RESUMO
Chronic venous disease (CVD) and its most frightening complication, chronic venous ulceration (CVU), represent an important socioeconomic burden in the western world. Metalloproteinases have been identified in the pathogenesis of several vascular diseases such as venous problems. The aim of this study was to evaluate a broad range of metalloproteinases, such as matrix metalloproteinases (MMPs), ADAMs (a disintegrin and metalloproteinases) and ADAMTSs (a disintegrin and metalloproteinases with thrombospondin motifs) and their inhibitors, tissue inhibitor of metalloproteinases (TIMPs) and a related protein, neutrophil gelatinase-associated lipocalin (NGAL), in patients with CVD in order to correlate their serum levels with each stage of the disease. We performed a multicenter open-label study that comprised the enrolment of 541 patients with CVD of clinical stages C1-C6, (178 males, 363 females; mean age 57·29, median age 53·72, age range 29-81); 29 subjects without CVD were included in this study (9 males and 20 females; mean age 54·44, median age 50, age range 28-84) as the control group. Enzyme-linked immunosorbent assay (ELISA) was performed for measuring serum levels of proteases and related proteins. The study found that the serum elevation of MMP-2, ADAMTS-1 and ADAMTS-7 appeared to be correlated with the initial stages of CVD, whereas the serum elevation of MMP-1, MMP-8, MMP-9, NGAL, ADAM-10, ADAM-17 and ADAMTS-4 was particularly involved in skin change complications. This study showed that each stage of CVD may be described by particular patterns of metalloproteinases, and this may have therapeutic implications in discovering new targets and new drugs for the treatment of CVD.
Assuntos
Metaloproteinases da Matriz/sangue , Úlcera Varicosa/fisiopatologia , Cicatrização/fisiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Doença Crônica , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , Itália , Masculino , Pessoa de Meia-IdadeRESUMO
Post-thrombotic syndrome (PTS) is a condition that can develop in about half of the patients with deep vein thrombosis (DVT) of lower limbs. In the present study, we evaluated the expression of inflammatory biomarkers in the early phases of DVT and their correlation with the onset of PTS. Patients were enrolled after the first episode of DVT and were followed up for 1, 4, 8, 12 and 18 months. At each visit, blood sample was collected to evaluate plasma levels of matrix metalloproteinase (MMP)-1,-2,-3,-7,-8 and -9 MMP inhibitors, TIMP-1,-2, neutrophil gelatinase-associated lipocalin (NGAL) and cytokines TNF-α and IL-6. Analysis included 201 patients [86 males (42·79%) and 115 females (57·21%); average age 56 ± 7 years]. Of the 201 patients, 47 (23·38%; 21 males, 26 females) developed PTS during the follow-up period. The control group was made up of 60 individuals without DVT (22 males and 38 females). High plasma levels of MMPs, NGAL and cytokines were recorded during the acute phase after DVT. Moreover, patients with PTS showed higher levels of MMP-1 and MMP-8 with respect to patients without PTS. There is a close relationship between DVT, the individual risk of PTS and specific biomarkers such as MMPs and other related molecules, which may help guide prevention and therapy based on the patient's individual risk profile, and has to be studied in future.
Assuntos
Metaloproteinases da Matriz/sangue , Síndrome Pós-Trombótica/sangue , Inibidor Tecidual de Metaloproteinase-1/sangue , Trombose Venosa/sangue , Análise de Variância , Biomarcadores/sangue , Progressão da Doença , Ensaio de Imunoadsorção Enzimática , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Síndrome Pós-Trombótica/fisiopatologia , Valor Preditivo dos Testes , Modelos de Riscos Proporcionais , Estudos Prospectivos , Medição de Risco , Índice de Gravidade de Doença , Trombose Venosa/complicações , Trombose Venosa/fisiopatologiaRESUMO
Ischaemia reperfusion (I/R) injury refers to tissue damage caused when blood supply returns to the tissue after a period of ischaemia. Matrix metalloproteinases (MMPs), neutrophil gelatinase-associated lipocalin (NGAL) and cytokines are biomarkers involved in several vascular complications. The aim of this study was to evaluate the role of MMPs, NGAL and inflammatory cytokines in I/R syndrome. We conducted an open label, multicentric, parallel group study, between January 2010 and December 2013. Patients with acute limb ischaemia were enrolled in this study and were divided into two groups: (i) those subjected to fasciotomy and (ii) those not subjected to fasciotomy, according to the onset of compartment syndrome. Plasma and tissue values of MMPs and NGAL as well as plasma cytokines were evaluated. MMPs, NGAL and cytokine levels were higher in patients with compartment syndrome. Biomarkers evaluated in this study may be used in the future as predictors of I/R injury severity and its possible evolution towards post-reperfusion syndrome.
Assuntos
Síndromes Compartimentais/metabolismo , Lipocalina-2/metabolismo , Extremidade Inferior/irrigação sanguínea , Metaloproteinases da Matriz/metabolismo , Traumatismo por Reperfusão/metabolismo , Doença Aguda , Idoso , Biomarcadores/metabolismo , Estudos de Casos e Controles , Síndromes Compartimentais/etiologia , Síndromes Compartimentais/cirurgia , Citocinas/sangue , Fasciotomia , Feminino , Humanos , Masculino , Traumatismo por Reperfusão/complicações , SíndromeRESUMO
Chronic venous ulcer (CVU) represents a dreaded complication of chronic venous disease (CVD). The onset of infection may further delay the already precarious healing process in such lesions. Some evidences have shown that matrix metalloproteinases (MMPs) are involved and play a central role in both CVUs and infectious diseases. Two groups of patients were enrolled to evaluate the expression of MMPs in infected ulcers and the levels of inflammatory cytokines as well as their prevalence. Group I comprised 63 patients (36 females and 27 males with a median age of 68·7 years) with infected CVUs, and group II (control group) comprised 66 patients (38 females and 28 males with a median age of 61·2 years) with non-infected venous ulcers. MMP evaluation and dosage of inflammatory cytokines in plasma and wound fluid was performed by means of enzyme-linked immunosorbent assay test; protein extraction and immunoblot analysis were performed on biopsied wounds. The first three most common agents involved in CVUs were Staphylococcus aureus (38·09%), Corynebacterium striatum (19·05%) and Pseudomonas aeruginosa (12·7%). In this study, we documented overall higher levels of MMP-1 and MMP-8 in patients with infected ulcers compared to those with uninfected ulcers that showed higher levels of MMP-2 and MMP-9. We also documented higher levels of interleukin (IL)-1, IL-6, IL-8, vascular endothelial growth factor and tumour necrosis factor-alpha in patients with infected ulcers with respect to those with uninfected ulcers, documenting a possible association between infection, MMP activation, cytokine secretions and symptoms. The present results could represent the basis for further studies on drug use that mimic the action of tissue inhibitors of metalloproteinases in order to make infected CVU more manageable.
Assuntos
Citocinas/metabolismo , Metaloproteinases da Matriz Secretadas/metabolismo , Úlcera Varicosa/metabolismo , Infecção dos Ferimentos/metabolismo , Idoso , Western Blotting , Doença Crônica , Ensaio de Imunoadsorção Enzimática , Feminino , Infecções por Bactérias Gram-Negativas/complicações , Infecções por Bactérias Gram-Positivas/complicações , Humanos , Masculino , Pessoa de Meia-Idade , Infecção dos Ferimentos/microbiologiaRESUMO
The mainstay of treatment of chronic venous ulceration (CVU), as also suggested by current treatment guidelines for chronic venous disease (CVD), is represented by surgery and compression therapy for which there is strong evidence of their role in clinically relevant improvement in wound healing and also in the reduction of CVU recurrence, but no information is available as to whether or not these treatments provide effective protection from the onset of CVU. In our study, we have followed, for a median time of 13 years, a total of 3947 patients with CVD at classes C2-C3 of CEAP classification, treated with our treatment protocol (surgery and compression therapy) in order to track the natural history of these patients with regards to CVU development. We identified four groups of patients: 2354 patients (59·64%) (Group A) fully adherent to protocols; 848 patients (21·48%) (Group B) fully adherent to surgery and non-compliant to compression therapy; 432 patients (10·95%) (Group C) fully adherent to compression therapy and non-compliant to surgery; and 313 patients (7·93%) (Group D) non-compliant to either treatments. Regardless of compliance to treatments, the ulcer development rates were very similar between groups (range: 3·23-4.79%), with no statistical significance (P = 0·1522). Currents treatments used in the early stages of CVD appear to have no effects to progression to CVU. Additional longitudinal studies are required to confirm these findings.
Assuntos
Bandagens Compressivas , Úlcera Varicosa/prevenção & controle , Úlcera Varicosa/terapia , Varizes/cirurgia , Cicatrização/fisiologia , Idoso , Doença Crônica , Estudos de Coortes , Terapia Combinada , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Prospectivos , Medição de Risco , Resultado do Tratamento , Úlcera Varicosa/etiologia , Varizes/complicações , Varizes/diagnóstico , Procedimentos Cirúrgicos Vasculares/métodosRESUMO
Chronic leg ulcers (CLUs) are a common occurrence in the western population and are associated with a negative impact on the quality of life of patients. They also cause a substantial burden on the health budget. The pathogenesis of leg ulceration is quite heterogeneous, and chronic venous ulceration (CVU) is the most common manifestation representing the main complication of chronic venous disease (CVD). Prevention strategies and early identification of the risk represent the best form of management. Fuzzy logic is a flexible mathematical system that has proved to be a powerful tool for decision-making systems and pattern classification systems in medicine. In this study, we have elaborated a computerised prediction system for chronic leg ulcers (PredyCLU) based on fuzzy logic, which was retrospectively applied on a multicentre population of 77 patients with CVD. This evaluation system produced reliable risk score patterns and served effectively as a stratification risk tool in patients with CVD who were at the risk of developing CVUs.
Assuntos
Lógica Fuzzy , Úlcera da Perna/epidemiologia , Flebite/epidemiologia , Idoso , Idoso de 80 Anos ou mais , Estudos de Casos e Controles , Doença Crônica , Feminino , Humanos , Incidência , Itália/epidemiologia , Úlcera da Perna/diagnóstico , Úlcera da Perna/terapia , Masculino , Flebite/diagnóstico , Valor Preditivo dos Testes , Estudos Retrospectivos , Medição de Risco , Índice de Gravidade de Doença , Úlcera Varicosa/diagnóstico , Úlcera Varicosa/epidemiologia , Cicatrização/fisiologiaRESUMO
Pathophysiological events involved in the onset of chronic venous ulceration (CVU) are inflammation, activation of polymorphonucleates (PMNs) and secretion of proteases such as matrix metalloproteinases (MMPs), which degrade extracellular matrix (ECM) that is a support for vascular and tissutal wall. MMPs, neutrophil gelatinase-associated lipocalin (NGAL) and inflammatory cytokines are overexpressed in CVUs and they could play a central role in pathophysiological mechanisms of skin lesion and delayed wound healing. Bioflavonoids, such as diosmin and other compounds, appear to have several provessel function activities including anti-inflammatory, antioxidant and phlebotonic effects and are widely used in the treatment of chronic venous disease (CVD)-related problems. In this article, we evaluated the effects of Axaven(®) , a new nutraceutical on both clinical and molecular parameters in patients with CVUs. During the study period, 83 patients with CVUs of both sexes were enrolled and divided into two groups: group A (treated group): 25 females and 19 males (median age is 67·7 years) received standard treatment (compression therapy and surgical correction of superficial venous incompetence) + Axaven(®) once a day for 8 months as adjunctive treatment. Group B (control group): 24 females and 15 males (median age is 65·2 years) were treated only with basic treatment according to their clinical conditions. In our study, the administration of Axaven(®) in patients with CVUs was able to decrease inflammatory cytokines, MMPs and NGAL, inducing an improvement of both symptoms with an increase of the speed of wound healing.
Assuntos
Suplementos Nutricionais , Úlcera Varicosa/terapia , Proteínas de Fase Aguda , Idoso , Idoso de 80 Anos ou mais , Doença Crônica/terapia , Bandagens Compressivas , Citocinas/sangue , Feminino , Humanos , Lipocalina-2 , Lipocalinas/sangue , Masculino , Metaloproteinases da Matriz/sangue , Pessoa de Meia-Idade , Proteínas Proto-Oncogênicas/sangue , CicatrizaçãoRESUMO
BACKGROUND: Absorbable sutures are not generally accepted by most vascular surgeons for the fear of breakage of the suture line and the risk of aneurysmal formation, except in cases of paediatric surgery or in case of infections. Aim of this study is to provide evidence of safety and efficacy of the use of absorbable suture materials in carotid surgery. PATIENTS AND METHODS: In an 11 year period, 1126 patients (659 male [58.5%], 467 female [41.5%], median age 72) underwent carotid endarterectomy for carotid stenosis by either conventional with primary closure (cCEA) or eversion (eCEA) techniques. Patients were randomised into two groups according to the type of suture material used. In Group A, absorbable suture material (polyglycolic acid) was used and in Group B non-absorbable suture material (polypropylene) was used. Primary end-point was to compare severe restenosis and aneurysmal formation rates between the two groups of patients. For statistical analysis only cases with a minimum period of follow-up of 12 months were considered. RESULTS: A total of 868 surgical procedures were considered for data analysis. Median follow-up was 6 years (range 1-10 years). The rate of postoperative complications was better for group A for both cCEA and eCEA procedures: 3.5% and 2.0% for group A, respectively, and 11.8% and 12.9% for group B, respectively. CONCLUSIONS: In carotid surgery, the use of absorbable suture material seems to be safe and effective and with a general lower complications rate compared to the use of non-absorbable materials.
Assuntos
Materiais Biocompatíveis , Artérias Carótidas/cirurgia , Estenose das Carótidas/cirurgia , Endarterectomia das Carótidas , Técnicas de Sutura/instrumentação , Suturas , Idoso , Aneurisma/diagnóstico , Aneurisma/etiologia , Estenose das Carótidas/diagnóstico , Desenho de Equipamento , Feminino , Humanos , Itália , Estimativa de Kaplan-Meier , Masculino , Ácido Poliglicólico , Polipropilenos , Recidiva , Fatores de Risco , Índice de Gravidade de Doença , Fatores de Tempo , Resultado do TratamentoRESUMO
Peripheral vascular disease is a common complication of type 2 diabetes and is often more severe and diffuse than in non-diabetic individuals with a higher risk of major amputations in the lower limbs. Diabetic foot revascularisation using both traditional bypass surgery and endovascular therapy are often burdened by the failure and the inevitable subsequent massive amputation. In this study, we examined the clinical response of diabetic patients with critical limb ischaemia and extended ischaemic wounds, treated with a new angiosome-based revascularisation technique. In a 3-year period, nine diabetic patients with imminent amputation threatening and foot ulcers with no feasible arterial revascularisation options were treated by the angiosome-based surgical technique by means of deep vein arterialisation. The postoperative tcPO2 evaluation showed a mean increase in the cutaneous oxygen tension in all patients treated. The overall survival rates were 88·88%, 88·88% and 77·77% at 12, 24 and 36 months, respectively. Limb salvage was 100% at 1 year and steady at 88·88% thereafter. Surgical deep venous arterialisation might be considered as an extreme alternative to attempt tissue preservation in limbs unfit for conventional arterial revascularisations. This technique would give advantages to the patients in terms of better compliance to the minor amputations and thus avoiding major limb amputations.
Assuntos
Pé Diabético/cirurgia , Salvamento de Membro/métodos , Idoso , Idoso de 80 Anos ou mais , Derivação Arteriovenosa Cirúrgica , Implante de Prótese Vascular , Estudos de Coortes , Feminino , Artéria Femoral/cirurgia , Humanos , Masculino , Pessoa de Meia-Idade , Veias/cirurgiaRESUMO
Diabetic patients are at high risk of foot ulcerations that may lead to limb amputations with important socio-economic impact. Peripheral vascular disease may be frequently associated in diabetes mellitus type II with its main symptom, intermittent claudication. Many studies reported the known efficacy of cilostazol in treating vascular claudication. Metalloproteinase-9 (MMP-9) seems to be a biochemical marker implicated in chronic wounds and in particular in diabetic foot ulcers. Cilostazol appears to have a lowering effect on MMP-9 levels and this may suggest a beneficial effect in order to prevent or retard the onset of foot ulcer in diabetic patients. In our study, two groups of diabetic patients with peripheral vascular disease were divided into two groups according to the presence of claudication in order to receive cilostazol. Group A (31 patients without claudication) were not eligible to receive cilostazol whereas Group B (47 patients with claudication) received cilostazol administration for 24 weeks (100 mg orally twice daily). Median follow up was of 16 months. During the follow up, 4·25% of patients of Group B and 35·48% of patients of Group A (P < 0·01) showed onset of foot ulceration. Although further randomised and controlled studies are required cilostazol seems to show beneficial effects for primary prevention of diabetic foot ulcers.
Assuntos
Úlcera do Pé/prevenção & controle , Claudicação Intermitente/complicações , Tetrazóis/administração & dosagem , Idoso , Cilostazol , Relação Dose-Resposta a Droga , Feminino , Seguimentos , Úlcera do Pé/enzimologia , Úlcera do Pé/etiologia , Humanos , Claudicação Intermitente/etiologia , Masculino , Metaloproteinase 9 da Matriz/sangue , Pessoa de Meia-Idade , Estudos Retrospectivos , Resultado do Tratamento , Vasodilatadores/administração & dosagemRESUMO
Pressure ulcers (PUs) are a common problem in critically ill patients admitted to the intensive care units (ICUs) and they account for more than 70% of patients with low serum albumin at admission. The aim of this study was to test the efficacy of intravenous administration of albumin in patients with low serum albumin < 3·3 g/dl. In a 1-year period, a total of 73 patients were admitted to the ICU (males 45, 61·64% and females 28, 38·36%); of these, 21 patients were admitted with hypoalbuminaemia (serum albumin < 3·3 g/dl) and randomised into two groups: 11 patients were treated with 25 g intravenous albumin for the first 3 days within the first week of ICU stay (group A) and 10 patients did not receive albumin (group B). Three patients (27·27%) showed the onset of PUs in group A, whereas seven patients (70%) showed the onset of PUs within the first 7 days of stay in group B. Moreover, ulcers of group B were more severe than those of group A. This study shows that intravenous administration of albumin reduces the onset of PUs in patients admitted to the ICU and in some cases it also reduces the risk of progression to advanced stages of PUs.
Assuntos
Albuminas/análise , Cuidados Críticos/métodos , Estado Terminal/terapia , Hipoalbuminemia/complicações , Úlcera por Pressão/etiologia , Úlcera por Pressão/prevenção & controle , Albumina Sérica/uso terapêutico , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/sangue , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Distribuição Aleatória , Fatores de RiscoRESUMO
Venous ulcers are common, especially in the elderly, accounting for more than 50% of all lower extremity ulcers with important socioeconomic problems. Improving extracellular matrix functioning, by heparin administration, seems to be a way to support wound healing. A total of 284 patients with venous ulcers were recruited in a 4-year period. All patients were subjected to the most appropriate treatment after considering their preference (compression therapy followed or not by vein surgery). Patients were randomised into two groups of 142 persons in each (group A and group B as cases and controls, respectively). Patients of group A, in addition to the basic treatment as described earlier, received administration of nadroparin 2850 IU/0.3 ml through subcutaneous injection once a day for 12 months, whereas group B patients received basic treatment alone. Healing was assessed by means of direct ulcer tracing with computerised planimetry. Group A showed a healing rate of 83·80% at 12 months, whereas that of group B was 60·56%. Results by age group surprisingly showed that the group of older patients took the most advantage from long-term treatment with low molecular weight heparin; this group also had lowest recurrence rate.
Assuntos
Anticoagulantes/uso terapêutico , Nadroparina/uso terapêutico , Úlcera Varicosa/tratamento farmacológico , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Doença Crônica , Esquema de Medicação , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Recidiva , Resultado do Tratamento , Úlcera Varicosa/complicações , Úlcera Varicosa/patologia , CicatrizaçãoRESUMO
Venous ulcers are common, with an overall prevalence of up to 2% in the general population of western countries, and have significant socioeconomic impact. Matrix metalloproteinases (MMPs) are involved in the alteration of extracellular matrix that could lead to venous ulceration. Sixty-four patients with venous ulcers were recruited in a 22-month period. All patients were subjected to the most appropriate treatment considering also the patient's wishes (compression therapy followed or not by vein surgery). Patients were randomised into two groups of 32 persons in each (groups A and B). Patients of group A in addition to the basic treatment, described above, received the administration of oral low doses of doxycycline 20 mg b.i.d. for 3 months, whereas patients of group B received basic treatment only. Healing was assessed by means of direct ulcer tracing with computerised planimetry. Group A showed a higher healing rate compared with group B. In group B, the lower healing rate was related to higher levels of MMP-9; neutrophil gelatinase-associated lipocalin and vascular endothelial growth factor, documented in plasma; wound fluid and biopsies executed and compared between both groups. Pharmacological treatments, as doxycycline administration, which by means of its immunomodulatory and anti-inflammatory actions, through the inhibition of MMP, could improve extracellular matrix functioning and represent a possible solution to support wound healing.
Assuntos
Antibacterianos/uso terapêutico , Doxiciclina/uso terapêutico , Úlcera Varicosa/tratamento farmacológico , Proteínas de Fase Aguda/metabolismo , Adulto , Doença Crônica , Feminino , Humanos , Lipocalina-2 , Lipocalinas/metabolismo , Masculino , Metaloproteinase 9 da Matriz/metabolismo , Pessoa de Meia-Idade , Proteínas Proto-Oncogênicas/metabolismo , Resultado do Tratamento , Úlcera Varicosa/metabolismo , Úlcera Varicosa/patologia , Fator A de Crescimento do Endotélio Vascular/metabolismo , CicatrizaçãoRESUMO
Chronic venous ulceration (CVU) of the lower limbs is a common condition affecting 1% of the adult population in Western countries, which is burdened with a high complication rate and a marked reduction in the quality of life often due to prolonged healing time. Several metalloproteinases (MMPs) such as MMP-9 together with neutrophil gelatinase-associated lipocalin (NGAL) appear to be involved in the onset and healing phases of venous ulcer, but it is still unclear how many biochemical components are responsible for prolonged healing time in those ulcers. In this study, we evaluate the role of MMP-1 and MMP-8 in long lasting and refractory venous ulcers. In a 2-year period we enroled 45 patients (28 female and 17 male, median age 65) with CVU. The enroled population was divided into two groups: group I were patients with non-healing ulcers (ulcers that had failed to heal for more than 2 months despite appropriate treatments) and group II were patients with healing ulcers (ulcers in healing phases). MMP-1 and MMP-8 were measured in fluids and tissues of healing and non-healing ulcers by means of enzyme-linked immunosorbent assay (ELISA) and Western blot analysis, respectively. In particular the patterns of the collagenases MMP-1 and MMP-8 in healing wounds were distinct, with MMP-8 appearing in significantly greater amounts especially in the non-healing group. Our findings suggest that MMP-1, and MMP-8 are overexpressed in long lasting CVU. Therefore, this dysregulation may represent the main cause of the pathogenesis of non-healing CVU.
Assuntos
Metaloproteinase 1 da Matriz/metabolismo , Metaloproteinase 8 da Matriz/metabolismo , Úlcera Varicosa/enzimologia , Cicatrização/fisiologia , Idoso , Estudos de Casos e Controles , Doença Crônica , Exsudatos e Transudatos/enzimologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Úlcera Varicosa/patologia , Úlcera Varicosa/terapiaRESUMO
Chronic venous ulceration (CVU) is the major cause of chronic wounds of lower extremities, and is a part of the complex of chronic venous disease. Previous studies have hypothesised that several thrombophilic factors, such as hyperhomocysteinaemia (HHcy), may be associated with chronic venous ulcers. In this study, we evaluated the prevalence of HHcy in patients with venous leg ulcers and the effect of folic acid therapy on wound healing. Eighty-seven patients with venous leg ulcers were enrolled in this study to calculate the prevalence of HHcy in this population. All patients underwent basic treatment for venous ulcer (compression therapy ± surgical procedures). Patients with HHcy (group A) received basic treatment and administered folic acid (1·2 mg/day for 12 months) and patients without HHcy (group B) received only basic treatment. Healing was assessed by means of computerised planimetry analysis. The prevalence of HHcy among patients with chronic venous ulcer enrolled in this study was 62·06%. Healing rate was significantly higher (P < 0·05) in group A patients (78·75%) compared with group B patients (63·33%). This study suggests a close association, statistically significant, between HHcy and CVU. Homocysteine-lowering therapy with folic acid seems to expedite wound healing. Despite these aspects, the exact molecular mechanisms between homocysteine and CVU have not been clearly defined and further studies are needed.
Assuntos
Ácido Fólico/uso terapêutico , Hiper-Homocisteinemia/tratamento farmacológico , Hiper-Homocisteinemia/epidemiologia , Úlcera Varicosa/complicações , Úlcera Varicosa/tratamento farmacológico , Complexo Vitamínico B/uso terapêutico , Idoso , Idoso de 80 Anos ou mais , Doença Crônica , Estudos de Coortes , Feminino , Humanos , Hiper-Homocisteinemia/diagnóstico , Masculino , Pessoa de Meia-Idade , Prevalência , Úlcera Varicosa/sangue , CicatrizaçãoRESUMO
BACKGROUND: Varicocele, inguinal hernia, and clinical manifestations related to chronic venous disorders are often associated, and collagen metabolism together with metalloproteinases (MMPs) alterations may be implicated. The aim of this study was to analyze the relationship between these factors. METHODS: We evaluated tissue and plasma samples from patients with varicocele, inguinal hernia, and great saphenous vein reflux, who underwent surgical treatment for their conditions. We then analyzed and correlated these findings with MMP levels. RESULTS: Significantly higher levels of MMP-1, -2, -12, and -13 were found in patients with inguinal hernia. MMP-9 levels were higher in patients with at least two of the conditions indicated. CONCLUSION: MMP-9 seems to be the common thread in various clinical conditions and is related to a more general and progressive disorder of collagen metabolism.
Assuntos
Hérnia Inguinal/enzimologia , Metaloproteinase 9 da Matriz/sangue , Veia Safena/enzimologia , Varicocele/enzimologia , Insuficiência Venosa/enzimologia , Adulto , Biomarcadores/sangue , Doença Crônica , Feminino , Hérnia Inguinal/sangue , Hérnia Inguinal/diagnóstico , Humanos , Masculino , Pessoa de Meia-Idade , Regulação para Cima , Varicocele/sangue , Varicocele/diagnóstico , Insuficiência Venosa/sangue , Insuficiência Venosa/diagnósticoRESUMO
BACKGROUND: The carotid body tumors (CBTs) are relatively rare neoplasms and may present into benign or life threatening malignant forms. Matrix metalloproteinases (MMPs) are often involved in vascular and cancer diseases. Objective of this study is to study the relationship between CBTs and MMPs. METHODS: We performed a multicenter study on 14 patients with CBTs. All tumors were resected. For each patient, we evaluated the MMPs' levels in both plasma (enzyme-linked immunosorbent assay [ELISA] test) and tissue samples (Western blot analysis). These MMPs' plasma levels were compared with the MMPs' plasma levels of healthy patients. RESULTS: Eleven patients had benign CBTs, whereas 3 patients had malignant CBTs. ELISA findings revealed significant higher levels (P < 0.01) of MMP-1, -2, -3, -8, and -9 in patients with paraganglioma with respect to healthy patients. Patients with malignant CBTs showed significantly higher levels (P < 0.01) of MMP-1, -2, and -3 compared with patients with benign CBTs. CONCLUSIONS: Because this is an exploratory study, the experience on this casuistry showed that MMPs' evaluation may help clinicians and surgeons to formulate a more rapid and clear diagnosis on CBTs' behavior. However, other studies on a large group of patients may be useful to validate these observations.
Assuntos
Tumor do Corpo Carotídeo/enzimologia , Metaloproteinases da Matriz/metabolismo , Paraganglioma/enzimologia , Adulto , Idoso , Biomarcadores/metabolismo , Biópsia , Western Blotting , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
Background. Cerebral aneurysms are relatively common in adults, with a prevalence ranging between 1% and 5%. Subarachnoid hemorrhage, following aneurismal rupture, is a major cause of death and disability in these patients. Matrix Metalloproteinases (MMPs) and Neutrophil Gelatinase-Associated Lipocalin (NGAL) seem to be involved in the pathogenesis and in the clinical course of aneurysms. In this study, we evaluated the relationship between tissue and plasma levels of MMP-9 and NGAL in patient with ruptured and unruptured middle cerebral artery aneurysms. Methods. An open label study was conducted on 7 patients with middle cerebral aneurysms. Three patients had ruptured aneurysms (Group I) and four patients had unruptured aneurysms (Group II). All patients underwent aneurysm clipping. Plasma levels of MMP-9 and NGAL were evaluated through ELISA Test. During the surgery, biopsies of the aneurysmatic arteries were taken and frozen (- 80°C) for Western blot evaluation of MMPs and NGAL expression. Four healthy volunteers (Group III) represented the control group for ELISA testing. Results. Both plasma MMP-9 and NGAL levels were significantly high in aneurysmatic patients respect to those of control patients, and these levels were higher (P < 0.01) in patients with ruptured aneurysms respect to patients with unruptured aneurysms (P < 0.01). The latest findings were similarly evident in tissue evaluation of MMP-9 and NGAL between ruptured and unruptured aneurysms. Conclusion. This study suggests that MMP-9 and NGAL plasma levels may be useful to predict the clinical course of a cerebral aneurysms in order to evaluate the progression of the disease and the tendency of an aneurysm to rupture.
RESUMO
Critically ill patients are at high risk of developing pressure ulcers (PUs) and patients who develop PUs remain significantly longer in the intensive care unit (ICU) with significantly increased morbidity and mortality. Therefore, the identification of patients at truly increased risk is important. The aim of this study was to examine the association of low serum albumin present at admission in ICU patients with the onset of PUs. We conducted a retrospective cohort study on 610 patients who were admitted to intensive care unit. Level of serum albumin and other biochemical indices, recorded at the time of admission, were collected. We collected information about PU occurrence after admission and conducted a statistical analysis with biomarkers at ICU admission and during hospital stay. The incidence of PU in the ICUs was 31% and about 70% of patients with PUs had hypoalbuminemia at admission. The lowest values of serum albumin in patients with PUs were directly proportional to the severity of ulcers. In this study, we found a close association between serum albumin and PUs. In fact serum albumin was negatively correlated with PU and may be considered one of the independent determinants of PU occurrence in patients admitted to ICUs.
Assuntos
Úlcera por Pressão/diagnóstico , Úlcera por Pressão/etiologia , Albumina Sérica/deficiência , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/sangue , Estudos de Coortes , Feminino , Humanos , Unidades de Terapia Intensiva , Masculino , Pessoa de Meia-Idade , Úlcera por Pressão/sangue , Estudos Retrospectivos , Fatores de Risco , Adulto JovemRESUMO
Venous ulcers are related to dysfunctions in extracellular matrix. Both matrix metalloproteinases (MMP) and neutrophil gelatinase-associated lipocalin (NGAL) could play a role in the healing process in patients with chronic venous ulcers. We evaluated the role of MMP-9 and NGAL in the healing process in venous ulceration. We performed an open-label, parallel groups, single clinical center study. Patients with chronic venous leg ulcers represented the test group (Group I), whereas patients without chronic ulcers represented the control group (Group II). In Group I plasma and wound fluid samples were collected at the time of admission, at the time of the surgery, and at the follow-up, while ulcer tissues were taken at the time of the surgery. In Group II, plasma and wound fluid were collected at admission and at the time of the surgery, whereas skin tissues were collected at the time of the surgery. Enzyme-linked immunosorbent assay test was used to evaluate the levels of MMP-9 and NGAL in plasma and wound fluid, whereas Western blot analysis was performed to estimate the expression of MMP-9 and NGAL in tissues. Enzyme-linked immunosorbent assay tests revealed significantly higher levels of MMP-9 and NGAL in both plasma and wound fluid of patients with ulcers compared to patients without ulcers (p < 0.01). Moreover, Western blot analysis documented an increased expression of MMP-9 and NGAL in biopsy tissue of patients with ulcers compared to patients without ulcers (p < 0.01). In conclusion MMP-9 and NGAL may correlate with the clinical course of venous ulcers.