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1.
Clin Transl Allergy ; 14(1): e12326, 2024 Jan.
Article in English | MEDLINE | ID: mdl-38282192

ABSTRACT

BACKGROUND: Immunoglobulin E (IgE) and immunoglobulin G4 (IgG4) to peanut and its components may influence the clinical reactivity to peanut. Allergen-specific immunotherapy is known for modifying both IgE and IgG4. Peanut oral immunotherapy may influence these serological parameters. METHODS: Exploratory analyses of serological data from participants receiving peanut (Arachis hypogaea) allergen powder-dnfp (PTAH) and placebo in the double-blind, randomized, phase 3 PALISADE trial were conducted to evaluate potential relationships between peanut-specific and peanut component-specific (Ara h 1, Ara h 2, Ara h 3, Ara h 6, Ara h 8, and Ara h 9) IgE and IgG4 levels and clinical outcomes. RESULTS: A total of 269 participants (PTAH, n = 202; placebo, n = 67) were analyzed. No relationship was observed between specific IgE and IgG4 levels at screening and maximum tolerated peanut protein dose during screening or response status during exit double-blind placebo-controlled food challenge (DBPCFC). In PTAH-treated participants, no relationship was observed between IgE and IgG4 levels at screening and maximum symptom severity during exit DBPCFC. Postscreening ratios (ie, postscreening/screening) in the PTAH group were significant at the end of updosing and exit visit for most components. Postscreening changes in specific IgE levels were more pronounced with PTAH versus placebo for most components. CONCLUSIONS: Specific IgE and IgG4 levels at screening are not correlated with screening or exit DBPCFC results, and are not predictive of clinical response to PTAH. Peanut (Arachis hypogaea) allergen powder-dnfp contains the relevant and immunodominant allergens, inducing immunological changes with the treatment. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT02635776.

2.
Front Allergy ; 4: 1279290, 2023.
Article in English | MEDLINE | ID: mdl-38093814

ABSTRACT

Background: Oral immunotherapy (OIT) with peanut (Arachis hypogaea) allergen powder-dnfp (PTAH; Aimmune Therapeutics) is an FDA-approved treatment to desensitize peanut allergic participants. Objective: Here we assessed shifts in IgE and IgG4 binding to peanut allergens and their epitopes recognized by United States (US) peanut allergic participants (n = 20) enrolled in phase 3 PTAH OIT clinical trials. Methods: Pre- and post- trial participant sera were collected approximately 12 months apart and tested for IgE binding to intact peanut proteins via ImmunoCAP ISAC immunoassays. IgE and IgG4 linear epitopes were identified based on binding to synthetic overlapping 15-mer linear peptides of 10 peanut allergens (Ara h 1-11) synthesized on microarray slides. Results: Statistically significant decreases in IgE binding were identified for intact Ara h 2, 3, and 6, and known and newly identified IgE epitopes were shown to exhibit shifts towards IgG4 binding post-OIT, with most linear peptides having increased IgG4 binding after treatment with PTAH. While PTAH does not seem to alter the actual peptide binding patterns significantly after one year of treatment, the IgE and IgG4 binding ratios and intensity are altered. Conclusion: At a population level, the linear IgE and IgG4 epitopes of 10 peanut allergens overlap and that increase in IgG4 with OIT results in displacement of IgE binding to both conformational and linear epitopes. Furthermore, it appears as though the increase in IgG4 is more important to achieve desensitization at the 12-month timepoint than the decrease in IgE. This type of knowledge can be useful in the identification of IgE and IgG4-binding allergen and peptide biomarkers that may indicate desensitization or sustained unresponsiveness of allergic individuals to peanut.

3.
Commun Chem ; 6(1): 234, 2023 Oct 28.
Article in English | MEDLINE | ID: mdl-37898658

ABSTRACT

Pregnancy-Associated Plasma Protein A isoforms, PAPP-A and PAPP-A2, are metalloproteases that cleave insulin-like growth factor binding proteins (IGFBPs) to modulate insulin-like growth factor signaling. The structures of homodimeric PAPP-A in complex with IGFBP5 anchor peptide, and inhibitor proteins STC2 and proMBP have been recently reported. Here, we present the single-particle cryo-EM structure of the monomeric, N-terminal LG, MP, and the M1 domains (with the exception of LNR1/2) of human PAPP-A2 to 3.13 Å resolution. Our structure together with functional studies provides insight into a previously reported patient mutation that inactivates PAPP-A2 in a distal region of the protein. Using a combinational approach, we suggest that PAPP-A2 recognizes IGFBP5 in a similar manner as PAPP-A and show that PAPP-A2 cleaves IGFBP5 less efficiently due to differences in the M2 domain. Overall, our studies characterize the cleavage mechanism of IGFBP5 by PAPP-A2 and shed light onto key differences with its paralog PAPP-A.

4.
Front Allergy ; 3: 1090114, 2022.
Article in English | MEDLINE | ID: mdl-36698378

ABSTRACT

Non-specific lipid transfer proteins (LTPs) are well studied allergens that can lead to severe reactions, but often cause oral allergy syndrome in the Mediterranean area and other European countries. However, studies focused on LTP reactivity in allergic individuals from the United States are lacking because they are not considered major allergens. The goal of this study is to determine if differences in immunoglobulin (Ig) E binding patterns to the peanut allergen Ara h 9 and two homologous LTPs (walnut Jug r 3 and peach Pru p 3) between the US and Spain contribute to differences observed in allergic reactivity. Synthetic overlapping 15-amino acid-long peptides offset by five amino acids from Ara h 9, Jug r 3, and Pru p 3 were synthesized, and the intact proteins were attached to microarray slides. Sera from 55 peanut-allergic individuals from the US were tested for IgE binding to the linear peptides and IgE binding to intact proteins using immunofluorescence. For comparison, sera from 17 peanut-allergic individuals from Spain were also tested. Similar IgE binding profiles for Ara h 9, Jug r 3, and Pru p 3 were identified between the US and Spain, with slight differences. Certain regions of the proteins, specifically helices 1 and 2 and the C-terminal coil, were recognized by the majority of the sera more often than other regions of the proteins. While serum IgE from peanut-allergic individuals in the US binds to peptides of Ara h 9 and its homologs, only IgE from the Spanish subjects bound to the intact LTPs. This study identifies Ara h 9, Jug r 3, and Pru p 3 linear epitopes that were previously unidentified using sera from peanut-allergic individuals from the US and Spain. Certain regions of the LTPs are recognized more often in US subjects, indicating that they represent conserved and possible cross-reactive regions. The location of the epitopes in 3D structure models of the LTPs may predict the location of potential conformational epitopes bound by a majority of the Spanish patient sera. These findings are potentially important for development of peptide or protein-targeting diagnostic and therapeutic tools for food allergy.

5.
Psychol Sch ; 58(9): 1844-1857, 2021 Sep.
Article in English | MEDLINE | ID: mdl-34538936

ABSTRACT

COVID-19 related social isolation measures and school closures have likely increased students' stress levels. In our study, we assess the level of psychological distress and psychosocial factors among students in Mexico at the beginning of the pandemic. We conducted a cross-sectional exploratory study with 848 participants, the majority undergraduate or postgraduate (79.7%). Participants completed the Impact of Event Scale-Revised to measure emotions, and a COVID-19 questionnaire. We conducted a logistic regression analysis to find variables associated with stress: 36% (n = 309) had elevated stress, 31.4% (n = 266) anxiety, and 18.2% (n = 154) sadness often or all the time. Those who identified as women and reported a reduction in their incomes also reported a higher stress level. Stress was positively correlated with anxiety, anger, sadness, days in isolation, and hours watching TV daily; and negatively correlated with relaxation and happiness. The variable most strongly correlated with stress was a high perception of infection risk. Our findings will inform mental health strategies for students who are at higher risk of stress due to the COVID-19 pandemic response.

6.
AJNR Am J Neuroradiol ; 41(8): 1357-1360, 2020 08.
Article in English | MEDLINE | ID: mdl-32616582

ABSTRACT

New York City has become the global epicenter of the coronavirus 2019 (COVID-19) pandemic. Despite a massive shift in health care resources, cerebrovascular disease continues to be a substantial burden. We review the first 10 patients undergoing thrombectomy following a series of governmental and institutional policy changes diverting resources to the care of critically ill patients with COVID-19. Ten patients with emergent large-vessel occlusion underwent thrombectomy between March 23 and April 1, 2020. Five patients tested positive for the COVID-19 virus. Successful reperfusion was achieved in 9 of 10 patients, at a median time of 37 minutes from vascular access. The postprocedural NIHSS score improved by an average of 7.7 points. Of the 5 patients positive for COVID-19, none have experienced a critical respiratory illness. We report the early incidence of COVID-19 positivity in patients with emergent large-vessel occlusion and demonstrate that thrombectomy continues to be an efficacious option, as well as safe for health care providers.


Subject(s)
Betacoronavirus , Coronavirus Infections , Pandemics , Pneumonia, Viral , Stroke/surgery , Thrombectomy , Adult , Aged , Aged, 80 and over , COVID-19 , Coronavirus Infections/complications , Coronavirus Infections/epidemiology , Female , Humans , Male , Middle Aged , New York City , Pneumonia, Viral/complications , Pneumonia, Viral/epidemiology , Reperfusion , Retrospective Studies , SARS-CoV-2 , Stroke/etiology , Treatment Outcome
7.
Protein J ; 38(5): 608, 2019 Oct.
Article in English | MEDLINE | ID: mdl-31236753

ABSTRACT

The original publication of this article contained a number of grammatical errors. Unfortunately, an incorrect version of the file that did not include some final language editing was inadvertently published online. The original article has been corrected.

8.
Toxicon ; 168: 98-102, 2019 Oct.
Article in English | MEDLINE | ID: mdl-31251992

ABSTRACT

The chemical and biological characterization of peptide and protein components of the paralyzing venom from three Pompilidae solitary spider wasps (Pepsis mexicana, Pepsis terminata, and Anoplius nigritus) is described for the first time. The molecular masses of the most abundant peptides were determined. The N-terminal sequences of two cysteine-rich peptides were obtained from Pepsis. Metalloproteinase and hyaluronidase activities were identified in the venom of P. mexicana. A novel non-lethal method to collect venom is described.


Subject(s)
Wasp Venoms/chemistry , Wasps , Animals , Female , Hyaluronoglucosaminidase/analysis , Insect Proteins/chemistry , Metalloproteases/analysis , Mexico , Wasp Venoms/enzymology
9.
Protein J ; 38(5): 598-607, 2019 10.
Article in English | MEDLINE | ID: mdl-31119598

ABSTRACT

Human cystatin C (HCC) binds and inhibits all types of cysteine proteases from the papain family, including cathepsins (a group of enzymes that participate in a variety of physiological processes), which are some of its natural targets. The affinities of diverse proteases for HCC, expressed as equilibrium binding constants (Kb), range from 106 to 1014 M-1. Isothermal titration calorimetry (ITC) is one of the most useful techniques to characterize the thermodynamics of molecular associations, making it possible to dissect the binding free energy into its enthalpic and entropic components. This information, together with the structural changes that occur during the different associations, could enable better understanding of the molecular basis of affinity. Notwithstanding the high sensitivity of modern calorimeters, ITC requires protein concentrations in at least the 10-100 µM range to obtain reliable data, and it is known that HCC forms oligomers in this concentration range. We present herein a comparative study of the structural, thermal stability, and oligomerization properties of HCC and its stabilized variant (sHCC) L47C/G69C (which possesses an additional disulfide bridge) as well as their binding thermodynamics to the protease chymopapain, analyzed by ITC. The results show that, because sHCC remains monomeric, it is a better reporter than wild-type HCC to characterize the thermodynamics of binding to cysteine proteases.


Subject(s)
Cystatin C/chemistry , Cystatin C/metabolism , Cysteine Proteases/metabolism , Cystatin C/genetics , Humans , Models, Molecular , Mutagenesis, Site-Directed , Point Mutation , Protein Conformation , Protein Multimerization , Protein Stability , Thermodynamics
10.
Acta Ortop Mex ; 33(3): 173-181, 2019.
Article in Spanish | MEDLINE | ID: mdl-32246610

ABSTRACT

INTRODUCTION: It is essential that orthopaedic resident physicians be highly proficient in all aspects, considering the balance between supply, demand, need and context. Fundamental to identify the capacity and quality installed for their training in Mexico. MATERIAL AND METHODS: Observational Study, transverse, non-probabilistic sampling-conglomerates, in two phases. The instrument has 8 domains, 57 variables and 4,867 items. 60 graduate professors of 20 states, 50 hospital sites, 22 university programs. RESULTS: 1,038 years of experience (collective intelligence), 17 years of experience/teacher (01 to 50 years). Identified: acute pathology 30 (2 to 90%), chronic pathology 30 (5 to 96%), patients 15 years, 10 (3 to 30%), patients between 15 and 65 years, 47 (2 to 78%), patients 65 years, 20 (2 to 60%), number of beds/seat 20 (2 to 510), number of clinics 3 (1 to 48), number of surgical procedures/headquarters per year at the national level, was 960 (50 to 24,650). The national average per resident doctor is 362 surgeries/year with 1,450 surgical times/year. CONCLUSIONS: The needs and resources for the training of physicians specializing in orthopedics/traumatology are highly heterogeneous, so it should be adapted to the epidemiological needs of the region of influence, in an area of epidemiological transition. 62.2% expressed not having or have bad academic and scientific infrastructure at its headquarters, more than 50% without rotation overseas and 90% without regular scientific production.


INTRODUCCIÓN: Es fundamental que los médicos residentes de ortopedia (traumatología) sean altamente competentes en todos los aspectos, considerando el equilibrio entre la oferta, demanda, necesidad y contexto. Es primordial identificar la capacidad y calidad instalada para su formación en México. MATERIAL Y MÉTODOS: Estudio observacional, transversal, muestreo no probabilístico-conglomerados, en dos fases. El instrumento tiene ocho dominios, 57 variables y 4,867 ítems. Sesenta profesores de postgrado de 20 estados, 50 sedes hospitalarias, 22 programas universitarios. RESULTADOS: 1,038 años de experiencia (inteligencia colectiva), 17 años de experiencia/profesor (01 a 50 años). Se identificó: patología aguda 30 (2 a 90%), patología crónica 30 (5 a 96%), pacientes 15 años, 10 (3 a 30%), pacientes entre 15 y 65 años, 47 (2 a 78%), pacientes 65 años, 20 (2 a 60%), número de camas/sede 20 (2 a 510), número de consultorios 3 (1 a 48), el número de procedimientos quirúrgicos/sede al año a nivel nacional fue de 960 (50 a 24,650). La media nacional por médico residente es de 362 cirugías/año con 1,450 momentos quirúrgicos/año. CONCLUSIONES: Las necesidades y recursos para la formación de médicos especialistas en ortopedia/traumatología son en alto grado heterogéneos, por lo cual se debería adaptar a las necesidades epidemiológicas de la región de influencia, en un ámbito de transición epidemiológica. Sesenta y dos punto dos por ciento expresó no tener o tener deficiente infraestructura académica y científica en su sede, más de 50% sin rotación al extranjero y 90% sin producción científica regular.


Subject(s)
Internship and Residency , Orthopedic Procedures , Orthopedics , Humans , Mexico , Surveys and Questionnaires
11.
J Nutr Health Aging ; 21(9): 980-987, 2017.
Article in English | MEDLINE | ID: mdl-29083438

ABSTRACT

INTRODUCTION: The executive function is a complex set of skills affected during the aging process and translate into subclinical cerebrovascular disease. Postural instability or motor slowness are some clinical manifestations, being consubstantial with the frailty phenotype, genuine expression of aging. Executive dysfunction is also considered a predictor of adverse health events in the elderly. AIM: To study whether the executive dysfunction can be used as an early marker for frailty and the viability of use as a predictor of mortality, hospitalization and/or disability in a Mediterranean population. DESIGN: A population-based cohort study using data from the Toledo Study for Healthy Aging (TSHA). METHODS: 1690 Spanish elders aged ≥65 years underwent a neuropsychological evaluation in order to measure executive function. To assess whether the accumulation of dysfunctions (in severity and amplitude) could increase the predictive value of adverse health events in relation to each dimension separately an executive dysfunction cumulative index was constructed. Cox proportional hazards model was used to examine mortality and hospitalization over 5.02 and 3.1 years of follow-up, respectively. RESULTS: Executive dysfunction is a powerful predictor of mortality, frailty and disability. Cumulative differences in executive function are associated with high risk of frailty and disability, thus, for each one point increment in the executive function index, the risk of death increased by 7 %, frailty by 13% and disability by 11% (P<0.05). Moreover, the executive impairment exhibits a strong positive tendency with age, comorbidity and mortality. CONCLUSIONS: Cumulative differences in four executive dimensions widely used in clinical practice improves the ability to predict frailty and disability compared to each dimension separately.


Subject(s)
Disabled Persons , Executive Function/physiology , Frailty/diagnosis , Aged , Cohort Studies , Comorbidity , Female , Frail Elderly , Humans , Male , Risk Factors
13.
Antimicrob Agents Chemother ; 60(4): 2292-301, 2016 Apr.
Article in English | MEDLINE | ID: mdl-26833157

ABSTRACT

Many serious bacterial infections are difficult to treat due to biofilm formation, which provides physical protection and induces a sessile phenotype refractory to antibiotic treatment compared to the planktonic state. A key structural component of biofilm is extracellular DNA, which is held in place by secreted bacterial proteins from the DNABII family: integration host factor (IHF) and histone-like (HU) proteins. A native human monoclonal antibody, TRL1068, has been discovered using single B-lymphocyte screening technology. It has low-picomolar affinity against DNABII homologs from important Gram-positive and Gram-negative bacterial pathogens. The disruption of established biofilm was observedin vitroat an antibody concentration of 1.2 µg/ml over 12 h. The effect of TRL1068in vivowas evaluated in a murine tissue cage infection model in which a biofilm is formed by infection with methicillin-resistantStaphylococcus aureus(MRSA; ATCC 43300). Treatment of the established biofilm by combination therapy of TRL1068 (15 mg/kg of body weight, intraperitoneal [i.p.] administration) with daptomycin (50 mg/kg, i.p.) significantly reduced adherent bacterial count compared to that after daptomycin treatment alone, accompanied by significant reduction in planktonic bacterial numbers. The quantification of TRL1068 in sample matrices showed substantial penetration of TRL1068 from serum into the cage interior. TRL1068 is a clinical candidate for combination treatment with standard-of-care antibiotics to overcome the drug-refractory state associated with biofilm formation, with potential utility for a broad spectrum of difficult-to-treat bacterial infections.


Subject(s)
Anti-Bacterial Agents/pharmacology , Antibodies, Monoclonal/pharmacology , Biofilms/drug effects , Foreign Bodies/drug therapy , Methicillin-Resistant Staphylococcus aureus/drug effects , Staphylococcal Infections/drug therapy , Amino Acid Sequence , Animals , Anti-Bacterial Agents/biosynthesis , Anti-Bacterial Agents/isolation & purification , Antibodies, Monoclonal/biosynthesis , Antibodies, Monoclonal/isolation & purification , Antibody Specificity , B-Lymphocytes/chemistry , B-Lymphocytes/cytology , B-Lymphocytes/immunology , Bacterial Proteins/antagonists & inhibitors , Bacterial Proteins/genetics , Bacterial Proteins/metabolism , Biofilms/growth & development , DNA-Binding Proteins/antagonists & inhibitors , DNA-Binding Proteins/genetics , DNA-Binding Proteins/metabolism , Daptomycin/pharmacology , Disease Models, Animal , Drug Therapy, Combination , Epitope Mapping , Female , Foreign Bodies/microbiology , Gene Expression , Injections, Intraperitoneal , Integration Host Factors/antagonists & inhibitors , Integration Host Factors/genetics , Integration Host Factors/metabolism , Methicillin-Resistant Staphylococcus aureus/genetics , Methicillin-Resistant Staphylococcus aureus/growth & development , Methicillin-Resistant Staphylococcus aureus/metabolism , Mice , Mice, Inbred C57BL , Models, Molecular , Plankton/drug effects , Plankton/genetics , Plankton/growth & development , Plankton/metabolism , Sequence Alignment , Single-Cell Analysis , Staphylococcal Infections/microbiology
14.
Scand J Med Sci Sports ; 26(11): 1313-1320, 2016 Nov.
Article in English | MEDLINE | ID: mdl-26634957

ABSTRACT

To determine the influence of androgen receptor CAG and GGN repeat polymorphisms on fat mass and maximal fat oxidation (MFO), CAG and GGN repeat lengths were measured in 128 young boys, from which longitudinal data were obtained in 45 of them [mean ± SD: 12.8 ± 3.6 years old at recruitment, and 27.0 ± 4.8 years old at adult age]. Subjects were grouped as CAG short (CAGS ) if harboring repeat lengths ≤ 21, the rest as CAG long (CAGL ); and GGN short (GGNS ) if GGN repeat lengths ≤ 23, or long if > 23 (GGNL ). CAGS and GGNS were associated with lower adiposity than CAGL or GGNL (P < 0.05). There was an association between the logarithm of CAG repeats polymorphism and the changes of body mass (r = 0.34, P = 0.03). At adult age, CAGS men showed lower accumulation of total body and trunk fat mass, and lower resting metabolic rate (RMR) and MFO per kg of total lean mass compared with CAGL (P < 0.05). GGNS men also showed lower percentage of body fat (P < 0.05). In summary, androgen receptor CAG and GGN repeat polymorphisms are associated with RMR, MFO, fat mass, and its regional distribution in healthy male adolescents, influencing fat accumulation from adolescence to adult age.


Subject(s)
Adiposity/genetics , Basal Metabolism/genetics , Receptors, Androgen/genetics , Absorptiometry, Photon , Adolescent , Adult , Body Composition/genetics , Body Fat Distribution , Calorimetry, Indirect , Child , Humans , Longitudinal Studies , Male , Oxidation-Reduction , Physical Fitness , Polymorphism, Genetic , Young Adult
15.
Scand J Med Sci Sports ; 26(9): 1045-51, 2016 Sep.
Article in English | MEDLINE | ID: mdl-26314285

ABSTRACT

End-tidal PCO2 (PET CO2 ) has been used to estimate arterial pressure CO2 (Pa CO2 ). However, the influence of blood temperature on the Pa CO2 has not been taken into account. Moreover, there is no equation validated to predict Pa CO2 during exercise in severe acute hypoxia. To develop a new equation to predict temperature-corrected Pa CO2 values during exercise in normoxia and severe acute hypoxia, 11 volunteers (21.2 ± 2.1 years) performed incremental exercise to exhaustion in normoxia (Nox, PI O2 : 143 mmHg) and hypoxia (Hyp, PI O2 : 73 mmHg), while arterial blood gases and temperature (ABT) were simultaneously measured together with end-tidal PCO2 (PET CO2 ). The Jones et al. equation tended to underestimate the temperature corrected (tc) Pa CO2 during exercise in hypoxia, with greater deviation the lower the Pa CO2 tc (r = 0.39, P < 0.05). The new equation has been developed using a random-effects regression analysis model, which allows predicting Pa CO2 tc both in normoxia and hypoxia: Pa CO2 tc = 8.607 + 0.716 × PET CO2 [R(2) = 0.91; intercept SE = 1.022 (P < 0.001) and slope SE = 0.027 (P < 0.001)]. This equation may prove useful in noninvasive studies of brain hemodynamics, where an accurate estimation of Pa CO2 is needed to calculate the end-tidal-to-arterial PCO2 difference, which can be used as an index of pulmonary gas exchange efficiency.


Subject(s)
Body Temperature/physiology , Carbon Dioxide/blood , Exercise/physiology , Hypoxia/physiopathology , Arteries , Blood Gas Analysis , Capnography , Carbon Dioxide/analysis , Humans , Hypoxia/blood , Male , Mathematical Concepts , Models, Biological , Partial Pressure , Pulmonary Gas Exchange , Tidal Volume , Young Adult
16.
J Med Chem ; 54(6): 1667-81, 2011 Mar 24.
Article in English | MEDLINE | ID: mdl-21341682

ABSTRACT

Through the application of TRAP (target-related affinity profiling), we identified a novel class of heteroaroylphenylureas that inhibit human CCL2-induced chemotaxis of monocytes/macrophages both in vitro and in vivo. This inhibition was concentration-dependent and selective with regard to other chemokines. The compounds, however, did not antagonize the binding of (125)I-labeled CCL2 to the CCR2 receptor nor did they block CCR2-mediated signal transduction responses such as calcium mobilization. Optimization of early leads for potency and pharmacokinetic parameters resulted in the identification of 17, a potent inhibitor of chemotaxis (IC(50) = 80 nM) with excellent oral bioavailability in rats (F = 60%). Compound 17 reduced swelling and joint destruction in two rat models of rheumatoid arthritis and delayed disease onset and produced near complete resolution of symptoms in a mouse model of multiple sclerosis.


Subject(s)
Anti-Inflammatory Agents, Non-Steroidal/chemical synthesis , Bridged Bicyclo Compounds, Heterocyclic/chemical synthesis , Chemokine CCL2/antagonists & inhibitors , Phenylurea Compounds/chemical synthesis , Administration, Oral , Animals , Anti-Inflammatory Agents, Non-Steroidal/pharmacokinetics , Anti-Inflammatory Agents, Non-Steroidal/pharmacology , Arthritis, Experimental/drug therapy , Arthritis, Experimental/pathology , Arthritis, Rheumatoid/drug therapy , Arthritis, Rheumatoid/pathology , Biological Availability , Bridged Bicyclo Compounds, Heterocyclic/pharmacokinetics , Bridged Bicyclo Compounds, Heterocyclic/pharmacology , CHO Cells , Cell Line, Tumor , Chemotaxis/drug effects , Cricetinae , Cricetulus , Humans , Joints/drug effects , Joints/pathology , Macrophages/drug effects , Macrophages/physiology , Mice , Mice, Inbred ICR , Monocytes/drug effects , Monocytes/physiology , Multiple Sclerosis/drug therapy , Phenylurea Compounds/pharmacokinetics , Phenylurea Compounds/pharmacology , Radioligand Assay , Rats , Receptors, CCR2/metabolism , Structure-Activity Relationship
17.
Reprod Domest Anim ; 44 Suppl 2: 287-90, 2009 Jul.
Article in English | MEDLINE | ID: mdl-19754588

ABSTRACT

The aim of this study was to asses the variation in the morphology of the seminal epithelium in relation to natural photoperiod in male cats. Tom cats (n = 240) were castrated every other week throughout the year. Each testis was fixed in Bouin's solution and cut into sections. The percentage of tubules with round spermatids (RS), elongated spermatids (ES), tailed spermatids (TS), mature spermatids (MS) and the number of Sertoli cells (SC) and Leydig cells (LC) were recorded in each sample. Testicles from males during short days (SHD) had a higher percentage of tubules with RS and ES compared to testicles from males during long days (LHD, 31.3 +/- 0.6 vs 2.1 +/- 0.6%, p < 0.001; 30.9 +/- 0.7 vs 11.0 +/- 0.7%, p < 0.001). Conversely, testicles from males during SHD had a lower percentage of tubules with TS and MS compared to testicles from males during LHD (24.5 +/- 0.8 vs 29.7 +/- 0.8%, p < 0.01; 13.1 +/- 1.2 vs 57.0 +/- 1.2%, p < 0.01). Furthermore, testicles from males during SHD had a higher number of SC and lower number of LC compared to testicles from males during LHD (11.4 +/- 0.1 vs 8.0 +/- 0.1%, p < 0.01; 19.2 +/- 1.0 vs 38.0 +/- 1.0%, p < 0.01). In conclusion, there are seasonal changes in testis cell morphology in the tom which may be related to seasonal sperm production.


Subject(s)
Seasons , Testis/anatomy & histology , Testis/physiology , Animals , Cats , Male , Photoperiod , Spermatogenesis/physiology
18.
Mar Biotechnol (NY) ; 11(3): 375-83, 2009.
Article in English | MEDLINE | ID: mdl-18931878

ABSTRACT

We aimed at determining the antagonistic behavior of bacteria derived from marine biofilms against terrestrial phytopathogenic fungi. Some bacteria closely related to Bacillus mojavensis (three isolates) and Bacillus firmus (one isolate) displayed antagonistic activity against Colletotrichum gloeosporioides ATCC 42374, selected as first screen organism. The four isolates were further quantitatively tested against C. gloeosporioides, Colletotrichum fragariae, and Fusarium oxysporum on two culture media, potato dextrose agar (PDA) and a marine medium-based agar [yeast extract agar (YEA)] at different times of growth of the antagonists (early, co-inoculation with the pathogen and late). Overall antagonistic assays showed differential susceptibility among the pathogens as a function of the type of culture media and time of colonization (P < 0.05). In general, higher suppressive activities were recorded for assays performed on YEA than on PDA; and also when the antagonists were allowed to grow 24 h earlier than the pathogen. F. oxysporum was the most resistant fungus while the most sensitive was C. gloeosporioides ATCC 42374. Significant differences in antagonistic activity (P < 0.05) were found between the different isolates. In general, Bacillus sp. MC3B-22 displayed a greater antagonistic effect than the commercial biocontrol strain Bacillus subtilis G03 (Kodiak). Further incubation studies and scanning electronic microscopy revealed that Bacillus sp. MC3B-22 was able to colonize, multiply, and inhibit C. gloeosporioides ATCC 42374 when tested in a mango leaf assay, showing its potential for fungal biocontrol. Additional studies are required to definitively identify the active isolates and to determine their mode of antifungal action, safety, and biocompatibility.


Subject(s)
Antibiosis/physiology , Antifungal Agents/metabolism , Bacillus/metabolism , Biofilms , Colletotrichum/growth & development , Bacillus/ultrastructure , Colletotrichum/metabolism , Culture Media , Microscopy, Electron, Scanning , Pest Control, Biological/methods , Time Factors
19.
Reprod Domest Anim ; 42(4): 410-7, 2007 Aug.
Article in English | MEDLINE | ID: mdl-17635779

ABSTRACT

The effect of gonadotropin releasing hormone (GnRH) treatment on the time of ovulation and the occurrence of follicular dominance during the non-breeding and breeding seasons (experiment 1), and on fertility after artificial insemination (AI) in the non-breeding season (experiment 2), was examined in Merino ewes. Oestrus was synchronized in 40 nulliparous ewes (experiment 1; n = 20, in the non-breeding and breeding seasons) and in 79 multiparous ewes (experiment 2) using intravaginal sponges and pregnant mare serum gonadotropin. Thirty six hours after sponge removal (SR), half the ewes were injected (i.m.) with 40 microg of synthetic GnRH and the remainder used as controls. GnRH improved the synchrony of ovulation compared with the controls in the breeding (SD = 2.8 vs 5.7 days, p = 0.04) but not the non-breeding season (SD = 3.8 vs 4.4 days, p = 0.69), with ewes ovulating from 42 to 54 h (mean 50.4 +/- 4.08 h) and 42-60 h (mean 54.4 +/- 5.47 h) after SR for GnRH and control, respectively. For both treated and control ewes, ovulation occurred earlier in the non-breeding than the breeding season (50.1 vs 54.6 h; p = 0.002). GnRH had no effect on follicular dominance, as assessed by divergence (D: the time the ovulatory follicle exceeded the average size of the other non-ovulating follicles) or on the interval from D to ovulation (IDO). However, follicular dynamics differed between seasons. The mean follicle diameter increased at a faster rate up to 36 h after SR in the non-breeding compared with the breeding season and then rapidly declined, compared with a later peak (42 h after SR) in mean follicular size during the breeding season. IDO was shorter in the non-breeding than in the breeding season (26.7 +/- 4.30 h vs 39.6 +/- 4.53 h; p = 0.05). In experiment 2, ewes (n = 38 GnRH-treated, n = 40 controls) were inseminated in the uterus by laparoscopy 42 h or 48 h after SR with frozen-thawed sperm. The fertility of ewes treated with GnRH (nine of 39, 23%) was not different to the controls (eight of 38, 21%; p = 0.01). In conclusion the application of GnRH improved synchronization of ovulation but did not improve fertility rates after AI.


Subject(s)
Estrus/drug effects , Gonadotropin-Releasing Hormone/pharmacology , Ovarian Follicle/drug effects , Ovulation Induction/veterinary , Ovulation/drug effects , Sheep/physiology , Animals , Breeding , Female , Gonadotropin-Releasing Hormone/administration & dosage , Injections, Intramuscular/veterinary , Insemination, Artificial/veterinary , Ovarian Follicle/diagnostic imaging , Ovarian Follicle/physiology , Pregnancy , Pregnancy Rate , Seasons , Ultrasonography
20.
Clín. investig. ginecol. obstet. (Ed. impr.) ; 33(4): 140-145, jul. 2006. tab
Article in Es | IBECS | ID: ibc-046221

ABSTRACT

Objetivo. Examinar la asociación entre la colonización genital de mujeres embarazadas con el serotipo III de Streptococcus del grupo B (SGB) y la rotura prematura de membranas (RPM) en comparación con el resto de los serotipos de SGB. Material y métodos. Por medio de un estudio de cohorte retrospectiva se serotipificaron cepas de SGB de mujeres embarazadas. Se definieron dos grupos: expuestos, pacientes en las que se documentó SGB serotipo III en cultivos vaginales o urinarios, y no expuestos, pacientes en las que se documentó cualquier serotipo diferente al III de SGB, en cultivos vaginales o urinarios. Resultados. Se serotipificaron 135 cepas de SGB: en el grupo de los expuestos se incluyó a 43 mujeres embarazadas, mientras que en el de los no expuestos se incluyó a 92 mujeres. Se documentó RPM en 27 pacientes expuestas (62,7%) y en 17 pacientes no expuestas (18,4%) (RR = 3,3; IC del 95%, 1,2-7; p < 0,05). Conclusiones. El serotipo III se asocia tres veces a RPM (AU)


Objective. To examine the association between maternal colonization with serotype III group B Streptococcus (GBS) and premature rupture of membranes (PROM) in comparison with other GBS serotypes. Material and method. We performed a retrospective cohort study. GBS strains were serotyped in pregnant women. The women were divided into 2 groups: group I consisted of patients with a positive vaginal or urinary culture for GBS serotype III and group II consisted of patients with a positive culture for serotypes Ia, Ib, II, IV, V or VI. Results. There were 135 GBS isolations. Group 1 included 43 pregnant women and group 2 included 92 pregnant women. PROM occurred in 27 patients in group I (62.7%) and in 17 patients in group 2 (18.4%) (RR = 3.3; 95% CI, 1.2-7.4; p < 0.05). Conclusions. Vaginal colonization with serotype III of GBS was associated with a 3-fold increase in the risk of PROM (AU)


Subject(s)
Streptococcus/isolation & purification , Fetal Membranes, Premature Rupture/complications , Fetal Membranes, Premature Rupture/diagnosis , Serotyping/methods , Culture Media , Risk Factors , Fetal Membranes, Premature Rupture/etiology , Retrospective Studies , Cross-Sectional Studies , Serotyping/classification , Serotyping/statistics & numerical data
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