Feasibility of dose adjustment based on differences in long-term clearance rates of inhaled particulate matter in humans and laboratory animals

Anesthesia for laboratory animals is a matter of biomedical concern and one of the most present dilemmas in the current bioethical debate. The use of anesthetic agents in experimental surgery aims at analgesia and restraining the animal, in order to achieve a reasonable degree of muscle relaxation and to produce sufficient analgesia. This practice requires the use of protocols for the administration of safe and efficient doses. Eight New Zealand rabbits were submitted to laparotomies demonstrating the surgical technique discipline of the local medical course. For pre-anesthetic medication, acepromazine 1 mg.kg-1 associated with ketamine 15 mg.kg-1 was used subcutaneously. Anesthesia was maintained with isoflurane and oxygen under a laryngeal mask in a Mapleson D anesthesia system and under spontaneous breathing. Hydration was performed with 10 ml.kg-1 saline every hour. A thermal mattress was used. Precordial stethoscope, pulse oximetry and clinical parameters were used for monitoring. For euthanasia, ketamine 10 mg.kg-1 associated with potassium chloride 19.1% 1 ml.kg-1 was used intravenously. The average weight of the rabbits was 2721.25 ± 275.01 grams and the duration of the anesthetic procedure was 120 ± 87 minutes. Discussion. In long-term anesthesia, such as laparotomies, the use of pre-anesthetic medication and then anesthetic induction by the combination of agents is recommended. However, anesthetic management requires monitoring to prevent insufficient or excessive doses from occurring.

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Leaded Aviation Fuel May Present Long-Term Effects on Campus Life from the Adjacent Albert Whitted Airport

10.26434/chemrxiv.12824741 ◽

2020 ◽

Author(s):

Joseph Matthews ◽

Madhu Pandey

Keyword(s):

United States ◽

Particulate Matter ◽

The United States ◽

Aviation Fuel ◽

University Campus ◽

Long Term Effects ◽

Aviation Gasoline ◽

Suspended Particulate ◽

Descent Line

Propeller planes and small engine aircraft around the United States, legally utilize leaded aviation gasoline. The purpose of this experiment was to collect suspended particulate matter from a university campus, directly below an airport’s arriving flight path’s descent line, and to analyze lead content suspended in the air. Two collection sets of three separate samples were collected on six separate days, one set in July of 2018 and the second set in January 2019.

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Faculty Opinions recommendation of Variation in warfarin dose adjustment practice is responsible for differences in the quality of anticoagulation control between centers and countries: an analysis of patients receiving warfarin in the randomized evaluation of long-term anticoagulation therapy (RE-LY) trial.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.717961998.793465540 ◽

2012 ◽

Author(s):

Jack Kron ◽

Eric Stecker

Keyword(s):

Dose Adjustment ◽

Anticoagulation Therapy ◽

Warfarin Dose ◽

Randomized Evaluation ◽

Anticoagulation Control

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A global association between Covid-19 cases and airborne particulate matter at regional level

Scientific Reports ◽

10.1038/s41598-021-85751-z ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Angelo Solimini ◽

F. Filipponi ◽

D. Alunni Fegatelli ◽

B. Caputo ◽

C. M. De Marco ◽

...

Keyword(s):

Air Pollution ◽

Particulate Matter ◽

Negative Binomial ◽

Numerical Models ◽

Regional Level ◽

Pollution Level ◽

Observation Data ◽

Cumulative Number ◽

Mixed Effect

AbstractEvidences of an association between air pollution and Covid-19 infections are mixed and inconclusive. We conducted an ecological analysis at regional scale of long-term exposure to air-borne particle matter and spread of Covid-19 cases during the first wave of epidemics. Global air pollution and climate data were calculated from satellite earth observation data assimilated into numerical models at 10 km resolution. Main outcome was defined as the cumulative number of cases of Covid-19 in the 14 days following the date when > 10 cumulative cases were reported. Negative binomial mixed effect models were applied to estimate the associations between the outcome and long-term exposure to air pollution at the regional level (PM10, PM2.5), after adjusting for relevant regional and country level covariates and spatial correlation. In total we collected 237,749 Covid-19 cases from 730 regions, 63 countries and 5 continents at May 30, 2020. A 10 μg/m3 increase of pollution level was associated with 8.1% (95% CI 5.4%, 10.5%) and 11.5% (95% CI 7.8%, 14.9%) increases in the number of cases in a 14 days window, for PM2.5 and PM10 respectively. We found an association between Covid-19 cases and air pollution suggestive of a possible causal link among particulate matter levels and incidence of COVID-19.

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The Diamond League athletic series: does the air quality sparkle?

International Journal of Biometeorology ◽

10.1007/s00484-021-02114-z ◽

2021 ◽

Author(s):

James R. Hodgson ◽

Lee Chapman ◽

Francis D. Pope

Keyword(s):

Particulate Matter ◽

Air Quality ◽

Performance Metrics ◽

Urban Air Pollution ◽

Quality Data ◽

Performance Variation ◽

Short And Long Term ◽

Respiratory Conditions ◽

Race Performance

AbstractUrban air pollution can have negative short- and long-term impacts on health, including cardiovascular, neurological, immune system and developmental damage. The irritant qualities of pollutants such as ozone (O3), nitrogen dioxide (NO2) and particulate matter (PM) can cause respiratory and cardiovascular distress, which can be heightened during physical activity and particularly so for those with respiratory conditions such as asthma. Previously, research has only examined marathon run outcomes or running under laboratory settings. This study focuses on elite 5-km athletes performing in international events at nine locations. Local meteorological and air quality data are used in conjunction with race performance metrics from the Diamond League Athletics series to determine the extent to which elite competitors are influenced during maximal sustained efforts in real-world conditions. The findings from this study suggest that local meteorological variables (temperature, wind speed and relative humidity) and air quality (ozone and particulate matter) have an impact on athletic performance. Variation between finishing times at different race locations can also be explained by the local meteorology and air quality conditions seen during races.

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Long-term efficacy and safety of oral semaglutide and the effect of switching from sitagliptin to oral semaglutide in patients with type 2 diabetes: a 52-week, randomized, open-label extension of the PIONEER 7 trial

BMJ Open Diabetes Research & Care ◽

10.1136/bmjdrc-2020-001649 ◽

2020 ◽

Vol 8 (2) ◽

pp. e001649

Author(s):

John B Buse ◽

Bruce W Bode ◽

Ann Mertens ◽

Young Min Cho ◽

Erik Christiansen ◽

...

Keyword(s):

Type 2 Diabetes ◽

Body Weight ◽

Dose Adjustment ◽

Main Phase ◽

Open Label ◽

Open Label Extension ◽

Registration Number ◽

Flexible Dose

IntroductionThe PIONEER 7 trial demonstrated superior glycemic control and weight loss with once-daily oral semaglutide with flexible dose adjustment versus sitagliptin 100 mg in type 2 diabetes. This 52-week extension evaluated long-term oral semaglutide treatment and switching from sitagliptin to oral semaglutide.Research design and methodsA 52-week, open-label extension commenced after the 52-week main phase. Patients on oral semaglutide in the main phase continued treatment (n=184; durability part); those on sitagliptin were rerandomized to continued sitagliptin (n=98) or oral semaglutide (n=100; initiated at 3 mg) (switch part). Oral semaglutide was dose-adjusted (3, 7, or 14 mg) every 8 weeks based on glycated hemoglobin (HbA1c) (target <7.0% (<53 mmol/mol)) and tolerability. Secondary endpoints (no primary) included changes in HbA1c and body weight.ResultsIn the durability part, mean (SD) changes in HbA1c and body weight from week 0 were –1.5% (0.8) and –1.3% (1.0) and –2.8 kg (3.8) and –3.7 kg (5.2) at weeks 52 and 104, respectively. In the switch part, mean changes in HbA1c from week 52 to week 104 were –0.2% for oral semaglutide and 0.1% for sitagliptin (difference –0.3% (95% CI –0.6 to 0.0); p=0.0791 (superiority not confirmed)). More patients achieved HbA1c <7.0% with oral semaglutide (52.6%) than sitagliptin (28.6%; p=0.0011) and fewer received rescue medication (9% vs 23.5%). Respective mean changes in body weight were –2.4 kg and –0.9 kg (difference –1.5 kg (95% CI –2.8 to –0.1); p=0.0321). Gastrointestinal adverse events were the most commonly reported with oral semaglutide.ConclusionsLong-term oral semaglutide with flexible dose adjustment maintained HbA1c reductions, with additional body weight reductions, and was well tolerated. Switching from sitagliptin to flexibly dosed oral semaglutide maintained HbA1c reductions, helped more patients achieve HbA1c targets with less use of additional glucose-lowering medication, and offers the potential for additional reductions in body weight.Trial registration numberNCT02849080.

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Memory impairment induced by amphetamine derivatives in laboratory animals and in humans: a review

BioMolecular Concepts ◽

10.1515/bmc.2011.048 ◽

2012 ◽

Vol 3 (1) ◽

pp. 1-12 ◽

Cited By ~ 7

Author(s):

Jordi Camarasa ◽

Teresa Rodrigo ◽

David Pubill ◽

Elena Escubedo

Keyword(s):

Illicit Drugs ◽

Molecular Mechanisms ◽

Memory Performance ◽

Laboratory Animals ◽

Club Drugs ◽

Synthetic Drugs ◽

History Of ◽

Amphetamine Derivatives ◽

Considerable Body

AbstractThe 20th century brought with it the so-called club drugs (the most notorious being amphetamine derivatives), which are used by young adults at all-night dance parties. Methamphetamine and 3,4-methylenedioxymethamphetamine (MDMA or ecstasy) are synthetic drugs with stimulant and psychoactive properties that belong to the amphetamine family. Here, we have reviewed the literature about the cognitive impairment induced by these two amphetamine derivatives and the preclinical and clinical outcomes. Although there is controversial evidence about the effect of methamphetamine and MDMA on learning and memory in laboratory animals, results from published papers demonstrate that amphetamines cause long-term impairment of cognitive functions. A large number of pharmacological receptors have been studied and screened as targets of amphetamine-induced cognitive dysfunction, and extensive research efforts have been invested to provide evidence about the molecular mechanisms behind these cognitive deficits. In humans, there is a considerable body of evidence indicating that methamphetamine and MDMA seriously disrupt memory and learning processes. Although an association between the impairments of memory performance and a history of recreational amphetamine ingestion has also been corroborated, a number of methodological difficulties continue to hamper research in this field, the most important being the concomitant use of other illicit drugs.

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Inhaled Particulate Matter Affects Immune Responsiveness of Human Lung Phagocytes to Mycobacteria

AJP Lung Cellular and Molecular Physiology ◽

10.1152/ajplung.00014.2021 ◽

2021 ◽

Author(s):

Brandon Anton Paarwater ◽

Jomien Mouton ◽

Samantha L Sampson ◽

Stephanus T Malherbe ◽

Jane A Shaw ◽

...

Keyword(s):

Particulate Matter ◽

Post Infection ◽

Ex Vivo ◽

Early Time ◽

Immune Responsiveness ◽

Phenotypic Profile ◽

Host Protection ◽

Tnf Α ◽

Long Term Impact

The influence of smoke- or air pollution-derived cytoplasmic particulate matter (PM) can be detrimental and lead to failed lung immunity. We investigated mycobacterial uptake, intracellular replication, and soluble immune mediator responses of human bronchoalveolar lavage cells (BALC) loaded with/without PM, to infection with mycobacterial strains. We observed that only BALC containing PM display an ex vivo phenotypic profile dominated by spontaneous interleukin (IL) -10 production. PM loaded BALC retained the ability to phagocytose both Mycobacterium bovis Bacille Calmette Guérin (BCG) and Mycobacterium tuberculosis (M.tb) ΔleuDΔpanCD at equal efficacy as clear non-PM loaded BALC. However, immune responsiveness, such as the production of IL-6 (p=0.015) and tumor necrosis factor (TNF)-α (p= 0.0172) immediately post M.bovis BCG infection, were dramatically lower in black BALC loaded with PM versus clear non-PM loaded BALC. By 24 hour post infection, differential immune responses to M.bovis BCG between black versus clear BALC waned, and instead, production of IL-6 (p= 0.03) and IL-1α (p= 0.04 ) by black BALC were lower versus clear BALC following M.tb ΔleuDΔpanCD infection. Considering that TNFα and IL-6 are characterized as critical to host protection against mycobacteria, our findings suggest that BALC loaded with inhaled PM, display lower levels of anti-mycobacterial mediators, and that the response magnitude differs according to infective mycobacterial strain. Even though this did not translate into altered mycobacterial killing at early time points post infection, the long-term impact of such changes remains to be established.

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