Miracle-dz/UniFAR-FTUs huggingface dataset:
Antimutagenicity of propolis against some mutagens in vivo and in vitro.

OBJECTIVE To evaluate the antimutagenicity of propolis in vivo and in vitro. METHODS Salmonella typhimurium strains TA98 and TA100 were used as a test model in vitro against a direct mutagen DMC and an indirect mutagen 2AF with or without S9 mix, and MN formation of mice bone marrow cell and CAs induction of mice testicle cell were applied as a test model in vivo against two mutagens CP and MMC. RESULTS The present study clearly demonstrated that propolis could inhibit mutagenicity of both DMC and 2AF directly in a dose-dependent manner, and significant antimutagenic effects (P < 0.05) were obtained in TA98 strain at 2000 and 3000 microg/plate. It also could inhibit mutagenicity of both DMC and 2AF to TA98 strain in a dose-dependent manner, with significant antimutagenic effects (P < 0.05) appeared at 1000, 2000, and 3000 microg/plate. The results of antimutagenicity test in vivo revealed that propolis could inhibit MN formation significantly (P < 0.05) at the doses of 45.0 and 135.0 mg/kg b. w. , and decrease the frequency of chromosome aberrants and chromosome aberrant cells significantly (P < 0.05) only at the dose of 135.0 mg/kg b. w. CONCLUSION The propolis is a good inhibitor for mutagencity of DMC and 2AF in vitro, as well as for CP and MMC in vivo.
Antioxidant and chemosensitizing effects of flavonoids with hydroxy and/or methoxy groups and structure-activity relationship.

PURPOSE Flavonoids have been used as antioxidant, chemopreventive and chemosensitizing agents. In this study, eleven flavonoids containing a variety of hydroxy (OH) and/or methoxy (OMe) groups were evaluated for their antioxidant, cytotoxic and chemosensitizing effects to create a structure-activity relationship (SAR). METHODS 1,1-Diphenyl-2-picrylhydrazyl (DPPH) radical solution-based chemical assay and and 2',7'-dichlorofluorescin diacetate (DCFH-DA) cellular-based assay were used to compare the free radical scavenging activity on the same molar concentration basis using the AML-2/DX100 cells which are characterized by the down-regulated expression of catalase and resulting supersensitiviy to hydrogen peroxide. The chemosensitization and cytotoxicity were determined by the MTT assay in the presence or absence of an anticancer drug using the P-glycoprotein-overexpressing AML-2 subline AML-2/D100 cells. RESULTS The antioxidant activity of the flavonoid (3,5,7,3',4'-OH) was higher than that of the flavonoid (5,7,3',4'-OH). Flavonoids substituted with the various number of OMe decreased antioxidant activity. Flavonoids with 7-OH or 5,7-OH groups have the highest cytotoxicity, and flavonoids with 5,7-OMe group intermediate cytotoxicity. The IC50 values of flavonoid (5,7-OMe, 3',4',5'-OMe) and flavonoid (5,7-OMe, 4'-OMe), 0.4 M and 1.4 M. The IC50 values of flavonoid (5,6,7-OMe, 3',4'-OMe) and flavonoid (5,6,7-OMe, 3',4',5'-OMe), 3.2 uM and 0.9 M, respectively, and those of flavonoid (5,6,7-OMe, 3',4',5'-OMe) and flavonoid (5,7-OMe,3',4',5'-OMe) were 0.9 M and 0.4 M, respectively. CONCLUSIONS These results suggest that flavonoids with 3-OH group play a positive role in antioxidant activities, flavonoids with 5-OH and/or 7-OH groups show the higher cytotoxicity, and flavonoids with 3'-OMe and/or 5'-OMe groups plays positive but 6-OMe groups negative roles in the P-glycoprotein (Pgp) inhibition. It is believed that these SAR results can be taken into account for the development of flavonoids with high therapeutic index.
Sitaxsentan, a selective endothelin-A receptor antagonist for the treatment of pulmonary arterial hypertension

Sitaxsentan, a highly selective endothelin-A (ETA) receptor antagonist (6500-fold more selective for ETA receptors than endothelin-B (ETB) receptors), may benefit patients with pulmonary artery hypertension (PAH) by blocking the vasoconstrictor effects of ETA receptors while maintaining the vasodilator/clearance functions of ETB receptors. In its first randomised, placebo-controlled study, Sitaxsentan to Relieve Impaired Exercise-1 (STRIDE-1), sitaxsentan improved exercise capacity assessed by 6 min walk, New York Heart Association functional class, cardiac index and pulmonary vascular resistance in New York Heart Association class II, III and IV patients with idiopathic PAH, PAH related to connective tissue disease or PAH related to congenital heart disease. In STRIDE-1, doses of 100 and 300 mg/day p.o. were evaluated. Although both doses showed equivalent efficacy, the lower dose had a more tolerable safety profile. Additional studies are ongoing to assess the relative safety and efficacy of 50 and 100 mg/day doses, both in de novo patients and in patients previously treated with the ETA/ETB receptor antagonist bosentan. Long-term comparative studies are necessary to determine whether there is a clinically meaningful difference between selective ETA receptor antagonism and ETA/ETB receptor antagonism.
Antibiotic dialogues: induction of silent biosynthetic gene clusters by exogenous small molecules

&NA; Natural products have traditionally served as a dominant source of therapeutic agents. They are produced by dedicated biosynthetic gene clusters that assemble complex, bioactive molecules from simple precursors. Recent genome sequencing efforts coupled with advances in bioinformatics indicate that the majority of biosynthetic gene clusters are not expressed under normal laboratory conditions. Termed ‘silent’ or ‘cryptic’, these gene clusters represent a treasure trove for discovery of novel small molecules, their regulatory circuits and their biosynthetic pathways. In this review, we assess the capacity of exogenous small molecules in activating silent secondary metabolite gene clusters. Several approaches that have been developed are presented, including coculture techniques, ribosome engineering, chromatin remodeling and high‐throughput elicitor screens. The rationale, applications and mechanisms attendant to each are discussed. Some general conclusions can be drawn from our analysis: exogenous small molecules comprise a productive avenue for the discovery of cryptic metabolites. Specifically, growth‐inhibitory molecules, in some cases clinically used antibiotics, serve as effective inducers of silent biosynthetic gene clusters, suggesting that old antibiotics may be used to find new ones. The involvement of natural antibiotics in modulating secondary metabolism at subinhibitory concentrations suggests that they represent part of the microbial vocabulary through which inter‐ and intraspecies interactions are mediated.
Broadly reactive antibodies to hypervariable region 1 in hepatitis C virus–infected patient sera: Relation to viral loads and response to interferon

To clarify the nature of serum anti‐hypervariable region 1 (HVR1) antibodies in patients infected with hepatitis C virus (HCV), we assessed the reactivity of 21 patients' sera with 42 HVR1 proteins by Western blot. HVR1 was expressed as fusion proteins with glutathione S‐transferase (GST). The patients' sera reacted with variable percentages of the HVR1 proteins, and always reacted with HVR1 proteins of the different genotype. In the genotype‐1b–infected patients, the percentage of genotype‐1b HVR1 proteins reactive with serum correlated significantly with viral loads; the sera reactive with the higher percentages of HVR1 proteins contained the larger viral loads. In addition, it was significantly lower in the responders of interferon (IFN) therapy than in nonresponders. The competition assays indicated that multiple fractions of anti‐HVR1 antibodies with different specificity in a serum reacted with different HVR1 proteins, and that, additionally, a single fraction of antibodies often reacted with more than one HVR1 protein through a similar amino acid sequence. In conclusion, serum anti‐HVR1 antibodies were broadly reactive by the mechanism of both the cross‐reactivity of a single fraction of anti‐HVR1 antibodies with more than one HVR1 protein and the presence of multiple fractions of anti‐HVR1 antibodies with different specificity in a serum. In genotype‐1b–infected patients, the broad reactivity of serum anti‐HVR1 antibodies correlated with viral loads and response to IFN. Further studies are necessary to elucidate the correlation among the broad reactivity of sera with multiple HVR1 proteins and clinical features of chronic hepatitis C patients.
Increasing the hosting capacity of distribution grids by implementing residential PV storage systems and reactive power control

The rapidly increasing number of implemented photovoltaic (PV) systems in the German distribution grid in recent years has led to power quality issues due to the intermittent generation and reverse power flows in periods of low demand. In order to decrease this impact, different solutions are being investigated. The aim of this study is to analyze the maximum possible grid relief by using residential PV storage systems and different reactive power control strategies from the viewpoint of a distribution system owner. To compare the different voltage control method scenarios the hosting capacity is used as a performance indicator.
Transforming growth factor beta-1 C-509T polymorphism and cancer risk: a meta-analysis of 55 case-control studies.

AIM To investigate the association of transforming growth factor-beta 1 (TGF-β1) C-509T polymorphism and susceptibility to cancer by means of meta-analysis. METHODS An extensive search was performed to identify eligible case-control studies investigating such a link. The strength of the association between TGF-β1 C-509T polymorphism and cancer risk was assessed by pooled odds ratios (ORs) and 95%confidence intervals (95%CIs) in fixed or random effects models. RESULTS 55 published case-control studies with a total number of 21,639 cases and 28,460 controls were included. Overall, there was no association between TGF-β1 C-509T and cancer risk in all genetic comparison models (TT vs. CC: OR=1.01, 95%CI=0.89-1.15; T vs. C: OR=1.01, 95%CI=0.94-1.07). However, a stratified analysis by cancer type indicated -509 T allele was significantly associated with decreased risk of colorectal cancer (CRC) (TT vs. CT/CC: OR=0.85, 95%CI=0.76-0.95), especially for Caucasians (TT vs. CT/CC: OR=0.83, 95%CI=0.71-0.98) and for population-based studies (TT vs. CT/CC: OR=0.78, 95%CI=0.68- 0.89). CONCLUSION This meta-analysis suggested that TGF-β1 C-509T polymorphism might contribute to a decreased risk on colorectal cancer susceptibility, especially for Caucasians.
Structural Basis for the Differential Binding Affinities of the HsfBD1 and HsfBD2 Domains in the Haemophilus influenzae Hsf Adhesin

ABSTRACT Haemophilus influenzae is a human-specific gram-negative coccobacillus that causes a variety of human infections ranging from localized respiratory infections to invasive diseases. Hsf is the major nonpilus adhesin in encapsulated strains of H. influenzae and belongs to the trimeric autotransporter family of proteins. The Hsf protein contains two highly homologous binding domains, designated HsfBD1 and HsfBD2. In this study we characterized the differential binding properties of HsfBD1 and HsfBD2. In assays using HeLa cells, we found that bacteria expressing either full-length Hsf or HsfBD1 by itself adhered at high levels, while bacteria expressing HsfBD2 by itself adhered at low levels. Immunofluorescence microscopy and a cellular enzyme-linked immunosorbent assay using purified proteins revealed that the binding affinity was significantly higher for HsfBD1 than for HsfBD2. Purified HsfBD1 was able to completely block adherence by bacteria expressing either HsfBD1 or HsfBD2, while purified HsfBD2 was able to block adherence by bacteria expressing HsfBD2 but had minimal activity against bacteria expressing HsfBD1. Conversion of the residue at position 1935 in the HsfBD1 binding pocket from Asp to Glu resulted in HsfBD2-like binding properties, and conversion of the residue at position 569 in the HsfBD2 binding pocket from Glu to Asp resulted in HsfBD1-like binding properties, as assessed by adherence assays with recombinant bacteria and by immunofluorescence microscopy with purified proteins. This work demonstrates the critical role of a single amino acid in the core of the binding pocket in determining the relative affinities of the HsfBD1 and HsfBD2 binding domains.
New Muslims in the European Context: The Experience of Scandinavian Converts

This volume deals with Scandinavian converts to Islam, discussing the process of conversion as well as the converts' role in Muslim communities and in majority society. As Islam is a new phenomenon in Scandinavia, the story of the new Muslims becomes also a story of the development of Scandinavian Islamic ideas. The book examines the specific features of Scandinavian society and Islamophobia in Scandinavia. It goes on to discuss the conversion process, Muslim convert trends common in Europe as well as in Scandinavia, and provides a detailed discussion of literature read or written by converts. The discussion of the new Muslims' experiences includes a discussion of the trend towards understanding Islam according to Scandinavian values.
Inhibition of hepatic stellate cell proliferation and activation by the semisynthetic analogue of fumagillin TNP‐470 in rats

Proliferation and activation of hepatic stellate cells (HSCs) are critical steps for the development of postnecrotic fibrosis in the liver. The present study aimed to reveal the inhibitory effect of the semisynthetic analogue of fumagillin TNP‐470 on these events for its possible use as an antifibrogenic agent. Rat models of carbon tetrachloride (CCl4)‐ and dimethylnitrosamine‐induced hepatic fibrosis were used for an in vivo study. In both models, the fibrotic area was considerably decreased by concurrent repetitive subcutaneous injections of 30 mg/kg body weight of TNP‐470. In CCl4‐induced fibrosis, factor VIII‐related antigen‐positive blood vessels, desmin‐, or α‐smooth muscle actin (αSMA)‐positive mesenchymal cells, bromodeoxyuridine (BrdU)‐positive mesenchymal cells also decreased in number by treatment with TNP‐470. In in vitro experiments, a supplement of 1,000 ng/mL TNP‐470 suppressed BrdU incorporation and cyclins D1, D2, and E expression by cultured HSCs in the absence and/or presence of platelet‐derived growth factor (PDGF). Expression of HSC activation markers, i.e., αSMA and PDGF receptor β, was also suppressed. The present results indicate that TNP‐470 inhibits HSC proliferation by blocking the cell‐cycle transition from G1 to S and HSC activation, and, as the consequence, prevents the progression of hepatic fibrosis, probably being coupled with its antiangiogenic effect.
Ramelteon: A Novel Approach in the Treatment of Insomnia

Objective: To review the pharmacology, pharmacokinetics, efficacy, and safety of ramelteon in the treatment of primary insomnia in adults, including elderly adults. Data Sources: MEDLINE (1966–July 2008) and PsyclNFO (1985–July 2008) literature searches were conducted to idontify clinical data involving ramelteon. The manufacturer provided a summary of clinical data and abstracts of unpublished studies. Study Selection And Data Extraction: All primary literature, including abstracts, focusing on the pharmacology and pharmacokinetics of ramelteon and clinical trials evaluating its use was reviewed. Information deemed most relevant was incorporated. Our search revealed 5 controlled trials evaluating the short-term efficacy and safety of ramelteon in the treatment of primary insomnia: 3 in adults and 2 in geriatric patients. Additionally, 2 studies in abstract form that evaluated the long-term effects of ramelteon were included. Data Synthesis: Ramelteon is the first selective melatonin receptor agonist approved by the Food and Drug Administration. It has no affinity for the γ-aminobutyric acid receptor complex or for receptors that bind acetylcholine, cytokines, dopamine, norepinephrine, neuropeptides, opiates, and serotonin. In the only published Phase 3 trial in adults, investigators found that latency to persistent sleep decreased with ramelteon to 31.5 ± 2.91 minutes with 8 mg and 29.5 ± 2.96 minutes with 16 mg compared with 42.5 ± 2.97 minutes with placebo (p = 0.007 and p = 0.002, respectively). Total sleep time was not significantly different from that with placebo. Safety data from short-term studies showed advantages of ramelteon over other sleep agents including no potential for abuse, no rebound insomnia, and lack of effect on motor and cognitive function. The adverse effects seen most frequently in ramelteon clinical trials were headache, somnolence, fatigue, nausea, dizziness, and insomnia. The overall incidence was similar to that of placebo. Conclusions: Ramelteon offers a novel mechanism of action for the treatment of insomnia. Studies support its short- and long-term use in adults and elderly adults for the treatment of primary insomnia characterized by difficulty with sleep initiation. Efficacy studies comparing ramelteon with other sleep agents are needed to further solidify the role of ramelteon in the treatment of insomnia.
Tympanoplasty Results in Patients with Cleft Palate: An Age- and Procedure-Matched Comparison of Preliminary Results with Patients without Cleft Palate

OBJECTIVE: Because of continued eustachian tube abnormalities, the presence of a cleft palate repair has been thought to be associated with poor outcomes after tympanoplastic surgery. However, little published data exist regarding the results of major otologic surgery in patients with cleft palate. The objective of this study was to review our results of otologic surgery in these patients and compare results with those of age- and procedure-matched controls. METHODS: Our otologic database was used to identify patients with a repaired cleft palate who underwent otologic surgery between March 1994 and December 1999. Two control patients were identified for each cleft palate patient. Results of hearing, graft take, and need for postoperative pressure-equalizing tubes were compared. RESULTS: No significant difference existed between patients with a repaired cleft palate and control patients with regard to postoperative air-bone gap (P = 0.6805), graft survival rate (P = 1.00), and need for postoperative intubation (P = 0.457). CONCLUSION: Results in patients with cleft palate appear to be similar to those in patients without cleft palate.
Relationship between electron density and effective densities of body tissues for stopping, scattering, and nuclear interactions of proton and ion beams.

PURPOSE In treatment planning of charged-particle radiotherapy, patient heterogeneity is conventionally modeled as variable-density water converted from CT images to best reproduce the stopping power, which may lead to inaccuracies in the handling of multiple scattering and nuclear interactions. Although similar conversions can be defined for these individual interactions, they would be valid only for specific CT systems and would require additional tasks for clinical application. This study aims to improve the practicality of the interaction-specific heterogeneity correction. METHODS The authors calculated the electron densities and effective densities for stopping power, multiple scattering, and nuclear interactions of protons and ions, using the standard elemental-composition data for body tissues to construct the invariant conversion functions. The authors also simulated a proton beam in a lung-like geometry and a carbon-ion beam in a prostate-like geometry to demonstrate the procedure and the effects of the interaction-specific heterogeneity correction. RESULTS Strong correlations were observed between the electron density and the respective effective densities, with which the authors formulated polyline conversion functions. Their effects amounted to 10% differences in multiple-scattering angle and nuclear interaction mean free path for bones compared to those in the conventional heterogeneity correction. Although their realistic effect on patient dose distributions would be generally small, it could be at the level of a few percent when a carbon-ion beam traverses a large bone. CONCLUSIONS The present conversion functions are invariant and may be incorporated in treatment planning systems with a common function relating CT number to electron density. This will enable improved beam dose calculation while minimizing initial setup and quality management of the user's specific system.
Proton magnetic resonance spectroscopy of late delayed radiation‐induced injury of the brain

We prospectively evaluated metabolite changes in late delayed radiation‐induced injury to the temporal lobes on proton (1H) magnetic resonance spectroscopy (MRS) in 34 patients. Morphologically more severe injury on imaging tended to have lower N‐acetyl aspartate (NAA)/creatine (Cr) and NAA/choline (Cho) ratios. A significantly higher Cho/Cr ratio was found in the most severe grade of cerebral necrosis, in which lactate might be present. The progressive decrease in NAA with increasing severity reflected neuronal loss at different stages of late delayed radiation‐induced brain injury. The absence of Cho elevation in mild and moderate lesions did not suggest demyelination or glial hyperplasia as an etiologic mechanism of late delayed radiation‐induced brain injury. The association of severe morphologic lesions with elevated lactate suggests ischemia as the underlying mechanism for severe lesions. 1H MRS may provide metabolite information conducive to the understanding of the pathophysiology of late radiation‐induced brain injury. J. Magn. Reson. Imaging 1999;10:130–137. © 1999 Wiley‐Liss, Inc.
Left Ventricular Myocardial Fibrosis, Atrophy, and Impaired Contractility in Patients With Pulmonary Arterial Hypertension and a Preserved Left Ventricular Function: A Cardiac Magnetic Resonance Study

Purpose: Using a cardiac magnetic resonance (CMR) approach we investigated left ventricular (LV) myocardial changes associated with pulmonary arterial hypertension (PAH) by strain analysis and mapping techniques. Materials and Methods: Seventeen patients with PAH (9 men; mean age, 64.2±13.6 y) and 20 controls (10 men, 63.2±10.5 y) were examined using CMR at 1.5 T. Native LV T1-relaxation times (T1) and extracellular volume fraction (ECV) were assessed using a MOLLI sequence, T2-relaxation times (T2) by means of a gradient spin-echo sequence, and LV longitudinal strain (LVS) and right ventricular (RV) longitudinal strain (RVS) by means of CMR feature tracking. The hematocrit and serum levels of pro-Brain Natriuretic Peptide were determined on the day of the CMR examination. Pulmonary arterial pressure and 6-minute walking distance were assessed as part of the clinical evaluation. Results: T1 and ECV were higher (1048.5±46.6 vs. 968.3±22.9 ms and 32.4%±5.7% vs. 28.4%±3.8%; P<0.05) and LVS was lower in patients with PAH (−18.0±5.6 vs. −23.0±2.9; P<0.01) compared with controls. LV mass and interventricular septal thickness were lower in PAH patients (65.7±18.0 vs. 86.7±26.9 g and 7.6±1.9 vs. 10±2.4 mm; P<0.05); there were no differences in LV ejection fraction (61.2%±6.9% vs. 61.9%±6.7%; P=0.86). T1-derived parameters correlated significantly with RVS, LVS, the 6-minute walking distance, RV ejection fraction, pro-Brain Natriuretic Peptide, and baseline mean pulmonary arterial pressure. There were no significant differences in T2. Conclusions: In patients with PAH, changes in T1 and ECV support the hypothesis of LV myocardial fibrosis and atrophy with a consecutively impaired contractility despite a preserved LV function, possibly due to longstanding PAH-associated LV underfilling.