Can intravenous oxytocin infusion counteract hyperinflammation in COVID-19 infected patients?

Objectives Based on its well-documented anti-inflammatory and restorative properties we propose trials with the natural hormone oxytocin for treatment of hospitalised Covid-19 patients. Methods We searched for, retrieved, and commented on specific literature regarding multiple functions of oxytocin with a special focus on its modulation of inflammatory, immune, and restorative functions. Results Available data gathered in animals and humans support the anti-inflammatory properties of oxytocin. The multiple anti-inflammatory effects of oxytocin have been demonstrated in vitro and in vivo in various animal models and also in humans in response to intravenous infusion of oxytocin. Furthermore, oxytocin has been documented to activate several types of protective and restorative mechanisms and to exert positive effects on the immune system. Conclusions In addition, to being anti-inflammatory, it may be hypothesised, that oxytocin may be less suppressive on adaptive immune systems, as compared with glucocorticoids. Finally, by its restorative effects coupled with its anti-stress and healing properties, oxytocin may shorten the recovery period of the Covid-19 patients

How much synthetic oxytocin is infused during labour? A review and analysis of regimens used in 12 countries.

OBJECTIVE: To compare synthetic oxytocin infusion regimens used during labour, calculate the International Units (IU) escalation rate and total amount of IU infused over eight hours. DESIGN: Observational study. SETTING: Twelve countries, eleven European and South Africa. SAMPLE: National, regional or institutional-level regimens on oxytocin for induction and augmentation labour. METHODS: Data on oxytocin IU dose, infusion fluid amount, start dose, escalation rate and maximum dose were collected. Values for each regimen were converted to IU in 1000ml diluent. One IU corresponded to 1.67μg for doses provided in grams/micrograms. IU hourly dose increase rates were based on escalation frequency. Cumulative doses and total IU amount infused were calculated by adding the dose administered for each previous hour. Main Outcome Measures Oxytocin IU dose infused. RESULTS: Data were obtained on 21 regimens used in 12 countries. Details on the start dose, escalation interval, escalation rate and maximum dose infused were available from 16 regimens. Starting rates varied from 0.06 IU/hour to 0.90 IU/hour, and the maximum dose rate varied from 0.90 IU/hour to 3.60 IU/hour. The total amount of IU oxytocin infused, estimated over eight hours, ranged from 2.38 IU to 27.00 IU, a variation of 24.62 IU and an 11-fold difference. CONCLUSION: Current variations in oxytocin regimens for induction and augmentation of labour are inexplicable. It is crucial that the appropriate minimum infusion regimen is administered because synthetic oxytocin is a potentially harmful medication with serious consequences for women and babies when inappropriately used. Estimating the total amount of oxytocin IU received by labouring women, alongside the institution's mode of birth and neonatal outcomes, may deepen our understanding and be the way forward to identifying the optimal infusion regimen

Polymorphism in the oxytocin promoter region in patients with lactase non-persistence is not related to symptoms

<p>Abstract</p> <p>Background</p> <p>Oxytocin and the oxytocin receptor have been demonstrated in the gastrointestinal (GI) tract and have been shown to exert physiological effects on gut motility. The role for oxytocin in the pathophysiology of GI complaints is unknown. The aim of this study was to examine genetic variations or polymorphism of oxytocin (<it>OXT</it>) and its receptor (<it>OXTR</it>) genes in patients with GI complaints without visible organic abnormalities.</p> <p>Methods</p> <p>Genetic variants in the <it>OXT </it>promoter region, and in the <it>OXTR </it>gene in DNA samples from 131 rigorously evaluated patients with Irritable Bowel Syndrome (IBS), 408 homozygous subjects referred for lactase (LCT-13910 C>T, rs4988235) genotyping, and 299 asymptomatic blood donors were compared. One polymorphism related to the <it>OXT </it>gene (rs6133010 A>G) and 4 related to the <it>OXTR </it>gene (rs1465386 G>T, rs3806675 G>A, rs968389 A>G, rs1042778 G>T) were selected for genotyping using Applied Biosystems 7900 HT allele discrimination assays.</p> <p>Results</p> <p>There were no statistically significant differences in the genotype or allele frequencies in any of the SNPs when IBS patients were compared to healthy controls. Among subjects referred for lactase genotyping, the rs6133010 A>G <it>OXT </it>promoter A/G genotype tended to be more common in the 154 non-persistent (27.3%) subjects than in the 254 lactase persistant (18.1%) subjects and in the healthy controls (19.4%) (p = 0.08). When direct comparing, the A/G genotype was less common in the <it>OXT </it>promoter region in controls (p = 0.09) and in subjects with lactase persistence (p = 0.03) compared to subjects with lactase non-persistence. When healthy controls were viewed according to their own LCT-13910 genotypes, the C/C lactase non-persistent controls had a higher frequency for the <it>OXT </it>promoter A/G genotype than LCT-13910 T/T lactase persistent controls (41.2% vs 13.1%).</p> <p>No significant differences in frequencies of the investigated <it>OXTR </it>SNPs were noted in this study.</p> <p>Conclusion</p> <p>The results suggest that polymorphism in the promoter region of the <it>OXT </it>gene is most common in subjects with lactase non-persistence. This polymorphism may not be related to GI symptoms, as it is related to lactase non-persistence also in healthy controls.</p

Neural correlates of a single-session massage treatment

The current study investigated the immediate neurophysiological effects of different types of massage in healthy adults using functional magnetic resonance imaging (fMRI). Much attention has been given to the default mode network, a set of brain regions showing greater activity in the resting state. These regions (i.e. insula, posterior and anterior cingulate, inferior parietal and medial prefrontal cortices) have been postulated to be involved in the neural correlates of consciousness, specifically in arousal and awareness. We posit that massage would modulate these same regions given the benefits and pleasant affective properties of touch. To this end, healthy participants were randomly assigned to one of four conditions: 1. Swedish massage, 2. reflexology, 3. massage with an object or 4. a resting control condition. The right foot was massaged while each participant performed a cognitive association task in the scanner. We found that the Swedish massage treatment activated the subgenual anterior and retrosplenial/posterior cingulate cortices. This increased blood oxygen level dependent (BOLD) signal was maintained only in the former brain region during performance of the cognitive task. Interestingly, the reflexology massage condition selectively affected the retrosplenial/posterior cingulate in the resting state, whereas massage with the object augmented the BOLD response in this region during the cognitive task performance. These findings should have implications for better understanding how alternative treatments might affect resting state neural activity and could ultimately be important for devising new targets in the management of mood disorders

Dysphoric milk ejection reflex: A case report

Dysphoric Milk Ejection Reflex (D-MER) is an abrupt emotional "drop" that occurs in some women just before milk release and continues for not more than a few minutes. The brief negative feelings range in severity from wistfulness to self-loathing, and appear to have a physiological cause. The authors suggest that an abrupt drop in dopamine may occur when milk release is triggered, resulting in a real or relative brief dopamine deficit for affected women. Clinicians can support women with D-MER in several ways; often, simply knowing that it is a recognized phenomenon makes the condition tolerable. Further study is needed

The Way to a Man's Heart Is through His Stomach: What about Horses?

International audienceBACKGROUND: How do we bond to one another? While in some species, like humans, physical contact plays a role in the process of attachment, it has been suggested that tactile contact's value may greatly differ according to the species considered. Nevertheless, grooming is often considered as a pleasurable experience for domestic animals, even though scientific data is lacking. On another hand, food seems to be involved in the creation of most relationships in a variety of species. METHODOLOGY/PRINCIPAL FINDINGS: In this study, we used the horse training context to test the effects of food versus grooming during repeated human-horse interactions. The results reveal that food certainly holds a key role in the attachment process, while tactile contact was here clearly insufficient for bonding to occur. CONCLUSION/SIGNIFICANCE: This study raises important questions on the way tactile contact is perceived, and shows that large inter-species differences are to be expected

Maternal plasma levels of oxytocin during physiological childbirth - a systematic review with implications for uterine contractions and central actions of oxytocin

Oxytocin is a key hormone in childbirth, and synthetic oxytocin is widely administered to induce or speed labour. Due to lack of synthetized knowledge, we conducted a systematic review of maternal plasma levels of oxytocin during physiological childbirth, and in response to infusions of synthetic oxytocin, if reported in the included studies. An a priori protocol was designed and a systematic search was conducted in PubMed, CINAHL, and PsycINFO in October 2015. Search hits were screened on title and abstract after duplicates were removed (n = 4039), 69 articles were examined in full-text and 20 papers met inclusion criteria. As the articles differed in design and methodology used for analysis of oxytocin levels, a narrative synthesis was created and the material was categorised according to effects. Basal levels of oxytocin increased 3-4-fold during pregnancy. Pulses of oxytocin occurred with increasing frequency, duration, and amplitude, from late pregnancy through labour, reaching a maximum of 3 pulses/10 min towards the end of labour. There was a maximal 3- to 4-fold rise in oxytocin at birth. Oxytocin pulses also occurred in the third stage of labour associated with placental expulsion. Oxytocin peaks during labour did not correlate in time with individual uterine contractions, suggesting additional mechanisms in the control of contractions. Oxytocin levels were also raised in the cerebrospinal fluid during labour, indicating that oxytocin is released into the brain, as well as into the circulation. Oxytocin released into the brain induces beneficial adaptive effects during birth and postpartum. Oxytocin levels following infusion of synthetic oxytocin up to 10 mU/min were similar to oxytocin levels in physiological labour. Oxytocin levels doubled in response to doubling of the rate of infusion of synthetic oxytocin. Plasma oxytocin levels increase gradually during pregnancy, and during the first and second stages of labour, with increasing size and frequency of pulses of oxytocin. A large pulse of oxytocin occurs with birth. Oxytocin in the circulation stimulates uterine contractions and oxytocin released within the brain influences maternal physiology and behaviour during birth. Oxytocin given as an infusion does not cross into the mother's brain because of the blood brain barrier and does not influence brain function in the same way as oxytocin during normal labour does

Do lambs perceive regular human stroking as pleasant? Behavior and heart rate variability analyses

Stroking by humans is beneficial to the human-animal relationship and improves welfare in many species that express intraspecific allogrooming, but very few studies have looked at species like sheep that do not express such contact except around parturition. This study investigated the way lambs perceive regular human tactile contact using behavioral and physiological responses. Twenty-four lambs were reared and bucket-fed in groups of four. All were stroked daily by their familiar caregiver. At 8 weeks of age, the lambs were individually tested in their home pen but in a 1×1m open-barred pen after a 15h period of habituation to physical separation from peers while remaining in visual and auditory contact. Half of the lambs received stroking by their caregiver for 8min and half were exposed to their caregiver’s immobile presence. Heart rate and heart rate variability were recorded and analyzed by 2-min slots over the same interval based on three measures: mean heart rate value (HR), root mean square of successive differences (RMSSD) and standard deviation of all intervals measured between consecutive sinus beats (SDNN). Behavioral responses (ear postures of the lamb and time spent in contact with the familiar caregiver, on the knees of the familiar caregiver, and moving) were recorded throughout the test. Lamb HR decreased continuously while in the presence of their caregiver. Lambs being stroked showed slower HR and higher RMSSD which reflected positive emotional states compared to lambs left unstroked. All behavioral variables were highly correlated with the main component axis of the PCA analyses: the more the animals stayed in contact with their caregiver, the less they moved and the more their ears were hanging. This first component clearly differentiates lambs being stroked or not. Behavioral and physiological observations support the hypothesis that gentle physical contact with the caregiver is perceived positively by lambs

C-tactile afferent stimulating touch carries a positive affective value

The rewarding sensation of touch in affiliative interactions is hypothesized to be underpinned by a specialized system of nerve fibers called C-Tactile afferents (CTs), which respond optimally to slowly moving, gentle touch, typical of a caress. However, empirical evidence to support the theory that CTs encode socially relevant, rewarding tactile information in humans is currently limited. While in healthy participants, touch applied at CT optimal velocities (1-10cm/sec) is reliably rated as subjectively pleasant, neuronopathy patients lacking large myelinated afferents, but with intact C-fibres, report that the conscious sensation elicited by stimulation of CTs is rather vague. Given this weak perceptual impact the value of self-report measures for assessing the specific affective value of CT activating touch appears limited. Therefore, we combined subjective ratings of touch pleasantness with implicit measures of affective state (facial electromyography) and autonomic arousal (heart rate) to determine whether CT activation carries a positive affective value. We recorded the activity of two key emotion-relevant facial muscle sites (zygomaticus major—smile muscle, positive affect & corrugator supercilii—frown muscle, negative affect) while participants evaluated the pleasantness of experimenter administered stroking touch, delivered using a soft brush, at two velocities (CT optimal 3cm/sec & CT non-optimal 30cm/sec), on two skin sites (CT innervated forearm & non-CT innervated palm). On both sites, 3cm/sec stroking touch was rated as more pleasant and produced greater heart rate deceleration than 30cm/sec stimulation. However, neither self-report ratings nor heart rate responses discriminated stimulation on the CT innervated arm from stroking of the non-CT innervated palm. In contrast, significantly greater activation of the zygomaticus major (smiling muscle) was seen specifically to CT optimal, 3cm/sec, stroking on the forearm in comparison to all other stimuli. These results offer the first empirical evidence in humans that tactile stimulation that optimally activates CTs carries a positive affective valence that can be measured implicitly