Study of anti-inflammatory activity of omeprazole in complete Freund’s adjuvant induced arthritic rats

Background: Rheumatoid arthritis (RA) is a chronic, progressive, and systemic inflammatory disease, characterized by synovial proliferation and joint erosions. Nonsteroidal anti-inflammatory drugs (NSAIDs) are used as an important part of therapeutic regime to suppress the pain and inflammation associated with RA. The modern drugs both steroidal and nonsteroidal anti-inflammatory drugs (NSAIDS) and disease modifying antirheumatic drugs (DMARDSs) are used for the amelioration of the symptoms of the disease; however, they offer only temporary relief and also produce adverse effects. This study was done to evaluate anti-inflammatory activity of Omeprazole in CFA induced arthritic rats.Methods: Animals were divided into five groups of six each, group I as control, group II as standard whereas groups III, IV and V as test groups (three doses). Anti-inflammatory effect of group II Diclofenac sodium (10 mg/kg orally) and group III, IV and V received Omeprazole (10mg/kg, 20mg/kg, and 30mg/kg bodyweight orally respectively) was evaluated in adult albino rats by Plethysmometer on 7th, 14th and 21st day post adjuvant injection.Results: Group 3 produced a significant suppression of paw volume with P value (<0.05) and Group 4 produced a very significant suppression with P value (<0.001) compared to other groups.Conclusions: Omeprazole, a PPI, has anti-inflammatory activity

Study of antinociceptive effect of paroxetine in acute pain in albino rats

Background: Pain is an unpleasant sensory and emotional experience associated with actual or potential tissue damage or described in terms of such damage. In spite of having a number of drugs like NSAIDS and opioids for the management of pain, there is still need for an ideal analgesic agent with favourable safety profile. Many studies have shown that antidepressant drugs also have analgesic activity and particularly, selective serotonin reuptake inhibitors (SSRI) are effective in mixed and chronic pain. This study was done to evaluate antinociceptive effect of Paroxetine in albino rat and to compare antinociceptive effect of Paroxetine with the standard drug pentazocine in albino rat.Methods: Animals were divided into five groups of six each, group I as control, group II as standard whereas groups III, IV and V as test groups (three doses). Antinociceptive effect of group II pentazocine (10 mg/kg intraperitoneal) and group III, IV and V received paroxetine (2.5 mg/kg, 5 mg/kg, and 10 mg/kg bodyweight intraperitoneally respectively) was evaluated in adult albino rats by Tail flick method.Results: Mean RT after 120 minutes of injection of Paroxetine (10 mg) was higher than baseline value of 3.42 second with, mean difference 9.55±0.45 and is significant when compared to control. No significant difference in RT was found between paroxetine 10 mg and pentazocine 10 mg. No significant difference found when baseline reading was compared with 120 minutes readings of paroxetine 2.5 group.Conclusions: Paroxetine, a SSRI antidepressant, has a clear antinociceptive activity

Study of antinociceptive effect of paroxetine in acute pain in albino rats

Background: Pain is an unpleasant sensory and emotional experience associated with actual or potential tissue damage or described in terms of such damage. In spite of having a number of drugs like NSAIDS and opioids for the management of pain, there is still need for an ideal analgesic agent with favourable safety profile. Many studies have shown that antidepressant drugs also have analgesic activity and particularly, selective serotonin reuptake inhibitors (SSRI) are effective in mixed and chronic pain. This study was done to evaluate antinociceptive effect of Paroxetine in albino rat and to compare antinociceptive effect of Paroxetine with the standard drug pentazocine in albino rat.Methods: Animals were divided into five groups of six each, group I as control, group II as standard whereas groups III, IV and V as test groups (three doses). Antinociceptive effect of group II pentazocine (10 mg/kg intraperitoneal) and group III, IV and V received paroxetine (2.5 mg/kg, 5 mg/kg, and 10 mg/kg bodyweight intraperitoneally respectively) was evaluated in adult albino rats by Tail flick method.Results: Mean RT after 120 minutes of injection of Paroxetine (10 mg) was higher than baseline value of 3.42 second with, mean difference 9.55±0.45 and is significant when compared to control. No significant difference in RT was found between paroxetine 10 mg and pentazocine 10 mg. No significant difference found when baseline reading was compared with 120 minutes readings of paroxetine 2.5 group.Conclusions: Paroxetine, a SSRI antidepressant, has a clear antinociceptive activity

Immune landscape, evolution, hypoxia-mediated viral mimicry pathways and therapeutic potential in molecular subtypes of pancreatic neuroendocrine tumours

A comprehensive analysis of the immune landscape of pancreatic neuroendocrine tumours (PanNETs) was performed according to clinicopathological parameters and previously defined molecular subtypes to identify potential therapeutic vulnerabilities in this disease

Genomic and Transcriptomic Determinants of Therapy Resistance and Immune Landscape Evolution during Anti-EGFR Treatment in Colorectal Cancer

Despite biomarker stratification, the anti-EGFR antibody cetuximab is only effective against a subgroup of colorectal cancers (CRCs). This genomic and transcriptomic analysis of the cetuximab resistance landscape in 35 RAS wild-type CRCs identified associations of NF1 and non-canonical RAS/RAF aberrations with primary resistance and validated transcriptomic CRC subtypes as non-genetic predictors of benefit. Sixty-four percent of biopsies with acquired resistance harbored no genetic resistance drivers. Most of these had switched from a cetuximab-sensitive transcriptomic subtype at baseline to a fibroblast- and growth factor-rich subtype at progression. Fibroblast-supernatant conferred cetuximab resistance in vitro, confirming a major role for non-genetic resistance through stromal remodeling. Cetuximab treatment increased cytotoxic immune infiltrates and PD-L1 and LAG3 immune checkpoint expression, potentially providing opportunities to treat cetuximab-resistant CRCs with immunotherapy.M.G., A.Woolston, L.J.B., and B.G. were supported by CRUK, a charitable donation from Tim Morgan, Cancer Genetics UK and the Constance Travis Trust. G.S. was funded by an Institute of Cancer PhD Studentship, R.G.E. by a Spanish Society of Medical Oncology (FSEOM) grant for Translational Research in Reference Centers. The study was also supported by the ICR/RMH NIHR Biomedical Research Center for Cancer, by the CRUK Immunotherapy Accelerator (ICR/RMH, UCL) and by a Wellcome Trust Strategic Grant (105104/Z/14/Z)