oxytocin and Asthma

To estimate whether the diagnosis of asthma is associated with the use of specific uterotonic and antihypertensive medications during delivery hospitalizations.. We used Perspective, an administrative database, to determine whether women hospitalized for delivery complicated by postpartum hemorrhage or preeclampsia received uterotonics and antihypertensive medications differentially based on the absence or presence of asthma from 2006 to 2015. Given that carboprost and intravenous (IV) labetalol may be associated with asthma exacerbation, adjusted models for receipt of these medications were created with adjusted risk ratios with 95% CIs as measures of effect. Risk for status asthmaticus based on receipt of carboprost and IV labetalol was analyzed.. Over the study period, a total of 5,691,178 women were analyzed, of whom 239,915 (4.2%) had preeclampsia and 139,841 postpartum hemorrhage (2.5%). Carboprost was used less frequently in patients with asthma compared with patients with no asthma (11.4% vs 18.0%) in comparison with IV labetalol, which was used more commonly when a diagnosis of asthma was present (18.5% vs 16.7%). In unadjusted analysis, the presence of asthma was associated with a 37% decrease in likelihood of carboprost use and an 11% increase in likelihood of labetalol use. In adjusted analysis, the presence of asthma was associated with a 32% decrease in likelihood of carboprost use (adjusted risk ratio 0.68, 95% CI 0.62-0.74) compared with a 7% decrease in labetalol use (adjusted risk ratio 0.93, 95% CI 0.90-0.97). Risk for status asthmaticus was significantly increased with use of IV labetalol compared with other antihypertensive medications (6.5 vs 1.7/1,000 delivery hospitalizations, P<.01).. There may be an opportunity to reduce use of β-blockers and carboprost among patients with asthma. Given their association with status asthmaticus, these drugs should be used cautiously in women with asthma.

Topics: Adult; Antihypertensive Agents; Asthma; Carboprost; Contraindications, Drug; Databases, Factual; Delivery, Obstetric; Drug Therapy, Combination; Female; Hospitalization; Humans; Labetalol; Odds Ratio; Oxytocics; Oxytocin; Postpartum Hemorrhage; Pre-Eclampsia; Pregnancy; Pregnancy Complications

CD38 encodes a ligand in the oxytocin signaling pathway. Some single nucleotide polymorphisms in this gene have been associated with low serum oxytocin levels in autism spectrum disorder (ASD) patients. Oxytocin disruption has been hypothesized to account for features of ASD, including impaired communication and social behavior, based on animal studies. Recent human studies have shown administration of oxytocin improving emotion recognition, promoting social behavior, and improving auditory processing of social stimuli in ASD patients. In addition to its role in oxytocin signaling, CD38 is involved in the regulation of calcium concentration in airway smooth muscle with impairment of CD38 being implicated in airway diseases like asthma. While a number of studies have implicated rare chromosomal deletions and duplications in helping determine genetic risk for autism, there are to our knowledge no reports describing rearrangements involving CD38 or deletions in patients with ASD. Here, we present two sisters diagnosed with autism and with features of regression-previously acquired speech lost in the second year of life. The younger sister, who also had asthma, inherited a maternal deletion of 4p15.32 that results in a BST1-CD38 fusion transcript. Their mother's deletion was mosaic and she was not affected. Although further work is required to assess functional consequences of the fusion transcript, we hypothesize that the proband's deletion may have served as a risk factor for autism that, when combined with other susceptibility variants, resulted in a more severe presentation than her sister.

Topics: Adolescent; ADP-ribosyl Cyclase; ADP-ribosyl Cyclase 1; Antigens, CD; Asthma; Child; Child Development Disorders, Pervasive; Chromosome Deletion; Female; Gene Fusion; Genetic Predisposition to Disease; GPI-Linked Proteins; Humans; Longitudinal Studies; Membrane Glycoproteins; Oxytocin; Phenotype; Polymorphism, Single Nucleotide; Signal Transduction; Transcription, Genetic

During pregnancy asthma may remain stable, improve or worsen. The factors underlying the deleterious effect of pregnancy on asthma remain unknown. Oxytocin is a neurohypophyseal protein that regulates a number of central and peripheral responses such as uterine contractions and milk ejection. Additional evidence suggests that oxytocin regulates inflammatory processes in other tissues given the ubiquitous expression of the oxytocin receptor. The purpose of this study was to define the role of oxytocin in modulating human airway smooth muscle (HASMCs) function in the presence and absence of IL-13 and TNFalpha, cytokines known to be important in asthma.. Expression of oxytocin receptor in cultured HASMCs was performed by real time PCR and flow cytomery assays. Responses to oxytocin was assessed by fluorimetry to detect calcium signals while isolated tracheal rings and precision cut lung slices (PCLS) were used to measure contractile responses. Finally, ELISA was used to compare oxytocin levels in the bronchoalveloar lavage (BAL) samples from healthy subjects and those with asthma.. PCR analysis demonstrates that OXTR is expressed in HASMCs under basal conditions and that both interleukin (IL)-13 and tumor necrosis factor (TNFalpha) stimulate a time-dependent increase in OXTR expression at 6 and 18 hr. Additionally, oxytocin increases cytosolic calcium levels in fura-2-loaded HASMCs that were enhanced in cells treated for 24 hr with IL-13. Interestingly, TNFalpha had little effect on oxytocin-induced calcium response despite increasing receptor expression. Using isolated murine tracheal rings and PCLS, oxytocin also promoted force generation and airway narrowing. Further, oxytocin levels are detectable in bronchoalveolar lavage (BAL) fluid derived from healthy subjects as well as from those with asthma.. Taken together, we show that cytokines modulate the expression of functional oxytocin receptors in HASMCs suggesting a potential role for inflammation-induced changes in oxytocin receptor signaling in the regulation of airway hyper-responsiveness in asthma.

Topics: Adult; Animals; Asthma; Bronchoalveolar Lavage Fluid; Bronchoconstriction; Bronchodilator Agents; Calcium Signaling; Case-Control Studies; Cells, Cultured; Enzyme-Linked Immunosorbent Assay; Female; Flow Cytometry; Fluorometry; Forced Expiratory Volume; Humans; Interleukin-13; Lung; Male; Mice; Mice, Inbred BALB C; Middle Aged; Myocytes, Smooth Muscle; Oxytocin; Receptors, Oxytocin; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger; Time Factors; Trachea; Tumor Necrosis Factor-alpha; Up-Regulation; Vital Capacity; Young Adult

Acupuncture is part of Traditional Chinese Medicine, a system with an empirical basis which has been used in the treatment and prevention of disease for centuries. A lack of scientific studies to prove or disprove its claimed effects led to rejection by many of the western scientific community. Now that the mechanisms can be partly explained in terms of endogenous pain inhibitory systems, the integration of acupuncture with conventional medicine may be possible. Its use for pain relief has been supported by clinical trials and this has facilitated its acceptance in pain clinics in most countries. Acupuncture effects must devolve from physiological and/or psychological mechanisms with biological foundations, and needle stimulation could represent the artificial activation of systems obtained by natural biological effects in functional situations. Acupuncture and some other forms of sensory stimulation elicit similar effects in man and other mammals, suggesting that they bring about fundamental physiological changes. Acupuncture excites receptors or nerve fibres in the stimulated tissue which are also physiologically activated by strong muscle contractions and the effects on certain organ functions are similar to those obtained by protracted exercise. Both exercise and acupuncture produce rhythmic discharges in nerve fibres, and cause the release of endogenous opioids and oxytocin essential to the induction of functional changes in different organ systems. Beta-endorphin levels, important in pain control as well as in the regulation of blood pressure and body temperature, have been observed to rise in the brain tissue of animals after both acupuncture and strong exercise. Experimental and clinical evidence suggest that acupuncture may affect the sympathetic system via mechanisms at the hypothalamic and brainstem levels, and that the hypothalamic beta-endorphinergic system has inhibitory effects on the vasomotorcenter, VMC. Post-stimulatory sympathetic inhibition which proceeds to a maximum after a few hours and can be sustained for more than 12 hours, has been demonstrated in both man and animals. Experimental and clinical studies suggest that afferent input in somatic nerve fibres has a significant effect on autonomic functions. Hypothetically, the physiological counterpart lies in physical exercise, and the effect can be artificially reproduced via various types of electrical or manual stimulation of certain nerve fibres.

Topics: Acupuncture Therapy; Afferent Pathways; Animals; Asthma; Cardiovascular Diseases; Clinical Trials as Topic; Electroacupuncture; Endorphins; Humans; Hypothalamus; Models, Neurological; Muscle Contraction; Oxytocin; Pain; Pain Management; Physical Exertion; Rats; Substance-Related Disorders; Synaptic Transmission

Topics: Adult; Asthma; Blood Pressure; Female; Humans; Injections, Intravenous; Labor, Induced; Oxytocin; Pre-Eclampsia; Pregnancy; Pregnancy Complications; Pregnancy Complications, Cardiovascular; Pregnancy, Prolonged; Prostaglandins

Topics: Animals; Asthma; Bronchi; Bronchodilator Agents; Ethanolamines; Gastrointestinal Motility; Guinea Pigs; Histamine; In Vitro Techniques; Isoproterenol; Male; Methacholine Compounds; Mice; Muscle, Smooth; Oxytocin; Papaverine; Quinolines