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1.
Eur Rev Med Pharmacol Sci ; 28(14): 4038-4045, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-39081153

RESUMO

OBJECTIVE: Fibromyalgia (FM) is a multifactorial disease characterized principally by chronic, widespread pain impairing a patient's quality of life. The management of FM requires a multidisciplinary approach that combines pharmacological and non-pharmacological strategies. Growing evidence suggests a potential beneficial role of micronutrients such as minerals and vitamins. Overall, the role of these supplements remains controversial, but clinical trials on vitamin D, vitamin B12, magnesium, and iron supplementation seem to provide promising results. The aim of this study was to investigate their role in an Italian female sample. SUBJECTS AND METHODS: An exploratory cross-sectional study was done to assess the association of selected micronutrients with symptoms of FM by using the Fibromyalgia Impact Questionnaire (FIQ) in twenty consecutive female patients with FM. A literature review was also conducted. RESULTS: FIQ results revealed that vitamin D and magnesium deficiency appear to play a role in FM symptoms, mainly in physical function and stiffness. From the literature review, only two studies investigating the role of micronutrients in FM were retrieved. CONCLUSIONS: Screening for micronutrient deficiencies in FM patients and supplementing them when levels are low might help counteract FM symptoms.


Assuntos
Fibromialgia , Micronutrientes , Humanos , Fibromialgia/diagnóstico , Feminino , Itália , Estudos Transversais , Pessoa de Meia-Idade , Adulto , Vitamina D/sangue , Qualidade de Vida , Inquéritos e Questionários , Suplementos Nutricionais
2.
J Endocrinol Invest ; 47(4): 959-971, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-37837555

RESUMO

BACKGROUND: The incidence of neuroendocrine neoplasm (NEN) and related carcinoid syndrome (CaS) has increased markedly in recent decades, and women appear to be more at risk than men. As per other tumors, gender may be relevant in influencing the clinical and prognostic characteristics of NEN-associated CS. However, specific data on carcinoid syndrome (CaS) are still lacking. PURPOSE: To evaluate gender differences in clinical presentation and outcome of CaS. METHODS: Retrospective analysis of 144 CaS patients from 20 Italian high-volume centers was conducted. Clinical presentation, tumor characteristics, therapies, and outcomes (progression-free survival, PFS, overall survival, OS) were correlated to gender. RESULTS: Ninety (62.5%) CaS patients were male. There was no gender difference in the site of primary tumor, tumor grade and clinical stage, as well as in treatments. Men were more frequently smokers (37.2%) and alcohol drinkers (17.8%) than women (9.5%, p = 0.002, and 3.7%, p = 0.004, respectively). Concerning clinical presentation, women showed higher median number of symptoms (p = 0.0007), more frequent abdominal pain, tachycardia, and psychiatric disorders than men (53.3% vs 70.4%, p = 0.044; 6.7% vs 31.5%, p = 0.001; 50.9% vs. 26.7%, p = 0.003, respectively). Lymph node metastases at diagnosis were more frequent in men than in women (80% vs 64.8%; p = 0.04), but no differences in terms of PFS (p = 0.51) and OS (p = 0.64) were found between gender. CONCLUSIONS: In this Italian cohort, CaS was slightly more frequent in males than females. Gender-related differences emerged in the clinical presentation of CaS, as well as gender-specific risk factors for CaS development. A gender-driven clinical management of these patients should be advisable.


Assuntos
Tumor Carcinoide , Tumores Neuroendócrinos , Humanos , Masculino , Feminino , Estudos Retrospectivos , Fatores Sexuais , Prognóstico , Tumores Neuroendócrinos/patologia , Tumor Carcinoide/diagnóstico , Tumor Carcinoide/secundário , Tumor Carcinoide/terapia , Itália
3.
Endocrine ; 80(1): 221-230, 2023 04.
Artigo em Inglês | MEDLINE | ID: mdl-36509928

RESUMO

PURPOSE: The immune environment represents a new, but little explored, tool for understanding neuroendocrine neoplasms (NENs) behavior. An immunosuppressed microenvironment is hypothesized to promote NENs progression. A missing profiling of circulating leukocyte and peripheral blood mononuclear cells (PBMCs) subpopulations would open new perspectives in the still limited diagnostic-therapeutic management of NENs. METHODS: A cross-sectional case-control pilot study was performed recruiting 30 consecutive subjects: 15 patients naïve to treatment, with histologically proven gastroenteropancreatic (GEP) neuroendocrine tumors (NETs) and 15 healthy controls, matched for age and sex. PBMCs subpopulations were studied by flow cytometry. Soluble Tie2 (sTie2), Angiopoietin-1 (Ang-1), Angiopoietin-2 (Ang-2) were evaluated by ELISA. RESULTS: Immune cell profiling revealed a significant lower CD3-CD56+ natural killer (NK) cell count in NETs vs controls (p = 0.04). NK subset analysis showed a reduced relative count of CD56+CD16+ NK cells (p =0.002) in NETs vs controls. Patients with NET showed a higher percentage of CD14+CD16++ non-classical monocytes (p = 0.01), and a lower percentage of CD14+CD16+ intermediate monocytes (p = 0.04). A decrease in percentage (p = 0.004) of CD4+ T-helper lymphocytes was found in NET patients. Evaluation of cellular and serum angiopoietin pathway mediators revealed in NET patients a higher relative count of Tie2-expressing monocytes (TEMs) (p < 0.001), and high levels of Ang-1 (p = 0.003) and Ang-2 (p = 0.002). CONCLUSIONS: Patients with GEP-NET presented an immunosuppressed environment characterized by a low count of cytotoxic NK cells, a high count of anti-inflammatory non-classical monocytes, and a low count of T-helper lymphocytes. Higher levels of TEMs and angiopoietins suggest a crosstalk between innate immunity and angiogenic pathways in NETs.


Assuntos
Angiopoietinas , Tumores Neuroendócrinos , Receptor TIE-2 , Humanos , Estudos Transversais , Leucócitos Mononucleares , Tumores Neuroendócrinos/metabolismo , Projetos Piloto , Microambiente Tumoral , Receptor TIE-2/metabolismo
4.
J Endocrinol Invest ; 45(11): 2193-2200, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-35867331

RESUMO

PURPOSE: Scientific knowledge on health-related quality of life (HRQoL) in patients with neuroendocrine neoplasm (NEN) is still limited and longitudinal assessment of HRQoL over the time in NEN patients are scarce. The current study aimed to assess the role of clinical severity and heterogeneity of NEN, as well as resilience, in the HRQoL of NEN patients over the course of a year. METHODS: 39 consecutive NEN patients (25 men and 14 women) aged from 29 to 73 years participated in a longitudinal Italian multicentric study. The main outcome measure concerned the severity and heterogeneity of NEN, HRQoL, and resilience. RESULTS: Over the course of a year, higher levels of the global health (GH) were associated to the absence of distant metastases, while the presence of metastases with higher levels of fatigue, diarrhea, and financial difficulties. Higher levels of resilience are still associated with better GH and lower levels of fatigue, diarrhea, and financial difficulties, but no longer with constipation. Furthermore, patients with gastroenteropancreatic NEN still have higher scores on constipation, but not on GH, fatigue, diarrhea, and financial difficulties. Patients with hereditary NEN continue to have greater GH than those with a sporadic NEN and lower fatigue, diarrhea, and financial difficulties. CONCLUSION: These findings showed that the effects of severity and clinical heterogeneity of the NEN on HRQoL may change over time. This evidence should lead clinicians to monitor the HRQoL of NEN patients throughout the course of the disease and psychologists to implement evidence-based resilience interventions.


Assuntos
Tumores Neuroendócrinos , Neoplasias Pancreáticas , Neoplasias Gástricas , Constipação Intestinal , Diarreia , Fadiga , Feminino , Humanos , Estudos Longitudinais , Masculino , Tumores Neuroendócrinos/patologia , Neoplasias Pancreáticas/patologia , Qualidade de Vida
5.
J Endocrinol Invest ; 45(4): 849-857, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-35040099

RESUMO

PURPOSE: Risk factors for sporadic GEP-NENs are still not well defined. To identify the main clinical risk factors represents the aim of this study performed by three Italian referral centers for NENs. METHODS: We performed a retrospective case-control study including 148 consecutive sporadic GEP-NENs and 210 age- and sex-matched controls. We collected data on clinical features, cancer family history and other potential risk factors. RESULTS: Mean age was 58.3 ± 15.8 years; 50% males, primary site was pancreas (50.7%), followed by ileum (22.3%). The 62.8% and 29.1% of cases were G1 and G2, respectively; the 40% had locally advanced or metastatic disease at diagnosis. Independent risk factors for GEP-NENs were: family history of non-neuroendocrine GEP cancer (OR 2.16, 95% CI 1.31-3.55, p = 0.003), type 2 diabetes mellitus (T2DM) (OR 2.5, 95% CI 1.39-4.51, p = 0.002) and obesity (OR 1.88, 95% CI 1.18-2.99, p = 0.007). In the T2DM subjects, metformin use was a protective factor (OR 0.28, 95% CI 0.08-0.93, p = 0.049). T2DM was also associated with a more advanced (OR 2.39, 95% CI 1.05-5.46, p = 0.035) and progressive disease (OR 2.47, 95% CI 1.08-5.34, p = 0.03). Stratifying cases by primary site, independent risk factors for pancreatic NENs were T2DM (OR 2.57, 95% CI 1.28-5.15, p = 0.008) and obesity (OR 1.98, 95% CI 1.11-3.52, p = 0.020), while for intestinal NENs family history of non-neuroendocrine GEP cancer (OR 2.46, 95% CI 1.38-4.38, p = 0.003) and obesity (OR 1.90, 95% CI 1.08-3.33, p = 0.026). CONCLUSION: This study reinforces a role for family history of non-neuroendocrine GEP cancer, T2DM and obesity as independent risk factors for GEP-NENs and suggests a role of metformin as a protective factor in T2DM subjects. If confirmed, these findings could have a significant impact on prevention strategies for GEP-NENs.


Assuntos
Neoplasias Intestinais/genética , Tumores Neuroendócrinos/genética , Neoplasias Pancreáticas/genética , Neoplasias Gástricas/genética , Adulto , Idoso , Estudos de Casos e Controles , Distribuição de Qui-Quadrado , Feminino , Humanos , Neoplasias Intestinais/classificação , Neoplasias Intestinais/epidemiologia , Itália/epidemiologia , Masculino , Anamnese/estatística & dados numéricos , Pessoa de Meia-Idade , Tumores Neuroendócrinos/classificação , Tumores Neuroendócrinos/epidemiologia , Neoplasias Pancreáticas/classificação , Neoplasias Pancreáticas/epidemiologia , Prognóstico , Estudos Retrospectivos , Fatores de Risco , Neoplasias Gástricas/classificação , Neoplasias Gástricas/epidemiologia
6.
Eur Rev Med Pharmacol Sci ; 26(24): 9327-9335, 2022 12.
Artigo em Inglês | MEDLINE | ID: mdl-36591841

RESUMO

OBJECTIVE: Orthorexia Nervosa (ON) is an eating disorder of growing interest that is characterized by an obsession with healthy eating. Nowadays, people spend an increasing amount of time on social media, which may negatively impact eating behaviors. The aim of this study was to investigate the relationship between social media usage and risk of ON. SUBJECTS AND METHODS: We conducted an online survey using the 10-item Italian-Düsseldorf Orthorexia Scale questionnaire (I-DOS). A total of 4,107 individuals participated and were classified according to sex, age, education level, marital status, BMI, main occupation, and diet. RESULTS: The prevalence of ON was 28.5%. Participants who reported using social media for over 60 minutes per day had a higher prevalence of ON than those using social media for less than 15 minutes per day. CONCLUSIONS: The results of this study suggest that longer time spent on social media is associated with ON.


Assuntos
Ortorexia Nervosa , Mídias Sociais , Humanos , Comportamentos Relacionados com a Saúde , Dieta , Inquéritos e Questionários , Comportamento Alimentar
7.
J Endocrinol Invest ; 43(8): 1115-1123, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32100197

RESUMO

PURPOSE: The classification of indeterminate cytopathology at thyroid fine-needle-aspiration (FNA) has been updated to reduce the number of unnecessary surgery; the 2014 Italian classification introduced the low-risk (TIR3A) and high-risk (TIR3B) subcategories. Aim of this study was to identify the ultrasonographic (US), clinical and cytological predictors of malignancy among TIR3B nodules from a single institution. METHODS: A prospective observational study including 1844 patients who underwent thyroid FNA from June 2014 to January 2019. Ultrasonographic, clinical and cytological features were recorded. All TIR3B diagnoses were referred to surgery. According to final histology, patients were divided into thyroid cancer (TC) or benign nodules. Chi-square test, or Fisher exact test when appropriate, were used to compare groups and logistic regression analyses were used to determine independent predictors of malignancy. RESULTS: Of 1844 FNAs, 96 (5.2%) were TIR3B. Histology report was available in 65. Among them, 25 (38.5%) were TC. Predictors of TC were nodule size < 20 mm [Odds Ratio (OR) = 5.88, 95% CI 1.91-18.11, p = 0.002], absence or weak intralesional flow [OR = 0.3, 95% CI 0.09-0.77, p = 0.015], microcalcifications [OR = 6.5, 95% CI 1.90-21.93, p = 0.003] at US; nuclear inclusions [OR = 25.3, 95% CI 1.34-476.07, p = 0.031] and chromatin clearing [OR = 3.7, 95% CI 1.27-10.99, p = 0.017] at cytopathology. Patients aged < 55 years had a significantly higher risk of TC [OR = 9.7, 95% CI 2.79-34.07, p < 0.001]. In multivariate analysis, age < 55 and nodule size < 20 mm resulted as independent risk factors. CONCLUSIONS: Patients < 55 years receiving a diagnosis TIR3B on nodules < 20 mm, with microcalcifications, showing specific nuclear atypia at cytopathology are more likely to have TC. Combining US, cytological and clinical features could help determining which patients with a TIR3B diagnosis should be referred to surgery.


Assuntos
Citodiagnóstico/métodos , Neoplasias da Glândula Tireoide/classificação , Neoplasias da Glândula Tireoide/patologia , Nódulo da Glândula Tireoide/patologia , Biópsia por Agulha Fina , Feminino , Seguimentos , Humanos , Itália/epidemiologia , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Prospectivos , Fatores de Risco , Neoplasias da Glândula Tireoide/epidemiologia
8.
Endocrine ; 67(3): 597-604, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-31679139

RESUMO

PURPOSE: Hypothyroidism is a common side effect of Sunitinib (SUN) treatment in metastatic renal cell carcinoma (mRCC) patients. We aimed to evaluate thyroid profile during the alternative 2/1 SUN treatment schedule and to assess the predictive value of hypothyroidism in terms of survival. METHODS: We performed a prospective observational study enrolling 42 consecutive mRCC patients starting first-line alternative SUN dosing 2/1 schedule. Thyroid function was assessed at baseline and during the first three SUN cycles (1 cycle = 6 weeks = 2 ON/1 OFF + 2 ON/1 OFF), and then after 6 and 12 months. Thyroid ultrasound was performed at baseline and after 3, 6, and 12 months. RESULTS: Subclinical hypothyroidism developed in 24% of patients during the first cycle; in other 24% in the second cycle and in 14% in the third cycle. The highest TSH values were reached during the second cycle, ON phase (6.58 ± 5.74 µI U/l). We observed a reduction in thyroid size, in echogenicity and in parenchymal perfusion in all patients. Progression-free survival (PFS) tended to be longer in patients with TSH ≥ 5 µI U/ml during the second cycle (p = 0.069). TSH level was an independent risk factor for PFS in men (p = 0.009) but not in women (p = 0.285). CONCLUSIONS: This is the first study investigating functional and morphological effects on thyroid during the alternative 2/1 SUN schedule in mRCC patients. We detected an early onset of subclinical hypothyroidism, observing the association between TSH ≥ 5 µI U/ml and: (i) longer PFS in men; (ii) progressive decrease of thyroid size in absence of significant changes in autoimmune thyroid profile.


Assuntos
Antineoplásicos , Carcinoma de Células Renais , Neoplasias Renais , Antineoplásicos/efeitos adversos , Carcinoma de Células Renais/tratamento farmacológico , Feminino , Humanos , Indóis/efeitos adversos , Neoplasias Renais/tratamento farmacológico , Masculino , Pirróis/uso terapêutico , Sunitinibe/uso terapêutico , Glândula Tireoide/diagnóstico por imagem
9.
Endocrine ; 66(3): 542-550, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31129812

RESUMO

PURPOSE: Selenium is frequently in nutraceuticals for pregnancy, given its role on fertility and thyroid metabolism. However, most evidence rise from non-controlled studies. We aimed to evaluate the protective effect of selenium against thyroid autoimmunity during and after pregnancy. METHODS: A multicenter, randomized, double-blind, placebo-controlled trial was performed and promoted by the Young Italian Endocrinologists Group (EnGioI)-Italian Society of Endocrinology. Forty-five women with thyroiditis in pregnancy were enrolled and randomly assigned to L-selenomethionine (L-Se-Met) 83 mcg/day or placebo (PLB) and evaluated at 10 ± 2 (T1), 36 ± 2 weeks of gestation (T2) and 6 months after delivery (postpartum, PP). RESULTS: We measured a significant reduction of autoantibodies after pregnancy in L-Se-Met group [at PP: TgAb 19.86 (11.59-52.60), p < 0.01; TPOAb 255.00 (79.00-292.00), p < 0.01], and an antibodies titer's rebound in PLB group (TgAb 151.03 ± 182.9, p < 0.01; TPOAb 441.28 ± 512.18, p < 0.01). A significant increase in selenemia was measured in L-Se-Met group at T2 (91.33 ± 25.49; p < 0.01) and PP (93.55 ± 23.53; p = 0.02). Two miscarriage occurred in PLB. No differences were found in thyroid volume, echogenicity, quality of life, maternal/fetal complications. CONCLUSIONS: SERENA study demonstrated a beneficial effect of L-Se-Met supplementation on autoantibody titer during pregnancy and on postpartum thyroiditis recurrence.


Assuntos
Doenças Autoimunes/prevenção & controle , Complicações na Gravidez/prevenção & controle , Selênio/uso terapêutico , Doenças da Glândula Tireoide/prevenção & controle , Oligoelementos/uso terapêutico , Adulto , Autoanticorpos/sangue , Suplementos Nutricionais , Método Duplo-Cego , Feminino , Humanos , Gravidez , Selênio/sangue
10.
J Endocrinol Invest ; 40(11): 1183-1190, 2017 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-28393316

RESUMO

PURPOSE: Autoimmune thyroiditis and its complications for the reproductive system are a growing problem. Selenium is a common ingredient in numerous food supplements recommended for thyroiditis and pregnancy. A fast, simple method to measure serum selenium concentration will improve knowledge of its pharmacokinetics and toxicity. AIM: To validate a useful method to measure serum selenium concentration and to study selenium absorption and accumulation in a prospective interventional study of prolonged treatment. METHODS: Thirty healthy volunteers received a single dose of L-selenomethionine one tablet (83 mcg) (Phase 1), a single dose of two tablets (Phase 2), and two tablets daily for 14 days (Phase 3). Total selenium and selenium time profiles were generated by serial sampling (T0, T3, T6, T12, and T24 hours after ingestion-Phases 1 and 2; and T0 and T24 hours-Phase 3). Selenium concentration was investigated by open-vessel acid digestion of small serum volumes followed by hydride generation atomic fluorescence spectroscopy analysis. RESULTS: There was a significant increase in serum selenium concentration (mcg/L) in all treatment phases. Significantly increased levels were reached at T3 in Phase 1 (baseline: 76.5 ± 2.47; T3: 82.8 ± 3.28) and at T6 in Phase 2 (83.8 ± 3.46). They remained significantly increased at T12 in Phase 1 and T24 in Phase 2 (79.03 ± 2.69). There was significant selenium accumulation after prolonged intake (14 days) (102.13 ± 5.61). CONCLUSIONS: Prolonged selenomethionine administration increases circulating blood selenium concentration and hydride generation atomic fluorescence spectroscopy enables its accurate quantification.


Assuntos
Suplementos Nutricionais , Selênio/sangue , Selenometionina/administração & dosagem , Adulto , Feminino , Voluntários Saudáveis , Humanos , Masculino , Estudos Prospectivos
11.
Andrology ; 4(6): 1193-1203, 2016 11.
Artigo em Inglês | MEDLINE | ID: mdl-27565451

RESUMO

The purpose of this study was to evaluate prospectively the accuracy of qualitative and strain ratio elastography (SE) in the differential diagnosis of non-palpable testicular lesions. The local review board approved the protocol and all patients gave their consent. One hundred and six patients with non-palpable testicular lesions were consecutively enrolled. Baseline ultrasonography (US) and SE were correlated with clinical and histological features and ROC curves developed for diagnostic accuracy. The non-palpable lesions were all ≤1.5 cm; 37/106 (34.9%) were malignant, 38 (35.9%) were benign, and 31 (29.2%) were non-neoplastic. Independent risk factors for malignancy were as follows: size (OR 17.788; p = 0.002), microlithiasis (OR 17.673, p < 0.001), intralesional vascularization (OR 9.207, p = 0.006), and hypoechogenicity (OR, 11.509, p = 0.036). Baseline US had 89.2% sensitivity (95% CI 74.6-97.0) and 85.5% specificity (95% CI 75.0-92.8) in identifying malignancies, and 94.6% sensitivity (95% CI 86.9-98.5) and 87.1% specificity (95% CI 70.2-96.4) in discriminating neoplasms from non-neoplastic lesions. An elasticity score (ES) of 3 out of 3 (ES3, maximum hardness) was recorded in 30/37 (81.1%) malignant lesions (p < 0.001). An intermediate score of 2 (ES2) was recorded in 19/38 (36.8%) benign neoplastic lesions and in 22/31 (71%) non-neoplastic lesions (p = 0.005 and p = 0.001 vs. malignancies). None of the non-neoplastic lesions scored ES3. Logistic regression analysis revealed a significant association between ES3 and malignancy (χ2  = 42.212, p < 0.001). ES1 and ES2 were predictors of benignity (p < 0.01). Overall, SE was 81.8% sensitive (95% CI 64.8-92.0) and 79.1% specific (95% CI 68.3-88.4) in identifying malignancies, and 58.6% sensitive (95% CI 46.7-69.9) and 100% specific (95% CI 88.8-100) in discriminating non-neoplastic lesions. Strain ratio measurement did not improve the accuracy of qualitative elastography. Strain ratio measurement offers no improvement over elastographic qualitative assessment of testicular lesions; testicular SE may support conventional US in identifying non-neoplastic lesions when findings are controversial, but its added value in clinical practice remains to be proven.


Assuntos
Técnicas de Imagem por Elasticidade , Doenças Testiculares/diagnóstico por imagem , Testículo/diagnóstico por imagem , Ultrassonografia/métodos , Adolescente , Adulto , Diagnóstico Diferencial , Humanos , Masculino , Pessoa de Meia-Idade , Adulto Jovem
12.
Cell Death Dis ; 7(7): e2317, 2016 07 28.
Artigo em Inglês | MEDLINE | ID: mdl-27468693

RESUMO

The role of endogenous c-Kit receptor activation on cardiac cell homeostasis and repair remains largely unexplored. Transgenic mice carrying an activating point mutation (TgD814Y) in the kinase domain of the c-Kit gene were generated. c-Kit(TgD814Y) receptor was expressed in the heart during embryonic development and postnatal life, in a similar timing and expression pattern to that of the endogenous gene, but not in the hematopoietic compartment allowing the study of a cardiac-specific phenotype. c-Kit(TgD814Y) mutation produced a constitutive active c-Kit receptor in cardiac tissue and cells from transgenic mice as demonstrated by the increased phosphorylation of ERK1/2 and AKT, which are the main downstream molecular effectors of c-Kit receptor signaling. In adult transgenic hearts, cardiac morphology, size and total c-Kit(+) cardiac cell number was not different compared with wt mice. However, when c-Kit(TgD814Y) mice were subjected to transmural necrotic heart damage by cryoinjury (CI), all transgenic survived, compared with half of wt mice. In the sub-acute phase after CI, transgenic and wt mice showed similar heart damage. However, 9 days after CI, transgenic mice exhibited an increased number of c-Kit(+)CD31(+) endothelial progenitor cells surrounding the necrotic area. At later follow-up, a consistent reduction of fibrotic area, increased capillary density and increased cardiomyocyte replenishment rate (as established by BrdU incorporation) were observed in transgenic compared with wt mice. Consistently, CD45(-)c-Kit(+) cardiac stem cells isolated from transgenic c-Kit(TgD814Y) mice showed an enhanced endothelial and cardiomyocyte differentiation potential compared with cells isolated from the wt. Constitutive activation of c-Kit receptor in mice is associated with an increased cardiac myogenic and vasculogenic reparative potential after injury, with a significant improvement of survival.


Assuntos
Miocárdio/metabolismo , Miocárdio/patologia , Proteínas Proto-Oncogênicas c-kit/metabolismo , Regeneração , Cicatrização , Substituição de Aminoácidos , Animais , Compartimento Celular , Diferenciação Celular , Células Endoteliais/metabolismo , Células Endoteliais/patologia , Ativação Enzimática , Hematopoese , Camundongos Transgênicos , Proteínas Quinases Ativadas por Mitógeno/metabolismo , Mutação/genética , Miocárdio/enzimologia , Fosforilação , Proteínas Proto-Oncogênicas c-akt/metabolismo , Proteínas Proto-Oncogênicas c-kit/genética , Células-Tronco/citologia , Células-Tronco/metabolismo , Análise de Sobrevida
13.
J Endocrinol Invest ; 39(2): 131-42, 2016 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-26142740

RESUMO

INTRODUCTION: Phosphodiesterase 5 inhibitors (PDE5i) were developed while investigating novel treatments for coronary artery disease, but their andrological side effects shifted their indication toward the management of erectile dysfunction. Although PDE5i are now also indicated for pulmonary arterial hypertension and there are mounting preclinical and clinical evidences about their potentially beneficial cardiac effects, their use remains controversial and the involved mechanisms remain unclear. MATERIALS AND METHODS: This review aimed to analyze the effects of PDE5i administration in various animal and humans models of cardiovascular diseases. RESULTS: Animal studies have shown that PDE5i have protective effects in several models of cardiac disease. In humans, some studies showed that PDE5i improves microvascular and endothelial dysfunction and exerts positive effects in different samples of cardiovascular (CV) impairment. In contrast, other studies found no benefit (and no harm) in heart failure with preserved ejection fraction. The discrepancies in these findings are likely related to the fact that the mechanisms targeted by PDE5i in human disease are still poorly understood and the target population not yet identified. The mechanisms of actions herein reviewed suggest that hypertrophy, microvascular impairment, and inflammation, should be variably present for PDE5i to work. All these conditions frequently coexist in diabetes. A gender responsiveness has also been recently proposed. CONCLUSIONS: Continuous PDE5 inhibition may exert cardioprotective effects, improving endothelial function and counteracting cardiac remodeling in some but not all conditions. A better patient selection could help to clarify the controversies on PDE5i use for CV disorders.


Assuntos
Cardiotônicos/uso terapêutico , Cardiopatias/tratamento farmacológico , Coração/efeitos dos fármacos , Inibidores da Fosfodiesterase 5/uso terapêutico , Animais , Cardiotônicos/efeitos adversos , Cardiotônicos/farmacologia , Fármacos Cardiovasculares/efeitos adversos , Fármacos Cardiovasculares/farmacologia , Fármacos Cardiovasculares/uso terapêutico , Doenças Cardiovasculares/tratamento farmacológico , Doenças Cardiovasculares/metabolismo , Doenças Cardiovasculares/fisiopatologia , Endotélio Vascular/efeitos dos fármacos , Endotélio Vascular/fisiopatologia , Coração/fisiopatologia , Cardiopatias/fisiopatologia , Humanos , Microvasos/efeitos dos fármacos , Microvasos/metabolismo , Microvasos/fisiopatologia , Miocárdio/enzimologia , Miocárdio/metabolismo , Inibidores da Fosfodiesterase 5/efeitos adversos , Inibidores da Fosfodiesterase 5/farmacologia , Reprodutibilidade dos Testes
14.
J Endocrinol Invest ; 36(10 Suppl): 28-36, 2013 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-24419057

RESUMO

Selenium (Se) is an essential element involved in normal gonadal development, gametogenesis, and fertilization. Molecular studies show that the gonads actively take up and store Se, most of which is incorporated in the glutathione peroxidase enzymes. We provide a systematic review of the original molecular studies, prospective observational data and randomized controlled trials on the role of Se in reproductive function conducted in the past 30 years. A critical appraisal of these findings suggests that Se supplementation produces a bell-shaped response curve, with negative effects observed for both low and high concentrations. The few available clinical trials support the use of Se supplementation (<200 µg/d) to improve male infertility, although their pre-treatment assessment of Se levels in enrolled subjects is inconsistent and their quality and size are insufficient to enable general recommendations. In females, a putative role in oocyte maturation and fertilization is suggested, but no large controlled trials have yet been performed. The role of Se supplementation on pregnancy outcomes is promising, and ongoing studies and meta-analysis should soon enable proper recommendations to be suggested. How best to assess Se in terms of cut-off value, sample type (serum, semen, other fluids) and the specific outcome of interest remains to be clarified. In the meantime, assessment of serum Se levels followed by low-dose replacement therapy when necessary is a reasonable approach to improve male idiopathic infertility and gestational outcome.

15.
Andrologia ; 44 Suppl 1: 600-4, 2012 May.
Artigo em Inglês | MEDLINE | ID: mdl-21966881

RESUMO

The application of nutraceuticals in the field of male sexual function -in particular for erectile dysfunction (ED)--remains relatively underexplored. In a group of 54 unselected men (35-75 years), consecutively presenting to our ED clinic and naive to other ED treatments, we carried out a single-blind, one-arm study to evaluate the effects of a 3-month supplementation with propionyl-L-carnitine, L-arginine and niacin on their sexual performance. All patients had the short-international index of erectile function (IIEF) questionnaire, global assessment questions (GAQs) and routine laboratory testing, at baseline and 3 months afterward. 51 (92%) patients of 54 completed the entire study period. After 3 months of treatment, a small, but statistically significant improvement in total and single items of the IIEF was found (Δ = 5.7 ± 4.1 P < 0.01). Analyses on GAQs revealed that treatment improved erections in 40% of cases, with a partial response occurring in up to 77% of subjects enrolled. These preliminary findings indicate that the favourable cardiovascular effects of nutraceuticals might also reflect on male sexual function with possible implication in the treatment and prevention of ED. This study documents a considerable patient's interest toward nutritional supplementation--as first-line or adjunctive treatment to PDE5 inhibitors--that goes beyond the measurable increment in penile rigidity.


Assuntos
Arginina/uso terapêutico , Carnitina/análogos & derivados , Suplementos Nutricionais , Disfunção Erétil/tratamento farmacológico , Niacina/uso terapêutico , Adulto , Idoso , Carnitina/uso terapêutico , Humanos , Masculino , Pessoa de Meia-Idade
16.
G Chir ; 27(5): 233-9, 2006 May.
Artigo em Italiano | MEDLINE | ID: mdl-16857114

RESUMO

Three cases of carcinoid tumour of the appendix (about 0,3 % of all performed appendectomies) has induced the Authors to a review of the literature with the aim to underline the most important biological and pathological findings and the current clinic and therapeutic knowledges. The diagnosis before surgery is rarely made; it is formulated incidentally in most patients by the histological exam during the operation for an appendicitis or during other surgical procedures. The kind of surgical intervention, that is the entity of the surgical demolition, for the treatment of the carcinoid tumours of the appendix is still controversial: appendectomy or right colectomy? It is possible identify, also during the operation for an appendicitis or for other abdominal lesions, criteria that can orient toward a major surgery (size of the neoplasia, subserosal lymphatic invasion, infiltration of the serosa, diffusion in the meso-appendix, location in closeness of the base of the appendix, invasion of the the locoregional lymph nodes, presence of metastases, section ?margins, number of mitoses, cellular pleiomorfism).


Assuntos
Apendicectomia , Neoplasias do Apêndice/cirurgia , Tumor Carcinoide/cirurgia , Colectomia , Adulto , Fatores Etários , Neoplasias do Apêndice/diagnóstico , Neoplasias do Apêndice/epidemiologia , Neoplasias do Apêndice/mortalidade , Tumor Carcinoide/diagnóstico , Tumor Carcinoide/epidemiologia , Tumor Carcinoide/mortalidade , Feminino , Seguimentos , Humanos , Masculino , Prognóstico , Fatores Sexuais , Fatores de Tempo
17.
G Chir ; 26(4): 143-52, 2005 Apr.
Artigo em Italiano | MEDLINE | ID: mdl-16035250

RESUMO

During the last two decades were observed 422 symptomatic patients with various degree of diverticular disease of the colon. 51 patients underwent surgery: 29 for stenosis (24) or occlusion (5), 4 for fistulas, 18 for perforation. The operations (26 emergencies, 25 elective) included: 21 cases of one-stage resection and anastomosis without protective colostomy, 16 with colostomy, 8 Hartmann's procedures, 7 Mikulicz's operations, 1 suturing of the diverticulum with colostomy. The incidence of complications was 17.6% (9 cases, 7 following emergency surgery and 2 after elective procedures). The intraoperative mortality was zero, while postoperative 5.8% (3 cases, 2 after emergency procedures and 1 following elective surgery). The best results (lowest morbidity and mortality rates) occurred with the radical procedures, especially the resection-anastomosis with or without colostomy, which allowed the removal of the septic focus from the peritoneal cavity and thus a shorter recovery in a high number of cases.


Assuntos
Doença Diverticular do Colo/cirurgia , Adulto , Idoso , Idoso de 80 Anos ou mais , Doença Diverticular do Colo/complicações , Doença Diverticular do Colo/diagnóstico , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Análise de Sobrevida , Resultado do Tratamento
18.
J Endocrinol Invest ; 28(10 Suppl): 73-9, 2005.
Artigo em Inglês | MEDLINE | ID: mdl-16550728

RESUMO

Epidemiological studies correlated the age-related decline of serum testosterone levels to the concomitant increase of cardiovascular diseases, osteoporosis and bone fractures. For this reason, testosterone replacement therapy (TRT) in older men with late-onset hypogonadism has been advocated. Testosterone has an anti-resorptive effect that may increase bone density at lumbar spine. Androgens may also have cardio-protective effects by improving endothelial function and reducing the risk factors for atherosclerosis. It has been proposed that atherosclerosis and osteoporosis share common pathophysiological mechanisms. The role of inflammatory cells, citokynes and calcium deposition into the vascular walls has been reviewed to explore the causal nexus between these frequently associated diseases. Experimental studies indicate that a deregulation in the commitment of pluripotent mesenchimal stem cells toward specialized phenotypes might participate in the development of these conditions. The crossed-over beneficial effect of bisphosphonate on the cardiovascular system and statins on bone metabolism supports the research for a unitary pharmacological approach to both conditions. The findings that androgens regulate mesenchimal cell differentiation, as well as body composition, lipid profile and bone metabolism, have claimed a role for TRT in aging men with late onset-hypogonadism.


Assuntos
Envelhecimento , Androgênios/fisiologia , Doenças Cardiovasculares/epidemiologia , Doenças Cardiovasculares/fisiopatologia , Osteoporose/epidemiologia , Osteoporose/fisiopatologia , Idoso , Idoso de 80 Anos ou mais , Envelhecimento/sangue , Androgênios/sangue , Androgênios/deficiência , Aterosclerose/epidemiologia , Aterosclerose/etiologia , Aterosclerose/fisiopatologia , Composição Corporal/efeitos dos fármacos , Composição Corporal/fisiologia , Densidade Óssea/efeitos dos fármacos , Conservadores da Densidade Óssea/uso terapêutico , Osso e Ossos/efeitos dos fármacos , Osso e Ossos/metabolismo , Doenças Cardiovasculares/tratamento farmacológico , Difosfonatos/farmacologia , Difosfonatos/uso terapêutico , Terapia de Reposição Hormonal , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases/farmacologia , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Inflamação/etiologia , Inflamação/patologia , Inflamação/fisiopatologia , Masculino , Pessoa de Meia-Idade , Osteoporose/tratamento farmacológico , Fatores de Risco , Testosterona/sangue , Testosterona/farmacologia , Testosterona/uso terapêutico
19.
J Hosp Infect ; 55(1): 26-32, 2003 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-14505606

RESUMO

An abrupt and persistent 30% increase in the rate of nosocomial infections was detected at a university teaching hospital after a prolonged period with a relatively constant nosocomial infection rate. Demographic data, risk factors for nosocomial infection, features of reported cases of nosocomial infection, and policy and procedure changes were evaluated for the periods of 1 January 1997 to 30 April 1998 (endemic period) and 1 May to 31 December 1998 (epidemic period). An extensive outbreak investigation revealed no evidence of a true outbreak of nosocomial infection. The apparent outbreak involved all four major body sites, began during the same month that an antibiotic management programme was started, involved the same adult medical and surgical units where antibiotics were being controlled, and occurred months before any significant change in antibiotic usage. A greater proportion of nosocomial infection during the epidemic period was reported by the nosocomial infection surveillance nurses, based on a treating physician's diagnosis rather than on specific clinical criteria. In an attempt to justify existing antibiotic prescribing practices after the implementation of an antibiotic management programme, clinicians altered the threshold at which they documented the presence of nosocomial infection. This change in documentation produced a large pseudo-outbreak of nosocomial infection.


Assuntos
Antibacterianos/efeitos adversos , Infecção Hospitalar/etiologia , Surtos de Doenças , Revisão de Uso de Medicamentos , Antibacterianos/administração & dosagem , Infecção Hospitalar/diagnóstico , Infecção Hospitalar/tratamento farmacológico , Coleta de Dados , Hospitais Universitários , Humanos , Virginia
20.
Arch Intern Med ; 160(21): 3294-8, 2000 Nov 27.
Artigo em Inglês | MEDLINE | ID: mdl-11088092

RESUMO

BACKGROUND: Urinary tract infections (UTIs) account for 30% to 40% of nosocomial infections resulting in morbidity, mortality, and increased length of hospital stay. OBJECTIVE: To assess the efficacy of a silver-alloy, hydrogel-coated latex urinary catheter for the prevention of nosocomial catheter-associated UTIs. METHODS: A 12-month randomized crossover trial compared rates of nosocomial catheter-associated UTI in patients with silver-coated and uncoated catheters. A cost analysis was conducted. RESULTS: There were 343 infections among 27,878 patients (1.23 infections per 100 patients) during 114,368 patient-days (3.00 infections per 1000 patient-days). The relative risk of infection per 1000 patient-days was 0.79 (95% confidence interval, 0.63-0.99; P =.04) for study wards randomized to silver-coated catheters compared with those randomized to uncoated catheters. Infections occurred in 291 of 11,032 catheters used on study units (2.64 infections per 100 catheters). The relative risk of infection per 100 silver-coated catheters used on study wards compared with uncoated catheters was 0.68 (95% confidence interval, 0.54-0.86; P =.001). Fourteen catheter-associated UTIs (4.1%) were complicated by secondary bloodstream infection. One death appeared related to the secondary infection. Estimated hospital cost savings with the use of the silver-coated catheters ranged from $14,456 to $573,293. CONCLUSIONS: The risk of infection declined by 21% among study wards randomized to silver-coated catheters and by 32% among patients in whom silver-coated catheters were used on the wards. Use of the more expensive silver-coated catheter appeared to offer cost savings by preventing excess hospital costs from nosocomial UTI associated with catheter use. Arch Intern Med. 2000;160:3294-3298.


Assuntos
Cateteres de Demora/economia , Infecção Hospitalar/economia , Infecção Hospitalar/prevenção & controle , Custos Hospitalares , Prata , Cateterismo Urinário/instrumentação , Infecções Urinárias/economia , Infecções Urinárias/prevenção & controle , Adulto , Idoso , Ligas , Redução de Custos , Infecção Hospitalar/complicações , Infecção Hospitalar/etiologia , Estudos Cross-Over , Contaminação de Equipamentos , Desenho de Equipamento , Feminino , Hospitais Universitários , Humanos , Incidência , Tempo de Internação , Masculino , Pessoa de Meia-Idade , Sepse/etiologia , Cateterismo Urinário/efeitos adversos , Cateterismo Urinário/economia , Infecções Urinárias/complicações , Infecções Urinárias/etiologia , Virginia/epidemiologia
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