A5102945742- Neuropeptides and Animal Physiology
- Drug Transport and Resistance Mechanisms
- Gastrointestinal motility and disorders
- Pain Mechanisms and Treatments
- Pediatric Hepatobiliary Diseases and Treatments
- Bone Metabolism and Diseases
- Liver Disease Diagnosis and Treatment
- Receptor Mechanisms and Signaling
- Cell Adhesion Molecules Research
- Protease and Inhibitor Mechanisms
- Helicobacter pylori-related gastroenterology studies
- Ion Channels and Receptors
- Osteoarthritis Treatment and Mechanisms
- Diet and metabolism studies
- Healthcare Systems and Practices
- Inflammatory mediators and NSAID effects
- Neuroendocrine Tumor Research Advances
- Health, Medicine and Society
- Liver Disease and Transplantation
- Biochemical Analysis and Sensing Techniques
- Botulinum Toxin and Related Neurological Disorders
- Electrolyte and hormonal disorders
- Pharmacological Receptor Mechanisms and Effects
- Liver Diseases and Immunity
- Regulation of Appetite and Obesity
University of Minnesota
2025
Albireo (Sweden)
2020-2024
Medivir (Sweden)
2010-2020
Zealand Pharma (Denmark)
2018
King's College London
2016
AstraZeneca (Sweden)
2006-2009
AstraZeneca (United Kingdom)
2006-2008
Lund University
1997-2001
Universitat de València
1998
Glanrhyd Hospital
1987
Cholemic nephropathy (CN) is a severe complication of cholestatic liver diseases for which there no specific treatment. We revisited its pathophysiology with the aim identifying novel therapeutic strategies.
Cholestasis is characterized by intrahepatic accumulation of bile constituents, including acids (BAs), which promote liver damage. The apical sodium-dependent BA transporter (ASBT) plays an important role in reabsorption and signaling ileum, ducts, kidneys. Our aim was to investigate the pharmacokinetics pharmacological activity A3907, oral systemically available ASBT inhibitor experimental mouse models cholestasis. In addition, tolerability, pharmacokinetics, pharmacodynamics A3907 were...
Activation of cannabinoid receptors (CB 1 , CB 2 and GPR 55 ) produces analgesic effects in several experimental pain models, including visceral arising from the gastrointestinal tract. We assessed role endogenous system on basal responses acute mechanical hyperalgesia during colorectal distension (CRD) rodents. The receptor agonists antagonists pain-related to CRD were rats wild-type knock-out mice. dual 1/2 agonist, WIN55,212-2, peripherally acting -selective SAB-378, inhibited repetitive...
Proteolytic processing of the amiloride-sensitive epithelial sodium channel (ENaC) by serine proteases is known to be important for activation. Inappropriate ENaC activation may contribute pathophysiology cystic fibrosis and could involved in retention pathogenesis arterial hypertension context renal disease. We hypothesized that addition proteases, cathepsin activate ENaC. Cathepsin belong group cysteine play a pathophysiological role inflammatory diseases. Under conditions, cathepsin-S...
MIV-711 is a highly potent and selective cathepsin K inhibitor. The current article summarizes the therapeutic effects of on joint pathology in rabbits subjected to anterior cruciate ligament transection (ACLT), prophylactic dogs partial medial meniscectomy, two surgical models osteoarthritis (OA). Starting 1 week after surgery, were dosed daily via oral gavage with either or vehicle (n = 7/group) for 7 weeks. four treatment groups were: (1) sham + vehicle; (2) ACLT (3) MIV-711, 30 µmol/kg...
We compared the neurokinin 1 receptor (NK<sub>1</sub>R) antagonists aprepitant, CP-99994 [(2<i>S</i>,3<i>S</i>)-3-(2-methoxybenzylamino)-2-phenylpiperidine], and ZD6021 [3-cyano-<i>N</i>-((2<i>S</i>)-2-(3,4-dichlorophenyl)-4-[4-[2-(methyl-(<i>S</i>)-sulfinyl)phenyl]piperidino]butyl)-<i>N</i>-methyl]napthamide]] with respect to interactions duration of efficacy in vivo. In Ca<sup>2+</sup> mobilization assays (fluorometric imaging plate reader), were applied human U373MG cells simultaneously...
BACE-1 is one of the aspartic proteases involved in cleavage β amyloid peptide, an initial step formation plaques whose toxicity induces neuron death Alzheimer's disease patients. One central issues search novel inhibitors optimum pH for binding to enzyme. It known that enzyme has optimal catalytic activity at acidic pH, while cell active may bind optimally higher pH. In this work we determine effect on affinities a set inhibitors, with variety chemical motifs, ectodomain region by surface...
Cathepsin K is an attractive therapeutic target for diseases in which bone resorption excessive such as osteoporosis and osteoarthritis (OA). The current paper characterized the pharmacological profile of potent selective cathepsin inhibitor, MIV-711, vitro cynomolgus monkeys, assessed translation to human based on a single dose clinical study man. potency selectivity MIV-711 were using recombinant enzyme assays differentiated osteoclasts. was administered healthy monkeys (3–30 µmol/kg,...
Metabotropic glutamate 5 receptor (mGluR5) antagonists are effective in animal models of inflammatory and neuropathic pain. The involvement mGluR5 visceral pain pathways from the gastrointestinal tract is as yet unknown. We evaluated effects on colorectal distension (CRD)-evoked visceromotor (VMR) cardiovascular responses conscious rats, mechanosensory mouse afferents vitro. Sprague-Dawley rats were subjected to repeated, isobaric CRD (12 x 80 mmHg, for 30s with min intervals). VMR...
Cathepsin S inhibitors attenuate mechanical allodynia in preclinical neuropathic pain models. The current study evaluated the effects when combining selective cathepsin inhibitor MIV-247 with gabapentin or pregabalin a mouse model of pain. Mice were rendered by partial sciatic nerve ligation. MIV-247, gabapentin, administered alone combination via oral gavage. Mechanical was assessed using von Frey hairs. Neurobehavioral side assessing beam walking. and concentrations various tissues...
Chronic itch is a debilitating condition characterised by excessive scratching and symptom frequently reported in skin diseases such as atopic dermatitis. It has been proposed that release of the cysteine protease Cathepsin S (CatS) from keratinocytes or immune cells resident infiltrating could act pruritogen chronic conditions. CatS known to activate protease-activated receptor 2 (PAR2). We therefore hypothesised enzymatic activation neuronally expressed PAR2 was responsible for sensory...
Chemotherapy-induced neuropathic pain is a dose-limiting side effect of many cancer therapies due to their propensity accumulate in peripheral nerves, which facilitated by the permeability blood-nerve barrier. Preclinically, chemotherapy agent vincristine (VCR) activates endothelial cells murine nervous system and doing so allows infiltration monocytes into nerve tissue where they orchestrate development VCR-induced nociceptive hypersensitivity. In this study we demonstrate that VCR also...
Background: Lipocalin 2 (LCN2), also known as neutrophil gelatinase-associated lipocalin, is a 25 kDa protein involved in immune defense, inflammation, and metabolism. Results: LCN2 widely expressed across various tissues, including cells, bone, adipose tissue, liver, kidneys, lung, spleen, epithelial exhibits sex- fat depot-specific expression patterns. Structurally, contains hydrophobic lipid-binding pocket glycosylation sites, enabling it to interact with diverse ligands form dimers. In...
Abstract: Gastrin stimulates rat stomach enterochromaffin‐like (ECL) cells via activation of cholecystokinin‐B/gastrin receptors. The stimulation is manifested in the histamine‐forming enzyme histidine decarboxylase and secretion histamine pancreastatin, a chromogranin A‐derived peptide. We have examined short‐term effects three novel receptor antagonists (YF476, JB93182 AG041R) on ECL intact fasted rats. drugs and/or gastrin were infused intravenously for 3 hr oxyntic mucosal activity serum...
The pathophysiology of irritable bowel syndrome (IBS) is complex and incompletely known. Very little has been studied regarding the role submucous neuronal activity. We therefore measured small intestinal transmural potential difference (PD, reflecting mainly electrogenic chloride secretion), its linkage with fasting motor activity [migrating (MMC)] in controls (n = 16) patients IBS [n 23, 14 diarrhoea predominant (d-IBS) nine constipation (c-IBS)]. Transmural-PD relation to MMC phase III...
Cathepsin X/Z/P is cysteine cathepsin with unique carboxypeptidase activity. Its expression associated cancer and neurodegenerative diseases, although its roles during normal physiology are still poorly understood. Advances in our understanding of function have been hindered by a lack available tools that can specifically measure the proteolytic activity X. We present series activity-based probes incorporate sulfoxonium ylide warhead, which exhibit improved specificity for X compared to...