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1.
Cells ; 11(10)2022 05 19.
Artículo en Inglés | MEDLINE | ID: mdl-35626733

RESUMEN

BACKGROUND: Breast cancer (BC) is the leading cause of death worldwide. The severity of BC strictly depends on the molecular subtype. The less aggressive hormone-positive subtype is treated with adjuvant endocrine therapy (AET), which causes both physical and psychological side effects. This condition strongly impacts the adherence and persistence of AET among oncologic patients. Moreover, viral infections also constitute a serious problem for public health. Despite their efficacy, antiviral agents present several therapeutic limits. Accordingly, in the present work, we investigated the antitumor and antiviral activities of Orobanche crenata Forssk. (O. crenata), a parasitic plant, endemic to the Mediterranean basin, traditionally known for its beneficial properties for human health. METHODS: The MTT assay was carried out to evaluate the cytotoxic effect of O. crenata leaf extract (OCLE) on human breast cancer cells (MCF-7 and MDA-MB-231) and the primary HFF-1 cell line. The lactic dehydrogenase (LDH) assay was performed on MCF-7 cells to analyze necrotic cell death. The antioxidant effect of OCLE was evaluated by intracellular determination of the reactive oxygen species and thiol groups, by DPPH and ABTS assays. The antiviral activity of OCLE was determined against Poliovirus 1, Echovirus 9, Human respiratory syncytial virus, Adenovirus type 2 and type 5, Coxsackievirus B1 (CoxB1) and B3 (CoxB3), Herpes simplex type 1 (HSV-1) and type 2 (HSV-2), and ß-Coronavirus by the plaque reduction assay. RESULTS: The extract, after 24 h of incubation, did not affect MDA-MB-231 and HFF-1 cell viability. However, at the same time point, it showed a dose-dependent inhibitory effect on MCF-7 cells, with an increase in LDH release. OCLE exhibited free radical scavenging activity and significantly increased non-protein thiol levels in MCF-7 cells. OCLE effectively inhibited HSV-1, HSV-2, CoxB1, and CoxB3 replication. CONCLUSIONS: The overall results showed an interesting inhibitory effect of OCLE on both MCF-7 cell survival and viral replication.


Asunto(s)
Neoplasias de la Mama , Herpesvirus Humano 1 , Orobanche , Femenino , Humanos , Antivirales/uso terapéutico , Neoplasias de la Mama/tratamiento farmacológico , Herpesvirus Humano 1/fisiología , Células MCF-7 , Extractos Vegetales/química , Extractos Vegetales/farmacología , Compuestos de Sulfhidrilo/farmacología , Replicación Viral
2.
Antibiotics (Basel) ; 10(2)2021 Feb 04.
Artículo en Inglés | MEDLINE | ID: mdl-33557378

RESUMEN

The difficulty to treat resistant strains-related hospital-acquired infections (HAIs) promoted the study of phytoextracts, known sources of bioactive molecules. Accordingly, in the present study, the pharmacological activities of Juglans regia (L.) pellicle extract (WPE) were investigated. The antiviral effect was tested against Herpes simplex virus type 1 and 2, Poliovirus 1, Adenovirus 2, Echovirus 9, Coxsackievirus B1 through the plaque reduction assay. The antibacterial and antifungal activities were evaluated against medically important strains, by the microdilution method. DPPH and superoxide dismutase (SOD)s-like activity assays were used to determine the antioxidant effect. Besides, the extract was screened for cytotoxicity on Caco-2, MCF-7, and HFF1 cell lines by the 3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide (MTT) assay. The total phenolic and flavonoid contents were also evaluated. Interestingly, WPE inhibited Herpes simplex viruses (HSVs) replication, bacterial and fungal growth. WPE showed free radical scavenging capacity and inhibited superoxide anion formation in a dose-dependent manner. These effects could be attributed to the high content of phenols and flavonoids, which were 0.377 ± 0.01 mg GE/g and 0.292 ± 0.08 mg CE/g, respectively. Moreover, WPE was able to reduce Caco-2 cell viability, at both 48 h and 72 h. The promising results encourage further studies aimed to better elucidate the role of WPE in the prevention of human infectious diseases.

3.
Nat Prod Res ; 35(12): 2076-2081, 2021 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-31397177

RESUMEN

Juglans regia L. (common walnut) is a deciduous tree belonging to Juglandaceae family. Since ancient time, walnut was widely used in traditional medicine for its antioxidant, antidiabetic, antimicrobial, anti-inflammatory, anti-atherogenic and liver-protective effects. In this work, the antibacterial and anti-biofilm activities of walnuts pellicle extract against coagulase-negative staphylococci were evaluated. Qualitative chemical analysis was performed by the thin layer chromatography. UPLC-Ms/Ms was used to identify the chemical composition of J. regia extract. The total flavonoid and phenolic contents were determined by the Aluminium chloride and Folin-Ciocalteu methods, respectively. The extract showed antibacterial activity with MIC ranging from 3.60 to 461.75 µg/ml and MBC ranging from 461.75 to >461.75 µg/ml. Furthermore, it significantly reduced biofilm biomass and cell viability in a dose-dependent manner. Biological activities of J. regia extract may be due to its high flavonoid and phenolic contents. The obtained results are promising and they deserve further scientific investigations.


Asunto(s)
Antibacterianos/farmacología , Juglans/química , Extractos Vegetales/farmacología , Staphylococcus/efectos de los fármacos , Antibacterianos/administración & dosificación , Antibacterianos/química , Biopelículas/efectos de los fármacos , Cromatografía Liquida , Coagulasa/análisis , Relación Dosis-Respuesta a Droga , Flavonoides/análisis , Nueces/química , Fenoles/análisis , Extractos Vegetales/administración & dosificación , Extractos Vegetales/análisis , Extractos Vegetales/química , Plantas Medicinales/química , Staphylococcus/fisiología , Espectrometría de Masas en Tándem
4.
Int J Mol Sci ; 21(17)2020 Sep 03.
Artículo en Inglés | MEDLINE | ID: mdl-32899428

RESUMEN

B-cell non-Hodgkin lymphomas (B-NHLs) are often characterized by the development of resistance to chemotherapeutic drugs and/or relapse. During drug-induced apoptosis, Yin Yang 1 (YY1) transcription factor might modulate the expression of apoptotic regulators genes. The present study was aimed to: (1) examine the potential oncogenic role of YY1 in reversing drug resistance in B-NHLs; and (2) identify YY1 transcriptional target(s) that regulate the apoptotic pathway in B-NHLs. Predictive analyses coupled with database-deposited data suggested that YY1 binds the promoter of the BIRC5/survivin anti-apoptotic gene. Gene Expression Omnibus (GEO) analyses of several B-NHL repositories revealed a conserved positive correlation between YY1 and survivin, both highly expressed, especially in aggressive B-NHLs. Further validation experiments performed in Raji Burkitt's lymphomas cells, demonstrated that YY1 silencing was associated with survivin downregulation and sensitized the cells to apoptosis. Overall, our results revealed that: (1) YY1 and survivin are positively correlated and overexpressed in B-NHLs, especially in BLs; (2) YY1 strongly binds to the survivin promoter, hence survivin may be suggested as YY1 transcriptional target; (3) YY1 silencing sensitizes Raji cells to drug-induced apoptosis via downregulation of survivin; (4) both YY1 and survivin are potential diagnostic markers and therapeutic targets for the treatment of resistant/relapsed B-NHLs.


Asunto(s)
Biomarcadores de Tumor/metabolismo , Resistencia a Antineoplásicos/genética , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Linfoma de Células B/patología , Survivin/metabolismo , Factor de Transcripción YY1/metabolismo , Protocolos de Quimioterapia Combinada Antineoplásica/farmacología , Apoptosis , Biomarcadores de Tumor/genética , Proliferación Celular , Silenciador del Gen , Humanos , Linfoma de Células B/tratamiento farmacológico , Linfoma de Células B/genética , Linfoma de Células B/metabolismo , Survivin/genética , Células Tumorales Cultivadas , Factor de Transcripción YY1/antagonistas & inhibidores , Factor de Transcripción YY1/genética
5.
Curr Microbiol ; 77(10): 2841-2846, 2020 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-32607824

RESUMEN

Chlamydophila pneumoniae is an intracellular pathogen responsible for respiratory tract infections. The isolation of the microorganism from clinical specimens is essential for a diagnosis. However, the identification of C. pneumoniae by cell cultures is very difficult besides strongly depending on the sample conditions. The study aimed to investigate, in adult patients with pharyngotonsillitis, the frequency of Chlamydophila pneumoniae detection by cell cultures and three conventional PCRs (a conventional PCR targeting the 16S rRNA gene and two nested PCRs, targeting the 16S rRNA gene and the ompA gene, respectively). The presence of chlamydial inclusion in cell cultures was observed in 11/94 samples (11.70%) by IFA. C. pneumoniae DNA was detected in 12/94 (12.76%) specimens by the 16S rRNA gene nested PCR, 4/94 (4.26%) by ompA gene nested PCR, and in 2/94 (2.13%) by 16S rRNA single-step PCR. Our data show poor agreement between the three applied DNA-amplification methods; in fact, only 16S rRNA gene nested PCR showed a statistically significant difference. Moreover, this result allowed us to achieve a definitive confirmation of the previous finding and to avoid the risk of an overestimation of the C. pneumoniae as a pathogen in pharyngotonsillitis.


Asunto(s)
Tonsila Faríngea , Técnicas de Cultivo de Célula , Chlamydophila pneumoniae , Técnicas Microbiológicas , Reacción en Cadena de la Polimerasa , Tonsilitis , Tonsila Faríngea/microbiología , Adulto , Chlamydophila pneumoniae/genética , ADN Bacteriano/genética , Técnicas de Diagnóstico del Sistema Respiratorio/normas , Humanos , Técnicas Microbiológicas/métodos , Técnicas Microbiológicas/normas , Reacción en Cadena de la Polimerasa/normas , ARN Ribosómico 16S/genética , Sensibilidad y Especificidad , Tonsilitis/microbiología
6.
Oncotarget ; 8(42): 71528-71535, 2017 Sep 22.
Artículo en Inglés | MEDLINE | ID: mdl-29069725

RESUMEN

Mixed cryoglobulinemia (MC), is a HCV-related, clinically benign, lymphoproliferative disorder (LPD) that may evolve into a non Hodgkin's lymphoma (NHL). Significant associations were found between two single nucleotide polymorphisms near NOTCH4 (rs2071286) and the HLA class II (rs9461776) genes and HCV-related MC syndrome (MCS). We analyzed NOTCH4 rs2071286 and HLA-II rs9461776 in 3 HCV-related LPD groups (asymptomatic MC, MCS, NHL) with HCV infection without lymphoproliferative disorders. We found a positive relationship between NOTCH4 rs207186 T minor allele frequency (MAF) and patients with HCV-related LPDs at risk of NHL (Chi-square test for trend = 14.84 p = 0.0001), in accordance with an over-dominant model in the NHL group (CT vs CC + TT, OR=1.88, 95% CI 1.24-2.83, p = 0.0026). Regarding HLA II rs9461776, G MAF increased in patients with HCV-related LPDs at risk of NHL (Chi-square test for trend = 8.40 p = 0.0038), in accordance with a recessive genotypic model in the NHL group (G/G vs A/A + A/G, OR = 11.07, 95% CI 2.37-51.64, p = 0.0022). Both NOTCH4 rs2071286 and HLA-II rs9461776 were present on chromosome 6 and showed D' and r values of linkage disequilibrium (LD) of about 0.5 values, thereby suggesting there is no extensive LD in the HCV+ population. This data shows that the previously demonstrated association between NOTCH4 rs2071286 and HLA-II rs9461776 polymorphisms and HCV-related MCS could be extended to overall patients with HCV-related LPDs. The significant relationship between rs2071286 and rs9461776 MAF and the increased risk for NHL, suggests their use as non-invasive markers to categorize patients at risk of lymphoma.

7.
Mol Med Rep ; 15(5): 3336-3339, 2017 May.
Artículo en Inglés | MEDLINE | ID: mdl-28339065

RESUMEN

Health care workers (HCWs) are frequently exposed to different biological agents during their activities and are frequently monitored. Among these infectious agents, human hepatitis C (HCV) can infect HCWs. In this review article, the risk of HCV infection among HCWs is discussed along with extrahepatic HCV-related malignancies, such as non­Hodgkin lymphoma. Accidental contamination, represented by percutaneous and mucocutaneous infections is the main risk factor for such infection. The compliance of the protection procedures, included in the current regulation for HCWs, is the most important issue to reduce the risk of pathogen infections that in turn may produce reduction of infection­associated malignancies.


Asunto(s)
Hepatitis C/complicaciones , Linfoma no Hodgkin/etiología , Personal de Salud/estadística & datos numéricos , Hepatitis C/diagnóstico , Humanos , Exposición Profesional , Factores de Riesgo
8.
Bioorg Med Chem ; 23(17): 5345-51, 2015 Sep 01.
Artículo en Inglés | MEDLINE | ID: mdl-26260341

RESUMEN

Hydroxytyrosol and dihydrocaffeoyl catechols with lipophilic properties have been synthesized in high yield using tyrosinase immobilized on multi-walled carbon nanotubes by the Layer-by-Layer technique. All synthesized catechols were evaluated against a large panel of DNA and RNA viruses, including Poliovirus type 1, Echovirus type 9, Herpes simplex virus type 1 (HSV-1), Herpes simplex virus type 2 (HSV-2), Coxsackievirus type B3 (Cox B3), Adenovirus type 2 and type 5 and Cytomegalovirus (CMV). A significant antiviral activity was observed in the inhibition of HSV-1, HSV-2, Cox B3 and CMV. The mechanism of action of the most active dihydrocaffeoyl derivative was investigated against a model of HSV-1 infection.


Asunto(s)
Antivirales/química , Antivirales/farmacología , Catecoles/química , Catecoles/farmacología , Virus ADN/efectos de los fármacos , Virus ARN/efectos de los fármacos , Agaricus/enzimología , Infecciones por Virus ADN/tratamiento farmacológico , Enzimas Inmovilizadas/química , Humanos , Modelos Moleculares , Monofenol Monooxigenasa/química , Nanotubos de Carbono/química , Alcohol Feniletílico/análogos & derivados , Alcohol Feniletílico/química , Alcohol Feniletílico/farmacología , Infecciones por Virus ARN/tratamiento farmacológico
9.
Molecules ; 20(4): 5260-75, 2015 Mar 24.
Artículo en Inglés | MEDLINE | ID: mdl-25812148

RESUMEN

A novel series of C-nucleosides, featuring the presence of a 1,2,3-triazole ring linked to an isoxazolidine system, has been designed as mimetics of the pyrimidine nucleobases. An antiproliferative effect was observed for compounds 17a and 17b: the growth inhibitory effect reaches the 50% in HepG2 and HT-29 cells and increases up to 56% in the SH-SY5Y cell line after 72 h of incubation at a 100 µM concentration.


Asunto(s)
Antineoplásicos/síntesis química , Antineoplásicos/farmacología , Isoxazoles/síntesis química , Isoxazoles/farmacología , Antineoplásicos/química , Proliferación Celular/efectos de los fármacos , Ensayos de Selección de Medicamentos Antitumorales , Células HT29 , Células Hep G2 , Humanos , Isoxazoles/química , Imitación Molecular , Estructura Molecular , Nucleósidos/síntesis química , Nucleósidos/química , Nucleósidos/farmacología , Pirimidinas/química , Relación Estructura-Actividad
10.
Beilstein J Org Chem ; 11: 328-34, 2015.
Artículo en Inglés | MEDLINE | ID: mdl-25815087

RESUMEN

A novel series of 2'-oxa-3'-aza-4'a-carbanucleosides, featured with a triazole linker at the 5'-position, has been developed by exploiting a click chemistry reaction of 5'-azido-2'-oxa-3'-aza-4'a-carbanucleosides with substituted alkynes. Biological tests indicate an antitumor activity for the synthesized compounds: most of them inhibit cell proliferation of Vero, BS-C-1, HEp-2, MDCK, and HFF cells with a CC50 in the range of 5.0-40 µM. The synthesized compounds do not show any antiviral activity.

11.
World J Gastroenterol ; 20(40): 14706-16, 2014 Oct 28.
Artículo en Inglés | MEDLINE | ID: mdl-25356033

RESUMEN

Obesity and liver steatosis are usually described as related diseases. Obesity is regarded as exclusive consequence of an imbalance between food intake and physical exercise, modulated by endocrine and genetic factors. Non-alcoholic fatty liver disease (NAFLD), is a condition whose natural history is related to, but not completely explained by over-nutrition, obesity and insulin resistance. There is evidence that environmental infections, and notably adipogenic adenoviruses (ADV) infections in humans, are associated not only with obesity, which is sufficiently established, but also with allied conditions, such as fatty liver. In order to elucidate the role, if any, of previous ADV36 infection in humans, we investigated association of ADV36-ADV37 seropositivity with obesity and fatty liver in humans. Moreover, the possibility that lifestyle-nutritional intervention in patients with NAFLD and different ADV36 seropositive status, achieves different clinical outcomes on ultrasound bright liver imaging, insulin resistance and obesity was challenged. ADV36 seropositive patients have a more consistent decrease in insulin resistance, fatty liver severity and body weight in comparison with ADV36 seronegative patients, indicating a greater responsiveness to nutritional intervention. These effects were not dependent on a greater pre-interventional body weight and older age. These results imply that no obvious disadvantage - and, seemingly, that some benefit - is linked to ADV36 seropositivity, at least in NAFLD. ADV36 previous infection can boost weight loss and recovery of insulin sensitivity under interventional treatment.


Asunto(s)
Infecciones por Adenovirus Humanos/virología , Adenovirus Humanos/patogenicidad , Adipogénesis , Hígado/virología , Enfermedad del Hígado Graso no Alcohólico/virología , Obesidad/virología , Infecciones por Adenovirus Humanos/diagnóstico , Infecciones por Adenovirus Humanos/epidemiología , Infecciones por Adenovirus Humanos/terapia , Animales , Biomarcadores/sangre , Humanos , Resistencia a la Insulina , Hígado/metabolismo , Hígado/patología , Enfermedad del Hígado Graso no Alcohólico/sangre , Enfermedad del Hígado Graso no Alcohólico/diagnóstico , Enfermedad del Hígado Graso no Alcohólico/epidemiología , Enfermedad del Hígado Graso no Alcohólico/terapia , Obesidad/sangre , Obesidad/diagnóstico , Obesidad/epidemiología , Obesidad/terapia , Factores de Riesgo , Resultado del Tratamiento , Pérdida de Peso
12.
Bioorg Med Chem ; 21(18): 5688-93, 2013 Sep 15.
Artículo en Inglés | MEDLINE | ID: mdl-23932449

RESUMEN

A series of modified N,O-nucleosides, characterized by the presence of a furopyrimidine moiety, has been synthesized by exploiting a Sonogashira cross coupling reaction of 1-isoxazolidinyl-5-iodouracil with alkynes, followed by treatment with CuI in refluxing TEA/MeOH mixture. The obtained compounds were screened against both RNA and DNA viruses. None of the compounds were endowed with antiviral activity at subtoxic concentrations. However, some of them were able to inhibit proliferation of MRC-5, Vero, BS-C-1 cells by 50% (CC50) at concentrations ranging from 0.7 to 62.5 mM.


Asunto(s)
Antivirales/síntesis química , Nucleósidos/química , Pirimidinas/química , Alquinos/química , Animales , Antivirales/química , Antivirales/farmacología , Línea Celular , Proliferación Celular/efectos de los fármacos , Chlorocebus aethiops , Nucleósidos/síntesis química , Nucleósidos/farmacología , Uracilo/análogos & derivados , Uracilo/química , Células Vero , Virus/efectos de los fármacos
13.
J Clin Gastroenterol ; 46(6): e46-54, 2012 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-22476041

RESUMEN

OBJECTIVE: Adenoviruses Ad36 and Ad37 increase adiposity in animals and are associated with obesity in humans; effects on the liver have been reported. The association of Adenovirus Ad36 seropositivity (Ad36+) with obesity but not with the severity of nonalcoholic fatty liver disease (NAFLD) has been previously shown. We investigate whether nondiabetic Ad37+ patients show a different prevalence of NAFLD and ultrasound Bright Liver score. PATIENTS: A total of 268 adult nondiabetic patients (146 men, 122 women) were included after lifestyle counseling including a personalized Mediterranean diet, increase in physical activity, and smoking withdrawal. After an Ad37+/Ad36+ assay, overweight obesity, insulin resistance, C-reactive protein, and bright liver prevalence and severity were compared according to Ad37+. RESULTS: Sixty-five of 268 patients were Ad37+ and 82/268 patients were both Ad37 seronegative (Ad37-) and Ad36-. The prevalence of obesity, defined as body mass index≥30, was not significantly different in Ad37+ (11/65; 16.9%) vs. Ad37- (15/82; 18.2%) patients; Bright Liver was present in 22/65 (33.8%) Ad37+ patients vs. 13/82 (15.8%) Ad37- patients (P<0.019). By odds ratio (OR), a consistent risk for NAFLD was associated with Ad37+, greater insulin resistance, and C-reactive protein. By a predictive multiple linear regression model, 40.0% of variance toward NAFLD and 50.4% toward the severity of Bright Liver score was explained significantly and independently by Ad37+ and by body mass index. CONCLUSIONS: Ad37+ status in nondiabetic patients on an appropriate diet is significantly associated with NAFLD; because fatty liver improves even without weight loss by a "healthy" diet, and not only by lower food caloric intake, Ad37+ may be an adjunctive hallmark of an unfavorable clinical-metabolic profile, if not a causative factor of NAFLD.


Asunto(s)
Infecciones por Adenovirus Humanos/complicaciones , Hígado Graso/fisiopatología , Estilo de Vida , Obesidad/epidemiología , Infecciones por Adenovirus Humanos/virología , Adenovirus Humanos/aislamiento & purificación , Adulto , Índice de Masa Corporal , Proteína C-Reactiva/metabolismo , Dieta Mediterránea , Hígado Graso/etiología , Hígado Graso/virología , Femenino , Humanos , Resistencia a la Insulina , Modelos Lineales , Masculino , Persona de Mediana Edad , Actividad Motora , Enfermedad del Hígado Graso no Alcohólico , Obesidad/virología , Prevalencia , Índice de Severidad de la Enfermedad , Cese del Hábito de Fumar
14.
Eur J Med Chem ; 52: 66-9, 2012 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-22465092

RESUMEN

Forty-two strains of Mycoplasma hominis (including PG21), 2 strain of Mycoplasma fermentans (Pg18 and K7), 1 strain of Mycoplasma pneumoniae (strain m129) were investigated for their susceptibilities to Citrus bergamia essential oil and to its major components (limonene, linalyl acetate and linalool). C. bergamia essential oil inhibited mycoplasmas at concentrations from 0.5 to 1% (MIC value as % v/v). M. hominis showed MIC(50) values of 0.5% and MIC(90) values of 1%; M. pneumoniae showed a MIC value of 0.5% while M. fermentans strains were inhibited by MIC values of 1%. M. pneumoniae and M. hominis shared the same susceptibility to linalyl acetate, with MIC values of 0.015% (corresponding to MIC(50) and MIC(90) for M. hominis); M. fermentans strains were less susceptible with MIC values of 0.12%. Among the major components tested, linalool showed higher activity against M. pneumoniae and M. fermentans (MIC values of 0.015 and 0.06%, respectively) but was less active against M. hominis (MIC(50) and MIC(90) values of both 1%); limonene was active against M. pneumoniae (MIC value of 0.03%) but was less active against M. fermentans (MIC values of 1%) and M. hominis (both MIC(50) and MIC(90) values of ≥4%). The results indicated that C. bergamia essential oil and its major components had shown an interesting in vitro antimycoplasmal activity.


Asunto(s)
Antibacterianos/química , Antibacterianos/farmacología , Citrus/química , Mycoplasma/efectos de los fármacos , Aceites Volátiles/química , Aceites Volátiles/farmacología , Monoterpenos Acíclicos , Ciclohexenos/farmacología , Limoneno , Monoterpenos/farmacología , Terpenos/farmacología
15.
Dig Dis Sci ; 57(2): 535-44, 2012 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-21953137

RESUMEN

BACKGROUND: Obesity and liver steatosis are both currently attributed to inappropriate lifestyle and nutrition. Higher prevalence of human adenovirus Ad36 seropositivity (Ad36+) is reported only in obesity. AIMS: To investigate whether a lifestyle-nutritional intervention achieves different outcomes in NAFLD patients, i.e., if is blunted or enhanced according to Ad36 seropositivity status. METHODS: One-year nutritional intervention was planned and accomplished for 62 non-alcoholic fatty liver disease overweight-obese patients, studied by liver ultrasound, evaluating Bright Liver Score (BLS), by Homeostatic Model assessment of Insulin Resistance (HOMA), by body composition and Ad36+ assay. Lower salt/lower calories Mediterranean diet, physical activity increase, smoking withdrawal and lifestyle counseling, provided by a health psychologist, were given. RESULTS: Ad36 seropositive patients have baseline greater BMI with the same level of BLS. Different prevalence of post-interventional response, significantly greater among Ad36+ patients, is observed: greater decrease of obesity, assessed by BMI, greater reduction of insulin resistance, assessed by HOMA and higher prevalence of bright liver disappearance. A BMI-adjusted multiple linear regression model explains significantly 23.8% (p < 0.04) of the variance; significant predictive variables are Ad36 seropositivity (p < 0.012) and fat mass loss (p < 0.011) accounting for the variance of the occurrence of bright liver disappearance. CONCLUSIONS: Ad36 previous infection is significantly associated with enhanced weight loss, bright liver disappearance, and recovery of insulin sensitivity through the chosen tailored nutritional interventional treatment. Nonetheless, Ad36 seronegative NAFLD patients' fatty liver pattern improves, at a lower extent, also without significant weight loss: an effect of dietary changes profile, Mediterranean diet, not only of lowered food caloric intake, is conceivably operating.


Asunto(s)
Infecciones por Adenovirus Humanos/inmunología , Adenovirus Humanos/inmunología , Hígado Graso/inmunología , Obesidad/virología , Infecciones por Adenovirus Humanos/epidemiología , Adenovirus Humanos/patogenicidad , Adulto , Índice de Masa Corporal , Comorbilidad , Dieta Mediterránea , Hígado Graso/epidemiología , Hígado Graso/virología , Femenino , Conductas Relacionadas con la Salud , Humanos , Resistencia a la Insulina/fisiología , Estilo de Vida , Masculino , Persona de Mediana Edad , Enfermedad del Hígado Graso no Alcohólico , Evaluación Nutricional , Obesidad/epidemiología , Obesidad/prevención & control , Estudios Seroepidemiológicos
16.
Liver Int ; 30(2): 184-90, 2010 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-19840251

RESUMEN

AIMS: Infection with specific pathogens may lead to increased adiposity. The human adenovirus 36 (Ad36) is a relatively new factor in promoting adipogenesis. It seems to improve the metabolic profile, expanding adipose tissue and enhancing insulin sensitivity in animal models. The aim of this study was to investigate whether any association or predictor effect of Ad36 seropositivity is present in non-alcoholic fatty liver disease (NAFLD), a condition associated with obesity and insulin resistance (IR). METHODS: Sixty-five NAFLD patients and 114 controls were investigated. Ultrasound bright liver score (BLS), body composition, IR evaluated by homeostasis model assessment of insulin resistance index (HOMA or HOMA-IR) and serum neutralization assay for antibodies to Ad36 were assessed. RESULTS: Ad36-seropositive patients have a lower risk of bright liver [OR 0.505 (95% confidence interval (CI) 0.265-0.962)]; greater IR leads to a higher risk of bright liver [OR 9.673 (95% CI 4.443-21.058)]. Among NAFLD, Ad36-seropositive vs. Ad36-seronegative patients did not show a significant IR difference. Ad36-seropositive NAFLD patients, with the same levels of HOMA and BLS, had greater body mass index and body fat mass, in comparison with seronegative NAFLD patients. By a multiple linear regression model, BLS was explained by HOMA (beta 0.513; P<0.0001), high density lipoprotein cholesterol (beta-0.219, P<0.006) and Ad36 seropositivity (beta-0.202, P<0.005); Ad36 seropositivity did not explain HOMA in the other multiple logistic regression model. CONCLUSIONS: Ad36 seropositivity is not associated with a significant difference of IR in NAFLD patients, but is associated with a greater adiposity. Ad36 seropositivity is associated with a lower occurrence of NAFLD and bright liver, which, conceivably, is not directly mediated by IR.


Asunto(s)
Infecciones por Adenovirus Humanos/virología , Adenovirus Humanos/patogenicidad , Adipogénesis/fisiología , Hígado Graso/virología , Resistencia a la Insulina/fisiología , Obesidad/virología , Infecciones por Adenovirus Humanos/sangre , Adenovirus Humanos/inmunología , Adenovirus Humanos/aislamiento & purificación , Anticuerpos Antivirales/sangre , Índice de Masa Corporal , Comorbilidad , Hígado Graso/sangre , Femenino , Humanos , Italia/epidemiología , Masculino , Persona de Mediana Edad , Obesidad/metabolismo , Estudios Seroepidemiológicos
17.
Antivir Chem Chemother ; 18(5): 277-83, 2007.
Artículo en Inglés | MEDLINE | ID: mdl-18046960

RESUMEN

We recently described the synthesis and antiviral activity of the compounds 5-phenyl-3-(4-cyano-5-phenylisothiazol-3-yl) disulphanyl-4-isothiazolecarbonitrile and S-(4-cyano-5-phenylisothiazol -3-yl)-O-ethyl thiocarbonate, which were found to be effective against both HIV-1 (IIIB) and HIV-2 (ROD). We have now evaluated these compounds against both RNA and DNA viruses, obtaining high selectivity indexes for poliovirus 1 (SI: 223 and 828, respectively) and Echovirus 9 (SI: 334 and 200, respectively). In our previous studies, 3-methylthio-5-(4-OBn-phenyl)-4-isothiazolecarbonitrile was found to exhibit a broad spectrum of action against picornaviruses, we therefore selected this compound and S-(4-cyano-5-phenylisothiazol-3-yl)-O-ethyl thiocarbonate as the model for the synthesis of a new isothiazole derivative, S-[4-cyano-5-(4-OBn-phenyl)isothiazol-3-yl]-O-ethyl thiocarbonate. This compound was evaluated against picornaviruses, measles virus, HIV-1 (IIIB) and HIV-2 (ROD), and some DNA viruses (adenovirus type 2 and herpes simplex virus type 1). The compound was shown to be active against rhinoviruses 2, 39, 86 and 89, Coxsackie B1 and measles virus.


Asunto(s)
Antivirales/farmacología , Disulfuros/farmacología , Tiazoles/farmacología , Virus/efectos de los fármacos , Animales , Antivirales/síntesis química , Antivirales/química , Línea Celular , Supervivencia Celular/efectos de los fármacos , Chlorocebus aethiops , Disulfuros/síntesis química , Disulfuros/química , Humanos , Ratones , Pruebas de Sensibilidad Microbiana , Estructura Molecular , Relación Estructura-Actividad , Tiazoles/síntesis química , Tiazoles/química
18.
Hum Reprod ; 21(1): 134-7, 2006 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-16126752

RESUMEN

BACKGROUND: Chlamydia trachomatis is responsible for a widespread sexually transmitted infection. In men, it is associated with a wide clinical spectrum causing infertility. Furthermore, C. trachomatis serovar E infection decreases motility and increases the number of non-viable sperm. No other effects of C. trachomatis have been reported on sperm despite the crucial role of DNA integrity for sperm function. The aim of this study was to investigate the effects of C. trachomatis on sperm apoptosis. METHODS: Sperm from eight normozoospermic men were incubated with increasing concentrations of C. trachomatis serovar E elementary bodies (EB) for 6 and 24 h. Sperm were then collected to evaluate phosphatidylserine (PS) membrane translocation and DNA fragmentation by Annexin V-propidium iodide staining, TUNEL assay and flow cytometry. RESULTS: After 6 h of incubation, C. trachomatis had no effect on the percentage of sperm showing PS externalization. However, a significant effect on this parameter was observed after 24 h. C. trachomatis also significantly increased the number of sperm with DNA fragmentation both after 6 and 24 h of incubation. CONCLUSIONS: C. trachomatis causes sperm PS externalization and DNA fragmentation. These effects may explain the negative direct impact of C. trachomatis infection on sperm fertilizing ability.


Asunto(s)
Apoptosis , Infecciones por Chlamydia/microbiología , Chlamydia trachomatis/patogenicidad , Fragmentación del ADN , Espermatozoides/microbiología , Transporte Biológico , Membrana Celular/metabolismo , Células Cultivadas , Humanos , Masculino , Fosfatidilserinas/metabolismo
19.
Antivir Chem Chemother ; 15(4): 201-5, 2004 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-15457681

RESUMEN

A series of 3,4,5-trisubstituted isothiazoles has been screened against HIV-1 (IIIB) and HIV-2 (ROD) at sub-toxic concentrations in acutely infected MT-4 cells. Among the tested compounds, only 3-mercapto-5-phenyl-4-isothiazolecarbonitrile was found to inhibit the replication of HIV-1 (IIIB) and HIV-2 (ROD) at 50% effective concentrations (EC50) of 7.8 and 9.7 microg/ml, respectively. The presence of a thioalkyl chain or dialkylamino function in the 3-position caused a loss of anti-HIV activity. New 4-cyano-5-phenylisothiazoles with other substituents in the 3-position have also been synthesized and studied as potential anti-HIV agents. Our results have demonstrated that 5-phenyl-3-(4-cyano-5-phenylisothiazol-3-yl) disulphanyl-4-isothiazolecarbonitrile and S-(4-cyano-5-phenylisothiazol-3-yl)-O-ethyl thiocarbonate are effective against both HIV-1 (IIIB) (EC50=13.6 and 15.2 microg/ml, respectively) and HIV-2 (ROD) (EC50=17.4 and 13.4 microg/ml, respectively).


Asunto(s)
Fármacos Anti-VIH/química , Fármacos Anti-VIH/farmacología , VIH-1/efectos de los fármacos , VIH-2/efectos de los fármacos , Tiazoles/química , Tiazoles/farmacología , Replicación Viral/efectos de los fármacos , Fármacos Anti-VIH/síntesis química , Línea Celular , Disulfuros , VIH-1/fisiología , VIH-2/fisiología , Humanos , Estructura Molecular , Tiazoles/síntesis química
20.
Int J Antimicrob Agents ; 22(2): 164-7, 2003 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-12927958

RESUMEN

The effect of sub-inhibitory concentrations (SICs) of netilmicin on bacterial hydrophobicity and adhesiveness to conjunctival cells was investigated. One strain each of Pseudomonas aeruginosa, Pseudomonas spp., Staphylococcus aureus and S. epidermidis was investigated for its susceptibility to netilmicin, its adherence to conjunctival cells and to the effect of hydrocarbon hexadecane before and after treatment with SIC of netilmicin. All of the bacteria tested were susceptible to netilmicin except for Pseudomonas spp. which showed intermediate resistance. Netilmicin-treated Pseudomonas strains exhibited a lower level of hydrophobicity towards n-hexadecane compared with non-treated strains, while netilmicin-treated S. epidermidis and S. aureus showed a slight increase of hydrophobicity. Adherence of the two Pseudomonas strains to conjunctival cells was significantly reduced after growth in the presence of netilmicin, while the adherence of the two staphylococci was only slightly reduced.


Asunto(s)
Antibacterianos/farmacología , Adhesión Bacteriana/efectos de los fármacos , Netilmicina/farmacología , Alcanos/farmacología , Antibacterianos/administración & dosificación , Línea Celular , Conjuntiva/microbiología , Células Epiteliales/microbiología , Humanos , Interacciones Hidrofóbicas e Hidrofílicas , Técnicas In Vitro , Netilmicina/administración & dosificación , Pseudomonas/efectos de los fármacos , Pseudomonas/patogenicidad , Pseudomonas aeruginosa/efectos de los fármacos , Pseudomonas aeruginosa/patogenicidad , Staphylococcus aureus/efectos de los fármacos , Staphylococcus aureus/patogenicidad , Staphylococcus epidermidis/efectos de los fármacos , Staphylococcus epidermidis/patogenicidad
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