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1.
Vaccines (Basel) ; 11(10)2023 Sep 26.
Article in English | MEDLINE | ID: mdl-37896930

ABSTRACT

During the COVID-19 pandemic, the importance of vaccinating children against SARS-CoV-2 was rapidly established. This study describes the safety of CoronaVac® in children and adolescents between 3- and 17-years-old in a multicenter study in Chile with two vaccine doses in a 4-week interval. For all participants, immediate adverse events (AEs), serious AEs (SAEs), and AEs of special interest (AESIs) were registered throughout the study. In the safety subgroup, AEs were recorded 28 days after each dose. COVID-19 surveillance was performed throughout the study. A total of 1139 individuals received the first and 1102 the second dose of CoronaVac®; 835 were in the safety subgroup. The first dose showed the highest number of AEs: up to 22.2% of participants reported any local and 17.1% systemic AE. AEs were more frequent in adolescents after the first dose, were transient, and mainly mild. Pain at the inoculation site was the most frequent AE for all ages. Fever was the most frequent systemic AE for 3-5 years old and headache in 6-17 years old. No SAEs or AESIs related to vaccination occurred. Most of the COVID-19 cases were mild and managed as outpatients. CoronaVac® was safe and well tolerated in children and adolescents, with different safety patterns according to age.

2.
Vaccines (Basel) ; 10(7)2022 Jul 06.
Article in English | MEDLINE | ID: mdl-35891246

ABSTRACT

Several vaccines have been developed to control the COVID-19 pandemic. CoronaVac®, an inactivated SARS-CoV-2 vaccine, has demonstrated safety and immunogenicity, preventing severe COVID-19 cases. We investigate the safety and non-inferiority of two immunization schedules of CoronaVac® in a non-inferiority trial in healthy adults. A total of 2302 healthy adults were enrolled at 8 centers in Chile and randomly assigned to two vaccination schedules, receiving two doses with either 14 or 28 days between each. The primary safety and efficacy endpoints were solicited adverse events (AEs) within 7 days of each dose, and comparing the number of cases of SARS-CoV-2 infection 14 days after the second dose between the schedules, respectively. The most frequent local AE was pain at the injection site, which was less frequent in participants aged ≥60 years. Other local AEs were reported in less than 5% of participants. The most frequent systemic AEs were headache, fatigue, and myalgia. Most AEs were mild and transient. There were no significant differences for local and systemic AEs between schedules. A total of 58 COVID-19 cases were confirmed, and all but 2 of them were mild. No differences were observed in the proportion of COVID-19 cases between schedules. CoronaVac® is safe, especially in ≥60-year-old participants. Both schedules protected against COVID-19 hospitalization.

3.
Clin Infect Dis ; 75(1): e792-e804, 2022 08 24.
Article in English | MEDLINE | ID: mdl-34537835

ABSTRACT

BACKGROUND: The development of effective vaccines against coronavirus disease 2019 is a global priority. CoronaVac is an inactivated severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine with promising safety and immunogenicity profiles. This article reports safety and immunogenicity results obtained for healthy Chilean adults aged ≥18 years in a phase 3 clinical trial. METHODS: Volunteers randomly received 2 doses of CoronaVac or placebo, separated by 2 weeks. A total of 434 volunteers were enrolled, 397 aged 18-59 years and 37 aged ≥60 years. Solicited and unsolicited adverse reactions were registered from all volunteers. Blood samples were obtained from a subset of volunteers and analyzed for humoral and cellular measures of immunogenicity. RESULTS: The primary adverse reaction in the 434 volunteers was pain at the injection site, with a higher incidence in the vaccine than in the placebo arm. Adverse reactions observed were mostly mild and local. No severe adverse events were reported. The humoral evaluation was performed on 81 volunteers. Seroconversion rates for specific anti-S1-receptor binding domain (RBD) immunoglobulin G (IgG) were 82.22% and 84.44% in the 18-59 year age group and 62.69% and 70.37% in the ≥60 year age group, 2 and 4 weeks after the second dose, respectively. A significant increase in circulating neutralizing antibodies was detected 2 and 4 weeks after the second dose. The cellular evaluation was performed on 47 volunteers. We detected a significant induction of T-cell responses characterized by the secretion of interferon-γ (IFN-γ) upon stimulation with Mega Pools of peptides from SARS-CoV-2. CONCLUSIONS: Immunization with CoronaVac in a 0-14 schedule in Chilean adults aged ≥18 years is safe, induces anti-S1-RBD IgG with neutralizing capacity, activates T cells, and promotes the secretion of IFN-γ upon stimulation with SARS-CoV-2 antigens.


Subject(s)
COVID-19 , Viral Vaccines , Adolescent , Adult , Antibodies, Neutralizing , Antibodies, Viral , COVID-19/prevention & control , COVID-19 Vaccines/adverse effects , Chile , Double-Blind Method , Humans , Immunogenicity, Vaccine , Immunoglobulin G , Middle Aged , SARS-CoV-2 , Vaccines, Inactivated/adverse effects , Young Adult
4.
Rev. chil. obstet. ginecol. (En línea) ; 86(6): 591-622, dic. 2021. ilus, tab
Article in Spanish | LILACS | ID: biblio-1388701

ABSTRACT

Resumen La Sociedad Chilena de Infectología, a través de su Comité de Infecciones Neonatales, en conjunto con la Sociedad Chilena de Obstetricia y Ginecología, proponen un documento de diagnóstico y manejo de la infección por citomegalovirus (CMV) en la mujer embarazada y el recién nacido. Esta guía aborda el manejo de la infección en el binomio, su enfrentamiento diagnóstico y terapéutico, orientado al equipo de salud que atiende a mujeres embarazadas y recién nacidos con infección por CMV en Chile. Considera la situación epidemiológica global y latinoamericana, con recomendaciones para la evaluación clínica y de laboratorio; establece criterios de diagnóstico, propone enfoques terapéuticos de acuerdo a la situación clínica, analiza las medidas de prevención y establece una propuesta nacional para el seguimiento de esta enfermedad. Se ha puesto especial énfasis en entregar, de forma práctica, y con la mayor evidencia posible, las recomendaciones para el manejo del binomio con infección por CMV.


Abstract The Chilean Society of Infectology, through its Neonatal Infections Committee in conjunction with the Chilean Society of Obstetrics and Gynecology, propose a document for the Diagnosis and Management of Cytomegalovirus Infection in Pregnancy and Newborn. This guideline suggests the management of mother and child infection, its diagnostic and therapeutic options. Considers the global and Latin American epidemiology, with recommendations for clinical and laboratory evaluation, diagnostic criteria, therapeutic approaches according to the clinical situation, analyzes prevention measures and establishes a national proposal for monitoring this disease.


Subject(s)
Humans , Female , Pregnancy , Infant, Newborn , Pregnancy Complications, Infectious/diagnosis , Pregnancy Complications, Infectious/therapy , Cytomegalovirus Infections/diagnosis , Cytomegalovirus Infections/therapy , Infant, Newborn, Diseases/diagnosis , Infant, Newborn, Diseases/therapy , Prenatal Diagnosis , Congenital Abnormalities/diagnosis , Congenital Abnormalities/therapy , Cytomegalovirus Infections/congenital
5.
Rev. chil. infectol ; 38(6): 824-856, dic. 2021. ilus, tab
Article in Spanish | LILACS | ID: biblio-1388313

ABSTRACT

Resumen La Sociedad Chilena de Infectología, a través de su Comité de Infecciones Neonatales, en conjunto con la Sociedad Chilena de Obstetricia y Ginecología, proponen un documento de diagnóstico y manejo de la Infección por Citomegalovirus en la Mujer Embarazada y el Recién Nacido. Esta guía aborda el manejo de la infección en el binomio, su enfrentamiento diagnóstico y terapéutico, orientado al equipo de salud que atiende a mujeres embarazadas y recién nacidos con infección por citomegalovirus (CMV) en Chile. Considera la situación epidemiológica global y latinoamericana, con recomendaciones para la evaluación clínica y de laboratorio; establece criterios de diagnóstico, propone enfoques terapéuticos de acuerdo a la situación clínica, analiza las medidas de prevención y establece una propuesta nacional para el seguimiento de esta enfermedad. Se ha puesto especial énfasis en entregar, de forma práctica, y con la mayor evidencia posible, las recomendaciones para el manejo del binomio con infección por CMV.


Abstract The Chilean Society of Infectology, through its Neonatal Infections Committee in conjunction with the Chilean Society of Obstetrics and Gynecology, propose a document for the Diagnosis and Management of Cytomegalovirus Infection in Pregnant Woman and Newborn Infant. This guideline suggests the management of mother and child infection, its diagnostic and therapeutic options. Considers the global and Latin American epidemiology, with recommendations for clinical and laboratory evaluation; diagnostic criteria, therapeutic approaches according to the clinical situation, analyzes prevention measures and establishes a national proposal for monitoring this disease.


Subject(s)
Humans , Female , Pregnancy , Infant, Newborn , Infant , Pregnancy Complications, Infectious/diagnosis , Pregnancy Complications, Infectious/drug therapy , Cytomegalovirus Infections/diagnosis , Cytomegalovirus Infections/drug therapy , Cytomegalovirus Infections/transmission , Chile , Pregnant Women , Gynecology
6.
Zootaxa ; 4958(1): zootaxa.4958.1.30, 2021 Apr 14.
Article in English | MEDLINE | ID: mdl-33903477

ABSTRACT

Carpocorini is the largest tribe of Pentatominae, containing 127 genera and more than 500 species distributed worldwide. A new genus, Jocezia n. gen., and a new species, Jocezia inusitata n. sp., from Argentina are described and illustrated. The new genus is included in the Hypatropis group, together with the genera Hypatropis, Amauromelpia, Luridocimex and Stysiana, and characterized by the head in lateral view with the mandibular plates in a higher level than clypeus and the absence of parameres. An updated key to the Hypatropis group genera is provided.


Subject(s)
Heteroptera , Animals , Heteroptera/classification
7.
Rev Chilena Infectol ; 38(6): 824-856, 2021 12.
Article in Spanish | MEDLINE | ID: mdl-35506860

ABSTRACT

The Chilean Society of Infectology, through its Neonatal Infections Committee in conjunction with the Chilean Society of Obstetrics and Gynecology, propose a document for the Diagnosis and Management of Cytomegalovirus Infection in Pregnant Woman and Newborn Infant. This guideline suggests the management of mother and child infection, its diagnostic and therapeutic options. Considers the global and Latin American epidemiology, with recommendations for clinical and laboratory evaluation; diagnostic criteria, therapeutic approaches according to the clinical situation, analyzes prevention measures and establishes a national proposal for monitoring this disease.


Subject(s)
Cytomegalovirus Infections , Pregnancy Complications, Infectious , Chile , Cytomegalovirus Infections/diagnosis , Cytomegalovirus Infections/drug therapy , Cytomegalovirus Infections/transmission , Female , Gynecology , Humans , Infant , Infant, Newborn , Pregnancy , Pregnancy Complications, Infectious/diagnosis , Pregnancy Complications, Infectious/drug therapy , Pregnant Women
8.
medRxiv ; 2021 Apr 01.
Article in English | MEDLINE | ID: mdl-35441164

ABSTRACT

Background: The ongoing COVID-19 pandemic has had a significant impact worldwide, with an incommensurable social and economic burden. The rapid development of safe and protective vaccines against this disease is a global priority. CoronaVac is a vaccine prototype based on inactivated SARS-CoV-2, which has shown promising safety and immunogenicity profiles in pre-clinical studies and phase 1/2 trials in China. To this day, four phase 3 clinical trials are ongoing with CoronaVac in Brazil, Indonesia, Turkey, and Chile. This article reports the safety and immunogenicity results obtained in a subgroup of participants aged 18 years and older enrolled in the phase 3 Clinical Trial held in Chile. Methods: This is a multicenter phase 3 clinical trial. Healthcare workers aged 18 years and older were randomly assigned to receive two doses of CoronaVac or placebo separated by two weeks (0-14). We report preliminary safety results obtained for a subset of 434 participants, and antibody and cell-mediated immunity results obtained in a subset of participants assigned to the immunogenicity arm. The primary and secondary aims of the study include the evaluation of safety parameters and immunogenicity against SARS-CoV-2 after immunization, respectively. This trial is registered at clinicaltrials.gov ( NCT04651790 ). Findings: The recruitment of participants occurred between November 27 th , 2020, until January 9 th , 2021. 434 participants were enrolled, 397 were 18-59 years old, and 37 were ≥60 years old. Of these, 270 were immunized with CoronaVac, and the remaining 164 participants were inoculated with the corresponding placebo. The primary adverse reaction was pain at the injection site, with a higher incidence in the vaccine arm (55.6%) than in the placebo arm (40.0%). Moreover, the incidence of pain at the injection site in the 18-59 years old group was 58.4% as compared to 32.0% in the ≥60 years old group. The seroconversion rate for specific anti-S1-RBD IgG was 47.8% for the 18-59 years old group 14 days post immunization (p.i.) and 95.6% 28 and 42 days p.i. For the ≥60 years old group, the seroconversion rate was 18.1%, 100%, and 87.5% at 14, 28, and 42 days p.i., respectively. Importantly, we observed a 95.7% seroconversion rate in neutralizing antibodies for the 18-59 years old group 28 and 42 days p.i. The ≥60 years old group exhibited seroconversion rates of 90.0% and 100% at 28 and 42 days p.i. Interestingly, we did not observe a significant seroconversion rate of anti-N-SARS-CoV-2 IgG for the 18-59 years old group. For the participants ≥60 years old, a modest rate of seroconversion at 42 days p.i. was observed (37.5%). We observed a significant induction of a T cell response characterized by the secretion of IFN-γ upon stimulation with Mega Pools of peptides derived from SARS-CoV-2 proteins. No significant differences between the two age groups were observed for cell-mediated immunity. Interpretation: Immunization with CoronaVac in a 0-14 schedule in adults of 18 years and older in the Chilean population is safe and induces specific IgG production against the S1-RBD with neutralizing capacity, as well as the activation of T cells secreting IFN-γ, upon recognition of SARS-CoV-2 antigens. Funding: Ministry of Health of the Chilean Government; Confederation of Production and Commerce, Chile; Consortium of Universities for Vaccines and Therapies against COVID-19, Chile; Millennium Institute on Immunology and Immunotherapy.

9.
Cell Mol Bioeng ; 5(2): 143-154, 2012 Jun 01.
Article in English | MEDLINE | ID: mdl-23487555

ABSTRACT

Endothelial cells sense mechanical forces of blood flow through mechanisms that involve focal adhesions (FAs). The mechanosensitive pathways that originate from FA-associated integrin activation may involve membrane rafts, small cholesterol- and sphigolipid-rich domains that are either immobilized, by virtue of their attachment to the cytoskeleton, or highly mobile in the plane of the plasma membrane. In this study, we fluorescently labeled non-mobile and mobile populations of GM1, a ganglioside associated with lipid rafts, and transfected cells with the red fluorescent protein-(RFP-) talin, an indicator of integrin activation at FAs, in order to determine the kinetics and sequential order of raft and talin mechanosensitivity. Cells were imaged under confocal microscopy during mechanical manipulation of a FA induced by a fibronectin (FN)-functionalized nanoelectrode with feedback control of position. First, FA deformation led to long range deformation of immobile rafts followed by active recoil of a subpopulation of displaced rafts. Second, initial adhesion between the FN-probe and the cell induced rapid accumulation of GM1 at the probe site with a time constant of 1.7 s. Talin accumulated approximately 20 s later with a time constant of 0.6 s. Third, a 1 µm deformation of the FA lead to immediate (0.3 s) increase in GM1 fluorescence and a later (6 s) increase in talin. Fourth, long term deformation of FAs led to continual GM1 accumulation at the probe site that was reversed upon removal of the deformation. These results demonstrate that rafts are directly mechanosensitive and that raft mobility may enable the earliest events related to FA mechanosensing and reinforcement upon force application.

10.
Bol. micol ; 26(1): 29-34, dic. 2011. ilus, graf
Article in Spanish | LILACS | ID: lil-679644

ABSTRACT

Se realizó una búsqueda en base de datos Cabdirect bajo los términos ®Pneumocystis-stain¼ entre los años 1990 a 2010., revisándose 109 trabajos relacionados al diagnóstico y estudio de la neumocistosis. Las metodologías empleadas fueron clasificadas en 6 grupos según su frecuencia: Tinción con Gomori-Grocott; Giemsa; Azul de toluidina; Otras tinciones (pap, blanco de calcofluor, gram, may grunwald giemsa);además de inmunofluorescencia directa y PCR (en cualquiera de sus variantes). Se observó una constante en el empleo de las tinciones histológicas en ambas décadas, mayormente con las tinciones de Gomori-Grocott y Giemsa. Sin embargo y como es de esperar, aumenta en la segunda década la tendencia del diagnóstico a través de técnicas moleculares.


Was performed a database search Cabdirect under the terms "pneumonia-stain" between the years 1990 to 2010, 109 papers being revised, and study related to the diagnosis of pneumocystosis. The methodologies used were classified into six groups according to their frequency: Gomori-Grocott stain, Giemsa, toluidine blue, Other stains (pap, calcofluor white, Gram, May Grunwald Giemsa), in addition to direct immunofluorescence and PCR (in any of their variants). There was a constant in the use of histological stains in both decades, mostly with Gomori Grocott staining and Giemsa. However, as expected, increases in the second decade, the trend of diagnosis using molecular techniques.


Subject(s)
Humans , Coloring Agents , Diagnostic Techniques and Procedures , AIDS-Related Opportunistic Infections/diagnosis , Pneumonia, Pneumocystis/diagnosis , Pneumonia, Pneumocystis/virology , Pneumocystis carinii
11.
Plant Physiol ; 157(3): 1114-27, 2011 Nov.
Article in English | MEDLINE | ID: mdl-21921116

ABSTRACT

Mitochondrial complex II (succinate dehydrogenase [SDH]) plays roles both in the tricarboxylic acid cycle and the respiratory electron transport chain. In Arabidopsis (Arabidopsis thaliana), its flavoprotein subunit is encoded by two nuclear genes, SDH1-1 and SDH1-2. Here, we characterize heterozygous SDH1-1/sdh1-1 mutant plants displaying a 30% reduction in SDH activity as well as partially silenced plants obtained by RNA interference. We found that these plants displayed significantly higher CO(2) assimilation rates and enhanced growth than wild-type plants. There was a strong correlation between CO(2) assimilation and stomatal conductance, and both mutant and silenced plants displayed increased stomatal aperture and density. By contrast, no significant differences were found for dark respiration, chloroplastic electron transport rate, CO(2) uptake at saturating concentrations of CO(2), or biochemical parameters such as the maximum rates of carboxylation by Rubisco and of photosynthetic electron transport. Thus, photosynthesis is enhanced in SDH-deficient plants by a mechanism involving a specific effect on stomatal function that results in improved CO(2) uptake. Metabolic and transcript profiling revealed that mild deficiency in SDH results in limited effects on metabolism and gene expression, and data suggest that decreases observed in the levels of some amino acids were due to a higher flux to proteins and other nitrogen-containing compounds to support increased growth. Strikingly, SDH1-1/sdh1-1 seedlings grew considerably better in nitrogen-limiting conditions. Thus, a subtle metabolic alteration may lead to changes in important functions such as stomatal function and nitrogen assimilation.


Subject(s)
Arabidopsis Proteins/metabolism , Arabidopsis/growth & development , Electron Transport Complex II/metabolism , Flavoproteins/metabolism , Mitochondria/metabolism , Nitrogen/pharmacology , Photosynthesis/drug effects , Succinate Dehydrogenase/metabolism , Arabidopsis/drug effects , Arabidopsis/enzymology , Arabidopsis/genetics , Arabidopsis Proteins/genetics , Flavoproteins/genetics , Gene Expression Profiling , Gene Expression Regulation, Plant/drug effects , Gene Silencing/drug effects , Genes, Plant/genetics , Kinetics , Metabolome/genetics , Mitochondria/drug effects , Mutation/genetics , Nitrates/metabolism , Plant Stomata/cytology , Plant Stomata/drug effects , Plant Stomata/genetics , Plant Stomata/physiology , RNA, Messenger/genetics , RNA, Messenger/metabolism , Seedlings/drug effects , Seedlings/growth & development , Succinate Dehydrogenase/deficiency , Succinate Dehydrogenase/genetics
12.
Plant Cell ; 23(2): 600-27, 2011 Feb.
Article in English | MEDLINE | ID: mdl-21307286

ABSTRACT

Transgenic tomato (Solanum lycopersicum) plants expressing a fragment of the Sl SDH2-2 gene encoding the iron sulfur subunit of the succinate dehydrogenase protein complex in the antisense orientation under the control of the 35S promoter exhibit an enhanced rate of photosynthesis. The rate of the tricarboxylic acid (TCA) cycle was reduced in these transformants, and there were changes in the levels of metabolites associated with the TCA cycle. Furthermore, in comparison to wild-type plants, carbon dioxide assimilation was enhanced by up to 25% in the transgenic plants under ambient conditions, and mature plants were characterized by an increased biomass. Analysis of additional photosynthetic parameters revealed that the rate of transpiration and stomatal conductance were markedly elevated in the transgenic plants. The transformants displayed a strongly enhanced assimilation rate under both ambient and suboptimal environmental conditions, as well as an elevated maximal stomatal aperture. By contrast, when the Sl SDH2-2 gene was repressed by antisense RNA in a guard cell-specific manner, changes in neither stomatal aperture nor photosynthesis were observed. The data obtained are discussed in the context of the role of TCA cycle intermediates both generally with respect to photosynthetic metabolism and specifically with respect to their role in the regulation of stomatal aperture.


Subject(s)
Citric Acid Cycle , Photosynthesis , Plant Proteins/metabolism , Plant Stomata/drug effects , Solanum lycopersicum/growth & development , Succinate Dehydrogenase/metabolism , Biomass , Carbon Dioxide/metabolism , Cloning, Molecular , Iron-Sulfur Proteins/metabolism , Solanum lycopersicum/genetics , Mitochondria/metabolism , Oxygen Consumption , Phylogeny , Plant Proteins/genetics , Plant Transpiration , Plants, Genetically Modified/genetics , Plants, Genetically Modified/growth & development , RNA, Antisense/genetics , RNA, Plant/genetics , Succinate Dehydrogenase/genetics
13.
Cell Mol Bioeng ; 4(4): 616-626, 2011 Dec.
Article in English | MEDLINE | ID: mdl-22247742

ABSTRACT

Cells dynamically interact with their physical micro-environment through the assembly of nascent focal contacts and focal adhesions. The dynamics and mechanics of these contact points are controlled by transmembrane integrins and an array of intracellular adaptor proteins. In order to study the mechanics and dynamics of focal adhesion assembly, we have developed a technique for the timed induction of a nascent focal adhesion. Bovine aortic endothelial cells were approached at the apical surface by a nanoelectrode whose position was controlled with a resolution of 10s of nanometers using changes in electrode current to monitor distance from the cell surface. Since this probe was functionalized with fibronectin, a focal contact formed at the contact location. Nascent focal adhesion assembly was confirmed using time-lapse confocal fluorescent images of red fluorescent protein (RFP) - tagged talin, an adapter protein that binds to activated integrins. Binding to the cell was verified by noting a lack of change of electrode current upon retraction of the electrode. This study demonstrates that functionalized nanoelectrodes can enable precisely-timed induction and 3-D mechanical manipulation of focal adhesions and the assay of the detailed molecular kinetics of their assembly.

14.
Resuscitation ; 81(2): 255-9, 2010 Feb.
Article in English | MEDLINE | ID: mdl-19944515

ABSTRACT

BACKGROUND: The term "postresuscitation syndrome" includes among other pathophysiology impaired microcirculation and endothelial leakage. GPIIb/IIIa receptor antagonists like abciximab have been shown to reduce endothelial leakage and to improve microcirculatory disturbances during experimental endotoxaemia where comparably similar endothelial dysfunction has been observed. Previous investigations on postresuscitation endothelial leakage have indicated a possible role of platelets. Therefore, we investigated effects of abciximab on postresuscitation microcirculation applying in vivo microscopy of postcapillary mesenteric venules after experimentally induced cardiac arrest and cardiopulmonary resuscitation in rats. METHODS: After 6 min of cardiac arrest (CA) and cardiopulmonary resuscitation (CPR), male Wistar rats were randomised into two groups (n=10) to receive abciximab (1mg/kg i.v.) or placebo (0.9% NaCl). Sham operated animals (n=10) served as non-ischaemic controls. At 360, 420 and 480 min after return of spontaneous circulation (ROSC) in vivo microscopy was performed to assess venular wall shear rate (WSR) and plasma extravasation (PE). RESULTS: Besides typical signs of severe endothelial leakage in both CA groups, no significant differences between the treatment groups were observed with regard to WSR and PE. CONCLUSION: In our study, a distinct postresuscitation microcirculatory splanchnic impairment after CA and successful CPR was observed. However, abciximab had no effects on WSR and PE. Our data does not support a valid resemblance between postresuscitation microcirculatory dysfunction observed in connection with experimental endotoxaemia. Furthermore, our data indicate that mechanisms other than GPIIb/IIIa mediated platelet activation play a role in postresuscitation syndrome. A better understanding of "postresuscitation disease" should enable the development of future therapeutic strategies for cardiac arrest survivors.


Subject(s)
Antibodies, Monoclonal/therapeutic use , Cardiopulmonary Resuscitation , Heart Arrest/physiopathology , Immunoglobulin Fab Fragments/therapeutic use , Microcirculation/drug effects , Platelet Aggregation Inhibitors/therapeutic use , Platelet Glycoprotein GPIIb-IIIa Complex/antagonists & inhibitors , Abciximab , Animals , Antibodies, Monoclonal/pharmacology , Immunoglobulin Fab Fragments/pharmacology , Male , Platelet Aggregation Inhibitors/pharmacology , Rats , Rats, Wistar
15.
Resuscitation ; 80(8): 940-5, 2009 Aug.
Article in English | MEDLINE | ID: mdl-19487065

ABSTRACT

BACKGROUND: The clinical symptoms and pathophysiologic mechanisms during and after ischaemia-reperfusion following cardiac arrest (CA) and successful cardiopulmonary resuscitation (CPR) closely resemble those observed in patients with severe sepsis. Impairment of microcirculation and endothelial leakage seem to play key roles in the underlying pathophysiology. Recombinant human activated protein C (rhAPC) is the first drug being licensed for the treatment of severe sepsis in patients. Therefore, for the first time, we investigated effects of rhAPC on microhaemodynamic changes and endothelial leakage applying in vivo microscopy of postcapillary mesenteric venules after CA and CPR in rats. METHODS: After 6 min of CA, male Wistar rats were randomised into two groups (n=10) to receive rhAPC or placebo (0.9% NaCl). Sham-operated animals (n=10) served as non-ischaemic controls. At 360, 420, and 480 min after CA in vivo microscopy was performed to assess wall shear rate (WSR) and plasma extravasation (PE). RESULTS: Both treatment groups showed typical signs of impaired microcirculation and a severe endothelial leakage after CA at all time points studied when compared to the sham group. However, no significant differences between the treatment groups were observed with regard to WSR and PE. CONCLUSION: Our results show that CA with consecutive successful CPR leads to a microcirculatory impairment closely resembling experimentally induced sepsis. Intriguingly, despite these similarities, rhAPC had no significant effects on WSR and PE. Our results strongly suggest that further mechanisms such as mast cell activation might play an important role and have therefore to be studied to elucidate the pathophysiology of "postresuscitation disease".


Subject(s)
Heart Arrest/physiopathology , Mesentery/blood supply , Microcirculation/drug effects , Protein C/administration & dosage , Sepsis/drug therapy , Animals , Anti-Infective Agents/administration & dosage , Cardiopulmonary Resuscitation/methods , Disease Models, Animal , Dose-Response Relationship, Drug , Fibrinolytic Agents , Follow-Up Studies , Heart Arrest/drug therapy , Heart Arrest/etiology , Male , Microcirculation/physiology , Rats , Rats, Wistar , Recombinant Proteins/administration & dosage , Sepsis/complications , Sepsis/physiopathology , Treatment Outcome
16.
Mar Biotechnol (NY) ; 10(6): 692-700, 2008.
Article in English | MEDLINE | ID: mdl-18478293

ABSTRACT

Dinoflagellates of the genus Alexandrium are photosynthetic microalgae that have an extreme importance due to the impact of some toxic species on shellfish aquaculture industry. Alexandrium catenella is the species responsible for the production of paralytic shellfish poisoning in Chile and other geographical areas. We have constructed a cDNA library from midexponential cells of A. catenella grown in culture free of associated bacteria and sequenced 10,850 expressed sequence tags (ESTs) that were assembled into 1,021 contigs and 5,475 singletons for a total of 6,496 unigenes. Approximately 41.6% of the unigenes showed similarity to genes with predicted function. A significant number of unigenes showed similarity with genes from other dinoflagellates, plants, and other protists. Among the identified genes, the most expressed correspond to those coding for proteins of luminescence, carbohydrate metabolism, and photosynthesis. The sequences of 9,847 ESTs have been deposited in Gene Bank (accession numbers EX 454357-464203).


Subject(s)
Dinoflagellida/genetics , Expressed Sequence Tags , Animals , Contig Mapping , DNA, Protozoan/genetics , Databases, Genetic , Gene Library , Genomics , Molecular Sequence Data , Sequence Analysis, DNA
17.
Plant Cell Physiol ; 47(9): 1295-308, 2006 Sep.
Article in English | MEDLINE | ID: mdl-16926165

ABSTRACT

Casein kinase 2 (CK2) is a ubiquitous enzyme essential for the viability of eukaryotic cells. In the present work we analyzed the Arabidopsis thaliana genome in a search for the genes coding for all CK2 alpha and beta subunits. We found four alpha subunit and four beta subunit genes. Expression analysis showed that all CK2 subunit genes are expressed in inflorescences, stems, leaves and roots. The level of expression of these genes is very similar, except for the one that codes for an alpha subunit harboring a putative chloroplastic destination peptide (alphacp), which shows a slightly higher expression level in all tissues. Using transgenic plants and agroinfiltration, we have also characterized the subcellular localization of all proteins encoded by CK2 genes. Our results show that all alpha subunits are localized in the nucleus, with the exception of alphacp, which is only found in the chloroplasts. On the other hand, beta subunits have a more diverse distribution, with some of them localizing both to the nucleus and to the cytosol, while others are exclusively located in one of these compartments. Remarkably, no CK2beta subunit was found in the chloroplasts. Finally, by directly measuring its activity, we have demonstrated that purified Arabidopsis chloroplasts have active CK2 that can be regulated by external addition of CK2beta. This study represents a complete survey of the CK2 gene family in Arabidopsis and the first step for future studies on CK2 cellular function in this species.


Subject(s)
Arabidopsis/enzymology , Casein Kinase II/metabolism , Amino Acid Sequence , Arabidopsis/classification , Arabidopsis/genetics , Casein Kinase II/chemistry , Casein Kinase II/genetics , Chloroplasts/enzymology , Gene Expression Regulation, Plant , Genes, Plant , Genome, Plant , Isoenzymes/analysis , Isoenzymes/chemistry , Isoenzymes/genetics , Isoenzymes/metabolism , Molecular Sequence Data , Phylogeny , Sequence Alignment
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