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1.
J Antimicrob Chemother ; 78(8): 1900-1908, 2023 08 02.
Article in English | MEDLINE | ID: mdl-37294305

ABSTRACT

BACKGROUND: Antibiotic use is associated with collateral damage to the healthy microbiota. Afabicin is a first-in-class prodrug inhibitor of the FabI enzyme that, when converted to the pharmacologically active agent afabicin desphosphono, demonstrates a staphylococcal-specific spectrum of activity. An expected benefit of highly targeted antibiotics such as afabicin is microbiome preservation. OBJECTIVES: To compare the effects of oral treatment with afabicin and standard-of-care antibiotics upon the murine gut microbiota, and to assess the effects of oral afabicin treatment on the human gut microbiota. METHODS: Gut microbiota effects of a 10 day oral course of afabicin treatment were monitored in mice and compared with clindamycin, linezolid and moxifloxacin at human-equivalent dose levels using 16S rDNA sequencing. Further, the gut microbiota of healthy volunteers was longitudinally assessed across 20 days of oral treatment with afabicin 240 mg twice daily. RESULTS: Afabicin treatment did not significantly alter gut microbiota diversity (Shannon H index) or richness (rarefied Chao1) in mice. Only limited changes to taxonomic abundances were observed in afabicin-treated animals. In contrast, clindamycin, linezolid and moxifloxacin each caused extensive dysbiosis in the murine model. In humans, afabicin treatment was not associated with alterations in Shannon H or rarefied Chao1 indices, nor relative taxonomic abundances, supporting the findings from the animal model. CONCLUSIONS: Oral treatment with afabicin is associated with preservation of the gut microbiota in mice and healthy subjects.


Subject(s)
Anti-Bacterial Agents , Microbiota , Humans , Mice , Animals , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/therapeutic use , Clindamycin/pharmacology , Moxifloxacin/therapeutic use , Linezolid/pharmacology , Staphylococcus
2.
Ann Ig ; 32(5 Supple 1): 3-16, 2020.
Article in English | MEDLINE | ID: mdl-33146363

ABSTRACT

The 2014-2018 National Prevention Plan (NPP), in order to promote a correct relationship between health and the environment, indicated, among the central objectives, the definition of guidelines to promote the building hygiene codes in an eco-compatible way, but also to develop specific skills on the subject of confined environments and residential construction in the operators of the Regional Health Services. The CCM2015 Project has therefore set itself the goal of taking stock of the best health practices available today in terms of sustainability and eco-compatibility in the buildings' construction and renovation actions. All this in order to define updated health performance targets to be made available to the competent Authorities, to adapt the current legislation at national, regional and local level, and finally to define the contents of a continuing education (training courses) capable to support operators in risk assessment related to the built environment and in the definition of effective preventive measures.


Subject(s)
Environment Design/standards , Facility Design and Construction/standards , Hygiene/standards , Environment Design/legislation & jurisprudence , Facility Design and Construction/legislation & jurisprudence , Guidelines as Topic , Humans , Hygiene/legislation & jurisprudence , Italy
3.
Public Health ; 161: 154-162, 2018 Aug.
Article in English | MEDLINE | ID: mdl-29751981

ABSTRACT

OBJECTIVES: The aim of the article is to evaluate the temporal change in the effect of heat on mortality in Italy in the last 12 years after the introduction of the national heat plan. STUDY DESIGN: Time series analysis. METHODS: Distributed lag non-linear models were used to estimate the association between maximum apparent temperature and mortality in 23 Italian cities included in the national heat plan in four study periods (before the introduction of the heat plan and three periods after the plan was in place between 2005 and 2016). The effect (relative risks) and impact (attributable fraction [AF] and number of heat-related deaths) were estimated for mild summer temperatures (20th and 75th percentile maximum apparent temperature [Tappmax]) and extreme summer temperatures (75th and 99th percentile Tappmax) in each study period. A survey of the heat preventive measures adopted over time in the cities included in the Italian heat plan was carried out to better describe adaptation measures and response. RESULTS: Although heat still has an impact on mortality in Italian cities, a reduction in heat-related mortality is observed progressively over time. In terms of the impact, the heat AF related to extreme temperatures declined from 6.3% in the period 1999-2002 to 4.1% in 2013-2016. Considering the entire temperature range (20th vs 99th percentile), the total number of heat-related deaths spared over the entire study period was 1900. CONCLUSIONS: Considering future climate change and the health burden associated to heat waves, it is important to promote adaptation measures by showing the potential effectiveness of heat prevention plans.


Subject(s)
Hot Temperature/adverse effects , Mortality/trends , National Health Programs , Acclimatization , Aged , Aged, 80 and over , Cities , Climate Change , Female , Humans , Italy/epidemiology , Male , Program Evaluation , Risk , Seasons , Time Factors
4.
Ann Ig ; 29(6): 481-493, 2017.
Article in English | MEDLINE | ID: mdl-29048447

ABSTRACT

The Erice 50 Charter titled "Strategies for Diseases Prevention and Health Promotion in Urban Areas" was unanimously approved at the conclusion of the 50th Residential Course "Urban Health. Instruments for promoting health and for assessing hygienic and sanitary conditions in urban areas", held from 29th March to 2nd April 2017 in Erice, at the "Ettore Majorana" Foundation and Centre for Scientific Culture and promoted by the International School of Epidemiology and Preventive Medicine "G. D'Alessandro" and the Study Group "Building Hygiene" of the Italian Society of Hygiene, Preventive Medicine and Public Health (SItI). At the conclusion of the intense learning experience during the Course, with more than 20 lectures, workshops and long-lasting discussions between Professors and Students, the participants identified the major points connecting urban features and Public Health, claiming the pivotal role of urban planning strategies for the management of Diseases Prevention and Health Promotion activities. The Erice 50 Charter is configured as a Decalogue for Healthy Cities and as a Think Tank for designing effective strategic actions and best practices to develop urban regeneration interventions and improve the urban quality of contemporary cities. The Decalogue is structured into the following key strategic objectives: 1. Promoting urban planning interventions that address citizens towards healthy behaviours; 2. Improving living conditions in the urban context; 3. Building an accessible and inclusive city, with a special focus on the frail population; 4. Encouraging the foundation of resilient urban areas; 5. Supporting the development of new economies and employment through urban renewal interventions; 6. Tackling social inequalities; 7. Improving stakeholders' awareness of the factors affecting Public Health in the cities; 8. Ensuring a participated urban governance; 9. Introducing qualitative and quantitative performance tools, capable of measuring the city's attitude to promote healthy lifestyles and to monitor the population's health status; 10. Encouraging sharing of knowledge and accessibility to informations. Finally, all the participants underlined that a multidisciplinary team, composed of Physicians specialized in Hygiene, Preventive Medicine, Public Health and Technicians as Architects, Urban planners and Engineers, is needed to deepen the research topic of Urban Health.


Subject(s)
Health Promotion/methods , Primary Prevention/methods , Urban Health , Humans , Italy
5.
Vet Pathol ; 53(6): 1172-1179, 2016 11.
Article in English | MEDLINE | ID: mdl-27154541

ABSTRACT

Ovine pulmonary adenocarcinoma (OPA) is a contagious lung cancer of sheep caused by jaagsiekte sheep retrovirus (JSRV). It is generally accepted that transmission by the respiratory route occurs under natural conditions. However recent studies strongly indicate that JSRV can also be transmitted to lambs perinatally via colostrum and milk (C/M). The aim of this work was to confirm that C/M can transmit JSRV infection to lambs under natural conditions and investigate the initial events associated with this transmission route. We have analyzed the presence of JSRV in C/M samples from 22 naturally infected, asymptomatic ewes throughout a lactation period, and in various tissues collected from a group of 36 of their lambs that were fed naturally. The lambs were euthanized at 12, 24, 48, and 72 hours and at 5 and 10 days after birth. We detected JSRV-provirus by PCR in the somatic C/M cells from 10/22 ewes (45.45%). The virus was also detected in 9/36 lambs (25%). JSRV-infected cells, with lymphoreticular-like morphology, were observed by immunohistochemistry (IHC) and in situ hybridization (ISH) in Peyer's patches (PP) from the small intestine of the youngest lambs and in mesenteric lymph nodes (MLN) from lambs older than 72 hours. The virus was also detected by PCR in white blood cells (WBC) in 2/36 lambs (5.5%). These results confirm colostral transmission of JSRV to lambs under natural conditions. Infected lymphoreticular cells contained in C/M appear to be involved. These cells can cross the intestinal barrier of newborn lambs, reach the MLN and enter into circulation.


Subject(s)
Infectious Disease Transmission, Vertical/veterinary , Jaagsiekte sheep retrovirus , Lymph Nodes/virology , Peyer's Patches/virology , Pulmonary Adenomatosis, Ovine/transmission , Animals , Animals, Suckling/virology , Female , Male , Mesentery , Milk/virology , Polymerase Chain Reaction/veterinary , Sheep
6.
Opt Express ; 23(3): 1951-66, 2015 Feb 09.
Article in English | MEDLINE | ID: mdl-25836067

ABSTRACT

Spectral Mueller matrices measured at multiple angles of incidence as well as Mueller matrix images are recorded on the exoskeletons (cuticles) of the scarab beetles Cetonia aurata and Chrysina argenteola. Cetonia aurata is green whereas Chrysina argenteola is gold-colored. When illuminated with natural (unpolarized) light, both species reflect left-handed and near-circularly polarized light originating from helicoidal structures in their cuticles. These structures are referred to as circular Bragg reflectors. For both species the Mueller matrices are found to be nondiagonal depolarizers. The matrices are Cloude decomposed to a sum of non-depolarizing matrices and it is found that the cuticle optical response, in a first approximation can be described as a sum of Mueller matrices from an ideal mirror and an ideal circular polarizer with relative weights determined by the eigenvalues of the covariance matrices of the measured Mueller matrices. The spectral and image decompositions are consistent with each other. A regression-based decomposition of the spectral and image Mueller matrices is also presented whereby the basic optical components are assumed to be a mirror and a circular polarizer as suggested by the Cloude decomposition. The advantage with a regression decomposition compared to a Cloude decomposition is its better stability as the matrices in the decomposition are determined a priori. The origin of the depolarizing features are discussed but from present data it is not possible to conclude whether the two major components, the mirror and the circular polarizer are laterally separated in domains in the cuticle or if the depolarization originates from the intrinsic properties of the helicoidal structure.

7.
Appl Opt ; 54(10): 2776-85, 2015 Apr 01.
Article in English | MEDLINE | ID: mdl-25967189

ABSTRACT

The purpose of this article is to present a new broadband Mueller ellipsometer designed to work in the mid-infrared range, from 3 to 14 µm. The Mueller ellipsometer, which can be mounted in reflection or in transmission configuration, consists of a polarization state generator (PSG), a sample holder, and a polarization state analyzer (PSA). The PSG consists of one linear polarizer and a retarder sequentially rotated to generate a set of four optimal polarization states. The retarder consists of a biprism made of two identical Fresnel rhombs disposed symmetrically and joined by an optical contact, giving the ensemble a "V" shape. Retardation is induced by the four total internal reflections that the beam undergoes when it propagates through the biprism. Total internal reflection allows the generation of a quasi-achromatic retardation. The PSA is identical to the PSG, but with its optical elements mounted in reverse order. After a measurement run, the instrument yields a set of sixteen independent values, which is the minimum amount of data required to calculate the Mueller matrix of the sample. The design of the Mueller ellipsometer is based on the optimization of an objective criterion that allows for minimizing the propagation of errors from raw data to the Mueller matrix of the sample. The pseudo-achromatic optical elements ensure a homogeneous quality of the measurements for all wavelengths. The performance of the Mueller ellipsometer, in terms of precision and accuracy, is discussed and illustrated with a few examples.

8.
Cell Microbiol ; 15(12): 1994-2005, 2013 Dec.
Article in English | MEDLINE | ID: mdl-23848406

ABSTRACT

Apoptosis modulation is a procedure amply utilized by intracellular pathogens to favour the outcome of the infection. Nevertheless, the role of apoptosis during infection with Mycobacterium tuberculosis, the causative agent of human tuberculosis, is subject of an intense debate and still remains unclear. In this work, we describe that apoptosis induction in host cells is clearly restricted to virulent M. tuberculosis strains, and is associated with the capacity of the mycobacteria to secrete the 6 kDa early secreted antigenic target ESAT-6 bothunder in vitro and in vivo conditions. Remarkably, only apoptosis-inducing strains are able to propagate infection into new cells, suggesting that apoptosis is used by M. tuberculosis as a colonization mechanism. Finally, we demonstrate that in vitro modulation of apoptosis affects mycobacterial cell-to-cell spread capacity, establishing an unambiguous relationship between apoptosis and propagation of M. tuberculosis. Our data further indicate that BCG and MTBVAC vaccines are inefficient in inducing apoptosis and colonizing new cells, correlating with the strong attenuation profile of these strains previously observed in vitro and in vivo.


Subject(s)
Antigens, Bacterial/metabolism , Apoptosis/immunology , Bacterial Proteins/metabolism , Homeodomain Proteins/metabolism , Mycobacterium tuberculosis/metabolism , Tuberculosis/transmission , Animals , Antigens, Bacterial/genetics , BCG Vaccine/immunology , Bacterial Proteins/genetics , Female , Green Fluorescent Proteins , Humans , Macrophages/microbiology , Mice , Mice, Inbred C57BL , Mycobacterium tuberculosis/pathogenicity
9.
Article in English | MEDLINE | ID: mdl-20706609

ABSTRACT

Characterizing the capabilities, key dependencies, and response to perturbations of genome-scale metabolic networks is a basic problem with important applications. A key question concerns the identification of the potentially most harmful reaction knockouts. The integration of combinatorial methods with sampling techniques to explore the space of viable flux states may provide crucial insights on this issue. We assess the replaceability of every metabolic conversion in the human red blood cell by enumerating the alternative paths from substrate to product, obtaining a complete map of he potential damage of single enzymopathies. Sampling the space of optimal steady state fluxes in the healthy and in the mutated cell reveals both correlations and complementarity between topologic and dynamical aspects.


Subject(s)
Enzymes/blood , Erythrocytes/metabolism , Models, Biological , Systems Biology/methods , Algorithms , Humans , Metabolic Diseases/blood , Metabolic Networks and Pathways , Mutation
10.
J Comp Pathol ; 176: 10-13, 2020 Apr.
Article in English | MEDLINE | ID: mdl-32359621

ABSTRACT

A 20-year-old male brown bear (Ursus arctos) with a 20 × 25 cm necrotic mass adjacent to the trachea was diagnosed as having an anaplastic thyroid carcinoma. Metastases were observed in the lungs and one adrenal gland and, histologically, these had anaplastic and follicular carcinoma patterns, respectively. E-cadherin labelling was observed in the adrenal mass only, while N-cadherin immunolabelling was detected in the thyroid gland and lung masses. Thyroid-specific markers (thyroid transcription factor-1, thyroglobulin) were expressed in the adrenal gland metastasis. This case illustrates an example of a primary epithelial-mesenchymal transition (EMT) enabling metastasis to distant organ sites, followed by a mesenchymal-epithelial transition within the adrenal gland microenvironment, allowing invasion and reacquisition of thyroid epithelial cell features. EMTs help to understand the phenomenon of carcinoma cell plasticity in enabling colonization and growth of metastases.


Subject(s)
Epithelial-Mesenchymal Transition , Thyroid Neoplasms/veterinary , Ursidae , Animals , Male
11.
Opt Express ; 17(15): 12794-806, 2009 Jul 20.
Article in English | MEDLINE | ID: mdl-19654685

ABSTRACT

The measurement of the Mueller matrix when the probing beam is placed on the boundary between two (or more) regions of the sample with different optical properties may lead to a depolarization in the Mueller matrix. The depolarization is due to the incoherent superposition of the optical responses of different sample regions in the probe beam. Despite of the depolarization, the measured Mueller matrix has information enough to subtract a Mueller matrix corresponding to one of the regions of sample provided that this subtracted matrix is non-depolarizing. For clarity, we will call these non-depolarizing Mueller matrices of one individual region of the sample simply as the non-depolarizing components. In the framework of the theory of Mueller matrix algebra, we have implemented a procedure allowing the retrieval of a non-depolarizing component from a depolarizing Mueller matrix constituted by the sum of several non-depolarizing components. In order to apply the procedure, the Mueller matrices of the rest of the non-depolarizing components have to be known. Here we present a numerical and algebraic approaches to implement the subtraction method. To illustrate our method as well as the performance of the two approaches, we present two practical examples. In both cases we have measured depolarizing Mueller matrices by positioning an illumination beam on the boundary between two and three different regions of a sample, respectively. The goal was to retrieve the non-depolarizing Mueller matrix of one of those regions from the measured depolarizing Mueller matrix. In order to evaluate the performance of the method we compared the subtracted matrix with the Mueller matrix of the selected region measured separately.


Subject(s)
Optics and Photonics , Algorithms , Image Processing, Computer-Assisted , Light , Microscopy, Polarization/methods , Models, Statistical , Physics/methods
12.
Cerebrovasc Dis ; 27(4): 375-83, 2009.
Article in English | MEDLINE | ID: mdl-19276620

ABSTRACT

BACKGROUND: To test whether supplementary antioxidants and n-3 fatty acids, alone or in combination, could improve functional status in stroke survivors. METHODS: We performed a randomized, double-blind, placebo-controlled clinical trial in 72 stroke patients (47 males; age 65.3 +/- 12.9 years) admitted to a rehabilitation hospital for sequelae of first-ever ischemic stroke, and divided them into 4 subgroups. Group 1 patients received daily oral antioxidants, group 2 received n-3 polyunsaturated fatty acids, group 3 both supplements, and group 4 placebo, all for 12 months. No difference at baseline was observed among groups in neurological severity or in disability. All measures were repeated after 6 and 12 months of treatment. All major clinical events were recorded. RESULTS: At baseline, 25% of the patients had a low plasma vitamin status, and 48.5% was at risk of undernutrition. At the 1-year follow-up, we observed a trend for lower mortality (p = 0.060) in subgroups treated with n-3 fatty acids, but without significant differences in rehabilitation result status among groups. CONCLUSIONS: Malnutrition is widely observed in patients admitted to a rehabilitative hospital for stroke rehabilitation, and dietary supplementation, even if not able to improve rehabilitation results, is likely to reduce mortality at the 1-year follow-up.


Subject(s)
Antioxidants/therapeutic use , Disability Evaluation , Fatty Acids, Omega-3/therapeutic use , Stroke Rehabilitation , Aged , Antioxidants/administration & dosage , Dietary Supplements , Double-Blind Method , Fatty Acids, Omega-3/administration & dosage , Female , Follow-Up Studies , Humans , Italy , Male , Middle Aged , Mortality , Nutritional Status , Stroke/physiopathology
13.
Rev Med Univ Navarra ; 53(2): 14-9, 2009.
Article in Spanish | MEDLINE | ID: mdl-19994764

ABSTRACT

The current knowledge status on the patogenesis of endometriosis as well as devastating consequences of disease evolution in women's reproductive health, have promoted researchers advances in a great manner during last years. The immunologic and neangiogenesis systems implication have opened new ways of knowledge over classic theories from the beginning of the xx century. The experimental resesearch, using animal induction models. Below we explain the first steps a new induction model ("PGR1-HotDog"), based on Wistar rats using a new disease autogeneration system, created for te study of the early stages of the endometriosis.


Subject(s)
Disease Models, Animal , Endometriosis , Animals , Female , Microsurgery , Rats , Rats, Wistar
14.
Clin Microbiol Infect ; 25(10): 1266-1276, 2019 Oct.
Article in English | MEDLINE | ID: mdl-30790685

ABSTRACT

OBJECTIVES: Weekly monitoring of European all-cause excess mortality, the EuroMOMO network, observed high excess mortality during the influenza B/Yamagata dominated 2017/18 winter season, especially among elderly. We describe all-cause excess and influenza-attributable mortality during the season 2017/18 in Europe. METHODS: Based on weekly reporting of mortality from 24 European countries or sub-national regions, representing 60% of the European population excluding the Russian and Turkish parts of Europe, we estimated age stratified all-cause excess morality using the EuroMOMO model. In addition, age stratified all-cause influenza-attributable mortality was estimated using the FluMOMO algorithm, incorporating influenza activity based on clinical and virological surveillance data, and adjusting for extreme temperatures. RESULTS: Excess mortality was mainly attributable to influenza activity from December 2017 to April 2018, but also due to exceptionally low temperatures in February-March 2018. The pattern and extent of mortality excess was similar to the previous A(H3N2) dominated seasons, 2014/15 and 2016/17. The 2017/18 overall all-cause influenza-attributable mortality was estimated to be 25.4 (95%CI 25.0-25.8) per 100,000 population; 118.2 (116.4-119.9) for persons aged 65. Extending to the European population this translates into over-all 152,000 deaths. CONCLUSIONS: The high mortality among elderly was unexpected in an influenza B dominated season, which commonly are considered to cause mild illness, mainly among children. Even though A(H3N2) also circulated in the 2017/18 season and may have contributed to the excess mortality among the elderly, the common perception of influenza B only having a modest impact on excess mortality in the older population may need to be reconsidered.


Subject(s)
Influenza B virus/isolation & purification , Influenza, Human/mortality , Influenza, Human/virology , Mortality , Adolescent , Adult , Age Factors , Aged , Aged, 80 and over , Child , Child, Preschool , Europe/epidemiology , Female , Humans , Infant, Newborn , Male , Middle Aged , Young Adult
15.
Water Res ; 42(3): 643-52, 2008 Feb.
Article in English | MEDLINE | ID: mdl-17904611

ABSTRACT

This study investigated the sorption of paraquat and 2,4-D on polymerin, the humic acid-like fraction of olive mill wastewater. Effects of pH, contact time, initial concentration and sorbent dosage on the sorption of both herbicides were studied. The sorption mechanism of paraquat on polymerin was consistent with the ion exchange of this herbicide with Ca, Mg and K natively occurring in the sorbent; in contrast, 2,4-D was bound to polymerin by hydrogen bonding. Simulated wastewaters contaminated with paraquat were purified after three sorption cycles on polymerin renewed at each cycle, at a solid/liquid ratio of 0.5, whereas those containing 2,4-D showed a maximal residue removal of 44% after two sorption cycles at the same ratio. The possible application of this model to other water-soluble herbicides, as well as the possible exploitation of polymerin as a bio-filter for the decontamination of pollution point sources is briefly discussed.


Subject(s)
2,4-Dichlorophenoxyacetic Acid/chemistry , Herbicides/chemistry , Industrial Waste , Olea , Paraquat/chemistry , Polymers/chemistry , Water Pollutants, Chemical/chemistry , Adsorption , Food-Processing Industry , Waste Disposal, Fluid/methods , Water Purification/methods
16.
Int J Cardiol ; 257: 243-246, 2018 04 15.
Article in English | MEDLINE | ID: mdl-28918896

ABSTRACT

BACKGROUND: Mobilization of endothelial progenitor cells (EPCs) into circulation from bone marrow in patients with acute myocardial infarction has strong scientific evidence; less is known about EPC mobilization in patients with stable coronary artery disease (CAD). The aim of this study was to investigate the association of stable ischemic heart disease with EPC levels in tissue and blood. METHODS: Fifty-five consecutive patients admitted to a single treatment center for valve or coronary artery bypass grafting (CABG) surgeries were included in the study. Blood samples were collected in the morning before surgery and analyzed by flow-cytometry to determine peripheral EPC levels (EPC/ml). Tissue EPC (CD34+VEGFR2+) levels were assessed on a right atrial appendage segment. RESULTS: Mean age was 76±5years, 48% were men, and 53% had CAD The number of CD34+ VEGFR2+ cells in the tissue of patients with CAD was significantly higher (p<0.005) and circulating EPC showed a tendency to be reduced by approximately 20% in peripheral blood of patients with CAD when compared to those without CAD. CONCLUSION: Patients with stable CAD had higher EPC density values (EPC/mm2) and were more likely to have lower EPC blood levels when compare with normal controls.


Subject(s)
Endothelial Progenitor Cells/physiology , Myocardial Ischemia/blood , Myocardial Ischemia/surgery , Aged , Aged, 80 and over , Cardiac Surgical Procedures/methods , Cardiac Surgical Procedures/trends , Coronary Artery Disease/blood , Coronary Artery Disease/diagnostic imaging , Coronary Artery Disease/surgery , Female , Flow Cytometry/methods , Flow Cytometry/trends , Humans , Male , Myocardial Ischemia/diagnostic imaging
17.
J Clin Invest ; 48(6): 1041-53, 1969 Jun.
Article in English | MEDLINE | ID: mdl-5771186

ABSTRACT

Tritium-labeled digitoxin, digitoxigenin, digoxin, and digoxigenin of established purity and chemcal authenticity were used to study the binding of these compounds to human plasma proteins. 97% of digitoxin in plasma was nondialyzable. Continuous flow paper electrophoresis of plasma containing digitoxin and dialysis experiments in which human serum albumin competed for the glycoside with plasma or plasma protein fractions demonstrated that digitoxin was almost exclusively bound by albumin. Equilibrium dialyses revealed that the interaction was characterized by a single binding site on the albumin molecule and an association constant of 9.62 x 10(4) liter/mole at 37 degrees C. At 1 degrees C the association constant was 4.64 x 10(4) liter/mole. The interaction therefore was endothermic; the gain in enthalpy of 3.5 kcal/mole and the free energy change of - 7.06 kcal/mole was derived from a large change in entropy of 33.8 cal/mole per degrees K. The direction of these thermodynamic changes suggested the formation of a hydrophobic bond between digitoxin and albumin. Quenching of the fluorescence of albumin by digitoxin indicated that the conformation of albumin was altered by the binding process.Digitoxigenin, its mono- and didigitoxosides, digoxin, and digoxigenin competed with digitoxn for its binding site on albumin. The affinity of the mono- and didigitoxosides for the site was equal to that of digitoxin, but that of digitoxigenin was only one-third as great. The ability of the digitoxose residues of the glycosides to enhance binding to albumin was also observed with digoxin, which was more extensively bound by the protein than digoxigenin. At concentrations of 2 mug/ml or less in plasma, only 23% of digoxin was bound. Albumin, which interacted with digoxin with an apparent association constant of 9 x 10(2) liter/mole at 37 degrees C, was entirely responsible for the binding. Lowering the temperature from 37 degrees to 1 degrees C decreased the fraction of digoxin bound to albumin by two-thirds. The marked difference in avidity of digitoxin and digoxin for serum albumin is reflected by the higher plasma concentrations, lower rate of urinary excretion, and longer half-time of digitoxin as compared to those of digoxin when these compounds are administered to man.


Subject(s)
Blood Proteins/metabolism , Cardanolides/blood , Digitoxin/blood , Blood Protein Electrophoresis , Calcium/pharmacology , Chemical Phenomena , Chemistry , Dialysis , Fluorescence , Glycosides/blood , Humans , Hydrogen-Ion Concentration , Potassium/pharmacology , Protein Binding , Serum Albumin/metabolism , Spectrum Analysis , Temperature , Tritium
18.
Chemosphere ; 68(9): 1798-805, 2007 Aug.
Article in English | MEDLINE | ID: mdl-17451785

ABSTRACT

A dark and complex salified organic polymeric mixture, named lignimerin, was for the first time recovered from Kraft cellulose mill wastewater (KCMW) and characterized by chemical, spectroscopic and relative molecular weight (RMW) analysis. Lignimerin proved to be composed of polyphenols (57.00%), carbohydrates (22.26%) and proteins (7.42%). It also contained metals (6.93%), mainly Ca and, to much lower extent, Mg, Na, Al, Fe, K, Mn, Zn and Cu, bound to the carboxylate and phenate groups. The distribution of lignimerin RMW was assessed to be approximately between 1000 and 8600Da, as well as to consist of lignin and tannin, protein and polysaccharide moieties, strongly aggregated each other. H-lignimerin, its acid derivative, revealed a chemical composition and a RMW distribution very close to that of lignimerin, but a marked metal cations decreasing (1.60%) with respect to lignimerin (6.93%). The humic acid-like nature of both the polymers was assessed. Their potential use as bio-adsorbents of heavy metals is briefly discussed.


Subject(s)
Cellulose/chemistry , Food Industry , Humic Substances/analysis , Industrial Waste/analysis , Lignin/chemistry , Waste Disposal, Fluid , Waste Products/analysis
19.
Chemosphere ; 69(2): 229-39, 2007 Sep.
Article in English | MEDLINE | ID: mdl-17544478

ABSTRACT

Dry olive mill residue (DOR) from the olive oil production by two phase centrifugation system was fractionated by a consecutive continuous solid-liquid extraction obtaining the EAF, PF, MF and WF fractions with ethyl acetate, n-propanol, methanol and water, respectively. The chemical, chromatographic and mass spectrometric analyses showed EAF, PF and MF to be mainly composed of simple phenols, phenolic acids, flavonoids and glycosilated phenols (glycosides of phenols, secoiridoids and flavonoids), whereas WF was mainly consisting of polymerin, the metal organic polymeric mixture previously identified in olive oil mill waste waters and composed of carbohydrates, melanin, proteins and metals (K, Na, Ca, Mg and Fe). The identification in DOR of oleoside, 6'-beta-glucopyranosyl-oleoside and 6'-beta-rhamnopyranosyl-oleoside, and of its organic polymeric component, known as polymerin, are reported for the first time in this paper. The inoculation of the previously mentioned fractions with saprobe fungi Coriolopsis rigida, Pycnoporus cynnabarinus or Trametes versicolor indicated these fungi to be able to metabolize both the phenols and glycosilated phenols, but not polymerin. In correspondence, EAF, PF, MF and WF, which proved to be toxic on Lepidium sativum, decreased their toxicity after incubation with the selected fungi, WF showing to be also able to stimulate the growth of the selected seeds. The phytotoxicity appeared mainly correlated to the monomeric phenols and, to a lesser extent, to the glycosilated phenols, whereas polymerin proved to be non toxic. However, the laccase activity was not associated with the decrease of phytotoxicity. The valorization of DOR as a producer of high added value substances of industrial and agricultural interest in native form and after their bioremediation for a final objective of the total DOR recycling is also discussed.


Subject(s)
Environmental Restoration and Remediation/methods , Lepidium sativum/chemistry , Plant Oils/chemistry , Chromatography, High Pressure Liquid , Olive Oil , Spectrometry, Mass, Electrospray Ionization , Spectrophotometry, Ultraviolet
20.
Chemosphere ; 66(1): 67-74, 2007 Jan.
Article in English | MEDLINE | ID: mdl-16814842

ABSTRACT

Some saprobe fungi (Phlebia radiata, Trametes versicolor, Coriolopsis rigida, Pycnoporus cinnabarinus, Fomes sclerodermus or Pleurotus pulmonarius) were able to bioconvert the ethyl acetate fraction (DEAF) and the corresponding aqueous exhausted fraction (EAF) of dry olive mill residue (DOR), reducing their phytotoxicity on Lepidium sativum seeds. Large amount of hydroxytyrosol together with other eight monomeric phenols were found in the native DEAF fraction, which represents a good source of antioxidants. P. radiata, T. versicolor and F. sclerodermus caused an effective phytotoxicity reduction of EAF in the concentration range of 25-3 gl(-1). In particular, in the range between 12.5 and 3 gl(-1), the EAF samples inoculated with P. radiata and F. sclerodermus surprisingly stimulated the germinability of L. sativum, suggesting their use as a potential biofertilizer. This is the first report which showed the bioconversion of the above fractions in shorter time with respect to the previous findings concerning DOR. The possible implications of laccase in the decrease of DEAF and EAF phytotoxicity was also discussed.


Subject(s)
Acetates/chemistry , Basidiomycota/metabolism , Industrial Waste/prevention & control , Plant Oils/chemistry , Acetates/metabolism , Basidiomycota/growth & development , Biodegradation, Environmental , Chromatography, High Pressure Liquid , Germination/drug effects , Industrial Waste/analysis , Laccase/metabolism , Lepidium sativum/drug effects , Molecular Structure , Olive Oil , Phenols/metabolism , Plant Oils/metabolism , Seeds/drug effects , Spectrometry, Mass, Electrospray Ionization , Water Pollutants, Chemical/metabolism , Water Pollutants, Chemical/toxicity
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