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1.
Pediatr Blood Cancer ; 70 Suppl 4: e29974, 2023 06.
Artigo em Inglês | MEDLINE | ID: mdl-36184716

RESUMO

Neuroblastoma is the most common extracranial solid neoplasm in children. This manuscript provides consensus-based imaging recommendations for pediatric neuroblastoma patients at diagnosis and during follow-up.


Assuntos
Neuroblastoma , Ressonância de Plasmônio de Superfície , Criança , Humanos , Neuroblastoma/patologia , Diagnóstico por Imagem , Estadiamento de Neoplasias
2.
Pediatr Blood Cancer ; 70 Suppl 4: e29973, 2023 06.
Artigo em Inglês | MEDLINE | ID: mdl-36193741

RESUMO

Adrenal tumors other than neuroblastoma are uncommon in children. The most frequently encountered are adrenocortical carcinoma and pheochromocytoma. This paper offers consensus recommendations for imaging of pediatric patients with a known or suspected primary adrenal malignancy other than neuroblastoma at diagnosis and during follow-up.


Assuntos
Neoplasias do Córtex Suprarrenal , Neoplasias das Glândulas Suprarrenais , Neuroblastoma , Criança , Humanos , Ressonância de Plasmônio de Superfície , Neoplasias das Glândulas Suprarrenais/diagnóstico por imagem , Neoplasias das Glândulas Suprarrenais/patologia , Neuroblastoma/diagnóstico por imagem , Diagnóstico por Imagem
3.
Pediatr Blood Cancer ; 70 Suppl 4: e30004, 2023 06.
Artigo em Inglês | MEDLINE | ID: mdl-36308415

RESUMO

Malignant renal tumors account for approximately 6% of pediatric malignancies, with Wilms tumor (WT) representing approximately 90% of pediatric renal tumors. This paper provides consensus-based imaging guidelines for the initial evaluation of a child with suspected WT and follow-up during and after therapy co-developed by the Children's Oncology Group (COG) Diagnostic Imaging and Society for Pediatric Radiology (SPR) oncology committees. The guidelines for Wilms Tumor Imaging in the Society of International Pediatric Oncology (SIOP) are briefly discussed to highlight some of the differences in imaging approach.


Assuntos
Neoplasias Renais , Radiologia , Tumor de Wilms , Criança , Humanos , Descanso , Ressonância de Plasmônio de Superfície , Neoplasias Renais/patologia , Tumor de Wilms/diagnóstico por imagem , Tumor de Wilms/terapia , Tumor de Wilms/patologia , Radiografia
4.
Anaerobe ; 75: 102582, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35533828

RESUMO

Desulfovibrio spp. is a commensal sulfate reducing bacterium that is present in small numbers in the gastrointestinal tract. Increased concentrations of Desulfovibrio spp. (blooms) have been reported in patients with inflammatory bowel disease and irritable bowel syndrome. Since stress has been reported to exacerbate symptoms of these chronic diseases, this study examined whether the stress catecholamine norepinephrine (NE) promotes Desulfovibrio growth. Norepinephrine-stimulated growth has been reported in other bacterial taxa, and this effect may depend on the availability of the micronutrient iron. OBJECTIVES: This study tested whether norepinephrine exposure affects the in vitro growth of Desulfovibrio vulgaris in an iron dependent manner. METHODS: DSV was incubated in a growth medium with and without 1 µm of norepinephrine. An additional growth assay added the iron chelator deferoxamine in NE exposed DSV. Iron regulatory genes were assessed with and without the treatment of NE and Deferoxamine. RESULTS: We found that norepinephrine significantly increased growth of D. vulgaris. Norepinephrine also increased bacterial production of hydrogen sulfide. Additionally, norepinephrine significantly increased bacterial expression in three of the four tested iron regulatory genes. The iron chelator deferoxamine inhibited growth of D. vulgaris in a dose-dependent manner and reversed the effect of norepinephrine on proliferation of D. vulgaris and on bacterial expression of iron regulatory genes. CONCLUSION: The data presented in this work suggests that promotion of D. vulgaris growth by norepinephrine is iron dependent.


Assuntos
Desulfovibrio vulgaris , Desulfovibrio , Desferroxamina/metabolismo , Desferroxamina/farmacologia , Desulfovibrio/metabolismo , Desulfovibrio vulgaris/genética , Humanos , Ferro/metabolismo , Quelantes de Ferro/metabolismo , Quelantes de Ferro/farmacologia , Norepinefrina/metabolismo , Norepinefrina/farmacologia
5.
BMC Anesthesiol ; 20(1): 214, 2020 08 26.
Artigo em Inglês | MEDLINE | ID: mdl-32847522

RESUMO

BACKGROUND: Shivering is a common side effect in women having cesarean delivery (CD) under spinal anesthesia, which can be bothersome to the patient, and it can also interfere with perioperative monitoring. In several studies, the intrathecal (IT) addition of a lipophilic opioid to local anesthetics has been shown to decrease the incidence of shivering. OBJECTIVE: We performed this network meta-analysis to evaluate the effects of intrathecal lipophilic opioids in preventing the incidence of shivering in patients undergoing CD. METHODS: This review was planned according to the PRISMA for Network Meta-Analysis (PRISMA-NMA) guidelines. An English literature search of multiple electronic databases was conducted. We included randomized controlled trials (RCTs) that reported on the incidence of shivering, with study groups receiving either IT fentanyl, sufentanil, or meperidine in women undergoing CD under spinal anesthesia. Quality of the studies was assessed using the modified Oxford scoring system. Using random-effects modeling, dichotomous data were extracted and summarized using odds ratio (OR) with a 95% credible interval (CrI). Statistical analysis was conducted using R studio version 1.0.153 - Inc. RESULTS: Twenty-one studies consisting of 1433 patients (Control group: 590 patients in twenty-one studies; Fentanyl group:199 patients in seven studies; Sufentanil group: 156 patients in five studies; Meperidine group: 488 patients in ten studies) met the inclusion criteria for this systematic review investigating the effect of intrathecal lipophilic opioids in preventing the incidence of shivering in women undergoing cesarean delivery under spinal anesthesia. Methodological validity scores ranged from 3 to 7. The Bayesian mixed network estimate showed the incidence of shivering was significantly lower with IT fentanyl (pooled odds ratio (OR): 0.13; 95% credible interval (CrI): 0.04 to 0.35; P = 0.0004) and IT meperidine (OR: 0.12; 95% CrI: 0.05 to 0.29; P < 0.00001), but not with IT sufentanil (OR: 0.37; 95% CrI: 0.11 to 1.22; P = 0.23). The IT fentanyl group had a significantly lower incidence of intraoperative discomfort [Risk Ratio (RR): 0.19; 95% CI: 0.10-0.35; P < 0.00001], the IT sufentanil group had a significantly higher incidence of pruritus (RR: 6.18; 95% CI: 1.18-32.46; P = 0.03) The IT meperidine group had a significantly lower incidence of intraoperative discomfort (2.7% vs. 13.6%; RR: 0.22; 95% CI: 0.09-0.55; P = 0.001), but there was a significant increase in nausea and vomiting (IT meperidine group vs. Control group: 42.7% vs. 19.4%; RR: 2.56; 95% CI: 1.14-5.75; P = 0.02). Meta-regression analysis based on the opioid dose and quality of the study did not impact the final inference of our result. CONCLUSION: IT fentanyl significantly decreased the incidence of shivering in women undergoing CD under spinal anesthesia without increasing maternal adverse events, confirming that routine use in this patient population is a good choice. IT sufentanil did not decrease the incidence of shivering. IT meperidine decreased the incidence and severity of shivering, but its use was also associated with significant nausea and vomiting.


Assuntos
Analgésicos Opioides/administração & dosagem , Raquianestesia/métodos , Cesárea/métodos , Injeções Espinhais/métodos , Ensaios Clínicos Controlados Aleatórios como Assunto/métodos , Estremecimento/efeitos dos fármacos , Analgésicos Opioides/efeitos adversos , Anestesia Obstétrica/efeitos adversos , Anestesia Obstétrica/métodos , Raquianestesia/efeitos adversos , Teorema de Bayes , Feminino , Fentanila/administração & dosagem , Fentanila/efeitos adversos , Humanos , Incidência , Injeções Espinhais/efeitos adversos , Metanálise em Rede , Náusea e Vômito Pós-Operatórios/induzido quimicamente , Gravidez , Estremecimento/fisiologia , Sufentanil/administração & dosagem , Sufentanil/efeitos adversos
6.
J Anaesthesiol Clin Pharmacol ; 35(1): 19-24, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31057234

RESUMO

The ex utero intrapartum treatment (EXIT) procedure is performed in cases of fetal congenital malformation. The anesthetic management is much more challenging and involves providing profound uterine relaxation, maintenance of Uteroplacental blood flow and fetal anesthesia. The aim of the article is to review the literature and compare the efficacy of both the anesthetic techniques with respect to maternal and fetal outcomes. The literature source for this review was obtained via PubMed, Medline, Google scholar and Cochrane database of systematic reviews until January 2017. In our literature review we found that both GA and Regional anesthesia were successfully described for EXIT procedure but GA was performed in the majority of cases. Consideration for anesthetic technique should be done on a case-by-case basis.

7.
Am J Emerg Med ; 36(5): 769-773, 2018 May.
Artigo em Inglês | MEDLINE | ID: mdl-29137905

RESUMO

BACKGROUND: Acute asthma exacerbations (AAE) account for many Pediatric Emergency Department (PED) visits. Chest radiography (CXR) is often performed in these patients to identify practice-changing findings such as pneumonia (PNA). Limited knowledge exists to balance the cost and radiation dose of CXR with expected yield of clinically meaningful information. OBJECTIVE: To determine in children with AAE with CXR, whether patient characteristics are associated with radiographic PNA; and significant practice change by initiation of antibiotic. DESIGN/METHODS: Retrospective chart review of AAE patients with CXR performed in a PED in 2014. We examined univariate associations between patient characteristics and PNA on CXR and administration of antibiotic. Multiple logistic regression models then subsequently examined adjusted associations between patient characteristics and both outcomes. RESULTS: Of 288 patients, 43 (15%) had PNA on CXR and 51 (17.8%) received antibiotics. There were no statistically significant univariate associations between either outcome and age, race, gender, insurance status, mode of PED arrival, fever or hypoxia (all p>0.11). Crackles were associated with antibiotic administration (p=0.03), but not PNA on CXR (p=0.07). Only previous antibiotic use within 7days had both significant univariate associations (p=0.002) and adjusted associations with both PNA on CXR (aOR 3.6) and antibiotic administration (aOR 3.3). CONCLUSION: CXR infrequently adds valuable information in children with AAE. Patients treated with antibiotic within 7days are more likely to have PNA identified on CXR and receive antibiotics. A larger study is needed to examine potential significance of hypoxia and crackles.


Assuntos
Antibacterianos/uso terapêutico , Asma/diagnóstico por imagem , Serviço Hospitalar de Emergência , Pneumonia/diagnóstico por imagem , Radiografia Torácica/métodos , Adolescente , Asma/complicações , Criança , Pré-Escolar , Progressão da Doença , Feminino , Humanos , Masculino , Pneumonia/tratamento farmacológico , Guias de Prática Clínica como Assunto , Doses de Radiação , Estudos Retrospectivos
8.
PLoS Genet ; 11(12): e1005675, 2015 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-26684013

RESUMO

Replication fork stalling and collapse is a major source of genome instability leading to neoplastic transformation or cell death. Such stressed replication forks can be conservatively repaired and restarted using homologous recombination (HR) or non-conservatively repaired using micro-homology mediated end joining (MMEJ). HR repair of stressed forks is initiated by 5' end resection near the fork junction, which permits 3' single strand invasion of a homologous template for fork restart. This 5' end resection also prevents classical non-homologous end-joining (cNHEJ), a competing pathway for DNA double-strand break (DSB) repair. Unopposed NHEJ can cause genome instability during replication stress by abnormally fusing free double strand ends that occur as unstable replication fork repair intermediates. We show here that the previously uncharacterized Exonuclease/Endonuclease/Phosphatase Domain-1 (EEPD1) protein is required for initiating repair and restart of stalled forks. EEPD1 is recruited to stalled forks, enhances 5' DNA end resection, and promotes restart of stalled forks. Interestingly, EEPD1 directs DSB repair away from cNHEJ, and also away from MMEJ, which requires limited end resection for initiation. EEPD1 is also required for proper ATR and CHK1 phosphorylation, and formation of gamma-H2AX, RAD51 and phospho-RPA32 foci. Consistent with a direct role in stalled replication fork cleavage, EEPD1 is a 5' overhang nuclease in an obligate complex with the end resection nuclease Exo1 and BLM. EEPD1 depletion causes nuclear and cytogenetic defects, which are made worse by replication stress. Depleting 53BP1, which slows cNHEJ, fully rescues the nuclear and cytogenetic abnormalities seen with EEPD1 depletion. These data demonstrate that genome stability during replication stress is maintained by EEPD1, which initiates HR and inhibits cNHEJ and MMEJ.


Assuntos
DNA Helicases/genética , Endodesoxirribonucleases/genética , Instabilidade Genômica , Recombinação Homóloga/genética , Peptídeos e Proteínas de Sinalização Intracelular/genética , Reparo de DNA por Recombinação/genética , Quebras de DNA de Cadeia Dupla , Dano ao DNA/genética , Reparo do DNA por Junção de Extremidades/genética , Proteínas de Escherichia coli/genética , Regulação da Expressão Gênica , Células HEK293 , Histonas/genética , Humanos , Proteína 1 de Ligação à Proteína Supressora de Tumor p53
9.
Dig Dis Sci ; 62(6): 1486-1497, 2017 06.
Artigo em Inglês | MEDLINE | ID: mdl-28466260

RESUMO

BACKGROUND: Defective autophagic machinery, such as that in Crohn's disease patients homozygous for ATG16L1 risk allele, is associated with alteration of resident gut bacterial communities. However, whether or not host autophagy responds to changes in the resident gut microbial community is not known. Here, we investigated the effect of antibiotic-induced disruption of the gut microbiome (dysbiosis) on autophagy gene expression and the expression of antimicrobial peptides/protein (AMP) over time. AIM: To test the hypothesis that antibiotic treatment may cause time-dependent changes in gut bacterial density, autophagy genes, and antimicrobial protein/peptide gene expression. METHODS: Mice (n = 8 per group) were treated with antibiotic cocktail and sacrificed at different intervals of recovery (days 3, 7, 10, 14, 21, 28, 35, and 42) post-antibiotics. DNA and RNA were extracted from small intestinal tissues. Bacterial density, expression of host autophagy genes, and AMP genes were analyzed by relative quantitative PCR. Fold change difference in comparison with untreated control group was calculated using 2-ΔΔCt method. Statistical analysis was performed using nonparametric Mann-Whitney test. RESULTS: Gut bacterial density changed in a time-dependent fashion in response to antibiotic treatment. These changes were concurrent with upregulation of autophagy genes and antimicrobial peptide/protein gene expression. We further showed that an oral gavage of a resident microbe Desulfovibrio, which bloomed in antibiotic-treated animals, induced Atg5 and lysozyme (Lyz) gene expression. CONCLUSION: Autophagy genes respond to dysbiosis induced by antibiotics. This response may be a host mechanism to detect and possibly correct dysbiosis by activating antimicrobial peptides/proteins that control the microbial load in the gut.


Assuntos
Antibacterianos/farmacologia , Peptídeos Catiônicos Antimicrobianos/genética , Autofagia/genética , Disbiose/microbiologia , Microbioma Gastrointestinal/efeitos dos fármacos , RNA Ribossômico 16S/análise , Animais , Proteína 5 Relacionada à Autofagia/genética , Proteínas Relacionadas à Autofagia/genética , Bacteroidetes , Células Cultivadas , Desulfovibrio , Desulfovibrio vulgaris , Disbiose/induzido quimicamente , Disbiose/genética , Células Epiteliais/efeitos dos fármacos , Feminino , Firmicutes , Expressão Gênica , Intestino Delgado/citologia , Intestino Delgado/microbiologia , Macrófagos/efeitos dos fármacos , Camundongos , Camundongos Endogâmicos C57BL , Muramidase/genética , Proteínas Associadas a Pancreatite , Proteínas/genética , Fatores de Tempo , Regulação para Cima , alfa-Defensinas/genética
10.
Pediatr Radiol ; 47(13): 1745-1750, 2017 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-28831577

RESUMO

BACKGROUND: Human metapneumovirus (HMPV) was identified in 2001 and is a common cause of acute respiratory illness in young children. The radiologic characteristics of laboratory-confirmed HMPV acute respiratory illness in young children have not been systematically assessed. OBJECTIVE: We systematically evaluated the radiographic characteristics of acute respiratory illness associated with HMPV in a prospective cohort of pediatric patients. MATERIALS AND METHODS: We included chest radiographs from children <5 years old with acute respiratory illness who were enrolled in the prospective New Vaccine Surveillance Network (NVSN) study from 2003 to 2009 and were diagnosed with HMPV by reverse transcription-polymerase chain reaction (RT-PCR). Of 215 HMPV-positive subjects enrolled at our tertiary care children's hospital, 68 had chest radiographs obtained by the treating clinician that were available for review. Two fellowship-trained pediatric radiologists, independently and then in consensus, retrospectively evaluated these chest radiographs for their radiographic features. RESULTS: Parahilar opacities were the most commonly observed abnormality, occurring in 87% of children with HMPV. Hyperinflation also occurred frequently (69%). Atelectasis (40%) and consolidation (18%) appeared less frequently. Pleural effusion and pneumothorax were not seen on any radiographs. CONCLUSION: The clinical presentations of HMPV include bronchiolitis, croup and pneumonia. Dominant chest radiographic abnormalities include parahilar opacities and hyperinflation, with occasional consolidation. Recognition of the imaging patterns seen with common viral illnesses like respiratory syncytial virus (RSV) and HMPV might facilitate diagnosis and limit unnecessary antibiotic treatment.


Assuntos
Metapneumovirus , Infecções por Paramyxoviridae/diagnóstico por imagem , Radiografia Torácica , Infecções Respiratórias/diagnóstico por imagem , Infecções Respiratórias/virologia , Doença Aguda , Pré-Escolar , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Estudos Prospectivos
11.
Blood ; 121(21): 4359-65, 2013 May 23.
Artigo em Inglês | MEDLINE | ID: mdl-23568489

RESUMO

Chromosomal translocations are common contributors to malignancy, yet little is known about the precise molecular mechanisms by which they are generated. Sequencing translocation junctions in acute leukemias revealed that the translocations were likely mediated by a DNA double-strand break repair pathway termed nonhomologous end-joining (NHEJ). There are major 2 types of NHEJ: (1) the classical pathway initiated by the Ku complex, and (2) the alternative pathway initiated by poly ADP-ribose polymerase 1 (PARP1). Recent reports suggest that classical NHEJ repair components repress translocations, whereas alternative NHEJ components were required for translocations. The rate-limiting step for initiation of alternative NHEJ is the displacement of the Ku complex by PARP1. Therefore, we asked whether PARP1 inhibition could prevent chromosomal translocations in 3 translocation reporter systems. We found that 2 PARP1 inhibitors or repression of PARP1 protein expression strongly repressed chromosomal translocations, implying that PARP1 is essential for this process. Finally, PARP1 inhibition also reduced both ionizing radiation-generated and VP16-generated translocations in 2 cell lines. These data define PARP1 as a critical mediator of chromosomal translocations and raise the possibility that oncogenic translocations occurring after high-dose chemotherapy or radiation could be prevented by treatment with a clinically available PARP1 inhibitor.


Assuntos
Leucemia/genética , Poli(ADP-Ribose) Polimerases/genética , Poli(ADP-Ribose) Polimerases/fisiologia , Translocação Genética/genética , Translocação Genética/fisiologia , Doença Aguda , Células Cultivadas , Quebras de DNA de Cadeia Dupla , Fibroblastos/citologia , Fibroblastos/fisiologia , Humanos , Indóis/farmacologia , Leucemia/tratamento farmacológico , Leucemia/prevenção & controle , Ftalazinas/farmacologia , Piperazinas/farmacologia , Poli(ADP-Ribose) Polimerase-1 , Inibidores de Poli(ADP-Ribose) Polimerases , RNA Interferente Pequeno/genética , Translocação Genética/efeitos dos fármacos
12.
Environ Monit Assess ; 187(3): 67, 2015 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-25647798

RESUMO

Abundance of CaCO3 rich soil dust is a typical feature of atmospheric environment in the Indian region. During prevailing dry weather conditions, dustfall is deposited onto the foliar surfaces of plant affecting their morphology, stomata and the levels of biochemical constituents. This study reports the chemical characteristics of dustfall, its effect on foliar morphology and biochemical constituents of a medicinal plant (Morus alba) at two sites which are differentiated on the basis of landuse pattern, viz., (i) residential, Jawaharlal Nehru University (JNU), and (ii) industrial, Sahibabad (SB), located in the National Capital Region (NCR) of Delhi. Dustfall was characterized for major anions (F(-), Cl(-), NO3 (-) and SO4 (--)) and cations (Na(+), NH4 (+), K(+), Mg(++) and Ca(++)). Biochemical parameters such as chlorophyll a, chlorophyll b, total chlorophyll, carotenoid, proline and ascorbic acid were determined in foliar samples. The results showed that the dustfall fluxes of all the major ions were found to be higher at the industrial site (SB) as compared to the residential site (JNU). Foliar analysis revealed that the levels of biochemical parameters were more affected at SB site due to higher levels of dust SO4 (--) contributed by various anthropogenic sources resulting in more stressful conditions affecting the biochemistry of the plant. The possible entry pathways for dust SO4 (--) into foliar cells are also discussed in the paper. It was noticed that the deposition of urban dust was responsible for the damage of trichome, epidermis, cuticle and stomatal guard cells significantly affecting foliar morphology. SB exhibited more damage to these morphological parts suggesting that industrial dust is harmful to the plants.


Assuntos
Poluentes Atmosféricos/toxicidade , Poeira/análise , Monitoramento Ambiental , Morus/efeitos dos fármacos , Sulfatos/toxicidade , Poluentes Atmosféricos/análise , Clorofila/análogos & derivados , Clorofila A , Indústrias , Íons/análise , Plantas , Solo , Sulfatos/análise
13.
Artigo em Inglês | MEDLINE | ID: mdl-38608232

RESUMO

Purpose: Previously, we identified increased retinal degeneration and cytokine response in a mouse model of dry age-related macular degeneration (AMD) in the presence of systemic inflammation from rheumatoid arthritis (RA). Histone deacetylases (HDACs) regulate cytokine production by reducing acetylation and are found to be dysregulated in inflammatory diseases, including RA and AMD. Therefore, this current study investigates the effect of HDAC inhibition on AMD progression in the presence of systemic inflammation. Methods: Collagen induced arthritis (CIA) was induced in C57BL6J mice, followed by sodium iodate (NaIO3)-induced retinal degeneration. Mice were treated with a selective HDAC class I inhibitor, MS-275, and retinal structure [optical coherence tomography (OCT)], function (electroretinography), and molecular changes quantitative real-time polymerase chain reaction (RT-qPCR, Western Blot) were assessed. Results: NaIO3 retinal damage was diminished in CIA mice treated with MS-275 (P ≤ 0.05). While no significant difference was observed in retinal pigment epithelium (RPE) function, a trend in increased c-wave amplitude was detected in CIA + NaIO3 mice treated with MS-275. Finally, we identified decreased Hdac1, Hdac3, and Cxcl9 expression in CIA + NaIO3 mouse RPE/choroid when treated with MS-275 (P ≤ 0.05). Conclusions: Our data demonstrate that HDAC inhibition can reduce the additive effect of NaIO3-induced retinal degeneration in the presence of systemic inflammation by CIA as measured by OCT analysis. In addition, HDAC inhibition in CIA + NaIO3 treated mice resulted in reduced cytokine production. These findings are highly innovative and provide additional support to the therapeutic potential of HDAC inhibitors for dry AMD treatment.

14.
Microorganisms ; 12(7)2024 Jul 14.
Artigo em Inglês | MEDLINE | ID: mdl-39065198

RESUMO

The gut microbiota-brain axis allows for bidirectional communication between the microbes in our gastrointestinal (GI) tract and the central nervous system. Psychological stress has been known to disrupt the gut microbiome (dysbiosis) leading to anxiety-like behavior. Pathogens administered into the gut have been reported to cause anxiety. Whether commensal bacteria affect the gut-brain axis is not well understood. In this study, we examined the impact of a commensal sulfate-reducing bacteria (SRB) and its metabolite, hydrogen sulfide (H2S), on anxiety-like behavior. We found that mice gavaged with SRB had increased anxiety-like behavior as measured by the open field test. We also tested the effects of magnesium oxide (MgO) on SRB growth both in vitro and in vivo using a water avoidance stress (WAS) model. We found that MgO inhibited SRB growth and H2S production in a dose-dependent fashion. Mice that underwent psychological stress using the WAS model were observed to have an overgrowth (bloom) of SRB (Deferribacterota) and increased anxiety-like behavior. However, WAS-induced overgrowth of SRB and anxiety-like behavioral effects were attenuated in animals fed a MgO-enriched diet. These findings supported a potential MgO-reversible relationship between WAS-induced SRB blooms and anxiety-like behavior.

15.
Anesth Analg ; 117(3): 677-685, 2013 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-23921652

RESUMO

BACKGROUND: A single dose of epidural morphine is effective in reducing pain after cesarean delivery but is associated with adverse effects. In this study, we sought to establish whether half the traditional dose of epidural morphine, when administered as part of a multimodal analgesia regimen after cesarean delivery, was associated with noninferior analgesia and fewer adverse effects. METHODS: Ninety term parturients undergoing cesarean delivery under epidural anesthesia were enrolled in this randomized, double-blinded, noninferiority study. Patients were randomly allocated to receive either 3 mg epidural morphine or, half this dose, 1.5 mg epidural morphine. In addition, subjects received regular systemic ketorolac and acetaminophen. Rescue analgesia (oral oxycodone) was administered for breakthrough pain. The primary outcome was the difference between groups in total opioid consumption (measured in median IV morphine equivalents) within the first 24 hours. A prespecified noninferiority margin of 3.33 mg was used. Secondary outcomes included total opioid consumption from 24 to 48 hours, numerical rating scale pain scores, time to first request for analgesics, overall pain relief, maternal satisfaction, quality of recovery, and adverse effects. RESULTS: Data were analyzed for 87 participants. Noninferiority was demonstrated as the difference in median 24-hour opioid consumption between the 1.5 mg epidural morphine (EM) and 3 mg EM groups was 0 mg (1-sided 95% confidence interval [CI], 2.5 mg), which was less than the prespecified noninferiority margin of 3.33 mg. No significant differences were found between groups in the median 24- to 48-hour opioid consumption or the median total opioid consumption within 48 hours. Pain scores, overall pain relief, and satisfaction at 24 and 48 hours were not significantly different between groups. The 1.5 mg EM group had a lower incidence of moderate and severe pruritus at 6 and 12 hours (relative risk [RR] 0.44, 95% CI, 0.2-0.9 and RR 0.41, 95% CI, 0.2-0.8, respectively) and had less nausea and vomiting at 6 hours (RR 0.22, 95% CI, 0.05-0.9). There was no difference in average pain scores at 12 weeks between the 2 groups. CONCLUSION: When used as part of a multimodal analgesia regimen, 1.5 mg epidural morphine provided noninferior postcesarean analgesia and caused fewer adverse effects compared with 3 mg epidural morphine.


Assuntos
Analgesia Obstétrica/métodos , Analgésicos Opioides/uso terapêutico , Cesárea , Morfina/uso terapêutico , Dor Pós-Operatória/tratamento farmacológico , Adolescente , Adulto , Analgésicos Opioides/administração & dosagem , Analgésicos Opioides/efeitos adversos , Anti-Inflamatórios não Esteroides/uso terapêutico , Relação Dose-Resposta a Droga , Método Duplo-Cego , Feminino , Humanos , Cetorolaco/uso terapêutico , Morfina/administração & dosagem , Morfina/efeitos adversos , Náusea/induzido quimicamente , Medição da Dor , Satisfação do Paciente , Gravidez , Prurido/induzido quimicamente , Resultado do Tratamento , Adulto Jovem
16.
Immunol Rev ; 227(1): 189-202, 2009 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-19120485

RESUMO

Autophagy is a physiologically and immunologically controlled intracellular homeostatic pathway that sequesters and degrades cytoplasmic targets including macromolecular aggregates, cellular organelles such as mitochondria, and whole microbes or their products. Recent advances show that autophagy plays a role in innate immunity in several ways: (i) direct elimination of intracellular microbes by digestion in autolysosomes, (ii) delivery of cytosolic microbial products to pattern recognition receptors (PRRs) in a process referred to as topological inversion, and (iii) as an anti-microbial effector of Toll-like receptors and other PRR signaling. Autophagy eliminates pathogens in vitro and in vivo but, when aberrant due to mutations, contributes to human inflammatory disorders such as Crohn's disease. In this review, we examine these relationships and propose that autophagy is one of the most ancient innate immune defenses that has possibly evolved at the time of alpha-protobacteria-pre-eukaryote relationships, leading up to modern eukaryotic cell-mitochondrial symbiosis, and that during the metazoan evolution, additional layers of immunological regulation have been superimposed and integrated with this primordial innate immunity mechanism.


Assuntos
Autofagia/imunologia , Proteínas de Ligação ao GTP/imunologia , Imunidade Inata , Proteínas Adaptadoras de Sinalização NOD/metabolismo , Receptores Toll-Like/metabolismo , Animais , Apresentação de Antígeno/imunologia , Autofagia/genética , Doença de Crohn/genética , Doença de Crohn/imunologia , Citocinas/genética , Citocinas/metabolismo , Evolução Molecular , Proteínas de Ligação ao GTP/genética , Proteínas de Ligação ao GTP/metabolismo , Humanos , Infecções/imunologia , Sistema de Sinalização das MAP Quinases/imunologia , Mitocôndrias/imunologia , Proteínas Adaptadoras de Sinalização NOD/imunologia , Células Th1/imunologia , Células Th1/metabolismo , Células Th2/imunologia , Células Th2/metabolismo , Receptores Toll-Like/imunologia
17.
J Anaesthesiol Clin Pharmacol ; 29(3): 303-7, 2013 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-24106351

RESUMO

Pruritus is a troublesome side-effect of neuraxial (epidural and intrathecal) opioids. Sometimes it may be more unpleasant than pain itself. The prevention and treatment still remains a challenge. A variety of medications with different mechanisms of action have been used for the prevention and treatment of opioid-induced pruritus, with mixed results. The aim of this article is to review the current body of literature and summarize the current understanding of the mechanisms and the pharmacological therapies available to manage opioid-induced pruritus. The literature source of this review was obtained via PubMed, Medline and Cochrane Database of Systematic Reviews until 2012. The search results were limited to the randomized controlled trials, systemic reviews and non-systemic reviews.

18.
Microorganisms ; 11(7)2023 Jul 07.
Artigo em Inglês | MEDLINE | ID: mdl-37512944

RESUMO

Desulfovibrio (DSV) are sulfate-reducing bacteria (SRB) that are ubiquitously present in the environment and as resident commensal bacteria within the human gastrointestinal tract. Though they are minor residents of the healthy gut, DSV are opportunistic pathobionts that may overgrow in the setting of various intestinal and extra-intestinal diseases. An increasing number of studies have demonstrated a positive correlation between DSV overgrowth (bloom) and various human diseases. While the relationship between DSV bloom and disease pathology has not been clearly established, mounting evidence suggests a causal role for these bacteria in disease development. As DSV are the most predominant genera of SRB in the gut, this review summarizes current knowledge regarding the relationship between DSV and a variety of diseases. In this study, we also discuss the mechanisms by which these bacteria may contribute to disease pathology.

19.
Microorganisms ; 11(2)2023 Feb 17.
Artigo em Inglês | MEDLINE | ID: mdl-36838472

RESUMO

The ability of bacteriophage (phage), abundant within the gastrointestinal microbiome, to regulate bacterial populations within the same micro-environment offers prophylactic and therapeutic opportunities. Bacteria and phage have both been shown to interact intimately with mucin, and these interactions invariably effect the outcomes of phage predation within the intestine. To better understand the influence of the gastrointestinal micro-environment on phage predation, we employed enclosed, in vitro systems to investigate the roles of mucin concentration and agitation as a function of phage type and number on bacterial killing. Using two lytic coliphage, T4 and PhiX174, bacterial viability was quantified following exposure to phages at different multiplicities of infection (MOI) within increasing, physiological levels of mucin (0-4%) with and without agitation. Comparison of bacterial viability outcomes demonstrated that at low MOI, agitation in combination with higher mucin concentration (>2%) inhibited phage predation by both phages. However, when MOI was increased, PhiX predation was recovered regardless of mucin concentration or agitation. In contrast, only constant agitation of samples containing a high MOI of T4 demonstrated phage predation; briefly agitated samples remained hindered. Our results demonstrate that each phage-bacteria pairing is uniquely influenced by environmental factors, and these should be considered when determining the potential efficacy of phage predation under homeostatic or therapeutic circumstances.

20.
J Biomed Phys Eng ; 12(5): 465-476, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-36313412

RESUMO

Background: Radiotherapy plays a major role in the treatment of the cervical cancer. Objective: Dosimetric comparison of intensity-modulated radiation therapy (IMRT) with three-dimensional conformal radiation therapy (3DCRT) in cervical cancer treatment was performed by modifying the beams arrangements to achieve better organ at risk (OAR) sparing. Material and Methods: The analytical evaluation study was made by modifying the IMRT plan, subtracting the rectal volume from planning target volume (PTV), and applying the field-in-field technique in 3DCRT. Eight patients in various cervical cancer stages, from I‒III, were inducted for this investigation. The prescribed dose was 5000 cGy in 25 fractions. For all cases, both IMRT and 3DCRT plans were generated. For PTV and OARs, dose volume histogram (DVH) comparative analysis was carried out. For safety checks and quality control, pre-treatment verification of all the plans was performed using an indigenously developed pelvic phantom (for IMRT and 3DCRT) and gamma analysis with Delta4 phantom (for IMRT). Results: This study indicated that IMRT can treat cervical cancer more efficiently with less damage to OARs as compare to 3DCRT. Conclusion: In this study, we observe that the IMRT plans with subtracting rectal volume achieve better OAR sparing.

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