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1.
Sci Rep ; 14(1): 7249, 2024 03 27.
Artigo em Inglês | MEDLINE | ID: mdl-38538661

RESUMO

Malaria is the leading parasitic disease worldwide, with P. vivax being a major challenge for its control. Several studies have indicated metabolomics as a promising tool for combating the disease. The study evaluated plasma metabolomic profiles of patients with recurrent and non-recurrent P. vivax malaria in the Brazilian Amazon. Metabolites extracted from the plasma of P. vivax-infected patients were subjected to LC-MS analysis. Untargeted metabolomics was applied to investigate the metabolic profile of the plasma in the two groups. Overall, 51 recurrent and 59 non-recurrent patients were included in the study. Longitudinal metabolomic analysis revealed 52 and 37 significant metabolite features from the recurrent and non-recurrent participants, respectively. Recurrence was associated with disturbances in eicosanoid metabolism. Comparison between groups suggest alterations in vitamin B6 (pyridoxine) metabolism, tyrosine metabolism, 3-oxo-10-octadecatrienoate ß-oxidation, and alkaloid biosynthesis II. Integrative network analysis revealed enrichment of other metabolic pathways for the recurrent phenotype, including the butanoate metabolism, aspartate and asparagine metabolism, and N-glycan biosynthesis. The metabolites and metabolic pathways predicted in our study suggest potential biomarkers of recurrence and provide insights into targets for antimalarial development against P. vivax.


Assuntos
Antimaláricos , Malária Vivax , Malária , Humanos , Malária Vivax/parasitologia , Metabolômica , Malária/parasitologia , Metaboloma , Antimaláricos/uso terapêutico
2.
Vet Res Commun ; 48(3): 1409-1421, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38305959

RESUMO

The microbiome plays a significant role in shaping the health and functioning of the systems it inhabits. The seminal microbiome of stallions has implications for the health of the reproductive tract, sperm quality during preservation and antibiotic use in semen extenders. Diverse bacteria are present on the external genital tract and a mix of commensal microorganisms populates various parts of the reproductive tract, influencing the seminal bacterial content. Other sources of bacteria include the environment, semen collection equipment, and personnel. The bacterial load can adversely affect sperm quality and fertility, particularly in artificial insemination, where semen is extended and stored before use. Antibiotics are frequently used to inhibit bacterial growth, but their effectiveness varies depending on the bacterial strains present. The aim of this study was to assess the bacterial diversity in semen from 37 healthy stallions across three European nations (Germany, Portugal, and Sweden) using 16S sequencing. Semen samples were collected from individual stallions at three AI centers; DNA extraction, sequencing, and bioinformatic analysis were performed. Differences in bacterial diversity among the stallions were seen; although bacterial phyla were shared across the regions, differences were observed at the genus level. Climate, husbandry practices, and individual variability likely contribute to these differences. These findings underscore the importance of tailoring antibiotic strategies for semen preservation based on regional bacterial profiles. The study presents a comprehensive approach to understanding the intricacies of the stallion seminal microbiome and its potential implications for reproductive technologies and animal health.


Assuntos
Bactérias , RNA Ribossômico 16S , Sêmen , Animais , Masculino , Cavalos/microbiologia , Sêmen/microbiologia , Bactérias/isolamento & purificação , Bactérias/classificação , Bactérias/genética , RNA Ribossômico 16S/genética , Microbiota , Suécia , Portugal , Alemanha
3.
Nucl Med Commun ; 45(2): 155-160, 2024 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-38010319

RESUMO

Radionuclide ventriculography or Multi Gated Acquisition (MUGA) employing [ 99m Tc]Technetium red blood cell (RBC) labeling is considered the gold standard for cardiotoxicity assessments in cancer patients undergoing chemotherapy. This in-vivo RBC labeling technique involves the reduction of [ 99m Tc]Technetium by the stannous chloride present in freeze-dried reagent kits, with the pyrophosphate kit (PYP) being the most employed for this purpose. The literature, however, describes diethylenetriaminepentaacetic acid (DTPA) as an alternative to PYP, although a lack of comparative data from MUGA images between both reagents is noted. A retrospective cross-sectional observational study was conducted at the Brazilian National Cancer Institute Nuclear Medicine Service concerning 80 randomized MUGA images, 20 obtained employing DTPA between 2020 and 2023 and 60 obtained employing PYP between 2017 and 2020, applying the mean count per pixel (ct/pixel) and heart background (C/F) ratios as quality image indicators. Although the heart ct/pixel ratio was statistically lower in the DTPA images compared with PYP ( P  = 0.02), the C/F ratio was statistically similar when comparing both radiopharmaceuticals ( P  = 0.697). A semi-quantitative analysis of MUGA images obtained with DTPA and PYP indicates similar image quality, supporting the use of DTPA as an alternative to PYP without compromising diagnostic interpretations.


Assuntos
Compostos Radiofarmacêuticos , Tecnécio , Humanos , Estudos Transversais , Estudos Retrospectivos , Ventriculografia com Radionuclídeos , Ácido Pentético , Eritrócitos
4.
Aust Endod J ; 50(1): 60-68, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-37876340

RESUMO

This study evaluated the impact of long-term storage conditions (medium and time) on the development of experimental dentinal microcracks through micro-computed tomography. Sixty freshly extracted premolars were stored in formalin, water, or dry conditions (n = 20) and scanned after 72 h, 30 days, 6 months and 3 years of extraction. The effect of the storage medium and time on the occurrence of dentinal defects was statistically evaluated. A total of 211 000 images were screened revealing the existence of 11 519 slices with dentinal defects. Dry conditions significantly contributed to the development of new defects in all time points. During the 3-year follow-up period, no new defects were detected in the teeth that were stored in water and, in a single tooth, in the formalin group, after 6 months of storage.


Assuntos
Fraturas dos Dentes , Humanos , Dentina/diagnóstico por imagem , Microtomografia por Raio-X , Preparo de Canal Radicular , Água , Formaldeído
5.
mSystems ; 8(6): e0072623, 2023 Dec 21.
Artigo em Inglês | MEDLINE | ID: mdl-37874139

RESUMO

IMPORTANCE: The SARS-CoV-2 virus infection in humans induces significant inflammatory and systemic reactions and complications of which corticosteroids like methylprednisolone have been recommended as treatment. Our understanding of the metabolic and metabolomic pathway dysregulations while using intravenous corticosteroids in COVID-19 is limited. This study will help enlighten the metabolic and metabolomic pathway dysregulations underlying high daily doses of intravenous methylprednisolone in COVID-19 patients compared to those receiving placebo. The information on key metabolites and pathways identified in this study together with the crosstalk with the inflammation and biochemistry components may be used, in the future, to leverage the use of methylprednisolone in any future pandemics from the coronavirus family.


Assuntos
COVID-19 , Humanos , Metilprednisolona/efeitos adversos , SARS-CoV-2 , Administração Intravenosa , Corticosteroides/efeitos adversos
6.
J Endod ; 49(12): 1722-1732, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37717910

RESUMO

INTRODUCTION: This study aimed to assess the canal transportation with 6 preparation systems. METHODS: Sixty curved mesial roots of mandibular molars were scanned, and their root canals (n = 20 per group) were prepared with XP-endo Shaper, BioRace, ProTaper Next, Twisted File Adaptive, Reciproc, or Reciproc Blue systems. After preparation, a new scan was conducted, and transportation was determined by comparing the geometric center of the canal in 13,542 cross-sectional slices. The transport direction frequencies were recorded, and linear transport were compared using a Univariate GLM model and Tukey honestly significant difference tests (α = 5 %). RESULTS: Transportation was affected by the preparation system and root third (P < .05), with no significant effect observed for the root canal (P > .05). The Twisted File Adaptive had the highest transport (P < .05), and the lowest transports were observed with XP-endo Shaper, ProTaper Next, and BioRace (P < .05). Reciproc Blue and Reciproc showed intermediate results (P < .05). The apical and coronal third exhibited the lowest and highest transportation, respectively (P < .05). A significant interaction was observed between the preparation system and root third (P < .05). In the coronal third, transportation was mostly toward the disto-inside direction, whereas in the middle and apical thirds, transportation was predominantly toward the mesio-outside direction. CONCLUSIONS: XP-endo Shaper had the lowest mean linear transportation followed by the ProTaper Next, BioRace, Reciproc Blue, and Reciproc systems. The Twisted File Adaptive system had the worst performance. The direction of transportation was generally toward the inner aspect of the canal at the coronal third and toward the outer aspect of the curve at the middle and apical thirds.


Assuntos
Cavidade Pulpar , Preparo de Canal Radicular , Cavidade Pulpar/diagnóstico por imagem , Preparo de Canal Radicular/métodos , Microtomografia por Raio-X/métodos , Estudos Transversais , Tratamento do Canal Radicular , Desenho de Equipamento
7.
Endocrinol Diabetes Metab ; 6(6): e445, 2023 11.
Artigo em Inglês | MEDLINE | ID: mdl-37697708

RESUMO

BACKGROUND: Nonfunctioning pituitary adenomas (NFPAs) constitute one of the most common tumours in the sellar region and are often discovered only when associated with compressive symptoms. With the frequent use of brain imaging, there has been an increase in the prevalence of incidentally discovered NFPAs. AIM: We aim to determine the prevalence of incidental diagnosis with NPAs observed over a decade and compare the analytical, clinical and treatment differences between those who were diagnosed either incidentally or symptomatically. We also intend to evaluate the pathology differences between both groups. METHODS: We retrospectively analysed patients aged ≥18 years with an apparent NFPA, defined as a pituitary lesion compatible with pituitary adenoma which is not associated with the clinical or biochemical evidence of a hormone-secreting tumour. Inclusion criteria included normal prolactin level for lesions <9 mm or a prolactin level <100 ng/mL for lesions ≥10 mm in maximal tumour diameter. RESULTS: We included 119 patients [53.8% males; mean age: 56.8 years (SD = 16.7)]. Diagnosis was incidental in 47.1% of patients, and many patients had unappreciated signs and symptoms of pituitary disease. In the symptomatic and incidental groups, 66.7% and 41.1% of patients had hypopituitarism, respectively (p = .005). Only 20.4% of patients incidentally diagnosed had microadenoma (p = .060). Hypopituitarism was present in 18.8% of those patients with microadenomas. Most tumours were macroadenomas (87.4%). Half of those patients diagnosed incidentally were submitted to surgery, compared with 75.8% of those who were diagnosed symptomatically (p = .004). CONCLUSIONS: Nonfunctioning pituitary adenomas are commonly diagnosed incidentally, with many manifesting symptoms on examination. NFPAs incidentally diagnosed are more commonly macroadenomas and less frequently associated with hypopituitarism than symptomatic. Accordingly, if there was a greater level of knowledge and more suspicion about these pathologies, it might be possible to discover them earlier.


Assuntos
Adenoma , Hipopituitarismo , Neoplasias Hipofisárias , Masculino , Humanos , Adolescente , Adulto , Pessoa de Meia-Idade , Feminino , Neoplasias Hipofisárias/diagnóstico , Neoplasias Hipofisárias/epidemiologia , Neoplasias Hipofisárias/complicações , Prolactina/uso terapêutico , Estudos Retrospectivos , Adenoma/diagnóstico , Adenoma/epidemiologia , Adenoma/patologia , Hipopituitarismo/diagnóstico , Hipopituitarismo/epidemiologia , Hipopituitarismo/etiologia
8.
Int J Mol Sci ; 24(13)2023 Jul 06.
Artigo em Inglês | MEDLINE | ID: mdl-37446332

RESUMO

Biochar-amended soils influence the degradation of herbicides depending on the pyrolysis temperature, application rate, and feedstock used. The objective of this study was to evaluate the influence of sugarcane straw biochar (BC) produced at different pyrolysis temperatures (350 °C, 550 °C, and 750 °C) and application rates in soil (0, 0.1, 0.5, 1, 1.5, 5, and 10% w/w) on metribuzin degradation and soil microbiota. Detection analysis of metribuzin in the soil to find time for 50% and 90% metribuzin degradation (DT50 and DT90) was performed using high-performance liquid chromatography (HPLC). Soil microbiota was analyzed by respiration rate (C-CO2), microbial biomass carbon (MBC), and metabolic quotient (qCO2). BC350 °C-amended soil at 10% increased the DT50 of metribuzin from 7.35 days to 17.32 days compared to the unamended soil. Lower application rates (0.1% to 1.5%) of BC550 °C and BC750 °C decreased the DT50 of metribuzin to ~4.05 and ~5.41 days, respectively. BC350 °C-amended soil at high application rates (5% and 10%) provided high C-CO2, low MBC fixation, and high qCO2. The addition of low application rates (0.1% to 1.5%) of sugarcane straw biochar produced at high temperatures (BC550 °C and BC750 °C) resulted in increased metribuzin degradation and may influence the residual effect of the herbicide and weed control efficiency.


Assuntos
Herbicidas , Poluentes do Solo , Temperatura , Dióxido de Carbono/análise , Solo/química , Pirólise , Poluentes do Solo/metabolismo , Herbicidas/química , Carvão Vegetal/química
9.
Theriogenology ; 208: 43-51, 2023 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-37295289

RESUMO

The objectives of this study were to establish baseline information for seminal traits in Lusitano stallions, to assess the impact of inbreeding, interval between collections and age on semen quality during the breeding and non-breeding seasons, and to estimate the corresponding genetic parameters. A total of 2129 ejaculates by 146 Lusitano stallions used for artificial insemination, obtained from four equine reproduction centers distributed throughout Portugal, over a period of 14 years (2008-2021), were included in the study. The seminal traits analyzed, and the corresponding means and standard deviations, were gel-free volume (56.95 ± 28.76 mL), concentration (186.48 ± 104.68 × 106), motility (64.1 ± 16.9%), total number of spermatozoa (TNS) (9.271 ± 4.956 × 109) and total number of motile spermatozoa per ejaculate (TNMS) (5.897 ± 3.587 × 109). These results are in the normal range of values described for other breeds. In the stallions analyzed, the mean value for the inbreeding coefficient was 7.93 ± 5.29%, and for age it was 12.70 ± 6.83 years. A significant decline in sperm concentration, motility, TNS, and TNMS was observed as inbreeding increased. The season also influenced sperm concentration, motility, TNS and TNMS, with the highest values observed during the breeding season. When considering the impact of age on Lusitano seminal parameters, results showed a nonlinear relationship, with a positive effect until 18 years of age for volume, motility, TNS and TNMS and a negative effect after this age, with a slow decrease. However, age had a markedly negative effect on sperm concentration. The interval between semen collections only affected (P < 0.05) sperm motility, with a regression coefficient of +1.89 ± 2.17% per additional day. Genetic parameters were estimated with an Animal Model, and the estimated heritability (repeatability) was 0.27 (0.35) for volume, 0.02 (0.38) for sperm concentration, 0.24 (0.44) for motility, 0.29 (0.39) for TNS and 0.41 (0.41) for TNMS. These results suggest that it is possible to improve semen quality by selection and that the properties of semen produced by a stallion tend to remain consistent throughout its lifetime. Furthermore, the impact of inbreeding should be taken into consideration when selecting Lusitano stallions for fertility.


Assuntos
Endogamia , Análise do Sêmen , Masculino , Animais , Cavalos/genética , Análise do Sêmen/veterinária , Sêmen , Motilidade dos Espermatozoides/genética , Contagem de Espermatozoides/veterinária
10.
Reprod Domest Anim ; 58(8): 1161-1163, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-37289190

RESUMO

This short communication describes a case of a 30-year-old stallion with a mass on the base of the penis causing paraphimosis. The patient was submitted to anti-inflammatory and diuretic therapy with no signs of improvement, so 16 days after the lesion was detected, the animal was euthanized. Necropsy was performed, and histopathological assessment of the lesion was conducted. The mass was composed primarily of channels and cavernous structures, lined by elongated cells of vascular origin, located in the preputium. The lesion was diagnosed as a preputial lymphangioma. To the authors' best knowledge, the anatomical location of this neoplasm (which is rare in veterinary medicine) has not been previously reported.


Assuntos
Doenças dos Cavalos , Linfangioma , Masculino , Animais , Cavalos , Linfangioma/cirurgia , Linfangioma/veterinária , Linfangioma/diagnóstico , Prepúcio do Pênis , Pênis/patologia , Doenças dos Cavalos/cirurgia
11.
Front Vet Sci ; 10: 1145742, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37065254

RESUMO

A 30-year-old Lusitano stallion presented with an enlarged right epididymis. The ultrasound scan revealed a cyst-like formation and the histopathological examination was compatible with epididymal cyst located at the body/tail transition, epididymal spermatocele and sperm granuloma and epididymitis. However, these conditions did not seem to affect the animal's reproductive performance, nor did the semen parameters analyzed over the 8 years after the diagnosis show significant changes. Nevertheless, since the ejaculate contains mostly sperm cells from the tail of the epididymis, where fertile spermatozoa are stored until ejaculated, a deep knowledge of the different conditions that can affect this organ is of the utmost importance.

12.
Chemosphere ; 308(Pt 1): 136250, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36057359

RESUMO

Biomass valorization is essential, particularly in emerging countries. Here, hydrochar from arabica coffee straw was functionalized with a triazole group (HD-TRz) for use as a support of palladium nanoparticles (PdNPs-HD-TRz) applied in the Ullmann coupling reaction for the first time. It provided remarkably excellent selectivities, conversions at a temperature as low as 45 °C and catalyst recyclability, surpassing previous literature performances. Hydrochar was obtained by one-pot reaction via hydrothermal synthesis, using NaOH solution as activating agent and functionalized with a 1,3-triazole group by CuAAC "click" reaction. The PdNPs were prepared via reduction of hydrochar-bound Pd(II) using NaBH4. Hydrochar functionalization was monitored by infrared spectroscopy, and X-ray diffraction (XRD) allowed to observe carbon and palladium planes in hydrochar and PdNPs HD-TRz structures. The PdNPs presented a spherical shape with 2.1 ± 0.1 nm size, homogeneously distributed in the carbon coverslips. The HD-TRz-supported PdNPs were used as a catalyst in the Ullmann reaction of iodobenzene, using ethanol as solvent with 100% of conversion and 91% selectivity at 45 °C. The material was reused, presenting 100% of conversion and selectivities of 92, 84 and 73% for the 1st, 2nd and 3rd cycle, respectively. The scope of the reaction was expanded to other molecules showing the potential of this and other triazole-hydrochar-supported nanocatalysts.


Assuntos
Iodobenzenos , Nanopartículas Metálicas , Carbono , Café , Etanol , Nanopartículas Metálicas/química , Paládio/química , Hidróxido de Sódio , Solventes , Triazóis
13.
PLoS One ; 17(8): e0272846, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35969526

RESUMO

BACKGROUND: Clinical Decision Support Systems (CDSS) are used to assist the decision-making process in the healthcare field. Developing an effective CDSS is an arduous task that can take advantage from prior assessment of the most promising theories, techniques and methods used at the present time. OBJECTIVE: To identify the features of Clinical Decision Support Systems and provide an analysis of their effectiveness. Thus, two research questions were formulated: RQ1-What are the most common trend characteristics in a CDSS? RQ2-What is the maturity level of the CDSS based on the decision-making theory proposed by Simon? METHODS: AIS e-library, Decision Support Systems journal, Nature, PlosOne and PubMed were selected as information sources to conduct this systematic literature review. Studies from 2000 to 2020 were chosen covering search terms in CDSS, selected according to defined eligibility criteria. The data were extracted and managed in a worksheet, based on the defined criteria. PRISMA statements were used to report the systematic review. RESULTS: The outcomes showed that rule-based module was the most used approach regarding knowledge management and representation. The most common technological feature adopted by the CDSS were the recommendations and suggestions. 19,23% of studies adopt the type of system as a web-based application, and 51,92% are standalone CDSS. Temporal evolution was also possible to visualize. This study contributed to the development of a Maturity Staging Model, where it was possible to verify that most CDSS do not exceed level 2 of maturity. CONCLUSION: The trend characteristics addressed in the revised CDSS were identified, compared to the four predefined groups. A maturity stage model was developed based on Simon's decision-making theory, allowing to assess the level of maturity of the most common features of the CDSS. With the application of the model, it was noticed that the phases of choice and implementation are underrepresented. This constitutes the main gap in the development of an effective CDSS.


Assuntos
Sistemas de Apoio a Decisões Clínicas , Software
14.
Porto Biomed J ; 7(6): e186, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-37152080

RESUMO

Background: KPC-producing K pneumoniae (KPC-Kp) is a public health problem with important clinical and epidemiological implications. We describe an outbreak of KPC-Kp at vascular surgery and neurosurgery wards in a central hospital in Porto, Portugal. Methods: A case of KPC-Kp was considered to be a patient positive for KPC-Kp with strong epidemiological plausibility of having acquired this microorganism in the affected wards and/or with genetic relationship ≥92% between KPC-Kp isolates. Active surveillance cultures (ASCs) and real-time polymerase chain reaction were used for the detection of carbapenemase genes through rectal swab in a selected population. Molecular analysis was performed using pulsed-field gel electrophoresis at the National Reference Laboratory. Patient risk factors were collected from the electronic medical record system. Information regarding outbreak containment strategy was collected from the Infection Control Unit records. Results: Of the 16 cases, 11 (69%) were identified through active screening, representing 1.4% of the total 766 ASCs collected. The most frequent risk factors identified were previous admission (63%), antibiotic exposure in the past 6 months (50%), and immunodepression (44%). The length of stay until KPC-Kp detection was high (0-121 days, mean 35.6), as was the total length of stay (5-173 days, mean 56.6). Three patients (19%) were infected by KPC-Kp, 2 of whom died. One previously colonized patient died later because of KPC-Kp infection. Conclusions: Multifactorial strategy based on contact precautions (with patient and healthcare professional cohorts) and ASC, as well as Antibiotic Stewardship Program reinforcement, allowed to contain this KPC-Kp outbreak.

15.
Braz. J. Psychiatry (São Paulo, 1999, Impr.) ; 43(5): 484-493, Sept.-Oct. 2021. tab, graf
Artigo em Inglês | LILACS | ID: biblio-1345467

RESUMO

Objective: Major depressive disorder (MDD) is related to glutamatergic dysfunction. Antagonists of glutamatergic N-methyl-D-aspartate receptor (NMDAR), such as ketamine, have antidepressant properties. Nitrous oxide (N2O) is also a NMDAR antagonist. Thus, this study aimed to evaluate the effects of augmenting antidepressant treatment with N2O. Methods: This double blind, placebo-controlled randomized parallel pilot trial was conducted from June 2016 to June 2018 at the Hospital das Clínicas, Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo. Twenty-three subjects with MDD (aged 18 to 65, on antidepressants, with a score > 17 on the 17-item-Hamilton Depression Rating Scale [HAM-D17]) received 50% N2O (n=12; 37.17±13.59 years) or placebo (100% oxygen) (n=11; 37.18±12.77 years) for 60 minutes twice a week for 4 weeks. The primary outcome was changes in HAM-D17 from baseline to week 4. Results: Depressive symptoms improved significantly in the N2O group (N2O: from 22.58±3.83 to 5.92±4.08; placebo: from 22.44±3.54 to 12.89±5.39, p < 0.005). A total of 91.7% and 75% of the N2O group subjects achieved response (≥ 50% reduction in HAM-D17 score) and remission (HAM-D17 < 7), respectively. The predominant adverse effects of N2O treatment were nausea, vomiting, and headache. Conclusion: N2O treatment led to a statistically significant reduction in HAM-D17 scores compared to placebo. Clinical trial registration: Brazilian Register of Clinical Trials, RBR-5rz5ch


Assuntos
Transtorno Depressivo Maior/tratamento farmacológico , Brasil , Projetos Piloto , Método Duplo-Cego , Resultado do Tratamento , Antidepressivos/uso terapêutico , Óxido Nitroso/uso terapêutico
16.
J Clin Psychopharmacol ; 41(3): 260-266, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33857028

RESUMO

BACKGROUND: Schizophrenia is a complex disabling mental disorder, and many patients present poor response to available treatments. Accumulating evidence about the role of the glutamate/nitric oxide pathway in mediating the positive and negative symptoms of schizophrenia suggests potential benefits of drugs that modulate this system. The aim of this study was to test the efficacy of isosorbide mononitrate (ISMN) as an adjunctive therapy for symptomatic outpatients with schizophrenia. METHODS: This was a 2-month randomized, double-blind, placebo-controlled trial with 24 schizophrenia patients. Participants were treated with ISMN 50 mg for 1 month and placebo for another month in a crossover design. The Positive and Negative Syndrome Scale (PANSS), Clinical Global Impression Scale, Global Assessment of Functioning, and MATRICS Cognitive Consensual Battery were used for symptom assessment and arterial spin labeling was used to assess brain activation patterns. RESULTS: We found significant differences in the total, general, and positive subscales of the PANSS, Global Assessment of Functioning scores, and Clinical Global Impression scores during treatment with ISMN relative to placebo. No treatment effects were found comparing scores in the MATRICS Cognitive Consensual Battery and the negative subscale of the PANSS between the active and placebo conditions. A post hoc analysis of neuroimaging data showed reduced activity in the thalamus in subgroup of patients with severe psychopathology. CONCLUSIONS: Schizophrenia patients with persistent symptoms showed significant improvement after 4 weeks of treatment with ISMN 50 mg/d compared with placebo. Isosorbide mononitrate added beneficial effects to antipsychotic treatment in terms of positive symptoms and functioning.


Assuntos
Antipsicóticos/administração & dosagem , Dinitrato de Isossorbida/análogos & derivados , Esquizofrenia/tratamento farmacológico , Adulto , Estudos Cross-Over , Método Duplo-Cego , Quimioterapia Combinada , Feminino , Humanos , Dinitrato de Isossorbida/administração & dosagem , Masculino , Escalas de Graduação Psiquiátrica , Esquizofrenia/fisiopatologia , Resultado do Tratamento , Vasodilatadores/administração & dosagem
17.
Porto Biomed J ; 6(2): e134, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33869886

RESUMO

BACKGROUND: Montelukast, a safe drug widely use in asthmatic patients, may be an adjuvant in the treatment of Covid-19, either by improving lung injury and inflammation, or by acting as an anti-viral drug. We aim to assess the efficacy and safety of montelukast as add-on treatment in patients with Covid-19. METHODS: We propose a randomized, controlled, parallel, open-label trial involving 160 hospitalized adult patients with confirmed Covid-19. Patients will be randomly assigned in a 1:1 ratio to receive either montelukast 10 mg, once a day for 14 days, in addition to standard of care (SoC), or SoC alone. SoC will follow the best practice for treating these patients, according to updated recommendations. The primary outcome is time to recovery. Participants will be assessed using diary cards to capture data on treatment-related improvements in an 8-point ordinal scale. Secondary endpoints will include changes in respiratory and inflammatory parameters, and adverse events. This phase IV clinical trial will take place at the University Hospital of São João, Porto. EudraCT number: 2020-001747-21. RESULTS: This study intends to generate scientific evidence on efficacy and safety of montelukast as add-on treatment in Covid-19. The results will be essential to improve clinical outcomes which remains to be determined. CONCLUSION: Montelukast has been suggested as a potential drug with 2 main actions on Covid-19. The validation of montelukast as an adjuvant treatment may improve lung injury, inflammation, and symptoms leading to a better prognosis. The use of this drug may fulfil the existing gap on therapeutic options.

18.
Braz J Psychiatry ; 43(5): 484-493, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33605397

RESUMO

OBJECTIVE: Major depressive disorder (MDD) is related to glutamatergic dysfunction. Antagonists of glutamatergic N-methyl-D-aspartate receptor (NMDAR), such as ketamine, have antidepressant properties. Nitrous oxide (N2O) is also a NMDAR antagonist. Thus, this study aimed to evaluate the effects of augmenting antidepressant treatment with N2O. METHODS: This double blind, placebo-controlled randomized parallel pilot trial was conducted from June 2016 to June 2018 at the Hospital das Clínicas, Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo. Twenty-three subjects with MDD (aged 18 to 65, on antidepressants, with a score > 17 on the 17-item-Hamilton Depression Rating Scale [HAM-D17]) received 50% N2O (n=12; 37.17±13.59 years) or placebo (100% oxygen) (n=11; 37.18±12.77 years) for 60 minutes twice a week for 4 weeks. The primary outcome was changes in HAM-D17 from baseline to week 4. RESULTS: Depressive symptoms improved significantly in the N2O group (N2O: from 22.58±3.83 to 5.92±4.08; placebo: from 22.44±3.54 to 12.89±5.39, p < 0.005). A total of 91.7% and 75% of the N2O group subjects achieved response (≥ 50% reduction in HAM-D17 score) and remission (HAM-D17 < 7), respectively. The predominant adverse effects of N2O treatment were nausea, vomiting, and headache. CONCLUSION: N2O treatment led to a statistically significant reduction in HAM-D17 scores compared to placebo. CLINICAL TRIAL REGISTRATION: Brazilian Register of Clinical Trials, RBR-5rz5ch.


Assuntos
Transtorno Depressivo Maior , Antidepressivos/uso terapêutico , Brasil , Transtorno Depressivo Maior/tratamento farmacológico , Método Duplo-Cego , Humanos , Óxido Nitroso/uso terapêutico , Projetos Piloto , Resultado do Tratamento
19.
Metabolism ; 116: 154704, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-33421507

RESUMO

BACKGROUND: Maternal high-caloric nutrition and related gestational diabetes mellitus (GDM) are associated with a high-risk for developing metabolic complications later in life and in their offspring. In contrast, exercise is recognized as a non-pharmacological strategy against metabolic dysfunctions associated to lifestyle disorders. Therefore, we investigated whether gestational exercise delays the development of metabolic alterations in GDM mothers later in life, but also protects 6-week-old male offspring from adverse effects of maternal diet. METHODS: Female Sprague-Dawley rats were fed with either control (C) or high-fat high-sucrose (HFHS) diet to induce GDM and submitted to gestational exercise during the 3 weeks of pregnancy. Male offspring were sedentary and fed with C-diet. RESULTS: Sedentary HFHS-fed dams exhibited increased gestational body weight gain (p < 0.01) and glucose intolerance (p < 0.01), characteristic of GDM. Their offspring had normal glucose metabolism, but increased early-age body weight, which was reverted by gestational exercise. Gestational exercise also reduced offspring hepatic triglycerides accumulation (p < 0.05) and improved liver mitochondrial respiration capacity (p < 0.05), contributing to the recovery of liver bioenergetics compromised by maternal HFHS diet. Interestingly, liver mitochondrial respiration remained increased by gestational exercise in HFHS-fed dams despite prolonged HFHS consumption and exercise cessation. CONCLUSIONS: Gestational exercise can result in liver mitochondrial adaptations in GDM animals, which can be preserved even after the exercise program cessation. Exposure to maternal GDM programs liver metabolic setting of male offspring, whereas gestational exercise appears as an important preventive tool against maternal diet-induced metabolic alterations.


Assuntos
Dieta Hiperlipídica , Fígado/metabolismo , Mitocôndrias Hepáticas/metabolismo , Condicionamento Físico Animal/fisiologia , Efeitos Tardios da Exposição Pré-Natal/metabolismo , Sacarose/administração & dosagem , Animais , Respiração Celular/efeitos dos fármacos , Diabetes Gestacional/metabolismo , Diabetes Gestacional/fisiopatologia , Dieta Hiperlipídica/efeitos adversos , Carboidratos da Dieta/efeitos adversos , Feminino , Metabolismo dos Lipídeos/efeitos dos fármacos , Masculino , Fenômenos Fisiológicos da Nutrição Materna , Mitocôndrias Hepáticas/efeitos dos fármacos , Mães , Gravidez , Efeitos Tardios da Exposição Pré-Natal/fisiopatologia , Ratos , Ratos Sprague-Dawley
20.
An Acad Bras Cienc ; 92(3): e20190222, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32935736

RESUMO

This study aimed to evaluate the performance in feedlot and temperament of Nellore bulls classified by residual feed intake. The residual feed intake was calculated as the difference between the observed and predicted dry matter intake. Bulls classified as low residual feed intake had lower dry matter intake (kg day-1) and dry matter intake (g kg-1 d-1) of body weight, and were more efficient in feed conversion ratio than those classified as medium and high. The average daily gain didn't differ among residual feed intake classes and was 1.69 kg day-1, 1.82 kg day-1 and 1.71 kg day-1 for bulls classified as low, medium, or high, respectively. The residual feed intake was positively associated with dry matter intake, feed conversion ratio and subcutaneous fat thickness. The subcutaneous fat thickness was lower in bulls classified as low residual feed intake than in those with medium and high. No differences were observed in flight speed and reactivity score among residual feed intake classes. Overall, we concluded that bulls classified as low residual feed intake consumed less dry matter than high, with no differences in average daily gain, temperamentand had better feed efficiency, albeit their subcutaneous fat thickness was lower.


Assuntos
Temperamento , Ração Animal/análise , Animais , Peso Corporal , Bovinos , Dieta , Masculino
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