Non adrenergic non cholinergic transmission(nanc)Merlin Binu
Neurotransmitters other than Acetyl choline and NorAdrenaline of parasympathetic and sympathetic nervous system play important role in synaptic junction transmission. That neurotransmitters are called NANC.
Nitric oxide supplements are a category of supplements that includes L-citrulline and L-arginine. Researchers have performed multiple clinical trials related to nitric oxide supplements and their effectiveness, often with mixed results.
Different types of receptors can drugs affect the body through interacting with these receptors.
this presentation is a part from special course in basics of pharmacology .. deep and simple
Non adrenergic non cholinergic transmission(nanc)Merlin Binu
Neurotransmitters other than Acetyl choline and NorAdrenaline of parasympathetic and sympathetic nervous system play important role in synaptic junction transmission. That neurotransmitters are called NANC.
Nitric oxide supplements are a category of supplements that includes L-citrulline and L-arginine. Researchers have performed multiple clinical trials related to nitric oxide supplements and their effectiveness, often with mixed results.
Different types of receptors can drugs affect the body through interacting with these receptors.
this presentation is a part from special course in basics of pharmacology .. deep and simple
Topic of the month.... Endothelial nitric oxide synthase (eNOS) And Stroke: P...Professor Yasser Metwally
Topic of the month.... Endothelial nitric oxide synthase (eNOS) And Stroke: Prevention, Treatment And Recovery
http://yassermetwally.com
http://yassermetwally.net
In the rapidly evolving landscape of technologies, XML continues to play a vital role in structuring, storing, and transporting data across diverse systems. The recent advancements in artificial intelligence (AI) present new methodologies for enhancing XML development workflows, introducing efficiency, automation, and intelligent capabilities. This presentation will outline the scope and perspective of utilizing AI in XML development. The potential benefits and the possible pitfalls will be highlighted, providing a balanced view of the subject.
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Further emphasis will be placed on the role of AI in developing XSLT, or schemas such as XSD and Schematron. We will address the techniques and strategies adopted to create prompts for generating code, explaining code, or refactoring the code, and the results achieved.
The discussion will extend to how AI can be used to transform XML content. In particular, the focus will be on the use of AI XPath extension functions in XSLT, Schematron, Schematron Quick Fixes, or for XML content refactoring.
The presentation aims to deliver a comprehensive overview of AI usage in XML development, providing attendees with the necessary knowledge to make informed decisions. Whether you’re at the early stages of adopting AI or considering integrating it in advanced XML development, this presentation will cover all levels of expertise.
By highlighting the potential advantages and challenges of integrating AI with XML development tools and languages, the presentation seeks to inspire thoughtful conversation around the future of XML development. We’ll not only delve into the technical aspects of AI-powered XML development but also discuss practical implications and possible future directions.
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- These are slides of the talk given at IEEE International Conference on Software Testing Verification and Validation Workshop, ICSTW 2022.
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Alt. GDG Cloud Southlake #33: Boule & Rebala: Effective AppSec in SDLC using ...James Anderson
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The software team must secure its software delivery process to avoid vulnerability and security breaches. This needs to be achieved with existing tool chains and without extensive rework of the delivery processes. This talk will present strategies and techniques for providing visibility into the true risk of the existing vulnerabilities, preventing the introduction of security issues in the software, resolving vulnerabilities in production environments quickly, and capturing the deployment bill of materials (DBOM).
Speakers:
Bob Boule
Robert Boule is a technology enthusiast with PASSION for technology and making things work along with a knack for helping others understand how things work. He comes with around 20 years of solution engineering experience in application security, software continuous delivery, and SaaS platforms. He is known for his dynamic presentations in CI/CD and application security integrated in software delivery lifecycle.
Gopinath Rebala
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Clients don’t know what they don’t know. What web solutions are right for them? How does WordPress come into the picture? How do you make sure you understand scope and timeline? What do you do if sometime changes?
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Join Maher Hanafi, VP of Engineering at Betterworks, in this new session where he'll share a practical framework to transform Gen AI prototypes into impactful products! He'll delve into the complexities of data collection and management, model selection and optimization, and ensuring security, scalability, and responsible use.
GDG Cloud Southlake #33: Boule & Rebala: Effective AppSec in SDLC using Deplo...James Anderson
Effective Application Security in Software Delivery lifecycle using Deployment Firewall and DBOM
The modern software delivery process (or the CI/CD process) includes many tools, distributed teams, open-source code, and cloud platforms. Constant focus on speed to release software to market, along with the traditional slow and manual security checks has caused gaps in continuous security as an important piece in the software supply chain. Today organizations feel more susceptible to external and internal cyber threats due to the vast attack surface in their applications supply chain and the lack of end-to-end governance and risk management.
The software team must secure its software delivery process to avoid vulnerability and security breaches. This needs to be achieved with existing tool chains and without extensive rework of the delivery processes. This talk will present strategies and techniques for providing visibility into the true risk of the existing vulnerabilities, preventing the introduction of security issues in the software, resolving vulnerabilities in production environments quickly, and capturing the deployment bill of materials (DBOM).
Speakers:
Bob Boule
Robert Boule is a technology enthusiast with PASSION for technology and making things work along with a knack for helping others understand how things work. He comes with around 20 years of solution engineering experience in application security, software continuous delivery, and SaaS platforms. He is known for his dynamic presentations in CI/CD and application security integrated in software delivery lifecycle.
Gopinath Rebala
Gopinath Rebala is the CTO of OpsMx, where he has overall responsibility for the machine learning and data processing architectures for Secure Software Delivery. Gopi also has a strong connection with our customers, leading design and architecture for strategic implementations. Gopi is a frequent speaker and well-known leader in continuous delivery and integrating security into software delivery.
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Unlocking Productivity: Leveraging the Potential of Copilot in Microsoft 365, a presentation by Christoforos Vlachos, Senior Solutions Manager – Modern Workplace, Uni Systems
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• Communication Mining Overview
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• How can it help today’s business and the benefits
• Phases in Communication Mining
• Demo on Platform overview
• Q/A
Sudheer Mechineni, Head of Application Frameworks, Standard Chartered Bank
Discover how Standard Chartered Bank harnessed the power of Neo4j to transform complex data access challenges into a dynamic, scalable graph database solution. This keynote will cover their journey from initial adoption to deploying a fully automated, enterprise-grade causal cluster, highlighting key strategies for modelling organisational changes and ensuring robust disaster recovery. Learn how these innovations have not only enhanced Standard Chartered Bank’s data infrastructure but also positioned them as pioneers in the banking sector’s adoption of graph technology.
Large Language Model (LLM) and it’s Geospatial Applications
Endothelium derived factors
1. Clinical Pharmacology
1
Mohanad AlBayati
Mohanad AbdulSattar Ali Al-Bayati, BVM&S, MS. Physiology, PhD.
Assistant Professor of Pharmacology and Toxicology
Department of Physiology and Pharmacology
College of Veterinary Medicine
University of Baghdad
Al-Ameria, Baghdad
Phone: 0964 7700766550
E. Mail: aumnmumu@covm.uobaghdad.edu.iq
aumnmumu@yahoo.com
Autacoidal Therapy
Endothelium-Derived Factors disorders
2. 1980
Furchgott and Zawadzki reported that acetylcholine (ACh)
causes relaxation of isolatedblood vessels only in the
presence of an intact endothelial cell layer.
1977
Murad discovered that nitric oxide (NO) release caused by
nitrates relaxes smooth muscle cells.
1986
Ignarro proposed that endothelium-derived relaxing factor
(EDRF) is identical to NO.
Robert Furchgott, Ferid Murad and Luis Ignarro were awarded
the Nobel Prize in Physiology and Medicine in
1998.
3. The involvement of
endothelium in coordination
of vasoactive factors and its
important role in regulation of
blood vessels tone has been
recognized.
4. Endothelium-derived vasorelaxing factors
The endothelium plays a direct role in vasomotor function by integrating the
controlling factors:
• Reflexes
• Humoral
• Local factors
Endothelial cells release substances
acting directly on vascular smooth
muscle cells, causing either
contraction or relaxation.
6. Nitric oxide
Endothelium-derived vasorelaxing
factors
Nitric oxide (NO) is a relatively stable gas, with ability to easily diffuse through the cell
membrane. NO is capable to interact with various substances in the cell
NO plays an important role in many physiological processes and is important in regulation
of vascular system, neurotransmission and various homeostatic events
Many pathological states are known, where NO synthesis dysfunction is one of the main
problems.
• Diabetes
• Shock
• Infarction
• Neurodegeneration
• Arthritis
• Chronic inflammation
7. Depending on protein structure, NO may have
strong or weak connection with different proteins.
NO interaction with proteins containing hem is
weak and manifests itself by changing their activity
(activates or inhibits).
Depending on protein structure, NO may have strong
or weak connection with different proteins. NO
interaction with proteins containing hem is weak and
manifests itself by changing their activity (activates or
inhibits)
NO inhibits
• Cytochromoxidase
• NO synthase
• cytochrome P450
• thromboxane synthetase
• Catalase
• peroxidase
Cytochromoxidase inhibition, oxidative phosphorylation in
mitochondria is inhibited.
Inhibition of thrombocyte activity and decreased cell
proliferation.
8. NO activates cytosolic guanylyl cyclase. Cyclic
GMP is increased and leads to vascular smooth
muscle relaxation,
Activation of prostacyclin synthesis by NO. that prostacyclin synthesis is activated
by activation of prostaglandin H synthase by increasing cyclooxygenase activity by a
c.GMP-independent pathway.
NO affects cell metabolism.
Endogenous NO inhibits mitochondrial respiration and ATP synthesis,
This is a consequence of inhibition of cytochromoxidase or indirectly
by NO metabolism products, such as peroxynitrite and reactive
oxygen species.
It is known that NO metabolism products inhibit Krebs cycle enzyme
aconitase.
It is also known that NO binds to the hem part of the
cytochromoxidase occupying the oxygen binding site, thus allowing
NO to regulate mitochondrial affinity for oxygen.
9. Nitric oxide inhibits glycolysis by inhibiting 3-phosphoglyceraldehyde
dehydrogenase. The product of this reaction, peroxynitrite, causes peroxidation of
lipids and other substances (e.g. DNA). This also leads to disturbance of energetic
metabolism. DNA synthesis depends on ribonucleotide reductase. This enzyme
has two subunits, each of which can bind NO.
The increase in NO synthesis decreases DNA synthesis.
Nitric oxide can influence transcription through
a cGMP-dependent mechanisms leading to
phosphorylation of transcription factors.
NO may interact with some of receptors, causing downstream effects. As an example could
be N-methyl-D-aspartate (NDMA) receptor, action of which is influenced by nitrosothiol
formation. Stimulation of this receptor is harmful because of Ca2+ overload in certain
neurons. Ca2+ overload activates proteases and phospholipases, as well as free radical
reactions.
As an example of biological effects of NO could
be activation of vascular smooth muscle cells Ca2+
dependent K+ channels (KCa) and possible involvement
in endothelial K+ channels.
10. Endothelium-derived hyperpolarizing factor
Endothelium-derived hyperpolarizing factor
(EDHF), which provides strong relaxing action
on smooth muscle, remains unidentified
substance could be labile arachidonic acid
metabolite released after stimulation with
bradykinin. The structure of the source of
this substance depends on cytochrome
P450 monooxygenase activity
possibly most convincing hypothesis, relates
origin of EDHF with phospholipase A2 (PLA2).
In perfused rat heart model with blocked NO
and prostaglandin synthesis (nitroarginine and
indomethacin), PLA2 inhibitor abolished
vasodilation caused by bradykinin
PLA2 importance in EDHF synthesis
11. Relaxation caused by bradykinin was
abolished by arachidonyl trifluoromethylketone,
cytosolic phospholipase A2 inhibitor. This
repeatedly confirms that arachidonic acid,
released by activating PLA2, plays a role in
EDHF formation.
In 1998
potassium ions (K+) were identified as possible EDHF
muscarinic receptor blocker, to smooth muscle relaxation
in presence of ouabain (Na+/K+ ATPase blocker)
The inhibition of relaxation by ouabain was decreased by
increasing the extracellular K+ concentration.
Acetylcholine - induced hyperpolarization of endothelial cells
and K+ concentration In blocking medium Ca2+ dependent K+
channels (K+ Ca) with charybdotoxin and apamin.
12. EDHF-evoked smooth muscle hyperpolarization
was also abolished by these blockers, but there
was no effect of them in hyperpolarization caused
by K+
hydrogen peroxide is EDHF (H2O2). H2O2 activates
highly permeable Ca2+ dependent and voltage
gated K+channels (BKCa)
Epoxyeicosatrienoic acids EETa’s are
synthesized from arachidonic acid with a help
of epoxygenases, this could be the same EDHF
acids activate Ca2+ dependent K+ channels
(KCa), causing hyperpolarization of smooth
muscle cells
EETa activates ribolysation of ADP-dependent
G protein a subunit. This kind of Gsa activation
could be additive to direct EETa effect on G
protein in further KCa activation pathway,
leading to smooth muscle hyperpolarization
13. Prostaglandins
Prostacyclin (PGI2) and prostaglandin E2
Prostacyclin was described as endothelium-
derived relaxing factor in 1979
Vasorelaxing effect of this substance is determined by
specific vascular smooth muscle cell receptors.
Therefore, prostacyclin is not involved in endothelium
dependent vasorelaxation in absence of these
receptors.
Effect of prostacyclin is tightly connected with NO effects.
It facilitates NO release from endothelial cells and in turn
NO potentiates prostacyclin effects in smooth muscle. NO
activates cyclic GMP synthesis and increases inhibition of
phosphodiesterase, which degrades cAMP. Cyclic AMP
prolongs effect of prostacyclin in smooth muscle cells.
14. Endothelium-derived vasoconstricting factors
Prostaglandins
Prostaglandin H2 is formed in the endothelial cells during arachidonic
acid metabolism pathway.
Prostaglandin H2 is a precursor of all
prostanoids including thromboxane A2.
Prostaglandin H2 and thromboxane A2
binds to endoperoxidase and
thromboxane receptors initiating
vascular smooth muscle contraction.
vasoconstrictor is overridden by
endothelium-derived
vasorelaxants.
15. Reactive oxygen radicals
Active oxygen radicals are formed in
endothelial cells in response to
increased blood pressure and
endothelial agonists
Destruction of NO by superoxide ions causes vasoconstriction.
Adjacent mechanism of action is believed to be
oxygen effect on smooth muscle cytosol Ca2+:
increase in concentration of Ca2+ causes
vasoconstriction. In addition, free radicals sensitize
muscle contractile apparatus for Ca2+, what also
stimulates contraction.
16. Endothelin-1 produced by endothelial cells is one of the most potent vasoconstrictors.
Its synthesis can be initiated by
thrombin,
interleukin- 1,
thrombocytes released factors,
growth factor 1,
vasopressin
catecholamine on endothelial cells
Synthesis of this vasoconstrictor is inhibited by released NO
Endothelin.
20. L-arginine is a substrate for NO synthesis. NO and L-citrulline are produced after induction of
Larginine metabolism by NO synthase (NOS). During L-arginine splitting oxygen and NADHP
are used; NH2 group of L-arginine is transformed to NOH group, from which NO separates in
the process of L-citrulline formation (Fig.1). L-arginine reserve is accumulated from
extracellular space and by intracellular synthesis. Endothelium released NO initiates smooth
muscle relaxation (Fig.2). NO activates soluble guanylyl cyclase, which initiates guanosine
triphosphate (GTP) transformation to cyclic GMP. Activation of cyclic GMP dependent
proteinkinase G is followed by cytosolic Ca2+ removal from the cell and inhibition of
contractile apparatus. Action of proteinkinase G has direct influence on phosphorylisation of
gap junctions, activity of potassium and calcium channels. Phosphorylisation of potassium
channels causes K+ outflow from cell, when phosphorylated calcium channels decrease Ca2+
influx. If Ca2+ cytoplasmic concentration decreases below 500 nM, the contraction is
stopped. It happens because of Ca2+ unbinding from calmodulin, followed by detachment
from myosin light chain kinase, causing its inactivation. Dephosphorylated myosin light chain
prevents from myosin head binding to actin, causing relaxation of smooth muscle. Level of
cyclic GMP is decreased via hydrolysis. In this process specific cyclic GMP phosphodiesterases
5th type (PDE5) is involved, resulting in cyclic GMP transformation to GMP. This is the action
mechanism of drugs inhibiting PDE5. One representative substance from this family is
sildenafil, which is known as specific PDE5 inhibitor potentiating relaxation caused by NO.
This active substance is used for treatment of erectile dysfunction. PDE5 inhibitors are tested
for their applicability in therapy of pulmonary hypertension and effects on human
hemodynamics.
21. Endothelium and endothelium-released substances play an
important role in maintaining vascular smooth muscle tone. The main
role in endothelial dysfunction is thought to be played by vasorelaxing
factors released after stimulation. This stimulation could be exerted via
autonomic and sensory nerves (ACh, norepinephrine, ATP, substance
P), circulating hormones (angiotensin II, insulin, catecholamine,
vasopressin), coagulation derivates and thrombocyte-released
substances (serotonin, ADP, thrombin). In addition, endothelial and
smooth muscle cells can produce autacoids: bradykinin, angiotensin II,
endothelin, ADP and ATP Endothelium responses to shear stress and
blood flow changes and endothelium-released vasorelaxing factors
control angiogenic and smooth muscle proliferation modifying factors.
In healthy arteries endothelium has anti-adhesive and antithrombic
properties. Age, hypertension, atherosclerosis, hyperlipidemia and
critical conditions of organism may provoke endothelial dysfunction.
Endothelial dysfunction