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1.
Int J Mol Sci ; 25(3)2024 Jan 25.
Artículo en Inglés | MEDLINE | ID: mdl-38338780

RESUMEN

The cryptoglandular perianal fistula is a common benign anorectal disorder that is managed mainly with surgery and in some cases may be an extremely challenging condition. Perianal fistulas are often characterized by significantly decreased patient quality of life. Lack of fully recognized pathogenesis of this disease makes it difficult to treat it properly. Recently, adipose tissue hormones have been proposed to play a role in the genesis of cryptoglandular anal fistulas. The expression of adipose tissue hormones and epithelial-to-mesenchymal transition (EMT) factors were characterized based on 30 samples from simple fistulas and 30 samples from complex cryptoglandular perianal fistulas harvested during surgery. Tissue levels of leptin, resistin, MMP2, and MMP9 were significantly elevated in patients who underwent operations due to complex cryptoglandular perianal fistulas compared to patients with simple fistulas. Adiponectin and E-cadherin were significantly lowered in samples from complex perianal fistulas in comparison to simple fistulas. A negative correlation between leptin and E-cadherin levels was observed. Resistin and MMP2 levels, as well as adiponectin and E-cadherin levels, were positively correlated. Complex perianal cryptoglandular fistulas have a reduced level of the anti-inflammatory adipokine adiponectin and have an increase in the levels of proinflammatory resistin and leptin. Abnormal secretion of these adipokines may affect the integrity of the EMT in the fistula tract. E-cadherin, MMP2, and MMP9 expression levels were shifted in patients with more advanced and complex perianal fistulas. Our results supporting the idea of using mesenchymal stem cells in the treatment of cryptoglandular perianal fistulas seem reasonable, but further studies are warranted.


Asunto(s)
Leptina , Fístula Rectal , Humanos , Resistina , Metaloproteinasa 2 de la Matriz , Metaloproteinasa 9 de la Matriz , Resultado del Tratamiento , Calidad de Vida , Adiponectina , Fístula Rectal/etiología , Tejido Adiposo/metabolismo , Cadherinas
2.
Int J Mol Sci ; 25(3)2024 Jan 30.
Artículo en Inglés | MEDLINE | ID: mdl-38338964

RESUMEN

In an increasingly aging society, there is a growing demand for the development of technology related to tissue regeneration. It involves the development of the appropriate biomaterials whose properties will allow the desired biological response to be obtained. Bioactivity is strongly affected by the proper selection of active ingredients. The aim of this study was to produce bioactive hydrogel materials based on hyaluronic acid and collagen modified by the addition of placenta. These materials were intended for use as dressings, and their physicochemical properties were investigated under simulated biological environmental conditions. The materials were incubated in vitro in different fluids simulating the environment of the human body (e.g., simulated body fluid) and then stored at a temperature close to body temperature. Using an FT-IR spectrophotometer, the functional groups present in the composites were identified. The materials with the added placenta showed an increase in the swelling factor of more than 300%. The results obtained confirmed the potential of using this material as an absorbent dressing. This was indicated by pH and conductometric measurements, sorption, degradation, and surface analysis under an optical microscope. The results of the in vitro biological evaluation confirmed the cytosafety of the tested biomaterials. The tested composites activate monocytes, which may indicate their beneficial properties in the first phases of wound healing. The material proved to be nontoxic and has potential for medical use.


Asunto(s)
Ácido Hialurónico , Hidrogeles , Humanos , Animales , Ovinos , Ácido Hialurónico/farmacología , Ácido Hialurónico/química , Hidrogeles/farmacología , Hidrogeles/química , Espectroscopía Infrarroja por Transformada de Fourier , Cicatrización de Heridas , Colágeno/farmacología , Colágeno/química , Materiales Biocompatibles/farmacología
3.
Dig Dis ; 41(3): 387-395, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-36412565

RESUMEN

BACKGROUND: Inflammatory bowel disease (IBD) care and education might differ around Europe. Therefore, we conducted this European Variation In IBD PracticE suRvey (VIPER) to investigate potential differences between countries. METHODS: This trainee-initiated survey, run through SurveyMonkey®, consisted of 47 questions inquiring basic demographics, IBD training, and clinical care. Results were compared according to gross domestic product (GDP) per capita, for which countries were divided into 2 groups (low/high income, according to the World Bank). RESULTS: The online survey was completed by 1,285 participants from 40 European countries, with a majority of specialists (65.3%) working in academic institutions (50.4%). Significant differences in IBD-specific training (55.9% vs. 38.4%), as well as availability of IBD units (58.4% vs. 39.7%) and multidisciplinary meetings (73.2% vs. 40.1%), were observed between respondees from high and low GDP countries (p < 0.0001). In high GDP countries, IBD nurses are more common (85.9% vs. 36.0%), also mirrored by more nurse-led IBD clinics (40.6% vs. 13.7%; p < 0.0001). IBD dieticians (33.4% vs. 16.5%) and psychologists (16.8% vs. 7.5%) are mainly present in high GDP countries (p < 0.0001). In the current COVID era, telemedicine is available in 73.2% versus 54.1% of the high/low GDP countries, respectively (p < 0.0001). Treat-to-target approaches are implemented everywhere (85.0%), though access to biologicals and small molecules differs significantly. CONCLUSION: Much variability in IBD practice exists across Europe, with marked differences between high and low GDP countries. Further work is required to help address some of these inequalities, aiming to improve and standardize IBD care and training across Europe.


Asunto(s)
Productos Biológicos , COVID-19 , Enfermedades Inflamatorias del Intestino , Humanos , Enfermedades Inflamatorias del Intestino/epidemiología , Enfermedades Inflamatorias del Intestino/terapia , Europa (Continente)/epidemiología , Encuestas y Cuestionarios
4.
Folia Med Cracov ; 63(1): 91-96, 2023 Apr 30.
Artículo en Inglés | MEDLINE | ID: mdl-37406279

RESUMEN

The Buschke-Löwenstein tumor is a rare disease associated with human papillomavirus infection. The condition manifests with an ulcerative, exophytic tumor localized in the perineal area. Generally considered as non-cancerous, the growth may develop malignant transformation. Our manuscript highlights the importance of early diagnosis with histopathological analysis.


Asunto(s)
Tumor de Buschke-Lowenstein , Carcinoma de Células Escamosas , Condiloma Acuminado , Humanos , Tumor de Buschke-Lowenstein/patología , Condiloma Acuminado/patología , Perineo/patología , Carcinoma de Células Escamosas/cirugía , Carcinoma de Células Escamosas/patología
5.
Rep Pract Oncol Radiother ; 28(5): 608-611, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-38179288

RESUMEN

Background: Thorough staging plays a significant role in determining therapy modality in esophageal cancer patients. The aim of this study was to assess whether positron emission tomography/computed tomography (PET/CT) may be safely omitted in selected groups of patients. Materials and methods: This retrospective analysis included 37 esophageal cancer patients recruited to chemoradiation by the Multidisciplinary Tumor Board (MTB) at the Greater Poland Cancer Center in 2021. Prior to radiotherapy planning every patient was referred to PET/CT to have the extent of their disease assessed. Results: Among 37 patients PET/CT changed the staging status to metastatic (M1) in six cases (3 planoepithelial and 3 adenocarcinomas). In all those cases but one (1 patient with supraclavicular node metastasis finally received chemoradiation) confirmation of distant metastases excluded patients from radical treatment. Interestingly, in the PET/CT distant positive group 3 patients were initially staged as locally advanced (without nodal involvement). The other 3 were initially identified as at least N2 in tomography. Conclusion: Results of this report allowed the conclusion that PET/CT plays a key role in esophageal cancer patients considered for radical chemoradiation; therefore, it remains a necessary tool to exclude metastatic disease in both main pathology types. Since the delayed time for PET/CT scan in esophageal cancer patients planned to chemoradiation may negatively influence treatment results, the data should be alarming for national health provider.

6.
Int J Mol Sci ; 23(22)2022 Nov 18.
Artículo en Inglés | MEDLINE | ID: mdl-36430791

RESUMEN

Synthetic implants are used to treat large bone defects that are often unable to regenerate, for example those caused by osteoporosis. It is necessary that the materials used to manufacture them are biocompatible and resorbable. Polymer-ceramic composites, such as those based on poly(L-lactide) (PLLA) and calcium phosphate ceramics (Ca-P), are often used for these purposes. In this study, we attempted to investigate an innovative strategy for two-step (dual) modification of composites and their components to improve the compatibility of composite components and the adhesion between PLA and Ca-P whiskers, and to increase the mechanical strength of the composite, as well as improve osteological bioactivity and prevent bone resorption in composites intended for bone regeneration. In the first step, Ca-P whiskers were modified with a saturated fatty acid namely, lauric acid (LA), or a silane coupling agent γ-aminopropyltriethoxysilane (APTES). Then, the composite, characterized by the best mechanical properties, was modified in the second stage of the work with an active chemical compound used in medicine as a first-line drug in osteoporosis-sodium alendronate, belonging to the group of bisphosphonates (BP). As a result of the research covered in this work, the composite modified with APTES and alendronate was found to be a promising candidate for future biomedical engineering applications.


Asunto(s)
Osteoporosis , Silanos , Humanos , Alendronato/farmacología , Porosidad , Poliésteres/química , Osteoblastos
7.
Pharmacol Res ; 172: 105840, 2021 10.
Artículo en Inglés | MEDLINE | ID: mdl-34450312

RESUMEN

Emerging evidence indicates that the gut microbiota play a crucial role in the bidirectional communication between the gut and the brain suggesting that the gut microbes may shape neural development, modulate neurotransmission and affect behavior, and thereby contribute to the pathogenesis and/or progression of many neurodevelopmental, neuropsychiatric, and neurological conditions. This review summarizes recent data on the role of microbiota-gut-brain axis in the pathophysiology of neuropsychiatric and neurological disorders including depression, anxiety, schizophrenia, autism spectrum disorders, Parkinson's disease, migraine, and epilepsy. Also, the involvement of microbiota in gut disorders co-existing with neuropsychiatric conditions is highlighted. We discuss data from both in vivo preclinical experiments and clinical reports including: (1) studies in germ-free animals, (2) studies exploring the gut microbiota composition in animal models of diseases or in humans, (3) studies evaluating the effects of probiotic, prebiotic or antibiotic treatment as well as (4) the effects of fecal microbiota transplantation.


Asunto(s)
Eje Cerebro-Intestino , Microbioma Gastrointestinal , Trastornos Mentales/microbiología , Enfermedades del Sistema Nervioso/microbiología , Animales , Humanos
8.
Int J Mol Sci ; 22(7)2021 Mar 30.
Artículo en Inglés | MEDLINE | ID: mdl-33808501

RESUMEN

In this research, we prepared foam scaffolds based on poly(l-lactide) (PLLA) and apatite whiskers (HAP) using thermally induced phase separation technique supported by the salt leaching process (TIPS-SL). Using sodium chloride having a size of (a) 150-315 µm, (b) 315-400 µm, and (c) 500-600 µm, three types of foams with different pore sizes have been obtained. Internal structure of the obtained materials has been investigated using SEM as well as µCT. The materials have been studied by means of porosity, density, and compression tests. As the most promising, the composite prepared with salt size of 500-600 µm was prepared also with the l-lysine modified apatite. The osteoblast hFOB 1.19 cell response for the scaffolds was also investigated by means of cell viability, proliferation, adhesion/penetration, and biomineralization. Direct contact cytotoxicity assay showed the cytocompatibility of the scaffolds. All types of foam scaffolds containing HAP whiskers, regardless the pore size or l-lysine modification induced significant stimulatory effect on the cal-cium deposits formation in osteoblasts. The PLLA/HAP scaffolds modified with l-lysine stimulated hFOB 1.19 osteoblasts proliferation. Compared to the scaffolds with smaller pores (150-315 µm and 315-400 µm), the PLLA/HAP foams with large pores (500-600 µm) promoted more effective ad-hesion of osteoblasts to the surface of the biomaterial.


Asunto(s)
Durapatita/química , Poliésteres/química , Ingeniería de Tejidos/métodos , Andamios del Tejido/química , Apatitas/química , Apatitas/metabolismo , Materiales Biocompatibles/química , Línea Celular Tumoral , Humanos , Ácido Láctico/metabolismo , Lisina/química , Lisina/metabolismo , Osteoblastos/metabolismo , Poliésteres/metabolismo , Polímeros/química , Porosidad
9.
Int J Mol Sci ; 22(24)2021 Dec 18.
Artículo en Inglés | MEDLINE | ID: mdl-34948389

RESUMEN

In this research, we describe the properties of three-component composite foam scaffolds based on poly(ε-caprolactone) (PCL) as a matrix and hydroxyapatite whiskers (HAP) and L-Lysine as fillers (PCL/HAP/Lys with wt% ratio 50/48/2). The scaffolds were prepared using a thermally induced phase separation technique supported by salt leaching (TIPS-SL). All materials were precisely characterized: porosity, density, water uptake, wettability, DSC, and TGA measurements and compression tests were carried out. The microstructure of the obtained scaffolds was analyzed via SEM. It was found that the PCL/HAP/Lys scaffold has a 45% higher Young's modulus and better wettability compared to the PCL/HAP system. At the same time, the porosity of the system was ~90%. The osteoblast hFOB 1.19 cell response was also investigated in osteogenic conditions (39 °C) and the cytokine release profile of interleukin (IL)-1ß, IL-6, and tumor necrosis factor (TNF)-α was determined. Modification of PCL scaffolds with HAP and L-Lysine significantly improved the proliferation of pre-osteoblasts cultured on such materials.


Asunto(s)
Materiales Biocompatibles/química , Durapatita/química , Lisina/análogos & derivados , Osteoblastos/citología , Poliésteres/química , Andamios del Tejido/química , Regeneración Ósea , Adhesión Celular , Línea Celular , Proliferación Celular , Humanos , Ingeniería de Tejidos/métodos
10.
Int J Mol Sci ; 22(16)2021 Aug 10.
Artículo en Inglés | MEDLINE | ID: mdl-34445293

RESUMEN

In this research, we synthesize and characterize poly(glycerol sebacate) pre-polymer (pPGS) (1H NMR, FTiR, GPC, and TGA). Nano-hydroxyapatite (HAp) is synthesized using the wet precipitation method. Next, the materials are used to prepare a PGS-based composite with a 25 wt.% addition of HAp. Microporous composites are formed by means of thermally induced phase separation (TIPS) followed by thermal cross-linking (TCL) and salt leaching (SL). The manufactured microporous materials (PGS and PGS/HAp) are then subjected to imaging by means of SEM and µCT for the porous structure characterization. DSC, TGA, and water contact angle measurements are used for further evaluation of the materials. To assess the cytocompatibility and biological potential of PGS-based composites, preosteoblasts and differentiated hFOB 1.19 osteoblasts are employed as in vitro models. Apart from the cytocompatibility, the scaffolds supported cell adhesion and were readily populated by the hFOB1.19 preosteoblasts. HAp-facilitated scaffolds displayed osteoconductive properties, supporting the terminal differentiation of osteoblasts as indicated by the production of alkaline phosphatase, osteocalcin and osteopontin. Notably, the PGS/HAp scaffolds induced the production of significant amounts of osteoclastogenic cytokines: IL-1ß, IL-6 and TNF-α, which induced scaffold remodeling and promoted the reconstruction of bone tissue. Initial biocompatibility tests showed no signs of adverse effects of PGS-based scaffolds toward adult BALB/c mice.


Asunto(s)
Sustitutos de Huesos/síntesis química , Decanoatos/química , Durapatita/química , Glicerol/análogos & derivados , Polímeros/química , Ingeniería de Tejidos/métodos , Andamios del Tejido/química , Animales , Materiales Biocompatibles/síntesis química , Materiales Biocompatibles/química , Materiales Biocompatibles/farmacología , Regeneración Ósea/efectos de los fármacos , Sustitutos de Huesos/química , Sustitutos de Huesos/farmacología , Sustitutos de Huesos/uso terapéutico , Huesos/efectos de los fármacos , Huesos/fisiología , Células Cultivadas , Femenino , Glicerol/química , Humanos , Invenciones , Masculino , Ensayo de Materiales , Ratones , Ratones Endogámicos BALB C , Osteoblastos/efectos de los fármacos , Osteoblastos/fisiología , Osteogénesis/efectos de los fármacos , Polímeros/síntesis química , Porosidad , Ingeniería de Tejidos/tendencias
11.
Scand J Gastroenterol ; 55(3): 294-300, 2020 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-32180483

RESUMEN

Background: The role of sleep disturbances in patients with inflammatory bowel disease (IBD) remained relatively unknown. The aim of this study was to identify the adipokine profile in the patients with IBD and its relationship with the circadian rhythm disorders.Methods: Prospective, observational cohort study was performed. In all the enrolled adult IBD patients, the disease activity was assessed by using Crohn's Disease Activity Index (CDAI) for Crohn's disease (CD) and Partial Mayo Score for ulcerative colitis (UC), respectively. All patients were also asked to respond to a questionnaire to define Pittsburgh Quality Sleep Index (PSQI). From all the enrolled patients, 15 mL venous blood was taken to determine adipokine levels and perform standard laboratory tests.Results: Sixty-five IBD patients were enrolled in our study: 30 with CD and 35 with UC. Poor sleep was noted in 69.2% patients with clinically active and in 7.7% patients with inactive disease (p = .0023). In the group of IBD patients with poor sleep, the significantly higher level of serum resistin (p = .0458), and lower level of serum adiponectin and leptin (p = .0215, p = .0201; respectively) were observed. In the IBD patients with exacerbation, the significantly higher level of serum resistin (p = .0396), significantly lower serum level of leptin (p = .0453) and tendency to lower serum level of adiponectin (p = .1214) were recorded.Conclusions: The relationship between circadian rhythm abnormalities and specific adipokine profile may show us a risk factor of developing inflammatory intestinal lesions in IBD patients. This knowledge may allow the treatment of sleep disturbances, body weight-control and dietary habits become new targets in IBD therapy.


Asunto(s)
Adipoquinas/sangre , Ritmo Circadiano , Enfermedades Inflamatorias del Intestino/sangre , Trastornos del Sueño-Vigilia/sangre , Trastornos del Sueño-Vigilia/etiología , Adulto , Femenino , Humanos , Enfermedades Inflamatorias del Intestino/fisiopatología , Leptina/sangre , Masculino , Persona de Mediana Edad , Polonia , Estudios Prospectivos , Curva ROC , Resistina/sangre , Índice de Severidad de la Enfermedad , Trastornos del Sueño-Vigilia/fisiopatología , Encuestas y Cuestionarios , Adulto Joven
12.
Curr Gastroenterol Rep ; 22(3): 11, 2020 Feb 10.
Artículo en Inglés | MEDLINE | ID: mdl-32040642

RESUMEN

PURPOSE OF REVIEW: In this study, we present the evidence-based management for patients hospitalized for ulcerative colitis (UC) with a special focus on the synergic approach of the two key actors of the inflammatory bowel disease multidisciplinary team (IBD-MDT): gastroenterologist and surgeon. RECENT FINDINGS: Focused treatment by a specialized IBD-MDT and early involvement of the colorectal surgeon in the management of hospitalized UC patients is advocated. The colectomy rate has not changed over the years. Moreover, delayed surgery after admission is burden by increase complication and mortality rates. Thus, it is pivotal to identify the patients who are likely to undergo surgery, by mean of predictors of outcome, and not to prolong ineffective medical treatment. The perfect timing based on clinical close monitoring is crucial. Up to 25% of patients with ulcerative colitis (UC) may require hospitalization. The aim of admission is to evaluate severity of the disease, exclude infections and establish proper treatment while monitoring the response. During admission, the patient has to be closely observed for the possible development of toxic megacolon or perforation, which should prompt emergency colectomy. Up to 30% of UC patients will fail to respond to initial intravenous corticosteroid. Non-responder or partial responder to medical therapy should be evaluated for timely surgery or could be considered for rescue medical therapy.


Asunto(s)
Colitis Ulcerosa/diagnóstico , Colitis Ulcerosa/terapia , Antiinflamatorios/uso terapéutico , Colectomía/métodos , Colitis Ulcerosa/complicaciones , Cirugía Colorrectal , Manejo de la Enfermedad , Gastroenterología , Fármacos Gastrointestinales/uso terapéutico , Glucocorticoides/uso terapéutico , Hospitalización , Humanos , Grupo de Atención al Paciente , Proctectomía/métodos , Tiempo de Tratamiento
13.
Int J Mol Sci ; 21(13)2020 Jun 27.
Artículo en Inglés | MEDLINE | ID: mdl-32605029

RESUMEN

Some intracellular pathogens are able to avoid the defense mechanisms contributing to host epigenetic modifications. These changes trigger alterations tothe chromatin structure and on the transcriptional level of genes involved in the pathogenesis of many bacterial diseases. In this way, pathogens manipulate the host cell for their own survival. The better understanding of epigenetic consequences in bacterial infection may open the door for designing new vaccine approaches and therapeutic implications. This article characterizes selected intracellular bacterial pathogens, including Mycobacterium spp., Listeria spp., Chlamydia spp., Mycoplasma spp., Rickettsia spp., Legionella spp. and Yersinia spp., which can modulate and reprogram of defense genes in host innate immune cells.


Asunto(s)
Bacterias/aislamiento & purificación , Infecciones Bacterianas/microbiología , Epigénesis Genética , Regulación de la Expresión Génica , Interacciones Huésped-Patógeno/genética , Inmunidad Innata/genética , Animales , Bacterias/genética , Humanos , Virulencia
14.
Int J Mol Sci ; 21(18)2020 Sep 13.
Artículo en Inglés | MEDLINE | ID: mdl-32933206

RESUMEN

Novel biocomposites of poly(L-lactide) (PLLA) and poly(l-lactide-co-glycolide) (PLLGA) with 10 wt.% of surface-modified hydroxyapatite particles, designed for applications in bone tissue engineering, are presented in this paper. The surface of hydroxyapatite (HAP) was modified with polyethylene glycol by using l-lysine as a linker molecule. The modification strategy fulfilled two important goals: improvement of the adhesion between the HAP surface and PLLA and PLLGA matrices, and enhancement of the osteological bioactivity of the composites. The surface modifications of HAP were confirmed by attenuated total reflectance-Fourier transform infrared spectroscopy (ATR-FTIR), TGA, and elemental composition analysis. The influence of hydroxyapatite surface functionalization on the thermal and in vitro biological properties of PLLA- and PLLGA-based composites was investigated. Due to HAP modification with polyethylene glycol, the glass transition temperature of PLLA was reduced by about 24.5 °C, and melt and cold crystallization abilities were significantly improved. These achievements were scored based on respective shifting of onset of melt and cold crystallization temperatures and 1.6 times higher melt crystallization enthalpy compared with neat PLLA. The results showed that the surface-modified HAP particles were multifunctional and can act as nucleating agents, plasticizers, and bioactive moieties. Moreover, due to the presented surface modification of HAP, the crystallinity degree of PLLA and PLLGA and the polymorphic form of PLLA, the most important factors affecting mechanical properties and degradation behaviors, can be controlled.


Asunto(s)
Materiales Biocompatibles/química , Durapatita/química , Poliésteres/química , Cristalización/métodos , Ensayo de Materiales , Espectroscopía Infrarroja por Transformada de Fourier/métodos , Propiedades de Superficie , Temperatura
15.
Int J Colorectal Dis ; 34(2): 217-227, 2019 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-30564910

RESUMEN

INTRODUCTION: Visceral pain is a symptom reported by over 70% of inflammatory bowel disease (IBD) sufferers. So far, a single, specific cause of this debilitating state has not been established. Chronic pain is one of the most important factors decreasing the quality of life in IBD course. Concurrently, management of pain is the most challenging issue encountered by clinicians in IBD treatment. AREAS COVERED: This review focuses on pathophysiology of inflammatory bowel disease-caused visceral pain and explores currently available approaches to its management. We also covered recent pharmacological developments in the field. CONCLUSIONS: Pain-related disability has major effects on quality of life and on functional and social outcomes in IBD patients. Currently, there is no one standardized method of managing chronic visceral pain in IBD. Therefore, future development, focusing primarily on alleviating the pain, but also on reducing inflammation, is essential.


Asunto(s)
Dolor Crónico/complicaciones , Dolor Crónico/terapia , Enfermedades Inflamatorias del Intestino/complicaciones , Enfermedades Inflamatorias del Intestino/terapia , Manejo del Dolor , Dolor Abdominal/complicaciones , Dolor Abdominal/terapia , Directrices para la Planificación en Salud , Humanos
16.
Int J Mol Sci ; 20(10)2019 May 24.
Artículo en Inglés | MEDLINE | ID: mdl-31137759

RESUMEN

The concept of „trained innate immunity" is understood as the ability of innate immune cells to remember invading agents and to respond nonspecifically to reinfection with increased strength. Trained immunity is orchestrated by epigenetic modifications leading to changes in gene expression and cell physiology. Although this phenomenon was originally seen mainly as a beneficial effect, since it confers broad immunological protection, enhanced immune response of reprogrammed innate immune cells might result in the development or persistence of chronic metabolic, autoimmune or neuroinfalmmatory disorders. This paper overviews several examples where the induction of trained immunity may be essential in the development of diseases characterized by flawed innate immune response.


Asunto(s)
Aterosclerosis/inmunología , Diabetes Mellitus/inmunología , Inmunidad Innata , Memoria Inmunológica , Enfermedades Neurodegenerativas/inmunología , Animales , Humanos
17.
Int J Toxicol ; 37(5): 373-382, 2018.
Artículo en Inglés | MEDLINE | ID: mdl-29923437

RESUMEN

Immunological memory is a key feature of adaptive immunity. It provides the organism with long-lived and robust protection against infection. The important question is whether cyclophosphamide (CP), as immunosuppressive agent used in cancer therapy and in some autoimmune diseases, may act on the memory T-cell population. We investigated the effect of CP on the percentage of central memory T cells (TCM) and effector memory T cells (TEM) in the mouse model of CP-induced immunosuppression (8-10-week-old male C57BL/6 mice CP treated for 7 days at the daily dose of 50 µg/g body weight [bw], manifested the best immunosuppression status, as compared to lower doses of CP: 10 or 20 µg/g bw). The CP induced a significant decrease in the percentage of CD8+ (TCM), compared to nonimmunosuppressed mice. This effect was not observed in the case of CD4+ TCM population. The percentage of gated TEM with CD4 and CD8 phenotype was significantly decreased in CP-treated mice, as compared to the control ones. Taken together, the above data indicate that CP-induced immunosuppression in mice leads to a reduction in the abundance of central memory cells possessing preferentially CD8+ phenotype as well as to a reduction in the percentage of effector memory cells (splenocytes both CD4+ and CD8+), compared to the cells from nonimmunosuppressed mice. These findings in mice described in this article may contribute to the understanding of the complexity of the immunological responses in humans and extend research on the impact of the CP model of immunosuppression in mice and memory T-cell populations.


Asunto(s)
Ciclofosfamida/toxicidad , Inmunosupresores/toxicidad , Linfocitos T/efectos de los fármacos , Animales , Médula Ósea/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Memoria Inmunológica , Ganglios Linfáticos/citología , Ganglios Linfáticos/efectos de los fármacos , Masculino , Ratones , Ratones Endogámicos C57BL , Bazo/citología , Bazo/efectos de los fármacos , Linfocitos T/inmunología
18.
Scand J Gastroenterol ; 52(6-7): 711-715, 2017.
Artículo en Inglés | MEDLINE | ID: mdl-28272905

RESUMEN

AIM: To investigate the levels of G protein-coupled receptor 55 (GPR55) expression in colonic tissue of inflammatory bowel disease (IBD) patients and healthy controls, and its potential implication in IBD treatment. METHODS: Fifty patients were enrolled in our prospective study: n = 21 with Crohn's disease (CD) and n = 16 with ulcerative colitis (UC); 19 women and 18 men. Control consisted of 13 non-IBD patients. In each subject, two biopsies were taken from different colonic locations. In IBD patients, biopsies both from endoscopically inflamed and non-inflamed areas were drawn and the development of inflammation confirmed in histopathological examination. GPR55 mRNA and protein expression were measured using real-time PCR and Western blot, respectively. RESULTS: GPR55 expression at mRNA and protein level was detected in all samples tested. The level of GPR55 mRNA expression in non-inflamed colonic areas was comparable in all analyzed groups (p = .2438). However, in the inflamed tissues GPR55 mRNA expression was statistically significantly (p < .0001) higher (6.9 fold) in CD patients compared to UC. Moreover, CD patients manifested higher (12.5 fold) GPR55 mRNA expression in inflamed compared with non-inflamed colonic tissues (p < .0001). Although no significant differences were stated, GPR55 protein level tends to decrease in IBD as compared to control. CONCLUSIONS: Different patterns of GPR55 expression at mRNA level were observed in IBD patients. We speculate that GPR55 is crucial for the mucosal inflammatory processes in IBD, particularly in CD and its expression may affect disease severity, and response to treatment. The GPR55 receptors may become an attractive target for novel therapeutic strategies in IBD.


Asunto(s)
Colitis Ulcerosa/genética , Colon/patología , Enfermedad de Crohn/genética , Receptores Acoplados a Proteínas G/metabolismo , Adulto , Western Blotting , Estudios de Casos y Controles , Colon/metabolismo , Femenino , Humanos , Masculino , Polonia , Estudios Prospectivos , ARN Mensajero/genética , ARN Mensajero/metabolismo , Reacción en Cadena en Tiempo Real de la Polimerasa , Receptores de Cannabinoides , Receptores Acoplados a Proteínas G/genética
19.
Dig Dis Sci ; 62(6): 1511-1517, 2017 06.
Artículo en Inglés | MEDLINE | ID: mdl-28391416

RESUMEN

BACKGROUND: Cyclophilin A (CyPA) is an immunomodulatory protein, high expression of which correlates with poor outcome of patients with inflammatory diseases. However, its role in inflammatory bowel disease (IBD) has not been studied. AIM: This study analyzes the correlation between cyclophilin A, matrix metalloproteinase (MMP)-9, and tissue inhibitor of MMP (TIMP)/MMP-9 complexes in the inflamed and non-inflamed colon mucosa of UC and CD patients. METHODS: Serum and biopsy specimens from inflamed and non-inflamed colonic mucosa of 38 patients with IBD (19 with UC and 19 with CD) and 16 controls were included in our study. We measured serum and tissue level of CyPA, and tissue level of TNF-α, MMP-9, TIMP-1/MMP-9, and TIMP-2/MMP-9 using ELISA method. RESULTS: Our results indicated that serum, but not tissue CyPA is increased in UC, rather than in CD patients, compared to the control. The increase correlated with higher tissue concentration of MMP-9 and TNF-α, especially in the UC group. Moreover, we observed significantly higher level of TIMP-1/MMP-9 in UC and CD group, which overlapped with the change in MMP-9. There was no change in TIMP-2/MMP-9 in the analyzed groups. CONCLUSION: The current study suggests that serum CyPA may be an independent additional marker of IBD, especially of UC. Higher CyPA level may be followed by increased MMP-9 in those patients. However, further studies are necessary to verify the role of CyPA in IBD development.


Asunto(s)
Colitis Ulcerosa/metabolismo , Colitis Ulcerosa/patología , Enfermedad de Crohn/metabolismo , Enfermedad de Crohn/patología , Ciclofilina A/sangre , Metaloproteinasa 9 de la Matriz/metabolismo , Adulto , Biomarcadores/sangre , Biopsia , Estudios de Casos y Controles , Colon/metabolismo , Colon/patología , Ciclofilina A/metabolismo , Femenino , Humanos , Mucosa Intestinal/metabolismo , Mucosa Intestinal/patología , Masculino , Persona de Mediana Edad , Inhibidor Tisular de Metaloproteinasa-1/metabolismo , Inhibidor Tisular de Metaloproteinasa-2/metabolismo , Factor de Necrosis Tumoral alfa/metabolismo , Adulto Joven
20.
Postepy Hig Med Dosw (Online) ; 71(0): 906-914, 2017 Nov 03.
Artículo en Inglés | MEDLINE | ID: mdl-29151063

RESUMEN

There are many interactions between species (including bacteria) in the environment. One of them is predation, which always leads to the death of a prey. Described in this review Bdellovibrio bacteriovorus (Deltaproteobacteria) and Micavibrio aeruginosavorus (Alfaproteobacteria) are uniflagellate, rod shaped and curved obligate predators of Gram-negative bacteria. Both species belong to the group of BALOs (Bdellovibrio and like organisms). B. bacteriovorus use periplasmic predatory strategy and M. aeruginosavorus are epibiotic hunters. BALOs have found application in both medicine in combating microorganisms responsible for food poisoning and outside of medicine (agriculture and food) as plant protection products and as measures used to prevent the spoiling of food. As a result of searching for effective therapies in the treatment of infections caused by drug-resistant strains of bacteria, it has been shown that predators feed on pathogenic bacteria without showing immunogenicity to humans. Predatory bacteria are able to destroy the multi - and single-species biofilms. Recent studies have indicated the possibility of B. bacteriovorus to destroy the biofilm formed by Staphylococcus aureus. It is postulated that a double predatory strategy of B. bacteriovorus and harmless BALOs towards mammalian cells could be used to treat infections in vivo, particularly in those cases when standard therapy fails.


Asunto(s)
Bdellovibrio , Bacterias Gramnegativas , Staphylococcus aureus , Biopelículas
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