The GPR39 Receptor Plays an Important Role in the Pathogenesis of Overactive Bladder and Corticosterone-Induced Depression.

Despite the close and clinically confirmed association between depression and overactive bladder, it remains unclear whether this affective disorder is a factor causing overactive bladder or whether overactive bladder is a specific symptom of psychosomatic disorders. This study examined the effects of repeated corticosterone administration on the occurrence of symptoms associated with depression and overactive bladder. Additionally, we examined whether administering TC-G 1008, an antidepressant that selectively activates the GPR39 receptor, could alleviate corticosterone-induced depression-like behavior and detrusor overactivity-related changes in cystometric measurements.

ALK-tyrosine kinase inhibitor intrinsic resistance due to -amplification in metastatic -rearranged non-small cell lung cancer effectively treated by alectinib-crizotinib combination-case report.

Background: Most patients with advanced anaplastic lymphoma kinase ()-rearranged (+) non-small cell lung cancer (NSCLC) experience prolonged response to second-generation (2G) ALK-tyrosine kinase inhibitors (TKIs). Herein, we present a case of metastatic + NSCLC rapidly progressing on first-line treatment due to amplification of the mesenchymal-epithelial transition factor () gene, which is a still elusive and underrecognized mechanism of primary resistance to ALK-TKIs.

Case Description: A 43-year-old, female diagnosed with T4N3M1c NSCLC harboring the echinoderm microtubule-associated protein-like 4 () fusion variant 1 ( v.

Memantine and the Kynurenine Pathway in the Brain: Selective Targeting of Kynurenic Acid in the Rat Cerebral Cortex.

Cytoprotective and neurotoxic kynurenines formed along the kynurenine pathway (KP) were identified as possible therapeutic targets in various neuropsychiatric conditions. Memantine, an adamantane derivative modulating dopamine-, noradrenaline-, serotonin-, and glutamate-mediated neurotransmission is currently considered for therapy in dementia, psychiatric disorders, migraines, or ischemia. Previous studies have revealed that memantine potently stimulates the synthesis of neuroprotective kynurenic acid (KYNA) in vitro via a protein kinase A-dependent mechanism.

Loop diuretics inhibit kynurenic acid production and kynurenine aminotransferases activity in rat kidneys.

Background: Loop diuretics became a cornerstone in the therapy of hypervolemia in patients with chronic kidney disease or heart failure. Apart from the influence on water and electrolyte balance, these drugs were shown to inhibit tissue fibrosis and renin-angiotensin-system activity. The kynurenine (KYN) pathway products are suggested to be uremic toxins.

A rare case report of a primary lung cancer comprising adenocarcinoma and atypical carcinoid tumor, with the carcinoid component harboring rearrangement.

Background: The occurrence of pulmonary adenocarcinoma coexisting with atypical carcinoid tumors is a rare phenomenon. The presence of fusion in an atypical carcinoid component of a histologically mixed tumor is even more uncommon. Due to their infrequency, the origin and pathogenesis of these mixed tumors remain largely unknown.

Lung cancer patients with anaplastic lymphoma kinase rearrangement lose affiliation with labor market at diagnosis.

The main purpose of the present study was to investigate the labor market affiliation of NSCLC patients in long-term treatment as well as overall survival and incidence/prevalence. Nationwide retrospective study of all patients with NSCLC in Denmark diagnosed between 2012 and 2018. During the study period NSCLC patients had a median overall survival of 44.

Microbiota, Tryptophan and Aryl Hydrocarbon Receptors as the Target Triad in Parkinson's Disease-A Narrative Review.

In the era of a steadily increasing lifespan, neurodegenerative diseases among the elderly present a significant therapeutic and socio-economic challenge. A properly balanced diet and microbiome diversity have been receiving increasing attention as targets for therapeutic interventions in neurodegeneration. Microbiota may affect cognitive function, neuronal survival and death, and gut dysbiosis was identified in Parkinson's disease (PD).

Novel Activity of Oral Hypoglycemic Agents Linked with Decreased Formation of Tryptophan Metabolite, Kynurenic Acid.

Kynurenic acid is a tryptophan (Trp) metabolite formed along the kynurenine (KYN) pathway in the brain and in peripheral tissues. The disturbed formation of kynurenic acid, which targets glutamate-mediated neurotransmission, GPR35, and aryl hydrocarbon receptors of immune or redox status, was implicated in the development of neuropsychiatric and metabolic disorders among others. Kynurenic acid exerts neuroprotective and immunomodulatory effects, yet its high brain levels may negatively impact cognition.

Effects of Fenofibrate and Gemfibrozil on Kynurenic Acid Production in Rat Kidneys In Vitro: Old Drugs, New Properties.

Kidney dysfunction significantly increases the cardiovascular risk, even in cases of minor functional declines. Hypertriglyceridemia is the most common lipid abnormality reported in patients with kidney disorders. PPAR-α (peroxisome proliferator-activated receptor-α) agonists called fibrates are the main agents used to lower triglyceride levels.

Clinical outcomes of + non-small cell lung cancer in Denmark.

Background: Real-world clinical outcomes of anaplastic lymphoma kinase positive (+) non-small cell lung cancer (NSCLC) patients vary. This study aimed to investigate the treatment and clinical outcomes of all + NSCLC patients in Denmark in the period 2011-2018, regardless of disease stage.

Materials And Methods: A national pathology database with complete coverage was used to identify + NSCLC patients diagnosed between 2011 and 2018.

Real-World Data on Combined EGFR-TKI and Crizotinib Treatment for Acquired and De Novo Amplification in Patients with Metastatic -Mutated NSCLC.

Amplification of the () gene is a mechanism of acquired resistance to epidermal growth factor receptor (EGFR)-tyrosine-kinase-inhibitors (TKIs) in over 20% of patients with advanced -mutated (m+) non-small lung cancer (NSCLC). However, it may also occur de novo in 2-8% of m+ NSCLC cases as a potential mechanism of intrinsic resistance. These patients represent a group with unmet needs, since there is no standard therapy currently approved.

New Perspective on Anorexia Nervosa: Tryptophan-Kynurenine Pathway Hypothesis.

Anorexia nervosa (AN), affecting up to 4% of all females and 0.3% of all males globally, remains the neuropsychiatric disorder with the highest mortality rate. However, the response to the current therapeutic options is rarely satisfactory.

Kynurenine Pathway in Diabetes Mellitus-Novel Pharmacological Target?

The tryptophan-kynurenine pathway (Trp-KYN) is the major route for tryptophan conversion in the brain and in the periphery. Kynurenines display a wide range of biological actions (which are often contrasting) such as cytotoxic/cytoprotective, oxidant/antioxidant or pro-/anti-inflammatory. The net effect depends on their local concentration, cellular environment, as well as a complex positive and negative feedback loops.

Kynurenic acid in neurodegenerative disorders-unique neuroprotection or double-edged sword?

Aims: The family of kynurenine pathway (KP) metabolites includes compounds produced along two arms of the path and acting in clearly opposite ways. The equilibrium between neurotoxic kynurenines, such as 3-hydroxykynurenine (3-HK) or quinolinic acid (QUIN), and neuroprotective kynurenic acid (KYNA) profoundly impacts the function and survival of neurons. This comprehensive review summarizes accumulated evidence on the role of KYNA in Alzheimer's, Parkinson's and Huntington's diseases, and discusses future directions of potential pharmacological manipulations aimed to modulate brain KYNA.

Uncommon Presentation of Granulomatosis with Polyangiitis Mimicking Metastatic Lung Cancer.

Diagnosis of anomalous intrathoracic lesions may be challenging and require a multidisciplinary approach. We present a case of granulomatosis with polyangiitis (GPA) clinically and radiologically mimicking metastatic lung cancer with a bilateral pulmonary mass, mediastinal and cervical lymph node involvement, and pleural effusion. Surgical biopsy of the thoracic lesion revealed necrotic granulomatous inflammation, and the final diagnosis was subsequently confirmed by kidney biopsy and biochemical parameters.

Fractalkine, sICAM-1 and Kynurenine Pathway in Restrictive Anorexia Nervosa-Exploratory Study.

The link between the kynurenine pathway and immunomodulatory molecules-fractalkine and soluble intercellular adhesion molecule-1 (sICAM-1)-in anorexia nervosa (AN) remains unknown. Fractalkine, sICAM-1, tryptophan (TRP), kynurenine (KYN), neuroprotective kynurenic acid (KYNA), neurotoxic 3-OH-kynurenine (3-OH-KYN), and the expression of mRNA for kynurenine aminotransferases () were studied in 20 female patients with restrictive AN (mostly drug-free, all during first episode of the disease) and in 24 controls. In AN, serum fractalkine, but not sICAM-1, KYNA, KYN, TRP or 3-OH-KYN, was higher; ratios TRP/KYN, KYN/KYNA, KYN/3-OH-KYN and KYNA/3-OH-KYN were unaltered.

Aortic stiffness-Is kynurenic acid a novel marker? Cross-sectional study in patients with persistent atrial fibrillation.

Objective: Although a number of modifiable and non-modifiable causes were implicated in arterial stiffness, its pathogenesis remains elusive, and very little is known about aortic elasticity in supraventricular arrhythmias. The potential role of disturbed kynurenine metabolism in the pathogenesis of cardiovascular disease has been recently suggested. Thus, we studied the correlations of aortic stiffness and echocardiographic parameters with biochemical markers and serum level of kynurenic acid (KYNA), an endothelial derivative of tryptophan, formed along the kynurenine pathway, among patients with atrial fibrillation (AF).