scholarly journals The cAMP-phosphodiesterase 4 (PDE4) controls β-adrenoceptor- and CFTR-dependent saliva secretion in mice.

2021 ◽  
Author(s):  
Abigail Boyd ◽  
Ileana V. Aragon ◽  
Lina Abou Saleh ◽  
Dylan Southers ◽  
Wito Richter

Saliva, while often taken for granted, is indispensable for oral health and overall well-being, as inferred from the significant impairments suffered by patients with salivary gland dysfunction. Here, we show that treatment with several structurally-distinct PAN-PDE4 inhibitors, but not a PDE3 inhibitor, induces saliva secretion in mice, indicating it is a class-effect of PDE4 inhibitors. In anesthetized mice, while neuronal regulations are suppressed, PDE4 inhibition potentiates a β-adrenoceptor-induced salivation, that is ablated by the β-blocker Propranolol and is absent in homozygous ΔF508-CFTR mice lacking functional CFTR. These data suggest that PDE4 acts within salivary glands to gate saliva secretion that is contingent upon the cAMP/PKA-dependent activation of CFTR. Indeed, PDE4 contributes the majority of total cAMP-hydrolytic capacity in submandibular-, sublingual-, and parotid glands, the three major salivary glands of the mouse. In awake mice, PDE4 inhibitor-induced salivation is reduced by CFTR deficiency or β-blockers, but also by the muscarinic blocker Atropine, suggesting an additional, central/neuronal mechanism of PDE4 inhibitor action. The PDE4 family comprises four subtypes, PDE4A-D. Ablation of PDE4D, but not PDE4A-C, produced a minor effect on saliva secretion, implying that while PDE4D may play a predominant role, PDE4 inhibitor-induced salivation results from the concurrent inactivation of multiple (at least two) PDE4 subtypes. Taken together, our data reveal a critical role for PDE4/PDE4D in controlling CFTR function in an in vivo model and in inducing salivation, hinting at a therapeutic potential of PDE4 inhibition for cystic fibrosis and conditions associated with xerostomia.

2005 ◽  
Vol 19 (1) ◽  
pp. 58-61 ◽  
Author(s):  
Melissa Turk-Gonzales ◽  
Ib R. Odderson

Drooling is common in patients with neurological disorders. Recently, botulinum toxin type B has been shown to be effective in the treatment of drooling. The authors present a unique case of a 57-year-old man with a history of a brainstem stroke and severe drooling. The patient’s parotid and submandibular glands were injected under ultra-sound guidance with botulinum toxin type B. Saliva was collected and quantified before and after the injections by 2 different collection methods: suctioning and dental rolls. Total saliva production decreased by 23.8% after injection of the parotid glands and by 85.8% after submandibular injection compared to the preinjection level. The 2 methods demonstrated similar results. In addition, the patient experienced less drooling and increased participation in therapies without any side effects. This case demonstrates that saliva secretion and drooling can effectively be treated by injections of botulinum toxin type B into the salivary glands.


2019 ◽  
Vol 98 (7) ◽  
pp. 786-794 ◽  
Author(s):  
H.W. Lee ◽  
Y.C. Hsiao ◽  
Y.C. Chen ◽  
T.H. Young ◽  
T.L. Yang

Dysfunctional salivary glands (SGs) are a clinical challenge due to the lack of effective treatments. Cell therapy with stem/progenitor cells may improve this situation by providing promising therapeutic solutions. Therefore, exploring abundant cellular sources is important. Three major pairs of SGs are located in different anatomic regions: the parotid glands, the submandibular glands, and the sublingual glands. Although SG stem/progenitor cells can be isolated and cultivated from all major SGs as salispheres, the differences among SG origins remain unclear. In this study, salispheres were successfully isolated from all major SGs. The salispheres demonstrated unique cellular features that originated from their native tissues. The characteristic expression profiles and cellular features of SG stem cells were demonstrated in all salispheres. When they were transplanted into irradiated animals, the salispheres were all capable of improving the saliva secretion that was disrupted by irradiation. Typical histologic structures could be observed in most parts of the treated glands, and the fibrotic environments of irradiated submandibular glands were remodeled by all salispheres regardless of origins. This study characterized the cellular features and in vivo effects of salispheres that were derived from different anatomic origins. The results suggest the possibility of functional redundancy among distinct pairs of major SGs, which is useful for the design of cell therapy to treat dysfunctional glandular organs.


1974 ◽  
Vol 31 (03) ◽  
pp. 403-414 ◽  
Author(s):  
Terence Cartwright

SummaryA method is described for the extraction with buffers of near physiological pH of a plasminogen activator from porcine salivary glands. Substantial purification of the activator was achieved although this was to some extent complicated by concomitant extraction of nucleic acid from the glands. Preliminary characterization experiments using specific inhibitors suggested that the activator functioned by a similar mechanism to that proposed for urokinase, but with some important kinetic differences in two-stage assay systems. The lack of reactivity of the pig gland enzyme in these systems might be related to the tendency to protein-protein interactions observed with this material.


2018 ◽  
Vol 20 (3) ◽  
pp. 99-110
Author(s):  
Na Zhang ◽  
Jingjing Li ◽  
Xing Bu ◽  
Zhenxing Gong ◽  
Gilal Faheem Gul

Author(s):  
Evi Zohar

Continuing the workshop I've given in the WPC Paris (2017), this article elaborates my discussion of the way I interlace Focusing with Differentiation Based Couples Therapy (Megged, 2017) under the systemic view, in order to facilitate processes of change and healing in working with intimate couples. This article presents the theory and rationale of integrating Differentiation (Bowen, 1978; Schnarch, 2009; Megged, 2017) and Focusing (Gendlin, 1981) approaches, and its therapeutic potential in couple's therapy. It is written from the point of view of a practicing professional in order to illustrate the experiential nature and dynamics of the suggested therapeutic path. Differentiation is a key to mutuality. It offers a solution to the central struggle of any long term intimate relationship: balancing two basic life forces - the drive for individuality and the drive for togetherness (Schnarch, 2009). Focusing is a body-oriented process of self-awareness and emotional healing, in which one learns to pay attention to the body and the ‘Felt Sense’, in order to unfold the implicit, keep it in motion at the precise pace it needs for carrying the next step forward (Gendlin, 1996). Combining Focusing and Differentiation perspectives can cultivate the kind of relationship where a conflict can be constructively and successfully held in the inner world of each partner, while taking into consideration the others' well-being. This creates the possibility for two people to build a mutual emotional field, open to changes, permeable and resilient.


2021 ◽  
pp. 108602662110316
Author(s):  
Tiziana Russo-Spena ◽  
Nadia Di Paola ◽  
Aidan O’Driscoll

An effective climate change action involves the critical role that companies must play in assuring the long-term human and social well-being of future generations. In our study, we offer a more holistic, inclusive, both–and approach to the challenge of environmental innovation (EI) that uses a novel methodology to identify relevant configurations for firms engaging in a superior EI strategy. A conceptual framework is proposed that identifies six sets of driving characteristics of EI and two sets of beneficial outcomes, all inherently tensional. Our analysis utilizes a complementary rather than an oppositional point of view. A data set of 65 companies in the ICT value chain is analyzed via fuzzy-set comparative analysis (fsQCA) and a post-QCA procedure. The results reveal that achieving a superior EI strategy is possible in several scenarios. Specifically, after close examination, two main configuration groups emerge, referred to as technological environmental innovators and organizational environmental innovators.


Biomolecules ◽  
2021 ◽  
Vol 11 (6) ◽  
pp. 864
Author(s):  
Christopher L. Cioffi

Among the myriad of cellular and molecular processes identified as contributing to pathological pain, disinhibition of spinal cord nociceptive signaling to higher cortical centers plays a critical role. Importantly, evidence suggests that impaired glycinergic neurotransmission develops in the dorsal horn of the spinal cord in inflammatory and neuropathic pain models and is a key maladaptive mechanism causing mechanical hyperalgesia and allodynia. Thus, it has been hypothesized that pharmacological agents capable of augmenting glycinergic tone within the dorsal horn may be able to blunt or block aberrant nociceptor signaling to the brain and serve as a novel class of analgesics for various pathological pain states. Indeed, drugs that enhance dysfunctional glycinergic transmission, and in particular inhibitors of the glycine transporters (GlyT1 and GlyT2), are generating widespread interest as a potential class of novel analgesics. The GlyTs are Na+/Cl−-dependent transporters of the solute carrier 6 (SLC6) family and it has been proposed that the inhibition of them presents a possible mechanism by which to increase spinal extracellular glycine concentrations and enhance GlyR-mediated inhibitory neurotransmission in the dorsal horn. Various inhibitors of both GlyT1 and GlyT2 have demonstrated broad analgesic efficacy in several preclinical models of acute and chronic pain, providing promise for the approach to deliver a first-in-class non-opioid analgesic with a mechanism of action differentiated from current standard of care. This review will highlight the therapeutic potential of GlyT inhibitors as a novel class of analgesics, present recent advances reported for the field, and discuss the key challenges associated with the development of a GlyT inhibitor into a safe and effective agent to treat pain.


Nutrients ◽  
2021 ◽  
Vol 13 (1) ◽  
pp. 199
Author(s):  
Kathrin Cohen Kadosh ◽  
Leilani Muhardi ◽  
Panam Parikh ◽  
Melissa Basso ◽  
Hamid Jan Jan Mohamed ◽  
...  

Proper nutrition is crucial for normal brain and neurocognitive development. Failure to optimize neurodevelopment early in life can have profound long-term implications for both mental health and quality of life. Although the first 1000 days of life represent the most critical period of neurodevelopment, the central and peripheral nervous systems continue to develop and change throughout life. All this time, development and functioning depend on many factors, including adequate nutrition. In this review, we outline the role of nutrients in cognitive, emotional, and neural development in infants and young children with special attention to the emerging roles of polar lipids and high quality (available) protein. Furthermore, we discuss the dynamic nature of the gut-brain axis and the importance of microbial diversity in relation to a variety of outcomes, including brain maturation/function and behavior are discussed. Finally, the promising therapeutic potential of psychobiotics to modify gut microbial ecology in order to improve mental well-being is presented. Here, we show that the individual contribution of nutrients, their interaction with other micro- and macronutrients and the way in which they are organized in the food matrix are of crucial importance for normal neurocognitive development.


Author(s):  
Mahnoosh Hassankhani ◽  
Mehdi Alidadi ◽  
Ayyoob Sharifi ◽  
Abolghasem Azhdari

COVID-19 shocked cities around the world and revealed the vulnerability of urban lives and functions. Most cities experienced a catastrophic disturbance that has lasted for a long time. Planning plays a critical role in responding efficiently to this crisis and enabling rapid functional recovery in the post-disaster era. Cities that have implemented digitalization initiatives and programs are likely to have more capacity to react appropriately. Specifically, digitalized cities could ensure the well-being of their residents and maintain continuity of urban functions. This research aims to analyze the role of technology in crisis management in the last two decades and provide appropriate policy recommendations for dealing with the COVID-19 pandemic. Systematic literature review and subjective content analysis are employed to investigate the effects of technology on community well-being and making cities more resilient in past crises. This study shows that different technology-driven policies and actions enable crisis management, enhance community well-being, and increase urban resilience. Technology has enhanced coping and recovery capacities by increasing participation and social connectedness, enhancing physical and mental health and maintaining the functionality of education and economic systems. These have been achieved through various solutions and technologies such as social media, telehealth, tracking and monitoring systems, sensors and locational applications, teleworking systems, etc. These solutions and technologies have also been used during the COVID-19 pandemic to enhance community well-being and sustain urban functions. However, technology deployment might have adverse effects such as social exclusion, digital divide, privacy and confidentiality violation, political bias and misinformation dissemination, and inefficient remote working and education. It is suggested that to mitigate these side effects, policymakers should liberate the process of digitalization, increase the accessibility to digital services, and enhance digital literacy.


AERA Open ◽  
2021 ◽  
Vol 7 ◽  
pp. 233285842110031
Author(s):  
Julia Holzer ◽  
Marko Lüftenegger ◽  
Selma Korlat ◽  
Elisabeth Pelikan ◽  
Katariina Salmela-Aro ◽  
...  

In the wake of COVID-19, university students have experienced fundamental changes of their learning and their lives as a whole. The present research identifies psychological characteristics associated with students’ well-being in this situation. We investigated relations of basic psychological need satisfaction (experienced competence, autonomy, and relatedness) with positive emotion and intrinsic learning motivation, considering self-regulated learning as a moderator. Self-reports were collected from 6,071 students in Austria (Study 1) and 1,653 students in Finland (Study 2). Structural equation modeling revealed competence as the strongest predictor for positive emotion. Intrinsic learning motivation was predicted by competence and autonomy in both countries and by relatedness in Finland. Moderation effects of self-regulated learning were inconsistent, but main effects on intrinsic learning motivation were identified. Surprisingly, relatedness exerted only a minor effect on positive emotion. The results inform strategies to promote students’ well-being through distance learning, mitigating the negative effects of the situation.


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