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1.
J Endocrinol Invest ; 2024 May 11.
Article in English | MEDLINE | ID: mdl-38733428

ABSTRACT

PURPOSE: Information on the general health of transgender and gender diverse (TGD) individuals continues to be lacking. To bridge this gap, the National Institute of Health in Italy together with the National Office against Racial Discriminations, clinical centres, and TGD organizations carried out a cross-sectional study to define the sociodemographic profile, health-related behaviours, and experiences of healthcare access in Italian TGD adult population. METHODS: A national survey was conducted by Computer-Assisted Web Interviewing (CAWI) technique. Collected data were compared within the TGD subgroups and between TGD people and the Italian general population (IGP). RESULTS: TGD respondents were 959: 65% assigned female at birth (AFAB) and 35% assigned male at birth (AMAB). 91.8% and 8.2% were binary and non-binary TGD respondents, respectively. More than 20% of the TGD population reported to be unemployed with the highest rate detectable in AMAB and non-binary people. Cigarette smoking and binge drinking were higher in the TGD population compared with IGP (p < 0.05), affecting TGD subgroups differently. A significant lower percentage of AFAB TGD people reported having had screening for cervical and breast cancer in comparison with AFAB IGP (p < 0.0001, in both cases). Over 40% was the percentage of AFAB and non-binary TGD people accessing healthcare who felt discriminated against because of their gender identity. CONCLUSIONS: Our results are a first step towards a better understanding of the health needs of TGD people in Italy in order to plan the best policy choices for a more inclusive public health.

2.
Mar Pollut Bull ; 196: 115573, 2023 Nov.
Article in English | MEDLINE | ID: mdl-37778243

ABSTRACT

Pollution is one of the main anthropogenic threats to marine ecosystems. Studies analysing the accumulation and transfer of contaminants in planktonic food webs tend to rely on samples collected in discrete water bodies. Here, we assessed the representativeness of measurements at the chlorophyll-a maximum layer during the MERITE-HIPPOCAMPE cruise for the entire water column by investigating the vertical distribution of particles and plankton obtained by in-situ optical profilers at nine stations across the Mediterranean Sea. We identified specific conditions where the interpretation of results from contaminant analyses can be improved by detailing plankton size structure and vertical distributions. First, the presence of higher than usual plankton concentrations can result in sampling issues that will affect biomass estimation within each size class and therefore bias our understanding of the contaminant dynamics. Secondly, the presence of an unsampled water layer with high zooplankton biomass might imply non-resolved contaminant pathways along the trophic structure. This study lays the basis for optimizing sampling strategy in contaminant studies.


Subject(s)
Plankton , Zooplankton , Animals , Plankton/chemistry , Ecosystem , Water , Food Chain
3.
Int J Cardiol ; 371: 516-522, 2023 Jan 15.
Article in English | MEDLINE | ID: mdl-36130621

ABSTRACT

INTRODUCTION: Due to their rare prevalence and marked heterogeneity, pediatric cardiomyopathies (CMPs) are little known and scarcely reported. We report the etiology, clinical profile and outcome of a consecutive cohort of children diagnosed with CMP and followed at Meyer Children's Hospital over a decade. PATIENTS AND METHODS: We retrospectively reviewed patients consecutively referred from May 2008 to May 2019 for pediatric onset CMP (<18 years). Heart disease caused by arrhythmic disorders, toxic agents, rheumatic conditions and maternal disease were excluded. RESULTS: We enrolled 110 patients (65 males), diagnosed at a median age of 27 [4-134] months; 35% had an infant onset (<1 year of age). A positive family history was more often associated with childhood-onset (38.8%). Hypertrophic cardiomyopathy (HCM; 48 patients) was the most frequent phenotype, followed by dilated cardiomyopathy (DCM; 35 patients). While metabolic and idiopathic etiologies were preponderant in infants, metabolic and sarcomeric diseases were most frequent in the childhood-onset group. Major adverse cardiac events (MACE) occurred in 31.8% of patients, including hospitalization for acute heart failure in 25.5% of patients, most commonly due to DCM. Overall, the most severe outcomes were documented in patients with metabolic diseases. CONCLUSIONS: In a consecutive cohort of pediatric patients with CMP, those with infantile onset and with a metabolic etiology had the worst prognosis. Overall, MACE occurred in 41% of the entire population, most commonly associated with DCM, inborn errors of metabolism and genetic syndromes. Systematic NGS genetic testing was critical for etiological diagnosis and management.


Subject(s)
Cardiomyopathies , Cardiomyopathy, Dilated , Cardiomyopathy, Hypertrophic , Humans , Male , Cardiomyopathies/diagnosis , Cardiomyopathies/epidemiology , Cardiomyopathies/genetics , Cardiomyopathy, Dilated/genetics , Cardiomyopathy, Hypertrophic/diagnosis , Cardiomyopathy, Hypertrophic/epidemiology , Cardiomyopathy, Hypertrophic/genetics , Retrospective Studies
4.
Front Physiol ; 13: 920952, 2022.
Article in English | MEDLINE | ID: mdl-35899021

ABSTRACT

Pharmaceuticals are now considered to be established contaminants, and their presence in water poses a real risk not only to the marine ecosystem, as they may adversely affect non-target organisms that are exposed to them, but also indirectly to humans. This is particularly true for the model organism considered in this work, Mytilus galloprovincialis (Lamarck, 1819), a suspensivore and bioaccumulating organism that enters the human food chain. Among the most commonly used over-the-counter medicines, anti-inflammatory drugs certainly feature prominently, with acetylsalicylic acid (ASA) at the top. In this work, M. galloprovincialis specimens were exposed to two concentrations of ASA (10 and 100 µg/L) for 10 and 20 days to evaluate possible alterations in the decrease in regulatory volume (RVD) in digestive gland cells and cell viability of both these cells and hemocytes. In addition, the histopathological condition index of the gills and digestive gland was evaluated. The data obtained showed that chronic exposure to ASA did not alter the cell viability of hemocytes and digestive gland cells but alters the physiological mechanisms of volume regulation in the digestive gland and, in addition, a time-dose reaction to ASA in the gills and digestive gland showing numerous alterations such as lipofuscin deposits and hemocyte infiltration was found. These results confirm the potential toxicity to the marine biota, highlighting the necessity to deepen the knowledge regarding the link between over-the-counter pharmaceuticals and non-target organisms.

5.
Eur Rev Med Pharmacol Sci ; 22(21): 7453-7457, 2018 11.
Article in English | MEDLINE | ID: mdl-30468494

ABSTRACT

OBJECTIVE: To describe and evaluate feasibility and efficacy of a saphenous ablation technique performed in patients with varicose veins (VVs), great saphenous vein (GSV) incompetence, and proximal femoral valve incompetence: the Excluded Saphenous Vein Technique (ESVT). PATIENTS AND METHODS: Patients with primary great saphenous and proximal femoral valve incompetence underwent ESVT. This technique is composed of selective crossectomy, GSV ligation next to the thigh incompetent tributary vein, and saphenous vein sclerosing performed from the proximal zone. Demographic, clinical and instrumental data were collected. CEAP classification was used to describe VVs severity. The primary outcome was perioperative complications. Secondary outcomes were 30-days, 6-months and 1-years GSV occlusion rate, and VVs recurrence rate. RESULTS: During a ten months period, 104 patients were analyzed. Among these, 82 patients underwent ESVT (59 female, age 50 ± 21 years), eighty C2 and two C5, according to CEAP classification. The average length of GSV treated was 23 ± 9 cm. No intraoperative complications occurred. A 1-year follow-up analysis revealed no partial or complete saphenous recanalization, deep venous thrombosis, pulmonary embolism. No VVs recurrence was detected during the follow-up period among the entire population. CONCLUSIONS: ESVT seems to be a safe and effective treatment for primary saphenous reflux and proximal femoral valve incompetence. Further studies are needed to assess long-term results.


Subject(s)
Femoral Vein/surgery , Saphenous Vein/surgery , Varicose Veins/surgery , Venous Insufficiency/surgery , Adult , Aged , Female , Humans , Male , Middle Aged , Pilot Projects
6.
Transfus Med ; 28(6): 405-412, 2018 Dec.
Article in English | MEDLINE | ID: mdl-30325081

ABSTRACT

OBJECTIVES: Using a multidisciplinary approach and simulation, a massive transfusion process (MTP) was developed to care for patients in need of emergency transfusion. It was then assessed for effectiveness. BACKGROUND: After a series of sentinel emergency bleeding events, a reliable process for hospital staff to deliver appropriate blood products and obtain relevant laboratory tests to guide therapy for patients with emergency bleeding was needed. METHODS: To determine the feasibility of the new MTP, multidisciplinary teams participated in simulation events. Each simulation event helped refine the MTP. A special laboratory testing panel was devised. To judge the effectiveness and timeliness of the MTP, process measures and patient survival was retrospectively evaluated during the time period before and after MTP implementation. RESULTS: A new emergency bleeding panel of laboratory tests significantly decreased the turn-around time for fibrinogen, haematocrit, International normalised ratio (INR) and platelet count. The speed of commencing the first red blood cells transfusion was also improved (2:00 h vs 0:20 min, P = 0·001). Of 78 patients, there was no change in survival before (n = 31, 48·4%) and after (n = 47, 42·6%; P = 0·6478) MTP implementation. However, there was significant improvement in survival associated with MTP events on the weekdays. CONCLUSIONS: A reliable emergency transfusion process consists of an automatic chain of events that keeps decision-making to a minimum and leads to the fast procurement of blood products and salient test results. This work shows that a multidisciplinary iterative process using simulation increases the efficiency of clinical care delivery for bleeding paediatric and neonatal patients.


Subject(s)
Emergency Medical Services , Erythrocyte Transfusion , Hemorrhage/therapy , Quality of Health Care , Simulation Training , Child, Preschool , Female , Hemorrhage/blood , Humans , Infant , Infant, Newborn , International Normalized Ratio , Male
7.
Vox Sang ; 2018 May 01.
Article in English | MEDLINE | ID: mdl-29714029

ABSTRACT

BACKGROUND AND OBJECTIVES: Blood utilization during liver transplant has decreased, but remains highly variable due to many complex surgical and physiologic factors. Previous models attempted to predict utilization using preoperative variables to stratify cases into two usage groups, usually using entire blood units for measurement. We sought to develop a practical predictive model using specific transfusion volumes (in ml) to develop a data-driven patient blood management strategy. MATERIALS AND METHODS: This is a retrospective evaluation of primary liver transplants at a single institution from 2013 to 2015. Multivariable analysis of preoperative recipient and donor factors was used to develop a model predictive of intraoperative red-blood-cell (pRBC) use. RESULTS: Of 256 adult liver transplants, 207 patients had complete transfusion volume data for analysis. The median intraoperative allogeneic pRBC transfusion volume was 1250 ml, and the average was 1563 ± 1543 ml. Preoperative haemoglobin, spontaneous bacterial peritonitis, preoperative haemodialysis and preoperative international normalized ratio together yielded the strongest model predicting pRBC usage. When it predicted <1250 ml of pRBCs, all cases with 0 ml transfused were captured and only 8·6% of the time >1250 ml were used. This prediction had a sensitivity of 0·91 and a specificity of 0·89. If predicted usage was >2000 ml, 75% of the time blood loss exceeded 2000 ml. CONCLUSION: Patients likely to require low or high pRBC transfusion volumes were identified with excellent accuracy using this predictive model at our institution. This model may help predict bleeding risk for each patient and facilitate optimized blood ordering.

8.
Vox Sang ; 113(3): 268-274, 2018 Apr.
Article in English | MEDLINE | ID: mdl-29359471

ABSTRACT

BACKGROUND: During massive transfusion, the volume ratio of administered plasma (PL Vol) to red blood cell (RBC Vol) appears to be associated with reduced blood utilization and improved survival. The aim of this study was to evaluate the optimal component ratio in the setting of liver transplantation. METHODS: This is a retrospective chart review of patients who underwent liver transplantation and received at least 500 ml of red blood cells from January 2013 through December 2015. Kernel smoothing analysis determined the proper component ratios to evaluate were a ≥0·85:1 ratio (high) to a ≤0·85:1 ratio (low). Two groups, plasma volume to RBC volume (PL Vol/RBC Vol) and plasma contained in the platelet units added to the plasma calculation [PL + PLT (platelet)] Vol/RBC Vol, were used to evaluate the component ratios. RESULTS: A total of 188 patients were included in the analysis. In the PL Vol/RBC Vol evaluation, a low ratio revealed that 1238 ml (977-1653 ml) (P < 0·0001) and 1178 ml (747-1178) (P < 0·0001) of RBC were used in excess compared to the high ratio, in the univariable and multivariable analysis, respectively. In the PL +PLT Vol/RBC Vol evaluation, a low ratio used 734 ml (193-1275) (P = 0·008) and 886 ml (431-1340) (P < 0·0001) of RBC in excess when compared to high ratio in the univariable and multivariable analysis, respectively. CONCLUSION: In patients undergoing liver transplantation, the transfusion of plasma to RBC ratio ≥0·85 was associated with decreased need of RBC transfusions.


Subject(s)
Erythrocyte Transfusion/methods , Liver Transplantation/methods , Adult , Erythrocyte Count , Erythrocyte Transfusion/adverse effects , Erythrocyte Transfusion/standards , Female , Humans , Male , Middle Aged , Plasma , Retrospective Studies
9.
Proc Natl Acad Sci U S A ; 113(36): E5308-17, 2016 09 06.
Article in English | MEDLINE | ID: mdl-27540115

ABSTRACT

Despite numerous reports implicating NADPH oxidases (Nox) in the pathogenesis of many diseases, precise regulation of this family of professional reactive oxygen species (ROS) producers remains unclear. A unique member of this family, Nox1 oxidase, functions as either a canonical or hybrid system using Nox organizing subunit 1 (NoxO1) or p47(phox), respectively, the latter of which is functional in vascular smooth muscle cells (VSMC). In this manuscript, we identify critical requirement of ezrin-radixin-moesin-binding phosphoprotein 50 (EBP50; aka NHERF1) for Nox1 activation and downstream responses. Superoxide (O2 (•-)) production induced by angiotensin II (AngII) was absent in mouse EBP50 KO VSMC vs. WT. Moreover, ex vivo incubation of aortas with AngII showed a significant increase in O2 (•-) in WT but not EBP50 or Nox1 nulls. Similarly, lipopolysaccharide (LPS)-induced oxidative stress was attenuated in femoral arteries from EBP50 KO vs. WT. In silico analyses confirmed by confocal microscopy, immunoprecipitation, proximity ligation assay, FRET, and gain-/loss-of-function mutagenesis revealed binding of EBP50, via its PDZ domains, to a specific motif in p47(phox) Functional studies revealed AngII-induced hypertrophy was absent in EBP50 KOs, and in VSMC overexpressing EBP50, Nox1 gene silencing abolished VSMC hypertrophy. Finally, ex vivo measurement of lumen diameter in mouse resistance arteries exhibited attenuated AngII-induced vasoconstriction in EBP50 KO vs. WT. Taken together, our data identify EBP50 as a previously unidentified regulator of Nox1 and support that it promotes Nox1 activity by binding p47(phox) This interaction is pivotal for agonist-induced smooth muscle ROS, hypertrophy, and vasoconstriction and has implications for ROS-mediated physiological and pathophysiological processes.


Subject(s)
ATPases Associated with Diverse Cellular Activities/metabolism , DNA Helicases/metabolism , Hypertrophy/metabolism , NADPH Oxidase 1/genetics , Phosphoproteins/metabolism , Proteins/metabolism , Sodium-Hydrogen Exchangers/metabolism , ATPases Associated with Diverse Cellular Activities/genetics , Adaptor Proteins, Signal Transducing , Angiotensin II/administration & dosage , Angiotensin II/adverse effects , Animals , DNA Helicases/genetics , Femoral Artery/drug effects , Femoral Artery/metabolism , Femoral Artery/pathology , Humans , Hypertrophy/chemically induced , Hypertrophy/pathology , Lipopolysaccharides/toxicity , Mice , Mice, Knockout , Muscle, Smooth, Vascular/metabolism , Muscle, Smooth, Vascular/pathology , NADPH Oxidase 1/metabolism , Oxidative Stress/drug effects , Phosphoproteins/genetics , Proteins/genetics , Reactive Oxygen Species/metabolism , Sodium-Hydrogen Exchangers/genetics , Superoxides/metabolism , Vasoconstriction/drug effects , Vasoconstriction/genetics
10.
Fish Shellfish Immunol ; 55: 529-34, 2016 Aug.
Article in English | MEDLINE | ID: mdl-27346153

ABSTRACT

The fan mussel Pinna nobilis (Linnaeus, 1758) is one of the biggest bivalves worldwide. Currently, no updated information is available in the literature concerning the morpho-functional aspects of haemocytes from this bivalve species. Consequently, in this study, we characterised P. nobilis haemocytes from both a morphological and functional point of view. The mean number of haemocytes was about 5 (×10(5)) cells mL haemolymph(-1), and the cell viability was about 92-100%. Two haemocyte types were distinguished under the light microscope: granulocytes (51.6%), with evident cytoplasmic granules, and hyalinocytes (48.4%), with a few granules. The granules of the granulocytes were mainly lysosomes, as indicated by the in vivo staining with Neutral Red. Haemocytes were further distinguished in basophils (83.75%), acidophils (14.75%) and neutrophils (1.5%). After adhesion to slides and fixation, the cell diameter was approximately 10 µm for granulocytes and 7 µm for hyalinocytes. The granulocytes and hyalinocytes were both positive to the Periodic Acid-Schiff reaction for carbohydrates. Only granulocytes were able to phagocytise yeast cells. The phagocytic index (6%) increased significantly up to twofold after preincubation of yeast in cell-free haemolymph, suggesting that haemolymph has opsonising properties. In addition, haemocytes produce superoxide anion and acid and alkaline phosphatases. Summarising, this preliminary study indicates that both the granulocytes and hyalinocytes circulate in the haemolymph of P. nobilis and that they are active immunocytes.


Subject(s)
Bivalvia/cytology , Bivalvia/physiology , Phagocytosis , Animals , Bivalvia/ultrastructure , Hemocytes/cytology , Hemocytes/physiology , Hemocytes/ultrastructure , Microscopy, Electron, Transmission
11.
Int J Impot Res ; 28(3): 114-9, 2016 May.
Article in English | MEDLINE | ID: mdl-27053154

ABSTRACT

The objective of this study was to anatomically describe the relationship of penile intracavernosal pillars to penile surgery, specifically corporal dilation during penile prosthesis placement. Corpora cavernosa from four embalmed male cadavers were dissected and subjected to probe dilation. Corpora were cross-sectioned and examined for the gross presence and location of pillars and dilated spaces. Infrapubic penile prosthesis insertion was performed on one fresh-frozen cadaveric male pelvis, followed by cross-sectioning. A single patient had intracavernosal pillars examined intraoperatively during Peyronie's plaque excision and penile prosthesis insertion. Intracavernosal pillars were identified in all cadavers and one surgical patient, passing obliquely from the dorsolateral tunica albuginea across the sinusoidal space to the ventral intercorporal septum. This delineated each corpus into two potential compartments for dilation: dorsomedial and ventrolateral. Dorsal dilation seated instruments and prosthetics satisfactorily in the dorsal mid glans and provided additional tissue coverage over weak ventral areas of the tunica albuginea, while ventrolateral dilation appeared to result in ventral seating and susceptibility to perforation. Intracavernosal pillars are an important anatomic consideration during penile prosthesis placement. Dorsal dilation appears to result in improved distal seating of cylinder tips, which may be protective against tip malposition, perforation or subsequent erosion.


Subject(s)
Penile Implantation/methods , Penile Prosthesis , Penis/anatomy & histology , Penis/surgery , Anatomy, Cross-Sectional , Cadaver , Humans , Male , Penile Induration/surgery , Penis/diagnostic imaging , Ultrasonography
12.
Nat Prod Res ; 30(17): 1934-7, 2016 Sep.
Article in English | MEDLINE | ID: mdl-26360806

ABSTRACT

Marine algae are important sources of phycocolloids like agar, carrageenans and alginates used in industrial applications. Algal polysaccharides have emerged as an important class of bioactive products showing interesting properties. The aim of our study was to evaluate the potential uses as anticoagulant drugs of algal sulphate polysaccharides extracted from Ulva fasciata (Chlorophyta) and Agardhiella subulata (Rhodophyta) collected in Ganzirri Lake (Cape Peloro Lagoon, north-eastern Sicily, Italy). Toxicity of algal extracts through trypan blue test and anticoagulant action measured by activated partial thromboplastin time (APTT), prothrombin time (PT) test has been evaluated. Algal extracts showed to prolong the PT and APTT during the coagulation cascade and to avoid the blood coagulation of samples. Furthermore, the algal extracts lack toxic effects towards cellular metabolism and their productions are relatively at low cost. This permits to consider the algae as the biological source of the future.


Subject(s)
Anticoagulants/pharmacology , Chlorophyta/chemistry , Polysaccharides/pharmacology , Rhodophyta/chemistry , Blood Coagulation/drug effects , Humans , Partial Thromboplastin Time , Prothrombin Time
13.
Curr Pharm Des ; 21(41): 6023-35, 2015.
Article in English | MEDLINE | ID: mdl-26510437

ABSTRACT

Oxidative stress-related diseases underlie many if not all of the major leading causes of death in United States and the Western World. Thus, enormous interest from both academia and pharmaceutical industry has been placed on the development of agents which attenuate oxidative stress. With that in mind, great efforts have been placed in the development of inhibitors of NADPH oxidase (Nox), the major enzymatic source of reactive oxygen species and oxidative stress in many cells and tissue. The regulation of a catalytically active Nox enzyme involves numerous protein-protein interactions which, in turn, afford numerous targets for inhibition of its activity. In this review, we will provide an updated overview of the available Nox inhibitors, both peptidic and small molecules, and discuss the body of data related to their possible mechanisms of action and specificity towards each of the various isoforms of Nox. Indeed, there have been some very notable successes. However, despite great commitment by many in the field, the need for efficacious and well-characterized, isoform-specific Nox inhibitors, essential for the treatment of major diseases as well as for delineating the contribution of a given Nox in physiological redox signalling, continues to grow.


Subject(s)
Drug Design , Enzyme Inhibitors/pharmacology , NADPH Oxidases/antagonists & inhibitors , Peptides/pharmacology , Small Molecule Libraries/pharmacology , Disease , Enzyme Inhibitors/chemical synthesis , Enzyme Inhibitors/chemistry , Humans , NADPH Oxidases/metabolism , Oxidative Stress/drug effects , Peptides/chemical synthesis , Peptides/chemistry , Small Molecule Libraries/chemical synthesis , Small Molecule Libraries/chemistry
14.
Int J Immunogenet ; 42(4): 294-6, 2015 Aug.
Article in English | MEDLINE | ID: mdl-25976429

ABSTRACT

The new allelic variant HLA-B*38:55Q differs from the closest related B*38:01:01 by one nucleotide substitution at position 373 in exon 3 (TGC>CGC). This results in a difference of one amino acid at residue 101 of the HLA-B heavy chain, from a neutral-polar Cys to a basic-polar Arg, thus impairing disulphide bridge formation in the alpha-2 domain. This alteration of the secondary structure probably affects the maturation of the heavy chain and the level of surface expression, making the HLA-B*38:55Q undetectable by standard serological typing.


Subject(s)
Alleles , Amino Acid Substitution/genetics , Gene Expression Regulation , HLA-B Antigens/genetics , Amino Acid Sequence/genetics , Exons , HLA-B Antigens/biosynthesis , Humans , Molecular Sequence Data , Protein Structure, Secondary , Sequence Alignment , White People
15.
Acta Biomed ; 85 Suppl 2: 5-19, 2014 Sep 24.
Article in English | MEDLINE | ID: mdl-25409713

ABSTRACT

Total knee replacement (TKR) procedures have evolved in the last 40 years to guarantee improvements implants life and an excellent joint function. The goals for the future evolutions are make easier prosthesis implantation and promote precision. The demand for TKR will rise for the life length increase and for the risk factors impact increase. Design evolution in total knee replacement has to satisfy these new necessities: anatomic congruence, range of motion, less material wear and better resistance to the weight bearing and to the stresses. This paper analyzes design evolution, materials development and future purposes in total knee arthroplasty. At the beginning, TKR history is treated; then we compare several prosthetic designs developed during years. At last the paper speak about recent innovations, like CAD (computer aided design) for example, born to reach the most important goal in the future: better TKR design, is the one that better imitate natural knee characteristics, and that is able to integrate it-self with capsule-ligaments and muscle-tendons patient structures.


Subject(s)
Arthroplasty, Replacement, Knee , Knee Prosthesis , Prosthesis Design , Humans
16.
Int J Tuberc Lung Dis ; 18(9): 1019-25, 2014 Sep.
Article in English | MEDLINE | ID: mdl-25189547

ABSTRACT

BACKGROUND: Effective treatment for drug-susceptible tuberculosis (TB) rapidly renders patients non-infectious, long before conversion of sputum acid-fast smear or culture to negative. Multidrug-resistant TB (MDR-TB) patients on treatment are currently assumed to remain infectious for months. While the resources required for prolonged hospitalization are a barrier to the scale-up of MDR-TB treatment, the safety of community treatment is clear. OBJECTIVES: To estimate the impact of treatment on infectiousness among MDR-TB patients. METHODS: A series of five human-to-guinea pig TB transmission studies was conducted to test various interventions for infection control. Guinea pigs in adjacent chambers were exposed to exhaust air from a hospital ward occupied by mostly sputum smear- and culture-positive MDR-TB patients. The guinea pigs then underwent tuberculin skin testing for infection. Only the control groups of guinea pigs from each study (no interventions used) provide the data for this analysis. The number of guinea pigs infected in each study is reported and correlated with Mycobacterium tuberculosis drug susceptibility relative to treatment. RESULTS: Despite exposure to presumably infectious MDR-TB patients, infection percentages among guinea pigs ranged from 1% to 77% in the five experiments conducted. In one experiment in which guinea pigs were exposed to 27 MDR-TB patients newly started on effective treatment for 3 months, there was minimal transmission. In four other experiments with greater transmission, guinea pigs had been exposed to patients with unsuspected extensively drug-resistant tuberculosis who were not on effective treatment. CONCLUSIONS: In this model, effective treatment appears to render MDR-TB patients rapidly non-infectious. Further prospective studies on this subject are needed.


Subject(s)
Air Microbiology , Antitubercular Agents/therapeutic use , Cross Infection/prevention & control , Cross Infection/transmission , Infection Control/methods , Mycobacterium tuberculosis/drug effects , Tuberculosis, Multidrug-Resistant/drug therapy , Tuberculosis, Multidrug-Resistant/transmission , Tuberculosis, Pulmonary/drug therapy , Adolescent , Adult , Aged , Animals , Cross Infection/diagnosis , Cross Infection/microbiology , Extensively Drug-Resistant Tuberculosis/drug therapy , Extensively Drug-Resistant Tuberculosis/microbiology , Extensively Drug-Resistant Tuberculosis/transmission , Female , Guinea Pigs , Humans , Male , Microbial Sensitivity Tests , Middle Aged , Mycobacterium tuberculosis/isolation & purification , Retrospective Studies , Sputum/microbiology , Time Factors , Treatment Outcome , Tuberculin Test , Tuberculosis, Multidrug-Resistant/diagnosis , Tuberculosis, Multidrug-Resistant/microbiology , Tuberculosis, Pulmonary/diagnosis , Tuberculosis, Pulmonary/microbiology , Tuberculosis, Pulmonary/transmission , Young Adult
17.
Cell Death Differ ; 21(10): 1535-45, 2014 Oct.
Article in English | MEDLINE | ID: mdl-24992930

ABSTRACT

Prostate apoptosis response protein 4 (Par-4) also known as PRKC apoptosis WT1 regulator is a tumor suppressor that selectively induces apoptosis in cancer cells. However, its post-translational regulation by ubiquitin-mediated proteolysis and the cellular machinery that is responsible for its proteasomal degradation are unknown. Using immunopurification and an unbiased mass spectrometry-based approach, we show that Par-4 interacts with the SPRY-domain containing E3 ubiquitin ligase Fbxo45 through a short consensus sequence motif. Fbxo45 interacts with Par-4 in the cytoplasm and mediates its ubiquitylation and proteasomal degradation. Fbxo45 silencing results in stabilization of Par-4 with increased apoptosis. Importantly, a Par-4 mutant that is unable to bind Fbxo45 is stabilized and further enhances staurosporine-induced apoptosis. Co-expression of Fbxo45 with Par-4 protects cancer cells against Par-4-induced apoptosis. Our studies reveal that Fbxo45 is the substrate-receptor subunit of a functional E3 ligase for Par-4 that has a critical role in cancer cell survival.


Subject(s)
Apoptosis Regulatory Proteins/metabolism , F-Box Proteins/metabolism , Neoplasms/metabolism , Amino Acid Sequence , Apoptosis/genetics , Apoptosis Regulatory Proteins/genetics , Cell Line, Tumor , Cell Survival/genetics , DEAD-box RNA Helicases/genetics , Enzyme Inhibitors/pharmacology , F-Box Proteins/genetics , HEK293 Cells , HeLa Cells , Humans , Molecular Sequence Data , Mutation , Proteasome Endopeptidase Complex/metabolism , Protein Binding/genetics , Protein Structure, Tertiary , RNA Interference , RNA, Small Interfering , Staurosporine/pharmacology , Ubiquitin-Protein Ligases/metabolism , Ubiquitination
19.
Article in English | MEDLINE | ID: mdl-24588558

ABSTRACT

Corticosteroids have become the most widespread illegal growth promoters in veal calves and beef cattle. Testing for corticosteroids relies on either direct detection of compounds or their metabolites or indirect detection to identify changes in biological pathways. We used a comparative proteomic approach, based on two-dimensional electrophoresis (2DE), to identify plasma protein markers after short-term dexamethasone administration in veal calves. Twenty-three male Friesian veal calves were treated experimentally with dexamethasone sodium phosphate: 10 received low-dose administration of the drug (0.4 mg day⁻¹ per os) for 20 consecutive days (treatment group); 10 received the drug at therapeutic dosage (2-4 mg kg⁻¹ i.m.) for 3 consecutive days (comparison group). Three animals were not treated (control group). Plasma samples were collected from each animal at six time points (T1-T6; treatment and control group) and at four time points (T1-T4; comparison group) and stored at -80°C until analysis. Plasma proteins were quantified and analysed in triplicate by 2DE. The images were analysed with Bionumerics® software. Comparison of 2DE maps obtained from blood samples at T1 (before treatment) and at T6 (final sampling) showed a significant disappearance (p < 0.001) of two protein spots at T6 in the treatment group. Liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysis and immunoblotting identified these isoforms as serum paraoxonase/arylesterase 1 precursor (PON1). Synthesised in the liver and released into the blood, PON1 has an important role in lipid metabolism. The absence of variation of this protein in the comparison group suggests that the marker has good specificity for detecting illicit corticosteroid treatment.


Subject(s)
Aryldialkylphosphatase/blood , Dexamethasone/analogs & derivatives , Down-Regulation/drug effects , Glucocorticoids/administration & dosage , Growth Substances/administration & dosage , Animals , Animals, Inbred Strains , Biomarkers/blood , Cattle , Dexamethasone/administration & dosage , Dexamethasone/pharmacology , Dose-Response Relationship, Drug , European Union , Food Contamination/prevention & control , Glucocorticoids/pharmacology , Growth Substances/pharmacology , Guideline Adherence , Guidelines as Topic , Italy , Male , Meat , Proteomics/methods , Random Allocation , Veterinary Drugs/administration & dosage , Veterinary Drugs/pharmacology , Veterinary Drugs/standards
20.
Neurologia ; 29(9): 567-72, 2014.
Article in English, Spanish | MEDLINE | ID: mdl-24140159

ABSTRACT

INTRODUCTION: Epidemiological studies have demonstrated that patients with diabetes mellitus have an increased risk of developing Alzheimer disease, but the relationship between the 2 entities is not clear. DEVELOPMENT: Both diseases exhibit similar metabolic abnormalities: disordered glucose metabolism, abnormal insulin receptor signalling and insulin resistance, oxidative stress, and structural abnormalities in proteins and ß-amyloid deposits. Different hypotheses have emerged from experimental work in the last two decades. One of the most comprehensive relates the microvascular damage in diabetic polyneuritis with the central nervous system changes occurring in Alzheimer disease. Another hypothesis considers that cognitive impairment in both diabetes and Alzheimer disease is linked to a state of systemic oxidative stress. Recently, attenuation of cognitive impairment and normalisation of values in biochemical markers for oxidative stress were found in patients with Alzheimer disease and concomitant diabetes. Antidiabetic drugs may have a beneficial effect on glycolysis and its end products, and on other metabolic alterations. CONCLUSIONS: Diabetic patients are at increased risk for developing Alzheimer disease, but paradoxically, their biochemical alterations and cognitive impairment are less pronounced than in groups of dementia patients without diabetes. A deeper understanding of interactions between the pathogenic processes of both entities may lead to new therapeutic strategies that would slow or halt the progression of impairment.


Subject(s)
Alzheimer Disease/etiology , Diabetes Mellitus, Type 2/complications , Cognition Disorders/etiology , Dementia/etiology , Diabetes Mellitus, Type 2/metabolism , Disease Progression , Humans , Oxidative Stress
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