Can We Better Understand, Diagnose, and Treat Ketamine-Induced Uropathy, and Can It Be Reversed? ICI-RS 2024.

Introduction: Ketamine, a versatile anesthetic, has seen increased recreational use, leading to significant health issues, including ketamine-induced uropathy (KIU). KIU manifests with lower urinary tract symptoms (LUTS) and can involve the upper urinary tract. This study aims to provide a comprehensive overview of KIU, addressing its pathophysiology, diagnostic strategies, and treatment options; and to define/identify future research priorities.

Evaluating the quality of multiple-choice question pilot database: A global educator-created tool for concept-based pharmacology learning.

The Core Concepts of Pharmacology (CCP) initiative is developing educational resources to transform pharmacology education into a concept-based approach. This study evaluated the quality of global educator-created MCQs in generating items for the pharmacology concept inventory (PCI) instrument and developed as a resource for learning pharmacology fundamental concepts. A panel of 22 global pharmacology experts recruited from the CCP initiative research team participated in the MCQ pilot database design and evaluation.

Beyond the urothelium: Interplay between autonomic nervous system and bladder inflammation in urinary tract infection, bladder pain syndrome with interstitial cystitis and neurogenic lower urinary tract dysfunction in spinal cord injury-ICI-RS 2023.

Introduction: Inflammation and neuronal hypersensitivity are reactive protective mechanisms after urothelial injury. In lower urinary tract dysfunctions (LUTD), such as urinary tract infection (UTI), bladder pain syndrome with interstitial cystitis (BPS/IC) and neurogenic LUTD after spinal cord injury (SCI), chronic inflammation can develop. It is unclear how the protective reactionary inflammation escalates into chronic disease in some patients.

Angiotensinergic and GABAergic transmission in the medial preoptic area: role in urinary bladder and cardiovascular control in female rats.

The medial preoptic area (mPOA) participates in thermoregulatory control and blood pressure modulation as shown by studies with electrical stimulation of this area or cobalt chloride injection, a non-selective synapse inhibitor. This study aimed to investigate whether angiotensin II (Ang II) and GABA could act or not in the mPOA to mediate the cardiovascular and micturition control pathways. Female Wistar rats were submitted to stereotaxic surgery for implantation of a guide cannula into the mPOA 7 days prior to the experiments.

Soluble guanylate cyclase mediates the relaxation of healthy and inflamed bladder smooth muscle by aqueous nitric oxide.

Due to its chemical properties, functional responses to nitric oxide (NO) are often difficult to examine. In the present study, we established a method to produce NO in an aqueous solution and validated its capacity to evoke functional responses in isolated rat bladders. Furthermore, we compared the NO responses to the commonly used NO donor sodium nitroprusside (SNP).

Defining and unpacking the core concepts of pharmacology: A global initiative.

Background And Purpose: Development of core concepts in disciplines such as biochemistry, microbiology and physiology have transformed teaching. They provide the foundation for the development of teaching resources for global educators, as well as valid and reliable approaches to assessment. An international research consensus recently identified 25 core concepts of pharmacology.

GABAergic and glutamatergic transmission reveals novel cardiovascular and urinary bladder control features in the shell nucleus accumbens.

The shell Nucleus Accumbens (NAcc) projects to the lateral preoptic area, which is involved in the central micturition control and receives inputs from medullary areas involved in cardiovascular control. We investigated the role of GABAergic and glutamatergic transmission in the shell NAcc on intravesical pressure (IP) and cardiovascular control. Male Wistar rats with guide cannulas implanted bilaterally in the shell NAcc 7 days prior to the experiments were anesthetized with 2% isoflurane in 100% O and subjected to cannulation of the femoral artery and vein for mean arterial pressure (MAP) and heart rate recordings (HR) and infusion of drugs, respectively.

6-OHDA-Induced Changes in Colonic Segment Contractility in the Rat Model of Parkinson's Disease.

Background: Gastrointestinal dysfunction is one of the most common non-motor symptoms in Parkinson's disease (PD). The exact mechanisms behind these symptoms are not clearly understood. Studies in the well-established 6-hydroxydopamine (6-OHDA) lesioned rats of PD have shown altered contractility in isolated circular and longitudinal smooth muscle strips of distal colon.

Identifying the core concepts of pharmacology education: A global initiative.

Background And Purpose: In recent decades, a focus on the most critical and fundamental concepts has proven highly advantageous to students and educators in many science disciplines. Pharmacology, unlike microbiology, biochemistry, or physiology, lacks a consensus list of such core concepts.

Experimental Approach: We sought to develop a research-based, globally relevant list of core concepts that all students completing a foundational pharmacology course should master.

Blockade of vasopressin receptors reduces the threshold pressure of micturition reflex in female rats.

The mechanisms involved in urinary bladder control are not fully understood, but it is well accepted that a complex central network is involved in micturition control. The micturition reflex can be modulated by direct cortical influence through facilitatory and inhibitory mechanisms. In addition, humoral mechanisms are involved in the bladder control.

Activation of 5-HT3 receptors in the medulla oblongata is involved in the phasic control of urinary bladder.

The control of micturition depends on reflex mechanisms, however, it undergoes modulation from cortex, pons and medullary areas. This study investigated if the activation of 5-HT3 receptors in the medulla influences the urinary bladder (UB) regulation in rats. Isoflurane female Wistar rats were submitted to catheterization of the femoral artery and vein for mean arterial pressure (MAP) and heart rate (HR) recordings and injection of drugs, respectively.

Treatment with the soluble guanylate cyclase activator BAY 60-2770 normalizes bladder function in an in vivo rat model of chronic prostatitis.

Background And Purpose: Chronic pelvic pain syndrome (CPPS) is a common and bothersome condition for which no pharmacological treatment options with acceptable efficacy exist. The aim of this study was to investigate the effects of the soluble guanylate cyclase (sGC) activator BAY 60-2770 and the COX-2 inhibitor celecoxib on bladder function in a rat model of CPPS.

Experimental Approach: Forty-eight male Sprague-Dawley rats were intraprostatically injected with either saline, serving as control, or zymosan, to induce prostatitis.

Novel Insights Into Muscarinic and Purinergic Responses in Primary Cultures of Rat Lacrimal Gland Myoepithelial Cells.

Purpose: The functional characteristics of receptors that regulate lacrimal gland myoepithelial cells are still somewhat unclear. To date, mainly muscarinic receptors have been of interest; however, further knowledge is needed regarding their expression and functional roles. For this purpose, primary cultures of rat lacrimal gland myoepithelial cells were established and examined functionally.

Cross-organ sensitization between the prostate and bladder in an experimental rat model of lipopolysaccharide (LPS)-induced chronic pelvic pain syndrome.

Background: The aim of the current study was to investigate the effects of chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) on bladder function via prostate-to-bladder cross-sensitization in a rat model of lipopolysaccharide (LPS)-induced prostate inflammation.

Methods: Male rats were intraprostatically injected with LPS or saline, serving as control. Micturition parameters were examined in a metabolic cage 10 or 14 days later.

Prostate-to-bladder cross-sensitization in a model of zymosan-induced chronic pelvic pain syndrome in rats.

Background: The aim of the present study was to investigate the effects of chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) on bladder function and pathophysiology.

Methods: To create a model for CPPS, rats were intraprostatically injected with zymosan or saline, serving as control. Metabolic cage experiments were performed 7, 14, or 21 days after zymosan injection and after 14 days in the control group.

Desipramine, commonly used as a noradrenergic neuroprotectant in 6-OHDA-lesions, leads to local functional changes in the urinary bladder and gastrointestinal tract in healthy rats.

The 6-hydroxydopamine (6-OHDA) rat model is one of the most common animal models of Parkinson's disease. When experimentally inducing dopaminergic neurodegeneration in the nigrostriatal pathway using 6-OHDA, the noradrenergic reuptake inhibitor desipramine is often systemically injected in order to protect against damages to the noradrenergic system in the brain. An increasing number of studies are focusing on understanding the pathophysiological changes underlying autonomic non-motor symptoms, in particular urinary bladder and gastrointestinal dysfunctions, of the disease.

Functional atropine sensitive purinergic responses in the healthy rat bladder.

While acetylcholine is regarded to be the main directly contractile transmitter substance in the urinary bladder, interactions with other transmitters likely occur. Presently, the interplay between purinergic and cholinergic signalling was investigated to unravel the involvement of the urothelium and efferent neurons in the functionally important purinergically evoked release of acetylcholine in vitro. Functional characterization of receptor subtypes involved in this interplay was also performed.

In vivo paracrine effects of ATP-induced urothelial acetylcholine in the rat urinary bladder.

Mechanical stretch of the urothelium induces the release of ATP that activates bladder afferent nerves. In the rat urinary bladder, ATP is also a contractile co-transmitter in the parasympathetic innervation. In isolated preparations, ATP evokes a urothelial release of acetylcholine that substantially contributes to ATP-evoked contractile responses.

Oxytocin Reduces Intravesical Pressure in Anesthetized Female Rats: Action on Oxytocin Receptors of the Urinary Bladder.

Urinary bladder dysfunction affects several people worldwide and shows higher prevalence in women. Micturition is dependent on the Barrington's nucleus, pontine urine storage center and periaqueductal gray matter, but other brain stem areas are involved in the bladder regulation. Neurons in the medulla oblongata send projections to hypothalamic nuclei as the supraoptic nucleus, which synthetizes oxytocin and in its turn, this peptide is released in the circulation.

Resistance Exercise Evokes Changes on Urinary Bladder Function and Morphology in Hypoestrogen Rats.

Serum levels of estrogen decrease at climacterium and directly interfere with the urogenital tract. Urinary bladder (UB) is responsive to hormonal changes, especially estrogen. Resistance exercise elicits benefits on severe chronic diseases.

Combination drug therapy against OAB normalizes micturition parameters and increases the release of nitric oxide during chemically induced cystitis.

Today, monotherapy is the most common pharmacological treatment option for patients suffering from overactive bladder (OAB). Recent reports have indicated potential benefits of combination therapy, using a muscarinic antagonist and a β -adrenoceptor agonist. This may be of particular interest for therapy-resistant patients with OAB and concomitant cystitis.