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Key Clinical Message: Stenotrophomonas maltophilia can cause rare odontogenic brain abscesses in immunocompetent patients, highlighting the importance of considering uncommon pathogens in central nervous system infections. With only three reported cases of cerebral abscesses and one pituitary abscess caused by this microorganism, tailored diagnostic methods and individualized treatment regimens are crucial for accurate management. Abstract: Brain abscesses present diagnostic and therapeutic challenges, with Stenotrophomonas maltophilia infections being exceptionally rare in the central nervous system. We present a case of odontogenic brain abscesses caused by S. maltophilia in an immunocompetent patient, highlighting the rarity and complexity of such infections. A 66-year-old male presented with spatial-temporal disorientation and left-sided weakness. Radiological investigations revealed an expansive lesion in the right posterior frontal region. A craniotomy and drainage were performed, identifying S. maltophilia in the purulent material. The patient responded well to tailored antibiotic therapy. S. maltophilia-related central nervous system infections are infrequent, emphasizing the need for a heightened clinical suspicion in atypical cases. This case contributes to the literature, emphasizing the importance of a multidisciplinary approach for successful diagnosis and management.
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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.
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Neoplasias da Mama , Herpesvirus Humano 1 , Orobanche , Feminino , Humanos , Antivirais/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Herpesvirus Humano 1/fisiologia , Células MCF-7 , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Compostos de Sulfidrila/farmacologia , Replicação ViralRESUMO
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.
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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.
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Antibacterianos/farmacologia , Juglans/química , Extratos Vegetais/farmacologia , Staphylococcus/efeitos dos fármacos , Antibacterianos/administração & dosagem , Antibacterianos/química , Biofilmes/efeitos dos fármacos , Cromatografia Líquida , Coagulase/análise , Relação Dose-Resposta a Droga , Flavonoides/análise , Nozes/química , Fenóis/análise , Extratos Vegetais/administração & dosagem , Extratos Vegetais/análise , Extratos Vegetais/química , Plantas Medicinais/química , Staphylococcus/fisiologia , Espectrometria de Massas em TandemRESUMO
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.
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Biomarcadores Tumorais/metabolismo , Resistencia a Medicamentos Antineoplásicos/genética , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Linfoma de Células B/patologia , Survivina/metabolismo , Fator de Transcrição YY1/metabolismo , Protocolos de Quimioterapia Combinada Antineoplásica/farmacologia , Apoptose , Biomarcadores Tumorais/genética , Proliferação de Células , Inativação Gênica , Humanos , Linfoma de Células B/tratamento farmacológico , Linfoma de Células B/genética , Linfoma de Células B/metabolismo , Survivina/genética , Células Tumorais Cultivadas , Fator de Transcrição YY1/antagonistas & inibidores , Fator de Transcrição YY1/genéticaRESUMO
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.
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Tonsila Faríngea , Técnicas de Cultura de Células , Chlamydophila pneumoniae , Técnicas Microbiológicas , Reação em Cadeia da Polimerase , Tonsilite , Tonsila Faríngea/microbiologia , Adulto , Chlamydophila pneumoniae/genética , DNA Bacteriano/genética , Técnicas de Diagnóstico do Sistema Respiratório/normas , Humanos , Técnicas Microbiológicas/métodos , Técnicas Microbiológicas/normas , Reação em Cadeia da Polimerase/normas , RNA Ribossômico 16S/genética , Sensibilidade e Especificidade , Tonsilite/microbiologiaRESUMO
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.
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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.
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Hepatite C/complicações , Linfoma não Hodgkin/etiologia , Pessoal de Saúde/estatística & dados numéricos , Hepatite C/diagnóstico , Humanos , Exposição Ocupacional , Fatores de RiscoRESUMO
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.
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Antivirais/química , Antivirais/farmacologia , Catecóis/química , Catecóis/farmacologia , Vírus de DNA/efeitos dos fármacos , Vírus de RNA/efeitos dos fármacos , Agaricus/enzimologia , Infecções por Vírus de DNA/tratamento farmacológico , Enzimas Imobilizadas/química , Humanos , Modelos Moleculares , Monofenol Mono-Oxigenase/química , Nanotubos de Carbono/química , Álcool Feniletílico/análogos & derivados , Álcool Feniletílico/química , Álcool Feniletílico/farmacologia , Infecções por Vírus de RNA/tratamento farmacológicoRESUMO
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.
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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.
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Antineoplásicos/síntese química , Antineoplásicos/farmacologia , Isoxazóis/síntese química , Isoxazóis/farmacologia , Antineoplásicos/química , Proliferação de Células/efeitos dos fármacos , Ensaios de Seleção de Medicamentos Antitumorais , Células HT29 , Células Hep G2 , Humanos , Isoxazóis/química , Mimetismo Molecular , Estrutura Molecular , Nucleosídeos/síntese química , Nucleosídeos/química , Nucleosídeos/farmacologia , Pirimidinas/química , Relação Estrutura-AtividadeRESUMO
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.
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Infecções por Adenovirus Humanos/virologia , Adenovírus Humanos/patogenicidade , Adipogenia , Fígado/virologia , Hepatopatia Gordurosa não Alcoólica/virologia , Obesidade/virologia , Infecções por Adenovirus Humanos/diagnóstico , Infecções por Adenovirus Humanos/epidemiologia , Infecções por Adenovirus Humanos/terapia , Animais , Biomarcadores/sangue , Humanos , Resistência à Insulina , Fígado/metabolismo , Fígado/patologia , Hepatopatia Gordurosa não Alcoólica/sangue , Hepatopatia Gordurosa não Alcoólica/diagnóstico , Hepatopatia Gordurosa não Alcoólica/epidemiologia , Hepatopatia Gordurosa não Alcoólica/terapia , Obesidade/sangue , Obesidade/diagnóstico , Obesidade/epidemiologia , Obesidade/terapia , Fatores de Risco , Resultado do Tratamento , Redução de PesoRESUMO
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.
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Antivirais/síntese química , Nucleosídeos/química , Pirimidinas/química , Alcinos/química , Animais , Antivirais/química , Antivirais/farmacologia , Linhagem Celular , Proliferação de Células/efeitos dos fármacos , Chlorocebus aethiops , Nucleosídeos/síntese química , Nucleosídeos/farmacologia , Uracila/análogos & derivados , Uracila/química , Células Vero , Vírus/efeitos dos fármacosRESUMO
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.
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Infecções por Adenovirus Humanos/complicações , Fígado Gorduroso/fisiopatologia , Estilo de Vida , Obesidade/epidemiologia , Infecções por Adenovirus Humanos/virologia , Adenovírus Humanos/isolamento & purificação , Adulto , Índice de Massa Corporal , Proteína C-Reativa/metabolismo , Dieta Mediterrânea , Fígado Gorduroso/etiologia , Fígado Gorduroso/virologia , Feminino , Humanos , Resistência à Insulina , Modelos Lineares , Masculino , Pessoa de Meia-Idade , Atividade Motora , Hepatopatia Gordurosa não Alcoólica , Obesidade/virologia , Prevalência , Índice de Gravidade de Doença , Abandono do Hábito de FumarRESUMO
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.
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Antibacterianos/química , Antibacterianos/farmacologia , Citrus/química , Mycoplasma/efeitos dos fármacos , Óleos Voláteis/química , Óleos Voláteis/farmacologia , Monoterpenos Acíclicos , Cicloexenos/farmacologia , Limoneno , Monoterpenos/farmacologia , Terpenos/farmacologiaRESUMO
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.
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Infecções por Adenovirus Humanos/imunologia , Adenovírus Humanos/imunologia , Fígado Gorduroso/imunologia , Obesidade/virologia , Infecções por Adenovirus Humanos/epidemiologia , Adenovírus Humanos/patogenicidade , Adulto , Índice de Massa Corporal , Comorbidade , Dieta Mediterrânea , Fígado Gorduroso/epidemiologia , Fígado Gorduroso/virologia , Feminino , Comportamentos Relacionados com a Saúde , Humanos , Resistência à Insulina/fisiologia , Estilo de Vida , Masculino , Pessoa de Meia-Idade , Hepatopatia Gordurosa não Alcoólica , Avaliação Nutricional , Obesidade/epidemiologia , Obesidade/prevenção & controle , Estudos SoroepidemiológicosRESUMO
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.
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Infecções por Adenovirus Humanos/virologia , Adenovírus Humanos/patogenicidade , Adipogenia/fisiologia , Fígado Gorduroso/virologia , Resistência à Insulina/fisiologia , Obesidade/virologia , Infecções por Adenovirus Humanos/sangue , Adenovírus Humanos/imunologia , Adenovírus Humanos/isolamento & purificação , Anticorpos Antivirais/sangue , Índice de Massa Corporal , Comorbidade , Fígado Gorduroso/sangue , Feminino , Humanos , Itália/epidemiologia , Masculino , Pessoa de Meia-Idade , Obesidade/metabolismo , Estudos SoroepidemiológicosRESUMO
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.
Assuntos
Antivirais/farmacologia , Dissulfetos/farmacologia , Tiazóis/farmacologia , Vírus/efeitos dos fármacos , Animais , Antivirais/síntese química , Antivirais/química , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Chlorocebus aethiops , Dissulfetos/síntese química , Dissulfetos/química , Humanos , Camundongos , Testes de Sensibilidade Microbiana , Estrutura Molecular , Relação Estrutura-Atividade , Tiazóis/síntese química , Tiazóis/químicaRESUMO
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.
Assuntos
Apoptose , Infecções por Chlamydia/microbiologia , Chlamydia trachomatis/patogenicidade , Fragmentação do DNA , Espermatozoides/microbiologia , Transporte Biológico , Membrana Celular/metabolismo , Células Cultivadas , Humanos , Masculino , Fosfatidilserinas/metabolismoRESUMO
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).