The necessity of oxygen for metabolic processes means that hypoxia can lead to serious cell and tissue damage. On the other hand, in some situations, hypoxia occurs under physiological conditions and serves as an important regulation factor. The airway epithelium is specific in that it gains oxygen not only from the blood supply but also directly from the luminal air. Many respiratory diseases are associated with airway obstruction or excessive mucus production thus leading to luminal hypoxia. The main goal of this review is to point out how the airway epithelium reacts to hypoxic conditions. Cells detect low oxygen levels using molecular mechanisms involving hypoxia-inducible factors (HIFs). In addition, the cells of the airway epithelium appear to overexpress HIFs in hypoxic conditions. HIFs then regulate many aspects of epithelial cell functions. The effects of hypoxia include secretory cell stimulation and hyperplasia, epithelial barrier changes, and ciliogenesis impairment. All the changes can impair mucociliary clearance, exacerbate infection, and promote inflammation leading to damage of airway epithelium and subsequent airway wall remodeling. The modulation of hypoxia regulatory mechanisms may be one of the strategies for the treatment of obstructive respiratory diseases or diseases with mucus hyperproduction. Keywords: Secretory cells, Motile cilia, Epithelial barrier, Oxygenation, Obstructive respiratory diseases.
- MeSH
- hypoxie * metabolismus MeSH
- kyslík metabolismus MeSH
- lidé MeSH
- respirační sliznice * metabolismus MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
Adverse events during the perinatal period are associated with an increased risk to develop cardiometabolic diseases later in life. We established a murine model to study long-term effects of perinatal hypoxia (PH) on the pulmonary circulation. We previously demonstrated that PH led to an impaired regulation of pulmonary vascular tone in adulthood, linked to alterations in K+ channels in males and in the nitric oxide (NO)/cyclic guanosine monophosphate pathway in females. Moreover, simultaneous administration of inhaled NO (iNO) during PH exposure prevented adverse effects of PH on adult pulmonary vasculature in females. The present study showed that PH induced a significant increase in right ventricular pressure in males and females, and an enhanced sensitivity to acute hypoxia in females. PH significantly reduced acetylcholine-induced relaxation in pulmonary artery, to a greater extent in females than in males. PH led to right ventricular hypertrophy in adulthood, appearing earlier in males than in females. Morphometric measurements showed a significant increase in the number of 25-75-μm pulmonary vessels in male lungs following PH, probably resulting in increased pulmonary vascular resistance. The effects of prolonged hypoxia in adulthood differed between males and females. Perinatal iNO during PH prevented PH-induced alterations in the cardiopulmonary system, whereas perinatal iNO alone could have some adverse effects. Therefore, PH led to long-lasting alterations in the regulation of adult pulmonary circulation, which vary between males and females. In males, the increased pulmonary vascular resistance was associated with morphological changes besides functional alterations, whereas females showed an important pulmonary vascular dysfunction. Keywords: Perinatal hypoxia, Pulmonary circulation, Endothelium-dependent relaxation, Phosphodiesterases, Sex differences.
- MeSH
- arteria pulmonalis metabolismus patofyziologie účinky léků MeSH
- cévní rezistence fyziologie MeSH
- hypoxie * patofyziologie metabolismus MeSH
- modely nemocí na zvířatech MeSH
- myši inbrední C57BL MeSH
- myši MeSH
- novorozená zvířata MeSH
- oxid dusnatý metabolismus MeSH
- plicní oběh * fyziologie MeSH
- pohlavní dimorfismus MeSH
- sexuální faktory MeSH
- těhotenství MeSH
- zvířata MeSH
- Check Tag
- mužské pohlaví MeSH
- myši MeSH
- těhotenství MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
An important complication of prolonged support of the left ventricle with an assist device when implanted in patients with heart failure is unloading-induced cardiac atrophy. Our recent study suggested that sex-linked differences in the development of atrophy induced by heterotopic heart transplantation (HTX) do exist, however, the role of the environmental conditions dependent on plasma concentrations of sex hormones remains elusive. We aimed to compare the course of HTX-induced cardiac atrophy in male and female rats after gonadectomy with substitution of steroid hormones of the opposite sex. In a separate series of experiments, we evaluated the course of unloading-induced cardiac atrophy in the female heart transplanted into a male recipient and vice versa. Cardiac atrophy was assessed as the ratio of the transplanted heart weight to native heart weight (HW), which was determined 14 days after HTX. In female rats, studied in both experimental variants, HTx resulted in significantly smaller decreases in whole HW when compared to those observed in male rats exposed to the same experimental conditions (-9 ± 1 and - 11 + 1 vs. -44 ± 2 and -42 ± 2 %, p?0.05 in both cases). The dynamic of changes in left and right ventricle was similar as in the whole HW. Our results show that the process of unloading-induced cardiac atrophy exhibits important sex-linked differences and that attenuation of this process in female rats cannot be simply ascribed to the protective effects of estradiol or to the absence of deleterious actions of testosterone. Keywords: Cardiac atrophy, Sex differences, Gonadectomy, Hormonal substitution, Heterotopic heart transplantation, Mechanical heart unloading.
- MeSH
- atrofie * MeSH
- estradiol krev MeSH
- heterotopická transplantace * MeSH
- krysa rodu rattus MeSH
- pohlavní dimorfismus * MeSH
- pohlavní steroidní hormony * krev MeSH
- potkani Wistar MeSH
- srdce MeSH
- testosteron krev MeSH
- transplantace srdce * škodlivé účinky MeSH
- zvířata MeSH
- Check Tag
- krysa rodu rattus MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
Experimental and clinical studies have clearly demonstrated significant sex differences in myocardial structure and function, both under physiological and pathological conditions. The best example are significant sex differences in the cardiac tolerance to ischemia/reperfusion injury: pre-menopausal adult female hearts are more resistant as compared to the male myocardium. The importance of these findings is supported by the fact that the number of studies dealing with this issue increased significantly in recent years. Detailed molecular and cellular mechanisms responsible for sex differences are yet to be elucidated; however, it has been stressed that the differences cannot be explained only by the effect of estrogens. In recent years, a promising new hypothesis has been developed, suggesting that mitochondria may play a significant role in the sex differences in cardiac tolerance to oxygen deprivation. However, one is clear already today: sex differences are so important that they should be taken into consideration in the clinical practice for the selection of the optimal diagnostic and therapeutic strategy in the treatment of ischemic heart disease. The present review attempts to summarize the progress in cardiovascular research on sex-related differences in cardiac tolerance to oxygen deprivation during the last 40 years, i.e. from the first experimental observation. Particular attention was paid to the sex-related differences of the normal heart, sex-dependent tolerance to ischemia-reperfusion injury, the role of hormones and, finally, to the possible role of cardiac mitochondria in the mechanism of sex-dependent differences in cardiac tolerance to ischemia/reperfusion injury. Key words: Female heart, Cardiac hypoxic tolerance, Ischemia-reperfusion injury, Sex differences.
- MeSH
- kyslík metabolismus MeSH
- lidé MeSH
- myokard metabolismus patologie MeSH
- pohlavní dimorfismus * MeSH
- reperfuzní poškození myokardu metabolismus patofyziologie MeSH
- sexuální faktory MeSH
- srdeční mitochondrie metabolismus patologie MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
Hypoxic pulmonary vasoconstriction (HPV) rapidly and reversibly matches lung ventilation (V) and perfusion (Q), optimizing oxygen uptake and systemic oxygen delivery. HPV occurs in small pulmonary arteries (PA), which uniquely constrict to hypoxia. Although HPV is modulated by the endothelium the core mechanism of HPV resides in PA smooth muscle cells (PASMC). The PASMC's mitochondrial oxygen sensor lies within the electron transport chain (ETC) and includes NDUFS2 in ETC Complex-I. PASMC mitochondria respond to hypoxia by varying production of reactive oxygen species (ROS) and hydrogen peroxide in proportion to alveolar oxygen tension. Hypoxic ROS inhibition results in a state of reduction which triggers a redox-mediated inhibition of oxygen-sensitive, voltage-gated, potassium channels, including Kv1.5 and Kv2.1. Kv channel inhibition depolarizes the PASMC, opening of large-conductance calcium channels (CaL), elevating cytosolic calcium and activating the contractile apparatus. HPV is strongest in small PAs where sensors (hypoxia-responsive mitochondria) and effectors (oxygen-sensitive K+ channels) are enriched. Oxygenation at birth reverses fetal HPV, contributing to the rapid neonatal drop in pulmonary vascular resistance (PVR). A similar mitochon-drial-K+ channel sensor-effector mechanism exists in the ductus arteriosus (DA), however in DASMC it is oxygen-induced increases in mitochondrial ROS that inhibit DASMC K+ channels, causing DA constriction. Atelectasis and pneumonia elicit HPV, which optimises V/Q matching, increasing systemic oxygenation. Whilst HPV in response to localized hypoxia in a single lung lobe does not increase PA pressure; global airway hypoxia, as occurs with altitude or sleep apnea, causes pulmonary hypertension. HPV can be inhibited by drugs, including calcium channel blockers, or used to maintain a dry operative field during single lung anesthesia for lung surgery. HPV does not normally cause lung edema but excessive, heterogenous HPV contributes to high altitude pulmonary edema. HPV is suppressed in COVID-19 pneumonia by a SARS-CoV-2 mitochondriopathy. HPV is a component of the body's homeostatic oxygen sensing system. Keywords: Ductus arteriosus, Redox, NDUFS2, Oxygen sensitive potassium, Channels, High altitude pulmonary edema (HAPE), Mitochondrial electron transport chain, COVID-19 pneumonia, Atelectasis.
- MeSH
- arteria pulmonalis metabolismus MeSH
- COVID-19 metabolismus komplikace MeSH
- homeostáza * fyziologie MeSH
- hypoxie * metabolismus patofyziologie MeSH
- kyslík * metabolismus MeSH
- lidé MeSH
- vazokonstrikce * fyziologie MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
The fetus develops normally in a hypoxic environment but exaggerated hypoxia late in pregnancy is a worrisome sign often observed in hypertensive disorders of pregnancy, placental insufficiency, or fetal growth restriction (FGR). Serial fetal biometry and the cerebroplacental ratio (CPR, calculated as the middle cerebral artery [MCA] / the umbilical artery [UmbA] pulsatility indices [PI]), are commonly used to indicate fetal "brain sparing" resulting from exaggerated fetal hypoxia. But unclear is the extent to which a low CPR indicates pathology or is a physiological response for maintaining cerebral blood flow. We studied 31 appropriate for gestational age (AGA) pregnancies at low (LA, 1670 m) or high (HA, 2879 m) altitude, given the chronic hypoxia imposed by HA residence, and 54 LA women with a clinical diagnosis of FGR. At week 34, the MCA PI was lower in the LA-FGR than the LA-AGA group but lower still in the HA-AGA compared to either LA groups due to a trend toward higher end-diastolic velocity (EDV). We concluded that the lower MCA PI was likely due to greater cerebral vasodilation in the HA AGA group and an indication of physiological versus pathological fetal hypoxia. Future reporting of serial MCA and UmbA values and their determinants along with the CPR could improve our ability to distinguish between physiological and pathological fetal brain sparing. Keywords: Birth weight, Cerebroplacental ratio, Fetal physiology, HDP, High altitude.
- MeSH
- arteria cerebri media * diagnostické zobrazování patofyziologie MeSH
- arteriae umbilicales diagnostické zobrazování patofyziologie MeSH
- dospělí MeSH
- hypoxie plodu * patofyziologie MeSH
- hypoxie patofyziologie MeSH
- lidé MeSH
- mozek patofyziologie krevní zásobení diagnostické zobrazování MeSH
- mozkový krevní oběh fyziologie MeSH
- nadmořská výška MeSH
- růstová retardace plodu * patofyziologie MeSH
- těhotenství MeSH
- ultrasonografie prenatální metody MeSH
- Check Tag
- dospělí MeSH
- lidé MeSH
- těhotenství MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
Pulmonary arterial hypertension is characterized by perivascular and systemic inflammation. The gut microbiome influences the host immune system. Here we review the emerging preclinical and clinical evidence that strongly suggests that alterations in the gut microbiome may either initiate or facilitate progression of established pulmonary arterial hypertension by modifying the systemic immune responses. We also briefly review the relationship between the gut microbiome and preeclampsia, a vascular disease also characterized by inflammation. Key words: Dysbiosis, Right ventricle, Inflammation.
- MeSH
- dysbióza * MeSH
- lidé MeSH
- plicní arteriální hypertenze * mikrobiologie patofyziologie MeSH
- plicní hypertenze mikrobiologie patofyziologie MeSH
- preeklampsie mikrobiologie patofyziologie imunologie MeSH
- střevní mikroflóra * fyziologie MeSH
- těhotenství MeSH
- zánět mikrobiologie imunologie MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- těhotenství MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
BACKGROUND: This research article delves into the battle against the COVID-19 pandemic, focusing on the efficacy and, particularly, the safety of the combination of nirmatrelvir with ritonavir, which is found in the pharmaceutical product Paxlovid®. This study aims to analyze the potential interactions of commonly prescribed medicinal products with Paxlovid®, shedding light on its utilization in specific medical fields. METHODS: Prescription data from the Czech Republic's Institute of Health Information and Statistics (IHIS CR) was analyzed, covering 4 million COVID-19 patients and 87.5 million medication records from September 2019 to February 2022. This study focused on potential drug interactions with Paxlovid among the 50 most frequently prescribed medications, with particular attention to four specialties: general medicine, internal medicine, infectious diseases, and diabetology. RESULTS: In this study of the 50 most commonly prescribed drugs, 56% showed no interaction with Paxlovid, 30% had a potential for interaction, and 14% were not specifically mentioned in relation to Paxlovid, with no drugs found to be contraindicated overall. However, in specific medical fields, including diabetology, infectious diseases, internal medicine, and general medicine, certain drugs had potential interactions when co-administered with Paxlovid. CONCLUSIONS: Paxlovid remains a valuable option for early COVID-19 treatment but requires a careful consideration of potential drug interactions, especially in high-risk specialties. A thorough assessment of concurrent medications is essential to optimize safety and efficacy in patients receiving Paxlovid.
- MeSH
- antivirové látky škodlivé účinky terapeutické užití MeSH
- COVID-19 epidemiologie MeSH
- farmakoterapie COVID-19 * MeSH
- fixní kombinace léků * MeSH
- lékové interakce * MeSH
- lidé MeSH
- ritonavir * terapeutické užití škodlivé účinky MeSH
- SARS-CoV-2 účinky léků MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- Geografické názvy
- Česká republika MeSH
- MeSH
- fibromyalgie * diagnóza psychologie terapie MeSH
- lidé MeSH
- psychosomatické a relaxační terapie MeSH
- somatoformní poruchy psychologie terapie MeSH
- syndrom chronické únavy * diagnóza psychologie terapie MeSH
- syndrom dráždivého tračníku * diagnóza psychologie terapie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- přehledy MeSH
