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1.
Ann Burns Fire Disasters ; 35(4): 334-345, 2022 Dec.
Article in English | MEDLINE | ID: mdl-38680629

ABSTRACT

This paper takes the form of a case study of forest fires that occurred in Indonesia from 2014 to 2019 and were reported on the social media of Twitter. The study was a corpus-assisted discourse study (CADS) using data scraping or text mining on Twitter based on the keyword "kebakaran hutan" [forest fire] and discourse analysis. The actor-network theory was used to map the actors involved. This study concludes that five discourses show a consistently large pattern of Twitter users responding to the problem of forest fires in Indonesia. Regarding the actors, the government takes an essential role of leadership and information arbitrage on Twitter. Seeing as it is the state's responsibility to ensure the safety of all people, the government must appear to be the main holder of control in managing disaster information traffic to avoid irresponsible information or hoaxes disseminated by parties or actors. These results indicate that the availability of information obtained from every conversation of Twitter users can be used as a study or input in the formulation of evidence-based policy about forest fires. It should be given more attention as an alternative means of solving the issue of forest fires, which has become an annual problem in Indonesia.


Nous rapportons ici l'étude des feux de forêts survenus en Indonésie entre 2014 et 2019, tels que rapportés sur Twitter. Nous réalisé une analyse lexicographique des tweets repérés par les mots clés « feux de forêts ¼, à partir des captures d'écran. Les acteurs impliqués ont été cartographiés selon la théorie sociologique de l'acteur-réseau. On peut alors répartir la grande majorité des utilisateurs de Twitter dans 5 catégories. Le gouvernement a des rôles d'information et de modération majeurs dans ce contexte. Ayant pour responsabilité d'assurer la sécurité de la population, il doit apparaître comme le régulateur principal du corpus de l'information, en évitant la dissémination de canulars et autres infoxes. L'ensemble des informations relayées par Twitter peut être utilisé pour construire un discours objectif qui pourrait être utilisé dans la gestion du problème des feux de forêts, qui se reproduisent chaque année en indonésie.

2.
Adv Ther ; 38(9): 4709-4721, 2021 09.
Article in English | MEDLINE | ID: mdl-34319549

ABSTRACT

INTRODUCTION: Drug-induced liver injury (DILI) is the most frequent cause of acute liver failure in North America and Europe, but it is often missed because of unstandardized diagnostic methods and criteria. This study aimed to develop and validate an automated algorithm to identify potential DILI cases in routine pharmacovigilance (PV) activities. METHODS: Post-marketing hepatic adverse events reported for a potentially hepatotoxic drug in a global PV database from 19 March 2017 to 18 June 2018 were assessed manually and with the automated algorithm. The algorithm provided case assessments by applying pre-specified criteria to all case data and narratives simultaneously. RESULTS: A total of 1456 cases were included for analysis and assessed manually. Sufficient data for algorithm assessment were available for 476 cases (32.7%). Of these cases, manual assessment identified 312 (65.5%) potential DILI cases while algorithm assessment identified 305 (64.1%) potential DILI cases. Comparison of manual and algorithm assessments demonstrated a sensitivity of 97.8% and a specificity of 79.3% for the algorithm. Given the prevalence of potential DILI cases in the population studied, the algorithm was calculated to have positive predictive value 56.3% and negative predictive value 99.2%. The time required for manual review compared to algorithm review suggested that application of the algorithm prior to manual screening would have resulted in a time savings of 42.2%. CONCLUSION: An automated algorithm to identify potential DILI cases was developed and successfully implemented. The algorithm demonstrated a high sensitivity, a high negative predictive value, along with significant efficiency and utility in a real-time PV database.


Subject(s)
Chemical and Drug Induced Liver Injury , Drug-Related Side Effects and Adverse Reactions , Algorithms , Chemical and Drug Induced Liver Injury/diagnosis , Chemical and Drug Induced Liver Injury/epidemiology , Chemical and Drug Induced Liver Injury/etiology , Databases, Factual , Drug-Related Side Effects and Adverse Reactions/diagnosis , Drug-Related Side Effects and Adverse Reactions/epidemiology , Humans , Pharmacovigilance
3.
Sensors (Basel) ; 20(24)2020 Dec 13.
Article in English | MEDLINE | ID: mdl-33322153

ABSTRACT

The article is devoted to the theoretical and experimental study of a magnetoelectric (ME) current sensor based on a gradient structure. It is known that the use of gradient structures in magnetostrictive-piezoelectric composites makes it possible to create a self-biased structure by replacing an external magnetic field with an internal one, which significantly reduces the weight, power consumption and dimensions of the device. Current sensors based on a gradient bidomain structure LiNbO3 (LN)/Ni/Metglas with the following layer thicknesses: lithium niobate-500 µm, nickel-10 µm, Metglas-29 µm, operate on a linear section of the working characteristic and do not require the bias magnetic field. The main characteristics of a contactless ME current sensor: its current range measures up to 10 A, it has a sensitivity of 0.9 V/A, its current consumption is not more than 2.5 mA, and its linearity is maintained to an accuracy of 99.8%. Some additional advantages of a bidomain lithium niobate-based current sensor are the increased sensitivity of the device due to the use of the bending mode in the electromechanical resonance region and the absence of a lead component in the device.

4.
Rev Sci Instrum ; 90(2): 023303, 2019 Feb.
Article in English | MEDLINE | ID: mdl-30831735

ABSTRACT

The Hybrid Photodetector (HPD) is a hybrid unit with a single accelerating gap between a common photocathode and an array of PIN diodes. Customised HPDs with 19 channels were used to detect scintillation light from hadron calorimeter in the Compact Muon Solenoid (CMS) experiment. In this paper, we present results on radiation damage studies carried out on the used HPDs in the outer hadron (HO) and the end-cap hadron (HE) calorimeter of the CMS experiment operating at CERN. The calorimeter is made of alternating layers of scintillating tiles and metals, such as brass or iron. The scintillating light was transmitted to the HPDs by means of optical fibres. Due to excessive exposure to scintillation light and ionising radiation during data taking at the Large Hadron Collider, the performance of the HPDs was expected to degrade significantly in the HE detector. Independent studies on radiation damage of these used photosensors were important to assess the degradation in the performance of the calorimeter. Microscopic scans of relative photon detection efficiencies for two HPDs (one each from HO and HE detector) were made using micron resolution optical scanner. The scanner was specially designed and built for microscopic characterisation of photosensors. Imprints of each fibre (∼1 mm in diameter) on the photocathode with varying damage within the same pixel of the HPD were observed. The localised damage of the photocathode was determined to vary with the amount of scintillation (or calibration) light transmitted by optical fibres to the HPD.

5.
Mini Rev Med Chem ; 19(9): 708-719, 2019.
Article in English | MEDLINE | ID: mdl-30058483

ABSTRACT

In this review, specific therapeutic and medicinal advantages including antiviral, antibacterial, antifungal and antitumor, strategies for drug designing, structure-activity relationship, advances in the syntheses of azo and hippuric acid derivatives of more than 50 compounds have been discussed since 2009-2018. It is found that phenyl-diazenyl azo derivatives and pyridinyl substituted hippuric acid derivatives showed promising antiretroviral potential. The incorporation of azo functionality to the respective quinolones and coumarin moieties and the insertion of thiocarbazone to hippuric acid displayed immense antibacterial activities. While, azo and hippuric acid derivatives of triazole and phenyl species gave maximum fungicidal as well as cytotoxic activities.


Subject(s)
Anti-Infective Agents/chemistry , Anti-Infective Agents/pharmacology , Antineoplastic Agents/chemistry , Antineoplastic Agents/pharmacology , Azo Compounds/chemistry , Azo Compounds/pharmacology , Hippurates/chemistry , Hippurates/pharmacology , Animals , Anti-Infective Agents/chemical synthesis , Antineoplastic Agents/chemical synthesis , Azo Compounds/chemical synthesis , Bacterial Infections/drug therapy , Drug Design , Hippurates/chemical synthesis , Humans , Mycoses/drug therapy , Neoplasms/drug therapy , Structure-Activity Relationship , Virus Diseases/drug therapy
7.
Opt Lett ; 43(7): 1455-1458, 2018 Apr 01.
Article in English | MEDLINE | ID: mdl-29601003

ABSTRACT

The Z-scan technique, using femtosecond (fs) laser pulses at 1480 nm laser pulses, was used to measure the nonlinear optical properties of gold (Au) nanoparticle (NP) films made by both nanosecond (ns) and fs pulsed laser deposition (PLD) in vacuum. At irradiance levels of 1×1012 Wm-2, the ns-PLD films displayed induced absorption with ß=4×10-5 mW-1, and a negative lensing effect with n2=-4.7×10-11 m2 W-1 with somewhat smaller values for the fs-PLD films. These values of n2 imply an unphysically large change in the real part of the refractive index, demonstrating the need to take account of nonlinear changes of the Fresnel coefficients and multiple beam interference in Z-scan measurements on nanoscale films. Following this approach, the Z-scan observations were analyzed to determine the effective complex refractive index of the NP film at high irradiance. It appears that at high irradiance the NP film behaves as a metal, while at low irradiance it behaves as a low-loss dielectric. Thus, it is conjectured that, for high irradiance near the waist of the Z-scan laser beam, laser driven electron tunneling between NPs gives rise to metal-like optical behavior.

8.
Trop Biomed ; 35(1): 140-148, 2018 Mar 01.
Article in English | MEDLINE | ID: mdl-33601786

ABSTRACT

Trypanosomiasis is one of the most pathogenic infection of livestock caused by several Trypanosoma species. The current study aims to determine the current prevalence of trypanosomiasis in livestock of Cholistan desert, Pakistan by molecular characterization. A total 272 animals, 61 camels, 59 cattle, 50 goats, 50 sheep and 52 donkeys that were bled and processed for thin smear microscopy, packed cell volume (PCV), DNA extraction, PCR, formol gel test and for cryo preservation. For diagnosis and molecular characterization, three sets of primers including TBR, RoTat 1.2, TRYP4 were used which detect their targets including repeated satellite DNA region, variant surface glycoprotein (VSG) gene and the ITS ribosomal DNA sequence of microbe. According to results, 6.2% animals were positive by microscopy, 51.1% by formol gel, 54.7% by PCV and 36.7% by PCR. The results of this study support the idea that PCR is a sensitive, robustic and reliable technique to diagnose trypanosomiasis and it should be added in conventional setup along with microscopy to avoid false negative and positive results. The PCR based order of prevalence of trypanosomiasis in Cholistani livestock was sheeps>camels>donkeys>goats>cattle. Similary, on the basis of thin smear microscopy the prevalence of trypanosomiasis was donkeys>camels>sheep>goats>cattle. It was observed that Trypanosoma evansi is the most prevalent specie involved in trypanosomiasis in Cholistani livestock.

9.
Trop Biomed ; 34(1): 137-142, 2017 Mar 01.
Article in English | MEDLINE | ID: mdl-33592991

ABSTRACT

Mycobacterium tuberculosis has infected one third of the world's population and 1.5 million people die each year due to tuberculosis. The research was conducted to make clones of M. tb gene Rv0378 during January-November, 2015. Gene Rv0378 has a gene length 222bp and was amplified using proper sequence specific primers. The size and quality of DNA fragments were determined by agarose gel electrophoresis. PCR product was then ligated in Vector PtZ57R/T (T/A vector) in order to be transformed into competent alpha-DH5 (E. coli) cells. Ampicillin positive clones were selected from the plates, introduced in the autoclaved test tubes with 2 to 3 ml. SOB broth was then placed in a shaker incubator for overnight at 37ºC. Next day turbidity was clearly observed in the test tubes indicating the culture was ready to use for plasmid extraction. DNA was extracted by using Genejet Plasmid extraction miniprep Kit by Thermo scientific. Size of the extracted construct was about >3000bp (other impurities of proteins and salts are washed away in EZ-Spin columns). In next step it will be cloned into pND14 (A mammalian expression vector) to make candidate vaccine and will be tested for its efficacy against M. tb.

10.
Transfus Med ; 27(1): 10-15, 2017 Feb.
Article in English | MEDLINE | ID: mdl-27730692

ABSTRACT

OBJECTIVE: The aim of the study was to determine the frequency and reasons for donor deferral prior to the blood donation process in our population. BACKGROUND: Transfusion is an irreversible event that carries potential risks as well as benefits to the recipient. Therefore, donor selection prior to blood donation is one of the most important steps in ensuring the safety of blood and blood products. METHODS: A cross-sectional study was carried out at the blood bank department in our hospital from January 2012 to December 2014. All the blood donors who visited our department in the study period were included in this study. RESULTS: A total of 25 901 potential donations were recorded during the study period, comprising 24 309 (93·8%) replacement and 1592 (6·2%) voluntary donations. Females accounted for only 222 (0·9%) of potential donations. Deferral occurred in 3156 (12·2%) of attempts; 280 (1·1%) were permanently deferred, while 2876 (11·1%) were temporarily deferred. The most common reason for permanent deferral was a history of hepatitis B infection (n = 147, 4·7% of all deferrals). Major reasons for temporary donor deferral were low levels of haemoglobin (n = 971, 30·76%), low levels of platelets (n = 611, 19·35%) and previous history of jaundice (n = 192, 6·1%). CONCLUSIONS: This study reported a fairly similar pattern of donor deferrals as in other regional studies. Low haemoglobin levels and a history of hepatitis B infection were the most common factors for temporary and permanent donor deferrals, respectively.


Subject(s)
Blood Donors , Donor Selection/methods , Adolescent , Adult , Cross-Sectional Studies , Donor Selection/organization & administration , Female , Hemoglobins/metabolism , Hepatitis B/blood , Humans , Male , Middle Aged , Pakistan
11.
Comput Methods Programs Biomed ; 137: 149-166, 2016 Dec.
Article in English | MEDLINE | ID: mdl-28110721

ABSTRACT

Therapies with magnetic/electromagnetic field are employed to relieve pains or, to accelerate flow of blood-particles, particularly during the surgery. In this paper, a theoretical study of the blood flow along with particles suspension through capillary was made by the electro-magneto-hydrodynamic approach. Analytical solutions to the non-dimensional blood velocity and non-dimensional particles velocity are obtained by means of the Laplace transform with respect to the time variable and the finite Hankel transform with respect to the radial coordinate. The study of thermally transfer characteristics is based on the energy equation for two-phase thermal transport of blood and particles suspension with viscous dissipation, the volumetric heat generation due to Joule heating effect and electromagnetic couple effect. The solution of the nonlinear heat transfer problem is derived by using the velocity field and the integral transform method. The influence of dimensionless system parameters like the electrokinetic width, the Hartman number, Prandtl number, the coefficient of heat generation due to Joule heating and Eckert number on the velocity and temperature fields was studied using the Mathcad software. Results are presented by graphical illustrations.


Subject(s)
Blood Circulation , Capillaries/physiology , Electromagnetic Fields , Hydrodynamics , Models, Theoretical , Static Electricity
12.
Clin Exp Pharmacol Physiol ; 42(10): 1059-67, 2015 Oct.
Article in English | MEDLINE | ID: mdl-26174505

ABSTRACT

Orexin/hypocretin neurons are located in and around the perifornical hypothalamus. Disinhibition of this area in the anaesthetized preparation evokes cardiorespiratory changes that can be reduced to nearly half or more by systemic Almorexant, a dual receptor antagonist of the two known orexin receptors, Ox1R and Ox2R. It is not clear if these reductions result from the blockade of one receptor or both. To determine the contribution of the two receptors, we compared the effects of Almorexant to those of the selective Ox1R antagonist ACT335827 and the selective Ox2R antagonists EMPA and TCS-OX2-29. Bicuculline (20 pmol) was injected in the perifornical hypothalamus of urethane-anaesthetized rats before and after administration of the drugs (all 15 mg/kg, intravenously). The pressor, tachycardic and tachypneic responses to bicuculline were attenuated/reduced by ACT335827 (by 19%, ns; 10%, ns and 24%, P < 0.01, respectively), EMPA (by 35% P < 0.01; 6%, ns; and 26% P < 0.05) and TCS-OX2-29 (by 13%, ns; 10%, ns and 42%, P < 0.001). These reductions represented only a fraction of the reduction after Almorexant (by 43%, P < 0.001; 42%, P < 0.001 and 65% P < 0.001). However, when the selective Ox1R and Ox2R antagonists were given in combination, the reductions were greater and closer to those of Almorexant (ACT335827 + EMPA, by 26%, P < 0.05; 24%, P < 0.05 and 47%, P < 0.001; ACT335827 + TCS-OX2-29, by 40%, P < 0.01; 26%, P < 0.001 and 59%, P < 0.0001). This was particularly clear with the tachypneic response. These results suggest that both orexin receptors contribute to the cardiorespiratory response evoked from the hypothalamus under anaesthesia. They are consistent with our previous study in the conscious animal.


Subject(s)
Blood Pressure/drug effects , Heart Rate/drug effects , Hypothalamus/physiology , Orexin Receptor Antagonists/pharmacology , Orexin Receptors/metabolism , Respiration/drug effects , Anesthesia , Animals , Hypothalamus/drug effects , Male , Rats , Rats, Wistar
13.
Am J Physiol Regul Integr Comp Physiol ; 308(10): R816-22, 2015 May 15.
Article in English | MEDLINE | ID: mdl-25761699

ABSTRACT

The dorsomedial hypothalamus (DMH) and the perifornical area (DMH/PeF) is one of the key regions of central autonomic processing. Previous studies have established that this region contains neurons that may be involved in respiratory processing; however, this has never been tested in conscious animals. The aim of our study was to investigate the involvement of the DMH/PeF area in mediating respiratory responses to stressors of various intensities and duration. Adult male Wistar rats (n = 8) received microinjections of GABAA agonist muscimol or saline into the DMH/PeF bilaterally and were subjected to a respiratory recording using whole body plethysmography. Presentation of acoustic stimuli (500-ms white noise) evoked transient responses in respiratory rate, proportional to the stimulus intensity, ranging from +44 ± 27 to +329 ± 31 cycles/min (cpm). Blockade of the DMH/PeF almost completely abolished respiratory rate and tidal volume responses to the 40- to 70-dB stimuli and also significantly attenuated responses to the 80- to 90-dB stimuli. Also, it significantly attenuated respiratory rate during the acclimatization period (novel environment stress). The light stimulus (30-s 2,000 lux) as well as 15-min restraint stress significantly elevated respiratory rate from 95 ± 4.0 to 236 ± 29 cpm and from 117 ± 5.2 to 189 ± 13 cpm, respectively; this response was abolished after the DMH/PeF blockade. We conclude that integrity of the DMH/PeF area is essential for generation of respiratory responses to both stressful and alerting stimuli.


Subject(s)
Arousal/physiology , Dorsomedial Hypothalamic Nucleus/physiopathology , Respiratory Rate/physiology , Stress, Physiological/physiology , Stress, Psychological/physiopathology , Acoustic Stimulation , Animals , Arousal/drug effects , Autonomic Nervous System/drug effects , Autonomic Nervous System/physiopathology , Dorsomedial Hypothalamic Nucleus/drug effects , GABA-A Receptor Agonists/pharmacology , Male , Muscimol/pharmacology , Photic Stimulation , Rats , Rats, Wistar , Respiratory Rate/drug effects , Stress, Physiological/drug effects
14.
Neuropharmacology ; 89: 146-56, 2015 Feb.
Article in English | MEDLINE | ID: mdl-25239810

ABSTRACT

Orexin contributes to the expression of the cardiovascular and behavioural response of some forms of stress, including novelty stress. Thus, Almorexant, a dual receptor antagonist that blocks the two known orexin receptors, Ox1R and Ox2R, reduces these responses. However, it is not known if the reduction results from blockade of one receptor only or both. To answer this question, the selective Ox1R antagonist ACT335827 and the selective Ox2R antagonist EMPA were injected intragastrically (300 mg/kg) or intraperitoneally (30 and 100 mg/kg) either alone or as a cocktail and compared to Almorexant in rats exposed to novelty stress. Cardiovascular and locomotor responses were recorded by radio-telemetry. Triple immunolabelling was also conducted to establish the distribution of Ox1R and Ox2R in sympathetic preganglionic neurons and orexin neurons. Intraperitoneal injections of ACT335827 (100 mg/kg) reduced the pressor and tachycardic but not the locomotor response of novelty (by 32% and 48%, respectively). Intraperitoneal injections of EMPA (100 mg/kg) only reduced the pressor response (42%). However when given together, ACT335827 and EMPA reduced all 3 components (65%, 60% and 57% of the tachycardic, pressor and locomotor responses, respectively) as Almorexant (100 mg/kg) did (69%, 87% and 72%, respectively). Triple immunolabelling revealed that sympathetic preganglionic neurons were mainly Ox1R positive only while orexin neurons were both Ox1R and Ox2R positive. This study shows that orexin's contribution to the cardiovascular and locomotor components of the novelty stress response is not mediated by one receptor alone, but by both receptors and at different levels of the neuraxis.


Subject(s)
Blood Pressure/physiology , Heart Rate/physiology , Motor Activity/physiology , Orexin Receptors/physiology , Stress, Psychological , Aminopyridines/pharmacology , Animals , Blood Pressure/drug effects , Heart Rate/drug effects , Male , Motor Activity/drug effects , Orexin Receptor Antagonists , Random Allocation , Rats , Rats, Wistar , Stress, Psychological/psychology , Sulfonamides/pharmacology
15.
J Family Community Med ; 21(2): 107-11, 2014 May.
Article in English | MEDLINE | ID: mdl-24987279

ABSTRACT

BACKGROUND: Ultrasound examination is very frequently used for the evaluation of abnormalities in various organs of the body. Our aim was to determine whether the requests by family physicians (FPs) for ultrasound examinations were appropriate. Our secondary objective was to enumerate positive and negative ultrasound reports for various diagnostic indications. MATERIALS AND METHODS: This cross-sectional study was conducted during the period of month between June and August 2010, at the Family Medicine Department of North West Armed Forces Prince Salman Hospital, Tabuk. We reviewed the ultrasound requests of all patients included in this study and the findings of the procedure. Data were analyzed using the Statistical Package for the Social Sciences (SPSS Inc., Chicago, IL), version 16.0. RESULTS: The requests and reports of 815 patients for ultrasound were reviewed. Females comprised 58.7% of the referred cases. The mean age of the sample at referral was 30 ± 18.5 for females and 34 ± 20.7 for males. Only 46% of the request forms contained conclusive information and instructions. Abdominal/pelvic ultrasounds were the most frequently requested; Nearly 71.2% of the ultrasound scans were normal. Abdominal/pelvis ultrasound was more likely to be reported as normal than ultrasound scans of other regions (P = 0.007). Patients aged 41-60 years were more likely to have an abnormal ultrasound (P = 0.02). CONCLUSION: Our findings suggest that FPs have to be educated about imaging referral protocols in order to achieve better outcomes.

16.
Nanotechnology ; 25(26): 265301, 2014 Jul 04.
Article in English | MEDLINE | ID: mdl-24915883

ABSTRACT

Nanoparticle (NP) films of silver were prepared using nanosecond (ns) and femtosecond (fs) pulsed laser deposition (PLD) in vacuum. The flux and energy distribution of the ions in the plasma part of the ablation plume were measured using a Langmuir ion probe. The deposition energy efficiencies of ns and fs silver PLD were also compared. For equivalent thickness up to ∼3 nm the NPs made by ns-PLD are well separated and roughly circular, but for higher thicknesses the NPs begin to coalesce. For equivalent thickness up to 7 nm the fs films are comprised of well separated NPs, though the mean NP size and the surface coverage increase with equivalent thickness. The mean Feret diameter for both ns- and fs-PLD films increases with increasing equivalent solid-density thickness. The surface plasmon resonance peak was observed to red shift for both ns- and fs-PLD films as the equivalent solid-density thickness was increased from 1 nm to 7 nm.

17.
Auton Neurosci ; 177(2): 217-23, 2013 Oct.
Article in English | MEDLINE | ID: mdl-23721955

ABSTRACT

The principal aim of this study was to determine whether prolonged chronic footshock stress can evoke sustained changes in blood pressure in rats and to elucidate possible underlying neurochemical mechanisms as mediated by the sympathoadrenal system. Adult male Wistar rats instrumented for telemetric recording of arterial pressure, heart rate and locomotor activity were subjected to six weeks of inescapable unpredictable electrical footshocks (FS+) or were exposed to shock chambers but were not shocked (FS-). Compared to FS- animals, FS+ animals had significantly reduced body weight gain (by 30%), locomotor activity (by 25%) and social interaction time (by 30%)--symptoms commonly induced by chronic stress and depression in humans. These changes were associated with small, but significant increases in systolic blood pressure (by 7%) and pulse pressure (by 11%) in FS+ rats relative to FS- rats. We have also found neurochemical alterations in sympathoadrenal pathways (that lasted for at least one week post-stress) including about 2-3 fold increases in the levels of tyrosine hydroxylase phosphorylation in the sympathetic ganglia and adrenal gland and a 1.8-fold increase in the expression of the Angiotensin II receptor type 1 protein in the adrenal gland of FS+ rats relative to FS- rats. We conclude that uncontrollable and unpredictable footshock stress can lead to elevation in systolic blood pressure when applied for an extended period of time (six weeks) in Wistar rats, and that these changes could be mediated by stress-induced modifications in sympathoadrenal pathways.


Subject(s)
Blood Pressure/physiology , Stress, Psychological/physiopathology , Stress, Psychological/psychology , Animals , Chronic Disease , Heart Rate/physiology , Male , Motor Activity/physiology , Random Allocation , Rats , Rats, Wistar
18.
PLoS One ; 8(3): e60072, 2013.
Article in English | MEDLINE | ID: mdl-23555888

ABSTRACT

Cyclohexylamine oxidase (CHAO) is a flavoprotein first described in Brevibacterium oxydans strain IH-35A that carries out the initial step of the degradation of the industrial chemical cyclohexylamine to cyclohexanone. We have cloned and expressed in Escherichia coli the CHAO-encoding gene (chaA) from B. oxydans, purified CHAO and determined the structures of both the holoenzyme form of the enzyme and a product complex with cyclohexanone. CHAO is a 50 kDa monomer with a PHBH fold topology. It belongs to the flavin monooxygenase family of enzymes and exhibits high substrate specificity for alicyclic amines and sec-alkylamines. The overall structure is similar to that of other members of the flavin monooxygenase family, but lacks either of the C- or N-terminal extensions observed in these enzymes. Active site features of the flavin monooxygenase family are conserved in CHAO, including the characteristic aromatic cage. Differences in the orientations of residues of the CHAO aromatic cage result in a substrate-binding site that is more open than those of its structural relatives. Since CHAO has a buried hydrophobic active site with no obvious route for substrates and products, a random acceleration molecular dynamics simulation has been used to identify a potential egress route. The path identified includes an intermediate cavity and requires transient conformation changes in a shielding loop and a residue at the border of the substrate-binding cavity. These results provide a foundation for further studies with CHAO aimed at identifying features determining substrate specificity and for developing the biocatalytic potential of this enzyme.


Subject(s)
Bacterial Proteins/chemistry , Bacterial Proteins/metabolism , Brevibacterium/enzymology , Oxidoreductases Acting on CH-NH Group Donors/chemistry , Oxidoreductases Acting on CH-NH Group Donors/metabolism , Substrate Specificity
19.
Cardiovasc Res ; 98(3): 428-36, 2013 Jun 01.
Article in English | MEDLINE | ID: mdl-23417038

ABSTRACT

AIMS: Inward remodelling of the resistance vasculature is predictive of hypertension and life-threatening cardiovascular events. We hypothesize that the contractile mechanisms responsible for maintaining a reduced diameter over time in response to prolonged stimulation with vasoconstrictor agonists are in part responsible for the initial stages of the remodelling process. Here we investigated the role of vascular smooth muscle (VSM) actin polymerization on agonist-induced vasoconstriction and development of inward remodelling. METHODS AND RESULTS: Experiments were conducted in Sprague-Dawley rat resistance vessels isolated from the cremaster and mesentery. Within blood vessels, actin dynamics of VSM were monitored by confocal microscopy after introduction of fluorescent actin monomers through electroporation and by differential centrifugation to probe globular (G) and filamentous (F) actin content. Results indicated that 4 h of agonist-dependent vasoconstriction induced inward remodelling and caused significant actin polymerization, elevating the F-/total-actin ratio. Inhibition of actin polymerization prevented vessels from maintaining prolonged vasoconstriction and developing inward remodelling. Activation of the small GTPases Rho/Rac/Cdc42 also increased the F-/total-actin ratio and induced inward remodelling, while inhibition of Rho kinase or Rac-1 prevented inward remodelling. Disruption of the actin cytoskeleton reversed the inward remodelling caused by prolonged vasoconstriction, but did not affect the passive diameter of freshly isolated vessels. CONCLUSION: These results indicate that vasoconstriction-induced inward remodelling is in part caused by the polymerization of actin within VSM cells through activation of small GTPases.


Subject(s)
Actin Cytoskeleton/metabolism , Actins/metabolism , Hypertension/metabolism , Muscle, Smooth, Vascular/metabolism , Vascular Resistance , Vasoconstriction , Actin Cytoskeleton/drug effects , Actin Cytoskeleton/pathology , Animals , Hypertension/pathology , Hypertension/physiopathology , Male , Mesenteric Arteries/metabolism , Mesenteric Arteries/pathology , Mesenteric Arteries/physiopathology , Muscle, Smooth, Vascular/drug effects , Muscle, Smooth, Vascular/pathology , Muscle, Smooth, Vascular/physiopathology , Polymerization , Protein Kinase Inhibitors/pharmacology , Rats , Rats, Sprague-Dawley , Signal Transduction , Time Factors , Vascular Resistance/drug effects , Vasoconstriction/drug effects , Vasoconstrictor Agents/pharmacology , cdc42 GTP-Binding Protein/metabolism , rac1 GTP-Binding Protein/antagonists & inhibitors , rac1 GTP-Binding Protein/metabolism , rho GTP-Binding Proteins/metabolism , rho-Associated Kinases/antagonists & inhibitors , rho-Associated Kinases/metabolism
20.
J Nepal Health Res Counc ; 10(1): 47-51, 2012 Jan.
Article in English | MEDLINE | ID: mdl-22929637

ABSTRACT

BACKGROUND: External validation of prognostic model for one-year mortality in patients ventilated for 21 days or more. A measure that identifies patients who are at high risk of mortality after prolonged ventilation will help physicians communicate prognoses to patients or surrogate decision makers. Our objective was to validate a prognostic model developed by Carson et al in a different setting. METHODS: An observational study was conducted from September 2002 to September 2007 in 30 beds Medical/Surgical Intensive Care Unit (ICU) at Mercy Fitzgerald Hospital (MFH) and 20 beds Medical/Surgical ICU at Mercy Philadelphia Hospital (MPH). One hundred and fifty medical and surgical patients requiring mechanical ventilation after acute illness for at least 21 days after initial intubation were enrolled. RESULTS: One year mortality was 45.4%. Area under the receiver operating characteristic curve for three month mortality was 0.90 and for one year mortality was 0.92. For identifying patients who had ≥90% risk of death at 3 month had sensitivity of 40% and specificity of 95% and risk of death at 1 year had sensitivity of 70% and specificity of 99%. Four predictive variables, requirement of vasopressors, hemodalysis, platelet count ≤ 150 x 10 9/L and age ≥50 yrs can be used as a simple prognostic score that clearly identifies low-risk patients and high-risk patients. CONCLUSIONS: Simple clinical variables measured on day 21 of mechanical ventilation can identify patients at highest and lowest risk of death from prolonged mechanical ventilation.


Subject(s)
Models, Theoretical , Respiration, Artificial/mortality , Adult , Aged , Aged, 80 and over , Female , Humans , Intensive Care Units , Male , Middle Aged , Philadelphia/epidemiology , Prognosis , Qualitative Research , ROC Curve , Sensitivity and Specificity , Surgery Department, Hospital , Time Factors
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