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1.
Sci Rep ; 10(1): 3107, 2020 Feb 20.
Artigo em Inglês | MEDLINE | ID: mdl-32080230

RESUMO

Intestinal alkaline phosphatase (IAP) regulates bicarbonate secretion, detoxifies lipopolysaccharide (LPS), regulates gut microbes, and dephosphorylates proinflammatory nucleotides. IAP also exhibits anti-inflammatory effects in a Toll-like Receptor-4 (TLR-4) dependent manner. However, it is not known whether IAP induces autophagy. We tested the hypothesis that IAP may induce autophagy which may mediate the anti-inflammatory effects of IAP. We found that exogenous IAP induced autophagy in intestinal epithelial cells and in macrophages. TLR4INC34 (C34), a TLR4 signaling inhibitor, suppressed IAP-induced autophagy. IAP also inhibited LPS-induced IL-1ß mRNA expression and activation of NF-κB. When autophagy was blocked by 3-methyladenine (3MA) or by Atg5 siRNA, IAP failed to block LPS-mediated effects. IAP also upregulated autophagy-related gene expression in small intestine in mice. We administered either vehicle or IAP (100 U/ml) in drinking water for 14 days in C57BL/6 mice. Mice were sacrificed and ileal tissues collected. Increased expression of Atg5, Atg16, Irgm1, Tlr4, and Lyz genes was observed in the IAP treated group compared to the vehicle treated group. Increase in Atg16 protein expression and fluorescence intensity of LC3 was also observed in IAP-treated tissues compared to the vehicle-treated tissues. Thus, our study lays the framework for investigating how IAP and autophagy may act together to control inflammatory conditions.

2.
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.

3.
IEEE/ACM Trans Comput Biol Bioinform ; 16(6): 1830-1842, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-29994537

RESUMO

Vitiligo is a well-known skin disorder with complex etiology. Vitiligo pathogenesis is multifaceted with many ramifications. A computational systemic path was designed to first propose candidate disease proteins by merging properties from protein interaction networks and gene ontology terms. All in all, 109 proteins were identified and suggested to be involved in the onset of disease or its progression. Later, a composite approach was employed to prioritize vitiligo disease proteins by comparing and benchmarking the properties against standard target identification criteria. This includes sequence-based, structural, functional, essentiality, protein-protein interaction, vulnerability, secretability, assayability, and druggability information. The existing information was seamlessly integrated into efficient pipelines to propose a novel protocol for assessment of targetability of disease proteins. Using the online data resources and the scripting, an illustrative list of 68 potential drug targets was generated for vitiligo. While this list is broadly consistent with the research community's current interest in certain specific proteins, and suggests novel target candidates that may merit further study, it can still be modified to correspond to a user-specific environment, either by adjusting the weights for chosen criteria (i.e., a quantitative approach) or by changing the considered criteria (i.e., a qualitative approach).

4.
Virusdisease ; 29(4): 461-467, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30539048

RESUMO

Recently three FDA approved existing drugs, namely-Oseltamivir, Peramivir and Zanamivir, used against Neuraminidase (NA) for the inhibitory effect on the process of viral progeny release to inhibit infection. All NA subtypes has been divided into two groups (Group 1 and Group 2) based on phylogenetic study. Oseltamivir and Zanamivir drugs are designed for Group 2 NA but are also used against 2009 H1N1 NA that lies in Group 1. There is no specific drug available for H1N1 and, consequently, there is an urgent requirement for the same. The structure-based drug design and fragment-based drug design methods are used for building more effective and economic drug molecules. In this work, the fragment-based drug development followed by fragment evolution on the basis of protein conformations after every 10 ns of 100 ns simulation. There are two analogs of Oseltamivir acid drug discovered in this study. Only analog 1, along with Oseltamivir acid, were then docked with the native protein. The analog 1 (benzoic acid inhibitor 11) exhibited higher binding affinity value of - 10.70 kcal/mol in comparison to its predecessor. The concept of conformations and protein-ligand interactions can be useful in designing new drugs for H1N1 with high specific binding.

5.
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
7.
Interdiscip Sci ; 10(3): 500-514, 2018 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-28290051

RESUMO

Vitiligo is an idiopathic disorder characterized by depigmented patches on the skin due to progressive loss of melanocytes. Several genetic, immunological, and pathophysiological investigations have established vitiligo as a polygenetic disorder with multifactorial etiology. However, no definite model explaining the interplay between these causative factors has been established hitherto. Therefore, we studied the disorder at the system level to identify the key proteins involved by exploring their molecular connectivity in terms of topological parameters. The existing research data helped us in collating 215 proteins involved in vitiligo onset or progression. Interaction study of these proteins leads to a comprehensive vitiligo map with 4845 protein nodes linked with 107,416 edges. Based on centrality measures, a backbone network with 500 nodes has been derived. This has presented a clear overview of the proteins and processes involved and the crosstalk between them. Clustering backbone proteins revealed densely connected regions inferring major molecular interaction modules essential for vitiligo. Finally, a list of top order proteins that play a key role in the disease pathomechanism has been formulated. This includes SUMO2, ESR1, COPS5, MYC, SMAD3, and Cullin proteins. While this list is in fair agreement with the available literature, it also introduces new candidate proteins that can be further explored. A subnetwork of 64 vitiligo core proteins was built by analyzing the backbone and seed protein networks. Our finding suggests that the topology, along with functional clustering, provides a deep insight into the behavior of proteins. This in turn aids in the illustration of disease condition and discovery of significant proteins involved in vitiligo.


Assuntos
Mapas de Interação de Proteínas , Vitiligo/metabolismo , Análise por Conglomerados , Bases de Dados de Proteínas , Redes Reguladoras de Genes , Humanos , Mapas de Interação de Proteínas/genética , Vitiligo/genética
8.
Invest Ophthalmol Vis Sci ; 58(14): 6489-6499, 2017 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-29288267

RESUMO

Purpose: This study examines the role of PI3K/Akt pathway in δ-opioid receptor agonist (SNC-121)-induced RGC neuroprotection in a chronic glaucoma rat model. Methods: Injecting hypertonic saline into the limbal veins of Brown Norway rats elevated IOP. Rats were treated either with 1 mg/kg SNC-121 or 3 mg/kg 2-(4-morpholinyl)-8-phenyl-1(4H)-benzopyran-4-one hydrochloride (LY-294002; PI3K/Akt inhibitor) plus SNC-121 once daily for 7 days. Pattern ERGs were recorded in response to contrast reversal of patterned visual stimuli. Retinal ganglion cells (RGC) were visualized by Fluorogold retrograde labeling. Optic nerve head (ONH) astrocytes were pretreated with PI3K/Akt inhibitors for 30 minutes followed by 1-µM SNC-121 treatment. Changes in matrix metalloproteinases (MMP-1, -2, and -3) production and PI3K/Akt activation in optic nerve and TNF-α treated ONH astrocytes were measured by immunohistochemistry and Western blotting. Results: SNC-121 activates the PI3K/Akt pathway in ONH astrocytes and the retina. In ONH astrocytes, SNC-121-induced Akt activation was fully inhibited by PI3K/Akt inhibitors. A sustained decline (7-42 days post injury) in Akt activation was seen in the ocular-hypertensive retina and optic nerve. This decline is reversed to normal levels by 1-mg/kg intraperitoneally (i.p.) SNC-121 treatment. Both pattern ERG amplitudes and RGC numbers were reduced in ocular hypertensive eyes, which were significantly increased in SNC-121-treated animals. Interestingly, SNC-121-induced increase in pattern-ERG amplitudes and RGC numbers were inhibited in LY-294002 pretreated animals. Additionally, SNC-121 treatment inhibited MMP-1, -2, and -3 production from the optic nerve of ocular hypertensive rats and TNF-α-treated ONH astrocytes. Conclusions: PI3K/Akt pathway plays a crucial role in SNC-121-mediated RGC neuroprotection against glaucomatous injury.


Assuntos
Glaucoma/complicações , Neuroproteção/efeitos dos fármacos , Proteínas Proto-Oncogênicas c-akt/genética , Receptores Opioides delta/metabolismo , Doenças Retinianas/prevenção & controle , Animais , Astrócitos/metabolismo , Astrócitos/patologia , Benzamidas/farmacologia , Western Blotting , Células Cultivadas , Doença Crônica , Modelos Animais de Doenças , Progressão da Doença , Eletrorretinografia , Glaucoma/genética , Glaucoma/metabolismo , Imuno-Histoquímica , Masculino , Disco Óptico , Nervo Óptico , Piperazinas/farmacologia , Proteínas Proto-Oncogênicas c-akt/efeitos dos fármacos , Proteínas Proto-Oncogênicas c-akt/metabolismo , Ratos , Ratos Endogâmicos BN , Receptores Opioides delta/agonistas , Doenças Retinianas/metabolismo , Doenças Retinianas/patologia , Células Ganglionares da Retina/metabolismo
9.
ACS Biomater Sci Eng ; 3(8): 1861-1868, 2017 Aug 14.
Artigo em Inglês | MEDLINE | ID: mdl-29152562

RESUMO

Polyamidoamine (PAMAM) dendrimers have been investigated as a potential platform for a number of ocular drugs, but only in aqueous solution. In this work we have developed fast dissolving dendrimer-based nanofibers (DNF) as a topical delivery vehicle for the glaucoma drug brimonidine tartrate (BT). The safety and drug release kinetics of these nanofiber mats were evaluated in vitro and in vivo. DNF caused no toxicity at therapeutic levels in cultured cells or ocular irritation in animal tests using a normotensive rat model. Intra-ocular pressure response was equivalent between DNF and BT solution in a single dose test, but DNF showed improved efficacy with daily dosing over a 3-week test period. This study indicates electrospun dendrimer nanofibers are a viable alternative to aqueous solutions as a more efficient method of administering antiglaucoma drug topically.

10.
Anc Sci Life ; 36(3): 141-150, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28867858

RESUMO

CONTEXT: Cyavanaprasa (CP) is an Ayurvedic immune booster formulation that confers vigor and vitality while delaying the ageing process. Benefits of CP have been studied widely in adult population. OBJECTIVES: Current study assessed beneficial effects of CP on health and immunity related parameters in healthy children. METHODS: This study was a 6 month long two armed, randomized, open labeled, prospective clinical study. School going healthy children between ages of 5-12 years were randomized to receive orally daily either CP (approx. 6 g) followed by a cup of milk (100 - 200 ml) or cup of milk only twice a day while continuing with their normal/routine diet. Results were analyzed based on number of episodes, severity, duration of illness (infections and allergies) and number of absent days due to illness during the study duration and changes in levels of energy, physical fitness, strength, stamina and quality of life in children which were recorded in subject diary by their parents/Legally Acceptable Representative (LAR). RESULTS: 702 participants were randomized, out of which 627 completed the study (CP n = 313; Control n = 314). Results of immunity (episodes of infections or allergy related conditions) showed more than 2 times protection from immunity related illness in CP Group as compared to the control. CP also showed better percentage improvement in energy levels, physical fitness, strength, stamina and quality of life assessed through KIDSCREEN QOL-27 questionnaires in children. CONCLUSION: Regular consumption of CP for a period of six months could significantly improve immunity, energy levels, physical fitness, strength, stamina and quality of life in school going healthy children. STUDY REGISTRATION: Clinical Trail Registry of India vide CTRI/2015/02/005574, Dated 24 February 2015.

11.
Innate Immun ; 23(6): 537-545, 2017 08.
Artigo em Inglês | MEDLINE | ID: mdl-28770667

RESUMO

Impaired Paneth cell expression of antimicrobial protein (AMP) lysozyme is found in patients with Crohn's disease with the autophagy gene ATG16L1 risk allele, in mice with mutations in autophagy genes Atg16L1, Atg5 and Atg7, and in Irgm1 knockout mice. Defective autophagy is also associated with expansion of resident Gram-negative bacteria in the intestinal lumen. These findings suggest that autophagy may control extracellular resident microbes by governing expression of lysozyme. To test the hypothesis that autophagy may have a defensive role in host response to resident extracellular microbes, we investigated the relationship between gut microbes, autophagy, and lysozyme. RAW 264.7 macrophages were treated with fecal slurry (FS), representing the resident microbial community; lipopolysaccharide (LPS); or butyrate, representing microbial products; or a representative resident Gram-negative bacterium Desulfovibrio vulgaris (DSV). FS, LPS, and DSV inhibited lysozyme expression, whereas butyrate had no effect. Induction of autophagy by rapamycin countered this inhibition, whereas silencing of the autophagy gene Irgm1 exacerbated the inhibitory effects of LPS on lysozyme expression. LPS also inhibited lysozyme activity against DSV and autophagy reversed this effect. Our results provide a novel insight into an interaction between gut bacteria, autophagy and AMP whereby autophagy may defend the host by countering the suppression of antimicrobial protein by Gram-negative bacteria.


Assuntos
Doença de Crohn/imunologia , Desulfovibrio vulgaris/imunologia , Infecções por Desulfovibrionaceae/imunologia , Microbioma Gastrointestinal/imunologia , Macrófagos/fisiologia , Muramidase/metabolismo , Celulas de Paneth/fisiologia , Animais , Autofagia , Fezes , Proteínas de Ligação ao GTP/genética , Proteínas de Ligação ao GTP/metabolismo , Regulação da Expressão Gênica , Humanos , Lipopolissacarídeos/imunologia , Camundongos , Camundongos Knockout , Muramidase/genética , Células RAW 264.7 , RNA Interferente Pequeno/genética , Sirolimo/farmacologia
12.
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
13.
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
14.
Reg Anesth Pain Med ; 42(3): 319-326, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28252523

RESUMO

BACKGROUND AND OBJECTIVES: Dexamethasone is a useful adjuvant in regional anesthesia that is used to prolong the duration of analgesia for peripheral nerve blocks. Recent randomized controlled trials (RCTs) have demonstrated conflicting results as to whether perineural versus intravenous (IV) administration is superior in this regard, and the perineural use of dexamethasone remains off-label. Therefore, we sought to perform a systematic review and meta-analysis of RCTs. METHODS: In accordance with PRISMA guidelines, we performed a random-effects meta-analysis of RCTs comparing perineural versus IV dexamethasone with duration of analgesia as the primary outcome. RESULTS: Eleven RCTs met the inclusion criteria with a total of 1076 subjects. Perineural dexamethasone prolonged the duration of analgesia by 3.77 hours (95% confidence interval [CI], 1.87-5.68 hours; P < 0.001) compared to IV dexamethasone, with high statistical heterogeneity. For secondary outcomes, perineural dexamethasone prolonged the duration of both motor (3.47 hours [95% CI, 1.49-5.45]; P < 0.001) and sensory (2.28 hours [95% CI, 0.38-4.17]; P = 0.019) block compared to IV administration. Furthermore, perineural dexamethasone patients consumed slightly less oral opioids at 24 hours than IV dexamethasone patients (7.1 mg of oral morphine equivalents [95% CI, 0.74-13.5 mg]; P = 0.029), and there were no statistically significant differences in the other secondary outcomes. Notably, no increase in adverse events was detected. CONCLUSIONS: Perineural dexamethasone prolongs the duration of analgesia across the RCTs included in our meta-analysis. The magnitude of effect of 3.77 hours raises the question as to whether perineural dexamethasone should be administered routinely over its IV counterpart-or reserved for selected patients where such prolongation would be clinically important.


Assuntos
Anti-Inflamatórios/administração & dosagem , Bloqueio Nervoso Autônomo/métodos , Dexametasona/administração & dosagem , Administração Intravenosa , Humanos , Ensaios Clínicos Controlados Aleatórios como Assunto/métodos
15.
Anesth Essays Res ; 10(2): 262-7, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27212758

RESUMO

BACKGROUND: Pregabalin and gabapentin are the gamma-aminobutyric acid analogs used as a part of multimodal analgesic regimen. AIM: To compare the postoperative analgesic benefits of gabapentin or pregabalin as a premedication for lower limb orthopedic surgery under combined spinal-epidural techniques. SETTINGS AND DESIGN: Randomized double-blind study. MATERIALS AND METHODS: A total of 90 patients were divided into three groups: G, P, C who received gabapentin 1200 mg, pregabalin 300 mg, and placebo, respectively 1.5 h before surgery. All patients received combined spinal-epidural block with 3 ml of 0.5% intrathecal bupivacaine. Assessment of pain was made with visual analog scale (VAS). Postoperative analgesia was provided with epidural top-ups with 2.5 ml of 0.5% bupivacaine and fentanyl 25 µg when VAS >3. Rescue analgesia in the form of injection diclofenac (75 mg) intramuscularly was given if VAS >3 even after epidural top-up. A total number of epidural top-ups, rescue analgesia, pain-free interval postspinal anesthesia, and sedation score were noted. STATISTICAL ANALYSIS: This was done using SPSS version 17. Mean and standard deviation were calculated using Chi-square test and analysis of variance. RESULTS: The total postoperative analgesic time was 7.23 h in Group G, 14.80 h in Group P, and 4.17 h in Group C. A total number of epidural top-ups were 2.43 in Group G, 0.77 in Group P, and 4.43 in Group C. CONCLUSION: Pregabalin 300 mg and gabapentin 1200 mg significantly reduce the need of postoperative rescue analgesia, epidural top-ups, and increase the duration of postspinal anesthesia without altering hemodynamics with sedation as a major side effect.

16.
Physiol Behav ; 157: 281-7, 2016 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-26861176

RESUMO

The ability of gut microbes to bi-directionally communicate with the brain and vice versa form the basis of the gut microbiome-central nervous system axis. It has been shown that inoculation with pathogenic gut bacteria alters the behavior of mice; however, it is not known whether or not non-pathogenic resident microbes have similar effects. In this study, we tested the hypothesis that the administration of sulfate-reducing bacteria (SRB), a specific group of resident gut bacteria that generate hydrogen sulfide (H2S), impair learning and memory performance in mice tested in an 8-arm radial maze and Morris water maze. We found that mice spent more time in the center of the maze when they were gavaged with live SRB as compared to mice given saline (control), lactulose+mannitol (L/M), or killed SRB. SRB-gavaged mice were also tested using the Morris water maze and were found to take longer to complete the test, spend more time further from the platform, and have a longer path length to reach the platform. This effect of SRB on maze performance was associated with a higher concentration of H2S in the small intestine and cecum. We conclude that SRB, a specific resident gut bacterial species, could impair cognitive function in mice.


Assuntos
Infecções por Bartonella/complicações , Gasotransmissores/uso terapêutico , Sulfeto de Hidrogênio/uso terapêutico , Transtornos da Memória , Memória de Curto Prazo/efeitos dos fármacos , Animais , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Aprendizagem em Labirinto/efeitos dos fármacos , Transtornos da Memória/tratamento farmacológico , Transtornos da Memória/etiologia , Transtornos da Memória/microbiologia , Camundongos , Fatores de Tempo
17.
J Am Coll Radiol ; 13(3): 320-5, 2016 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-26482815

RESUMO

PURPOSE: Traditionally, the pediatric radiology elective for medical students and pediatric residents constituted a morning teaching session focused mainly on radiography and fluoroscopy. A more structured elective was desired to broaden the exposure to more imaging modalities, create a more uniform educational experience, and include assessment tools. METHODS: In 2012, an introductory e-mail and formal syllabus, including required reading assignments, were sent to participants before the start date. A rotating weekly schedule was expanded to include cross-sectional imaging (ultrasound, CT, MR) and nuclear medicine. The schedule could accommodate specific goals of the pediatric resident or medical student, as requested. Starting in 2013, an online pre-test and post-test were developed, as well as an online end-of-rotation survey specific to the pediatric radiology elective. Taking the Image Gently pledge was required. A scavenger hunt tool, cue cards, and electronic modules were added. RESULTS: Pre-test and post-test scores, averaged over 2 years, showed improvement in radiology knowledge, with scores increasing by 27% for medical students and 21% for pediatric residents. Surveys at the end of the elective were overwhelmingly positive, with constructive criticism and complimentary comments. CONCLUSIONS: We have successfully created an elective experience in radiology that dedicates time to education while preserving the workflow of radiologists. We have developed tools to provide a customized experience with many self-directed learning opportunities. Our tools and techniques are easily translatable to a general or adult radiology elective.


Assuntos
Currículo , Diagnóstico por Imagem , Educação Médica/organização & administração , Modelos Organizacionais , Radiologia/educação , Ensino/organização & administração , Avaliação Educacional/métodos , Modelos Educacionais , Tennessee
18.
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
19.
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
20.
Microorganisms ; 3(4): 866-89, 2015 Nov 12.
Artigo em Inglês | MEDLINE | ID: mdl-27682122

RESUMO

Hydrogen sulfide (H2S) is a Janus-faced molecule. On one hand, several toxic functions have been attributed to H2S and exposure to high levels of this gas is extremely hazardous to health. On the other hand, H2S delivery based clinical therapies are being developed to combat inflammation, visceral pain, oxidative stress related tissue injury, thrombosis and cancer. Since its discovery, H2S has been found to have pleiotropic effects on physiology and health. H2S is a gasotransmitter that exerts its effect on different systems, such as gastrointestinal, neuronal, cardiovascular, respiratory, renal, and hepatic systems. In the gastrointestinal tract, in addition to H2S production by mammalian cystathionine-ß-synthase (CBS), cystathionine-γ-lyase (CSE), H2S is also generated by the metabolic activity of resident gut microbes, mainly by colonic Sulfate-Reducing Bacteria (SRB) via a dissimilatory sulfate reduction (DSR) pathway. In the gut, H2S regulates functions such as inflammation, ischemia/ reperfusion injury and motility. H2S derived from gut microbes has been found to be associated with gastrointestinal disorders such as ulcerative colitis, Crohn's disease and irritable bowel syndrome. This underscores the importance of gut microbes and their production of H2S on host physiology and pathophysiology.

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