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2.
Environ Geochem Health ; 44(2): 465-485, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33881674

RESUMO

Thermal waters near the city of Viterbo (Central Italy) are known to show high As contents (up to 600 µg/l). Travertine is precipitated by these waters, forming extended plateau. In this study, we determine the As content, speciation and bioaccessibility in soil and travertine samples collected near a recreational area highly frequented by local inhabitants and tourists to investigate the risk of As exposure through accidental ingestion of soil particles. (Pseudo)total contents in the studied soils range from 17 to 528 mg/kg, being higher in soil developed on a travertine substrate (197 ± 127 mg/kg) than on volcanic rocks (37 ± 13 mg/kg). In travertines, most As is bound to the carbonatic fraction, whereas in soil the semimetal is mostly associated with the oxide and residual fractions. Accordingly, bioaccessibility (defined here by the simplified bioaccessibility extraction test, SBET; Oomen et al., 2002.) is maximum (up to 139 mg/kg) for soil developed on a travertine substrate, indicating a control of calcite dissolution on As bioaccessibility. On the other hand, risk analysis suggests a moderate carcinogenic risk associated with accidental soil ingestion, while dermal contact is negligible. By contrast, ingestion of thermal water implies a higher carcinogenic and systemic health risk.


Assuntos
Arsênio , Poluentes do Solo , Arsênio/análise , Disponibilidade Biológica , Cidades , Humanos , Medição de Risco , Solo/química , Poluentes do Solo/análise
3.
J Appl Anim Welf Sci ; 23(1): 1-9, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-30773055

RESUMO

Commercially available dog treats have become very popular and a common part of the pet's diet, yet very little is known about peoples' opinions and feeding habits; therefore, a survey was shared on a popular social network.Most of the self-selected interviewed owners (n = 1833, 83%) use treats regularly, mainly to reward their dog's behavior or during training-sports activities. Owners usually buy several types of treats, of which biscuits and dental care sticks are the most common, and usually hand out one to five pieces to their dogs every day. Most owners read the labels of the treats to seek the ingredients list and the claimed health benefits; contrarily, many owners look for non-nutritional values, such as flavor (n = 321, 18%), brand (n = 72, 4%) or shape (n = 46, 3%). Seventy-five percent of the owners (n = 1369) follow the feeding instructions provided by the producers on the label.Treat feeding is a common practice among dog owners and there is great variability among regimens (e.g., types and quantities provided). Understanding the owner's attitudes could help veterinarians educate them to manage treats in the dog's diet.


Assuntos
Atitude , Dieta/veterinária , Cães , Adulto , Ração Animal/análise , Animais , Feminino , Vínculo Humano-Animal , Humanos , Itália , Masculino , Pessoa de Meia-Idade , Motivação , Reforço Psicológico , Inquéritos e Questionários
4.
Environ Pollut ; 255(Pt 1): 113191, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31542668

RESUMO

This paper reports the results of a joint project carried out by three regional environmental agencies of Italy to evaluate long-range mercury (Hg) transport from the abandoned Mt. Amiata Hg district in southern Tuscany (the third largest worldwide site for Hg production) to the fluvial ecosystems of the Paglia and Tiber rivers. Most of the work focused on stream sediments, surface waters and soils. A preliminary survey of Hg0 content in air was also conducted. Data obtained by public health authorities on Hg in vegetables and fish were also included. The highest Hg concentrations (up to thousands of µg/g Hg) were observed in stream sediments and soils directly impacted by Hg mine runoff. Although progressive Hg dilution was observed from north to south along the river, sediments and soils show anomalous Hg levels for over 200 km downstream of Mt. Amiata, testifying to an extreme case of long-range Hg contamination. A pervasive redistribution of Hg is observed in all sediment compartments. Presumably, the width of the impacted fluvial corridor corresponds to the entire alluvial plains of the rivers. The floodplains can be considered new sources for downstream Hg redistribution, especially during large flood events. On the other hand, results from water, air, and vegetable sampling indicate low potential for human exposure to Hg. The extent and distribution of the contamination make remediation not viable. Therefore, people and human activities must coexist with such an anomaly. On the technical side, the most urgent action to be taken is a better definition of the exact extent of the contaminated area. On the management side, it is necessary to identify which public institution(s) can best deal with such a widespread phenomenon. According to the precautionary principle, the impact of the contamination on human activities in the affected areas should be considered.


Assuntos
Monitoramento Ambiental/estatística & dados numéricos , Sedimentos Geológicos/química , Mercúrio/análise , Rios/química , Solo/química , Poluentes Químicos da Água/análise , Animais , Conservação dos Recursos Naturais , Ecossistema , Exposição Ambiental/estatística & dados numéricos , Peixes , Humanos , Itália
5.
Andrology ; 6(4): 564-567, 2018 07.
Artigo em Inglês | MEDLINE | ID: mdl-29733116

RESUMO

Peyronie's disease (PD) is a common condition which results in penile curvature making sexual intercourse difficult or impossible. Collagenase clostridium histolyticum (CCH) is the first licensed drug for the treatment of PD and is indicated in patients with palpable plaque and curvature deformity of at least 30° of curvature. However, only few monocentric studies are available in the current literature and this is the first national multicentric study focusing on this new treatment. In five Italian centres, 135 patients have completed the treatment with three injections of CCH using Ralph's shortened modified protocol. The protocol consisted of three intralesional injections of CCH (0.9 mg) given at 4-weekly intervals in addiction to a combination of home modelling, stretching and a vacuum device on a daily basis. An improvement in the angle of curvature was recorded in 128/135 patients (94.8%) by a mean (range) of 19.1 (0-40)° or 42.9 (0-67)% from baseline (p < 0.001). There was also a statistically significant improvement in all IIEF and PDQ questionnaires subdomains (p < 0.001 in all subdomains). This prospective multicentric study confirms that the three-injection protocol is effective enough to achieve a good result and to minimize the cost of the treatment.


Assuntos
Colagenase Microbiana/uso terapêutico , Induração Peniana/tratamento farmacológico , Adulto , Idoso , Humanos , Itália , Masculino , Pessoa de Meia-Idade , Pênis/efeitos dos fármacos , Resultado do Tratamento , Adulto Jovem
6.
Aliment Pharmacol Ther ; 45(1): 115-126, 2017 01.
Artigo em Inglês | MEDLINE | ID: mdl-27790729

RESUMO

BACKGROUND: Chronic hepatitis C virus therapy in patients with advanced liver disease remains a clinical challenge. HCV-TARGET collects data in patients treated at tertiary academic and community centres. AIM: To assess efficacy of all-oral HCV therapy in advanced liver disease. METHODS: Between December 2013 and October 2014, 240 patients with a MELD score of ≥10 initiated HCV treatment with an all-oral regimen. Data from the 220 patients who completed 12-week follow-up were analysed. RESULTS: Genotype 1 (GT1) patients had higher sustained virological response (SVR) when treated with sofosbuvir plus simeprevir ± ribavirin than with sofosbuvir plus ribavirin (66-74% vs. 54%); GT1b vs GT1a (84% vs. 64%). SVR for GT2 was 72% with sofosbuvir plus ribavirin, while GT3 patients had a substantially lower response (35%). A decrease in MELD score was not clearly related to SVR over the short course of follow-up although some had improvements in MELD score, serum bilirubin and albumin. A predictor of virological response was albumin level while negative predictors were elevated bilirubin level and GT1a. Most patients with GT1 were treated with approximately 12-week duration of sofosbuvir and simeprevir ± ribavirin therapy while GT2 and GT3 patients were treated with approximately 12 and 24 weeks of sofosbuvir plus ribavirin respectively. CONCLUSIONS: All-oral therapies are effective among patients with advanced liver disease with high levels of success in GT2 and GT1b, and may serve to reduce the severity of liver disease after SVR. Treatment for GT3 patients remains an unmet need. Clinical trial number: NCT01474811.


Assuntos
Antivirais/administração & dosagem , Bases de Dados Factuais , Hepatite C Crônica/diagnóstico , Hepatite C Crônica/tratamento farmacológico , Cirrose Hepática/diagnóstico , Cirrose Hepática/tratamento farmacológico , Administração Oral , Adulto , Quimioterapia Combinada , Feminino , Hepacivirus/efeitos dos fármacos , Hepatite C Crônica/epidemiologia , Humanos , Internacionalidade , Cirrose Hepática/epidemiologia , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Ribavirina/administração & dosagem , Simeprevir/administração & dosagem , Sofosbuvir/administração & dosagem
7.
ScientificWorldJournal ; 2015: 237930, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26167521

RESUMO

The design and execution of consolidation treatment of settled foundations by means of injection of polyurethane expanding resins require a proper investigation of the state of the foundation soil, in order to better identify anomalies responsible for the instability. To monitor the injection process, a procedure has been developed, which involves, in combination with traditional geotechnical tests, the application of a noninvasive, geophysical technique based on the electrical resistivity, which is strongly sensitive to presence of water or voids. Three-dimensional electrical resistivity tomography is a useful tool to produce effective 3D images of the foundation soils before, during, and after the injections. The achieved information allows designing the consolidation scheme and monitoring its effects on the treated volumes in real time. To better understand the complex processes induced by the treatment and to learn how variations of resistivity accompany increase of stiffness, an experiment was carried out in a full-scale test site. Injections of polyurethane expanding resin were performed as in real worksite conditions. Results confirm that the experimented approach by means of 3D resistivity imaging allows a reliable procedure of consolidation, and geotechnical tests demonstrate the increase of mechanical stiffness.

8.
J Exp Bot ; 66(16): 5043-53, 2015 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-25911742

RESUMO

The homeodomain-leucine zipper (HD-Zip) class of transcription factors is unique to plants. HD-Zip proteins bind to DNA exclusively as dimers recognizing dyad symmetric sequences and act as positive or negative regulators of gene expression. On the basis of sequence homology in the HD-Zip DNA-binding domain, HD-Zip proteins have been grouped into four families (HD-Zip I-IV). Each HD-Zip family can be further divided into subfamilies containing paralogous genes that have arisen through genome duplication. Remarkably, all the members of the HD-Zip IIγ and -δ clades are regulated by light quality changes that induce in the majority of the angiosperms the shade-avoidance response, a process regulated at multiple levels by auxin. Intriguingly, it has recently emerged that, apart from their function in shade avoidance, the HD-Zip IIγ and -δ transcription factors control several auxin-regulated developmental processes, including apical embryo patterning, lateral organ polarity, and gynoecium development, in a white-light environment. This review presents recent advances in our understanding of HD-Zip II protein function in plant development, with particular emphasis on the impact of loss-of-function HD-Zip II mutations on auxin distribution and response. The review also describes evidence demonstrating that HD-Zip IIγ and -δ genes are directly and positively regulated by HD-Zip III transcription factors, primary determinants of apical shoot development, known to control the expression of several auxin biosynthesis, transport, and response genes. Finally, the interplay between HD-Zip II and III transcription factors in embryo apical patterning and organ polarity is discussed.


Assuntos
Proteínas de Arabidopsis/genética , Arabidopsis/genética , Regulação da Expressão Gênica de Plantas , Proteínas de Homeodomínio/genética , Ácidos Indolacéticos/metabolismo , Zíper de Leucina , Arabidopsis/crescimento & desenvolvimento , Arabidopsis/metabolismo , Proteínas de Arabidopsis/metabolismo , Regulação da Expressão Gênica no Desenvolvimento , Proteínas de Homeodomínio/metabolismo , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo
9.
Cell Death Differ ; 21(11): 1696-708, 2014 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-24926615

RESUMO

The development of the cerebral cortex requires coordinated regulation of proliferation, specification, migration and differentiation of cortical progenitors into functionally integrated neurons. The completion of the neurogenic program requires a dynamic interplay between cell intrinsic regulators and extrinsic cues, such as growth factor and neurotransmitters. We previously demonstrated a role for extrasynaptic glycine receptors (GlyRs) containing the α2 subunit in cerebral cortical neurogenesis, revealing that endogenous GlyR activation promotes interneuron migration in the developing cortical wall. The proliferative compartment of the cortex comprises apical progenitors that give birth to neurons directly or indirectly through the generation of basal progenitors, which serve as amplification step to generate the bulk of cortical neurons. The present work shows that genetic inactivation of Glra2, the gene coding the α2 subunit of GlyRs, disrupts dorsal cortical progenitor homeostasis with an impaired capability of apical progenitors to generate basal progenitors. This defect results in an overall reduction of projection neurons that settle in upper or deep layers of the cerebral cortex. Overall, the depletion of cortical neurons observed in Glra2-knockout embryos leads to moderate microcephaly in newborn Glra2-knockout mice. Taken together, our findings support a contribution of GlyR α2 to early processes in cerebral cortical neurogenesis that are required later for the proper development of cortical circuits.


Assuntos
Córtex Cerebral/embriologia , Neurogênese , Neurônios/fisiologia , Receptores de Glicina/genética , Animais , Córtex Cerebral/fisiologia , Regulação da Expressão Gênica no Desenvolvimento , Camundongos , Camundongos Knockout , Neurogênese/genética , Neurônios/metabolismo
10.
Aliment Pharmacol Ther ; 37(1): 91-7, 2013 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-23094860

RESUMO

BACKGROUND: Sorafenib is currently the only approved systemic therapy shown to have efficacy in the treatment of advanced hepatocellular carcinoma (HCC). Recent studies suggest that hepatitis C (HCV)-related HCC patients derive more clinical benefit from sorafenib than other subgroups, but the mechanism for this effect is unknown. In vitro data suggest that sorafenib may exert anti-viral properties, and thus our aim in this study was to evaluate potential anti-viral activity of sorafenib in patients with HCV-related HCC. AIM: To evaluate potential anti-viral activity of sorafenib in patients with HCV-related HCC. METHODS: We prospectively enrolled patients with HCV-related HCC treated with sorafenib for up to 6 months. Baseline clinical, viral and oncologic data were collected. Patients' HCV viral loads were obtained at various time points, and compared with their baseline viral levels. No patients received any known anti-viral therapy during this time. RESULTS: Thirty-three patients were identified with baseline and subsequent HCV levels available for analysis. Six patients completed 6 months of full dose sorafenib, and comparisons of their HCV viral loads showed no significant change at week 24 (difference of means = 0.3500, CI: -0.1799-0.8799, P = 0.150), or the interim time points. Similarly, the HCV viral loads of all patients who received sorafenib and the viral loads of those patients who had tumour response to sorafenib showed no significant changes at any time point. CONCLUSION: Despite preclinical data and previous subgroup analyses suggesting that sorafenib has an anti-viral effect against HCV, this study suggests that sorafenib lacks significant anti-viral activity in HCV patients with HCC.


Assuntos
Antineoplásicos/uso terapêutico , Carcinoma Hepatocelular/tratamento farmacológico , Hepatite C/tratamento farmacológico , Neoplasias Hepáticas/tratamento farmacológico , Niacinamida/análogos & derivados , Compostos de Fenilureia/uso terapêutico , Idoso , Idoso de 80 Anos ou mais , Carcinoma Hepatocelular/virologia , Estudos de Coortes , Feminino , Hepatite C/virologia , Humanos , Neoplasias Hepáticas/virologia , Masculino , Pessoa de Meia-Idade , Niacinamida/uso terapêutico , Sorafenibe , Resultado do Tratamento , Carga Viral
11.
Cell Death Dis ; 3: e440, 2012 Dec 06.
Artigo em Inglês | MEDLINE | ID: mdl-23222510

RESUMO

The phosphoinositide 3-kinases (PI3Ks) are heterodimers consisting of the catalytic subunit p110 and the regulatory subunit p85. The PI3K/Akt pathway is strongly deregulated in breast cancer (BC) representing one of the mechanisms of resistance to therapies. Therefore, the identification of inhibitors of PI3K components represents one of the main goals to produce therapeutic agents. Here, we evaluated the efficacy of a phosphopeptide 1257 (P-1257) that targeting p85 strongly inhibits PI3K activity. We tested the effects of P-1257 administration in vitro and in vivo using BC cells expressing different levels of ErbB-2 and resistant or responsive to Trastuzumab. We demonstrated that inhibition of p85 activity by P-1257 induces cell death and sensitizes JIMT-1 and KPL-4 ErbB-2-overexpressing BC cells to Trastuzumab treatment. It is noteworthy that P-1257 delivery in vivo by electroporation or liposomes significantly inhibits the proliferation of tumor cells engrafted at subcutaneous and visceral sites. Overall, our data indicate that the p85 subunit is a valid target for therapeutic approaches and suggest that the structure of the peptide used in our study could be utilized for the development of novel drugs to apply in combination with therapies that fail to cure BCs with high PI3K activity.


Assuntos
Antineoplásicos/farmacologia , Neoplasias da Mama/enzimologia , Regulação para Baixo , Inibidores Enzimáticos/farmacologia , Fosfatidilinositol 3-Quinases/metabolismo , Animais , Apoptose/efeitos dos fármacos , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/genética , Domínio Catalítico , Feminino , Humanos , Proteínas Substratos do Receptor de Insulina/metabolismo , Camundongos , Camundongos SCID , Fosfatidilinositol 3-Quinases/genética , Inibidores de Fosfoinositídeo-3 Quinase , Fosfopeptídeos/farmacologia , Ligação Proteica/efeitos dos fármacos , Proteínas Proto-Oncogênicas c-akt/genética , Proteínas Proto-Oncogênicas c-akt/metabolismo , Receptor ErbB-3/metabolismo
12.
Biotechnol Adv ; 30(5): 1047-58, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-21888962

RESUMO

The success of competitive interactions between plants determines the chance of survival of individuals and eventually of whole plant species. Shade-tolerant plants have adapted their photosynthesis to function optimally under low-light conditions. These plants are therefore capable of long-term survival under a canopy shade. In contrast, shade-avoiding plants adapt their growth to perceive maximum sunlight and therefore rapidly dominate gaps in a canopy. Daylight contains roughly equal proportions of red and far-red light, but within vegetation that ratio is lowered as a result of red absorption by photosynthetic pigments. This light quality change is perceived through the phytochrome system as an unambiguous signal of the proximity of neighbors resulting in a suite of developmental responses (termed the shade avoidance response) that, when successful, result in the overgrowth of those neighbors. Shoot elongation induced by low red/far-red light may confer high relative fitness in natural dense communities. However, since elongation is often achieved at the expense of leaf and root growth, shade avoidance may lead to reduction in crop plant productivity. Over the past decade, major progresses have been achieved in the understanding of the molecular basis of shade avoidance. However, uncovering the mechanisms underpinning plant response and adaptation to changes in the ratio of red to far-red light is key to design new strategies to precise modulate shade avoidance in time and space without impairing the overall crop ability to compete for light.


Assuntos
Adaptação Fisiológica , Meio Ambiente , Fenômenos Fisiológicos Vegetais , Adaptação Fisiológica/efeitos da radiação , Produtos Agrícolas/fisiologia , Produtos Agrícolas/efeitos da radiação , Luz , Transdução de Sinal Luminoso/efeitos da radiação , Fenômenos Fisiológicos Vegetais/efeitos da radiação
13.
Aliment Pharmacol Ther ; 34(2): 205-13, 2011 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-21605146

RESUMO

BACKGROUND: Standard of practice involves using transarterial therapy for multifocal hepatocellular carcinoma (HCC) alone and sorafenib only for more advanced HCC, but the sorafenib and transarterial therapy combination may provide greater efficacy. AIM: To evaluate the safety and efficacy of concurrent sorafenib and transarterial therapy in HCC. METHODS: Consecutive cases of HCC were treated with sorafenib and transarterial therapy, receiving sorafenib 2 to 4weeks before transarterial therapy. Baseline clinical parameters, adverse events (AEs) and survival were collected. RESULTS: A total of 47 patients received sorafenib and transarterial therapy. The majority of the patients were male (70%) with HCV (60%), median age of 60years, good performance status (0-1), stable cirrhosis (Child: A 72%; B 28%), unresectable tumour (stage: B 81%; C 19%) and median AFP of 24ng/mL. Median follow-up was 12months and median time on sorafenib was 6months. LC Bead TACE was used with a median frequency of 3. The majority of the patients (89%) experienced AEs. The most common AEs were fatigue (51%), hand-foot skin reaction (51%) and diarrhoea (43%). Grade 3 and 4 AEs included fatigue (13%) and hand-foot skin reaction (26%). Most patients required a dose reduction (66%). The main AE related to transarterial therapy was post-TACE syndrome (23%). The disease control rate was 68% at 6months. Overall median survival rate was 18.5months (95% CI 16.1-20.9months). CONCLUSION: Concurrent sorafenib and transarterial therapy is overall safe with no unexpected side effects and encouraging efficacy that warrants further study.


Assuntos
Antineoplásicos/uso terapêutico , Benzenossulfonatos/uso terapêutico , Carcinoma Hepatocelular/terapia , Quimioembolização Terapêutica , Neoplasias Hepáticas/terapia , Piridinas/uso terapêutico , Idoso , Antineoplásicos/efeitos adversos , Benzenossulfonatos/efeitos adversos , Carcinoma Hepatocelular/tratamento farmacológico , Terapia Combinada , Feminino , Humanos , Neoplasias Hepáticas/tratamento farmacológico , Masculino , Pessoa de Meia-Idade , Niacinamida/análogos & derivados , Compostos de Fenilureia , Piridinas/efeitos adversos , Sorafenibe , Resultado do Tratamento
14.
Aliment Pharmacol Ther ; 33(7): 845-54, 2011 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-21272047

RESUMO

BACKGROUND: Novel rabeprazole extended-release (ER) formulations were developed to provide prolonged gastric acid suppression and potentially improved clinical outcomes in GERD patients. AIM: To evaluate the pharmacodynamics and pharmacokinetics of six rabeprazole-ER formulations vs. esomeprazole 40 mg and rabeprazole delayed-release (DR) 20 mg. METHODS: Helicobacter pylori-negative healthy subjects were randomised to receive one of eight treatments once daily for 5 days. Twenty-four-hour intragastric pH was monitored on days -1, 1 and 5. Rabeprazole plasma concentrations were measured on day 5. RESULTS: A total of 248 subjects (N=31/group) were enrolled in the study. On day 5, rabeprazole-ER groups provided mean durations of 18.5-20.2 h (77.0-84.1% of 24-h) with intragastric pH >4.0 vs. esomeprazole 40 mg (15.9 h/66.1% of 24-h) and rabeprazole-DR 20 mg (15.2 h/63.2% of 24-h). A similar increase was observed on day 1. While percentage of daytime (8 am-10 pm) with intragastric pH >4.0 on day 5 was overall similar across the groups, percentage of night-time (10 pm-8 am) with intragastric pH >4.0 was higher with the rabeprazole-ER groups (57.0-72.4%) vs. esomeprazole 40 mg (32.8%) and rabeprazole-DR 20 mg (34.0%). CONCLUSION: Rabeprazole-ER once daily for 5 days demonstrated a significantly longer duration of gastric acid suppression in 24 h vs. esomeprazole 40 mg and rabeprazole-DR 20 mg. The increase in acid suppression was predominantly due to prolonged acid suppression during the night-time; this was supported by the extended-release pharmacokinetic characteristics.


Assuntos
2-Piridinilmetilsulfinilbenzimidazóis/administração & dosagem , Antiulcerosos/administração & dosagem , Preparações de Ação Retardada/administração & dosagem , Esomeprazol/administração & dosagem , 2-Piridinilmetilsulfinilbenzimidazóis/farmacocinética , Adulto , Antiulcerosos/farmacocinética , Quimioterapia Combinada , Esomeprazol/farmacocinética , Feminino , Ácido Gástrico/fisiologia , Determinação da Acidez Gástrica , Humanos , Concentração de Íons de Hidrogênio/efeitos dos fármacos , Masculino , Pessoa de Meia-Idade , Rabeprazol , Estatística como Assunto , Adulto Jovem
15.
Aliment Pharmacol Ther ; 33(2): 235-42, 2011 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-21083674

RESUMO

BACKGROUND: Newer therapies are needed for patients with primary biliary cirrhosis and incomplete response to ursodeoxycholic acid (UDCA). Fenofibrate is a fibric acid postulated to regulate immune response and cell proliferation. AIM: To evaluate the efficacy and safety of fenofibrate in patients with primary biliary cirrhosis and incomplete response to UDCA. METHODS: We undertook a pilot study involving 20 patients with primary biliary cirrhosis and serum alkaline phosphatase (ALP) ≥ 2× ULN. Nonparametric statistical tests and Spearman correlation test were used as appropriate. RESULTS: Twenty patients received fenofibrate (160 mg/day) in addition to UDCA for 48 weeks. Median serum ALP decreased significantly at 48 weeks compared with baseline values [351 (214-779) U/L at baseline vs. 177 (60-384) U/L at 48 weeks, P < 0.05]. A rebound in ALP occurred upon drug discontinuation. Serum aspartate aminotransferase and Immunoglobulin M also decreased significantly, while bilirubin and albumin remained unchanged. Median IL-1 decreased from 28.9 (2.7-10 000) to 11.3 (2.5-277.7) pg/mL (P = 0.049), and median IL-6 from 4.6 (3.2-5205) to 3.5 (3.2-73.4) pg/mL (P = 0.027). Heartburn was the most frequent adverse event, leading to discontinuation of two study subjects. CONCLUSIONS: Combination therapy of fenofibrate and UDCA induced significant biochemical improvement in patients with primary biliary cirrhosis and incomplete response to UDCA. Further studies are warranted.


Assuntos
Colagogos e Coleréticos/administração & dosagem , Fenofibrato/administração & dosagem , Hipolipemiantes/administração & dosagem , Cirrose Hepática Biliar/tratamento farmacológico , Ácido Ursodesoxicólico/administração & dosagem , Adulto , Idoso , Colagogos e Coleréticos/efeitos adversos , Quimioterapia Combinada , Feminino , Fenofibrato/efeitos adversos , Humanos , Hipolipemiantes/efeitos adversos , Masculino , Pessoa de Meia-Idade , Projetos Piloto , Estatística como Assunto , Resultado do Tratamento , Ácido Ursodesoxicólico/efeitos adversos
16.
J Clin Pediatr Dent ; 36(1): 75-8, 2011.
Artigo em Inglês | MEDLINE | ID: mdl-22900448

RESUMO

OBJECTIVE: The purpose of the present manuscript is to describe the location and extent of hyperbilirubinemic stain in a primary molar of a 3-year-old who was diagnosed with cystic fibrosis shortly after birth, subsequently developed liver disease and hyperbilirubinemia, and received a liver transplant at age 10-months. STUDY DESIGN: Clinical and histological assessments were performed to evaluate the location and extent of hyperbilirubinemic stain in an extracted primary molar. RESULTS: The clinical image, and macroscopic and microscopic histological examinations of a primary molar showed hyperbilirubinemic staining of enamel and of the coronal dentin that developed between birth and when the liver transplant took place, irregular dentin tubules, and an irregular cementum-dentinal junction. CONCLUSIONS: The findings of the present manuscript indicate that hyperbilirubinemc staining of primary teeth affects dental hard tissues at the time of their calcification, and the clinical picture of the stain may be related to stained enamel and/or dentin, and underlying stained dentin visible through translucent unstained enamel.


Assuntos
Fibrose Cística/complicações , Dentina/patologia , Hiperbilirrubinemia Neonatal/patologia , Dente Molar/patologia , Pré-Escolar , Fibrose Cística/patologia , Hipoplasia do Esmalte Dentário/etiologia , Hipoplasia do Esmalte Dentário/patologia , Polpa Dentária/patologia , Dentina/anormalidades , Humanos , Hiperbilirrubinemia Neonatal/complicações , Hiperbilirrubinemia Neonatal/etiologia , Falência Hepática/etiologia , Falência Hepática/cirurgia , Transplante de Fígado , Masculino , Dente Decíduo/patologia
17.
Eur J Surg Oncol ; 36(3): 287-91, 2010 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-19796914

RESUMO

AIMS: To investigate the incidence and long-term effects on kidney function of obstructive and nonobstructive dilatation of the upper urinary tract in patients with ileal neobladder with refluxing ureterointestinal anastomoses. METHODS: We retrospectively analyzed a prospectively derived database of 110 patients with bladder cancer and who were treated with an ileal neobladder between 1996 and 2007 using refluxing end-to-side ureterointestinal anastomoses on a short afferent limb. The mean follow up was 65 months. At every follow up visit the patients had an analysis of serum creatinine, urine culture, abdominal CT or ultrasonography, and, if there was dilatation of the upper urinary tract, 99mTc-DTPA renal scintigraphy was requested. RESULTS: In all, 206 renoureteral units were included in the study. Overall, seven had anastomotic stricture and of those, three were symptomatic and were corrected; while four were asymptomatic and of those, only two, with preserved split GFR, were surgically treated, while the remaining two, with a poor split GFR, were followed up. The last 99mTc-DTPA showed a preserved split GFR in the reimplanted units and further split renal function decrease in untreated units. Nonobstructive dilatation of the upper urinary tract, caused by reflux, was diagnosed in 13 units. The dilatation was bilateral in three patients with recurrent UTIs and urosepsis, and the split GFR was bilaterally reduced at diagnosis with a further reduction at the last 99mTc-DTPA. The remaining seven units with sterile urine, showed a preserved split GFR during follow up. CONCLUSIONS: All strictures, regardless of their severity, should be immediately corrected. Reflux per se does not provoke renal impairment unless recurrent UTIs and urosepsis are present.


Assuntos
Cistectomia/efeitos adversos , Taxa de Filtração Glomerular/fisiologia , Íleo/cirurgia , Obstrução Ureteral/fisiopatologia , Neoplasias da Bexiga Urinária/cirurgia , Coletores de Urina , Refluxo Vesicoureteral/fisiopatologia , Idoso , Anastomose Cirúrgica , Cistectomia/métodos , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias , Prognóstico , Estudos Prospectivos , Fatores de Tempo , Obstrução Ureteral/diagnóstico , Obstrução Ureteral/cirurgia , Bexiga Urinária/cirurgia , Refluxo Vesicoureteral/diagnóstico
18.
Int J Impot Res ; 21(5): 311-4, 2009.
Artigo em Inglês | MEDLINE | ID: mdl-19458620

RESUMO

Using our prospectively derived database, we identified 17 patients with squamous-cell carcinoma involving the glans penis, who were treated using organ-sparing surgery between March 2003 and January 2008. Of them, two were treated with partial glansectomy with primary glans closure, and 15 underwent total glans amputation and reconstruction of a new glans using a split-thickness skin graft (STSG). These 15 patients represent the subject of our study (mean age 51 years, range 42 to 59 years). Overall, two patients had early partial loss of the graft and of them, one required surgical regrafting. Two late complications occurred, consisting of one meatal stenosis and one postoperative phimosis. At a mean follow-up of 36 months, functional results were extremely satisfactory. All patients maintained their erectile function with good vaginal penetration starting from 3 months after surgery, with a range between 2 and 6 months. Orgasm and ejaculation were preserved in all patients, although reduced glans sensitivity was reported by all patients. No local recurrences were reported.


Assuntos
Carcinoma de Células Escamosas/cirurgia , Neoplasias Penianas/cirurgia , Pênis/cirurgia , Transplante de Pele/métodos , Adulto , Carcinoma de Células Escamosas/patologia , Carcinoma de Células Escamosas/terapia , Terapia Combinada , Ejaculação/efeitos dos fármacos , Humanos , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia , Orgasmo/fisiologia , Neoplasias Penianas/patologia , Neoplasias Penianas/terapia , Complicações Pós-Operatórias/patologia , Reoperação , Estudos Retrospectivos , Resultado do Tratamento
19.
Expert Opin Pharmacother ; 9(17): 2939-45, 2008 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-19006470

RESUMO

BACKGROUND: Prescription omega-3-acid ethyl esters (P-OM3) have been used as adjunctive therapy to statin drugs in patients with mixed hyperlipidemia. OBJECTIVE: To assess the effect of concomitant administration of 4 g P-OM3 on the steady-state pharmacokinetics of the maximum recommended daily dose of atorvastatin (80 mg) in healthy volunteers. METHODS: This was a randomized, open-label, repeated-dose, two-way crossover, drug interaction study of two treatments: 4 g of P-OM3 with 80 mg atorvastatin daily or 80 mg atorvastatin daily, each administered for 14 days under fasting conditions to 50 healthy adults. MAIN OUTCOME MEASURES: The primary determinants of drug interaction were the ln-transformed area under the plasma concentration versus time curve (AUCtau) and maximum measured steady-state plasma concentration (C(max,ss)) over the final 24 h dosing interval (day 14) for atorvastatin and 2-hydroxyatorvastatin. Safety assessment included clinical laboratory evaluations and adverse event reporting. RESULTS: The extent and rate of exposure (AUCtau, C(max,ss)) to atorvastatin and its active metabolites following daily administration of P-OM3 with atorvastatin (80 mg) were similar to those following the administration of atorvastatin (80 mg) alone. Both treatments were well tolerated. CONCLUSIONS: After 14 days of dosing, the rate and extent of exposure (AUCtau, C(max,ss)) to atorvastatin and its active metabolites were similar with both treatments, indicating that administration of P-OM3 did not affect the steady-state bioavailability of orally administered atorvastatin.


Assuntos
Ácidos Graxos Ômega-3/farmacologia , Saúde , Ácidos Heptanoicos/sangue , Ácidos Heptanoicos/farmacocinética , Pirróis/sangue , Pirróis/farmacocinética , Adulto , Atorvastatina , Feminino , Ácidos Heptanoicos/administração & dosagem , Ácidos Heptanoicos/efeitos adversos , Humanos , Masculino , Pessoa de Meia-Idade , Pirróis/administração & dosagem , Pirróis/efeitos adversos
20.
Clin Radiol ; 63(10): 1142-8, 2008 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-18774362

RESUMO

AIM: To investigate whether sonographic (US) surveillance of polytetrafluoroethylene covered transjugular intrahepatic portosystemic shunts (TIPS) is necessary. MATERIALS AND METHODS: We identified 128 patients who underwent TIPS for complications of portal hypertension between January 2001 and December 2005 at a large tertiary centre. Procedural data were retrospectively analysed. US surveillance of the TIPS was performed at baseline with scheduled follow-up or whenever shunt dysfunction was suspected. Clinical and radiology reports were compared to assess US surveillance of the TIPS. RESULTS: Four hundred and twenty-six US studies were performed, with a median of three per patient (range 1-5). The median follow-up period was 378 days (range 1-1749 days). Twenty-three patients (18%) had baseline US studies performed only whereas 105 (82%) also had follow-up studies. Forty-one (32%) of 128 patients [32 (78%) Wallstent, nine (22%) Viatorr] had Doppler ultrasound abnormalities noted. Venography was performed in all 41 patients. Abnormal venography and elevated hepatic venous pressure gradient (HVPG) was seen in 34 (82.9%) of the 41 patients [29 (85.3%) Wallstent, five (14.7%) Viatorr]. Among the 34 patients, 17 (50%) [13 (76.5%) Wallstent, four (23.5%) Viatorr] had venographic abnormalities noted at the hepatic venous end accompanied by increased HVPG. All four of the Viatorr patients had minor narrowing at the hepatic venous end and HVPG measurements that ranged 3-4 mm Hg above 12 mm Hg. CONCLUSION: Considering the improved patency of covered stents in TIPS, US surveillance may be superfluous after the baseline study.


Assuntos
Hipertensão Portal/cirurgia , Derivação Portossistêmica Transjugular Intra-Hepática/instrumentação , Stents , Adolescente , Adulto , Idoso , Materiais Revestidos Biocompatíveis , Feminino , Seguimentos , Humanos , Assistência de Longa Duração/métodos , Masculino , Pessoa de Meia-Idade , Politetrafluoretileno , Derivação Portossistêmica Transjugular Intra-Hepática/métodos , Portografia , Cuidados Pós-Operatórios/métodos , Falha de Prótese , Estudos Retrospectivos , Ultrassonografia Doppler , Procedimentos Desnecessários , Grau de Desobstrução Vascular
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