scholarly journals Possibilities of Pharmacological Preconditioning

2016 ◽  
Vol 71 (1) ◽  
pp. 16-24 ◽  
Author(s):  
O. S. Levchenkova ◽  
V. E. Novikov
Keyword(s):  
Opioid Analgesics ◽  
Metabolic Adaptation ◽  
Tolerance Development ◽  
Inhalation Anesthesia ◽  
Pharmacological Agents ◽  
Adenosine Receptor Agonists ◽  
Clinical Data Analysis ◽  
Potassium Channel Activators ◽  
Pharmacological Preconditioning

The review is devoted to the experimental and clinical data analysis about the effectiveness of preconditioning as a method of organism’s tolerance development to ischemia/hypoxia. Characteristics of the trigger, signaling and effector stages of the preconditioning mechanism are described. Medicinal agents which can stimulate processes of endogenous metabolic adaptation are discussed. As is shown in the review the role of inducers of preconditioning can play drugs from different pharmacological groups: adenosine receptor agonists, some agents for inhalation anesthesia, potassium channel activators, opioid analgesics, antagonists of excitatory amino acids, inducers of transcription factors, drugs of erythropoietin, inhibitors of the mitochondrial pore, bioflavonoids, drugs with antihypoxic action. Examples of successful preconditioning with help of pharmacological agents are presented. The prospects of pharmacological preconditioning usage in cerebral ischemia and myocardial infarction are discussed in the article.

scholarly journals Chronic Pain in Dogs and Cats: Is There Place for Dietary Intervention with Micro-Palmitoylethanolamide?

Animals ◽  
2021 ◽  
Vol 11 (4) ◽  
pp. 952
Author(s):  
Giorgia della Rocca ◽  
Davide Gamba
Keyword(s):  
Chronic Pain ◽  
Dietary Intervention ◽  
Neuronal Cells ◽  
Small Animal ◽  
Food Sources ◽  
Dietary Interventions ◽  
Tolerance Development ◽  
Pharmacological Agents ◽  
Inflammatory Drugs

The management of chronic pain is an integral challenge of small animal veterinary practitioners. Multiple pharmacological agents are usually employed to treat maladaptive pain including opiates, non-steroidal anti-inflammatory drugs, anticonvulsants, antidepressants, and others. In order to limit adverse effects and tolerance development, they are often combined with non-pharmacologic measures such as acupuncture and dietary interventions. Accumulating evidence suggests that non-neuronal cells such as mast cells and microglia play active roles in the pathogenesis of maladaptive pain. Accordingly, these cells are currently viewed as potential new targets for managing chronic pain. Palmitoylethanolamide is an endocannabinoid-like compound found in several food sources and considered a body’s own analgesic. The receptor-dependent control of non-neuronal cells mediates the pain-relieving effect of palmitoylethanolamide. Accumulating evidence shows the anti-hyperalgesic effect of supplemented palmitoylethanolamide, especially in the micronized and co-micronized formulations (i.e., micro-palmitoylethanolamide), which allow for higher bioavailability. In the present paper, the role of non-neuronal cells in pain signaling is discussed and a large number of studies on the effect of palmitoylethanolamide in inflammatory and neuropathic chronic pain are reviewed. Overall, available evidence suggests that there is place for micro-palmitoylethanolamide in the dietary management of chronic pain in dogs and cats.

Haemostatic Platelet Plug Formation in the Isolated Rabbit Mesenteric Preparation - An Analysis of Red Blood Cell Participation

1980 ◽  
Vol 44 (01) ◽  
pp. 006-008 ◽  
Author(s):  
D Bergqvist ◽  
K-E Arfors
Keyword(s):  
Whole Blood ◽  
Platelet Rich Plasma ◽  
Adenosine Diphosphate ◽  
In Vitro Test ◽  
Pharmacological Agents ◽  
Vitro Test ◽  
Releasing Effect ◽  
Plug Formation

SummaryIn a model using an isolated rabbit mesenteric preparation microvessels were transected and the time until haemostatic plugs formed was registered. Perfusion of platelet rich plasma gave no haemostasis whereas whole blood did. Addition of chlorpromazine or adenosine to the whole blood significantly prolonged the time for haemostasis, and addition of ADP to the platelet rich plasma significantly shortened it. It is concluded that red cells are necessary for a normal haemostasis in this model, probably by a combination of a haemodynamic and ADP releasing effect.The fundamental role of platelets in haemostatic plug formation is unquestionable but there are still problems concerning the stimulus for this process to start. Three platelet aggregating substances have been discussed – thrombin, adenosine diphosphate (ADP) and collagen. Evidence speaking in favour of thrombin is, however, very minimal, and the discussion has to be focused on collagen and ADP. In an in vitro system using polyethylene tubings we have shown that "haemostasis" can be obtained without the presence of collagen but against these results can be argued that it is only another in vitro test for platelet aggregation (1).To be able to induce haemostasis in this model, however, the presence of red blood cells is necessary. To further study this problem we have developed a model where haemostatic plug formation can be studied in the isolated rabbit mesentery and we have briefly reported on this (2).Thus, it is possible to perfuse the vessels with whole blood as well as with platelet rich plasma (PRP) and different pharmacological agents of importance.

scholarly journals New Insights into the Role of miR-29a in Hepatocellular Carcinoma: Implications in Mechanisms and Theragnostics

2021 ◽  
Vol 11 (3) ◽  
pp. 219
Author(s):  
Ya-Ling Yang ◽  
Yen-Hsiang Chang ◽  
Chia-Jung Li ◽  
Ying-Hsien Huang ◽  
Ming-Chao Tsai ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Tumor Microenvironment ◽  
Crucial Role ◽  
Human Cancer ◽  
Metabolic Adaptation ◽  
Advanced Hcc ◽  
Diagnosis And Prognosis ◽  
Competitive Endogenous Rnas ◽  
Growing Body

Hepatocellular carcinoma (HCC) remains one of the most lethal human cancer globally. For advanced HCC, curable plan for advanced HCC is yet to be established, and the prognosis remains poor. The detail mechanisms underlying the progression of HCC tumorigenicity and the corruption of tumor microenvironment (TME) is complex and inconclusive. A growing body of studies demonstrate microRNAs (miRs) are important regulators in the tumorigenicity and TME development. Notably, mounting evidences indicate miR-29a play a crucial role in exerting hepatoprotective effect on various types of stress and involved in the progression of HCC, which elucidates their potential theragnostic implications. In this review, we reviewed the advanced insights into the detail mechanisms by which miR-29a dictates carcinogenesis, epigenetic program, and metabolic adaptation, and implicated in the sponging activity of competitive endogenous RNAs (ceRNA) and the TME components in the scenario of HCC. Furthermore, we highlighted its clinical significance in diagnosis and prognosis, as well as the emerging therapeutics centered on the activation of miR-29a.

scholarly journals Acid tolerance in early colonizers of oral biofilms

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Gabriella Boisen ◽  
Julia R. Davies ◽  
Jessica Neilands
Keyword(s):  
Acid Tolerance ◽  
Low Ph ◽  
Salivary Proteins ◽  
Confocal Scanning Laser Microscopy ◽  
Planktonic Cells ◽  
Tolerance Development ◽  
Salivary Pellicle ◽  
Oral Biofilms ◽  
Acid Tolerant

Abstract Background In caries, low pH drives selection and enrichment of acidogenic and aciduric bacteria in oral biofilms, and development of acid tolerance in early colonizers is thought to play a key role in this shift. Since previous studies have focussed on planktonic cells, the effect of biofilm growth as well as the role of a salivary pellicle on this process is largely unknown. We explored acid tolerance and acid tolerance response (ATR) induction in biofilm cells of both clinical and laboratory strains of three oral streptococcal species (Streptococcus gordonii, Streptococcus oralis and Streptococcus mutans) as well as two oral species of Actinomyces (A. naeslundii and A. odontolyticus) and examined the role of salivary proteins in acid tolerance development. Methods Biofilms were formed on surfaces in Ibidi® mini flow cells with or without a coating of salivary proteins and acid tolerance assessed by exposing them to a challenge known to kill non-acid tolerant cells (pH 3.5 for 30 min) followed by staining with LIVE/DEAD BacLight and confocal scanning laser microscopy. The ability to induce an ATR was assessed by exposing the biofilms to an adaptation pH (pH 5.5) for 2 hours prior to the low pH challenge. Results Biofilm formation significantly increased acid tolerance in all the clinical streptococcal strains (P < 0.05) whereas the laboratory strains varied in their response. In biofilms, S. oralis was much more acid tolerant than S. gordonii or S. mutans. A. naeslundii showed a significant increase in acid tolerance in biofilms compared to planktonic cells (P < 0.001) which was not seen for A. odontolyticus. All strains except S. oralis induced an ATR after pre-exposure to pH 5.5 (P < 0.05). The presence of a salivary pellicle enhanced both acid tolerance development and ATR induction in S. gordonii biofilms (P < 0.05) but did not affect the other bacteria to the same extent. Conclusions These findings suggest that factors such as surface contact, the presence of a salivary pellicle and sensing of environmental pH can contribute to the development of high levels of acid tolerance amongst early colonizers in oral biofilms which may be important in the initiation of caries.

scholarly journals The Role of Microbiota in Primary Sclerosing Cholangitis and Related Biliary Malignancies

2021 ◽  
Vol 22 (13) ◽  
pp. 6975
Author(s):  
Burcin Özdirik ◽  
Tobias Müller ◽  
Alexander Wree ◽  
Frank Tacke ◽  
Michael Sigal
Keyword(s):  
Primary Sclerosing Cholangitis ◽  
Gut Microbiome ◽  
Sclerosing Cholangitis ◽  
Functional Characterization ◽  
Significant Risk ◽  
Pharmacological Agents ◽  
Experimental Mouse ◽  
Biliary Malignancies ◽  
End Stage

Primary sclerosing cholangitis (PSC) is an immune-related cholangiopathy characterized by biliary inflammation, cholestasis, and multifocal bile duct strictures. It is associated with high rates of progression to end-stage liver disease as well as a significant risk of cholangiocarcinoma (CCA), gallbladder cancer, and colorectal carcinoma. Currently, no effective medical treatment with an impact on the overall survival is available, and liver transplantation is the only curative treatment option. Emerging evidence indicates that gut microbiota is associated with disease pathogenesis. Several studies analyzing fecal and mucosal samples demonstrate a distinct gut microbiome in individuals with PSC compared to healthy controls and individuals with inflammatory bowel disease (IBD) without PSC. Experimental mouse and observational human data suggest that a diverse set of microbial functions may be relevant, including microbial metabolites and bacterial processing of pharmacological agents, bile acids, or dietary compounds, altogether driving the intrahepatic inflammation. Despite critical progress in this field over the past years, further functional characterization of the role of the microbiota in PSC and related malignancies is needed. In this review, we discuss the available data on the role of the gut microbiome and elucidate important insights into underlying pathogenic mechanisms and possible microbe-altering interventions.

scholarly journals Anti-neoplastic Potential of Flavonoids and Polysaccharide Phytochemicals in Glioblastoma

Molecules ◽  
2020 ◽  
Vol 25 (21) ◽  
pp. 4895
Author(s):  
Ayesha Atiq ◽  
Ishwar Parhar
Keyword(s):  
Cancer Progression ◽  
Therapeutic Option ◽  
Normal Brain ◽  
Current Standard ◽  
Pharmacological Agents ◽  
Initiation Phase ◽  
Therapeutic Outcomes ◽  
Effective Therapeutic Option ◽  
Patient Prognosis

Clinically, gliomas are classified into four grades, with grade IV glioblastoma multiforme being the most malignant and deadly, which accounts for 50% of all gliomas. Characteristically, glioblastoma involves the aggressive proliferation of cells and invasion of normal brain tissue, outcomes as poor patient prognosis. With the current standard therapy of glioblastoma; surgical resection and radiotherapy followed by adjuvant chemotherapy with temozolomide, it remains fatal, because of the development of drug resistance, tumor recurrence, and metastasis. Therefore, the need for the effective therapeutic option for glioblastoma remains elusive. Previous studies have demonstrated the chemopreventive role of naturally occurring pharmacological agents through preventing or reversing the initiation phase of carcinogenesis or arresting the cancer progression phase. In this review, we discuss the role of natural phytochemicals in the amelioration of glioblastoma, with the aim to improve therapeutic outcomes, and minimize the adverse side effects to improve patient’s prognosis and enhancing their quality of life.

The potential role of stress and sex steroids in heritable effects of sevoflurane

2021 ◽  
Author(s):  
Anatoly E Martynyuk ◽  
Ling-Sha Ju ◽  
Timothy E Morey
Keyword(s):  
Sex Steroids ◽  
Age Groups ◽  
Postnatal Period ◽  
Health Concern ◽  
General Anesthetics ◽  
Pharmacological Agents ◽  
Experimental Findings ◽  
Heritable Effects

Abstract Most surgical procedures require general anesthesia, which is a reversible deep sedation state lacking all perception. The induction of this state is possible because of complex molecular and neuronal network actions of general anesthetics (GAs) and other pharmacological agents. Laboratory and clinical studies indicate that the effects of GAs may not be completely reversible upon anesthesia withdrawal. The long-term neurocognitive effects of GAs, especially when administered at the extremes of ages, are an increasingly recognized health concern and the subject of extensive laboratory and clinical research. Initial studies in rodents suggest that the adverse effects of GAs, whose actions involve enhancement of GABA type A receptor activity (GABAergic GAs), can also extend to future unexposed offspring. Importantly, experimental findings show that GABAergic GAs may induce heritable effects when administered from the early postnatal period to at least young adulthood, covering nearly all age groups that may have children after exposure to anesthesia. More studies are needed to understand when and how the clinical use of GAs in a large and growing population of patients can result in lower resilience to diseases in the even larger population of their unexposed offspring. This minireview is focused on the authors’ published results and data in the literature supporting the notion that GABAergic GAs, in particular sevoflurane, may upregulate systemic levels of stress and sex steroids and alter expressions of genes that are essential for the functioning of these steroid systems. The authors hypothesize that stress and sex steroids are involved in the mediation of sex-specific heritable effects of sevoflurane.

scholarly journals Elucidating the Beneficial Role of PPAR Agonists in Cardiac Diseases

2018 ◽  
Vol 19 (11) ◽  
pp. 3464 ◽  
Author(s):  
Zaza Khuchua ◽  
Aleksandr I. Glukhov ◽  
Arnold W. Strauss ◽  
Sabzali Javadov
Keyword(s):  
Animal Models ◽  
Hormone Receptors ◽  
Lipid Lowering ◽  
Acid Oxidation ◽  
Peroxisome Proliferator ◽  
Pharmacological Agents ◽  
Beneficial Effects ◽  
Ppar Agonists ◽  
Energy Deprivation

Peroxisome proliferator-activated receptors (PPARs) are nuclear hormone receptors that bind to DNA and regulate transcription of genes involved in lipid and glucose metabolism. A growing number of studies provide strong evidence that PPARs are the promising pharmacological targets for therapeutic intervention in various diseases including cardiovascular disorders caused by compromised energy metabolism. PPAR agonists have been widely used for decades as lipid-lowering and anti-inflammatory drugs. Existing studies are mainly focused on the anti-atherosclerotic effects of PPAR agonists; however, their role in the maintenance of cellular bioenergetics remains unclear. Recent studies on animal models and patients suggest that PPAR agonists can normalize lipid metabolism by stimulating fatty acid oxidation. These studies indicate the importance of elucidation of PPAR agonists as potential pharmacological agents for protection of the heart from energy deprivation. Here, we summarize and provide a comprehensive analysis of previous studies on the role of PPARs in the heart under normal and pathological conditions. In addition, the review discusses the PPARs as a therapeutic target and the beneficial effects of PPAR agonists, particularly bezafibrate, to attenuate cardiomyopathy and heart failure in patients and animal models.

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