RESUMO
INTRODUCTION: Environmental sustainability (ES) in healthcare is an important current challenge in the wider context of reducing the environmental impacts of human activity. Identifying key routes to making clinical radiology and radiotherapy (CRR) practice more environmentally sustainable will provide a framework for delivering greener clinical services. This study sought to explore and integrate current evidence regarding ES in CRR departments, to provide a comprehensive guide for greener practice, education, and research. METHODS: A systematic literature search and review of studies of diverse evidence including qualitative, quantitative, and mixed methods approach was completed across six databases. The Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) guidelines and the Quality Assessment Tool for Studies with Diverse Designs (QATSDD) was used to assess the included studies. A result-based convergent data synthesis approach was employed to integrate the study findings. RESULTS: A total of 162 articles were identified. After applying a predefined exclusion criterion, fourteen articles were eligible. Three themes emerged as potentially important areas of CRR practice that contribute to environmental footprint: energy consumption and data storage practices; usage of clinical consumables and waste management practices; and CRR activities related to staff and patient travel. CONCLUSIONS: Key components of CRR practice that influence environmental impact were identified, which could serve as a framework for exploring greener practice interventions. Widening the scope of research, education and awareness is imperative to providing a holistic appreciation of the environmental burden of healthcare. IMPLICATIONS FOR PRACTICE: Encouraging eco-friendly travelling options, leveraging artificial Intelligence (AI) and CRR specific policies to optimise utilisation of resources such as energy and radiopharmaceuticals are recommended for a greener practice.
Assuntos
Inteligência Artificial , Radioterapia (Especialidade) , Humanos , Atenção à SaúdeRESUMO
PURPOSE: Radiosurgery (SRS) is an effective treatment option for brain metastases (BMs). Long-term results of the first worldwide experience with a mono-isocentric, non-coplanar, linac-based stereotactic technique in the treatment of multiple BMs are reported. METHODS: patients with multiple BMs, life expectancy > 3 months, and good performance status (≤ 2) were treated with simultaneous SRS with volumetric modulated arc technique. Data were retrospectively evaluated. RESULTS: 172 patients accounting for 1079 BMs were treated at our institution from 2017 to 2020. The median number of treated metastases was 4 (range 2-22). Primary tumor histology was: lung (44.8%), breast (32%), and melanoma (9.4%). The 2-year LPFS was 71.6%, respectively. A biological effective dose (BED) ≥ 51.3 Gy10 correlated with higher local control. Uncontrolled systemic disease and melanoma histology were independent prognostic factors correlated with decreased iPFS. Patients with > 10 BMs had a trend towards shorter iPFS (p = 0.055). 31 patients received multiple SRS courses (2-7) in case of intracranial progression. The median iOS was 22.4 months. Brainstem metastases and total PTV > 7.1 cc correlated with shorter iOS. The 1- and 2-year WBRT-free survival was 83.2% and 61.1%, respectively. CONCLUSION: Long-term results in a large patient population treated with a mono-isocentric, dedicated technique demonstrated its effectiveness and safety also in the case of multiple courses. The shortened treatment time and the possibility to safely spare healthy brain tissue allows the safe treatment of patients with a large number of metastases and to deliver multiple courses of SRS. In selected cases, the administration of WBRT can be delayed.
Assuntos
Neoplasias Encefálicas/radioterapia , Neoplasias Encefálicas/secundário , Irradiação Craniana/métodos , Radiocirurgia/métodos , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias Encefálicas/mortalidade , Neoplasias da Mama/patologia , Estudos de Coortes , Irradiação Craniana/efeitos adversos , Irradiação Craniana/instrumentação , Feminino , Humanos , Estimativa de Kaplan-Meier , Neoplasias Pulmonares/patologia , Masculino , Melanoma/radioterapia , Melanoma/secundário , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/radioterapia , Órgãos em Risco/efeitos da radiação , Intervalo Livre de Progressão , Lesões por Radiação/prevenção & controle , Radiocirurgia/efeitos adversos , Radiocirurgia/instrumentação , Dosagem Radioterapêutica , Eficiência Biológica Relativa , Estudos Retrospectivos , Fatores de Tempo , Resultado do TratamentoRESUMO
In the present work, an existing vegetation/air/litter/soil model (SoilPlusVeg) was modified to improve organic chemical fate description in terrestrial/aquatic ecosystems accounting for horizontal and vertical particulate organic carbon (POC) transport in soil. The model was applied to simulate the fate of three pesticides (terbuthylazine, chlorpyrifos and etofenprox), characterized by increasing hydrophobicity (log KOW from about 3 to 7), in the soil compartment and more specifically, their movement towards surface and groundwater through infiltration and runoff processes. The aim was to evaluate the role of dissolved organic carbon (DOC) and POC in the soil in influencing the peak exposure of pesticides in terrestrial/aquatic ecosystems. Simulation results showed that while terbuthylazine and chlorpyrifos dominated the free water phase (CW-FREE) of soil, etofenprox was mainly present in soil porewater as POC associated chemical. This resulted in an increase of this highly hydrophobic chemical movement towards groundwater and surface water, up to a factor of 40. The present work highlighted the importance of DOC and POC as an enhancer of mobility in the water of poor or very little mobile chemicals. Further studies are necessary to evaluate the bioavailability change with time and parameterize this process in multimedia fate models.
Assuntos
Carbono/química , Herbicidas/análise , Inseticidas/análise , Material Particulado/química , Poluentes do Solo/análise , Clorpirifos/análise , Clorpirifos/química , Herbicidas/química , Interações Hidrofóbicas e Hidrofílicas , Inseticidas/química , Modelos Teóricos , Piretrinas/análise , Piretrinas/química , Relação Quantitativa Estrutura-Atividade , Poluentes do Solo/química , Triazinas/análise , Triazinas/químicaRESUMO
Cardiovascular disease in women differs in clinical presentation, pathophysiology and prognosis from that in men. The role of estrogens and androgens may help explain such sex dimorphisms, being involved in cardiac function, endothelial function and vascular tone. In particular, the cardioprotective effect of estrogen replacement therapy is observed in postmenopausal women in a time-dependent manner, i.e. when it is initiated at their first menopausal symptoms. Postmenopausal women, beyond aged men, may also benefit from testosterone supplementation therapy. Testosterone has been found to be an effective and safe therapy for elderly women with chronic heart failure. However, further studies are needed to clarify doses and routes of administration of androgens in postmenopausal women.
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Doenças Cardiovasculares/fisiopatologia , Terapia de Reposição de Estrogênios/métodos , Caracteres Sexuais , Idoso , Idoso de 80 Anos ou mais , Androgênios/uso terapêutico , Doenças Cardiovasculares/prevenção & controle , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Pós-Menopausa/fisiologia , Testosterona/uso terapêutico , Fatores de TempoRESUMO
BACKGROUND: Information on the impact of other cancers (OCs) in long-term survivors (LTSs) of chronic lymphocytic leukemia (CLL) is limited. PATIENTS AND METHODS: Patients with CLL who survived >10 years were defined as LTSs of CLL. We calculated standardized incidence ratios (SIRs) to compare the incidence of OC in LTS of CLL versus the general population. A multivariable model was used to identify independent predictors of OC. Overall survival was analyzed as a function of the presence of OC. RESULTS: Among 797 LTSs of CLL, the cumulative frequency of OC was 36%, similar between 570 patients (72%) who required treatment for CLL (TRT) and 227 (28%) who remained untreated (UT). The most common OC in both groups was non-melanoma skin cancer, followed by prostate cancer, breast cancer, melanoma, lung cancer, and leukemia in TRT patients, and by prostate cancer, breast cancer, melanoma, lung cancer, and gastrointestinal tumors in the UT group. The SIR for all OC was 1.2 (P = 0.034). It was higher in males (SIR 1.31; P = 0.013) and patients <60 years (SIR 1.27; P = 0.027). A higher SIR was shown for secondary leukemia, melanoma, and head-and-neck cancers, whereas a lower SIR was found for gastrointestinal and bladder cancers. Independent predictors of OC development were advanced age, male gender, and lower platelets. The survival of patients with OC was 16.2 months and that of patients without OC 22.9 years. CONCLUSIONS: LTSs of CLL have an increased incidence of OC compared with the general population. CLL therapy is not a risk factor for OC in LTSs of CLL. The presence of an OC in these patients may be associated with shorter survival.
Assuntos
Sobreviventes de Câncer , Leucemia Linfocítica Crônica de Células B/epidemiologia , Segunda Neoplasia Primária/epidemiologia , Prognóstico , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/epidemiologia , Neoplasias da Mama/patologia , Feminino , Neoplasias Gastrointestinais/tratamento farmacológico , Neoplasias Gastrointestinais/epidemiologia , Neoplasias Gastrointestinais/patologia , Humanos , Leucemia Linfocítica Crônica de Células B/tratamento farmacológico , Leucemia Linfocítica Crônica de Células B/patologia , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/epidemiologia , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Segunda Neoplasia Primária/tratamento farmacológico , Segunda Neoplasia Primária/patologia , Neoplasias da Próstata/tratamento farmacológico , Neoplasias da Próstata/epidemiologia , Neoplasias da Próstata/patologia , Fatores de Risco , Programa de SEERRESUMO
The ecto-enzyme CD38 is gaining momentum as a novel therapeutic target for patients with hematological malignancies, with several anti-CD38 monoclonal antibodies in clinical trials with promising results. In chronic lymphocytic leukemia (CLL) CD38 is a marker of unfavorable prognosis and a central factor in the pathogenetic network underlying the disease: activation of CD38 regulates genetic pathways involved in proliferation and movement. Here we show that CD38 is enzymatically active in primary CLL cells and that its forced expression increases disease aggressiveness in a xenograft model. The effect is completely lost when using an enzyme-deficient version of CD38 with a single amino-acid mutation. Through the enzymatic conversion of NAD into ADPR (ADP-ribose) and cADPR (cyclic ADP-ribose), CD38 increases cytoplasmic Ca(2+) concentrations, positively influencing proliferation and signaling mediated via chemokine receptors or integrins. Consistently, inhibition of the enzymatic activities of CD38 using the flavonoid kuromanin blocks CLL chemotaxis, adhesion and in vivo homing. In a short-term xenograft model using primary cells, kuromanin treatment traps CLL cells in the blood, thereby increasing responses to chemotherapy. These results suggest that monoclonal antibodies that block the enzymatic activities of CD38 or enzyme inhibitors may prove therapeutically useful.
Assuntos
ADP-Ribosil Ciclase 1/genética , ADP-Ribosil Ciclase 1/metabolismo , Leucemia Linfocítica Crônica de Células B/metabolismo , Leucemia Linfocítica Crônica de Células B/terapia , Animais , Antocianinas/farmacologia , Anticorpos Monoclonais/farmacologia , Cálcio/metabolismo , Adesão Celular , Movimento Celular , Proliferação de Células , Quimiotaxia , Flavonoides/farmacologia , Perfilação da Expressão Gênica , Glucosídeos/farmacologia , Humanos , Integrinas/metabolismo , Masculino , Microdomínios da Membrana , Camundongos , Camundongos Endogâmicos NOD , Camundongos SCID , Camundongos Transgênicos , Microscopia de Fluorescência , Mutação , Transplante de Neoplasias , Molécula-1 de Adesão Celular Endotelial a Plaquetas/metabolismo , Prognóstico , Ligação Proteica , Receptores de Quimiocinas/metabolismo , Transdução de SinaisRESUMO
The active metabolite of vitamin D, 1α, 25 dihydroxyvitamin D3 (calcitriol) is classically known to regulate calcium and phosphate homeostasis and bone mineralization. In addition, calcitriol has also been documented to act as a potent anticancer agent in multiple cell culture and animal models of cancer. However, major side effects, such as hypercalcemia, hinder broad-spectrum therapeutic uses of calcitriol in cancer chemotherapy. Synthesis of calcitriol analogues with the same or increased antiproliferative and pro-differentiating activities, and with reduced undesired effects on calcium and bone metabolism, is getting significant attention towards rational therapeutics to treat cancer. In this regard, phosphonate analogues have been shown to display a certain degree of dissociation between the vitamin D activity in vitro and undesired hypercalcemia in vivo. However, few phosphonates have been described in the literature and fewer of them tested for antitumoral effects. Our group has synthesized a novel vitamin D analogue (EM1) bearing an alkynylphosphonate moiety that combines the low calcemic properties of phosphonates with the decreased metabolic inactivation due to the presence of a triple bond between C-23 and C-24. Biological assays demonstrated that this analogue has potent antiproliferative effects in a wide panel of tumour cell lines, even in those resistant to calcitriol treatment. Importantly, EM1 does not show toxic effects in animals, even administered at high doses and for extended periods of time. In the current review we discuss the effects and the potential application in cancer of vitamin D and its derivatives, with an emphasis on phosphonate analogues.
Assuntos
Antineoplásicos/química , Antineoplásicos/farmacologia , Di-Hidroxicolecalciferóis/química , Di-Hidroxicolecalciferóis/farmacologia , Neoplasias/tratamento farmacológico , Organofosfonatos/química , Animais , HumanosRESUMO
Androgens play a pivotal role in cardiovascular function and their effects differ between men and women. In postmenopausal women, testosterone replacement within physiological levels is associated with overall well-being. However, a definitive explanation as to how androgens have an impact on cardiovascular health in postmenopausal women and whether they may be used for cardiovascular treatment has yet to be established. With these aims, a systematic review of the existing studies on the link between androgens and cardiovascular disease and the effects of testosterone therapy on cardiovascular outcomes in postmenopausal women has been conducted. The few existing studies on cardiovascular outcomes in postmenopausal women indicate no effect or a deleterious effect of increasing androgens and increased cardiovascular risk. However, there is evidence of a favorable effect of androgens on surrogate cardiovascular markers in postmenopausal women, such as high density lipoprotein cholesterol, total cholesterol, body fat mass and triglycerides. Further studies are therefore needed to clarify the impact of therapy with androgens on cardiovascular health in postmenopausal women. The cardiovascular effect of testosterone or methyltestosterone with or without concomitant estrogens needs to be elucidated.
Assuntos
Androgênios , Doenças Cardiovasculares , Pós-Menopausa , Doenças Cardiovasculares/induzido quimicamente , Doenças Cardiovasculares/prevenção & controle , Sistema Cardiovascular/efeitos dos fármacos , Terapia de Reposição de Estrogênios , Feminino , Humanos , MEDLINE , Metiltestosterona/uso terapêutico , Pessoa de Meia-Idade , Fatores de Risco , Testosterona/efeitos adversos , Testosterona/fisiologia , Testosterona/uso terapêuticoRESUMO
OBJECTIVE: To evaluate whether non-contrast-enhanced computed tomography (CT) as a stand-alone imaging modality can be used to define the Hansen type I intervertebral disc herniation (IVDH) lesion and also whether the Hounsfield unit (HU) value of herniated disc is relevant to clinical duration and to histopathological chronicity of extruded disc material. METHODS: Information from a series of CT studies performed on 45 dogs with a presumptive diagnosis of Hansen type I IVDH was used. Clinical duration of IVDH was estimated based on time from onset of signs per owner communication to time of surgical intervention. Hansen type I IVDH was confirmed at surgery. Retrieved herniated disc was histologically examined. The HU values were analyzed to correlate the clinical duration and histopathological chronicity of the disc lesion. RESULTS: Non-contrast-enhanced CT provided sufficient diagnostic information to plan surgery in 42 of 45 dogs (93%). The value of the HU was significantly higher in clinically chronic cases (n = 12) compared to peracute cases (n = 11) (p <0.05). The HU values were significantly correlated with clinical duration (r = 0.482, p = 0.0008) and histopathological chronicity of the herniated disc (r = 0.408, p = 0.0056). CONCLUSION: Consistent with the previous reports, the use of non-contrast-enhanced CT alone was sufficient for the diagnosis and surgical planning in most patients with Hansen type I IVDH in the thoracolumbar spine. In addition, the present study suggested that HU values on CT images may be useful in the evaluation of disease chronicity of IVDH.
Assuntos
Meios de Contraste/administração & dosagem , Doenças do Cão/diagnóstico por imagem , Deslocamento do Disco Intervertebral/veterinária , Animais , Doenças do Cão/patologia , Doenças do Cão/cirurgia , Cães , Feminino , Deslocamento do Disco Intervertebral/diagnóstico por imagem , Deslocamento do Disco Intervertebral/patologia , Deslocamento do Disco Intervertebral/cirurgia , Masculino , RadiografiaRESUMO
We report a case of hypercalcemia in a female patient who was restarted on hemodialysis 22 years after renal transplantation. Graft biopsy showed chronic post-transplant nephropathy. Treatment with immunosuppressants and steroids was maintained owing to residual graft function. She was then given oral paracalcitol 1 µg/d for secondary hyperparathyroidism (iPTH 850 pg/mL) and her transplant medication was reduced and then discontinued. After this, the patient referred widespread joint pain, especially in the hips and subsequently presented with erythema nodosum. She also developed hypercalcemia and hyperphosphatemia which persisted after stopping paracalcitol. The clinical picture of increased serum calcitriol, with depressed PTH, suggested sarcoidosis, despite normal ACE levels, a chest X-ray and skin biopsy confirmed the diagnosis, and the patient was started on prednisone 50 mg/day, resulting in prompt normalization of both symptoms and blood chemistry. This is a rare case of hypercalcemia secondary to sarcoidosis in an uremic patient. The sarcoidosis was most likely suppressed by the transplant therapy and rapidly developed after this was suspended. Prompt diagnosis resulted in a good therapeutic response.
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Hipercalcemia , Diálise Renal , Adulto , Feminino , Humanos , Hipercalcemia/diagnóstico , Hipercalcemia/tratamento farmacológicoRESUMO
The cardiovascular effects of hormone replacement therapy (HRT) have been the subject of much debate since the initial findings from the Women's Health Initiative (WHI) were reported. However, re-analyses of WHI results have suggested that the association between HRT use and cardiovascular risk is influenced by several factors and that, among these, age and time since menopause may play a key role. Preclinical and human studies have shown differential effects of estrogen on the vasculature of healthy subjects compared with those with existing atherosclerosis. Indeed, while HRT has shown no protective effects in the presence of established atherosclerotic disease, it may have beneficial or neutral effects on healthy vasculature or early atherosclerosis. However, the final cardiovascular effects of estrogens in non-hysterectomized women are influenced by the type, dosage, and route of administration of the progestin used in association. The results of ongoing studies on the timing of HRT initiation will help women make better informed decisions regarding their menopausal health. Current treatment guidelines recommend initiation of HRT in recently postmenopausal women for the relief of vasomotor symptoms.
Assuntos
Doenças Cardiovasculares/epidemiologia , Estrogênios/administração & dosagem , Terapia de Reposição Hormonal/estatística & dados numéricos , Pós-Menopausa/efeitos dos fármacos , Progestinas/administração & dosagem , Fatores Etários , Doenças Cardiovasculares/etiologia , Esquema de Medicação , Feminino , Humanos , Pessoa de Meia-Idade , Fatores de RiscoRESUMO
Tumor cells in chronic lymphocytic leukemia (CLL) are more prone to apoptosis when cultured ex vivo, because they lack prosurvival signals furnished in vivo via B-cell receptor (BCR)-dependent and -independent pathways. This study compared the susceptibility of unmutated (UM) and mutated (M) CLL B cells to spontaneous apoptosis and prosurvival signals. UM CLL B cells showed a significantly higher rate of spontaneous apoptosis than M CLL B cells. Nuclear factor-kB (NF-kB) was rapidly inactivated, and B-cell leukemia/lymphoma 2 (Bcl-2) expression progressively down-regulated in the UM CLL B cells. CD40-Ligand, interleukin-4 and stromal cells significantly improved their viability and partially recovered Bcl-2, but not NF-kB expression. Peripheral blood mononuclear cells also offered protection of UM CLL B cells, and recovered both NF-kB and Bcl-2 expression. T cells, rather than nurse-like cells, were responsible for protecting UM CLL B cells by means of cell-to-cell contact and soluble factors. Despite their more aggressive features, UM CLL B cells are more susceptible to spontaneous apoptosis and depend from environmental prosurvival signals. This vulnerability of UM CLL B cells can be exploited as a selective target of therapeutic interventions.
Assuntos
Apoptose , Linfócitos B/patologia , Cadeias Pesadas de Imunoglobulinas/genética , Região Variável de Imunoglobulina/genética , Leucemia Linfocítica Crônica de Células B/genética , Leucemia Linfocítica Crônica de Células B/patologia , Mutação/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Linfócitos B/metabolismo , Western Blotting , Ligante de CD40/metabolismo , Ensaio de Desvio de Mobilidade Eletroforética , Feminino , Humanos , Leucemia Linfocítica Crônica de Células B/imunologia , Masculino , Pessoa de Meia-Idade , NF-kappa B/genética , NF-kappa B/metabolismo , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Receptores de Antígenos de Linfócitos B/metabolismo , Transdução de Sinais , Células Tumorais CultivadasRESUMO
OBJECTIVES: To describe the effects of low-dose hormonal replacement therapy (HRT) on quality of life, metabolic parameters and blood pressure in postmenopausal women. METHODS: Postmenopausal women untreated with HRT or sex steroids in the previous 12 months were randomized to treatment with 17ß-estradiol (1 mg/day) plus drospirenone (2 mg/day) (E2+DRSP) or to calcium (controls). Quality of life was evaluated by the Women's Health Questionnaire (WHQ) at baseline and after 6 and 12 weeks of treatment. Anthropometric, metabolic and blood pressure measurements were performed before and after 3 months of treatment. RESULTS: WHQ domain scores for vasomotor and somatic symptoms, anxiety/fears, depressed mood, sexual behavior and sleep problems decreased significantly in the E2+DRSP group relative to both baseline and control values (pâ<â0.05). Body mass index was unchanged, while waist circumference decreased significantly (pâ<â0.001) after E2+DRSP treatment. Significant decreases were also observed after E2+DRSP treatment for blood insulin values, insulin resistance (estimated by homeostasis model assessment) and systolic blood pressure (pâ<â0.001, all). In subjects with systolic blood pressureâ<â130 mmHg at baseline, no changes in systolic values were registered, while women with baseline high-normal systolic blood pressure (130-139 mmHg) showed significant decreases (pâ<â0.0069). E2+DRSP did not modify diastolic blood pressure values. In the calcium-treatment group, there were no significant changes in WHQ scores or in anthropometric, metabolic or blood pressure measurements. CONCLUSION: In postmenopausal women, E2+DRSP administration improves vasomotor symptoms and general aspects of quality of life and may positively influence cardiovascular risk factors.
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Androstenos/administração & dosagem , Estradiol/administração & dosagem , Estrogênios/administração & dosagem , Terapia de Reposição Hormonal , Antagonistas de Receptores de Mineralocorticoides/administração & dosagem , Qualidade de Vida , Ansiedade , Pressão Sanguínea , Depressão/epidemiologia , Medo , Feminino , Humanos , Insulina/sangue , Resistência à Insulina , Pessoa de Meia-Idade , Pós-Menopausa , Estudos Prospectivos , Comportamento Sexual , Transtornos do Sono-Vigília/epidemiologia , Sístole , Circunferência da CinturaRESUMO
BACKGROUND: Middle-aged women have a lower prevalence of coronary artery disease (CAD) compared with age-matched men, but mechanisms underlying this phenomenon remain controversial. To verify whether there is a link between circulating endothelial progenitor cells (EPCs) and gender-specific difference of CAD, we compared subpopulations of EPCs among postmenopausal normal women, patients with CAD, and age-matched men. METHODS: We studied 71 consecutive middle-aged patients with stable CAD (30 postmenopausal women and 41 men) and 40 middle-aged normal controls (20 postmenopausal women and 20 men). Blood samples were drawn at time of coronary angiography and subpopulations of EPCs were measured by flow cytometry. RESULTS: Women and men with CAD had similar age, risk factors, clinical presentation, left ventricular function, extension of CAD, and medical therapy at time of coronary angiography. Hematologic analysis showed that men and women with CAD had similar white cell count, mononuclear cells, and subpopulations of EPCs. Postmenopausal normal women, conversely, had significantly higher absolute numbers of CD34+, CD133+, CD105+ and CD14+ cells than other groups. CONCLUSIONS: Increased numbers of subpopulations of EPCs in normal postmenopausal women might contribute to the gender-specific difference of CAD in middle age. Lack of difference in EPCs between women and men with CAD suggests that stem cells become unable to play a protective role when the disease is clinically evident.
Assuntos
Células Endoteliais/metabolismo , Pós-Menopausa/metabolismo , Células-Tronco/metabolismo , Antígeno AC133 , Antígenos CD/metabolismo , Estudos de Casos e Controles , Angiografia Coronária , Doença da Artéria Coronariana/metabolismo , Endoglina , Feminino , Citometria de Fluxo , Glicoproteínas/metabolismo , Humanos , Masculino , Pessoa de Meia-Idade , Peptídeos/metabolismo , Receptores de Superfície Celular/metabolismoRESUMO
OBJECTIVE: Diabetic patients have a reduced endothelial response to phosphodiesterase-5 inhibitors. The aim of this study was to determine the effects of chronic therapy with sildenafil on endothelial function in patients with Type 2 diabetes mellitus (DM2). METHODS: In a double-blind, placebo-controlled parallel design, 20 patients without erectile dysfunction randomly received a loading dose of sildenafil (100 mg) for 3 days, followed by either sildenafil 25 mg three times a day (t.d.s.) for 4 weeks or sildenafil 25 mg t.d.s. for 4 days followed by placebo t.d.s. for 3 weeks. RESULTS: After 1 week, flow-mediated dilatation (FMD) improved significantly (> 50% compared with baseline) in patients allocated to both sildenafil arms (62 and 64%, respectively). In patients allocated to chronic sildenafil, a progressive increase in percentage of patients with FMD improvement was noted (78, 86 and 94% at 2, 3 and 4 weeks, respectively) while a progressive decrease in the placebo group occurred (45, 18 and 6% at 2, 3 and 4 weeks, respectively). At the end of the study, a significant improvement in FMD compared with baseline was noted after chronic sildenafil (FMD from 6.8 +/- 0.5 to 12.5 +/- 0.7%, P = 0.01 vs. baseline). A decrease in endothelin-1 levels and an increase in nitrite/nitrate levels were found after chronic sildenafil; significant changes from baseline in C-reactive protein, interleukin 6, intercellular adhesion molecule and vascular adhesion molecule levels were also found. CONCLUSIONS: In DM2 patients, daily sildenafil administration improves endothelial function and reduces markers of vascular inflammation, suggesting that the diabetes-induced impairment of endothelial function may be improved by prolonged phosphodiesterase-5 inhibition.
Assuntos
Diabetes Mellitus Tipo 2/tratamento farmacológico , Angiopatias Diabéticas/tratamento farmacológico , Endotélio Vascular/efeitos dos fármacos , Inibidores de Fosfodiesterase/administração & dosagem , Piperazinas/administração & dosagem , Sulfonas/administração & dosagem , Vasodilatadores/administração & dosagem , Adulto , Idoso , Biomarcadores/metabolismo , Artéria Braquial/fisiopatologia , Proteína C-Reativa/metabolismo , Moléculas de Adesão Celular/metabolismo , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/fisiopatologia , Angiopatias Diabéticas/sangue , Angiopatias Diabéticas/fisiopatologia , Relação Dose-Resposta a Droga , Método Duplo-Cego , Humanos , Interleucina-6/metabolismo , Masculino , Pessoa de Meia-Idade , Purinas/administração & dosagem , Citrato de Sildenafila , Resultado do Tratamento , Vasodilatação/efeitos dos fármacosRESUMO
Menopause is a risk factor for cardiovascular disease (CVD) because estrogen withdrawal has a detrimental effect on cardiovascular function and metabolism. The menopause compounds many traditional CVD risk factors, including changes in body fat distribution from a gynoid to an android pattern, reduced glucose tolerance, abnormal plasma lipids, increased blood pressure, increased sympathetic tone, endothelial dysfunction and vascular inflammation. Many CVD risk factors have different impacts in men and women. In postmenopausal women, treatment of arterial hypertension and glucose intolerance should be priorities. Observational studies and randomized clinical trials suggest that hormone replacement therapy (HRT) started soon after the menopause may confer cardiovascular benefit. In contrast to other synthetic progestogens used in continuous combined HRTs, the unique progestogen drospirenone has antialdosterone properties. Drospirenone can therefore counteract the water- and sodium-retaining effects of the estrogen component of HRT via the renin-angiotensin-aldosterone system, which may otherwise result in weight gain and raised blood pressure. As a continuous combined HRT with 17beta-estradiol, drospirenone has been shown to significantly reduce blood pressure in postmenopausal women with elevated blood pressure, but not in normotensive women. Therefore, in addition to relieving climacteric symptoms, drospirenone/17beta-estradiol may offer further benefits in postmenopausal women, such as improved CVD risk profile.
Assuntos
Androstenos/uso terapêutico , Doenças Cardiovasculares/etiologia , Terapia de Reposição de Estrogênios , Hipertensão/complicações , Menopausa/fisiologia , Antagonistas de Receptores de Mineralocorticoides/uso terapêutico , Diabetes Mellitus/fisiopatologia , Feminino , Humanos , Hipertensão/tratamento farmacológico , Fatores de Risco , Aumento de PesoRESUMO
Historically, high androgen levels have been linked with an increased risk for coronary artery disease (CAD). However, more recent data suggest that low androgen levels are associated with adverse cardiovascular risk factors, including an atherogenic lipid profile, obesity and insulin resistance. The aim of the present study was to evaluate the relationship between plasma sex hormone levels and presence and degree of CAD in patients undergoing coronary angiography and in matched controls. We evaluated 129 consecutive male patients (mean age 58+/-4 years, range 43-72 years) referred for diagnostic coronary angiography because of symptoms suggestive of CAD, but without acute coronary syndromes or prior diagnosis of hypogonadism. Patients were matched with healthy volunteers. Out of 129 patients, 119 had proven CAD; in particular, 32 of them had one, 63 had two and 24 had three vessel disease, respectively. Patients had significantly lower levels of testosterone than controls (9.8+/-6.5 and 13.5+/-5.4 nmol/l, P<0.01) and higher levels of gonadotrophin (12.0+/-1.5 vs 6.6+/-1.9 IU/l and 7.9+/-2.1 vs 4.4+/-1.4, P<0.01 for follicle-stimulating hormone and luteinizing hormone, respectively). Also, both bioavailable testosterone and plasma oestradiol levels were lower in patients as compared to controls (0.84+/-0.45 vs 1.19+/-0.74 nmol/l, P<0.01 and 10.7+/-1.4 vs 13.3+/-3.5 pg/ml, P<0.05). Hormone levels were compared in cases with one, two or three vessel disease showing significant differences associated with increasing severity of coronary disease. An inverse relationship between the degree of CAD and plasma testosterone levels was found (r=-0.52, P<0.01). In conclusion, patients with CAD have lower testosterone and oestradiol levels than healthy controls. These changes are inversely correlated to the degree of CAD, suggesting that low plasma testosterone may be involved with the increased risk of CAD in men.
Assuntos
Angina Pectoris/sangue , Doença da Artéria Coronariana/sangue , Testosterona/sangue , Adulto , Idoso , Estudos de Casos e Controles , Angiografia Coronária , Doença da Artéria Coronariana/diagnóstico por imagem , Estradiol/sangue , Hormônio Foliculoestimulante/sangue , Humanos , Hormônio Luteinizante/sangue , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Valores de ReferênciaRESUMO
BACKGROUND: The cervico-oculo-acoustic syndrome comprises Klippel-Feil anomaly, sensorineural deafness and Duane's retraction syndrome. Polygenic, autosomal dominant, and X-linked inheritance have been hypothesized. The disorder has rarely been reported in males. CASE REPORT: A 42-year-old male, born of consanguineous parents, presented with Duane's syndrome, mixed hearing loss, C2-C3 fusion, neck stiffness, and right facial palsy. A variety of cardiac, neurological and urogenital anomalies occurred in his relatives. The electro-oculographic studies showed impaired abduction and adduction of the right eye and impaired abduction of the left eye. Vergence, vertical eye movements and peripheral vestibular responses were normal. Somatosensory evoked potentials showed absence of the N13 peak and brainstem auditory evoked potentials bilateral delay of the I-III interpeak latencies. CONCLUSIONS: Consanguinity of the patient's parents, not previously reported, suggests autosomal recessive inheritance, but autosomal dominant inheritance is indicated by the family history. The pattern of the oculomotor deficit is consistent with bilateral dysplasia of the abducens nuclei with preserved internuclear neurons in the right abducens nucleus. Neurophysiological investigations revealed lower brainstem and cervical cord involvement.