third year with no significant differences between any of the years. 32.20% joined other sporting activities and only 6.78% gave up vigorous physical activity. Conclusion: Joint activity of parents and children contributed to maintaining vigorous physical activity at the recommended levels in the child population with only 6.78% (n = 8) of the participants dropping out.

11.
Antibiotics (Basel) ; 13(4)2024 Mar 22.
Artigo em Inglês | MEDLINE | ID: mdl-38666965

RESUMO

After pulp infection and necrosis, the passage of microbial antigens into the periapical space causes apical periodontitis (AP). Most of the clinical forms of AP can be managed without prescribing antibiotics, only with root canal treatment and abscess drainage or, where appropriate, tooth extraction. However, the scientific literature provides evidence of inappropriate antibiotic prescriptions by dentists in the management of apical disease. OBJECTIVES: The aim of this systematic review and meta-analysis was to analyze the global pattern of antibiotic prescription in the treatment of apical disease. METHODS: PRISMA Guidelines were followed to carry out this systematic review. The research question was as follows: What is the pattern of antibiotic prescription by dentists in the treatment of the different clinical forms of apical periodontitis? A systematic search was conducted on MEDLINE/PubMed, Wiley Online Database, Web of Science and Scopus. All studies reporting data about the pattern of antibiotic prescription by dentists in the treatment of apical disease were included. The meta-analyses were calculated using the Open Meta Analyst version 10.10 software. Random-effects meta-analyses were performed. The risk of bias was assessed using the Newcastle-Ottawa Scale. The certainty of evidence was assessed using GRADE. RESULTS: The search strategy identified 96 articles and thirty-nine cross-sectional studies fulfilled the inclusion criteria. The overall percentage of antibiotic prescriptions by dentists in cases of symptomatic AP was 25.8%, and 31.5% in cases of asymptomatic AP with sinus tract present. The percentage of dentists prescribing antibiotics in cases of acute apical abscess with no/mild symptoms was 47.7%, whereas, in cases of acute apical abscess with moderate/severe symptoms, 88.8% of dentists would prescribe antibiotics. Endodontists prescribe antibiotics at a lower rate than general practitioners. The total risk of bias was considered moderate, and the final rating for the certainty of the evidence was low. CONCLUSIONS: Dentists worldwide are over-prescribing antibiotics in the management of apical disease. It is necessary to improve antibiotic prescribing habits in the treatment of endodontic infections, as well as educational initiatives to encourage the rational and appropriate prescription of antibiotics in periapical diseases.

12.
bioRxiv ; 2024 Apr 08.
Artigo em Inglês | MEDLINE | ID: mdl-38645180

RESUMO

Acinetobacter baumannii is associated with multidrug resistant (MDR) infections in healthcare settings, with fluoroquinolones such as ciprofloxacin being currently ineffective. Clinical isolates largely harbor mutations in the GyrA and TopoIV fluoroquinolone targets, as well as mutations that increase expression of drug resistance-nodulation-division (RND) efflux pumps. Factors critical for maintaining fitness levels of pump overproducers are uncharacterized despite their prevalence in clinical isolates. We here identify proteins that contribute to the fitness of FQR strains overexpressing three known RND systems using high-density insertion mutagenesis. Overproduction of the AdeFGH efflux pump caused hypersensitization to defects in outer membrane homeostatic regulation, including lesions that reduced LOS biosynthesis and blocked production of the major A. baumannii porin. In contrast, AdeAB pump overproduction, which does not affect the outer membrane pump component, was relatively tolerant to loss of these functions, consistent with outer membrane protein overproduction being the primary disruptive component. Surprisingly, overproduction of proton-transporting efflux pumps had little impact on cytosolic pH, consistent with a compensatory response to pump activity. The most striking transcriptional changes were associated with AdeFGH pump overproduction, resulting in activation of the phenylacetate (PAA) degradation regulon. Disruption of the PAA pathway resulted in cytosolic acidification and defective expression of genes involved in protection from peroxide stress. These results indicate that the RND outer membrane protein overproduction is compensated by cytoplasmic buffering and maintenance of outer membrane integrity in A. baumannii to facilitate fitness of FQR isolates.

13.
Open Forum Infect Dis ; 11(5): ofae192, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38680614

RESUMO

Background: Human adenoviruses (HAdVs) can cause outbreaks of flu-like illness in university settings. Most infections in healthy young adults are mild; severe illnesses rarely occur. In Fall 2022, an adenovirus outbreak was identified in university students. Methods: HAdV cases were defined as university students 17-26 years old who presented to the University Health Service or nearby emergency department with flu-like symptoms (eg, fever, cough, headache, myalgia, nausea) and had confirmed adenovirus infections by polymerase chain reaction (PCR). Demographic and clinical characteristics were abstracted from electronic medical records; clinical severity was categorized as mild, moderate, severe, or critical. We performed contact investigations among critical cases. A subset of specimens was sequenced to confirm the HAdV type. Results: From 28 September 2022 to 30 January 2023, 90 PCR-confirmed cases were identified (51% female; mean age, 19.6 years). Most cases (88.9%) had mild illness. Seven cases required hospitalization, including 2 critical cases that required intensive care. Contact investigation identified 44 close contacts; 6 (14%) were confirmed HAdV cases and 8 (18%) reported symptoms but never sought care. All typed HAdV-positive specimens (n = 36) were type 4. Conclusions: While most students with confirmed HAdV had mild illness, 7 otherwise healthy students had severe or critical illness. Between the relatively high number of hospitalizations and proportion of close contacts with symptoms who did not seek care, the true number of HAdV cases was likely higher. Our findings illustrate the need to consider a wide range of pathogens, even when other viruses are known to be circulating.

14.
J Clin Med ; 13(8)2024 Apr 12.
Artigo em Inglês | MEDLINE | ID: mdl-38673531

RESUMO

(1) Background: Trainers and athletes have always sought to reduce the failure of muscle function during long endurance events. However, nowadays, it is a topic that is generating much debate in the scientific field. Currently, deep-sea water (DSW) intake seems to be a suitable hydration alternative for this type of endurance event. Therefore, the aim of this study was to determine whether DSW consumption during a triathlon event could preserve muscle function after exercise. (2) Methods: Nineteen trained male triathletes (age = 39.0 ± 4.25 years; BMI = 23.67 ± 1.81 kg/m2) randomly performed three triathlons, one of them consuming DSW (Totum SPORT 30 AB, Laboratories Quinton International, S.L., Spain), the other consuming isotonic placebo and the last with tap water-hydration. A vertical jump test with countermovement and an isometric muscle strength test were conducted before and after the triathlon test. (3) Results: There was a significant difference between treatment × time during the isometric muscle strength test. Based on the Tukey post hoc analysis, the peak net force decreased statistically in the placebo (p = 0.045) and control conditions (p = 0.026), but not in the experimental condition (p = 0.121). In addition, all of the conditions studied obtained similar results in the countermovement vertical jump after exercise. (4) Conclusions: As a result, consumption of DSW seems to delay the failure of muscle function specifically in isometric exercises but does not improve performance in sports. Thus, DSW does not alter muscle capacity in a negative way; therefore, its consumption may be recommended.

15.
bioRxiv ; 2024 May 17.
Artigo em Inglês | MEDLINE | ID: mdl-38798593

RESUMO

Acinetobacter baumannii causes life-threatening infections that are becoming difficult to treat due to increasing rates of multi-drug resistance (MDR) among clinical isolates. This has led the World Health Organization and the CDC to categorize MDR A. baumannii as a top priority for the research and development of new antibiotics. Colistin is the last-resort antibiotic to treat carbapenem-resistant A. baumannii . Not surprisingly, reintroduction of colistin has resulted in the emergence of colistin-resistant strains. Diclofenac is a nonsteroidal anti-inflammatory drug used to treat pain and inflammation associated with arthritis. In this work, we show that diclofenac sensitizes colistin-resistant A. baumannii clinical strains to colistin, in vitro and in a murine model of pneumonia. Diclofenac also reduced the colistin MIC of Klebsiella pneumoniae and Pseudomonas aeruginosa isolates. Transcriptomic and proteomic analyses revealed an upregulation of oxidative stress-related genes and downregulation of type IV pili induced by the combination treatment. Notably, the concentrations of colistin and diclofenac effective in the murine model were substantially lower than those determined in vitro , implying a stronger synergistic effect in vivo compared to in vitro . A pilA mutant strain, lacking the primary component of the type IV pili, became sensitive to colistin in the absence of diclofenac. This suggest that the downregulation of type IV pili is key for the synergistic activity of these drugs in vivo and indicates that colistin and diclofenac exert an anti-virulence effect. Together, these results suggest that the diclofenac can be repurposed with colistin to treat MDR A. baumannii .

16.
Front Immunol ; 15: 1425938, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38953020

RESUMO

Introduction: P2X receptors are a family of homo- and heterotrimeric cation channels gated by extracellular ATP. The P2X4 and P2X7 subunits show overlapping expression patterns and have been involved in similar physiological processes, such as pain and inflammation as well as various immune cell functions. While formation of P2X2/P2X3 heterotrimers produces a distinct pharmacological phenotype and has been well established, functional identification of a P2X4/P2X7 heteromer has been difficult and evidence for and against a physical association has been found. Most of this evidence stems, however, from in vitro model systems. Methods: Here, we used a P2X7-EGFP BAC transgenic mouse model as well as P2X4 and P2X7 knock-out mice to re-investigate a P2X4-P2X7 interaction in mouse lung by biochemical and immunohistochemical experiments as well as quantitative expression analysis. Results: No detectable amounts of P2X4 could be co-purified from mouse lung via P2X7-EGFP. In agreement with these findings, immuno-histochemical analysis using a P2X7-specific nanobody revealed only limited overlap in the cellular and subcellular localizations of P2X4 and P2X7 in both the native lung tissue and primary cells. Comparison of P2X4 and P2X7 transcript and protein levels in the respective gene-deficient and wild type mice showed no mutual interrelation between their expression levels in whole lungs. However, a significantly reduced P2rx7 expression was found in alveolar macrophages of P2rx4 -/- mice. Discussion: In summary, our detailed analysis of the cellular and subcellular P2X4 and P2X7 localization and expression does not support a physiologically relevant direct association of P2X4 and P2X7 subunits or receptors in vivo.


Assuntos
Pulmão , Camundongos Knockout , Camundongos Transgênicos , Receptores Purinérgicos P2X4 , Receptores Purinérgicos P2X7 , Animais , Receptores Purinérgicos P2X4/metabolismo , Receptores Purinérgicos P2X4/genética , Receptores Purinérgicos P2X7/genética , Receptores Purinérgicos P2X7/metabolismo , Camundongos , Pulmão/metabolismo , Pulmão/imunologia , Camundongos Endogâmicos C57BL , Ligação Proteica
18.
Rev. méd. Chile ; 151(1): 7-14, feb. 2023. ilus, tab
Artigo em Espanhol | LILACS | ID: biblio-1515411

RESUMO

BACKGROUND: Diabetic retinopathy (DR) is an important cause of decreased visual acuity, whose prevalence has increased between 1990 and 2020. In Chile the prevalence of diabetic retinopathy was estimated at 24.8%. AIM: To assess the prevalence of DR in a southern Chilean city. MATERIAL AND METHODS: From a database of diabetic patients attending primary health care centers at Puerto Montt, Chile, 196 patients with DR and 392 patients without DR, matched by age and presence of chronic complications, were chosen for this case-control study. RESULTS: The prevalence of DR in the database of diabetic patients was 33.3%. glycated hemoglobin, the frequency insulin use, systolic blood pressure, HDL cholesterol, microalbuminuria, and proteinuria were significantly worse in cases. A multivariate analysis showed that retinopathy is much more likely to occur when the variables insulin use, neuropathy, and microalbuminuria concur. CONCLUSIONS: DR was associated with worse metabolic parameters and the presence of neuropathy in this case control study.


Assuntos
Humanos , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Idoso , Idoso de 80 Anos ou mais , Diabetes Mellitus Tipo 2 , Retinopatia Diabética/epidemiologia , Insulinas , Estudos de Casos e Controles , Chile/epidemiologia , Prevalência , Fatores de Risco
19.
Artigo em Inglês | LILACS-Express | LILACS | ID: biblio-1535947

RESUMO

Introduction: There is no clarity about manometric findings in patients with proctalgia fugax; evidence shows different results. This study aims to evaluate dyssynergic defecation through anorectal manometry in Colombian patients in two gastroenterology centers in Bogotá, Colombia. Materials and methods: A cross-sectional descriptive observational study in adult patients with proctalgia fugax undergoing anorectal manometry and treated in two gastroenterology centers in Bogotá between 2018 and 2020. Results: 316 patients were included, predominantly women (65%), with a median age of 45.2 (range: 18-78; standard deviation [SD]: 28.3). Four percent of patients had hypertonicity, 50% were normotonic, and 46% were hypotonic. Regarding manometric parameters, 50% had normal pressure, and 46% had anal sphincter hypotonia; 76% had a normal voluntary contraction test. Dyssynergic defecation was documented in 5% of patients, and the most frequent was type I, followed by type III. A rectoanal inhibitory reflex was identified in all patients, 42% with altered sensory threshold and 70% with abnormal balloon expulsion. There was an agreement between the results of the anorectal manometry and the subjective report of the digital rectal exam by the head nurse who performed the procedure. Conclusions: The data obtained in the present study suggest that proctalgia is not related to the elevated and sustained basal contracture of the sphincter but neither to the alteration in voluntary contraction since most patients have typical values.


Introducción: Actualmente, no hay claridad acerca de los hallazgos manométricos en pacientes con proctalgia fugaz, y la evidencia muestra diferentes resultados. Se plantea como objetivo en el presente estudio evaluar la presencia de disinergia defecatoria con manometría anorrectal en pacientes colombianos en dos centros de gastroenterología en Bogotá, Colombia. Metodología: Estudio observacional descriptivo de corte transversal en pacientes adultos sometidos a manometría anorrectal con proctalgia fugaz y atendidos en dos centros de gastroenterología de la ciudad de Bogotá entre el 2018 y el 2020. Resultados: Se incluyó a 316 pacientes, predominantemente mujeres (65%), con mediana de edad 45,2 (rango: 18-78; desviación estándar [DE]: 28,3). El 4% de los pacientes presentaban hipertonicidad, el 50% eran normotónicos y el 46%, hipotónicos. En cuanto a parámetros manométricos, el 50% tenía presión normal y el 46%, hipotonía de esfínter anal. El 76% tuvo una prueba de contracción voluntaria normal. En 5% pacientes se documentó disinergia defecatoria, y la más frecuente fue el tipo I, seguido del tipo III. En todos los pacientes se identificó reflejo recto anal inhibitorio, 42% con alteración en umbral sensitivo y 70% con expulsión de balón anormal, y hubo concordancia entre los resultados de la manometría anorrectal y el reporte subjetivo del tacto rectal de la jefe de enfermería que realizó el procedimiento. Conclusiones: Los datos obtenidos en el presente estudio sugieren que la proctalgia no está relacionada con la contractura basal elevada y sostenida del esfínter, pero tampoco con la alteración en la contracción voluntaria, ya que la mayoría de los pacientes presentan valores normales.

20.
Rev. gastroenterol. Perú ; 43(2)abr. 2023.
Artigo em Espanhol | LILACS-Express | LILACS | ID: biblio-1450029

RESUMO

En Colombia no hay datos acerca de la percepción de la calidad de vida (CdV) en enfermedad infamatoria intestinal (EII). Se plantea como objetivo determinar la percepción de la CdV mediante el cuestionario IBDQ-32 en pacientes con EII a partir de una muestra de pacientes de diferentes centros de referencia. Se realizó un estudio de corte transversal en adultos, con EII en remisión clínica, en seguimiento ambulatorio, en 3 instituciones en diferentes ciudades, entre junio 2022 a noviembre 2022, se identificaron sujetos elegibles, se recolectó información en fechas distintas, acerca aspectos sociodemográficos y clínicos, se evaluó el cuestionario IBDQ-32 en una ocasión y se realizó análisis descriptivo y analítico de las variables evaluadas. Como resultado, se obtuvieron 80 pacientes, 70% mujeres, edad media 38,5 (rango18-72; SD 13,25) años. 67,5% colitis ulcerosa (CU), 32,5% enfermedad de Crohn (EC). Se encontró compromiso moderado de la CdV (mediana 150 puntos, rango-intercuartílico 118,3-181,5) en EII, en CU mediana 151 (rango-intercuartílico 120-174,75) puntos, mientras en EC 133(rango-intercuartílico 106,25-186,25) puntos. Hubo mayor afección en dominio sistémico, con medianas 21 (rango-intercuartílico 15,8-27) puntos, y 18,5 (rango-intercuartílico 12,8-25,3) puntos, para CU y EC, respectivamente. Y, los menos afectados correspondieron al dominio digestivo y función social, en CU medianas 48,5 (rango-intercuartílico 40-58,3), y 27 (rango-intercuartílico 20,8-33); en EC medianas 43 (rango-intercuartílico 35,5-61,75) y 24,5 (rango-intercuartílico 18-32,5), respectivamente. No se encontraron diferencias estadísticamente significativas. Este estudio aporta información única acerca CdV de los pacientes con EII en Colombia. Se requiere seguir reforzando el acompañamiento, apoyo, y educación a los pacientes con EII.


In Colombia there are no data about perception of quality of life (QoL) in inflammatory bowel disease (IBD). The aim of this study was to determine the perception of QoL by means of the IBDQ-32 questionnaire in patients with IBD from a sample of patients from different referral centers. We carried out a cross-sectional study in adults with IBD in clinical remission, in outpatient follow-up, in 3 institutions in different cities, between June 2022 and November 2022, eligible subjects were identified, information was collected on different dates, about socio-demographic and clinical aspects, and the IBDQ-32 questionnaire was evaluated on one occasion. Descriptive and analytical analysis of the variables evaluated was performed. 80 patients, 70% women, mean age 38.5(range 18-72; SD 13.25) years. 67.5% ulcerative colitis (UC), 32.5% Crohn´s disease (CD). Moderate QoL involvement (median 150 points, interquartile range118.3-181.5) was found in IBD, in UC median 151 (interquartile range120-174.75) points, while in CD 133 (interquartile range106.25-186.25) points. There was greater involvement in the systemic domain, with median 21 (interquartile range 15.8-27) points, and 18.5 (interquartile range 12.8-25.3) points, for UC and CD, respectively. The least affected corresponded to the digestive domain and social function, in median UC 48.5 (interquartile range 40-58.3), and 27(interquartile range 20.8-33); in median CD 43 (interquartile range 35.5-61.75) and 24.5(interquartile range 18-32.5), respectively. No statistically significant differences were found. This study provides unique information about QoL of patients with IBD in Colombia. It is necessary to continue reinforcing the accompaniment, support, and education of patients with IBD.

SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA