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1.
Clin Exp Rheumatol ; 42(1): 1-9, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38306017

RESUMO

Gout is a chronic joint disease caused by the deposition of monosodium urate crystals into and around the articular tissues. In the last two years, new insights regarding diagnosis, genetic involvement, pathogenesis, comorbidities, and clinical data, have allowed the identification of new strategies to improve the control of the disease and its flares. In keeping, the discover of new mechanisms concerning crystal-induced inflammation have suggested new ways for the management not only of gout, but also other systemic diseases, mainly including renal and cardiovascular disorders. In this context it is very representative the case of colchicine which, given the surprising results obtained both in laboratory and clinical experiments, has recently received by FDA the approval for the prevention of cardiovascular disorders.


Assuntos
Gota , Ácido Úrico , Humanos , Gota/diagnóstico , Gota/tratamento farmacológico , Gota/epidemiologia , Supressores da Gota/uso terapêutico , Colchicina/uso terapêutico , Comorbidade
2.
Int J Mol Sci ; 24(6)2023 Mar 13.
Artigo em Inglês | MEDLINE | ID: mdl-36982526

RESUMO

Genome damage has been related to the induction of autoimmune processes, chronic inflammation, and apoptosis. Recent studies suggest that some rheumatological diseases are associated with overall genomic instability in the T cell compartment. However, no data regarding leucocyte abnormalities in synovial fluid (SF) and their relationship with inflammation are available. The aim of this study was to investigate cellular phenotypes in SF collected from patients with different inflammatory arthropathies, including rhematoid arthritis (RA), psoriatic arthritis (PsA), crystal-induced arthritis (CIA), and non-inflammatory arthropathies, such as osteoarthritis (OA). We found high percentage of micronuclei in SF from CIA compared to the other groups and a high frequency of pyknotic cell in RA and CIA patients. A correlation between pyknosis and immature polymorphonuclear cells with local inflammatory indices was observed. The study of the apoptosis process revealed an increased BAX expression in CIA and RA compared to OA and PsA, while Bcl-2 was higher in CIA. Caspase-3 activity was increased in SF from RA patients and correlates with inflammatory and anti-inflammatory cytokines. In conclusion, our results showed that inflammatory SF is associated with genomic instability and abnormal cell subsets.


Assuntos
Artrite Psoriásica , Artrite Reumatoide , Osteoartrite , Humanos , Líquido Sinovial/metabolismo , Artrite Reumatoide/metabolismo , Artrite Psoriásica/metabolismo , Osteoartrite/metabolismo , Inflamação/metabolismo
3.
Curr Issues Mol Biol ; 44(11): 5173-5190, 2022 Oct 25.
Artigo em Inglês | MEDLINE | ID: mdl-36354664

RESUMO

Gout is caused by the deposition of monosodium urate crystals in the joint and represents the most common form of inflammatory arthritis in men. Its prevalence is rising worldwide mainly due to the increase of risk factors associated with the disease, in particular hyperuricemia. Besides gout, hyperuricemia leads to an increased inflammatory state of the body with consequent increased risk of comorbidities such as cardiovascular diseases. Increasing evidence shows that bioactive compounds have a significant role in fighting inflammatory and immune chronic conditions. In gout and hyperuricemia, these molecules can exert their effects at two levels. They can either decrease serum uric acid concentrations or fight inflammation associated with monosodium urate crystals deposits and hyperuricemia. In this view, they might be considered valuable support to the pharmacological therapy and prevention of the disease. This review aims to provide an overview of the beneficial role of bioactive compounds in hyperuricemia, gout development, and inflammatory pathways of the disease.

4.
Int J Mol Sci ; 23(21)2022 Oct 28.
Artigo em Inglês | MEDLINE | ID: mdl-36361854

RESUMO

We investigated the effects of bactericidal/permeability-increasing protein (BPI) alone or in combination with hyaluronic acid (HA) in two animal models: collagen-induced arthritis (CIA) and crystal-induced inflammation. In CIA, mice were intraperitoneally injected with PBS, HA, or BPI plus or minus HA, twice a week for 2 months, and then euthanized to collect paw and blood. Arthritis was assessed in ankle joints by clinical and histological evaluation. Pathogenic crystals were intraperitoneally injected in mice plus or minus BPI, or with a composition of BPI and HA. After sacrifice, total and differential leukocyte counts were determined. Cytokine levels were measured in serum and peritoneal fluids. In CIA mice, BPI improved clinical and histological outcomes (histological scores ≥2-fold), and downregulated inflammatory mediators (47-93%). In crystal-induced inflammation, BPI reduced leukocyte infiltration (total count: ≥60%; polymorphonuclear cells: ≥36%) and inhibited cytokine production (35-74%). In both models, when mice were co-treated with BPI and HA, the improvement of all parameters was greater than that observed after administration of the two substances alone. Results show that BPI attenuates CIA and inflammation in mice, and this effect is enhanced by HA co-administration. Combined use of BPI and HA represents an interesting perspective for new potential treatments in arthritis.


Assuntos
Artrite Experimental , Camundongos , Animais , Artrite Experimental/tratamento farmacológico , Artrite Experimental/patologia , Mediadores da Inflamação/metabolismo , Citocinas/metabolismo , Inflamação/tratamento farmacológico , Inflamação/patologia , Ácido Hialurônico/metabolismo , Permeabilidade
5.
J Autoimmun ; 111: 102443, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32265078

RESUMO

BACKGROUND: Pentraxin3 (PTX3) is an emerging player in lupus nephritis (LN). Anti-PTX3 antibodies showed to delay LN occurrence in vivo. AIM: To evaluate renal changes following immunization with PTX3 in a murine model of LN. MATERIALS AND METHODS: Twenty-two lupus-prone New Zealand Black/White (NZB/W)F1 mice were divided into two groups (n = 11) and subcutaneously injected with human recombinant (hr)PTX3 100 µg or phosphate buffer saline (PBS) 200 µl, three times 3 weeks apart, starting before development of proteinuria. Five mice from each group were scheduled for sacrifice at week 22 and 6 from each group at week 29. Renal lesions included electron-dense deposits (EDD), glomerular deposition of IgG, complement and PTX3 as markers of renal inflammation. They were evaluated by immunofluorescence (IF), confocal and immunoelectron microscopy (IEM). Validated semiquantitative scores were used when available to score renal lesions. Chi-squared test with Fisher exact test was used for comparison. RESULTS: Nineteen out of 22 mice were sacrificed as scheduled. Only hrPTX3-immunized mice developed anti-PTX3 antibodies. Compared to PBS-injected mice, they displayed a dramatic decrease in glomerular deposits of IgG, C1q and PTX3, as well as in the amount of EDD (p = 0.006) and podocyte effacement (p = 0.043). Importantly, PTX3 was pinpointed inside the EDD and co-localized with nuclear material. CONCLUSIONS: Immunization with PTX3 prevented progression from the preclinical to the clinical stage of LN, inciting anti-PTX3 antibodies and preventing renal PTX3 deposition. PTX3 is a novel component of EDD, submitting it as one initiating autoantigen in LN and as potential target for early treatment.


Assuntos
Formação de Anticorpos/imunologia , Complexo Antígeno-Anticorpo/ultraestrutura , Proteína C-Reativa/metabolismo , Glomérulos Renais/ultraestrutura , Nefrite Lúpica/imunologia , Componente Amiloide P Sérico/metabolismo , Animais , Proteína C-Reativa/genética , Proteína C-Reativa/imunologia , Proteínas do Sistema Complemento/metabolismo , Modelos Animais de Doenças , Resistência à Doença , Feminino , Humanos , Imunização , Glomérulos Renais/metabolismo , Camundongos , Camundongos Endogâmicos , Microscopia Eletrônica , Componente Amiloide P Sérico/genética , Componente Amiloide P Sérico/imunologia
6.
Ann Surg Oncol ; 27(6): 1919, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31900807

RESUMO

BACKGROUND: Hepatic resection represents the best treatment for primary and metastatic liver tumors but is not always feasible. In early 1980, Piclmayr described a complex liver resection technique, termed "ex vivo liver resection," for the treatment of locally advanced tumors not conventionally resectable. The authors approached this technique with translational research in a preclinical setting and then similarly reproduced it in human patients. METHODS: In the swine median xyphopubic laparotomy, the liver was mobilized to expose the vena cava. A temporary porto-caval shunt was previously prepared on the back table using a segment of thoracic aorta, and a vascular anastomosis between the supra-hepatic vena cava and a caval graft was quickly performed. The liver was placed in a machine perfusion system and continuously perfused for 2 h for its final implantation orthotopically in the same animal. The anastomoses were performed as usual. Based on this experience, the intervention was reproduced in the human model of a 39-year-old woman affected by large intrahepatic cholangiocarcinoma considered unresectable.' RESULTS: All animals survived the procedure. The peak aspartate aminotransferase level (460 ± 87 U/L) was recorded 60 min after reperfusion. Lactate levels flared up for 120 min (3.6 ± 0.2 mmol/L). In the clinical case, the postoperative period was uneventful, and the patient was discharged on day 22. CONCLUSIONS: The described procedure is feasible only for surgeons with a transplantation background. The study showed that this translational approach enhances the surgeon's ability to perform the intervention systematically in a shorter time and with a good outcome.


Assuntos
Neoplasias dos Ductos Biliares/cirurgia , Colangiocarcinoma/cirurgia , Hepatectomia/métodos , Perfusão/métodos , Adulto , Animais , Neoplasias dos Ductos Biliares/patologia , Colangiocarcinoma/patologia , Feminino , Veias Hepáticas/cirurgia , Humanos , Modelos Animais , Suínos , Pesquisa Translacional Biomédica , Veia Cava Inferior/cirurgia
7.
Clin Exp Rheumatol ; 38(5): 807-821, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33034561

RESUMO

Gout is the most prevalent form of inflammatory arthritis, with a strong impact on individual health and healthcare systems. This article reviews clinical and experimental evidences about gout emerged throughout the 2019. Starting with an epidemiological analysis, the review explores new insights on genetic factors influencing the development of gout flare, pathogenetic mechanisms, risk factors for the disease and comorbidities. An overview on pharmacological therapies and recent knowledge on the impact of lifestyle and dietary habits are also included. Finally, the review contains a novel section on animal models, which reflects the renewed interest of researchers in the acute process triggered by monosodium urate crystals.


Assuntos
Gota , Animais , Gota/tratamento farmacológico , Gota/epidemiologia , Supressores da Gota/uso terapêutico , Humanos , Estilo de Vida , Fatores de Risco , Exacerbação dos Sintomas
8.
J Autoimmun ; 74: 208-216, 2016 11.
Artigo em Inglês | MEDLINE | ID: mdl-27405845

RESUMO

BACKGROUND: Anti-pentraxin 3 (PTX3) antibodies were associated with the absence of lupus glomerulonephritis in humans. AIM: To explore the effects of anti-PTX3 antibodies in New Zealand Black/White (NZB/NZW F1) mice and their inherent mechanisms of action. MATERIALS AND METHODS: 30 NZB/NZW F1 mice were subdivided into 3 groups of 10 mice each and subcutaneously injected with PTX3, alum and PBS (group 1), alum and PBS (group 2) or PBS alone (group 3), 3 times 3 weeks apart, before development of renal disease. Mice were followed until natural death. Histological analysis and immunohistochemistry were performed on harvested kidneys. Effects of anti-PTX3 antibodies on C1q binding to immobilized PTX3-anti-PTX3 immune complexes were evaluated in vitro using human SLE sera. Qualitative characterization of human IgG anti-PTX3 was performed. RESULTS: Only group 1 mice developed anti-PTX3 antibodies. Anti-dsDNA and anti-C1q antibodies appeared significantly later and at lower levels in group 1 mice vs. controls (p < 0.0001). Proteinuria-free and overall survival were significantly increased in group 1 mice vs. controls (p < 0.05 and p = 0.03, respectively). Histopathological analysis showed that glomerular and tubular PTX3 staining and renal lesions were increased in controls compared with immunized mice. Addition of human SLE sera positive for anti-PTX3 antibodies to C1q and fixed PTX3 interfered with C1q binding to PTX3-anti-PTX3 immune complexes. Qualitative characterization of human IgG anti-PTX3 showed an increased proportion of IgG4. CONCLUSIONS: Anti-PTX3 antibodies delay lupus-like nephritis and prolong survival of NZB/NZW F1 mice. In vitro observations suggest anti-PTX3 antibodies may dampen complement activation via their Fc fragment, likely hindering renal inflammation.


Assuntos
Autoanticorpos/imunologia , Proteína C-Reativa/imunologia , Nefrite Lúpica/imunologia , Componente Amiloide P Sérico/imunologia , Animais , Anti-Inflamatórios/imunologia , Anti-Inflamatórios/farmacologia , Autoanticorpos/sangue , Autoanticorpos/farmacologia , Biomarcadores , Biópsia , Proteína C-Reativa/genética , Proteína C-Reativa/metabolismo , Ativação do Complemento/imunologia , Complemento C1q/imunologia , Modelos Animais de Doenças , Feminino , Humanos , Imunização , Imunoglobulina G/sangue , Imunoglobulina G/imunologia , Imuno-Histoquímica , Testes de Função Renal , Nefrite Lúpica/diagnóstico , Nefrite Lúpica/metabolismo , Nefrite Lúpica/mortalidade , Camundongos , Camundongos Endogâmicos NZB , Substâncias Protetoras , Componente Amiloide P Sérico/genética , Componente Amiloide P Sérico/metabolismo , Fatores de Tempo
9.
Artigo em Inglês | MEDLINE | ID: mdl-26751102

RESUMO

AIMS: To evaluate the feasibility and safety of Roux-en-Y gastrojejunal bypass procedure using a hybrid NOTES-12 mm trocar technique in a survival porcine model. MATERIAL AND METHODS: The procedure was carried out on ten pigs. Two gastroscopes were introduced through the mouth and through a 12 mm trocar, respectively. A mechanical circular gastro-jejunal anastomosis was created by introducing a stapler after the trocar incision was enlarged. A 21 mm EEA OrVil circular stapler was utilized in the first six pigs and a 25 mm one was used in the other four. All pigs were fed beginning 24 hours after the procedure and were euthanized three weeks later. RESULTS: The procedure was successfully completed in all ten animals. The mean length of the skin incision was 2.5 cm. All pigs survived without complications. Endoscopic inspection detected anastomotic strictures in 5/6 of the 21 mm-stapler and in 0/4 of the 25 mm-stapler anastomoses (p < 0.05). CONCLUSION: Roux-en-Y gastrojejunal bypass using a hybrid NOTES-single 12 mm trocar access technique is a simple and safe procedure in a survival porcine model. Functional results need to be evaluated by further studies.


Assuntos
Derivação Gástrica/métodos , Gastroscópios , Cirurgia Endoscópica por Orifício Natural/métodos , Grampeamento Cirúrgico/métodos , Anastomose em-Y de Roux/métodos , Animais , Estudos de Viabilidade , Modelos Animais , Suínos
10.
Ann Rheum Dis ; 74(3): 587-94, 2015 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-24326007

RESUMO

OBJECTIVES: To investigate the effects and mechanisms of action of high-density lipoproteins (HDL) in monosodium urate (MSU) crystal-induced inflammation -that is, gouty inflammation, in vivo. METHODS: Air pouches raised on the backs of mice were injected with MSU crystals or tumour necrosis factor (TNF) in the presence or absence of HDL and/or interleukin (IL)-1 receptor antagonist (IL-1Ra) for 3 h. Leucocyte count and neutrophil percentage in pouch fluids were measured using a haemocytometer and May-Grünwald-Giemsa staining. The cytokine production and expression in the pouch were measured by ELISA and quantitative RT-PCR. RESULTS: MSU crystals induced leucocyte infiltration, mostly neutrophils, and the release of IL-1ß, IL-6, chemokine (C-X-C motif) ligand 1 (CXCL1), chemokine (C-C motif) ligand 2 (CCL2) and IL-1Ra in pouch fluids. TNF remained under the detection limit. MSU crystals triggered IL-1ß, IL-6 and CXCL1 expression in both pouch exudates and membranes, whereas CCL2 and TNF mRNA were not modulated. The co-injection of MSU crystals and HDL inhibited leucocyte influx by 59% and neutrophil infiltration by 83% and, in turn, both protein and mRNA levels of all assessed proinflammatory cytokines were reduced, but not those of IL-1Ra. Similar results were obtained when mice were injected with MSU crystals pretreated with HDL or TNF instead of crystals. When HDL and IL-1Ra were added together they displayed additional inhibition, suggesting different mechanisms of action. CONCLUSIONS: This study demonstrated that HDL may represent an important factor in the modulation of gouty inflammation by acting on both tissue and infiltrating cells -that is, synovial tissue and synovial fluid cells. HDL display anti-inflammatory activity, in part, by interacting with crystals but also by directly acting on cells.


Assuntos
Gota , Inflamação/imunologia , Proteína Antagonista do Receptor de Interleucina 1/farmacologia , Lipoproteínas HDL/farmacologia , Tela Subcutânea/efeitos dos fármacos , Fator de Necrose Tumoral alfa/farmacologia , Ácido Úrico/farmacologia , Animais , Dorso , Quimiocina CCL2/efeitos dos fármacos , Quimiocina CCL2/imunologia , Quimiocina CXCL1/efeitos dos fármacos , Quimiocina CXCL1/imunologia , Modelos Animais de Doenças , Proteína Antagonista do Receptor de Interleucina 1/efeitos dos fármacos , Interleucina-1beta/efeitos dos fármacos , Interleucina-1beta/imunologia , Interleucina-6/imunologia , Leucócitos/efeitos dos fármacos , Leucócitos/imunologia , Camundongos , Tela Subcutânea/imunologia
11.
Front Med (Lausanne) ; 11: 1417318, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38846138

RESUMO

The deposition of calcium pyrophosphate (CPP) crystals in joint tissues causes acute and chronic arthritis that commonly affect the adult and elderly population. Experimental calcium pyrophosphate deposition disease (CPPD) models are divided into genetically modified models and crystal-induced inflammation models. The former do not reproduce phenotypes overlapping with the human disease, while in the latter, the direct injection of crystals into the ankles, dorsal air pouch or peritoneum constitutes a useful and reliable methodology that resembles the CPP induced-inflammatory condition in humans. The translational importance of the induced model is also strengthened by the fact that the key molecular and cellular mediators involved in inflammation are shared between humans and laboratory rodents. Although, in vivo models are indispensable tools for studying the pathogenesis of the CPPD and testing new therapies, their development is still at an early stage and major efforts are needed to address this issue. Here, we analyze the strenghts and limitations of each currently available CPPD in vivo model, and critically discuss their translational value.

12.
Arthritis Rheumatol ; 76(2): 279-284, 2024 02.
Artigo em Inglês | MEDLINE | ID: mdl-37695218

RESUMO

OBJECTIVE: Calcium pyrophosphate (CPP) crystal deposition in the joints is associated with a heterogeneous set of debilitating syndromes characterized by inflammation and pain, for which no effective therapies are currently available. Because we found that the mitochondrial enzyme monoamine oxidase B (MAO-B) plays a fundamental role in promoting inflammatory pathways, this study aims at assessing the efficacy of two clinical-grade inhibitors (iMAO-Bs) in preclinical models of this disease to pave the way for a novel treatment. METHODS: We tested our hypothesis in two murine models of CPP-induced arthritis, by measuring cytokine and chemokine levels, along with immune cell recruitment. iMAO-Bs (rasagiline and safinamide) were administered either before or after crystal injection. To elucidate the molecular mechanism, we challenged in vitro primed macrophages with CPP crystals and assessed the impact of iMAO-Bs in dampening proinflammatory cytokines and in preserving mitochondrial function. RESULTS: Both in preventive and therapeutic in vivo protocols, iMAO-Bs blunted the release of proinflammatory cytokines (interleukin [IL]-6 and IL1-ß) and chemokines (CXCL10, CXCL1, CCL2 and CCL5) (n > 6 mice/group). Importantly, they also significantly reduced ankle swelling (50.3% vs 17.1%; P < 0.001 and 23.1%; P = 0.005 for rasagiline and safinamide, respectively). Mechanistically, iMAO-Bs dampened the burst of reactive oxygen species and the mitochondrial dysfunction triggered by CPP crystals in isolated macrophages. Moreover, iMAO-Bs blunted cytokine secretion and NLRP3 inflammasome activation through inhibition of the NF-κB and STAT3 pathways. CONCLUSION: iMAO-Bs dampen inflammation in murine models of crystal-induced arthropathy, thereby uncovering MAO-B as a promising target to treat these diseases.


Assuntos
Alanina/análogos & derivados , Artrite , Benzilaminas , Pirofosfato de Cálcio , Indanos , Camundongos , Animais , Monoaminoxidase/metabolismo , Citocinas , Inflamação/metabolismo , Artrite/metabolismo , Quimiocinas/metabolismo , Interleucina-6/metabolismo , NF-kappa B/metabolismo , Estresse Oxidativo , Mitocôndrias/metabolismo , Inflamassomos , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo
13.
Nat Aging ; 2024 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-38951692

RESUMO

Accumulating senescent cells within tissues contribute to the progression of aging and age-related diseases. Botanical extracts, rich in phytoconstituents, present a useful resource for discovering therapies that could target senescence and thus improve healthspan. Here, we show that daily oral administration of a standardized extract of Salvia haenkei (Haenkenium (HK)) extended lifespan and healthspan of naturally aged mice. HK treatment inhibited age-induced inflammation, fibrosis and senescence markers across several tissues, as well as increased muscle strength and fur thickness compared with age-matched controls. We also found that HK treatment reduced acutely induced senescence by the chemotherapeutic agent doxorubicin, using p16LUC reporter mice. We profiled the constituent components of HK by mass spectrometry, and identified luteolin-the most concentrated flavonoid in HK-as a senomorphic compound. Mechanistically, by performing surface plasmon resonance and in situ proximity ligation assay, we found that luteolin disrupted the p16-CDK6 interaction. This work demonstrates that administration of HK promotes longevity in mice, possibly by modulating cellular senescence and by disrupting the p16-CDK6 interaction.

14.
Sci Rep ; 13(1): 20692, 2023 11 24.
Artigo em Inglês | MEDLINE | ID: mdl-38001135

RESUMO

Osteoarthritis (OA) is a chronic degenerative joint disease characterized by pain and cartilage damage. Intra-articular (i.a) viscosupplementation with hyaluronic acid (HA) is frequently used for the management of OA. Preclinical studies have reported that bisphosphonates (BPs) may have a therapeutic potential to slow down or reverse the progression of OA. Among these, alendronate (ALN) has demonstrated chondroprotective effects in both in vitro and vivo experiments. This study evaluated the effects of a novel alendronate-hyaluronic acid (ALN-HA) conjugate on an OA in vivo model induced by medial meniscus destabilization (DMM). DMM surgery was performed on the knees of Sprague Dawley rats that received, after four weeks, one intra-articular (i.a.) injection of: (1) ALN-HA; (2) HA; (3) sodium chloride (NaCl). Sham-operated rats were used as control. Allodynia was assessed by Von Frey test. Joint degeneration was evaluated eight weeks after treatment by micro-computed tomography (micro-CT), histology, and immunohistochemistry. Collagen cross-linked C-telopeptides (CTX-I and CTX-II) serum levels were determined by ELISA. Paw withdrawal threshold increased in ALN-HA group when compared to rats treated with NaCl or HA. Micro-CT did not show differences between ALN-HA, HA and NaCl groups. ALN-HA injection produced significant improvements in articular cartilage degeneration showing an OARSI score lower than those of HA and NaCl, and reduced matrix metalloproteinase (MMP)-13, MMP-3, interleukin-6, vascular endothelial growth factor and Caspase-3 expression. CTX-I was reduced after ALN-HA treatment when compared to NaCl. Our results indicate that i.a. use of ALN after conjugation with HA limits OA development and progression in the rat DMM model, and may lead to the development of novel therapeutic strategies in OA management.


Assuntos
Cartilagem Articular , Osteoartrite , Ratos , Animais , Ácido Hialurônico/farmacologia , Alendronato/farmacologia , Alendronato/uso terapêutico , Meniscos Tibiais/patologia , Cloreto de Sódio/farmacologia , Microtomografia por Raio-X , Fator A de Crescimento do Endotélio Vascular/farmacologia , Ratos Sprague-Dawley , Osteoartrite/tratamento farmacológico , Osteoartrite/etiologia , Osteoartrite/patologia , Injeções Intra-Articulares , Cartilagem Articular/patologia , Modelos Animais de Doenças
15.
Surg Endosc ; 26(9): 2527-31, 2012 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-22476830

RESUMO

BACKGROUND: The aim of this study was to evaluate the feasibility of a totally stapled gastrojejunal anastomosis performed using one transabdominal 12-mm trocar and a gastroscope in a porcine model. METHODS: The procedure was carried out on six domestic pigs weighing 45 kg using a hybrid technique with a gastroscope and a 12-mm Hasson trocar, positioned in the left hypochondrium. At the end of the procedure a mechanical circular 21-mm gastrojejunal anastomosis was performed by inserting the stapler through a small gastrotomy after enlarging the trocar incision. RESULTS: In all six cases the procedure was completed through a single 3 cm abdominal incision and without complications. The mean operating time was 2 h, and endoscopic investigation showed that the anastomoses were intact, patent, and airtight. CONCLUSIONS: Totally stapled gastrojejunal anastomosis using a hybrid NOTES-single 12-mm trocar approach is a feasible procedure in the porcine model. Further survival studies are warranted, particularly to evaluate the functional results of this procedure.


Assuntos
Gastroscópios , Jejuno/cirurgia , Cirurgia Endoscópica por Orifício Natural/instrumentação , Estômago/cirurgia , Grampeamento Cirúrgico , Anastomose Cirúrgica/instrumentação , Anastomose Cirúrgica/métodos , Animais , Desenho de Equipamento , Estudos de Viabilidade , Feminino , Modelos Animais , Suínos
16.
Exp Biol Med (Maywood) ; 247(12): 1061-1066, 2022 06.
Artigo em Inglês | MEDLINE | ID: mdl-35470716

RESUMO

STING (stimulator of interferon genes) has been recognized as an important signaling molecule in the innate immune response to cytosolic nucleic acids. Although it has been proposed that STING signaling pathway may play a pathogenic role in developing autoimmune and autoinflammatory diseases, its involvement in rheumatic disease processes remains to be elucidated. Here, we evaluated STING protein levels, expression and relationship with inflammatory parameters in synovial fluid (SF) of patients with psoriatic arthritis (PsA), rheumatoid arthritis (RA), gout, calcium pyrophosphate crystal-induced arthritis (CPP-IA), osteoarthritis (OA), and OA with CPP crystals (OA + CPP). The correlation with its negative regulator, nuclear factor erythroid 2-related factor 2 (Nrf2), was also investigated. SFs from 72 patients were analyzed for white blood cell (WBC) count, polymorphonuclear cell percentage (PMN%), and IL-1ß, IL-6, IL-8, extra- and intracellular STING levels. STING and Nrf2 expression was also determined. WBC count and PMN% were greater in SF from inflammatory arthritis, while they were lower in OA groups. RA and gouty SFs have the highest levels of IL-1ß, IL-8, and IL-6; while OA and OA + CPP showed the lowest concentrations. Gout and RA had the highest intracellular STING levels, while extracellular STING was greater in CPP-IA and OA SFs. STING was not detectable in PsA. STING mRNA was lower in PsA than other arthritides. Nrf2 mRNA was not detectable in OA. This study determines the presence of STING in SF of different arthritides, except for PsA, and suggests that it may be involved in pathogenesis and progression of arthropathies.


Assuntos
Artrite Psoriásica , Artrite Reumatoide , Gota , Proteínas de Membrana , Osteoartrite , Artrite Psoriásica/metabolismo , Gota/metabolismo , Humanos , Interleucina-1beta/metabolismo , Interleucina-6/metabolismo , Interleucina-8/metabolismo , Proteínas de Membrana/metabolismo , Fator 2 Relacionado a NF-E2/metabolismo , Osteoartrite/metabolismo , Líquido Sinovial/química
17.
Expert Opin Biol Ther ; 22(4): 509-517, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-34860146

RESUMO

INTRODUCTION: Near-Infrared Photoimmunotherapy (NIR-PIT) is a novel molecularly targeted phototherapy. This technique is based on a conjugate of a near-infrared photo-inducible molecule (antibody-photon absorber conjugate, APC) and a monoclonal antibody that targets a tumor-specific antigen. To date, this novel approach has been successfully applied to several types of cancer. AREAS COVERED: The authors discuss the possible use of NIR-PIT for the management of skin diseases, with special attention given to squamous cell carcinomas, advanced melanomas, and primary cutaneous lymphomas. EXPERT OPINION: NIR-PIT may be an attractive strategy for the treatment of skin disorders. The main advantage of NIR-PIT therapy is its low toxicity to healthy tissues. Cutaneous lymphocyte antigen is a potential molecular target for NIR-PIT for both cutaneous T-cell lymphomas and inflammatory skin disorders.


Assuntos
Imunoterapia , Dermatopatias , Animais , Linhagem Celular Tumoral , Humanos , Imunoterapia/métodos , Camundongos , Camundongos Nus , Fármacos Fotossensibilizantes/uso terapêutico , Fototerapia/métodos , Dermatopatias/tratamento farmacológico
18.
Medicine (Baltimore) ; 101(46): e31833, 2022 Nov 18.
Artigo em Inglês | MEDLINE | ID: mdl-36401489

RESUMO

INTRODUCTION: Vitiligo is an acquired chronic pigmentation disorder of the skin. Even if the role of the immune system seems to be well established, new pathogenetic hypothesis are rising in these years. It has been recently suggested by the development of an animal model that a protein called Melanoma Inhibitory Activity (MIA) is involved in the pathogenesis of vitiligo. This protein interacts with the adhesion molecules expressed on the melanocytes causing its detachment from extracellular matrix proteins and creating the depigmented macules. A topical preparation based on oligopeptides able to inhibit the actions of the MIA protein has been introduced to the market, claiming activity on vitiligo. PATIENT CONCERNS AND DIAGNOSIS: A patient affected by non-segmental vitiligo for 10 years, recalcitrant to any treatment (such as steroids, immunomodulators, kellin, UVB-NB and UVA) came to our observation. INTERVENTIONS: We used this topical preparation containing the MIA inhibitors peptides in selected areas (face and sides of the trunk) leaving untreated other areas as control (legs and arms). The patient was required to be sun exposed or to have some UVA sessions during the treatment to stimulate the melanocytes replications. OUTCOMES: After 9 months of treatments, he recovered from 50% to 80% of repigmentation only in the treated areas, without any side effects locally or systemically. CONCLUSION: Even if other studies are required to better determine the efficacy of this approach, this first observation about the use of the MIA-inhibitors peptides for the treatment of non-segmental vitiligo indicates that this topical preparation containing the MIA inhibitors peptides could be a very promising option for the cure of this disease.


Assuntos
Melanoma , Terapia Ultravioleta , Vitiligo , Masculino , Humanos , Vitiligo/etiologia , Terapia Ultravioleta/efeitos adversos , Resultado do Tratamento , Peptídeos/uso terapêutico
19.
Surg Endosc ; 25(9): 3022-7, 2011 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-21484531

RESUMO

BACKGROUND: Natural orifice transluminal endoscopic surgery (NOTES), a new frontier of minimally invasive surgery, uses the body's natural orifices to create an access for surgical procedures. This study aimed to verify the technical feasibility of ileorectal bypass performed entirely through a transanal access. METHODS: The procedure was performed on 10 domestic pigs, after which they were killed. A transanal endoscopic microsurgery (TEM) device and endoscopic and laparoscopic instruments were used. RESULTS: The findings demonstrated that an ileorectal bypass through a transanal access is feasible. The principal steps of a standardized transanal procedure are as follows: confirm a rectal perforation above the peritoneal reflection, perform peritoneoscopy using a standard gastroscope, grasp the small bowel with retrieval forceps and pull it through the rectal hole, suture the ileum and the rectum together using a TEM device, open the ileal loop, and perform endoscopic exploration. Satisfactory anastomosis and no signs of procedure-related complications were confirmed by a post procedure laparotomy. CONCLUSIONS: Ileorectal bypass through a transanal access is technically feasible in a porcine model, and although still at an experimental stage, it could become a surgical option for treating some types of colonic strictures.


Assuntos
Íleo/cirurgia , Cirurgia Endoscópica por Orifício Natural/métodos , Reto/cirurgia , Canal Anal , Anastomose Cirúrgica , Animais , Doenças do Colo/cirurgia , Constrição Patológica/cirurgia , Desenho de Equipamento , Estudos de Viabilidade , Feminino , Modelos Animais , Suínos
20.
Expert Rev Clin Immunol ; 17(7): 773-787, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-34053376

RESUMO

Introduction: Accumulation of abnormal crystals in the body, derived from endogenous or exogenous materials can drive a wide spectrum of inflammatory disease states. It is well established that intra-articular deposition of monosodium urate (MSU) and calcium pyrophoshate (CPP) crystals contributes to joint destruction through pro-inflammatory processes.Areas covered: This review will focus on current understanding and recent novelty about the mechanisms and the clinical implications of the inflammation induced by MSU and CPP crystals.Expert opinion: Advances in molecular biology reveal that at the base of the inflammatory cascade, stimulated by MSU or CPP crystals, there are many complex cellular mechanisms mainly involving the NLRP3 inflammasome, the hallmark of autoinflammatory syndromes. The extensive studies carried out through in vitro and in vivo models along with a better clinical definition of the disease has led to an optimized use of existing drugs and the introduction of novel therapeutic strategies. In particular, the identification of IL-1 as the most important target in gout and pseudogout has made it possible to expand the pharmacological indications of anti-IL-1 biological drugs, opening new therapeutic perspectives for patients.


Assuntos
Gota , Macrófagos , Humanos , Inflamassomos , Inflamação , Interleucina-1beta , Ácido Úrico/farmacologia
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