Israel Medical Association Journal

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), the pathogen that causes coronavirus disease-2019 (COVID-19), is thought to be transmitted via droplets and aerosols, and was detected in saliva of infected individuals. These droplets from the upper airway may infect the inhalation sedation mask and tubing. The authors determined the adequate measures needed to prevent the transmission of COVID-19 by nitrous-oxide (N₂O) system during inhalation sedation in dentistry and provided evidence on mask and tubing sterilization. Additional measures to protect patients and healthcare workers from COVID-19 that may be transmitted by the inhalation sedation system are discussed. The authors recommend minimal use of a N₂O system during inhalation sedation in dentistry. In case of need, the practitioners should have more than one scavenger kit and nasal masks for each N₂O/O₂ mixer. Biologic barriers should be mounted between the scavenger's tubing and the central evacuation system. Strict cleansing and sterilization should be performed for all parts of the N₂O system. The use a disposable scavenger system and nasal mask should be considered as a viable option

Erectile dysfunction (ED) is a syndrome associated with endothelial dysfunction, which may predict cardiovascular events in men presenting with this syndrome. It has been shown to be associated with a higher rate of acute myocardial infarction and cardiovascular mortality, vascular inflammation, and impaired endothelial function. In this review we present the literature findings and describe the mechanistic pathways that are known to be involved in this syndrome and its related clinical consequences.

Management of asthma is currently based on symptoms (in children, usually a second-hand report from parents) and lung function measurements. Inhaled steroids, targeted at controlling airway inflammation, are the mainstay of asthma management. Due to possible side effects they should be used at the lowest possible doses while asthma is adequately controlled. Fractional exhaled nitric oxide is a simple non-invasive method to assess inflammation in asthma and its role in asthma management is increasing in popularity. The present review summarizes recent research on the use of FeNO[1] in monitoring airway inflammation and optimizing asthma management. The addition of FeNO measurements to the conventional assessment of asthma control appears promising. The practicability of including this measuring method into everyday clinical practice is currently being evaluated.

Background: Leukotriene antagonist therapy in asthmatic patients alleviates symptoms and improves exercise tolerance, however the effect of these drugs on bronchial provocation tests and exhaled nitric oxide levels are less clearly established.

Objective: To determine the effect of montelukast treatment on airway hyperresponsiveness to exercise, methacholine and adenosine-5’-monophosphate and on exhaled nitric oxide levels in steroid-naive asthmatics.

Methods: Following a 2 week run-in period, 20 mild to moderate asthmatics were enrolled in an open label 6 week trial of oral montelukast-sodium therapy. Bronchial hyperreactivity (exercise, methacholine and adenosine-5’-monophosphate challenges) and exhaled nitric oxide levels were measured before and after the 6 week period.

Results: Montelukast treatment resulted in a significant improvement in exercise tolerance: median DFEV₁ 20.0% (range 0–50) prior to treatment vs. 15.0% (range 0–50) post-treatment (P = 0.029). A significant difference was also observed for exhaled NO[1] following therapy: median NO 16.0 ppb (range 7–41) vs. 13.0 (range 4.8–26) (P = 0.016). No change was seen in baseline lung function tests (FEV₁, MEF₅₀) or in the bronchial responsiveness (PC₂₀) for methacholine and adenosine-5’-monophosphate.

Conclusions: This study demonstrates that the leukotriene antagonist, montelukast-sodium, reduces bronchial hyperreactivity in response to exercise and reduces exhaled nitric oxide levels but has little effect on bronchial responsiveness to methacholine and adenosine challenges.

Background: High frequency oscillatory ventilation has proved valuable in recruiting and sustaining lung volume; the combined treatment may augment nitric oxide delivery to target vessels. NO[1] therapy lowers pulmonary resistance and improves oxygenation.

Objective: To retrospectively review data on changes in oxygenation – indicated by arterial/alveolar PO₂ ratio, oxygenation index, and outcome – in a cohort of 10 infants with hypoxemic respiratory failure in whom nitric oxide inhalation was instituted in a compassionate-use protocol after deteriorated oxygenation.

Methods: NO inhalation was administered at a range of 0.12–122 days of life using the SensorMedics system in 10 infants who developed hypoxemic respiratory failure associated with a variety of lung diseases while on HFOV[2].

Results: The infants' birthweight was 1,717 ± 1,167 g and their gestational age 31.1 ± 6.5 weeks. Mean exposure to NO inhalation was 14.2 days and ranged from 3–59 days. Oxygenation index decreased from 39.3 ± 13.2 to 12.7 ± 6.9 (P < 0.0002) after NO therapy. Despite an initial prompt response to NO inhalation, two patients died of progressive intractable respiratory failure and one term infant died of extrapulmonary complications (hypoxic ischemic encephalopathy grade III and multiorgan failure).

Conclusion: Our results indicate that the combined treatment of HFOV and NO inhalation is superior to HFOV alone for improving oxygenation in a selected cohort of infants ventilated for a variety of lung diseases.

The leukocyte NADPH oxidase catalyzes the reduction of oxygen to O₂- (superoxide) at the expense of NADPH. The O₂- then dismutes to H₂O₂, which serves to oxidize Cl- to HOCl, a potent microbicidal agent that is used by leukocytes to kill invading microorganisms. This oxidation is catalyzed by myeloperoxidase. O₂ is also used to make other microbicidal oxidants, some in reactions with nitric oxide. The oxidase itself is highly complex, consisting of four unique subunits and Rac2. In the resting cell, two of the subunits, p22PHOX and gp91PHOX, are located in the membrane, and the other two, p47PHOX and p67PHOX, are in the cytosol. The electron-carrying components of the oxidase are

located in gp91PHOX; the NADPH binding site is generally regarded to be in gp91PHOX as well, but there is some evidence that it may be in p67PHOX. When the oxidase is activated, p47PHOX is phosphorylated at specific sites, and the cytosolic components plus Rac2 migrate to the membrane to assemble the active oxidase.

Background: Multiple factors are involved in the pathogenesis of hypertension in the obese individual.

Objective: To evaluate the role of a decrease in sympathetically mediated thermogenesis and the effect of the correlation between the plasma leptin and daily urinary nitric oxide levels on obesity-related hypertension.

Methods: We evaluated three groups: 25 obese hypertensive patients (age 45.7±1.37 years, body mass index 34.2±1.35 kg/m², systolic/diastolic blood pressure 155±2.9/105±1.3, mean arterial pressure 122±1.50 mmHg); 21 obese normotensive patients (age 39.6±1.72, BMI[1] 31.3±0.76, SBP/DBP[2] 124±2.1/85.4±1.8, MAP[3] 98.2±1.80); and 17 lean normotensive subjects (age 38.1±2.16, BMI 22.1±0.28, SBP/DBP 117±1.7/76.8±1.5, MAP 90.1±1.50). We determined basal resting metabolic rates, plasma insulin (radioimmunoassay), norepinephrine (high performance liquid chromatography) in all subjects. Thereafter, 14 obese hypertensives underwent a weight reduction diet. At weeks 6 (n=14) and 14 (n=10) of the diet the above determinations were repeated. Plasma leptin (enzyme-linked immunosorbent assay) and UNOx[4] (spectrophotometry) were assayed in 17 obese hypertensives and 17 obese normotensives, and in 19 obese hypertensives versus 11 obese normotensives, respectively.

Results: Obese hypertensive patients had significantly higher basal RMR[5] and plasma NE[6] levels. Insulin levels were lower in the lean group, with no difference between the hypertensive and normotensive obese groups. At weeks 6 and 14, BMI was significantly lower, as were insulin and NE levels. RMR decreased to values of normotensive subjects. MAP normalized but remained significantly higher than that of obese normotensives. Leptin blood levels and the leptin/UNOx ratio were significantly higher in the obese hypertensive compared to the obese normotensive patients. Both these parameters were strongly correlated to BMI, MAP⁵, RMR, and plasma NE and insulin .Obese hypertensive patients excreted less urinary NO metabolites. A strong correlation was found between MAP and the leptin/UNOx ratio.  

Conclusions: A reduction of sympathetically mediated thermogenesis, as reflected by RMR, results in normalization of obesity-related hypertension. In contrast, insulin does not seem to play a major role in the pathogenesis of hypertension associated with obesity. Increased leptin levels in conjunction with decreased NO production in the presence of enhanced sympathetic activity may contribute to blood pressure elevation in the obese.

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[1] BMI = body mass index

[2] SBP/DBP = systolic blood pressure/diastolic blood pressure

[3] MAP = mean arterial pressure

[4] UNOx = urinary nitric oxide

[5] RMR – resting metabolic rate

[6] NE = norepinephrine