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1.
EMBO J ; 41(5): e109386, 2022 03 01.
Artículo en Inglés | MEDLINE | ID: mdl-35112724

RESUMEN

The mechanisms whereby neutrophils respond differentially to live and dead organisms are unknown. We show here that neutrophils produce 5- to 30-fold higher levels of the Cxcl2 chemokine in response to live bacteria, compared with killed bacteria or isolated bacterial components, despite producing similar levels of Cxcl1 or pro-inflammatory cytokines. Secretion of high levels of Cxcl2, which potently activates neutrophils by an autocrine mechanism, requires three signals. The first two signals are provided by two different sets of signal peptides released by live bacteria, which selectively activate formylated peptide receptor 1 (Fpr1) and Fpr2, respectively. Signal 3 originates from Toll-like receptor activation by microbial components present in both live and killed bacteria. Mechanistically, these signaling pathways converge at the level of the p38 MAP kinase, leading to activation of the AP-1 transcription factor and to Cxcl2 induction. Collectively, our data demonstrate that the simultaneous presence of agonists for Fpr1, Fpr2, and Toll-like receptors represents a unique signature associated with viable bacteria, which is sensed by neutrophils and induces Cxcl2-dependent autocrine cell activation.


Asunto(s)
Bacterias/metabolismo , Neutrófilos/metabolismo , Proteínas Proto-Oncogénicas c-fes/metabolismo , Receptores Toll-Like/metabolismo , Animales , Citocinas/metabolismo , Femenino , Ratones , Ratones Endogámicos C57BL , Ratones Noqueados , Transducción de Señal/fisiología
2.
BMC Microbiol ; 24(1): 221, 2024 Jun 22.
Artículo en Inglés | MEDLINE | ID: mdl-38909237

RESUMEN

BACKGROUND: Group B Streptococcus (GBS) is a commensal of healthy adults and an important pathogen in newborns, the elderly and immunocompromised individuals. GBS displays several virulence factors that promote colonisation and host infection, including the ST-17 strain-specific adhesin Srr2, previously characterised for its binding to fibrinogen. Another common target for bacterial adhesins and for host colonization is fibronectin, a multi-domain glycoprotein found ubiquitously in body fluids, in the extracellular matrix and on the surface of cells. RESULTS: In this study, fibronectin was identified as a novel ligand for the Srr2 adhesin of GBS. A derivative of the ST-17 strain BM110 overexpressing the srr2 gene showed an increased ability to bind fibrinogen and fibronectin, compared to the isogenic wild-type strain. Conversely, the deletion of srr2 impaired bacterial adhesion to both ligands. ELISA assays and surface plasmon resonance studies using the recombinant binding region (BR) form of Srr2 confirmed a direct interaction with fibronectin with an estimated Kd of 92 nM. Srr2-BR variants defective in fibrinogen binding also exhibited no interaction with fibronectin, suggesting that Srr2 binds this ligand through the dock-lock-latch mechanism, previously described for fibrinogen binding. The fibronectin site responsible for recombinant Srr2-BR binding was identified and localised in the central cell-binding domain of the protein. Finally, in the presence of fibronectin, the ability of a Δsrr2 mutant to adhere to human cervico-vaginal epithelial cells was significantly lower than that of the wild-type strain. CONCLUSION: By combining genetic and biochemical approaches, we demonstrate a new role for Srr2, namely interacting with fibronectin. We characterised the molecular mechanism of this interaction and demonstrated that it plays a role in promoting the adhesion of GBS to human cervico-vaginal epithelial cells, further substantiating the role of Srr2 as a factor responsible for the hypervirulence of GBS ST-17 strains. The discovery of the previously undescribed interaction between Srr2 and fibronectin establishes this adhesin as a key factor for GBS colonisation of host tissues.


Asunto(s)
Adhesinas Bacterianas , Adhesión Bacteriana , Fibronectinas , Unión Proteica , Streptococcus agalactiae , Streptococcus agalactiae/genética , Streptococcus agalactiae/metabolismo , Streptococcus agalactiae/patogenicidad , Fibronectinas/metabolismo , Humanos , Adhesinas Bacterianas/metabolismo , Adhesinas Bacterianas/genética , Fibrinógeno/metabolismo , Fibrinógeno/genética , Células Epiteliales/microbiología , Femenino , Infecciones Estreptocócicas/microbiología , Factores de Virulencia/metabolismo , Factores de Virulencia/genética
3.
Mol Microbiol ; 117(6): 1479-1492, 2022 06.
Artículo en Inglés | MEDLINE | ID: mdl-35570359

RESUMEN

The binding of Streptococcus pneumoniae to collagen is likely an important step in the pathogenesis of pneumococcal infections, but little is known of the underlying molecular mechanisms. Streptococcal surface repeats (SSURE) are highly conserved protein domains present in cell wall adhesins from different Streptococcus species. We find here that SSURE repeats of the pneumococcal adhesin plasminogen and fibronectin binding protein B (PfbB) bind to various types of collagen. Moreover, deletion of the pfbB gene resulted in a significant impairment of the ability of encapsulated or unencapsulated pneumococci to bind collagen. Notably, a PfbB SSURE domain is also bound to the complement component C1q that bears a collagen-like domain and promotes adherence of pneumococci to host cells by acting as a bridge between bacteria and epithelial cells. Accordingly, deletion of PfbB or pre-treatment with anti-SSURE antibodies markedly decreased pneumococcal binding to C1q as well as C1q-dependent adherence to epithelial and endothelial cells. Further data indicated that C1q promotes pneumococcal adherence by binding to integrin α2 ß1 . In conclusion, our results indicate that the SSURE domains of the PfbB protein promote interactions of pneumococci with various types of collagen and with C1q. These repeats may be useful targets in strategies to control S. pneumoniae infections.


Asunto(s)
Infecciones Neumocócicas , Streptococcus pneumoniae , Adhesión Bacteriana , Proteínas Bacterianas/metabolismo , Colágeno/genética , Colágeno/metabolismo , Complemento C1q/genética , Complemento C1q/metabolismo , Células Endoteliales/metabolismo , Humanos , Infecciones Neumocócicas/metabolismo , Streptococcus pneumoniae/genética , Streptococcus pneumoniae/metabolismo
4.
J Immunol ; 207(5): 1448-1455, 2021 09 01.
Artículo en Inglés | MEDLINE | ID: mdl-34362834

RESUMEN

Identification of the receptors involved in innate immune recognition of Staphylococcus aureus, a major cause of morbidity and mortality in humans, is essential to develop alternative strategies to treat infections caused by antibiotic-resistant strains. In the current study, we examine the role of endosomal TLRs, which sense the presence of prokaryotic-type nucleic acids, in anti-staphylococcal host defenses using infection models involving genetically defective mice. Single deficiencies in TLR7, 9, or 13 resulted in mild or no decrease in host defenses. However, the simultaneous absence of TLR7, 9, and 13 resulted in markedly increased susceptibility to cutaneous and systemic S. aureus infection concomitantly with decreased production of proinflammatory chemokines and cytokines, neutrophil recruitment to infection sites, and reduced production of reactive oxygen species. This phenotype was significantly more severe than that of mice lacking TLR2, which senses the presence of staphylococcal lipoproteins. Notably, the combined absence of TLR7, 9, and 13 resulted in complete abrogation of IL-12 p70 and IFN-ß responses to staphylococcal stimulation in macrophages. Taken together, our data highlight the presence of a highly integrated endosomal detection system, whereby TLR7, 9, and 13 cooperate in sensing the presence of staphylococcal nucleic acids. We demonstrate that the combined absence of these receptors cannot be compensated for by cell surface-associated TLRs, such as TLR2, or cytosolic receptors. These data may be useful to devise strategies aimed at stimulating innate immune receptors to treat S. aureus infections.


Asunto(s)
Endosomas/metabolismo , Glicoproteínas de Membrana/metabolismo , Neutrófilos/inmunología , Infecciones Estafilocócicas/inmunología , Staphylococcus aureus/fisiología , Receptor Toll-Like 7/metabolismo , Receptor Toll-Like 9/metabolismo , Receptores Toll-Like/metabolismo , Animales , Citocinas/metabolismo , Modelos Animales de Enfermedad , Susceptibilidad a Enfermedades , Femenino , Humanos , Inmunidad Innata , Mediadores de Inflamación/metabolismo , Glicoproteínas de Membrana/genética , Ratones , Ratones Endogámicos C57BL , Ratones Noqueados , Receptor Toll-Like 7/genética , Receptor Toll-Like 9/genética , Receptores Toll-Like/genética
5.
J Cardiothorac Vasc Anesth ; 35(6): 1594-1602, 2021 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-33293216

RESUMEN

Fascial plane chest wall blocks are an integral component to optimal multimodal postoperative analgesia in breast and cardiothoracic surgery, facilitating faster functional recovery and earlier discharge. Pectoral nerves block and serratus plane block have been used to treat postsurgical pain after breast and cardiothoracic surgeries; however, they cannot be used to anesthetize the anterior chest wall. Ultrasound parasternal block, or pectointercostal fascial block and transversus thoracis muscle plane block are two novel ultrasound-guided anesthetic and analgesic techniques that block the anterior cutaneous branches T2 to T6 intercostal nerves, providing anesthesia and analgesia to the anterior chest wall. Ultrasound parasternal block/pectointercostal fascial block and transversus thoracis muscle plane block are performed in the region of the internal mammary artery and could be considered to treat post-thoracotomy pain. This anatomic region is innervated by the anterior cutaneous branches T2-to-T6 intercostal nerves, which are obliterated during cardiac surgery artery harvesting. At the level of the fourth parasternal rib interspace, the internal mammary artery can be identified between the internal intercostal muscle and transversus thoracis muscle as a longitudinal pulsatile structure approximately 1.5 cm from the lateral border of the sternum. The transversus thoracis muscle is variable in many people and, thus, is an unreliable target and is difficult to visualize with ultrasound. Moreover, patients with a history of coronary artery bypass grafting could have tissue disruption in the transversus thoracis plane because of the internal mammary artery harvest, making transversus thoracis muscle identification more difficult. Despite ultrasound parasternal block and transversus thoracis muscle plane block having good safety profiles and reduced risk of complications, pneumothorax, local anesthetic systemic toxicity, and internal mammary artery injury or hematoma should be considered. If the block is performed before cardiac surgery, both the right and left internal mammary arteries could be damaged. The injury could render the internal mammary artery unusable for bypass grafting. If the block is performed after left internal mammary artery harvesting at the end of coronary artery bypass grafting, only the right internal mammary artery could be damaged. In patients in whom the internal mammary artery has been surgically used and the transversus thoracis muscle is difficult to visualize, ultrasound parasternal block should be considered. In patients in whom the internal mammary artery could be difficult to visualize or considering that it is in the vicinity of the transversus thoracis muscle plane block target and that the transversus thoracis muscle is difficult to visualize with ultrasound after internal mammary artery harvesting, then ultrasound parasternal block should be considered. The authors believe that ultrasound parasternal block is the safer regional technique for protecting the internal mammary artery and the pleura because it is more superficial. For this reason, ultrasound parasternal block also could be performed by inexperienced anesthesiologists. Although ultrasound parasternal block is more superficial, its superiority in terms of safety is yet to be proven. Additional studies are warranted to validate the authors' hypothesis.


Asunto(s)
Analgesia , Arterias Mamarias , Bloqueo Nervioso , Nervios Torácicos , Humanos , Arterias Mamarias/diagnóstico por imagen , Bloqueo Nervioso/efectos adversos , Dolor Postoperatorio/etiología , Dolor Postoperatorio/prevención & control
6.
BMC Anesthesiol ; 20(1): 290, 2020 11 23.
Artículo en Inglés | MEDLINE | ID: mdl-33225913

RESUMEN

BACKGROUND: Breast surgery in the United States is common. Pain affects up to 50% of women undergoing breast surgery and can interfere with postoperative outcomes. General anesthesia is the conventional, most frequently used anaesthetic technique. Various locoregional anesthetic techniques are also used for breast surgeries. A systematic review of the use of locoregional anesthesia for postoperative pain in breast surgery is needed to clarify its role in pain management. OBJECTIVES: To systematically review literature to establish the efficacy and the safety of locoregional anesthesia used in the treatment of pain after breast surgery. METHODS: Embase, MEDLINE, Google Scholar and Cochrane Central Trials Register were systematically searched in Mars 2020 for studies examining locoregional anesthesia for management of pain in adults after breast surgery. The methodological quality of the studies and their results were appraised using the Consensus-based Standards for the Selection of Health Measurement Instruments (COSMIN) checklist and specific measurement properties criteria, respectively. RESULTS: Nineteen studies evaluating locoregional anesthesia were included: 1058 patients underwent lumpectomy/mastectomy, 142 breast augmentation and 79 breast reduction. Locoregional anesthesia provides effective anesthesia and analgesia in the perioperative setting, however no statistically significant difference emerged if compared to other techniques. For mastectomy only, the use of locoregional techniques reduces pain in the first hour after the end of the surgery if compared to other procedures (p = 0.02). Other potentially beneficial effects of locoregional anesthesia include decreased need for opioids, decreased postoperative nausea and vomiting, fewer complications and increased patient satisfaction. All this improves postoperative recovery and shortens hospitalization stay. In none of these cases, locoregional anesthesia was statistically superior to other techniques. CONCLUSION: The results of our review showed no differences between locoregional anesthesia and other techniques in the management of breast surgery. Locoregional techniques are superior in reducing pain in the first hour after mastectomy.


Asunto(s)
Analgésicos Opioides/administración & dosificación , Anestesia de Conducción/métodos , Mamoplastia/métodos , Mastectomía/métodos , Dolor Postoperatorio/tratamiento farmacológico , Satisfacción del Paciente/estadística & datos numéricos , Anestesia Local/métodos , Mama/cirugía , Femenino , Humanos
7.
Front Microbiol ; 15: 1367898, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38511003

RESUMEN

The gut represents an important site of colonization of the commensal bacterium Streptococcus agalactiae (group B Streptococcus or GBS), which can also behave as a deadly pathogen in neonates and adults. Invasion of the intestinal epithelial barrier is likely a crucial step in the pathogenesis of neonatal infections caused by GBS belonging to clonal complex 17 (CC17). We have previously shown that the prototypical CC17 BM110 strain invades polarized enterocyte-like cells through their lateral surfaces using an endocytic pathway. By analyzing the cellular distribution of putative GBS receptors in human enterocyte-like Caco-2 cells, we find here that the alpha 3 (α3) and alpha 2 (α2) integrin subunits are selectively expressed on lateral enterocyte surfaces at equatorial and parabasal levels along the vertical axis of polarized cells, in an area corresponding to GBS entry sites. The α3ß1 and α2ß1 integrins were not readily accessible in fully differentiated Caco-2 monolayers but could be exposed to specific antibodies after weakening of intercellular junctions in calcium-free media. Under these conditions, anti-α3ß1 and anti-α2ß1 antibodies significantly reduced GBS adhesion to and invasion of enterocytes. After endocytosis, α3ß1 and α2ß1 integrins localized to areas of actin remodeling around GBS containing vacuoles. Taken together, these data indicate that GBS can invade enterocytes by binding to α3ß1 and α2ß1 integrins on the lateral membrane of polarized enterocytes, resulting in cytoskeletal remodeling and bacterial internalization. Blocking integrins might represent a viable strategy to prevent GBS invasion of gut epithelial tissues.

8.
Life (Basel) ; 14(5)2024 May 10.
Artículo en Inglés | MEDLINE | ID: mdl-38792635

RESUMEN

(1) Background: Infections caused by multidrug-resistant (MDR) bacteria represent one of the major global public health problems of the 21st century. Beta-lactam antibacterial agents are commonly used to treat infections due to Gram-negative pathogens. New ß-lactam/ß-lactamase inhibitor combinations are urgently needed. Combining relebactam (REL) with imipenem (IMI) and cilastatin (CS) can restore its activity against many imipenem-nonsusceptible Gram-negative pathogens. (2) Methods: we performed a systematic review of the studies reporting on the use of in vivo REAL/IPM/CS. (3) Results: A total of eight studies were included in this review. The primary diagnosis was as follows: complicated urinary tract infection (n = 234), complicated intra-abdominal infections (n = 220), hospital-acquired pneumonia (n = 276), and ventilator-associated pneumonia (n = 157). Patients with normal renal function received REL/IPM/CS (250 mg/500 mg/500 mg). The most frequently reported AEs occurring in patients treated with imipenem/cilastatin plus REL/IPM/CS were nausea (11.5%), diarrhea (9.8%), vomiting (9.8%), and infusion site disorders (4.0%). Treatment outcomes in these high-risk patients receiving REL/IPM/CS were generally favorable. A total of 70.6% of patients treated with REL/IPM/CS reported a favorable clinical response at follow-up. (4) Conclusions: this review indicates that REL/IPM/CS is active against important MDR Gram-negative organisms.

9.
Behav Neurol ; 2024: 1228194, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38524401

RESUMEN

Amyotrophic lateral sclerosis (ALS) is the most frequent neurodegenerative disease of the motor system that affects upper and lower motor neurons, leading to progressive muscle weakness, spasticity, atrophy, and respiratory failure, with a life expectancy of 2-5 years after symptom onset. In addition to motor symptoms, patients with ALS have a multitude of nonmotor symptoms; in fact, it is currently considered a multisystem disease. The purpose of our narrative review is to evaluate the different types of pain, the correlation between pain and the disease's stages, the pain assessment tools in ALS patients, and the available therapies focusing above all on the benefits of cannabis use. Pain is an underestimated and undertreated symptom that, in the last few years, has received more attention from research because it has a strong impact on the quality of life of these patients. The prevalence of pain is between 15% and 85% of ALS patients, and the studies on the type and intensity of pain are controversial. The absence of pain assessment tools validated in the ALS population and the dissimilar study designs influence the knowledge of ALS pain and consequently the pharmacological therapy. Several studies suggest that ALS is associated with changes in the endocannabinoid system, and the use of cannabis could slow the disease progression due to its neuroprotective action and act on pain, spasticity, cramps, sialorrhea, and depression. Our research has shown high patients' satisfaction with the use of cannabis for the treatment of spasticity and related pain. However, especially due to the ethical problems and the lack of interest of pharmaceutical companies, further studies are needed to ensure the most appropriate care for ALS patients.


Asunto(s)
Esclerosis Amiotrófica Lateral , Enfermedades Neurodegenerativas , Humanos , Esclerosis Amiotrófica Lateral/complicaciones , Dimensión del Dolor , Calidad de Vida , Enfermedades Neurodegenerativas/complicaciones , Dolor/tratamiento farmacológico
10.
BMC Surg ; 13 Suppl 2: S53, 2013.
Artículo en Inglés | MEDLINE | ID: mdl-24267789

RESUMEN

BACKGROUND: Purpose of the study is to define the role of conventional radiology and MRI in the evaluation of pelvic floor hernias in female pelvic floor disorders. METHODS: A MEDLINE and PubMed search was performed for journals before March 2013 with MeSH major terms 'MR Defecography' and 'pelvic floor hernias'. RESULTS: The prevalence of pelvic floor hernias at conventional radiology was higher if compared with that at MRI. Concerning the hernia content, there were significantly more enteroceles and sigmoidoceles on conventional radiology than on MRI, whereas, in relation to the hernia development modalities, the prevalence of elytroceles, edroceles, and Douglas' hernias at conventional radiology was significantly higher than that at MRI. CONCLUSIONS: MRI shows lower sensitivity than conventional radiology in the detection of pelvic floor hernias development. The less-invasive MRI may have a role in a better evaluation of the entire pelvic anatomy and pelvic organ interaction especially in patients with multicompartmental defects, planned for surgery.


Asunto(s)
Defecografía/métodos , Hernia/diagnóstico por imagen , Imagen por Resonancia Magnética , Trastornos del Suelo Pélvico/diagnóstico por imagen , Femenino , Humanos
11.
Recenti Prog Med ; 104(7-8): 409-11, 2013.
Artículo en Italiano | MEDLINE | ID: mdl-24042418

RESUMEN

In the study of inflammatory kidney diseases, the use of integrated imaging is considered the best diagnostic approach. However, given the high cost of radiological examinations, the radiologist is responsible for the choice of the best method to solve the question asked by the clinician. In this paper are presented the main imaging methods for the study of pyelonephritis and, based on our experience, it is emphasized the role of multidetector Computed Tomography urographic technique in the identification, characterization and subsequent follow-up of inflammatory kidney diseases.


Asunto(s)
Tomografía Computarizada Multidetector/métodos , Pielonefritis/diagnóstico por imagen , Urografía/métodos , Anciano , Medios de Contraste , Femenino , Humanos , Procesamiento de Imagen Asistido por Computador , Imagenología Tridimensional , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Sensibilidad y Especificidad , Urolitiasis/diagnóstico por imagen
12.
Recenti Prog Med ; 104(7-8): 425-9, 2013.
Artículo en Italiano | MEDLINE | ID: mdl-24042422

RESUMEN

Endodontics is the branch of deciduous teeth pediatric dentistry that deals with the treatment of the root canal system. The goal of therapy is to maintain as long as possible the element in the dental arch to prevent alterations of orthognathodontic, infectious, and functional history and eruptive sequence. Although manual instrumentation has been widely used and still preferred by some practitioners, has limitations that affect the actual ability to clean the channel, the ability to create steps, perforations, dentinal plugs and fractures of the instrument. On the other hand, the disadvantages are the high cost of the instruments in nickel-titanium, which must be frequently replaced, and the risk of compromising the stability of the tooth due to an excessive consumption of dentinal tissue. The use of computed microtomography (µCT) of extracted elements has a considerable advantage in the study of dental hard tissues. The purpose of this study was to analyze the anatomy of the endodontic system of the elements deciduous.


Asunto(s)
Cavidad Pulpar/diagnóstico por imagen , Odontometría/métodos , Diente Primario/diagnóstico por imagen , Microtomografía por Rayos X/métodos , Dentina/diagnóstico por imagen , Humanos , Imagenología Tridimensional , Técnicas In Vitro , Tamaño de los Órganos , Preparación del Conducto Radicular/instrumentación , Preparación del Conducto Radicular/métodos
13.
Recenti Prog Med ; 104(7-8): 412-4, 2013.
Artículo en Italiano | MEDLINE | ID: mdl-24042419

RESUMEN

Ultrasound examination of the testis is the imaging modality of choice for the evaluation of intratesticular focal lesions. In spite of its high sensibility, eco-Doppler-elastography is lacking of specificity in discrimination between benign and malign lesions, not always allowing us to make a definitive diagnosis of malignancy. When a diagnostic doubt persists, for such lesions that are indeterminate at clinical and radiological evaluation, it is possible to recur to ultrasound-guided testicular needle biopsy. This paper describes the main application scenarios of testicular fine-needle aspiration under ultrasound guidance and the experience in our institute.


Asunto(s)
Biopsia con Aguja Fina/métodos , Diagnóstico por Imagen de Elasticidad , Testículo/patología , Ultrasonografía Doppler en Color/métodos , Ultrasonografía Intervencional/métodos , Adolescente , Adulto , Anciano , Niño , Criptorquidismo/patología , Cistoadenoma Papilar/patología , Fibrosis , Humanos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Teratoma/patología , Neoplasias Testiculares/patología , Testículo/diagnóstico por imagen , Adulto Joven
14.
Pathogens ; 12(1)2023 Jan 10.
Artículo en Inglés | MEDLINE | ID: mdl-36678467

RESUMEN

Two-component signaling systems (TCSs) are finely regulated mechanisms by which bacteria adapt to environmental conditions by modifying the expression of target genes. In bacterial pathogenesis, TCSs play important roles in modulating adhesion to mucosal surfaces, resistance to antibiotics, and metabolic adaptation. In the context of urinary tract infections (UTI), one of the most common types infections causing significant health problems worldwide, uropathogens use TCSs for adaptation, survival, and establishment of pathogenicity. For example, uropathogens can exploit TCSs to survive inside bladder epithelial cells, sense osmolar variations in urine, promote their ascension along the urinary tract or even produce lytic enzymes resulting in exfoliation of the urothelium. Despite the usefulness of studying the function of TCSs in in vitro experimental models, it is of primary necessity to study bacterial gene regulation also in the context of host niches, each displaying its own biological, chemical, and physical features. In light of this, the aim of this review is to provide a concise description of several bacterial TCSs, whose activity has been described in mouse models of UTI.

15.
Antibiotics (Basel) ; 12(6)2023 May 26.
Artículo en Inglés | MEDLINE | ID: mdl-37370284

RESUMEN

The number of multidrug-resistant bacteria is rapidly spreading worldwide. Among the various mechanisms determining resistance to antimicrobial agents, multidrug efflux pumps play a noteworthy role because they export extraneous and noxious substrates from the inside to the outside environment of the bacterial cell contributing to multidrug resistance (MDR) and, consequently, to the failure of anti-infective therapies. The expression of multidrug efflux pumps can be under the control of transcriptional regulators and two-component systems (TCS). TCS are a major mechanism by which microorganisms sense and reply to external and/or intramembrane stimuli by coordinating the expression of genes involved not only in pathogenic pathways but also in antibiotic resistance. In this review, we describe the influence of TCS on multidrug efflux pump expression and activity in some Gram-negative and Gram-positive bacteria. Taking into account the strict correlation between TCS and multidrug efflux pumps, the development of drugs targeting TCS, alone or together with already discovered efflux pump inhibitors, may represent a beneficial strategy to contribute to the fight against growing antibiotic resistance.

16.
Cell Rep Med ; 4(7): 101098, 2023 07 18.
Artículo en Inglés | MEDLINE | ID: mdl-37390829

RESUMEN

During differentiation, neutrophils undergo a spontaneous pro-inflammatory program that is hypothesized here to be under caspase-8 control. In mice, intraperitoneal administration of the caspase-8 inhibitor z-IETD-fmk is sufficient to unleash the production of pro-inflammatory cytokines and neutrophil influx in the absence of cell death. These effects are due to selective inhibition of caspase-8 and require tonic interferon-ß (IFN-ß) production and RIPK3 but not MLKL, the essential downstream executioner of necroptotic cell death. In vitro, stimulation with z-IETD-fmk is sufficient to induce significant cytokine production in murine neutrophils but not in macrophages. Therapeutic administration of z-IETD-fmk improves clinical outcome in models of lethal bacterial peritonitis and pneumonia by augmenting cytokine release, neutrophil influx, and bacterial clearance. Moreover, the inhibitor protects mice against high-dose endotoxin shock. Collectively, our data unveil a RIPK3- and IFN-ß-dependent pathway that is constitutively activated in neutrophils and can be harnessed therapeutically using caspase-8 inhibition.


Asunto(s)
Apoptosis , Infecciones Bacterianas , Animales , Ratones , Infecciones Bacterianas/tratamiento farmacológico , Caspasa 8/metabolismo , Caspasa 8/farmacología , Citocinas/metabolismo , Activación Neutrófila
17.
Life (Basel) ; 13(6)2023 Jun 07.
Artículo en Inglés | MEDLINE | ID: mdl-37374117

RESUMEN

(1) Background: Osteoarthritis (OA) is a debilitating joint disease. The are several therapies available for OA. According to current knowledge, the combination of Platelet-Rich Plasma (PRP) and Pulsed Radiofrequency (PRF) can be applied in the treatment of pain of nociceptive origin due to peripheral tissue damage. (2) Methods: We performed a narrative review identifying the articles by searching electronic databases. A retrospective analysis of patients with OA treated with PRF and PRP in "Vito Fazzi" Hospital (Lecce, Italy) was performed. (3) Results: A total of four publications on the use of PRP and PRF in degenerative joint arthritis were included in our review. In our experience, two patients with OA were treated with PRP and PRF after unsuccessful conservative treatment. Patient pain score, daily activity ability, active range of activity, and muscle strength improved after treatment. Patients reported a higher level of satisfaction. No major adverse events were reported. (4) Conclusions: The goal of the combined application of the two treatments is to make full use of the analgesic effect of PRF and the repairing effect of PRP. At present, the therapeutic potential of PRP and PRF in OA remains unmet.

18.
J Clin Med ; 12(19)2023 Sep 24.
Artículo en Inglés | MEDLINE | ID: mdl-37834812

RESUMEN

(1) Background: In the last few years, many randomized controlled trials (RCTs) have compared direct Macintosh laryngoscopy with McGrath videolaryngoscopy in order to assess the potential benefits of the latter; the results were sometimes controversial. (2) Methods: We conducted a comprehensive literature search to identify our articles according to inclusion and exclusion criteria: to be included, each study had to be a prospective randomized trial or comparison between the McGrath videolaryngoscope and the Macintosh laryngoscope in an adult population. We did not include manikin trials or studies involving double-lumen tubes. (3) Results: 10 studies met the inclusion criteria necessary. In total, 655 patients were intubated with the McGrath and 629 with the Macintosh. In total, 1268 of 1284 patients were successfully intubated, showing equivalent results for the two devices: 648 of 655 patients with the McGrath videolaryngoscope and 620 of 629 patients with the Macintosh laryngoscope. No differences were noted in terms of hemodynamic changes or the incidence of adverse events. (4) Conclusions: We can assert that the McGrath videolaryngoscope and Macintosh laryngoscope, even if with equivalent tracheal intubation results, supplement each other.

19.
Life (Basel) ; 13(2)2023 Jan 30.
Artículo en Inglés | MEDLINE | ID: mdl-36836734

RESUMEN

Infective endocarditis (IE) is a rare but potentially life-threatening disease, sometimes with longstanding sequels among surviving patients. The population at high risk of IE is represented by patients with underlying structural heart disease and/or intravascular prosthetic material. Taking into account the increasing number of intravascular and intracardiac procedures associated with device implantation, the number of patients at risk is growing too. If bacteremia develops, infected vegetation on the native/prosthetic valve or any intracardiac/intravascular device may occur as the final result of invading microorganisms/host immune system interaction. In the case of IE suspicion, all efforts must be focused on the diagnosis as IE can spread to almost any organ in the body. Unfortunately, the diagnosis of IE might be difficult and require a combination of clinical examination, microbiological assessment and echocardiographic evaluation. There is a need of novel microbiological and imaging techniques, especially in cases of blood culture-negative. In the last few years, the management of IE has changed. A multidisciplinary care team, including experts in infectious diseases, cardiology and cardiac surgery, namely, the Endocarditis Team, is highly recommended by the current guidelines.

20.
Infect Dis Rep ; 15(5): 494-503, 2023 Sep 04.
Artículo en Inglés | MEDLINE | ID: mdl-37736996

RESUMEN

Multivalvular endocarditis (MVE) is an uncommon infection that mostly involves mitral and aortic valves, and it is related to a higher risk of congestive heart failure and a higher mortality. We described a case of a bilateral MVE and performed a review of the literature on similar clinical cases. We reported an unusual case of a 68-year-old male patient with a tricuspid and mitral infective endocarditis due to a methicillin-resistant Staphylococcus aureus complicated by multiple right- and left-sided septic embolization (lungs, brain, spleen, L2-L3 vertebral bones) due to an unknown atrial septal defect identified and repaired during cardiac surgery. Despite the severity of the clinical case, the patient experienced a good clinical outcome also thanks to a multidisciplinary approach. We identified 21 case reports describing bilateral MVE. A multidisciplinary approach is essential in the management of valve diseases to improve the prognosis of patients, especially in bilateral MVE.

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