Experimental antibacterial activity of selective cyclooxygenase antagonist

Background: From the history of the development of pharmaceutical compounds it is evident that any drug may have the possibility of possessing diverse functions and thus may have useful activity in completely different fields of medicine and different studies showed that newer antimicrobials have revealed antimicrobial action involved in the management of diseases of non-infectious etiology. This study was done to determine in vitro antibacterial activity of selected selective cyclooxygenase-2 inhibitor.Methods: Twenty two strains of gram positive and gram negative bacteria, which were isolated from skin and urinary tract infected patient. These bacteria were being cultured on specific optimal growth media. The antibacterial activity of selective COX-2 (meloxicam, celecoxib, valdecoxib and nimesulide). Inhibitors determined by measuring zone of inhibition and minimal inhibitory concentration (MIC).Results: Results showed that MIC of celecoxib and meloxicam in µg/ml was ranged from 5-80µg/ml on selected bacteria compared with negative control distilled water (D.W) ,valdecoxib was 80-160µg/ml, while and nimesulide was ranged from 5-40 µg/ml .All the selected bacteria were showed sensitivity for all coxib used in this experimental study except Pseudomonas aeruginosa which showed resistant to meloxicam and valdecoxib, Klebsiella pneumoniae resist to nimesulide while Staphylococcus aureus was resist to valdecoxib. The smaller zone of inhibition showed by valdecoxib and celecoxib which was 3mm against Klebsiella pneumoniae, while the larger zone of inhibition showed by nimesulide which was 26mm against Escherichia coli.Conclusions: In conclusion selective cyclooxygenase (cox-2) inhibitor possesses antibacterial activity this is especially for nimesulide and little by valdecoxib. Escherichia coli are sensitive bacteria to all coxib. Consequently; coxib may be regarded as anti-inflammatory and antibacterial agent especially for urinary tract infection where Escherichia coli are the major causative organism

The Potential Role of Renin Angiotensin System (RAS) and Dipeptidyl Peptidase-4 (DPP-4) in COVID-19: Navigating the Uncharted

Novel coronavirus (COVID-19) led to infected pneumonia and acute respiratory distress syndrome (ARDS) and acute kidney injury (AKI). The entry-point receptor for COVID-19 is angiotensin-converting enzyme 2 (ACE2) at lung, and dipeptidyl peptidase-4 (DPP-4) is a receptor for Middle East respiratory syndrome coronavirus (MERS-CoV). There is 80% similarity between MERS-CoV and COVID-19. This study was planned to review the potential link between the incidence and severity of COVID-19 regarding the modulation of DPP-4 and ACE2 by DPP-4 and renin angiotensin system (RAS). In COVID-19, SARS-CoV2 binds ACE2 which is highly expressed by the epithelial cells of the blood vessel, intestine, and lung. However, pulmonary ACE2 seems to be a protective defense pathway during ARDS. DPP-4 is not concerned with the entry of COVID-19 but mediates the inflammatory reactions and cytokine storm that induced ARDS and AKI by COVID-19. The interaction between DPP4i and RAS inhibitors seem to augment the expression of AT2 receptor and ACE2 which are under extensive researches to find the pathophysiological pathway of COVID-19 infection. This beneficial interaction between DPP4i and RAS shed light for possible attenuation of COVID-19-induced ARDS and AKI mainly in critically ill patients with systemic hypertension

The role of statins in amyotrophic lateral sclerosis: protective or not?

Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease of motor neurons characterized by muscle weakness, muscle twitching, and muscle wasting. ALS is regarded as the third-most frequent neurodegenerative disease, subsequent to Alzheimer's disease (AD) and Parkinson's disease (PD). The World Health Organization (WHO) in 2007 declared that prolonged use of statins may induce development of ALS-like syndrome and may increase ALS risk. Subsequently, different studies have implicated statins in the pathogenesis of ALS. In contrast, results from preclinical and clinical studies highlighted the protective role of statins against ALS neuropathology. Recently, meta-analyses and systematic reviews illustrated no association between long-term use of statins and ALS risk. These findings highlighted controversial points regarding the effects of statins on ALS pathogenesis and risk. The neuroprotective effects of statins against the development and progression of ALS may be mediated by regulating dyslipidemia and inflammatory changes. However, the mechanism for induction of ALS neuropathology by statins may be related to the dysregulation of liver X receptor signaling (LXR) signaling in the motor neurons and reduction of cholesterol, which has a neuroprotective effect against ALS neuropathology. Nevertheless, the exact role of statins on the pathogenesis of ALS was not fully elucidated. Therefore, this narrative review aims to discuss the role of statins in ALS neuropathology

MFG-E8 Regulates the Immunogenic Potential of Dendritic Cells Primed with Necrotic Cell-Mediated Inflammatory Signals

Dendritic cells (DC) manipulate tissue homeostasis by recognizing dying cells and controlling immune functions. However, the precise mechanisms by which DC recognize different types of dying cells and devise distinct immunologic consequences remain largely obscure. Herein, we demonstrate that Milk-fat globule-EGF VIII (MFG-E8) is a critical mediator controlling DC immunogenicity in inflammatory microenvironments. MFG-E8 restrains DC-mediated uptake and recognition of necrotic cells. The MFG-E8-mediated suppression of necrotic cell uptake by DC resulted in the decreased proinflammatory cytokines production and activated signal components such as STAT3 and A20, which are critical to maintain tolerogenic properties of DC. Furthermore, the DC-derived MFG-E8 negatively regulates the cross-priming and effector functions of antigen-specific T cells upon recognition of necrotic cells. MFG-E8 deficiency enhances an ability of necrotic cell-primed DC to stimulate antitumor immune responses against established tumors. Our findings define what we believe to a novel mechanism whereby MFG-E8 regulates the immunogenicity of DC by modulating the modes of recognition of dying cells. Manipulating MFG-E8 levels in DC may serve as a useful strategy for controlling inflammatory microenvironments caused by various pathological conditions including cancer and autoimmunity

Activation of TORC1 transcriptional coactivator through MEKK1-induced phosphorylation

CREB is a prototypic bZIP transcription factor and a master regulator of glucose metabolism, synaptic plasticity, cell growth, apoptosis, and tumorigenesis. Transducers of regulated CREB activity (TORCs) are essential transcriptional coactivators of CREB and an important point of regulation on which various signals converge. In this study, we report on the activation of TORC1 through MEKK1-mediated phosphorylation. MEKK1 potently activated TORC1, and this activation was independent of downstream effectors MEK1/MEK2, ERK2, JNK, p38, protein kinase A, and calcineurin. MEKK1 induced phosphorylation of TORC1 both in vivo and in vitro. Expression of the catalytic domain of MEKK1 alone in cultured mammalian cells sufficiently caused phosphorylation and subsequent activation of TORC1. MEKK1 physically interacted with TORC1 and stimulated its nuclear translocation. An activation domain responsive to MEKK1 stimulation was mapped to amino acids 431-650 of TORC1. As a physiological activator of CREB, interleukin 1α triggered MEKK1-dependent phosphorylation of TORC1 and its consequent recruitment to the cAMP response elements in the interleukin 8 promoter. Taken together, our findings suggest a new mechanism for regulated activation of TORC1 transcriptional coactivator and CREB signaling. © 2008 by The American Society for Cell Biology.published_or_final_versio

Immune-neuroendocrine and metabolic disorders in human and experimental T. cruzi infection: New clues for understanding Chagas disease pathology

Studies in mice undergoing acute Trypanosoma cruzi infection and patients with Chagas disease, led to identify several immune-neuroendocrine disturbances and metabolic disorders. Here, we review relevant findings concerning such abnormalities and discuss their possible influence on disease physiopathology.Fil: González, Florencia Belén. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Inmunología Clinica y Experimental de Rosario. Universidad Nacional de Rosario. Facultad de Ciencias Médicas. Instituto de Inmunología Clinica y Experimental de Rosario; ArgentinaFil: Villar, Silvina Raquel. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Inmunología Clinica y Experimental de Rosario. Universidad Nacional de Rosario. Facultad de Ciencias Médicas. Instituto de Inmunología Clinica y Experimental de Rosario; ArgentinaFil: Pacini, María Florencia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Inmunología Clinica y Experimental de Rosario. Universidad Nacional de Rosario. Facultad de Ciencias Médicas. Instituto de Inmunología Clinica y Experimental de Rosario; ArgentinaFil: Bottasso, Oscar Adelmo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Inmunología Clinica y Experimental de Rosario. Universidad Nacional de Rosario. Facultad de Ciencias Médicas. Instituto de Inmunología Clinica y Experimental de Rosario; ArgentinaFil: Perez, Ana Rosa. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Inmunología Clinica y Experimental de Rosario. Universidad Nacional de Rosario. Facultad de Ciencias Médicas. Instituto de Inmunología Clinica y Experimental de Rosario; Argentin

Levothyroxine improves Paraoxonase (PON-1) serum levels in patients with primary hypothyroidism: Case–control study

Primary hypothyroidism is associated with oxidative stress and insufficient antioxidant capacity. This study was conducted to evaluate the effects of levothyroxine replacement therapy on paraoxonase 1 (PON-1) serum levels in a patients with primary hypothyroidism. Thirty-one patients with primary hypothyroidism compared to 20 healthy controls were recruited from. A venous blood sample were taken after an overnight fasting for biochemical parameters, before and after starting levothyroxine therapy (100 μ g/day) for 3 months duration. The biochemical variables were PON-1 serum levels, lipid profiles, triiodothyronine (T3), thyroxin (T4), and thyroid stimulating hormone (TSH) serum levels. Levothyroxine replacement therapy leads to a significant amelioration of thyroid functions, lipid profile, cardiometabolic measures P < 0.05 in patients with primary hypothyroidism. Levothyroxine leads to significant elevation in PON-1 serum levels from 188.42 ± 19.81 (U/mL) to 361.23 ± 33.62 (U/mL) P < 0.0001. This study concluded that levothyroxine replacement therapy significantly increases PON-1 serum levels in patients with primary hypothyroidism and attenuating hypothyroidism-induced oxidative stress