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1.
Parasit Vectors ; 17(1): 200, 2024 May 04.
Article in English | MEDLINE | ID: mdl-38704595

ABSTRACT

BACKGROUND: Mayaro virus (MAYV) is an emerging alphavirus, primarily transmitted by the mosquito Haemagogus janthinomys in Central and South America. However, recent studies have shown that Aedes aegypti, Aedes albopictus and various Anopheles mosquitoes can also transmit the virus under laboratory conditions. MAYV causes sporadic outbreaks across the South American region, particularly in areas near forests. Recently, cases have been reported in European and North American travelers returning from endemic areas, raising concerns about potential introductions into new regions. This study aims to assess the vector competence of three potential vectors for MAYV present in Europe. METHODS: Aedes albopictus from Italy, Anopheles atroparvus from Spain and Culex pipiens biotype molestus from Belgium were exposed to MAYV and maintained under controlled environmental conditions. Saliva was collected through a salivation assay at 7 and 14 days post-infection (dpi), followed by vector dissection. Viral titers were determined using focus forming assays, and infection rates, dissemination rates, and transmission efficiency were calculated. RESULTS: Results indicate that Ae. albopictus and An. atroparvus from Italy and Spain, respectively, are competent vectors for MAYV, with transmission possible starting from 7 dpi under laboratory conditions. In contrast, Cx. pipiens bioform molestus was unable to support MAYV infection, indicating its inability to contribute to the transmission cycle. CONCLUSIONS: In the event of accidental MAYV introduction in European territories, autochthonous outbreaks could potentially be sustained by two European species: Ae. albopictus and An. atroparvus. Entomological surveillance should also consider certain Anopheles species when monitoring MAYV transmission.


Subject(s)
Aedes , Alphavirus Infections , Alphavirus , Culex , Mosquito Vectors , Animals , Aedes/virology , Mosquito Vectors/virology , Alphavirus/physiology , Alphavirus/isolation & purification , Culex/virology , Europe , Alphavirus Infections/transmission , Alphavirus Infections/virology , Saliva/virology , Anopheles/virology , Spain , Italy , Female , Belgium
2.
Microbiol Spectr ; : e0502722, 2023 Feb 14.
Article in English | MEDLINE | ID: mdl-36786659

ABSTRACT

Here, we report the validation of a new reporter cell line, Hec1a-IFNB-Luc, for use in inhibition studies of various flaviviruses relevant to human pathology. The reporter system allows the detection of viral replication after luciferase gene activation driven by an interferon beta (IFN-ß) promoter. We found the reporter cell line to be highly responsive to all 10 flaviviruses tested, including the 4 dengue virus serotypes. The applicability of the Hec1a-IFNB-Luc reporter cell line for serodiagnostic purposes in neutralizing antibody assays was confirmed by comparison of its sensitivity and specificity to those of "gold-standard," clinically applied, cytopathic effect-based assays, showing comparable performances. The reporter cell line used for the assessment of viral inhibition by small-molecule antiviral compounds was also confirmed, and the sensitivity of the Hec1a-IFNB-Luc reporter cell line was compared to those from published data reporting on the activity of the antivirals in various other assays, indicating that the Hec1a-IFNB-Luc reporter cell line allowed the determination of the inhibitory capacity at least as sensitive as alternative assays. By measuring luciferase activity as a proxy for viral replication, the reporter cell line allows early detection, reducing the time to results from often 5 to 7 days to 3 days, without the need for optical inspection of cytopathic effects, which often differ between viruses and cell lines, streamlining the development of flavivirus assays. IMPORTANCE The Hec1a-IFNB-Luc reporter cell line allows the detection of all 10 flaviviruses tested, including the 4 dengue virus serotypes. Its use for serodiagnostic purposes, measuring neutralizing antibody activity in sera, and the assessment of the antiviral activities of small-molecule compounds was confirmed, and it was found to be comparable to clinically applied assays. The Hec1a-IFNB-Luc reporter cell line allows the rapid and quantitative determination of antiviral effects on multiple human pathological flaviviruses using a single protocol.

3.
Biomolecules ; 14(1)2023 Dec 25.
Article in English | MEDLINE | ID: mdl-38254633

ABSTRACT

Culex quinquefasciatus resistance to the binary (Bin) toxin, the major larvicidal component from Lysinibacillus sphaericus, is associated with mutations in the cqm1 gene, encoding the Bin-toxin receptor. Downregulation of the cqm1 transcript was found in the transcriptome of larvae resistant to the L. sphaericus IAB59 strain, which produces both the Bin toxin and a second binary toxin, Cry48Aa/Cry49Aa. Here, we investigated the transcription profiles of two other mosquito colonies having Bin resistance only. These confirmed the cqm1 downregulation and identified transcripts encoding the enzyme pantetheinase as the most downregulated mRNAs in both resistant colonies. Further quantification of these transcripts reinforced their strong downregulation in Bin-resistant larvae. Multiple genes were found encoding this enzyme in Cx. quinquefasciatus and a recombinant pantetheinase was then expressed in Escherichia coli and Sf9 cells, with its presence assessed in the midgut brush border membrane of susceptible larvae. The pantetheinase was expressed as a ~70 kDa protein, potentially membrane-bound, which does not seem to be significantly targeted by glycosylation. This is the first pantetheinase characterization in mosquitoes, and its remarkable downregulation might reflect features impacted by co-selection with the Bin-resistant phenotype or potential roles in the Bin-toxin mode of action that deserve to be investigated.


Subject(s)
Amidohydrolases , Bacillaceae , Bacillus , Culex , Animals , Down-Regulation , Escherichia coli , Larva , GPI-Linked Proteins
4.
Viruses ; 15(1)2022 12 27.
Article in English | MEDLINE | ID: mdl-36680112

ABSTRACT

Bacillus thuringiensis svar. israelensis (Bti) larvicides are effective in controlling Aedes aegypti; however, the effects of long-term exposure need to be properly evaluated. We established an Ae. aegypti strain that has been treated with Bti for 30 generations (RecBti) and is still susceptible to Bti, but females exhibited increased susceptibility to Zika virus (ZIKV). This study compared the RecBti strain to a reference strain regarding: first, the relative transcription of selected immune genes in ZIKV-challenged females (F30) with increased susceptibility detected in a previous study; then, the whole transcriptomic profile using unchallenged females (F35). Among the genes compared by RT-qPCR in the ZIKV-infected and uninfected females from RecBti (F30) and the reference strain, hop, domeless, relish 1, defensin A, cecropin D, and gambicin showed a trend of repression in RecBti infected females. The transcriptome of RecBti (F35) unchallenged females, compared with a reference strain by RNA-seq, showed a similar profile and only 59 differentially expressed genes were found among 9202 genes analyzed. Our dataset showed that the long-term Bti exposure of the RecBti strain was associated with an alteration of the expression of genes potentially involved in the response to ZIKV infection in challenged females, which is an important feature found under this condition.


Subject(s)
Aedes , Bacillus thuringiensis , Zika Virus Infection , Zika Virus , Animals , Female , Bacillus thuringiensis/genetics , Larva
5.
Toxins (Basel) ; 13(8)2021 07 27.
Article in English | MEDLINE | ID: mdl-34437394

ABSTRACT

Larvicides based on the bacteria Bacillus thuringiensis svar. israelensis (Bti) and Lysinibacillus sphaericus are effective and environmentally safe compounds for the control of dipteran insects of medical importance. They produce crystals that display specific and potent insecticidal activity against larvae. Bti crystals are composed of multiple protoxins: three from the three-domain Cry type family, which bind to different cell receptors in the midgut, and one cytolytic (Cyt1Aa) protoxin that can insert itself into the cell membrane and act as surrogate receptor of the Cry toxins. Together, those toxins display a complex mode of action that shows a low risk of resistance selection. L. sphaericus crystals contain one major binary toxin that display an outstanding persistence in field conditions, which is superior to Bti. However, the action of the Bin toxin based on its interaction with a single receptor is vulnerable for resistance selection in insects. In this review we present the most recent data on the mode of action and synergism of these toxins, resistance issues, and examples of their use worldwide. Data reported in recent years improved our understanding of the mechanism of action of these toxins, showed that their combined use can enhance their activity and counteract resistance, and reinforced their relevance for mosquito control programs in the future years.


Subject(s)
Bacterial Toxins/toxicity , Mosquito Control/methods , Pest Control, Biological/methods , Animals , Bacillaceae , Bacillus thuringiensis , Culicidae
6.
J Proteomics ; 227: 103918, 2020 09 15.
Article in English | MEDLINE | ID: mdl-32712372

ABSTRACT

Bacterial insecticidal proteins, such as the Bin toxin from Lysinibacillus sphaericus, could be used more extensively to control insecticide resistant mosquitoes. This study was aimed at identification of mosquito cell proteins binding Bin toxin. Results showed that purified toxin was toxic to Anopheles gambiae larvae and Ag55 cultured cells. Clathrin heavy chain (an endocytosis protein) and glycolytic enzymes such as pyruvate kinase, enolase and dihydrolipoamide dehydrogenase were identified as binders of Bin toxin. The viability of Ag55 cells in the presence of endocytosis inhibitor, pitstop2, was significantly decreased upon Bin treatment, while the inhibitor chlorpromazine did not affect Bin toxicity. Bin toxin treatment decreased ATP production and mitochondrial respiration in Ag55 cells, whereas non-mitochondrial oxygen consumption significantly increased after Bin toxin treatment. These findings are steps towards understanding how Bin toxin kills mosquitoes. SIGNIFICANCE: Mosquitoes are vectors of pathogens causing human diseases such as dengue fever, yellow fever, zika virus and malaria. An insecticidal toxin from Lysinibacillus sphaericus called Binary, or Bin, toxin could be used more extensively to control insecticide resistant mosquitoes. Bin toxin enter cells in susceptible mosquitoes and induces apoptosis or autophagy. In the current research, we used the malaria mosquito Anopheles gambiae Ag55 cell line as a model. A proteomic-based approach identified proteins that interact with Bin toxin. Interacting proteins include clathrin heavy chain (endocytosis protein) and glycolysis enzymes such as pyruvate kinase, enolase and dihydrolipoamide dehydrogenase. In Ag55 cell toxicity assays, an endocytosis inhibitor, pitstop2, increased Bin toxicity. Real time assays with a Seahorse™ flux analyzer showed that Bin significantly affects mitochondrial respiration, a result consistent with cell death via apoptosis or autophagy. These research findings add insights into how an unusual binary protein exploits cellular machinery to kill mosquitoes.


Subject(s)
Bacterial Toxins , Culex , Malaria , Zika Virus Infection , Zika Virus , Animals , Bacillaceae , Carrier Proteins , Cell Line , Humans , Larva , Mosquito Control , Mosquito Vectors , Proteomics
7.
PLoS One ; 15(1): e0226098, 2020.
Article in English | MEDLINE | ID: mdl-31914137

ABSTRACT

The chikungunya East/Central/South/Africa virus lineage (CHIKV-ECSA) was first detected in Brazil in the municipality of Feira de Santana (FS) by mid 2014. Following that, a large number of CHIKV cases have been notified in FS, which is the second-most populous city in Bahia state, northeastern Brazil, and plays an important role on the spread to other Brazilian states due to climate conditions and the abundance of competent vectors. To better understand CHIKV dynamics in Bahia state, we generated 5 complete genome sequences from a local outbreak raised in Serraria Brasil, a neighbourhood in FS, by next-generation sequencing using Illumina approach. Phylogenetic reconstructions revealed that the new FS genomes belongs to the ECSA genotype and falls within a single strongly supported monophyletic clade that includes other older CHIKV sequences from the same location, suggesting the persistence of the virus during distinct epidemic seasons. We also performed minor variants analysis and found a small number of SNPs per sample (b_29L and e_45SR = 16 SNPs, c_29SR = 29 and d_45PL and f_45FL = 21 SNPs). Out of the 93 SNPs found, 71 are synonymous, 21 are non-synonymous and one generated a stop codon. Although those mutations are not related to the increase of virus replication and/or infectivity, some SNPs were found in non-structural proteins which may have an effect on viral evasion from the mammal immunological system. These findings reinforce the needing of further studies on those variants and of continued genomic surveillance strategies to track viral adaptations and to monitor CHIKV epidemics for improved public health control.


Subject(s)
Chikungunya Fever/epidemiology , Chikungunya virus/genetics , Chikungunya virus/physiology , Disease Outbreaks , Genotype , Residence Characteristics/statistics & numerical data , Social Class , Adult , Brazil/epidemiology , Chikungunya virus/classification , Female , Humans , Male , Phylogeny , Young Adult
8.
Infect Genet Evol ; 80: 104180, 2020 06.
Article in English | MEDLINE | ID: mdl-31918041

ABSTRACT

Zika virus (ZIKV) is a negative sense RNA virus from the Flaviviridae family, which was relatively unknown until the first human epidemic in Micronesia, in 2007. Since then, it spread to French Polynesia and the Americas. Recife, the capital of Pernambuco state and epicenter of the Zika epidemic in Brazil, experienced a large number of microcephaly cases and other congenital abnormalities associated to the ZIKV infection from, 2015 to 16. Evidences suggest that both Aedes aegypti and Culex quinquefasciatus mosquitoes from Recife are capable of replicating and transmitting the virus. Here, we conducted high throughput sequencing of ZIKV genomes directly from Ae. aegypti and Cx. quinquefasciatus mosquitoes collected during the ZIKV epidemics in Recife, in order to investigate the variability and evolution of the virus. We obtained 11 draft ZIKV genomes derived from 5 pools from each Ae. aegypti and Cx. quinquefasciatus species. Genome coverage breadth ranged from 16 to 100% and average depth from 45 to 46,584×. Two of these genomes were obtained from pools of Cx. quinquefasciatus females with no sign of blood in the abdomen. Amino acid substitutions found here were not species-specific. In addition, molecular clock dating estimated that ZIKV draft genomes obtained here were co-circulating in other regions of the country during the epidemics. Overall results highlight that viral mutations and even minor variants can be detected in genomes directly sequenced from mosquito samples and insights about natural viral genomic variability and viral evolution can be useful when designing tools for mosquito control programs.


Subject(s)
Genome, Viral , Whole Genome Sequencing , Zika Virus Infection/epidemiology , Zika Virus Infection/virology , Zika Virus/classification , Zika Virus/genetics , Aedes/virology , Animals , Brazil/epidemiology , Computational Biology/methods , Culex/virology , Epidemics , Genetic Drift , Genomics/methods , Geography, Medical , Host-Pathogen Interactions , Mosquito Vectors/virology , Phylogeny , Zika Virus/isolation & purification , Zika Virus Infection/transmission
9.
Parasit Vectors ; 12(1): 407, 2019 Aug 20.
Article in English | MEDLINE | ID: mdl-31429782

ABSTRACT

BACKGROUND: The study of the mechanisms by which larvae of the Culex quinquefasciatus mosquito survive exposure to the entomopathogen Lysinibacillus sphaericus has benefited substantially from the generation of laboratory-selected colonies resistant to this bacterium. One such colony, RIAB59, was selected after regular long-term exposure of larvae to the L. sphaericus IAB59 strain. This strain is characterized by its ability to produce the well known Binary (Bin) toxin, and the recently characterized Cry48Aa/Cry49Aa toxin, able to kill Bin-resistant larvae. Resistance to Bin is associated with the depletion of its receptor, Cqm1 α-glucosidase, from the larvae midgut. This study aimed to identify novel molecules and pathways associated with survival of the RIAB59 larvae and the resistance phenotype. METHODS: A transcriptomic approach and bioinformatic tools were used to compare the profiles derived from the midguts of larvae resistant and susceptible to L. sphaericus IAB59. RESULTS: The RNA-seq profiles identified 1355 differentially expressed genes (DEGs), with 673 down- and 682 upregulated transcripts. One of the most downregulated DEGs was cqm1, which validates the approach. Other strongly downregulated mRNAs encode the enzyme pantetheinase, apolipoprotein D, lipases, heat-shock proteins and a number of lesser known and hypothetical polypeptides. Among the upregulated DEGs, the top most encodes a peroxisomal enzyme involved in lipid metabolism, while others encode enzymes associated with juvenile hormone synthesis, ion channels, DNA binding proteins and defense polypeptides. Further analyses confirmed a strong downregulation of several enzymes involved in lipid catabolism while the assignment of DEGs into metabolic pathways highlighted the upregulation of those related to DNA synthesis and maintenance, confirmed by their clustering into related protein networks. Several other pathways were also identified with mixed profiles of down- and upregulated transcripts. Quantitative RT-PCR confirmed the changes in levels seen for selected mRNAs. CONCLUSIONS: Our transcriptome-wide dataset revealed that the RIAB59 colony, found to be substantially more resistant to Bin than to the Cry48Aa/Cry49Aa toxin, developed a differential expression profile as well as metabolic features co-selected during the long-term adaptation to IAB59 and that are most likely linked to Bin resistance.


Subject(s)
Bacillus/pathogenicity , Culex/genetics , Culex/microbiology , Disease Resistance/genetics , Animals , Bacterial Toxins/metabolism , Computational Biology , Digestive System/enzymology , Female , Gene Expression Profiling , Genes, Insect , Larva/genetics , Larva/microbiology , Phenotype , RNA-Seq , alpha-Glucosidases/metabolism
10.
Rev. psiquiatr. clín. (São Paulo) ; 44(6): 149-153, Nov.-Dec. 2017. graf
Article in English | LILACS | ID: biblio-903047

ABSTRACT

Abstract Background: Recent evidence has shown improvements in schizophrenia symptoms after the infusion of sodium nitroprusside (SNP), a nitric oxide (NO) donor. In the rat model of schizophrenia using ketamine injection, pretreatment with SNP seems to prevent behavioral changes associated with positive symptoms for up to one week. Objective: We investigated whether SNP would have preventative effects on psychogenic symptoms induced by ketamine in healthy subjects. Methods: Healthy subjects (N = 38) were assigned to distinct groups that received SNP in different doses (0.15, 0.25, and 0.5 mcg/kg/min). First, participants received an infusion of SNP or placebo over 75 minutes. After 10 minutes, they were injected for 1 minute with a bolus of 0.26 mg/kg of ketamine and a maintenance dose was started 5 minutes later, with 0.25 mg/kg/h of ketamine for 50 minutes. Results: Ketamine-induced psychopathological alterations induced were reduced by SNP, as assessed with the Brief Psychological Rating Scale. Scores in the objective subscale of the Clinician-Administered Dissociative States Scale were also lower in SNP sessions compared to placebo. SNP had protective effects against deterioration in facial emotion and identity recognition tasks induced by ketamine. Discussion: Our findings support the view that SNP has preventative properties against psychotic manifestations.

12.
Insect Biochem Mol Biol ; 88: 63-70, 2017 09.
Article in English | MEDLINE | ID: mdl-28780070

ABSTRACT

A binary mosquitocidal toxin composed of a three-domain Cry-like toxin (Cry48Aa) and a binary-like toxin (Cry49Aa) was identified in Lysinibacillus sphaericus. Cry48Aa/Cry49Aa has action on Culex quinquefasciatus larvae, in particular, to those that are resistant to the Bin Binary toxin, which is the major insecticidal factor from L. sphaericus-based biolarvicides, indicating that Cry48Aa/Cry49Aa interacts with distinct target sites in the midgut and can overcome Bin toxin resistance. This study aimed to identify Cry48Aa/Cry49Aa ligands in C. quinquefasciatus midgut through binding assays and mass spectrometry. Several proteins, mostly from 50 to 120 kDa, bound to the Cry48Aa/Cry49Aa toxin were revealed by toxin overlay and pull-down assays. These proteins were identified against the C. quinquefasciatus genome and after analysis a set of 49 proteins were selected which includes midgut bound proteins such as aminopeptidases, amylases, alkaline phosphatases in addition to molecules from other classes that can be potentially involved in this toxin's mode of action. Among these, some proteins are orthologs of Cry receptors previously identified in mosquito larvae, as candidate receptors for Cry48Aa/Cry49Aa toxin. Further investigation is needed to evaluate the specificity of their interactions and their possible role as receptors.


Subject(s)
Bacterial Proteins/metabolism , Culex/enzymology , Endotoxins/metabolism , Hemolysin Proteins/metabolism , Insecticides/metabolism , Animals , Bacillus thuringiensis Toxins , Culex/genetics , Gastrointestinal Tract/enzymology , Larva/enzymology , Ligands
13.
Emerg Microbes Infect ; 6(8): e69, 2017 Aug 09.
Article in English | MEDLINE | ID: mdl-28790458

ABSTRACT

Zika virus (ZIKV) is a flavivirus that has recently been associated with an increased incidence of neonatal microcephaly and other neurological disorders. The virus is primarily transmitted by mosquito bite, although other routes of infection have been implicated in some cases. The Aedes aegypti mosquito is considered to be the main vector to humans worldwide; however, there is evidence that other mosquito species, including Culex quinquefasciatus, transmit the virus. To test the potential of Cx. quinquefasciatus to transmit ZIKV, we experimentally compared the vector competence of laboratory-reared Ae. aegypti and Cx. quinquefasciatus. Interestingly, we were able to detect the presence of ZIKV in the midgut, salivary glands and saliva of artificially fed Cx. quinquefasciatus. In addition, we collected ZIKV-infected Cx. quinquefasciatus from urban areas with high microcephaly incidence in Recife, Brazil. Corroborating our experimental data from artificially fed mosquitoes, ZIKV was isolated from field-caught Cx. quinquefasciatus, and its genome was partially sequenced. Collectively, these findings indicate that there may be a wider range of ZIKV vectors than anticipated.


Subject(s)
Culex/virology , Mosquito Vectors/virology , Virus Replication , Zika Virus/physiology , Aedes/virology , Animals , Brazil/epidemiology , Genome, Viral , Humans , Microcephaly/epidemiology , Mosquito Vectors/physiology , Saliva/virology , Salivary Glands/virology , Sequence Analysis, DNA , Zika Virus/genetics , Zika Virus/isolation & purification , Zika Virus Infection/epidemiology , Zika Virus Infection/transmission , Zika Virus Infection/virology
14.
Ther Adv Psychopharmacol ; 3(2): 83-8, 2013 Apr.
Article in English | MEDLINE | ID: mdl-24167679

ABSTRACT

BACKGROUND: Dengue is a febrile illness that is most common in tropical areas but is recognized worldwide as one of the most important arbovirus diseases of humans. This febrile illness generally has a course with mild alterations in white blood cell count, but there are also rare cases of severe neutropenia or agranulocytosis during dengue infection. Clozapine (CLZ) remains the most effective treatment for schizophrenia, but because of its poor side effect profile, in particular due to the increased risk of neutropenia and agranulocytosis, it is generally used for patients whose condition responds poorly to other antipsychotics. METHODS: We report three cases of dengue infection in patients with refractory schizophrenia who were using CLZ, and we discuss the implications of this infection on the continuation of CLZ treatment in these patients. RESULTS: Of these three cases with dengue infection and co-occurence of CLZ use, the first would be classified as severe neutropenia and the second as moderate leucopenia; the last case had a white blood cell (WBC) count inside the normal range, and had no need to change his antipsychotic. The first and the second patient presented a worsening in their schizophrenic psychopathologies, after CLZ withdrawal, evolving into catatonic states, that were reverted after the careful reintroduction of CLZ. DISCUSSION: It is very likely that during dengue epidemics many patients with schizophrenia and using CLZ have their treatment permanently discontinued given WBC count concerns, causing relapse of symptoms of schizophrenia and impairment of quality of life of these patients.This is the first report of neutropenia cases among CLZ-treated patients during dengue infection that describes the withdrawal of CLZ and its successful readministration.

15.
Braz. J. Psychiatry (São Paulo, 1999, Impr.) ; 34(supl.2): s149-s155, Oct. 2012. tab
Article in English | LILACS | ID: lil-662765

ABSTRACT

For the last 40 years, schizophrenia has been considered to be the result primarily of a dysfunction in brain dopaminergic pathways. In this review, it is described and discussed findings concerning nitric oxide-mediated neurotransmission in schizophrenia. Studies were searched in PubMed, SciELO, and LILACS using the terms schizophrenia and nitric oxide plasma levels or nitric oxide serum levels, with no time limit. The reference lists of selected articles were also hand-searched for additional articles. From 15 potential reports, 10 were eligible to be included in the review and meta-analysis. These studies included a total of 505 patients with schizophrenia and 339 healthy volunteers. No significant difference was found between patients and healthy controls regarding total nitrite plasma/serum levels (effect size g = 0.285, 95%CI = -0.205 to 0.774, p = 0.254). However, when studies with patients under antipsychotic treatment were examined separately, there was a significant difference between patients and healthy volunteers (effect size g = 0.663, 95%CI = 0.365 to 0.961, p < 0.001), showing that patients under treatment have higher levels of plasma/serum nitric oxide than controls. These results suggest that antipsychotics increase nitric oxide plasma/serum levels and that the nitrergic pathway would be a fertile target for the development of new treatments for patients with schizophrenia.


Durante os últimos 40 anos, a esquizofrenia foi considerada, principalmente, como o resultado de disfunções dopaminérgicas no cérebro. Esta revisão descreve e discute algumas descobertas sobre a neurotransmissão mediada pelo óxido nítrico na esquizofrenia. A busca foi feita nas bases PubMed, SciELO e LILACS usando-se os termos schizophrenia e nitric oxide plasma levels ou nitric oxide serum levels, sem limites de tempo. As listas de referências dos artigos selecionados foram examinadas em busca de outras publicações pertinentes. Dentre 15 artigos passíveis de serem incluídos, 10 preenchiam os critérios estabelecidos para a revisão e metanálise. Esses estudos incluíram 505 pacientes com esquizofrenia e 339 voluntários saudáveis. Não foram encontradas diferenças significativas entre pacientes e voluntários saudáveis quanto aos níveis plasmáticos de nitrito total (effect size g = 0,285, IC 95% = -0,205 a 0,774, p = 0,254). No entanto, o exame separado dos estudos envolvendo pacientes em tratamento antipsicótico apresentou diferenças significativas entre pacientes e voluntários saudáveis (effect size g = 0,663, IC 95% = 0,365 to 0,961, p < 0,001), demonstrando que pacientes em tratamento possuem níveis plasmáticos mais altos de óxido nítrico. Esses resultados sugerem que os antipsicóticos podem aumentar os níveis plasmáticos de óxido nítrico e que a via nitrérgica (e sua estimulação) constituiria um alvo propício para o desenvolvimento de novos tratamentos para pacientes com esquizofrenia.


Subject(s)
Humans , Nitric Oxide/blood , Schizophrenia/blood , Antipsychotic Agents/pharmacology , Data Interpretation, Statistical , Empirical Research , Schizophrenia/drug therapy , Schizophrenia/physiopathology
16.
Braz J Psychiatry ; 34 Suppl 2: S149-55, 2012 Oct.
Article in English, Portuguese | MEDLINE | ID: mdl-23429845

ABSTRACT

For the last 40 years, schizophrenia has been considered to be the result primarily of a dysfunction in brain dopaminergic pathways. In this review, it is described and discussed findings concerning nitric oxide-mediated neurotransmission in schizophrenia. Studies were searched in PubMed, SciELO, and LILACS using the terms schizophrenia and nitric oxide plasma levels or nitric oxide serum levels, with no time limit. The reference lists of selected articles were also hand-searched for additional articles. From 15 potential reports, 10 were eligible to be included in the review and meta-analysis. These studies included a total of 505 patients with schizophrenia and 339 healthy volunteers. No significant difference was found between patients and healthy controls regarding total nitrite plasma/serum levels (effect size g = 0.285, 95%CI = -0.205 to 0.774, p = 0.254). However, when studies with patients under antipsychotic treatment were examined separately, there was a significant difference between patients and healthy volunteers (effect size g = 0.663, 95%CI = 0.365 to 0.961, p < 0.001), showing that patients under treatment have higher levels of plasma/serum nitric oxide than controls. These results suggest that antipsychotics increase nitric oxide plasma/serum levels and that the nitrergic pathway would be a fertile target for the development of new treatments for patients with schizophrenia.


Subject(s)
Nitric Oxide/blood , Schizophrenia/blood , Antipsychotic Agents/pharmacology , Data Interpretation, Statistical , Empirical Research , Humans , Schizophrenia/drug therapy , Schizophrenia/physiopathology
17.
Arch Gerontol Geriatr ; 51(1): 41-4, 2010.
Article in English | MEDLINE | ID: mdl-19665807

ABSTRACT

The aim of this study was to determine whether age influences the concordance between different methods of blood pressure (BP) measurement and ambulatory BP monitoring (ABPM) in hypertensive subjects. We studied two groups: I, individuals younger than 50 years (n=57), and II, individuals aged 60 years or older (n=55). They were submitted to the performance of one ABPM, office BP measurements, home BP monitoring (HBPM), and BP measurements at a public health center (PHCBP). Student's t-test, Fisher's test and Lin coefficient were calculated. For Group II, systolic and diastolic pressures measured by HBPM were higher than by day ABPM (p<0.01). The concordance between day ABPM and the other methods was lower for Group II than for Group I. There was a good concordance between systolic day ABPM and office BP, and between systolic ABPM and PHCBP only for Group I (Lin coefficient=0.71 and 0.73). Group II reported better sleep quality after ABPM (p<0.05). Considering 24-h ABPM, 52.6% of Group I and 29% of Group II were controlled (p<0.01). Concluding, there was worse concordance between different methods of BP measurements and day ABPM in the older group, which had lower hypertension control rate and better tolerance of ABPM.


Subject(s)
Aging/physiology , Hypertension/diagnosis , Hypertension/epidemiology , Age Factors , Female , Humans , Male , Middle Aged , Severity of Illness Index
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