Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 20 de 34
Filter
1.
Int J Biol Macromol ; 253(Pt 7): 127392, 2023 Dec 31.
Article in English | MEDLINE | ID: mdl-37827412

ABSTRACT

Alzheimer's disease (AD) is a neurodegenerative disorder that leads to cognitive decline and memory loss. Unfortunately, there is no effective treatment for this condition, so there is a growing interest in developing new anti-AD agents. In this research project, a series of phenyl-quinoline derivatives were designed as potential anti-AD agents. These derivatives were substituted at two different positions on benzyl and phenyl rings. The structures of the derivatives were characterized using techniques such as IR spectroscopy, 1H NMR, 13C NMR, and elemental analysis. During the in vitro screening, the derivatives were tested against both acetylcholinesterase (AChE) and butyrylcholinesterase (BChE). It was observed that most of the derivatives showed higher selectivity against BChE compared to AChE. Among the derivatives, analog 7n (with a methoxy group at R1 and a 4-bromine substituent at R2 exhibited the highest potency, with a 75-fold improvement in the activity compared to the positive control. Importantly, this potent analog demonstrated no toxicity at the tested concentration on SH-SY5Y cells, indicating its potential as a safe anti-AD agent. The level of GSK-3ß was also reduced after treatments with 7n at 50 µM. Overall, this study highlights the design and evaluation of phenyl-quinoline derivatives as promising candidates for developing novel anti-AD agents.


Subject(s)
Alzheimer Disease , Neuroblastoma , Quinolines , Humans , Cholinesterase Inhibitors/pharmacology , Cholinesterase Inhibitors/chemistry , Butyrylcholinesterase/metabolism , Glycogen Synthase Kinase 3 beta , Acetylcholinesterase/metabolism , Alzheimer Disease/drug therapy , Quinolines/pharmacology , Structure-Activity Relationship , Molecular Docking Simulation
2.
Arch Pharm (Weinheim) ; 356(6): e2200571, 2023 Jun.
Article in English | MEDLINE | ID: mdl-37017555

ABSTRACT

A new series of indole-carbohydrazide-phenoxy-N-phenylacetamide derivatives 7a-l were designed, synthesized, and screened for their α-glucosidase inhibitory abilities and cytotoxic effects. The results obtained in the α-glucosidase inhibition assay indicated that most of the synthesized derivatives displayed good to moderate inhibitory abilities (Ki values ranging from 14.65 ± 2.54 to 37.466 ± 6.46 µM) when compared with the standard drug acarbose (Ki = 42.38 ± 5.73 µM). Among them, 2-mehoxy-phenoxy derivatives 7l and 7h with 4-nitro and 4-chloro substituents on the phenyl ring of the N-phenylacetamide moiety, respectively, displayed the most inhibition effects. The inhibitory mechanism of these compounds was investigated by molecular docking studies. The in vitro cytotoxicity assay showed that only one compound, 2-methoxy-phenoxy derivative 7k with a 4-bromo substituent on the phenyl ring of the N-phenylacetamide moiety, exhibited moderate cytotoxicity against the human non-small-cell lung cancer cell line A549 and the rest of the compounds show almost no cytotoxicity. Further cytotoxic evaluations were also performed on compound 7k. The in silico pharmacokinetic study predicted that the selected compounds 7l and 7h are likely to be orally active.


Subject(s)
Carcinoma, Non-Small-Cell Lung , Lung Neoplasms , Humans , Structure-Activity Relationship , Molecular Structure , Glycoside Hydrolase Inhibitors/pharmacology , alpha-Glucosidases/metabolism , Molecular Docking Simulation , Indoles/pharmacology
3.
mSphere ; 7(6): e0047122, 2022 12 21.
Article in English | MEDLINE | ID: mdl-36377882

ABSTRACT

Antimicrobial resistance in urinary tract infections (UTIs) is a major public health concern. This study aims to characterize the phenotypic and genetic basis of multidrug resistance (MDR) among expanded-spectrum cephalosporin-resistant (ESCR) uropathogenic Escherichia coli (UPEC) causing UTIs in California patient populations. Between February and October 2019, 577 ESCR UPEC isolates were collected from patients at 6 clinical laboratory sites across California. Lineage and antibiotic resistance genes were determined by analysis of whole-genome sequence data. The lineages ST131, ST1193, ST648, and ST69 were predominant, representing 46%, 5.5%, 4.5%, and 4.5% of the collection, respectively. Overall, 527 (91%) isolates had an expanded-spectrum ß-lactamase (ESBL) phenotype, with blaCTX-M-15, blaCTX-M-27, blaCTX-M-55, and blaCTX-M-14 being the most prevalent ESBL genes. In the 50 non-ESBL phenotype isolates, 40 (62%) contained blaCMY-2, which was the predominant plasmid-mediated AmpC (pAmpC) gene. Narrow-spectrum ß-lactamases, blaTEM-1B and blaOXA-1, were also found in 44.9% and 32.1% of isolates, respectively. Among ESCR UPEC isolates, isolates with an ESBL phenotype had a 1.7-times-greater likelihood of being MDR than non-ESBL phenotype isolates (P < 0.001). The cooccurrence of blaCTX-M-15, blaOXA-1, and aac(6')-Ib-cr within ESCR UPEC isolates was strongly correlated. Cooccurrence of blaCTX-M-15, blaOXA-1, and aac(6')-Ib-cr was associated with an increased risk of nonsusceptibility to piperacillin-tazobactam, cefepime, fluoroquinolones, and amikacin as well as MDR. Multivariate regression revealed the presence of blaCTX-M-55, blaTEM-1B, and the ST131 genotype as predictors of MDR. IMPORTANCE The rising incidence of resistance to expanded-spectrum cephalosporins among Escherichia coli strains, the most common cause of UTIs, is threatening our ability to successfully empirically treat these infections. ESCR E. coli strains are often MDR; therefore, UTI caused by these organisms often leads to treatment failure, increased length of hospital stay, and severe complications (D. G. Mark, Y.-Y. Hung, Z. Salim, N. J. Tarlton, et al., Ann Emerg Med 78:357-369, 2021, https://doi.org/10.1016/j.annemergmed.2021.01.003). Here, we performed an in-depth analysis of genetic factors of ESCR E. coli associated with coresistance and MDR. Such knowledge is critical to advance UTI diagnosis, treatment, and antibiotic stewardship.


Subject(s)
Escherichia coli Infections , Uropathogenic Escherichia coli , Humans , Cephalosporins/pharmacology , Uropathogenic Escherichia coli/genetics , Escherichia coli Infections/epidemiology , beta-Lactamases/genetics , Phenotype , Monobactams , Drug Resistance, Multiple, Bacterial/genetics
4.
Plant Biol (Stuttg) ; 24(4): 697-703, 2022 Jun.
Article in English | MEDLINE | ID: mdl-34783125

ABSTRACT

Hydrogen sulphide (H2 S) has emerged as a potential regulator of plant defence against different abiotic stresses. As a climacteric fruit, banana undergoes oxidative stresses shortly after harvest, resulting in faster ripening and senescence. This work examines the effects of vacuum infiltrated H2 S on ripening inhibition of banana. Banana fruits were vacuum infiltrated with 1 mm H2 S. Effects on oxidative stress markers, physiological changes, bioactive compounds and antioxidant potentials were examined during storage at 25 °C and 75-80% RH. Results indicate that treated fruits were less affected by oxidative stress, as evident by lower accumulation of ROS (superoxide and peroxide ions), elevated phenols content and antioxidant capacity. The ripening inhibitory effects of H2 S delayed chlorophyll loss and reduced ethylene and CO2 production. H2 S infiltration also reduced MDA accumulation and electrolytic leakage, resulting in longer shelf life. Vacuum infiltration with H2 S had a protective effect on postharvest banana through overcoming the deleterious effect of ROS and strengthening antioxidant potential. Thus, this method could be promising for enhanced preservation of banana during storage.


Subject(s)
Hydrogen Sulfide , Musa , Antioxidants/metabolism , Fruit/metabolism , Hydrogen Sulfide/metabolism , Hydrogen Sulfide/pharmacology , Musa/metabolism , Oxidative Stress , Reactive Oxygen Species/metabolism
5.
S D Med ; 75(12): 561-564, 2022 Dec.
Article in English | MEDLINE | ID: mdl-36893351

ABSTRACT

BACKGROUND: Propofol provides sedation in the pediatric setting for MRIs, ensuring minimal movement from patients and high-quality pictures. Sanford Children's outpatient sedation clinic currently does not have a standard protocol for using propofol for sedation. The purpose of the project was to determine if we could decrease the dose of propofol while maintaining adequate sedation during MRI imaging. METHODS: The study had three phases of retrospective chart review. The first phase was a six-month review of propofol dosing. The second phase introduced a goal propofol drip dose of 200-300 mcg/kg/min with reviewing success of sedation for six months. Lastly, the third phase introduced a goal propofol drip dose of 175-200 mcg/kg/min with reviewing success of sedation for four months. A successful sedation was determined by completing the imaging study without the child awakening. RESULTS: A total of 181 patients ranging in ages 6 months to 16 years were recruited. Percentage of successful sedations in phase 2 and phase 3 were 83 percent and 84 percent, respectively. The average total propofol dose used in sedations decreased from 15.43 mg/kg in phase 1 to 12.31 mg/kg in phase 3. On average of the three phases, the mean arterial pressure (MAP) overall was below the normal range in 60 percent of sedations. CONCLUSION: We conclude that creating a protocol with a baseline propofol drip rate of 175-199 mcg/kg/min for pediatric sedations would allow for successful sedations and prevent unnecessary excess dosing.


Subject(s)
Propofol , Child , Humans , Hypnotics and Sedatives , Retrospective Studies , Quality Improvement , Magnetic Resonance Imaging
6.
J Biochem Mol Toxicol ; 35(4): e22688, 2021 Apr.
Article in English | MEDLINE | ID: mdl-33368871

ABSTRACT

A series of new benzofuran-1,3,4-oxadiazole containing 1,2,3-triazole-acetamides 12a-n as potential anti-α-glucosidase agents were designed and synthesized. α-Glucosidase inhibition assay demonstrated that all the synthesized compounds 12a-n (half-maximal inhibitory concentration [IC50 ] values in the range of 40.7 ± 0.3-173.6 ± 1.9 µM) were more potent than standard inhibitor acarbose (IC50 = 750.0 ± 12.5 µM). Among them, the most potent compound was compound 12c, with inhibitory activity around 19-fold higher than acarbose. Since the most potent compound inhibited α-glucosidase in a competitive mode, a docking study of this compound was also performed into the active site of α-glucosidase. In vitro and in silico toxicity assays of the title compounds were also performed.


Subject(s)
Acetamides , Glycoside Hydrolase Inhibitors , Oxadiazoles , Saccharomyces cerevisiae Proteins , Saccharomyces cerevisiae/enzymology , alpha-Glucosidases/chemistry , Acetamides/chemical synthesis , Acetamides/chemistry , Glycoside Hydrolase Inhibitors/chemical synthesis , Glycoside Hydrolase Inhibitors/chemistry , Oxadiazoles/chemical synthesis , Oxadiazoles/chemistry , Saccharomyces cerevisiae Proteins/antagonists & inhibitors , Saccharomyces cerevisiae Proteins/chemistry
7.
J Acoust Soc Am ; 150(6): 4095, 2021 12.
Article in English | MEDLINE | ID: mdl-34972282

ABSTRACT

Although X-Ray Computed Tomography (CT) is widely used for detecting pulmonary nodules inside the parenchyma, it cannot be used during video-assisted surgical procedures. Real-time, non-ionizing, ultrasound-based techniques are an attractive alternative for nodule localization to ensure safe resection margins during surgery. Conventional ultrasound B-mode imaging of the lung is challenging due to multiple scattering. However, the multiple scattering contribution can be exploited to detect regions inside the lung containing no scatterers. Pulmonary nodules are homogeneous regions in contrast to the highly scattering parenchyma containing millions of air-filled alveoli. We developed a method relying on mapping the multiple scattering contribution inside the highly scattering lung to detect and localize pulmonary nodules. Impulse response matrices were acquired in ex-vivo pig and dog lungs using a linear array transducer to semi-locally investigate the backscattered field. Extracting the multiple-scattering contribution using singular-value decomposition and combining it with a depression detection algorithm allowed us to detect and localize regions with less multiple scattering, associated with the nodules. The feasibility of this method was demonstrated in five ex-vivo lungs containing a total of 20 artificial nodules. Ninety-five percent of the nodules were detected. Nodule depth and diameter significantly correlated with their ex-vivo CT-estimated counterparts (R = 0.960, 0.563, respectively).


Subject(s)
Lung Neoplasms , Multiple Pulmonary Nodules , Animals , Dogs , Lung/diagnostic imaging , Lung Neoplasms/surgery , Multiple Pulmonary Nodules/diagnostic imaging , Multiple Pulmonary Nodules/surgery , Swine , Thoracic Surgery, Video-Assisted , Tomography, X-Ray Computed/methods
8.
Sci Rep ; 9(1): 9927, 2019 07 09.
Article in English | MEDLINE | ID: mdl-31289314

ABSTRACT

The ability to manipulate the structure and function of promising systems via external stimuli is emerging with the development of reconfigurable and programmable multifunctional materials. Increasing antifungal and antitumor activity requires novel, effective treatments to be diligently sought. In this work, the synthesis, characterization, and in vitro biological screening of pure α-Ag2WO4, irradiated with electrons and with non-focused and focused femtosecond laser beams are reported. We demonstrate, for the first time, that Ag nanoparticles/α-Ag2WO4 composite displays potent antifungal and antitumor activity. This composite had an extreme low inhibition concentration against Candida albicans, cause the modulation of α-Ag2WO4 perform the fungicidal activity more efficient. For tumor activity, it was found that the composite showed a high selectivity against the cancer cells (MB49), thus depleting the populations of cancer cells by necrosis and apoptosis, without the healthy cells (BALB/3T3) being affected.


Subject(s)
Antifungal Agents/pharmacology , Antineoplastic Agents/pharmacology , Candida albicans/drug effects , Electrons , Metal Nanoparticles/chemistry , Oxides/chemistry , Silver/chemistry , Tungsten/chemistry , Urinary Bladder Neoplasms/drug therapy , Animals , Apoptosis , BALB 3T3 Cells , Cell Proliferation , Humans , Metal Nanoparticles/administration & dosage , Metal Nanoparticles/radiation effects , Mice , Oxides/radiation effects , Silver/radiation effects , Tumor Cells, Cultured , Tungsten/radiation effects , Urinary Bladder Neoplasms/pathology , Xenograft Model Antitumor Assays
9.
J Hosp Infect ; 101(4): 475-479, 2019 Apr.
Article in English | MEDLINE | ID: mdl-30012377

ABSTRACT

Antibiotic resistance (ABR) is a major global health threat that increases the risk of treatment failure and increases medical costs. One of the most common factors contributing to the spread of ABR is self-medication. The public, as well as workers in clinical and veterinary sectors, commit false practices towards appropriate antibiotic use, favouring the spread of resistance. As such, the first Lebanese Antibiotic Awareness Week campaign was initiated with a human-centred and interactive approach. The data showed a strikingly low level of antibiotic awareness. Cooperation between relevant stakeholders, policy-makers and health actors is crucial to control and overcome the problem of ABR.


Subject(s)
Anti-Bacterial Agents/adverse effects , Anti-Bacterial Agents/therapeutic use , Drug Resistance, Microbial , Health Knowledge, Attitudes, Practice , Adult , Female , Health Care Costs , Humans , Lebanon , Male , Middle Aged , Surveys and Questionnaires , Young Adult
10.
J Cell Physiol ; 234(3): 2765-2777, 2019 03.
Article in English | MEDLINE | ID: mdl-30073650

ABSTRACT

Hydatid cyst, the larval stage of the tapeworm Echinococcus granulosus and a causative agent of cystic echinococcosis, possesses a vast number of antigenic peptides that are constantly presented in the host immune system during infection. Here, we sought to provide more information about the cellular/humoral components engaged in the peripheral immune reactions to the fertile-cyst-derived Echinococcus alkaline phosphatase (E.ALP) in human hosts. Lymphoproliferative and cytokine responses after recall of E.ALP suggested the presence of specific immune reactions against the antigen. Interferon gamma (IFN-γ), tumor necrosis factor alpha (TNF-α), and interleukin (IL)-10 had the highest fold increase over the spontaneous levels in response to hydatid crude antigen (HCA). Recall of E.ALP, as well as its encounter, boosted IFN-γ, TNF-α, IL-2, and IL-6 responses in peripheral blood mononuclear cells cultures (PBMCs). The HCA-driven levels of all the cytokines in the culture supernatants of normal PBMCs were higher than those measured after E.ALP encounter. Immunoglobulin G (IgG)-profile in response to HCA showed the dominance of specific IgG1, IgG2, and IgG4 antibodies, but relatively lower affinity of IgG3 to this antigen. IgG1 and IgG3 were the only isotypes detected in serum responses to E.ALP. Our findings suggested that E.ALP contributes to the early phase of immune responses to the parasite, likely by induction of proinflammatory profiles and clonal expansion of high-affinity IgG1- and IgG3-secreting plasma cells, suggesting the value of E.ALP as a candidate to develop novel therapeutic and immunization strategies.


Subject(s)
Alkaline Phosphatase/immunology , Echinococcosis/immunology , Immunity, Humoral/immunology , Leukocytes, Mononuclear/immunology , Adult , Aged , Cytokines/metabolism , Female , Humans , Immunoglobulin G/immunology , Interferon-gamma/immunology , Male , Middle Aged , Tumor Necrosis Factor-alpha/immunology
11.
J Am Med Inform Assoc ; 25(3): 353-359, 2018 Mar 01.
Article in English | MEDLINE | ID: mdl-29202185

ABSTRACT

OBJECTIVE: To assess clinical documentation variations across health care institutions using different electronic medical record systems and investigate how they affect natural language processing (NLP) system portability. MATERIALS AND METHODS: Birth cohorts from Mayo Clinic and Sanford Children's Hospital (SCH) were used in this study (n = 298 for each). Documentation variations regarding asthma between the 2 cohorts were examined in various aspects: (1) overall corpus at the word level (ie, lexical variation), (2) topics and asthma-related concepts (ie, semantic variation), and (3) clinical note types (ie, process variation). We compared those statistics and explored NLP system portability for asthma ascertainment in 2 stages: prototype and refinement. RESULTS: There exist notable lexical variations (word-level similarity = 0.669) and process variations (differences in major note types containing asthma-related concepts). However, semantic-level corpora were relatively homogeneous (topic similarity = 0.944, asthma-related concept similarity = 0.971). The NLP system for asthma ascertainment had an F-score of 0.937 at Mayo, and produced 0.813 (prototype) and 0.908 (refinement) when applied at SCH. DISCUSSION: The criteria for asthma ascertainment are largely dependent on asthma-related concepts. Therefore, we believe that semantic similarity is important to estimate NLP system portability. As the Mayo Clinic and SCH corpora were relatively homogeneous at a semantic level, the NLP system, developed at Mayo Clinic, was imported to SCH successfully with proper adjustments to deal with the intrinsic corpus heterogeneity.

12.
Orthop Traumatol Surg Res ; 102(6): 707-10, 2016 10.
Article in English | MEDLINE | ID: mdl-27496661

ABSTRACT

INTRODUCTION: With the cost of healthcare in the United States reaching $2.9 trillion in 2013 and expected to increase with a growing geriatric population, the Center for Medicare and Medicaid Services (CMS) and Hospital Quality Alliance (HQA) began publicly reporting 30-day mortality rates so that hospitals and physicians may begin to confront clinical problems and promote high-quality and patient-centered care. Though the 30-day mortality is considered a highly effective tool in measuring hospital performance, little data actually exists that explores the rate and risk factors for trauma-related hip and pelvis fractures. Therefore, in this study, we sought to explore the risk factors associated with 30-day mortality in trauma-related hip and pelvic fractures. MATERIALS AND METHODS: Utilizing the American College of Surgeons National Surgical Quality Improvement Program (ACS-NSQIP) database, 341,062 patients undergoing orthopaedic procedures from 2005 to 2013 were identified through a Current Procedural Terminology (CPT) code search. A second CPT code search identified 24,805 patients who sustained a hip/pelvis fracture. Patient demographics, preoperative comorbidities, operative characteristics and postoperative complications were collected and compared using Chi-squared test, Wilcoxon-Mann-Whitney test and multivariate logistic regression analysis. RESULTS: Preoperative and postoperative risk factors for 30-day mortality following a hip/pelvis fracture were found: ASA classification, ascites, disseminated cancer, dyspnea, functional status, history of congestive heart failure (CHF), history of chronic obstructive pulmonary disease (COPD), a recent blood transfusion, and the postoperative complications: pneumonia, myocardial infarction, stroke, and septic shock. DISCUSSION: Several preoperative patient risk factors and postoperative complications greatly increased the odds for patient mortality following 30-days after initial surgery. Orthopaedic surgeons can utilize these predictive risk factors to better improve patient care. LEVEL OF EVIDENCE: Retrospective study. Level IV.


Subject(s)
Ascites/epidemiology , Dyspnea/epidemiology , Heart Failure/epidemiology , Hip Fractures/mortality , Pelvic Bones/injuries , Pulmonary Disease, Chronic Obstructive/epidemiology , Aged , Aged, 80 and over , Blood Transfusion , Comorbidity , Databases, Factual , Female , Health Status , Hip Fractures/surgery , Humans , Male , Myocardial Infarction/epidemiology , Neoplasm Metastasis , Orthopedic Procedures/adverse effects , Postoperative Complications/epidemiology , Retrospective Studies , Risk Factors , Shock, Septic/epidemiology , Stroke/epidemiology , United States/epidemiology
13.
S D Med ; 69(7): 303-307, 2016 Jul.
Article in English | MEDLINE | ID: mdl-28806018

ABSTRACT

The intent of this paper is to raise awareness to primary care and pediatric colleagues of how a clinically insignificant appearing condition like sinusitis can lead to a major complication. Subdural empyema is a rare but life-threatening complication of paranasal sinusitis, otitis media, or mastoid disease. We report a case of a 12-year-old male patient who originally presented with clinically insignificant symptoms and later developed intracranial abscess requiring aggressive neurosurgical intervention. We hope that this article will raise awareness among colleagues who can educate parents on high-alert symptoms to watch out for if the patient is discharged home after initial presentation.


Subject(s)
Acute Disease , Empyema, Subdural/etiology , Sinusitis/complications , Brain Abscess/surgery , Child , Humans , Male , Tomography, X-Ray Computed
14.
Sultan Qaboos Univ Med J ; 15(3): e305-16, 2015 Aug.
Article in English | MEDLINE | ID: mdl-26357550

ABSTRACT

Alzheimer's disease (AD), a neurodegenerative disorder associated with advanced age, is the most common cause of dementia globally. AD is characterised by cognitive dysfunction, deposition of amyloid plaques, neurofibrillary tangles and neuro-inflammation. Inflammation of the brain is a key pathological hallmark of AD. Thus, clinical and immunopathological evidence of AD could be potentially supported by inflammatory mediators, including cytokines, chemokines, the complement system, acute phase proteins and oxidative mediators. In particular, oxidative mediators may actively contribute to the progression of AD and on-going inflammation in the brain. This review provides an overview of the functions and activities of inflammatory mediators in AD. An improved understanding of inflammatory processes and their role in AD is needed to improve therapeutic research aims in the field of AD and similar diseases.

15.
J Neural Eng ; 12(4): 046020, 2015 Aug.
Article in English | MEDLINE | ID: mdl-26065874

ABSTRACT

OBJECTIVE: Our experiments explored the effect of visual stimuli degradation on cognitive workload. APPROACH: We investigated the subjective assessment, event-related potentials (ERPs) as well as electroencephalogram (EEG) as measures of cognitive workload. MAIN RESULTS: These experiments confirm that degradation of visual stimuli increases cognitive workload as assessed by subjective NASA task load index and confirmed by the observed P300 amplitude attenuation. Furthermore, the single-trial multi-level classification using features extracted from ERPs and EEG is found to be promising. Specifically, the adopted single-trial oscillatory EEG/ERP detection method achieved an average accuracy of 85% for discriminating 4 workload levels. Additionally, we found from the spatial patterns obtained from EEG signals that the frontal parts carry information that can be used for differentiating workload levels. SIGNIFICANCE: Our results show that visual stimuli can modulate cognitive workload, and the modulation can be measured by the single trial EEG/ERP detection method.


Subject(s)
Cognition/physiology , Electroencephalography/methods , Event-Related Potentials, P300/physiology , Photic Stimulation/methods , Psychomotor Performance/physiology , Visual Perception/physiology , Adaptation, Physiological/physiology , Cues , Executive Function/physiology , Humans
16.
Cell Prolif ; 48(3): 363-74, 2015 Jun.
Article in English | MEDLINE | ID: mdl-25858552

ABSTRACT

OBJECTIVES: Radiation and chemical mutagens are direct DNA-damaging agents and ultraviolet (UV) radiation is frequently used in biological studies. Consequent to ozone depletion, UV-C could become a great challenge to living organisms on earth, in the near future. The present study has focused on the role of poly (ADP-ribose) polymerase (PARP) during UV-C-induced growth and developmental changes in Dictyostelium discoideum, a phylogenetically important unicellular eukaryote. MATERIALS AND METHODS: Dictyostelium discoideum cells were exposed to different doses of UV-C and PARP activity, and effects of its inhibition were studied. Expression of developmentally regulated genes yakA, car1, aca, csA, regA, ctnA, ctnB, gp24, hspD and dsn were analysed using semiquantitative RT-PCR. RESULTS: We report that the D. discoideum cells displayed PARP activation within 2 min of UV-C irradiation and there was increase in NO levels in a dose-dependent manner. UV-C-irradiated cells had impaired growth, delayed or blocked development and delayed germination compared to control cells. In our previous studies we have shown that inhibition of PARP recovered oxidative stress-induced changes in D. discoideum; however, intriguingly PARP inhibition did not correct all defects as effectively in UV-C-irradiated cells. This possibly was due to interplay with increased NO signalling. CONCLUSIONS: Our results signify that UV-C and oxidative stress affected growth and development in D. discoideum by different mechanisms; these studies could provide major clues to complex mechanisms of growth and development in higher organisms.


Subject(s)
3',5'-Cyclic-AMP Phosphodiesterases/metabolism , Dictyostelium/radiation effects , Gene Expression Regulation, Developmental , Nitric Oxide/metabolism , Poly(ADP-ribose) Polymerases/genetics , Protozoan Proteins/metabolism , 3',5'-Cyclic-AMP Phosphodiesterases/genetics , Cell Adhesion Molecules/genetics , Cell Adhesion Molecules/metabolism , Dictyostelium/enzymology , Dictyostelium/genetics , Dose-Response Relationship, Radiation , Heat-Shock Proteins/genetics , Heat-Shock Proteins/metabolism , Poly(ADP-ribose) Polymerases/metabolism , Protein Kinases/genetics , Protein Kinases/metabolism , Protozoan Proteins/genetics , Signal Transduction , Ultraviolet Rays
17.
Indian J Med Microbiol ; 33 Suppl: 26-31, 2015 Feb.
Article in English | MEDLINE | ID: mdl-25657152

ABSTRACT

BACKGROUND: Rapid point-of-care (POC) tests provide an economical alternative for rapid diagnosis and treatment of influenza, especially in public health emergency situations. OBJECTIVES: To test the performance of a rapid influenza diagnostic test, QuickVue (Quidel) as a POC test against a real-time polymerase chain reaction (RT-PCR) assay for detection of influenza A and B in a developing country setting. STUDY DESIGN: In a prospective observational design, 600 patients with influenza-like illness (ILI) or with severe acute respiratory illness (SARI) who were referred to the Influenza Clinic of a tertiary care hospital in Srinagar, India from September 2012 to April 2013, were enrolled for diagnostic testing for influenza using QuickVue or RT-PCR. All influenza A-positive patients by RT-PCR were further subtyped using primers and probes for A/H1pdm09 and A/H3. RESULTS: Of the 600 patients, 186 tested positive for influenza A or B by RT-PCR (90 A/H1N1pdm09, 7 A/H3 and 89 influenza B), whereas only 43 tested positive for influenza (influenza A=22 and influenza B=21) by QuickVue. Thus, the sensitivity of the QuickVue was only 23% (95% confidence interval, CI: 17.3-29.8) and specificity was 100% (95% CI: 99.1-100) with a positive predictive value (PPV) of 100% (95% CI 91.8-100) and a negative predictive value (NPV) of 74.3% (95% CI: 70.5-77.9) as compared to RT-PCR. CONCLUSIONS: The high specificity of QuickVue suggest that this POC test can be a useful tool for patient management or triaging during a public health crisis but a low sensitivity suggests that a negative test result need to be further tested using RT-PCR.


Subject(s)
Influenza A virus/genetics , Influenza B virus/genetics , Influenza, Human/diagnosis , Point-of-Care Systems , Real-Time Polymerase Chain Reaction , Adult , Female , Humans , India , Male , Point-of-Care Systems/economics , Real-Time Polymerase Chain Reaction/methods , Reproducibility of Results , Sensitivity and Specificity , Young Adult
18.
Aliment Pharmacol Ther ; 38(6): 596-602, 2013 Sep.
Article in English | MEDLINE | ID: mdl-23889765

ABSTRACT

BACKGROUND: Excessive alcohol use has been reported to be responsible for 80 000 annual deaths in the United States. However, the exact cause of death related to the excessive use of alcohol has not been fully explored. AIM: To assess the effect of alcoholic liver disease (ALD) on all-cause, liver-related and cardiovascular mortality using population-based data. METHODS: Data were obtained from the Third National Health and Nutrition Examination Survey (NHANES III) Linked Mortality Files. Alcohol consumption was estimated as grams per day. Multivariate Cox proportional hazards model was utilised to assess the effects of ALD on follow-up time to mortality from all causes, cardiovascular disease and liver disease. RESULTS: A total of 8,306 participants were included [ALD (n = 148)]. Mortality follow-up data were available for a median time of 178.27 months. Participants with ALD had increased risk for liver-related mortality [adjusted hazard ratios or aHR 7.06 (2.09-23.79)], but not for overall mortality [aHR 1.14 (0.70-1.85)] or cardiovascular mortality [aHR 0.61 (0.11-3.25)]. CONCLUSION: Alcoholic liver disease increases the risks for liver-related mortality but not for cardiac or overall mortality.


Subject(s)
Alcohol Drinking/adverse effects , Cardiovascular Diseases/mortality , Liver Diseases, Alcoholic/mortality , Adult , Aged , Cause of Death , Female , Humans , Liver Diseases, Alcoholic/etiology , Male , Middle Aged , Proportional Hazards Models , Risk Factors , Young Adult
19.
Aliment Pharmacol Ther ; 37(7): 703-9, 2013 Apr.
Article in English | MEDLINE | ID: mdl-23432436

ABSTRACT

BACKGROUND: The impact of moderate alcohol consumption on long-term outcomes of chronic hepatitis C (CH-C) infected patients remains controversial. AIM: To assess the impact of moderate alcohol consumption on long-term outcomes of CH-C patients using population-based data. METHODS: Data were obtained from the Third National Health and Nutrition Examination Survey (NHANES III)-mortality linked files. Alcohol consumption was estimated as grams/day. Multivariate Cox proportional hazards model was utilized to assess the effects of CH-C and alcohol consumption on mortality (all causes, cardiovascular disease, and liver disease). RESULTS: A total of 8985 participants were included as the study cohort. Of these, 218 had CH-C. The follow-up time was 162.95 months for CH-C and 178.27 months for controls. CH-C patients had increased risk for both overall mortality and liver-related mortality. CH-C patients with excessive alcohol consumption had even higher risks for overall mortality and liver-related mortality. The risk of overall mortality associated with CH-C increased with moderate alcohol consumption of 1-19 g/day and heavy alcohol consumption ≥30 g/day. CONCLUSION: Although chronic hepatitis C is associated with increased risks for overall and liver-related mortality, these risks are even higher for patients consuming moderate and excessive amounts of alcohol.


Subject(s)
Alcohol Drinking/mortality , Hepatitis C, Chronic/mortality , Adult , Aged , Alcohol Drinking/adverse effects , Cardiovascular Diseases/mortality , Cause of Death , Cohort Studies , Female , Humans , Male , Middle Aged , Multivariate Analysis , Nutrition Surveys , Proportional Hazards Models , Risk Factors , Surveys and Questionnaires , United States/epidemiology , Young Adult
20.
Helicobacter ; 17(2): 116-20, 2012 Apr.
Article in English | MEDLINE | ID: mdl-22404441

ABSTRACT

BACKGROUND: Cardiac syndrome X (CSX) is a condition in which patients have the pain of angina despite normal coronary angiogram. Helicobacter pylori (H. pylori) infection causes chronic inflammation which may play a pathogenic role in CSX. We surveyed the association of inflammation with H. pylori and its virulent strain (cytotoxin-associated gene A positive; CagA+) infections with CSX. MATERIAL AND METHODS: Sixty patients with CSX (38 women/22 men; mean age: 51.8 ± 12.3) and 60 age- and gender-matched healthy controls (39 women/21 men; mean age: 48.9 ± 6.3) were enrolled. Plasma samples were tested for the presence of IgG antibody to H. pylori using enzyme linked immunosorbent assay (ELISA) method. IgG- positive patients were determined by the presence of IgG antibody to CagA, also by ELISA method. Also, plasma levels of interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α) were measured by ELISA method. RESULTS: Patients with CSX were detected to have significantly higher plasma IL-6 and TNF-α level in comparison with normal controls (33.6 ± 3.5 vs 3.2 ± 0.4 and 24.2 ± 2.3 vs 3.1 ± 0.4, respectively; p < 0.01). The plasma levels of these inflammatory factors in CgA+ were significantly higher than those in CagA- (CSX: IL-6: 43.05 ± 5.04 vs 23.97 ± 4.58 and TNF-α: 31.43 ± 3.13 vs 16.47 ± 2.93, CONTROLS: IL-6: 3.52 ± 1.39 vs 2.90 ± 0.67 and TNF-α: 5.39 ± 1.17 vs 2.22 ± 0.43, respectively; p < 0.05). CONCLUSION: The CagA+ strain of H. pylori, can not only be a trigger, and may also have a role via chronic inflammation in the pathogenesis of CSX.


Subject(s)
Antigens, Bacterial/genetics , Bacterial Proteins/genetics , Helicobacter Infections/immunology , Helicobacter Infections/microbiology , Helicobacter pylori/isolation & purification , Microvascular Angina/immunology , Microvascular Angina/microbiology , Adult , Antigens, Bacterial/immunology , Bacterial Proteins/immunology , Case-Control Studies , Female , Helicobacter pylori/genetics , Helicobacter pylori/immunology , Humans , Interleukin-6/immunology , Male , Middle Aged
SELECTION OF CITATIONS
SEARCH DETAIL
...