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2.
Eur Rev Med Pharmacol Sci ; 25(6): 2752-2784, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33829462

RESUMO

The coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has proved to be one of the most challenging infectious diseases in the modern era, and despite several countermeasures to lessen its impact, the spread of the virus is still affecting most countries. This renders the goal of active immunization of the population through vaccination a worldwide public health priority. In fact, only when efficient vaccination programs will be successfully implemented, a return to pre-pandemic normality can be considered. The scientific community has made a tremendous effort to blow the lid off the pathogenesis of the disease, and unprecedented efforts are ongoing with governments, private organizations, and academics working together to expeditiously develop safe and efficacious vaccines. Previous research efforts in the development of vaccines for other coronaviruses (Severe Acute Respiratory Syndrome Coronavirus 1 and Middle East Respiratory Syndrome Coronavirus) as well other emerging viruses have opened the door for exploiting several strategies to design a new vaccine against the pandemic virus. Indeed, in a few months, a stunning number of vaccines have been proposed, and almost 50 putative vaccine candidates have entered clinical trials. The different vaccine candidates use different vaccine development platforms, from inactivated whole virus vaccine to subunit vaccine, nucleic acid, and vectored vaccines. In this review, we describe strengths, flaws, and potential pitfalls of each approach to understand their chances of success.


Assuntos
Vacinas contra COVID-19/uso terapêutico , COVID-19/prevenção & controle , SARS-CoV-2/imunologia , COVID-19/transmissão , COVID-19/virologia , Desenvolvimento de Medicamentos , Humanos , SARS-CoV-2/isolamento & purificação , Tratamento Farmacológico da COVID-19
4.
Pathog Glob Health ; 114(8): 451-456, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-33012280

RESUMO

Methicillin-resistant Staphylococcus aureus (MRSA) is one of the important pathogens worldwide showing resistance to several widely used antibiotics. This has made the treatment of MRSA infections harder, especially due to their prevalence in the hospital setting. We evaluated the antibiotic susceptibility patterns of healthcare-associated MRSA infections with a focus on Vancomycin Intermediate S. Aureus (VISA) and macrolide-licosamide-streptogramin B (MLSB) phenotypes. A total of 417 Staphylococcus aureus (S. aureus) cases were isolated between January 2017 and December 2018, through several clinical specimens collected from the University Hospital 'Luigi Vanvitelli' of Naples. We identified bacterial strains using Matrix-Assisted Laser Desorption/Ionization-Time of Flight (MALDI-TOF) and antimicrobial susceptibility using Phoenix BD (Becton Dickinson, NJ, USA). Out of the total 417 S. aureus cases, 140 were MRSA (33.6%) and of these, 50% were soft tissue infections. All MRSA and Methicillin sensible S.aureus MSSA isolates were susceptible to linezolid and daptomycin. Two MRSA cases exhibited intermediate resistance to vancomycin and were of constitutive MLSB phenotype. Among the MRSA strains, 11.4% were constitutive and 43.6% were inducible MLSB phenotypes and 8.6% were macrolide-streptogramin B phenotype. This study characterized the epidemiological status, antibiotic resistance patterns, and current prevalent phenotypes of healthcare-associated MRSA. This knowledge can aid clinicians in improving the antimicrobial stewardship program by adapting appropriate guidelines for the proper use of MRSA antibacterial agents.


Assuntos
Farmacorresistência Bacteriana , Staphylococcus aureus Resistente à Meticilina , Infecções Estafilocócicas , Antibacterianos/farmacologia , Hospitais Universitários , Humanos , Itália/epidemiologia , Staphylococcus aureus Resistente à Meticilina/efeitos dos fármacos , Testes de Sensibilidade Microbiana , Infecções Estafilocócicas/tratamento farmacológico , Infecções Estafilocócicas/epidemiologia
5.
Water Sci Technol ; 77(3-4): 1062-1071, 2018 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-29488969

RESUMO

A mixed culture of oleaginous yeast Lipomyces starkeyi and wastewater native microalgae (mostly Scenedesmus sp. and Chlorella sp.) was performed to enhance lipid and biomass production from urban wastewaters. A 400 L raceway pond, operating outdoors, was designed and used for biomass cultivation. Microalgae and yeast were inoculated into the cultivation pond with a 2:1 inoculum ratio. Their concentrations were monitored for 14 continuous days of batch cultivation. Microalgal growth presented a 3-day initial lag-phase, while yeast growth occurred in the first few days. Yeast activity during the microalgal lag-phase enhanced microalgal biomass productivity, corresponding to 31.4 mgTSS m-2 d-1. Yeast growth was limited by low concentrations in wastewater of easily assimilated organic substrates. Organic carbon was absorbed in the first 3 days with a 3.7 mgC L-1 d-1 removal rate. Complete nutrient removal occurred during microalgal linear growth with 2.9 mgN L-1 d-1 and 0.96 mgP L-1 d-1 removal rates. Microalgal photosynthetic activity induced high pH and dissolved oxygen values resulted in natural bactericidal and antifungal activity. A 15% lipid/dry weight was measured at the end of the cultivation time. Fatty acid methyl ester (FAME) analysis indicated that the lipids were mainly composed of arachidic acid.


Assuntos
Chlorella , Lipomyces , Microalgas , Scenedesmus , Eliminação de Resíduos Líquidos/métodos , Biocombustíveis , Biomassa , Chlorella/crescimento & desenvolvimento , Chlorella/metabolismo , Lipídeos/biossíntese , Lipomyces/crescimento & desenvolvimento , Lipomyces/metabolismo , Microalgas/crescimento & desenvolvimento , Microalgas/metabolismo , Projetos Piloto , Lagoas , Scenedesmus/crescimento & desenvolvimento , Scenedesmus/metabolismo , Águas Residuárias
6.
Artigo em Inglês | MEDLINE | ID: mdl-29483113

RESUMO

The herpes simplex virus 1 (HSV-1) is widespread in the population, and in most cases its infection is asymptomatic. The currently available anti-HSV-1 drugs are acyclovir and its derivatives, although long-term therapy with these agents can lead to drug resistance. Thus, the discovery of novel antiherpetic compounds deserves additional effort. Naturally occurring antimicrobial peptides (AMPs) represent an interesting class of molecules with potential antiviral properties. To the best of our knowledge, this study is the first demonstration of the in vitro anti-HSV-1 activity of temporin B (TB), a short membrane-active amphibian AMP. In particular, when HSV-1 was preincubated with 20 µg/ml TB, significant antiviral activity was observed (a 5-log reduction of the virus titer). Such an effect was due to the disruption of the viral envelope, as demonstrated by transmission electron microscopy. Moreover, TB partially affected different stages of the HSV-1 life cycle, including the attachment and the entry of the virus into the host cell, as well as the subsequent postinfection phase. Furthermore, its efficacy was confirmed on human epithelial cells, suggesting TB as a novel approach for the prevention and/or treatment of HSV-1 infections.


Assuntos
Anti-Infecciosos/farmacologia , Antivirais/farmacologia , Proteínas/farmacologia , Simplexvirus/efeitos dos fármacos , Animais , Peptídeos Catiônicos Antimicrobianos , Microscopia Eletrônica de Transmissão , Simplexvirus/ultraestrutura
7.
Vet Parasitol ; 212(3-4): 175-80, 2015 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-26283464

RESUMO

The relationship between Dicrocoelium dendriticum and cancer has been poorly investigated so far, but a large amount of findings suggest that other trematodes can favour cancer in both animals and humans. In this study, the effects of D. dendriticum on cell proliferation, cell death mechanisms and oxidative stress induction were evaluated in hepatocellular carcinoma (HCC) cell lines (HepG2 and HuH7). Results showed that short time exposure to low concentrations of somatic antigens from D. dendriticum caused slight proliferation in both HepG2 and HuH7 cells while high concentrations and long exposure time to extracts from D. dendriticum caused a significant growth inhibition. This effect was, however, not paralleled by apoptosis but it occurred with an about 40% increase of the formation of autophagic vacuoles. In the same experimental conditions, a strong oxidative stress was recorded with an about 100% increase of the intracellular O(2-). These data suggest the occurrence of an escape anti-apoptotic mechanism in HCC cells. In conclusion, these results suggest a role for D. dendriticum in the chronic oxidative stress and in the regulation of transformation processes in HCC warranting additional investigations in this specific area of research.


Assuntos
Autofagia/fisiologia , Carcinoma Hepatocelular , Dicrocoelium/fisiologia , Neoplasias Hepáticas , Vacúolos/fisiologia , Animais , Linhagem Celular Tumoral , Glioblastoma , Humanos , Estresse Oxidativo
8.
J Endocrinol Invest ; 36(10): 825-30, 2013 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-23801271

RESUMO

BACKGROUND: Endothelial progenitor cells (EPCs), involved in the repairing mechanisms of vascular damage, are positively correlated to insulin-like growth factor I (IGF-I) concentrations in healthy adults. However, the levels of EPCs and their role in acromegalic patients have never been investigated. AIM: We conducted a cross-sectional study in order to assess the levels of the different phenotypes of circulating EPC in acromegalic patients. SUBJECTS AND METHODS: The study was performed at the Endocrinology Unit of Federico II University and at the Unit of Metabolic Diseases and Endocrinology of the Second University of Naples. Fifty-five acromegalic patients and 65 healthy controls were studied. EPCs were assessed by flow cytometry and IGF-I by immunoradiometric assay. RESULTS: Compared with subjects of the control group, acromegalic patients showed significantly higher levels of EPCs phenotypes expressing KDR antigen [KDR+, cells per 106 events, median and interquartile range, 44 (28-67) vs 23 (13-40), p=0.006; CD34+KDR+ 25 (18-38) vs 12 (8-17), p<0.001; CD133+KDR+ 17 (13-30) vs 8 (6-12), p<0.001; CD34+KDR+CD133+ 16 (12-25) vs 8 (6-10), p<0.001]. There was a positive correlations between CD34+KDR+CD133+ cells count and IGF-I in acromegaly group (r=0.79, p<0.001). CONCLUSIONS: Acromegalic patients show higher circulating EPCs levels expressing KDR, positively correlated with IGF-I, suggesting a role for IGF-I in regulating the expression of this surface marker in the early phase of EPCs differentiation.


Assuntos
Acromegalia/sangue , Acromegalia/patologia , Biomarcadores/metabolismo , Endotélio Vascular/patologia , Células-Tronco/patologia , Adulto , Estudos de Casos e Controles , Estudos Transversais , Endotélio Vascular/metabolismo , Feminino , Citometria de Fluxo , Seguimentos , Humanos , Fator de Crescimento Insulin-Like I/metabolismo , Masculino , Pessoa de Meia-Idade , Prognóstico , Radioimunoensaio , Células-Tronco/metabolismo
9.
Minerva Endocrinol ; 38(1): 113-22, 2013 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-23435447

RESUMO

UNLABELLED: Deficiency of 17ß-hydroxysteroid dehydrogenase type 3 (17ßHSD3), an enzyme converting androstenedione (A) to testosterone (T), is a rare cause of autosomal recessive 46,XY disorder of sexual development (DSD). A 18-years phenotypically female patient from southern Italy presented with primary amenorrhea. She had deep voice, macrocephaly, enlarged and bulbous nasal tip, macrostomia, facial acne, breast asymmetry, hypoplasia of the first finger of right hand, proximal implant of the fifth metatarsus bilaterally as well as an increased muscle mass and hirsutism, with hair distribution on face, neck, chest, abdomen, pubic region and on upper and lower limbs. Genital exam showed thickened labra majora with absence of labra minora and a blind-ending pseudo-vagina with clitoris enlargement. Karyotype analysis showed a male genotype (46,XY). Hormonal evaluation showed decreased T (188 ng/dL-6.5 nmol/L) and increased A (10 ng/mL-34,96 nmol/L), considering male reference ranges, resulting in a decreased T/A ratio (0,186). MRI identified testicles in inguinal regions. Human Chorionic Gonadotropin test showed T/A ratio permanently under 0,8. These evidences were suggestive of a 46,XY DSD due to 17ßHSD3 deficiency. An homozygous mutation (IVS3 -1 G>C or c.326-1G>C) of the 17ßHSD3 gene was discovered. Psychologist identified a well determined female gender identity. It was decided to proceed with gonadectomy and vaginal enlargement by use of dilatators. CONCLUSION: The case described represents a new case of DSD due to 17ßHSD3 deficiency. This patient, raised as a girl, is diagnosed in a very late stage. The identified mutation, previously reported only in Dutch and Brazilian population, is one of 27 presently known mutations of 17ßHSD3 gene and is never reported in Italian population.


Assuntos
17-Hidroxiesteroide Desidrogenases/genética , Disgenesia Gonadal 46 XY/genética , Mutação , 17-Hidroxiesteroide Desidrogenases/deficiência , Adolescente , Amenorreia/genética , Androstenodiona/metabolismo , Face/anormalidades , Feminino , Genitália/anormalidades , Disgenesia Gonadal 46 XY/patologia , Disgenesia Gonadal 46 XY/cirurgia , Hirsutismo/genética , Humanos , Masculino , Orquiectomia , Fenótipo , Testosterona/metabolismo
10.
J Endocrinol Invest ; 35(8): 782-94, 2012 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-23014134

RESUMO

GH and PRL, although not considered as 'classical' sexual hormones, could play a role in the endocrine control of sexual function both in men and women. Physiologically, PRL seems to be involved in the central control of sexual behavior and activity, by modulating mainly the effects of dopaminergic and serotoninergic systems on sexual function. Indeed, circulating PRL levels increase after orgasm and may potentially play a role in the acute regulation of further sexual arousal following orgasm both in men and women. On the other hand, either short-term or long-term PRL increase can modulate central nervous system areas involved in the control of sexual function and, peripherally, can directly influence mechanisms of penile erection in men, and presently only as an hypothesis, mechanisms related to the sexual response of genitalia in women. Furthermore, chronic hyperprolactinemia is classically associated with hypogonadotropic hypogonadism and sexual dysfunction in both sexes. Successful treatment of chronic hyperprolactinemia generally restores normal sexual function both in men and women although this effect is not only related to relapse of gonadal function. Hypoprolactinemia is recently recognised as a possible risk factor of arteriogenic erectile dysfunction while a possible role on female sexual function is not known. The physiological role of GH on sexual function is not fully elucidated. GH is an important regulator of hypothalamuspituitary- gonadal axis and seems to participate in the regulation of the sexual response of genitalia in men, and potentially also in women. Sexual function in men and women with GH deficiency (GHD) and GH excess, particularly in acromegaly, is scantily studied and GH- or IGF-I-dependent effects are difficult to quantify. Nevertheless, a decrease of desire and arousability both in men and women, together with an impairment of erectile function in men, have been described both in patients with GHD and acromegaly, although it is not clear whether they are dependent directly on the hormone defect or excess or they are consequence of the hypogonadism or the different clinical complications or the physical disfigurement and psychological imbalance, which are associated with the diseases, and are potentially affecting sexual function. Data on beneficial effects of GH replacement therapy and specific surgical or pharmacological approach for acromegaly are far to be fully elucidated although restoring normal GH/IGF-I levels have been associated to improvement of sexual function.


Assuntos
Hormônio do Crescimento Humano/uso terapêutico , Prolactina/uso terapêutico , Disfunções Sexuais Fisiológicas/prevenção & controle , Feminino , Humanos , Masculino
11.
Chem Immunol Allergy ; 96: 50-60, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-22433371

RESUMO

Angiogenesis and morphological and functional alterations of microvessels are hallmark features of chronic inflammatory disorders, including certain skin diseases. Vascular endothelial growth factors (VEGFs) are key regulators of blood vessel growth. The VEGF family includes VEGF-A, -B, -C, -D and placental growth factor. VEGF-A and -B are the most important proangiogenic factors, while VEGF-C and -D primarily regulate lymphangiogenesis. Angiopoietins are promoters of neovascularization by interacting with Tie-1 and Tie-2 receptors present on endothelial cells. High levels of VEGF-A have been detected in skin tissue of atopic dermatitis (AD) patients and correlate with disease activity. The vascular changes in the skin of AD patients appear to be linked to the inflammatory process. Effector cells of skin inflammation (human mast cells, basophils, eosinophils, macrophages, lymphocytes, etc.) are major sources of a vast array of angiogenic and lymphangiogenic factors. The role of lymphangiogenesis in AD is largely unknown.


Assuntos
Dermatite Atópica/metabolismo , Linfangiogênese , Neovascularização Fisiológica , Dermatite Atópica/imunologia , Dermatite Atópica/patologia , Humanos , Receptor de TIE-1/metabolismo , Receptor TIE-2/metabolismo , Pele/irrigação sanguínea , Fatores de Crescimento do Endotélio Vascular/metabolismo
12.
J Endocrinol Invest ; 35(2): 154-9, 2012 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-21532330

RESUMO

BACKGROUND: Diabetes mellitus is frequently observed in patients with acromegaly. Current therapies for acromegaly may impact glucose regulation, influencing insulin sensitivity and secretion. The question whether these therapies modify control and progression of diabetes once present is still open. AIM: Aim of our study is to analyze glucose control in acromegalic patients with diabetes, evaluating the relation with treatments for GH excess and for diabetes. METHODS: Seventy patients with acromegaly and diabetes were studied. Duration and treatments of acromegaly and diabetes were recorded, together with clinical and metabolic parameters. RESULTS: Most patients (92.8%) were treated with somatostatin analogs (SSA), either alone or in combination with dopamine-agonists (20%) or pegvisomant (15.7%); 7.1% of patients had been treated by surgery alone. Metformin (65.7%), alone or in combination with other hypoglycemic drugs, was the most frequent treatment for diabetes, followed by insulin (21.5%). Only 15.7% were treated with diet alone. The whole cohort showed a very good control of diabetes and acromegaly. Median glycated hemoglobin was 6.4% (5.9-7). IGF-I was within normal range for age in most patients. No relation was observed between duration of acromegaly or diabetes and metabolic control. SSA had a negative effect on insulin secretion, but these effects did not influence glucose control. Finally, we observed a low prevalence of nephropathy (6%) and retinopathy (20%). CONCLUSIONS: Our study shows that a good control of hyperglycemia can be obtained with success in the majority of acromegalic patients with diabetes, independently of the type of treatment for GH excess.


Assuntos
Acromegalia/metabolismo , Acromegalia/terapia , Glicemia/metabolismo , Complicações do Diabetes/metabolismo , Diabetes Mellitus/metabolismo , Diabetes Mellitus/terapia , Acromegalia/sangue , Acromegalia/complicações , Idoso , Glicemia/efeitos dos fármacos , Estudos de Coortes , Complicações do Diabetes/sangue , Complicações do Diabetes/terapia , Diabetes Mellitus/sangue , Agonistas de Dopamina/uso terapêutico , Procedimentos Cirúrgicos Endócrinos , Hemoglobinas Glicadas/metabolismo , Hormônio do Crescimento Humano/sangue , Humanos , Hiperglicemia/sangue , Hiperglicemia/metabolismo , Hiperglicemia/terapia , Pessoa de Meia-Idade , Somatostatina/análogos & derivados , Somatostatina/uso terapêutico
13.
J Endocrinol Invest ; 35(8): 782-794, 2012 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-28726215

RESUMO

GH and PRL, although not considered as 'classi cal' sexual hormones, could play a role in the endocrine control of sexual function both in men and women. Physiologically, PRL seems to be involved in the central control of sexual behavior and activity, by modulating mainly the effects of dopaminergic and serotoninergic systems on sexual function. Indeed, circulating PRL levels increase after orgasm and may potentially play a role in the acute regulation of further sexual arousal following orgasm both in men and women. On the other hand, either short-term or long-term PRL in crease can modulate central nervous system areas involved in the control of sexual function and, peripherally, can directly influence mechanisms of penile erection in men, and presently only as an hypothesis, mechanisms related to the sexual response of genitalia in women. Furthermore, chronic hyperprolactinemia is classically associated with hypogonadotropic hypogonadism and sexual dysfunction in both sexes. Successful treatment of chronic hyperprolactinemia generally restores normal sexual function both in men and women although this effect is not only related to relapse of gonadal function. Hypoprolactinemia is recently recognised as a possible risk factor of arteriogenic erectile dysfunction while a possible role on female sexual function is not known. The physiological role of GH on sexual function is not fully elucidated. GH is an important regulator of hypothalamus-pituitary-gonadal axis and seems to participate in the regulation of the sexual response of genitalia in men, and potentially also in women. Sexual function in men and women with GH deficiency (GHD) and GH excess, particularly in acromegaly, is scantily studied and GH- or IGF-I-dependent effects are difficult to quantify. Nevertheless, a decrease of desire and arousability both in men and women, together with an impairment of erectile function in men, have been described both in patients with GHD and acromegaly, although it is not clear whether they are dependent directly on the hormone defect or excess or they are consequence of the hypogonadism or the different clinical complications or the physical disfigurement and psychological imbalance, which are associated with the diseases, and are potentially affecting sexual function. Data on beneficial effects of GH replacement therapy and specific surgical or pharmacological approach for acromegaly are far to be fully elucidated although restoring normal GH/IGF-I levels have been associated to improvement of sexual function.

14.
Oncogene ; 29(47): 6203-15, 2010 Nov 25.
Artigo em Inglês | MEDLINE | ID: mdl-20729915

RESUMO

In different human carcinoma types, mast cell infiltrate increases with respect to normal tissue and mast cell density correlates with a bad prognosis. To assess the role of mast cells in human thyroid cancer, we compared the density of tryptase-positive mast cells in 96 papillary thyroid carcinomas (PTCs) versus normal thyroid tissue from 14 healthy individuals. Mast cell density was higher in 95% of PTCs (n=91) than in control tissue. Mast cell infiltrate correlated with extrathyroidal extension (P=0.0005) of PTCs. We show that thyroid cancer cell-line-derived soluble factors induce mast cell activation and chemoattraction in vitro. Different mast cell lines (HMC-1 and LAD2) and primary human lung mast cells induced thyroid cancer cell invasive ability, survival and DNA synthesis in vitro. The latter effect was mainly mediated by three mast-cell-derived mediators: histamine, and chemokines CXCL1/GROα and CXCL10/IP10. We show that xenografts of thyroid carcinoma cells (8505-C) could recruit mast cells injected into the tail vein of mice. Co-injection of human mast cells accelerated the growth of thyroid cancer cell (8505-C) xenografts in athymic mice. This effect was mediated by increased tumor vascularization and proliferation, and was reverted by treating mice with sodium cromoglycate (Cromolyn), a specific mast cell inhibitor. In conclusion, our study data suggest that mast cells are recruited into thyroid carcinomas and promote proliferation, survival and invasive ability of cancer cells, thereby contributing to thyroid carcinoma growth and invasiveness.


Assuntos
Mastócitos/fisiologia , Neoplasias da Glândula Tireoide/patologia , Animais , Contagem de Células , Linhagem Celular Tumoral , Proliferação de Células , Sobrevivência Celular , Transformação Celular Neoplásica , Humanos , Masculino , Mastócitos/imunologia , Camundongos , Camundongos Endogâmicos BALB C , Invasividade Neoplásica , Transplante de Neoplasias , Prognóstico , Neoplasias da Glândula Tireoide/irrigação sanguínea , Neoplasias da Glândula Tireoide/metabolismo , Fator A de Crescimento do Endotélio Vascular/metabolismo
15.
J Endocrinol Invest ; 33(9): 663-70, 2010 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-20595800

RESUMO

BACKGROUND: Acromegaly is known to be associated to vascular damage characterized by an increase of vascular wall thickness and an impairment of vascular function. AIM: The aim of this study was to evaluate the effect of medical treatment with the GH receptor antagonist pegvisomant on vascular structure and function in acromegalic patients resistant to somatostatin analogues. PATIENTS: Ten patients (4 males and 6 females, 28-58 yr) and 20 sex-, age-, and body mass index-matched healthy controls entered the study. All patients were treated for 18 months with pegvisomant at doses ranging from 10 to 40 mg/day. OUTCOME MEASURES: Primary outcome measures were measurement of carotid arteries intima-media thickness (IMT), and brachial arteries flow mediated dilation (FMD); secondary outcome measures were blood pressure, blood glucose and lipids levels. RESULTS: Carotid arteries maximal IMT was significantly higher in patients than in controls at baseline (1.18±0.59 vs 0.69±0.13, p=0.001) and slightly, but not significantly, decreased after treatment (0.97±0.17). Brachial arteries FMD was significantly lower in patients than controls at baseline (7.5±2.5 vs 13.1±1.4, p<0.001) and significantly increased after treatment (8.8±3.7, p=0.016). Systolic (SBP) and diastolic (DBP) blood pressure values, serum glucose and insulin levels and homeostasis model assessment (HOMA) index were higher, whereas HDL-cholesterol levels were lower in patients than controls at baseline. After treatment, SBP and DBP, as well as serum glucose and insulin levels and HOMA index significantly decreased whereas no significant change was found in serum lipid profile. CONCLUSIONS: The results of the current study suggested that long-term treatment with pegvisomant induced a slight reduction of carotid arteries wall thickness and a significant improvement of brachial arteries vascular function in patients with acromegaly resistant to somatostatin analogues.


Assuntos
Acromegalia/tratamento farmacológico , Vasos Sanguíneos/efeitos dos fármacos , Resistência a Medicamentos/efeitos dos fármacos , Antagonistas de Hormônios/uso terapêutico , Receptores da Somatotropina/antagonistas & inibidores , Somatostatina/análogos & derivados , Acromegalia/complicações , Acromegalia/diagnóstico por imagem , Adulto , Vasos Sanguíneos/diagnóstico por imagem , Vasos Sanguíneos/fisiologia , Artéria Braquial/anatomia & histologia , Artéria Braquial/diagnóstico por imagem , Doenças Cardiovasculares/etiologia , Artérias Carótidas/anatomia & histologia , Artérias Carótidas/diagnóstico por imagem , Feminino , Antagonistas de Hormônios/farmacologia , Hormônio do Crescimento Humano/análogos & derivados , Hormônio do Crescimento Humano/farmacologia , Hormônio do Crescimento Humano/uso terapêutico , Humanos , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Ultrassonografia
16.
J Endocrinol Invest ; 32(11): 934-8, 2009 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-19955846

RESUMO

Hypogonadotropic hypogonadism (HH), or secondary hypogonadism, is a clinical condition due to an impairment of the pituitary function, characterized by low testosterone plasma levels associated with normal or low FSH and LH plasma levels. An impairment of gonadotropin secretion and, therefore, a reduced efficiency of spermatogenesis was reported to be frequently associated to conditions different from the classical causes of secondary hypogonadism. These conditions (metabolic, endocrine and eating disorders, physical exercise etc.) have been associated with a non-classical form of HH that could be called "functional" HH (FHH). FHH differs from the classical one by the evidence that gonadotropin levels are in the low-normal range, but are inadequate for the testosterone levels, that often are also in the low-normal range. This commentary aims at reviewing knowledge on the forms of male HH in order to indicate and discuss clinical context, diagnostic and therapeutic approach in the less known non-classical form, i.e. FHH.


Assuntos
Hipogonadismo , Adulto , Criança , Gonadotropina Coriônica/uso terapêutico , Hormônio Foliculoestimulante/uso terapêutico , Terapia de Reposição Hormonal , Humanos , Hipogonadismo/classificação , Hipogonadismo/diagnóstico , Hipogonadismo/tratamento farmacológico , Hipogonadismo/etiologia , Masculino , Puberdade
17.
Int J Immunopathol Pharmacol ; 21(2): 415-20, 2008.
Artigo em Inglês | MEDLINE | ID: mdl-18547487

RESUMO

Chlamydia pneumoniae, an obligate intracellular pathogen, is well-known as etiological agent of acute respiratory infections; the repeated or prolonged exposure to chlamydial antigens may promote the persistence of C. pneumoniae in the respiratory tract leading to chronic diseases, such as chronic obstructive pulmonary disease and asthma. The predilection of C. pneumoniae to cause respiratory tract infections combined with its persistent nature suggest that it might play a role in lung cancer. The aim of our study is to evaluate the involvement of C. pneumoniae in pathogenesis of lung cancer. We therefore investigated the presence of C. pneumoniae DNA in tumor lung tissues by using real-time PCR assay. Simultaneously, tumor and healthy tissues from the same patient with primary carcinoma lung were analyzed. C. pneumoniae DNA was not detected in a single lung tumor tissue by means of an highly sensitive, and specific real-time PCR assay based on FRET hybridization probes. In conclusion, this study does not support the involvement of C. pneumoniae in the pathogenesis of lung cancer, suggesting that further investigations are needed to clarify other potential causative factors for the development of this malignancy.


Assuntos
Chlamydophila pneumoniae/genética , DNA Bacteriano/genética , DNA Bacteriano/isolamento & purificação , Neoplasias Pulmonares/microbiologia , Idoso , Chlamydophila pneumoniae/fisiologia , Feminino , Humanos , Imuno-Histoquímica , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Plasmídeos/genética , Reação em Cadeia da Polimerase Via Transcriptase Reversa
18.
J Endocrinol Invest ; 31(11): 956-65, 2008 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-19169050

RESUMO

No head-to-head comparisons are available to analyze the efficacy of octreotide (LAR) and lanreotide (LAN) as first-line treatment of acromegaly.We compared the efficacy of these two drugs in 54 newly diagnosed patients (21 women, 33 men), 27 treated with LAR (10-30 mg every 28 days) and 27 with LAN (60-90 mg/28 days), for 12 months. Each LAR-treated patient was matched with one LAN-treated patient as for GH levels, sex, and age (+/-5 yr). Outcome measures were GH and IGF-I levels and tumor shrinkage and secondarily classical cardiovascular risk factors (total/HDL-cholesterol ratio, glucose tolerance), blood pressure and drug tolerability. In LAR- and in LAN-treated patients, respectively: GH and IGF-I were controlled in 21 (77.7%) and in 16 patients (59.3%; p=0.26); tumor shrinkage was absent (<25%) in 4 and 5 patients (p=1), mild (25.1-50%) in 9 and 12 (p=0.57), moderate (50.1-75%) in 10 and 6 (p=0.37) and notable (>75%) in 4 and 4 patients (p=1). The total/HDL-cholesterol ratio and insulin levels significantly decreased while glucose levels significantly increased in both groups. None of the patients with normal glucose tolerance at diagnosis developed diabetes mellitus. Side effects were mostly at the gastrointestinal level and were similar with both drugs. In conclusion, newly diagnosed patients with acromegaly treated with LAR and LAN have no significantly different prevalence of disease control, tumor shrinkage, improvement of cardiovascular risk markers and side effects. Therefore, both drugs can be safely employed as first-line therapy of acromegaly.


Assuntos
Acromegalia/tratamento farmacológico , Octreotida/uso terapêutico , Peptídeos Cíclicos/uso terapêutico , Somatostatina/análogos & derivados , Acromegalia/sangue , Acromegalia/patologia , Adulto , Idoso , Feminino , Hormônio do Crescimento Humano/sangue , Humanos , Fator de Crescimento Insulin-Like I/metabolismo , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Somatostatina/uso terapêutico
19.
J Endocrinol Invest ; 30(6): 497-506, 2007 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-17646725

RESUMO

This analytical, observational, retrospective, case-control study was designed to describe clinical presentation, biochemical disease severity, presence, and severity of metabolic and cardiovascular complications in patients diagnosed as having acromegaly at 60 yr or older (no.=57) as compared to sex- and age-matched healthy controls. Patients and controls underwent a complete endocrine, metabolic, and cardiovascular check-up. The age at diagnosis was equally distributed between 60 to 75 yr while only a minority of the patients (5.3%) was diagnosed after 75 yr. Median GH and IGF-I levels were 15 microg/l and 557 microg/l. The prevalence of microadenomas, enclosed macroadenomas, and extrasellar/invasive macroadenomas was 30%, 49%, and 21%, respectively. All patients had joint complaints and goiter (euthyroid in 65% and pre-toxic/toxic in 35%), 82% had hypertension, 58% diabetes and 54% had both. As compared to controls, a higher number of patients were receiving treatment with anti-arrhythmiacs (p=0.033), anti-aggregants (p=0.013), levothyroxine (p=0.015), and metformin (p=0.022). Nevertheless, the patients had higher systolic and diastolic blood pressure, heart rate, left ventricular mass index, lipids, glucose and insulin levels as well as percent function of beta cells than controls. In conclusion, the high prevalence of systemic complications makes elderly acromegalics more susceptible than controls to cardiovascular events. We suggest that an accurate clinical check-up and, possibly, a more aggressive treatment of hypertension and diabetes are required in elderly acromegalics.


Assuntos
Acromegalia , Cardiomiopatias , Acromegalia/complicações , Acromegalia/metabolismo , Acromegalia/fisiopatologia , Idade de Início , Idoso , Idoso de 80 Anos ou mais , Cardiomiopatias/etiologia , Cardiomiopatias/metabolismo , Cardiomiopatias/fisiopatologia , Fenômenos Fisiológicos Cardiovasculares , Estudos de Casos e Controles , Feminino , Glucose/metabolismo , Hormônio do Crescimento Humano/sangue , Humanos , Fator de Crescimento Insulin-Like I/metabolismo , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Risco
20.
Int J Immunopathol Pharmacol ; 19(1): 111-8, 2006.
Artigo em Inglês | MEDLINE | ID: mdl-16569349

RESUMO

We evaluated, in 415 patients with asymptomatic carotid atherosclerosis: (i) the prevalence of C. pneumoniae DNA in atherosclerotic carotid plaques and peripheral blood mononuclear cells (PBMC); (ii) the distribution of C. pneumoniae in atherosclerotic carotid plaques and PBMC from the same patients; (iii) the correlation between circulating anti-chlamydial antibodies and the presence of C. pneumoniae DNA. Overall, 160 atherosclerotic carotid plaques and 174 PBMC specimens from patients with asymptomatic carotid atherosclerosis were examined by ompA nested touchdown PCR for presence of C. pneumoniae. In addition, C. pneumoniae DNA was detected in 81 specimens of atherosclerotic carotid plaque and PBMC obtained from the same patients. C. pneumoniae DNA was found in 36.9% of atherosclerotic carotid plaques and in 40.2% of PBMC specimens examined (P=NS). With regard to 81 patients, C. pneumoniae DNA was detected in 27.2% of atherosclerotic carotid plaques and in 44.4% of PBMC specimens(P=0.05). In 18 patients, the presence of C. pneumoniae DNA in PBMC specimens and atherosclerotic carotid plaques coincided (P=0.005). No statistically significant association was found between anti-C. pneumoniae antibodies (IgG and IgA) and positive PCR results. In conclusion, our results suggest that the detection of C. pneumoniae DNA in PBMC specimens seems to be a first-choice method to identify the patients at risk for endovascular chlamydial infection.


Assuntos
Doenças das Artérias Carótidas/microbiologia , Chlamydophila pneumoniae/metabolismo , Idoso , Anticorpos Antibacterianos/biossíntese , Anticorpos Antibacterianos/química , Doenças das Artérias Carótidas/patologia , Chlamydophila pneumoniae/imunologia , DNA Bacteriano/química , DNA Bacteriano/isolamento & purificação , DNA Bacteriano/metabolismo , Feminino , Humanos , Imunoglobulina A/análise , Imunoglobulina G/análise , Contagem de Leucócitos , Masculino , Pessoa de Meia-Idade , Monócitos/fisiologia , Reação em Cadeia da Polimerase Via Transcriptase Reversa
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