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Despite the bioaccessibility of nutrients and contaminants present in individual seafood products has been thoroughly studied, information is extremely limited in what concerns complete seafood-based meals, where interactions between ingredients may occur. Hence, this study aimed to evaluate the effect of different ingredients and cooking processes in mercury (Hg) and cadmium (Cd) bioaccessibility in complete meals of tuna (Thunnus spp.) and edible crab (Cancer pagurus), respectively. The addition of ingredients/side dishes decreased Hg levels in cooked tuna meals, but increased Hg bioaccessibility (up to 31% of bioaccessible Hg in complete meals, against 13.5% in stewed tuna alone). Cd levels in edible crab meals were significantly decreased by the addition of ingredients (~36% and ~65% decrease in boiled crab and paté, respectively), but its' bioaccessibility was not significantly affected (>94% in all cases). Results showed that the weekly consumption of 2 complete tuna meals does not exceed MeHg tolerable weekly intake (TWI), whereas Cd's TWI is largely surpassed with the consumption of 50 g/week of edible crab meals. This highlights the importance of determining contaminant levels and bioaccessibility in a whole seafood-based meal context, as such approach enables a more realistic assessment of the risks that seafood can pose to consumers., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Purpose: Little is known about the pharmacological effects of the phenolic compounds of Pennyroyal (Mentha pulegium). This Mediterranean aromatic plant, used as a gastronomic spice and as food preservative by the food industry has been studied mainly due to its essential oil antibacterial properties, composed primarily by monoterpenes. With this work, we aimed to evaluate the effects of a phenolic extract of pennyroyal in the impairment of inflammatory processes in Inflammatory Bowel Diseases (IBD) and in the potential inhibition of progression to colorectal cancer (CRC)., Methods: To that purpose, we evaluated the effect of pennyroyal extract administration in a model of TNBS-induced colitis in mice and further determined its effect on human colon carcinoma cell proliferation and invasion., Results: The phenolic extract of pennyroyal exhibited antioxidant properties in in vitro assays and administration of the extract in a rat model of carrageenan-induced paw oedema led to significant anti-inflammatory effects. Further results evidenced a beneficial effect of the phenolic extract in the attenuation of experimental colitis and a potential antiproliferative effect on cultured colon cancer cells, effects not previously described, to our knowledge. A reduction in several markers of colon inflammation was observed following administration of the extract to colitis-induced mice, including functional and histological indicators. A successful inhibition of cancer cell invasion and proliferation was also observed in in vitro studies with HT-29 cells. Furthermore, the extract also led to a reduced expression of iNOS/COX-2 in the colon of colitis-induced mice, both being crucial mediators of intestinal inflammation., Conclusions: Taking into consideration the central role of inflammation in the pathophysiology of CRC and the recognised connection between inflammatory events and cancer, these results enlighten the relevance of the phenolic constituents of pennyroyal as important pharmacological sources in the investigation of new treatment options for patients with inflammatory bowel diseases., (Copyright © 2019 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

Industrial cooking of common octopus ( Octopus vulgaris ) under well-established procedures is advantageous for current consumers, which demand healthy and convenient food. This work aimed to evaluate the effect of industrial water boiling, without the addition of salt, on the nutritional profile of common octopus. True retentions (TRs) were calculated for essential nutrients and toxic elements. After boiling, the moisture content decreased, resulting in a concentration of other constituents (protein, fat, fatty acids, majority of amino acids, phosphorus, zinc, and iodine). High TRs were obtained for some essential nutrients: 90.2% (eicosapentaenoic acid, EPA), 89.1% (docosahexaenoic acid, DHA), ≥74.6% (indispensable amino acids, IAA), and 86.8% (iodine). In both raw and boiled octopus, polyunsaturated fatty acids (252.2 and 425.1 mg/100 g), leucine (940.1 and 1613.4 mg/100 g), glutamate (1971.5 and 3257.1 mg/100 g), sodium (393.3 and 332.5 mg/100 g), and zinc (12.6 and 16.6 mg/kg) were, respectively, the most abundant fatty acids, IAA, dispensable amino acids, macro, and micro elements. Cadmium, lead, and mercury levels found in boiled octopus were 0.02, 0.10, and 0.08 mg/kg, respectively. The consumption of 150 g (usual portion) of boiled octopus is advisable because it contributes to significant daily intakes of EPA+DHA (>100%), selenium (75.6%), and iodine (12.4%), and 25% of the daily adequate intake of sodium for adults.

Despite being highly appreciated and consumed, the nutritional value of Chaceon maritae from Namibe (Angola) had never been studied. In the present work, edible tissues (muscle, ovaries, and hepatopancreas) of boiled female C. maritae caught off Namibe coast in two distinct seasons were analyzed in terms of proximate chemical composition (fat, ash, protein, and moisture), fatty acid and amino acid profiles, cholesterol, essential minerals (macro and trace) and toxic elements. Results showed that, in both seasons, C. maritae muscle was a valuable source of protein, essential amino acids, polyunsaturated fatty acids, and essential elements, especially zinc, selenium, iodine, and copper. Ovaries and hepatopancreas are also good sources of protein, but were richer in fat, particularly when caught in October. Ovarian fat is rich in polyunsaturated fatty acids and that of hepatopancreas has higher values of monounsaturated and saturated fatty acids. Hepatopancreas and ovaries are also good sources of copper and, especially ovaries, of zinc. Moreover, in both seasons, all the edible tissues of C. maritae analyzed presented very low contents of heavy metals (mercury, cadmium, lead, and arsenic).

Background : Inflammatory Bowel Diseases (IBD) encompasses both Crohn's Disease and Ulcerative Colitis, known to be connected to an enlarged risk for developing colorectal cancer (CRC). Spearmint ( Mentha spicata L.) is a Mediterranean plant used as an aromatic agent, and studies have mainly focused on the essential oil suggesting an anti-inflammatory activity. This work aimed to perform a preliminary screening of the in vivo anti-inflammatory effects of a spearmint phenolic extract in an acute inflammation model, in a chronic inflammation model of colitis, and also study the effects in vitro on a colon cancer model. Methods : Spearmint extract was administered to rats of a paw oedema model (induced by carrageenan) and to mice from a TNBS-induced colitis model in parallel with studies using HT-29 CRC cells. Results : Administration of the extract led to reduced paw inflammation, reduction of colon injury and inflammation, with attenuation of histological markers, and reduction of iNOS expression. It repressed the in vitro movement of HT-29 cells in a wound healing assay. Conclusions : These findings suggest that spearmint extract exhibits acute and chronic anti-inflammatory activity and is able to inhibit migration of cancer cells, suggesting a potential role in the supplementary therapy of IBD patients.

The phenolic profile and antioxidant activity of Cape Verde's Artemisia gorgonum Webb and Hyptis pectinata (L.) Poit. infusions before and after in vitro simulation of the gastrointestinal digestion were determined. The LC-UV/DAD fingerprinting analysis allowed the identification of 3-O-caffeoylquinic acid, chlorogenic acid, 3,5 dicaffeoylquinic acid, 4,5-dicaffeoylquinic acid and other caffeoylquinic acids derivatives on A. gorgonum infusion, and of caffeoylquinic acid and quercetin derivatives on H. pectinata infusion. Despite some decrease in the chromatographic area of several peaks, no relevant qualitative alterations on the chromatographic profile were observed between the digested and undigested herbal infusions. Results obtained showed a decrease on the antioxidant capacity of both tested herbal infusions after the in vitro digestion. This decrease was more pronounced for H. pectinata than for A. gorgonum and was also more pronounced regarding the radical scavenging capacity than regarding the reducing capacity. After complete digestion the superoxide anion and the DPPH-radical scavenging capacities decreased ≈ 43 and 75% for H. pectinata and ≈ 31 and 70% for A. gorgonum. Despite the observed differences before and after simulated gastrointestinal digestion, both infusions still had antioxidant activity at the end of this process. Thus, the antioxidant potential of A. gorgonum and H. pectinata infusions from Cape Verde, prepared as traditionally used, seems to be kept in some extend throughout the digestive system., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Introduction  Treatment of unstable distal radial fractures (DRFs) in elderly patients is controversial, and considering the increasing life expectancy, their appropriate treatment is of growing importance. Our aim was to analyze the clinical and radiologic outcomes in the elderly patients with AO type C DRF treated with volar locking plate (VLP). Materials and Methods  Between 2007 and 2011, 572 DRFs were operated on in our hospital with open reduction and internal fixation with VLP. Of these, only 64 patients (66 DRFs) met the selection criteria (AO type C DRF, age > 70 years, minimum 12-month follow-up). Mean follow-up was 28 months. Outcome assessment included range of motion, grip strength, VAS pain, Mayo Clinic Score, and DASH score. Analysis of pre- and postoperative radiographs was performed. Complications were recorded. Statistical analysis was performed comparing the results with the contralateral side. Results  Mean postoperative range of motion of the injured wrist compared with the control contralateral side was 86% for flexion ( p  < 0.001), 92% for extension ( p  < 0.001). The average DASH was 12. Mayo Clinic Wrist Score showed 43 excellent results, 15 good, 4 satisfactory, and 4 poor. Articular step-offs were reduced in 34 of 38 wrists. Five (7%) patients required plate removal. Conclusion  The treatment of articular DRF (AO type C) with VLP in the elderly patients achieved greater than 90% of the wrist range of motion and grip strength with no residual pain in greater than 90% of the patients. Level of Evidence  Therapeutic IV, case series.

Background: Several studies have included different co-morbid conditions in prediction models for stroke patients. For subarachnoid haemorrhage (SAH), it is not known whether the Charlson Co-morbidity Index (CCI) is associated with outcome. We evaluated if this index was associated with outcome in patients with ruptured intracerebral aneurysms., Methods: The data of all consecutive aneurysmal SAH (aSAH) patients treated at the Radboudumc, Nijmegen, The Netherlands and entered in the database were retrospectively analysed. Clinical condition at admission was recorded using the WFNS (World Federation of Neurological Surgeons Grading System) grade was collected, as were the age and treatment modality. The burden of co-morbidity was retrospectively registered using the CCI. Outcome was dichotomised on the modified Rankin Scale (mRS; 0-2, favourable outcome; 3-6, unfavourable outcome). A binary logistic regression analysis was performed., Results: Between 6th May 2008 and 31st July 2013, 457 patients were admitted because of non-traumatic SAH (aSAH). Seventy-seven (16.8 %) patients had no aneurysm. Of the 380 patients with aSAH, information on co-morbid conditions was available for 371 patients. Thirty-six of those 371 had no treatment because of: bad clinical condition in 34 (9.2 %), a non-treatable dissecting aneurysm in 1 (0.3 %) and the explicit wishes of another. Co-morbidity was present in 113 (31.5 %) patients. Binary logistic regression analysis revealed no added value of using the CCI in predicting the outcome (p = 0.91)., Conclusions: This study reports that the CCI is not associated with the outcome classified on the mRS at 6 months in patients after aSAH. The CCI has no added value in case-mix correction.

Perspectives on invasive and noninvasive ventilatory support for critically ill patients are evolving, as much evidence indicates that ventilation may have positive effects on patient survival and the quality of the care provided in intensive care units in Brazil. For those reasons, the Brazilian Association of Intensive Care Medicine (Associação de Medicina Intensiva Brasileira - AMIB) and the Brazilian Thoracic Society (Sociedade Brasileira de Pneumologia e Tisiologia - SBPT), represented by the Mechanical Ventilation Committee and the Commission of Intensive Therapy, respectively, decided to review the literature and draft recommendations for mechanical ventilation with the goal of creating a document for bedside guidance as to the best practices on mechanical ventilation available to their members. The document was based on the available evidence regarding 29 subtopics selected as the most relevant for the subject of interest. The project was developed in several stages, during which the selected topics were distributed among experts recommended by both societies with recent publications on the subject of interest and/or significant teaching and research activity in the field of mechanical ventilation in Brazil. The experts were divided into pairs that were charged with performing a thorough review of the international literature on each topic. All the experts met at the Forum on Mechanical Ventilation, which was held at the headquarters of AMIB in São Paulo on August 3 and 4, 2013, to collaboratively draft the final text corresponding to each sub-topic, which was presented to, appraised, discussed and approved in a plenary session that included all 58 participants and aimed to create the final document.

Perspectives on invasive and noninvasive ventilatory support for critically ill patients are evolving, as much evidence indicates that ventilation may have positive effects on patient survival and the quality of the care provided in intensive care units in Brazil. For those reasons, the Brazilian Association of Intensive Care Medicine (Associação de Medicina Intensiva Brasileira - AMIB) and the Brazilian Thoracic Society (Sociedade Brasileira de Pneumonia e Tisiologia - SBPT), represented by the Mechanical Ventilation Committee and the Commission of Intensive Therapy, respectively, decided to review the literature and draft recommendations for mechanical ventilation with the goal of creating a document for bedside guidance as to the best practices on mechanical ventilation available to their members. The document was based on the available evidence regarding 29 subtopics selected as the most relevant for the subject of interest. The project was developed in several stages, during which the selected topics were distributed among experts recommended by both societies with recent publications on the subject of interest and/or significant teaching and research activity in the field of mechanical ventilation in Brazil. The experts were divided into pairs that were charged with performing a thorough review of the international literature on each topic. All the experts met at the Forum on Mechanical Ventilation, which was held at the headquarters of AMIB in São Paulo on August 3 and 4, 2013, to collaboratively draft the final text corresponding to each sub-topic, which was presented to, appraised, discussed and approved in a plenary session that included all 58 participants and aimed to create the final document.

The characterization of a coffee gene encoding a protein similar to miraculin-like proteins, which are members of the plant Kunitz serine trypsin inhibitor (STI) family of proteinase inhibitors (PIs), is described. PIs are important proteins in plant defence against insects and in the regulation of proteolysis during plant development. This gene has high identity with the Richadella dulcifica taste-modifying protein miraculin and with the tomato protein LeMir; and was named as CoMir (Coffea miraculin). Structural protein modelling indicated that CoMir had structural similarities with the Kunitz STI proteins, but suggested specific folding structures. CoMir was up-regulated after coffee leaf miner (Leucoptera coffella) oviposition in resistant plants of a progeny derived from crosses between C. racemosa (resistant) and C. arabica (susceptible). Interestingly, this gene was down-regulated during coffee leaf miner herbivory in susceptible plants. CoMir expression was up-regulated after abscisic acid application and wounding stress and was prominent during the early stages of flower and fruit development. In situ hybridization revealed that CoMir transcripts accumulated in the anther tissues that display programmed cell death (tapetum, endothecium and stomium) and in the metaxylem vessels of the petals, stigma and leaves. In addition, the recombinant protein CoMir shows inhibitory activity against trypsin. According to the present results CoMir may act in proteolytic regulation during coffee development and in the defence against L. coffeella. The similarity of CoMir with other Kunitz STI proteins and the role of CoMir in plant development and plant stress are discussed.

The purpose of this review is to highlight the indications, complications, and outcomes observed with endovascular or open repair for abdominal aortic aneurysms. We selected literature published during 2005 to 2008, encompassing a research period from 1987 to 2005 which compared these 2 techniques and followed various outcomes of morbidity and mortality.

Y459H and V492E mutations of cytochrome P450 reductase (CYPOR) cause Antley-Bixler syndrome due to diminished binding of the FAD cofactor. To address whether these mutations impaired the interaction with drug-metabolizing CYPs, a bacterial model of human liver expression of CYP1A2 and CYPOR was implemented. Four models were generated: POR(null), POR(wt), POR(YH), and POR(VE), for which equivalent CYP1A2 and CYPOR levels were confirmed, except for POR(null), not containing any CYPOR. The mutant CYPORs were unable to catalyze cytochrome c and MTT reduction, and were unable to support EROD and MROD activities. Activity was restored by the addition of FAD, with V492E having a higher apparent FAD affinity than Y459H. The CYP1A2-activated procarcinogens, 2-aminoanthracene, 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone, and 2-amino-3-methylimidazo(4,5-f)quinoline, were significantly less mutagenic in POR(YH) and POR(VE) models than in POR(wt), indicating that CYP1A2, and likely other drug-metabolizing CYPs, are impaired by ABS-related POR mutations as observed in the steroidogenic CYPs.

Nevirapine (NVP) is a non-nucleoside reverse transcriptase inhibitor used against the human immunodeficiency virus type 1 (HIV-1), mostly to prevent mother-to-child HIV transmission in developing countries. One of the limitations of nevirapine use is severe hepatotoxicity, which raises concerns about its administration, particularly in the perinatal and pediatric settings. Nevirapine metabolism involves oxidation of the 4-methyl substituent to 12-hydroxy-NVP and the formation of phenolic derivatives. Further metabolism of 12-hydroxy-NVP by phase II esterification may produce electrophilic derivatives capable of reacting with DNA to yield covalent adducts, which could potentially be involved in the initiation of mutagenic and carcinogenic events. In the present study, we have investigated the reactivity of the synthetic model electrophile, 12-mesyloxy-NVP, toward 2'-deoxynucleosides and DNA. Parallel synthetic studies were conducted with 12-bromo-NVP and 3',5'- O-bis( tert-butyldimethylsilyl)-2'-deoxynucleosides, using palladium(0) catalysis. Multiple adducts from deoxyguanosine, deoxyadenosine, and deoxycytidine were isolated in the reactions with 12-mesyloxy-NVP and characterized by NMR and MS. The adduct structures consistently involved binding through C12 of NVP and N7 or N9 of deoxyguanosine; N1, N3, or N9 of deoxyadenosine; and N3 of deoxycytidine. Reactions conducted under palladium(0) catalysis yielded adducts through O (6) and N1 of deoxyguanosine, N1 of deoxyadenosine, and N3 of deoxycytidine. At least seven deoxynucleoside-NVP adducts were present in DNA reacted with 12-mesyloxy-NVP and enzymatically hydrolyzed. Four of these adducts were identified as 12-(deoxyadenosin-N1-yl)nevirapine, 12-(deoxycytidin-N3-yl)nevirapine, 12-(deoxyguanosin- O(6)-yl)nevirapine, and 12-(deoxyadenosin- N(6)-yl)nevirapine. One depurinating adduct, 12-(guanin-N7-yl)nevirapine, was identified in the thermal neutral DNA hydrolysate. If formed in vivo, some of these adducts would have considerable mutagenic potential. Our results thus suggest that NVP metabolism to 12-hydroxy-NVP may be a factor in NVP hepatocarcinogenicity.

A 78-year-old female patient with a lesion in the distal tibia is shown to have conventional intramedullary chondrosarcoma. Typical considerations for this end-of-bone neoplastic lesion are giant cell tumor, clear cell chondrosarcoma, and chondroblastoma. Salient clinical and radiographic features and behavior of this lesion broaden the typical view of conventional intramedullary chondrosarcoma.

A 65-year-old woman presenting with chronic headaches and without overt visual symptomatology was found to have herniation of the cuneus gyrus into the superior cerebellar cistern. Only one prior case of idiopathic brain herniation has been described, in which the parahippocampal gyrus herniated into the ambient cistern. In that case a biopsy was performed as the herniation was mistaken for a tumor. We describe the features of idiopathic brain herniation that would mitigate the necessity for undergoing brain biopsy.

Serine oligopeptidases of trypanosomatids are emerging as important virulence factors and therapeutic targets in trypanosome infections. A complete open reading frame of oligopeptidase B from Leishmania amazonensis was amplified with polymerase chain reaction with gradient annealing temperatures using primers designed for the oligopeptidase B gene from L. major. The 2,196-bp fragment coded for a protein of 731 amino acids with a predicted molecular mass of 83.49 KDa. The encoded protein (La&#95;OpB) shares a 90% identity with oligopeptidases of L. major and L. infantum, 84% with L. braziliensis, and approximately 62 identity with Trypanosoma peptidases. The oligopeptidase B gene is expressed in all cycle stages of L. amazonensis. The three dimensional model of La&#95;OpB was obtained by homology modeling based on the structure of prolyl oligopeptidases. We mapped a La&#95;OpB model that presents a greater negative charge than prolyl oligopeptidases; our results suggest a difference in the S2 subsite when compared to oligopeptidases B from Trypanosoma and bacterial oligopeptidases B. The La&#95;OpB model serves as a starting point for its exploration as a potential target source for a rational chemotherapy.

Background and Objectives: There are few epidemiological studies in mechanical ventilation, and the aim of the study is to show how this procedure is being used in Brazil., Methods: A 1-day point prevalence study was performed in 40 ICUs, with 390 patients; 217 of these patients were in mechanical ventilation. The results evaluated were the characteristics of ventilated patients, their distribution in Brazil, the mechanical ventilation's causes, the main ventilatory modes, the more important ventilators settings, and the weaning stage of mechanical ventilation., Results: The median age of the ventilated patients was 66 years old. The median APACHE II was 20, while the median time of mechanical ventilation was 11 days. Acute respiratory failure occurred in 71% of the patients, coma in 21.2%, acute exacerbation of chronic respiratory failure in 5.5%, and the neuromuscular disease in 2.3%. The volume-controlled ventilation (VCV) (30%), the pressure support ventilation (PSV) (29.5%), and the pressure-controlled ventilation (PCV) (18%) were the ventilatory modes most used; the PSV had been the main mode in weaning (63.5%). The median of tidal volume (8 mL/kg) was higher in VCV. The median of maximal inspiratory pression (30 cmH2O) and the median of positive end-expiration pressure (PEEP) (8 cmH2O) were higher in PCV., Conclusions: The predominance of ventilated patients in ICUs was marked by clinical severity of them, and a longer hospital stay time; acute respiratory failure was the principal mechanical ventilation cause; VCV and PSV ventilated more patients, with PSV being more used in weaning patients.

Background: There has been a growing interest in treating postmenopausal women with androgens. However, hyperandrogenemia in females has been associated with increased risk of cardiovascular disease., Objective: We aimed to assess the effects of androgen replacement on cardiovascular risk factors., Design: Thirty-seven postmenopausal women aged 42-62 years that had undergone hysterectomy were prospectively enrolled in a double-blind protocol to receive, for 12 months, percutaneous estradiol (E2) (1 mg/day) combined with either methyltestosterone (MT) (1.25 mg/day) or placebo., Methods: Along with treatment, we evaluated serum E2, testosterone, sex hormone-binding globulin (SHBG), free androgen index, lipids, fibrinogen, and C-reactive protein; glucose tolerance; insulin resistance; blood pressure; body-mass index; and visceral and subcutaneous abdominal fat mass as assessed by computed tomography., Results: A significant reduction in SHBG (P < 0.001) and increase in free testosterone index (P < 0.05; Repeated measures analysis of variance) were seen in the MT group. Total cholesterol, triglycerides, fibrinogen, and systolic and diastolic blood pressure were significantly lowered to a similar extent by both regimens, but high-density lipoprotein cholesterol decreased only in the androgen group. MT-treated women showed a modest rise in body weight and gained visceral fat mass relative to the other group (P < 0.05), but there were no significant detrimental effects on fasting insulin levels and insulin resistance., Conclusion: This study suggests that the combination of low-dose oral MT and percutaneous E2, for 1 year, does not result in expressive increase of cardiovascular risk factors. This regimen can be recommended for symptomatic postmenopausal women, although it seems prudent to perform baseline and follow-up lipid profile and assessment of body composition, especially in those at high risk of cardiovascular disease.

Background: Early recognition of heart disease in diabetics is a highly desirable goal, and diastolic dysfunction, one of its earliest manifestations, can be readily assessed by tissue Doppler imaging. We tested in normotensive diabetics without signs of coronary artery disease whether tissue Doppler imaging would improve the diagnosis of diastolic dysfunction beyond classical criteria and identify patients already presenting impaired cardiac performance., Methods: We studied 79 patients (56 males, 55 type-2 diabetes mellitus) who underwent Doppler echocardiography, and exercise testing. Diastolic dysfunction was diagnosed either based on European Study Group on Diastolic Heart Failure guidelines or by tissue Doppler imaging provided that both of the following criteria were met: Em/Am ratio <1; and Em < 8.5 cm/sec., Results: Tissue Doppler imaging identified diastolic dysfunction in 26.6% of diabetics, while classical criteria did so in 40.5% of the cases. The group identified by classical criteria did not differ significantly from patients without diastolic dysfunction, while in the group identified by Tissue Doppler imaging, significant differences were highlighted, including worse exercise tolerance and higher left ventricular mass index. Moreover, in multiple regression analysis, Em myocardial velocity and body mass index were the only variables independently related to exercise tolerance., Conclusion: Differently from classical criteria based on pulsed Doppler, Tissue Doppler imaging identifies a group of asymptomatic normotensive diabetics with diastolic dysfunction and reduced exercise tolerance. Confirmation of the prognostic importance of our findings could justify the use of Tissue Doppler imaging for diastolic function assessment in diabetics with otherwise healthy hearts.

We report here on strain BTC, a new Escherichia coli mutagenicity tester strain for the expression of human cytochrome P450 (CYP) with an enhanced sensitivity for the detection of alkylating agents. This strain was developed first through knocking out of the genes ada and ogt in our previously developed strain BMX100, resulting in PD1000. Strain PD1000 demonstrated a significantly higher detection sensitivity towards several alkylating agents such as N-nitrosodiethylamine (NNdEA), N-nitrosodi-n-propylamine (NNdPA), 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) and N-methyl-N'-nitro-N-nitrosoguanidine (MNNG). Unexpectedly, this strain also showed an enhanced sensitivity towards 2-aminoanthracene (2AA), 4-aminobiphenyl (4AbPh), 2-aminofluorene (2AF) and 2-nitroanthracene (2NA) mutagenicity. Subsequently, our previously developed bi-plasmid system for the co-expression of a specific human CYP form (CYP1A2, 2A6 or 2E1) with human NADPH-cytochrome P450 reductase (RED) was introduced in strain PD1000, resulting in strains BTC1A2, BTC2A6 and BTC2E1, respectively. The mutagenicity of NNdEA and NNK was successfully detected with strains BTC2A6 and BTC2E1 and with strains BTC1A2 and BTC2A6, respectively, in contrast to the corresponding MTC (ada+ ogt+) CYP strains. The (ada- ogt-) deficient strain BTC1A2 also showed an enhanced sensitivity towards the detection of 2AA mutagenicity, when compared with the proficient repair strain MTC1A2. This enhancement was much more pronounced with strain PD1000 using the rat liver S9 fraction than with strain BTC1A2.

Women in their fourth decade and older experience a decrease in androgen serum levels. This may lead to the clinical syndrome of female androgen insufficiency expressed by insidious tiredness, diminished sense of well-being and libido, alterations in body composition and bone loss. If there is a past history of bilateral oophorectomy, hypopituitarism, androgen adrenal suppression and/or free testosterone serum levels are low, it is probable that these signs and symptoms could be relieved by a discerning androgen administration, which has been largely accepted. When current recommended doses are used, it appears that the benefits regarding bone mass, sexuality and well-being may be achieved without important signs of masculinizing. Nonetheless, it is necessary to conduct well-controlled, long-term studies, in order to validate the hypothesis that therapeutic administration of androgens to women does not lead to an increased incidence of breast cancer or metabolic complications.

Cytochrome b(5) (b(5)) is increasingly recognized to be of importance for specific cytochrome P450 (CYP) activities. We developed human b(5)/CYP-competent mutagenicity tester bacteria to study the role of b(5) in the bioactivation activity of human CYP. These new tester bacteria were derived from the previously engineered human CYP-competent Escherichia coli K12 tester strain MTC, containing a bi-plasmid system for the co-expression of a specific CYP form (CYP1A2, 2A6 or 2E1) with human b(5), and human NADPH cytochrome P450 reductase (RED), resulting in the strain BTC-b(5)-1A2, BTC-b(5)-2A6 and BTC-b(5)-2E1, respectively. The relative content of b(5) with CYP and RED in these three BTC-b(5)-CYP strains demonstrated physiologically relevant co-expression levels and typical CYP-specific activities could be determined with their specific chemical probes. These strains were applied in mutagenicity assays along with their corresponding b(5)-void strains to determine the effect of b(5) on the CYP1A2-, CYP2A6- and CYP2E1-mediated bioactivation of several promutagens. For CYP1A2, of the 5 compounds tested [2-aminoanthracene (2AA), 1-aminopyrene, 6-aminochrysene, 2-amino-3-methylimidazo(4,5-f)quinoline and 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK)], only the mutagenicity of 2AA was slightly increased ( approximately 1.5-fold) in the presence of b(5). The CYP2E1- and CYP2A6-dependent mutagenicity of N-nitrosodiethylamine increased approximately 3- and 23-fold, respectively when the bacteria contained b(5). The CYP2A6-mediated mutagenicity of NNK increased approximately 9-fold when co-expressed with b(5). The stimulatory effect of b(5) on the bioactivation of N-nitrosodi-n-propylamine was most striking. The mutagenicity of this procarcinogen was completely dependent on the co-expression of b(5) with CYP2A6 or CYP2E1. This demonstrates the prominent role of b(5) in the bioactivation of this carcinogen.

Disturbances in Calcium-PTH-Vitamin D axis are frequently associated with chronic liver diseases (CLD). In patients with CLD, a trend toward decreased serum calcium and vitamin D has already been demonstrated with compensatory increases in PTH levels. Even though reduced vitamin D hydroxylation has been considered the most important mechanism for these alterations, recent studies demonstrates an adequate production of 25(OH) Vitamin D even in end-stage liver disease. Therefore, other factors (i.e. inadequate diet, reduced exposure to sun light) would be responsible for the disturbances in calcium-PTH-vitamin D axis. Furthermore, antiviral drugs (such as ribavirin for hepatitis C) and glucocorticoids (cystic fibrosis) may also contribute to the worsening of these disturbances. On the other hand, osteoporosis, but not osteomalacia or secondary hyperparathyroidism, seems to be the main alteration in CLD. Thus, the clinical relevance of calcium-PTH-vitamin D disturbances in hepatic osteodystrophy is still under discussion.

Catechols from abietic acid were prepared by a short and good yielding chemical process and further evaluated for several biological activities namely, antifungal, antitumoral, antimutagenic, antiviral, antiproliferative and inhibition of nitric oxide. Their properties were compared with those of carnosic acid (6), a naturally occurring catechol with an abietane skeleton and known to possess potent antioxidant activity, as well as anticancer and antiviral properties. From all the synthetic catechols tested compound 2 showed the best activities, stronger than carnosic acid.

Background: The main process involved in hepatic osteodystrophy seems to be osteoporosis, but decreased 25-hydroxylation of vitamin D might lead to osteomalacia and secondary hyperparathyroidism., Methods and Results: We studied bone mineral density (BMD) by using DEXA-Expert Lunar, biochemical markers of bone turnover and calcium-parathyroid hormone (PTH)-vitamin D axis in 100 patients with chronic viral hepatitis secondary to hepatitis C virus: 49 non-cirrhotic (NCir) and 51 with cirrhosis (Cir) confirmed by liver biopsy and/or clinical and biochemical features. When compared to the age-matched population, 25% of the patients had low BMD at the lumbar spine (LS), 26.2% at Ward's triangle, 15.5% at the femoral neck (FN), and 20.2% at the trochanter. No difference was found either between Cir and NCir groups or between sexes. Urinary N-telopeptide was increased in 31.86% of the patients, and negatively correlated with BMD at the LS and trochanter (P < 0.02). Serum bone-specific alkaline phosphatase was elevated in 21% of the patients and negatively correlated with BMD at the trochanter and Ward's triangle (P < 0.02). Fasting 25-hydroxyvitamin D was low in only three Cir patients, with no difference between the Cir and NCir groups, but it was higher in men (51.8 +/- 16.0 ng/mL) compared to women (40.4 +/- 14.4 ng/mL; P = 0.001). Fasting serum calcium was lower in Cir than NCir patients, P = 0.019. Fasting intact PTH was elevated in 42% of the patients, but the mean serum levels were similar in Cir and NCir groups., Conclusion: We found no evidence of vitamin D deficiency, but cannot exclude the participation of PTH in the high bone turnover and bone loss in the population with chronic viral hepatitis.

Instant coffee exhibits genotoxic activity upon nitrosation at acidic pH values in the Ames tester strain TA100. Using adsorption chromatography (Amberlit XAD-2) it was observed that the major fraction of molecules responsible for the genotoxic activity upon nitrosation was not retained on this resin, suggesting that the polar molecules present in instant coffee could be responsible for the genotoxicity observed upon nitrosation. Some phenolic molecules present in instant coffee (catechol, caffeic acid, and chlorogenic acid) were also genotoxic upon nitrosation under the same experimental conditions. The concentrations of nitrosatable phenolic compounds in the studied coffee were determined by HPLC and their contributions to the total genotoxicity observed were studied. The results obtained suggest that besides phenolic compounds other molecules were also involved in the genotoxicity of this beverage upon nitrosation. Teratogenesis Carcinog. Mutagen. 20:241-249, 2000., (Copyright 2000 Wiley-Liss, Inc.)

Instant coffee exhibits direct genotoxic activity in the tester strains TA 98, 100, 102, 104 and YG 1024. In the Ames tester strain TA 100, the presence of S9 mix, S100 mix, S9 mix without cofactors led to a significant decrease of the genotoxicity observed. The decrease observed in the presence of S9 mix seems to be highly correlated with the catalase content of S9 mix. The genotoxicity of instant coffee detected in strain TA 100 was dependent on the pH, with higher genotoxic effects at pH values above neutrality. Also, dependent on the pH was the ability of some phenolic molecules present in coffee promoting the degradation of deoxyribose in the presence of Fe3+/EDTA. These results suggest that apart from other molecules present in instant coffee responsible for their genotoxicity in several short term assays, phenolic molecules could also be implicated in the genotoxicity of coffee, via reactive oxygen species arising from its auto-oxidation., (Copyright 1999 Elsevier Science B.V.)