Displaying publications 1 - 20 of 263 in total

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  1. Shehabi Y, Howe BD, Bellomo R, Arabi YM, Bailey M, Bass FE, et al.
    N Engl J Med, 2019 Jun 27;380(26):2506-2517.
    PMID: 31112380 DOI: 10.1056/NEJMoa1904710
    BACKGROUND: Dexmedetomidine produces sedation while maintaining a degree of arousability and may reduce the duration of mechanical ventilation and delirium among patients in the intensive care unit (ICU). The use of dexmedetomidine as the sole or primary sedative agent in patients undergoing mechanical ventilation has not been extensively studied.

    METHODS: In an open-label, randomized trial, we enrolled critically ill adults who had been undergoing ventilation for less than 12 hours in the ICU and were expected to continue to receive ventilatory support for longer than the next calendar day to receive dexmedetomidine as the sole or primary sedative or to receive usual care (propofol, midazolam, or other sedatives). The target range of sedation-scores on the Richmond Agitation and Sedation Scale (which is scored from -5 [unresponsive] to +4 [combative]) was -2 to +1 (lightly sedated to restless). The primary outcome was the rate of death from any cause at 90 days.

    RESULTS: We enrolled 4000 patients at a median interval of 4.6 hours between eligibility and randomization. In a modified intention-to-treat analysis involving 3904 patients, the primary outcome event occurred in 566 of 1948 (29.1%) in the dexmedetomidine group and in 569 of 1956 (29.1%) in the usual-care group (adjusted risk difference, 0.0 percentage points; 95% confidence interval, -2.9 to 2.8). An ancillary finding was that to achieve the prescribed level of sedation, patients in the dexmedetomidine group received supplemental propofol (64% of patients), midazolam (3%), or both (7%) during the first 2 days after randomization; in the usual-care group, these drugs were administered as primary sedatives in 60%, 12%, and 20% of the patients, respectively. Bradycardia and hypotension were more common in the dexmedetomidine group.

    CONCLUSIONS: Among patients undergoing mechanical ventilation in the ICU, those who received early dexmedetomidine for sedation had a rate of death at 90 days similar to that in the usual-care group and required supplemental sedatives to achieve the prescribed level of sedation. More adverse events were reported in the dexmedetomidine group than in the usual-care group. (Funded by the National Health and Medical Research Council of Australia and others; SPICE III ClinicalTrials.gov number, NCT01728558.).

    Matched MeSH terms: Respiration, Artificial*
  2. Suhaily Amran, Ahmad Sayuti Zainal Abidin, Shoffian Amin Jaafar, Mohd Talib Latif, Abdul Mutalib Leman
    MyJurnal
    There are several alternative sampling and analytical methods available for the determination of respirable
    crystalline silica exposure among workers. The commonly used ones are, (1) NIOSH Manual Analytical Method
    No.7500(NMAM 7500) which is Silica, crystalline, by X-ray difractometer via filter deposition(NIOSH 2003), and
    (2) MDHS 101 (Methods for the Determination of Hazardous Substances (MDHS) Guidance No.101: Respirable
    crystalline silica in respirable airborne dust). The aim of this study is to compare applicability of respirable crystalline
    silica sampling and analysis between method MDHS 101 and NMAM 7500. Laboratory procedures will be performed
    strictly based on MDHS 101 and NMAM 7500. Both methods apply X-ray diffraction as analytical technique with
    many variations on sampling techniques and laboratory preparations. Quality assurance values such as detection
    limits, accuracy and precision are derived from both data and will be compared to determine which of the method
    establishes better quality assurance. The method which establishes better quality assurance will be recommend to be
    used in Malaysian respirable crystalline silica monitoring programme. The strength of this research lies on its potential
    to provide local capabilities in analysis of respirable crystalline silica in Malaysian setting.
    Matched MeSH terms: Respiration; Cell Respiration
  3. Faisal M, Harun H, Hassan TM, Ban AY, Chotirmall SH, Abdul Rahaman JA
    BMC Pulm Med, 2016;16(1):53.
    PMID: 27080697 DOI: 10.1186/s12890-016-0209-1
    Tracheobronchial stenosis is a known complication of endobronchial tuberculosis. Despite antituberculous and steroid therapy, the development of bronchial stenosis is usually irreversible and requires airway patency to be restored by either bronchoscopic or surgical interventions. We report the use of balloon dilatation and topical mitomycin-C to successful restore airway patency.
    Matched MeSH terms: Respiration Disorders
  4. Huan NC, Ng KL, Nasaruddin MZ, Muhammad NA, Daut UN, Abdul Rahaman JA
    Respirol Case Rep, 2021 Mar;9(3):e00711.
    PMID: 33532074 DOI: 10.1002/rcr2.711
    Tracheobronchial stenosis secondary to endobronchial tuberculosis (TSTB) is a rare but debilitating complication of endobronchial tuberculosis (EBTB). Topical mitomycin-C (TMC) has been successfully utilized to restore airway patency and to prevent recurrence of TSTB, although little is known about its exact efficacy. Here, we report the biggest case series to date involving seven patients who received TMC as part of multimodality endoscopic treatment for TSTB with varying levels of success. All patients presented with dyspnoea during or after treatment completion for pulmonary tuberculosis (PTB). Four patients had short-segment concentric membranous TSTB while two patients had concurrent bronchomalacia. Another one patient had a thick fibrotic band adjacent to luminal opening. We hypothesize that TMC is more efficacious in short membranous stenosis without concurrent bronchomalacia and/or thick fibrotic bands. More studies are needed to bridge the current gaps in knowledge regarding the optimal role and benefits of TMC for TSTB patients.
    Matched MeSH terms: Respiration Disorders
  5. Isa R, Wan Adnan WA, Ghazali G, Idris Z, Ghani AR, Sayuthi S, et al.
    Neurosurg Focus, 2003 Dec 15;15(6):E1.
    PMID: 15305837
    The determination of cerebral perfusion pressure (CPP) is regarded as vital in monitoring patients with severe traumatic brain injury. Besides indicating the status of cerebral blood flow (CBF), it also reveals the status of intracranial pressure (ICP). The abnormal or suboptimal level of CPP is commonly correlated with high values of ICP and therefore with poor patient outcomes. Eighty-two patients were divided into three groups of patients receiving treatment based on CPP and CBF, ICP alone, and conservative methods during two different observation periods. The characteristics of these three groups were compared based on age, sex, time between injury and hospital arrival, Glasgow Coma Scale score, pupillary reaction to light, surgical intervention, and computerized tomography scanning findings according to the Marshall classification system. Only time between injury and arrival (p = 0.001) was statistically significant. There was a statistically significant difference in the proportions of good outcomes between the multimodality group compared with the group of patients that underwent a single intracranial-based monitoring method and the group that received no monitoring (p = 0.003) based on a disability rating scale after a follow up of 12 months. Death was the focus of outcome in this study in which the multimodality approach to monitoring had superior results.
    Matched MeSH terms: Respiration, Artificial
  6. Ismail, I., Yap, B.W., Abidin, A.S.Z.
    MyJurnal
    Prolonged mechanical ventilation (PMV) is associated with increase in mortality and resource utilisation as well as hospitalisation costs. This study evaluates the risk factors of PMV. A retrospective study was conducted involving 890 paediatric patients comprising 237 neonates, 306 infants, 223 of pre-school age and 124 who are of school going age. The data mining decision trees algorithms and logistic regression was employed to develop predictive models for each age category. The independent variables were classified into four categories, that is, demographic data, admission factors, medical factors and score factors. The dependent variable is the duration of ventilation where it is categorized 0 denoting non-PMV and 1 denoting PMV. The performances of three decision tree models (CHAID, CART and C5.0) and logistic regression were compared to determine the best model. The results indicated that the decision tree outperformed the logistic regression model for all age categories, given its good accuracy rate for testing dataset. Decision trees results identified length of stay and inotropes as significant risk factors in all age categories. PRISM 12 hours and principal diagnosis were identified as significant risk factors for infants.
    Matched MeSH terms: Respiration, Artificial
  7. Chua EX, Zahir SMISM, Ng KT, Teoh WY, Hasan MS, Ruslan SRB, et al.
    J Clin Anesth, 2021 Nov;74:110406.
    PMID: 34182261 DOI: 10.1016/j.jclinane.2021.110406
    STUDY OBJECTIVE: To review the effects of prone position and supine position on oxygenation parameters in patients with Coronavirus Disease 2019 (COVID-19).

    DESIGN: Systematic review and meta-analysis of non-randomized trials.

    PATIENTS: Databases of EMBASE, MEDLINE and CENTRAL were systematically searched from its inception until March 2021.

    INTERVENTIONS: COVID-19 patients being positioned in the prone position either whilst awake or mechanically ventilated.

    MEASUREMENTS: Primary outcomes were oxygenation parameters (PaO₂/FiO₂ ratio, PaCO₂, SpO₂). Secondary outcomes included the rate of intubation and mortality rate.

    RESULTS: Thirty-five studies (n = 1712 patients) were included in this review. In comparison to the supine group, prone position significantly improved the PaO₂/FiO₂ ratio (study = 13, patients = 1002, Mean difference, MD 52.15, 95% CI 37.08 to 67.22; p 

    Matched MeSH terms: Respiration, Artificial*
  8. Viswabhargav CSS, Tripathy RK, Acharya UR
    Comput Biol Med, 2019 05;108:20-30.
    PMID: 31003176 DOI: 10.1016/j.compbiomed.2019.03.016
    Sleep is a prominent physiological activity in our daily life. Sleep apnea is the category of sleep disorder during which the breathing of the person diminishes causing the alternation in the upper airway resistance. The electrocardiogram derived respiration (EDR) and heart rate (RR-time-series) signals are normally used for the detection of sleep apnea as these two signals capture cardio-pulmonary activity information. Hence, the analysis of these two signals provides vital information about sleep apnea. In this paper, we propose the novel sparse residual entropy (SRE) features for the automated detection of sleep apnea using EDR and heart rate signals. The features required for the automated detection of sleep apnea are extracted in three steps: (i) atomic decomposition based residual estimation from both EDR and heart rate signals using orthogonal matching pursuit (OMP) with different dictionaries, (ii) estimation of probabilities from each sparse residual, and (iii) calculation of the entropy features. The proposed SRE features are fed to the combination of fuzzy K-means clustering and support vector machine (SVM) to pick the best performing classifier. The experimental results demonstrate that the proposed SRE features with radial basis function (RBF) kernel-based SVM classifier yielded higher performance with accuracy, sensitivity and specificity values of 78.07%, 78.01%, and 78.13%, respectively with Fourier dictionary and 10-fold cross-validation. For subject-specific or leave-one-out validation case, the SVM classifier has sensitivity and specificity of 85.43% and 92.60%, respectively using SRE features with Fourier dictionary (FD).
    Matched MeSH terms: Respiration*
  9. Mallhi TH, Khan YH, Adnan AS
    Am J Trop Med Hyg, 2020 Dec;103(6):2164-2167.
    PMID: 33124548 DOI: 10.4269/ajtmh.20-0794
    Despite myriad improvements in the care of COVID-19 patients, atypical manifestations are least appreciated during the current pandemic. Because COVID-19 is primarily manifesting as an acute respiratory illness with interstitial and alveolar pneumonia, the possibility of viral invasions into the other organs cannot be disregarded. Acute kidney injury (AKI) has been associated with various viral infections including dengue, chikungunya, Zika, and HIV. The prevalence and risks of AKI during the course of COVID-19 have been described in few studies. However, the existing literature demonstrate great disparity across findings amid variations in methodology and population. This article underscores the propensity of AKI among COVID-19 patients, limitations of the exiting evidence, and importance of timely identification during the case management. The prevalence of AKI is variable across the studies ranging from 4.7% to 81%. Evidence suggest old age, comorbidities, ventilator support, use of vasopressors, black race, severe infection, and elevated levels of baseline serum creatinine and d-dimers are independent risk factors of COVID-19 associated with AKI. COVID-19 patients with AKI also showed unsatisfactory renal recovery and higher mortality rate as compared with patients without AKI. These findings underscore that AKI frequently occurs during the course of COVID-19 infection and requires early stratification and management.
    Matched MeSH terms: Respiration, Artificial/adverse effects
  10. Hamid SA, Adnan WW, Naing NN, Adnan AS
    Saudi J Kidney Dis Transpl, 2018 11 2;29(5):1109-1114.
    PMID: 30381507 DOI: 10.4103/1319-2442.243961
    Acute kidney injury (AKI) was frequently encountered complication among intensive care unit (ICU) patients and recognized as a major public health problem. The present study aimed to determine the basic features of AKI patients admitted to ICU. A retrospective cohort study was conducted among 106 AKI patients admitted to ICU, Hospital Universiti Sains Malaysia from January 1, 2007 until the end of December 2013. The AKI patients ranged from 18 to 80 years old with the mean (standard deviation) of 58.93 (15.76) years, 60.4% were male and 91.5% were Malay ethnicity. Hypertension and diabetes were in 38.1% and 28.8%, respectively. The median (interquartile range) length of ICU stay was 4.50 (9.00) days. Eighty-two patients (79.6%) were classified as the Acute Kidney Injury Network (AKIN)-I, 12 (11.7%) as AKIN-II, and nine (8.7%) as AKIN-III. Sepsis was the common etiology among AKI patients (74.3%). Twenty-four patients (22.9%) required dialysis and 90.5% were mechanically ventilated. In conclusion, AKI developed more in male patients, Malay ethnicity, presented with comorbid, caused by sepsis, admitted to ICU, required mechanical ventilation, and need for renal replacement therapy.
    Matched MeSH terms: Respiration, Artificial
  11. Nor Mohd Razif Noraini, Leman, A.M., Ahmad Sayuti Zainal Abidin
    MyJurnal
    A preliminary study has been conducted in a new constructed 8 stories building (2 level of Hostels facility, 3 level of Training Room, 2 Level of Offices and 1 level of Exhibition Halls and Rooms) in Bandar Baru Bangi, Selangor. The Hostels facility is a floor tile and furnished with build in locker and use split air conditioning system while the Training Room and Exhibition Rooms used floor tile. The Offices and Exhibition Hall are carpeted furnished. All these spaces were using centralized air conditioning systems. A pre-commissioning assessment on 5 chemical parameters of indoor air pollutants such Total Volatile Organic Compounds (TVOC), Formaldehyde, Respirable Particulates (PM!
    Matched MeSH terms: Respiration; Cell Respiration
  12. Boo NY, Ong LC, Lye MS, Chandran V, Teoh SL, Zamratol S, et al.
    J Paediatr Child Health, 1996 Oct;32(5):439-44.
    PMID: 8933407
    OBJECTIVE: To compare the morbidities in the very low birthweight (VLBW; < 1500 g) and normal birthweight (NBW; > or = 2500 g) Malaysian infants during the first year of life.

    METHODOLOGY: Prospective observational cohort study of consecutive surviving VLBW infants and randomly sampled NBW infants born in the Kuala Lumpur Maternity Hospital between 1 December 1989 and 31 December 1992. Infants were followed up regularly during the first year of life, after correction for prematurity.

    RESULTS: Compared with NBW infants (n = 106), VLBW infants (n = 127) had significantly higher risk of failure to thrive (odds ratio [OR] = 8.0, 95% confidence intervals [CI]: 1.1 to 354.3), wheezing (OR = 3.7, 95% CI: 1.6 to 9.3), rehospitalization (OR = 2.3, 95% CI: 1.1 to 5.0), cerebral palsy (OR = 8.6, 95% CI: 2.0 to 77.6), neurosensory hearing loss (OR = 12.0, 95% CI: 1.7 to 513.6) and visual loss (7.9 vs 0%, P = 0.002). The mean mental developmental index (MDI) and mean psychomotor developmental index (PDI) at 1 year of age were significantly lower among VLBW infants (MDI 99 [SD = 28], PDI 89 [SD = 25]) than NBW infants (MDI 106 [SD = 18], PDI 101 [SD = 18]) (95% CI for difference between means being MDI: -14.1 to -1.7; and PDI: -17.6 to -6.0). Logistic regression analysis showed that among VLBW infants: (i) male sex, Malay ethnicity and bronchopulmonary dysplasia were significant risk factors associated with wheezing; (ii) longer duration of oxygen therapy during the neonatal period, seizures after the post-neonatal period and wheezing were significant risk factors associated with rehospitalization; and (iii) longer duration of oxygen therapy during the neonatal period was a significant risk factor associated with adverse neurodevelopmental outcome during the first year of life.

    CONCLUSIONS: Compared with NBW infants, VLBW Malaysian infants had significantly higher risks of physical and neuro-developmental morbidities.

    Matched MeSH terms: Respiration Disorders/etiology
  13. Azrina, M.R., Basri, M.N., Abdul Hadi, M., Fahmi, M.L., Asmarawati, M.Y., Ariff, O.
    MyJurnal
    High frequency oscillating ventilation (HFOV) provides a rescue therapy for patients with refractory hypoxaemia in severe acute respiratory distress syndrome (ARDS). HFOV utilizes high mean airway pressures to maintain an open lung and low tidal volumes at a high frequency that allows for adequate ventilation while at the same time preventing alveolar overdistension. This seems to be an ideal lung protective ventilation strategies to prevent ventilator-induced lung injury (VILI)2. We reported a case of severe extrapulmonary ARDS secondary to acute lymphoblastic leukaemia responding to the use of HFOV.
    Matched MeSH terms: Respiration; Respiration, Artificial
  14. Rashid FAA, Scafaro AP, Asao S, Fenske R, Dewar RC, Masle J, et al.
    New Phytol, 2020 10;228(1):56-69.
    PMID: 32415853 DOI: 10.1111/nph.16661
    Leaf respiration in the dark (Rdark ) is often measured at a single time during the day, with hot-acclimation lowering Rdark at a common measuring temperature. However, it is unclear whether the diel cycle influences the extent of thermal acclimation of Rdark , or how temperature and time of day interact to influence respiratory metabolites. To examine these issues, we grew rice under 25°C : 20°C, 30°C : 25°C and 40°C : 35°C day : night cycles, measuring Rdark and changes in metabolites at five time points spanning a single 24-h period. Rdark differed among the treatments and with time of day. However, there was no significant interaction between time and growth temperature, indicating that the diel cycle does not alter thermal acclimation of Rdark . Amino acids were highly responsive to the diel cycle and growth temperature, and many were negatively correlated with carbohydrates and with organic acids of the tricarboxylic acid (TCA) cycle. Organic TCA intermediates were significantly altered by the diel cycle irrespective of growth temperature, which we attributed to light-dependent regulatory control of TCA enzyme activities. Collectively, our study shows that environmental disruption of the balance between respiratory substrate supply and demand is corrected for by shifts in TCA-dependent metabolites.
    Matched MeSH terms: Cell Respiration
  15. Norhaya MR, Wazi RA, Azhar AA
    Med J Malaysia, 2009 Mar;64(1):77-9.
    PMID: 19852329
    Treatment for chronic respiratory failure has advanced since the introduction of domiciliary non-invasive ventilatory devices. This has given a new light of hope for patients with chronic respiratory failure secondary to various causes. We report a series of patients with respiratory failure of different origins and types of management that they received. Four patients received bilevel positive airway pressure (BiPAP) and one patient received continuous positive airway pressure (CPAP).
    Matched MeSH terms: Positive-Pressure Respiration; Respiration, Artificial/instrumentation*
  16. Ahmad N, Tan CC, Balan S
    Med J Malaysia, 2007 Jun;62(2):122-6.
    PMID: 18705443 MyJurnal
    We sought to review the current practice of sedation and analgesia in intensive care units (ICUs) in Malaysian public hospitals. A questionnaire survey was designed and sent by mail to 40 public hospitals with ICU facility in Malaysia. The anaesthesiologists in charge of ICU were asked to complete the questionnaire. Thirty seven questionnaires were returned (92.5% response rate). Only 35% respondents routinely assess the degree of sedation. The Ramsay scale was used prevalently. A written protocol for sedation was available in only 14 centers (38%). Although 36 centers (95%) routinely adjust the degree of sedation according to patient's clinical progress, only 10 centers (14%) interrupt sedation on a daily basis. Most respondents agreed that the selection of agents for sedation depends on familiarity (97%), pharmacology (97%), the expected duration for sedation (92%), patient's clinical diagnosis (89%) and cost (73%). Midazolam (89%) and morphine (86%) were the most commonly used agents for sedation and analgesia, respectively. Only 14% respondents still frequently use neuromuscular blocking agents, mostly in head injury patients. Our survey showed similarity in the choice of sedative and analgesic agents in ICUs in Malaysian public hospitals comparable to international practice. Nevertheless, the standard of practice could still be improved by implementing the practice of sedation score assessment and daily interruption of sedative infusion as well as having a written protocol for sedation and analgesia.
    Matched MeSH terms: Respiration, Artificial
  17. Lee ZY, Noor Airini I, Barakatun-Nisak MY
    Clin Nutr, 2018 08;37(4):1264-1270.
    PMID: 28599979 DOI: 10.1016/j.clnu.2017.05.013
    BACKGROUND & AIMS: The effect of provision of full feeding or permissive underfeeding on mortality in mechanically ventilated critically ill patients in the intensive care unit (ICU) is still controversial. This study investigated the relationship of energy and protein intakes with 60-day mortality, and the extent to which ICU length of stay and nutritional risk status influenced this relationship.

    METHODS: This is a prospective observational study conducted among critically ill patients aged ≥18 years, intubated and mechanically ventilated within 48 h of ICU admission and stayed in the ICU for at least 72 h. Information on baseline characteristics and nutritional risk status (the modified Nutrition Risk in Critically ill [NUTRIC] score) was collected on day 1. Nutritional intake was recorded daily until death, discharge, or until the twelfth evaluable days. Mortality status was assessed on day 60 based on the patient's hospital record. Patients were divided into 3 groups a) received <2/3 of prescribed energy and protein (both <2/3), b) received ≥2/3 of prescribed energy and protein (both ≥2/3) and c) either energy or protein received were ≥2/3 of prescribed (either ≥2/3). The relationship between the three groups with 60-day mortality was examined by using logistic regression with adjustment for potential confounders. Sensitivity analysis was performed to examine the influence of ICU length of stay (≥7 days) and nutritional risk status.

    RESULTS: Data were collected from 154 mechanically ventilated patients (age, 51.3 ± 15.7 years; body mass index, 26.5 ± 6.7 kg/m2; 54% male). The mean modified NUTRIC score was 5.7 ± 1.9, with 56% of the patients at high nutritional risk. The patients received 64.5 ± 21.6% of the amount of energy and 56.4 ± 20.6% of the amount of protein prescribed. Provision of energy and protein at ≥2/3 compared with <2/3 of the prescribed amounts was associated with a trend towards increased 60-day mortality (Adjusted odds ratio [Adj OR] 2.23; 95% confidence interval [CI], 0.92-5.38; p = 0.074). No difference in mortality status was found between energy and protein provision at either ≥2/3 compared with <2/3 of the prescribed amounts (Adj OR 1.61, 95% CI, 0.58-4.45; p = 0.357). Nutritional risk status, not ICU length of stay, influenced the relationship between nutritional adequacy and 60-day mortality.

    CONCLUSIONS: Energy and protein adequacy of ≥2/3 of the prescribed amounts were associated with a trend towards increased 60-day mortality among mechanically ventilated critically ill patients. However, neither energy nor protein adequacy alone at ≥ or <2/3 adequacy affect 60-day mortality. Increased mortality was associated with provision of energy and protein at ≥2/3 of the prescribed amounts, which only affected patients with low nutritional risk.

    Matched MeSH terms: Respiration, Artificial/mortality*
  18. Yu EPK, Reinhold J, Yu H, Starks L, Uryga AK, Foote K, et al.
    Arterioscler Thromb Vasc Biol, 2017 12;37(12):2322-2332.
    PMID: 28970293 DOI: 10.1161/ATVBAHA.117.310042
    OBJECTIVE: Mitochondrial DNA (mtDNA) damage is present in murine and human atherosclerotic plaques. However, whether endogenous levels of mtDNA damage are sufficient to cause mitochondrial dysfunction and whether decreasing mtDNA damage and improving mitochondrial respiration affects plaque burden or composition are unclear. We examined mitochondrial respiration in human atherosclerotic plaques and whether augmenting mitochondrial respiration affects atherogenesis.

    APPROACH AND RESULTS: Human atherosclerotic plaques showed marked mitochondrial dysfunction, manifested as reduced mtDNA copy number and oxygen consumption rate in fibrous cap and core regions. Vascular smooth muscle cells derived from plaques showed impaired mitochondrial respiration, reduced complex I expression, and increased mitophagy, which was induced by oxidized low-density lipoprotein. Apolipoprotein E-deficient (ApoE-/-) mice showed decreased mtDNA integrity and mitochondrial respiration, associated with increased mitochondrial reactive oxygen species. To determine whether alleviating mtDNA damage and increasing mitochondrial respiration affects atherogenesis, we studied ApoE-/- mice overexpressing the mitochondrial helicase Twinkle (Tw+/ApoE-/-). Tw+/ApoE-/- mice showed increased mtDNA integrity, copy number, respiratory complex abundance, and respiration. Tw+/ApoE-/- mice had decreased necrotic core and increased fibrous cap areas, and Tw+/ApoE-/- bone marrow transplantation also reduced core areas. Twinkle increased vascular smooth muscle cell mtDNA integrity and respiration. Twinkle also promoted vascular smooth muscle cell proliferation and protected both vascular smooth muscle cells and macrophages from oxidative stress-induced apoptosis.

    CONCLUSIONS: Endogenous mtDNA damage in mouse and human atherosclerosis is associated with significantly reduced mitochondrial respiration. Reducing mtDNA damage and increasing mitochondrial respiration decrease necrotic core and increase fibrous cap areas independently of changes in reactive oxygen species and may be a promising therapeutic strategy in atherosclerosis.

    Matched MeSH terms: Cell Respiration
  19. Yap KH, Yee GS, Candasamy M, Tan SC, Md S, Abdul Majeed AB, et al.
    Biomolecules, 2020 09 24;10(10).
    PMID: 32987623 DOI: 10.3390/biom10101360
    Catalpol was tested for various disorders including diabetes mellitus. Numerous molecular mechanisms have emerged supporting its biological effects but with little information towards its insulin sensitizing effect. In this study, we have investigated its effect on skeletal muscle mitochondrial respiration and insulin signaling pathway. Type-2 diabetes (T2DM) was induced in male C57BL/6 by a high fat diet (60% Kcal) and streptozotocin (50 mg/kg, i.p.). Diabetic mice were orally administered with catalpol (100 and 200 mg/kg), metformin (200 mg/kg), and saline for four weeks. Fasting blood glucose (FBG), HbA1c, plasma insulin, oral glucose tolerance test (OGTT), insulin tolerance test (ITT), oxygen consumption rate, gene (IRS-1, Akt, PI3k, AMPK, GLUT4, and PGC-1α) and protein (AMPK, GLUT4, and PPAR-γ) expression in muscle were measured. Catalpol (200 mg/kg) significantly (p < 0.05) reduced the FBG, HbA1C, HOMA_IR index, and AUC of OGTT whereas, improved the ITT slope. Gene (IRS-1, Akt, PI3k, GLUT4, AMPK, and PGC-1α) and protein (AMPK, p-AMPK, PPAR-γ and GLUT4) expressions, as well as augmented state-3 respiration, oxygen consumption rate, and citrate synthase activity in muscle was observed in catalpol treated mice. The antidiabetic activity of catalpol is credited with a marked improvement in insulin sensitivity and mitochondrial respiration through the insulin signaling pathway and AMPK/SIRT1/PGC-1α/PPAR-γ activation in the skeletal muscle of T2DM mice.
    Matched MeSH terms: Respiration
  20. Doufas AG, Shafer SL, Rashid NHA, Kushida CA, Capasso R
    Anesthesiology, 2019 02;130(2):213-226.
    PMID: 30247202 DOI: 10.1097/ALN.0000000000002430
    BACKGROUND: Evidence suggests that obstructive sleep apnea promotes postoperative pulmonary complications by enhancing vulnerability to opioid-induced ventilatory depression. We hypothesized that patients with moderate-to-severe obstructive sleep apnea are more sensitive to remifentanil-induced ventilatory depression than controls.

    METHODS: After institutional approval and written informed consent, patients received a brief remifentanil infusion during continuous monitoring of ventilation. We compared minute ventilation in 30 patients with moderate-to-severe obstructive sleep apnea diagnosed by polysomnography and 20 controls with no to mild obstructive sleep apnea per polysomnography. Effect site concentrations were estimated by a published pharmacologic model. We modeled minute ventilation as a function of effect site concentration and the estimated carbon dioxide. Obstructive sleep apnea status, body mass index, sex, age, use of continuous positive airway pressure, apnea/hypopnea events per hour of sleep, and minimum nocturnal oxygen saturation measured by pulse oximetry in polysomnography were tested as covariates for remifentanil effect site concentration at half-maximal depression of minute ventilation (Ce50) and included in the model if a threshold of 6.63 (P < 0.01) in the reduction of objective function was reached and improved model fit.

    RESULTS: Our model described the observed minute ventilation with reasonable accuracy (22% median absolute error). We estimated a remifentanil Ce50 of 2.20 ng · ml (95% CI, 2.09 to 2.33). The estimated value for Ce50 was 2.1 ng · ml (95% CI, 1.9 to 2.3) in patients without obstructive sleep apnea and 2.3 ng · ml (95% CI, 2.2 to 2.5) in patients with obstructive sleep apnea, a statistically nonsignificant difference (P = 0.081). None of the tested covariates demonstrated a significant effect on Ce50. Likelihood profiling with the model including obstructive sleep apnea suggested that the effect of obstructive sleep apnea on remifentanil Ce50 was less than 5%.

    CONCLUSIONS: Obstructive sleep apnea status, apnea/hypopnea events per hour of sleep, or minimum nocturnal oxygen saturation measured by pulse oximetry did not influence the sensitivity to remifentanil-induced ventilatory depression in awake patients receiving a remifentanil infusion of 0.2 μg · kg of ideal body weight per minute.

    Matched MeSH terms: Respiration/drug effects*
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