scholarly journals Comparative Investigation of Five Cobras’ Venoms Analgesic Capacity

2021 ◽  
pp. 113-124
Author(s):  
Lilya Parseghyan
Keyword(s):  
Physical Dependence ◽  
Rapid Development ◽  
Drug Market ◽  
Sublethal Dose ◽  
Experimental Conditions ◽  
Bioactive Substances ◽  
Naja Naja ◽  
Antinociceptive Action ◽  
Inflammatory Phase ◽  
Ophiophagus Hannah

Every day, a lot of people suffer from different types and intensity pain. Pain is probably the most common symptomatic reason to seek medical consultation. Unfortunately, despite improved knowledge of underlying mechanisms and better treatments, many people who have any type of pain receive inadequate care and non-effective drugs. Although the pain transmission channels are intensively studied, and the drug market is constantly replenished with new analgesics, it is well known that existing medications for the treatment of pain are often associated with serious side effects and rapid development of tolerance (moderate efficiency, physical dependence, respiratory arrest, suffocation, cardiac arrest, etc.). Thus, there is a need for new, more effective remedies. For this reason, despite the presence of a large number of anti-pain drugs, research and development of more effective and safe means for anaesthesia continue. Natural resources, particularly venoms, are a perspective supplier of antinociceptive and anti-inflammatory medicines. Venoms are complex mixtures of bioactive substances with high selectivity for physiological processes, including modulation of different ion channels, receptors function, and metabolic pathways. Thus, venoms represent an extensive source of molecules for the development of therapeutic agents. The goal of this study was the comparison of antinociceptive effects of five different cobras' venom antinociceptive action of cobras’ venoms was carried out under the same experimental conditions, at the same doses, during acute and inflammatory pain in mice in “formalin test”. To avoid toxic effects, the sublethal dose of each cobra venom (approximately 1/10 LD 50 ) was selected. The behavioural study showed that all tested venoms had a slight sensitizing effect in the acute phase during the first 5 min. In the second, inflammatory phase (16*25min), all tested cobra’s venoms (3μg/0.1ml, intraperitoneal) showed significant antinociceptive action, particularly the Naja naja oxiana venom decreased pain sensitivity by 48.4%, the Naja naja pallida venom by 75.4%, the Naja naja nigricincta venom by 38.5%, the Naja naja kaouthia venom by 33.2%, and the Ophiophagus Hannah venom by 78.3%, (p<0.05). The analgesic capacity of Analgin and Diclofenac under the same conditions were 77.9% and 88.7%, respectively. Thus, the Naja n. pallida and Ophiophagus Hannah venoms have shown the most expressed antinociceptive action, and they have competitive effectiveness compared to classic analgesics. They may be chosen as the most effective from tested venoms for further development of pain relief remedies.

scholarly journals Spontaneous Mutations That Confer Antibiotic Resistance inHelicobacter pylori

2001 ◽  
Vol 45 (3) ◽  
pp. 727-733 ◽  
Author(s):  
Ge Wang ◽  
Trevor J. M. Wilson ◽  
Qin Jiang ◽  
Diane E. Taylor
Keyword(s):  
Mutant Allele ◽  
Rapid Development ◽  
Mutagenic Effect ◽  
Serial Passage ◽  
Sublethal Dose ◽  
23S Rrna ◽  
Rrna Gene ◽  
Spontaneous Mutations ◽  
H Pylori

ABSTRACT In this study, we systematically examined in vitro frequencies and spectra of the spontaneous mutations in Helicobacter pylori that confer resistance to clarithromycin (Clar), metronidazole (Mtzr), amoxicillin (Amxr), ciprofloxacin (Cipr), and rifampin (Rifr). The mutation rate of Rifror Cipr determined in a fluctuation assay is 1 × 10−8 to 2 × 10−8 per cell per division. In contrast, the mutation rates of Clar, Mtzr, and Amxr are much lower (<10−9). However, Mtzr mutants could be readily selected in vitro by using the serial passage method, suggesting that the mutagenic effect and selective effect of a sublethal dose of metronidazole contribute to the rapid development of Mtzr. Analysis of spontaneous Rifr, Clar, and Cipr mutants confirmed previous results indicating that mutations within therpoB gene, the 23S rRNA gene, and thegyrA gene, respectively, are responsible; also, several new mutant alleles were identified. Mtzrmutants resulted most frequently, but not always, from mutations in the rdxA gene. DNA fragments containing each mutant allele could readily transform susceptibleH. pylori strains to resistance, confirming that each mutant allele is responsible for the resistance phenotype.

Current Trends in the Therapeutic Strategies for Diabetes Management

2021 ◽  
Vol 28 ◽  
Author(s):  
Ponnurengam Malliappan Siva Kumar ◽  
V. Prabhawathi ◽  
Ali Zarrabi ◽  
Sohail Akthar ◽  
Pranav Kumar Prabhakar
Keyword(s):  
Diabetes Mellitus ◽  
Diabetes Management ◽  
Pancreatic Beta Cell ◽  
Drug Market ◽  
Noncommunicable Disease ◽  
Management Approach ◽  
Peroxisome Proliferator ◽  
Bioactive Substances ◽  
Middle Income ◽  
Antidiabetic Therapy

Abstract: Diabetes mellitus is one of the fastest growing noncommunicable disease. Diabetes mellitus is causes due to destruction of pancreatic beta cell or due to insulin resistance and characterised by hyperglycaemia. Diabetes imposes a very serious economic crisis as the diabetic drug market is growing very rapidly. Even after very path breaking scientific discoveries, availability of a better healthcare infrastructure, rise in literacy rates, the diabetes burden is continuously spreading in various sections all over the worlds but more especially in low- and middle-income countries. The recent development in scientific discoveries have given a number of new generations of antidiabetic medicines such as sulphonylurea, biguanides, thiazolidinedione, alpha glucosidease inhibitors. All these drugs have proved significant reduction in blood glucose level. There are some new classes of hypoglycaemic drugs have also been developed and reported such as GLP-1 analogous, DPP-IV inhibitors, amylin inhibitors, Peroxisome proliferator activated receptors. There are some active molecules and bioactive substances have been purified from herbs and plants which adds values to the war against diabetes. These phytoconstituents have overturned the drug development and lead identification for drug against diabetes. The review also focusses on some critical area of diabetes with more focus on statin-based diabetes management approach and stem cell therapy based next generation antidiabetic therapy.

scholarly journals Effects of bioactive substances in milk on mineral and trace element metabolism with special reference to casein phosphopeptides

2000 ◽  
Vol 84 (S1) ◽  
pp. 147-153 ◽  
Author(s):  
Katharina E. Scholz-Ahrens ◽  
J. Schrezenmeir
Keyword(s):  
Basal Diet ◽  
Calcium Balance ◽  
Short Term ◽  
Experimental Conditions ◽  
Bioactive Substances ◽  
Positive Effects ◽  
Mineral Solubility ◽  
Iron And Zinc ◽  
Bone Mineralisation

Bioactivity of phosphopeptides yielded after tryptic hydrolysis of casein (CPP) was reported more than 50 years ago when CPP were found to improve calcium balance in rachitic newborns. Several investigations have been carried out to study the effects of CPP mainly on calcium metabolism but also on other minerals like iron and zinc. Most of the experiments were in vitro studies or short-term experiments like the effects of CPP after single meals or their effect on mineral disappearance from intestinal everted sac or ligated loop. Investigations on calcium balance were also mainly short term, i.e. 3–4 weeks, and mainly done in rats. A few experiments have been carried out in minipigs, an animal model that is closer to the human than the rat. Studies in human were rare and short term. To date a variety of other peptides have been isolated after enzymatic hydrolysis, and some have been investigated for bioactivity, with equivocal findings. Bioactivity of phosphopeptides seemed to be more obvious when investigations were done in vitro or short term. Results were less clear in metabolic balance studies, especially under physiological conditions. The composition of the basal diet, i.e. content of calcium and phytate, or the protein source had a significant impact on the effect of phosphopeptides. It was concluded that phosphopeptides revealed positive effects on mineral solubility and absorbability, and bone mineralisation under certain experimental conditions. Accordingly they could have a beneficial effect on bone health for some groups of the population.

THE PHARMACOLOGIST'S DILEMMA: WHEN IS A DRUG SAFE FOR GENERAL CONSUMPTION?

PEDIATRICS ◽  
1970 ◽  
Vol 45 (1) ◽  
pp. 3-6
Author(s):  
Peter B. Dews
Keyword(s):  
Bone Marrow ◽  
Social Factors ◽  
Physical Dependence ◽  
Rapid Development ◽  
Therapeutic Agents ◽  
Toxic Effects ◽  
Development Of Tolerance

The inclusion of marijuana with heroin under the Harrison Narcotic Act, and in the criminal codes of most states, was never based on pharmacological evidence. Heroin can cause a rapid development of tolerance and physical dependence. The routine of securing and injecting regular doses becomes preemptive. The normal physiological and social factors governing conduct tend to be replaced by the heroin habit, constituting what may be called malignant addiction. Marijuana does not cause malignant addiction. By the standards applied to therapeutic agents, marijuana is also a safe drug. Like heroin, it seems to be free from direct toxic effects to parenchymatous organs—liver, lung, kidney, bone marrow, and so on.

scholarly journals Fungal screening and phylogenetic tree construction

2020 ◽  
Vol 185 ◽  
pp. 04004
Author(s):  
Jianyang Zhou
Keyword(s):  
Phylogenetic Tree ◽  
Marine Fungi ◽  
Biological Activities ◽  
Low Cost ◽  
Rapid Development ◽  
Bioactive Substances ◽  
Tree Construction ◽  
Second Generation Sequencing ◽  
Specific Species ◽  
Biological Methods

The second-generation sequencing technology has achieved rapid development in recent years. It has the advantages of fast speed, high accuracy and low cost compared to the former sequence, so it has a widely application. Marine fungi are important sources of active Marine natural products. Due to the differences in the thermodynamic properties of land and sea and the concentration of salt oxygen, it has a great potential to produce new bioactive substances. Nowadays, scientists isolate and identify a large number of secondary metabolites with novel structures which is from marine fungi, and these compounds show excellent biological activities. For example, some are potential drugs to treat cancer. In order to search for new fungi, this article used a series of biological methods to isolate and study the bacteria isolated from huimin wharf and determine their specific species. And this paper also uses 18S rDNA to analyse the gene sequence and construe the phylogenetic tree.

scholarly journals Possible Mechanisms of Action of Two Pseudomonas fluorescens Isolates as Probiotics on Saprolegniosis Control in Rainbow Trout (Oncorhynchus mykiss Walbaum)

Animals ◽  
2020 ◽  
Vol 10 (9) ◽  
pp. 1507 ◽  
Author(s):  
Concepción González-Palacios ◽  
Juan-Miguel Fregeneda-Grandes ◽  
José-Miguel Aller-Gancedo
Keyword(s):  
Immune Response ◽  
Rainbow Trout ◽  
Pseudomonas Fluorescens ◽  
Serum Proteins ◽  
Mechanisms Of Action ◽  
Experimental Conditions ◽  
Bioactive Substances ◽  
Chemical Treatments ◽  
Rainbow Trout Oncorhynchus Mykiss ◽  
Tank Water

Probiotics have been proposed as one of the alternatives to the chemical treatments currently used in aquaculture. Recently, the possible usefulness of certain microorganisms, mainly bacteria, has been highlighted as a potential biocontrol for saprolegniosis. In the present work we investigated the possible mechanisms of action of two isolates of Pseudomonas fluorescens (LE89 and LE141) with proven ability to reduce Saprolegnia parasitica infection in rainbow trout under experimental conditions when they are added to the tank water. The stimulation of the innate immune response and the production of siderophores and bioactive substances inhibiting S. parasitica present in cells and supernatants of LE89 and LE141 were studied. Regarding the immune response the only noteworthy points were the increase in the phagocytic activity of macrophages and the concentration of serum proteins when LE141 was administered. Both bacteria produced siderophores. When analyzing the protein substances present in supernatants, it was observed that in both isolates the proteins with inhibitory activity present might be siderophores. In LE141, besides siderophores, a protein of 66 kDa was identified in the fraction responsible for inhibition. To sum up, the two P. fluorescens isolates might be usable for biocontrol of saprolegniosis and that the mode of action of these bacteria is likely to be related to the production of siderophores.

scholarly journals Proton (or hydroxide) fluxes and the biphasic osmotic response of human red blood cells.

1993 ◽  
Vol 102 (1) ◽  
pp. 99-123 ◽  
Author(s):  
J D Bisognano ◽  
J A Dix ◽  
P R Pratap ◽  
T S Novak ◽  
J C Freedman
Keyword(s):  
Membrane Potential ◽  
Red Blood Cells ◽  
Blood Cells ◽  
Time Course ◽  
Rapid Development ◽  
Disulfonic Acid ◽  
Proton Efflux ◽  
Experimental Conditions ◽  
Human Red Blood Cells ◽  
Hydroxide Fluxes

Upon exposure of human red blood cells to hypertonic sucrose, the fluorescence of the potentiometric indicator 3,3'-dipropylthiadicarbocyanine iodide, denoted diS-C3(5), displays a biphasic time course indicating the rapid development of an inside-positive transmembrane voltage, followed by a slow DIDS (4,4'-diisothiocyano-2,2'-disulfonic acid stilbene)-sensitive decline of the voltage. In addition to monitoring membrane potential, proton (or hydroxide) fluxes were measured by a pH stat method, cell volume was monitored by light scattering, and cell electrolytes were measured directly when red cells were shrunken either with hypertonic NaCl or sucrose. Shrinkage by sucrose induced an initial proton efflux (or OH- influx) of 5.5 mu eq/g Hb.min and a Cl shift of 21-31 mu eq/g Hb in 15 min. Upon shrinkage with hypertonic NaCl, the cells are initially close to Donnan equilibrium and exhibit no detectable shift of Cl or protons. Experiments with the carbonic anhydrase inhibitor ethoxzolamide demonstrate that for red cell suspensions exposed to air and shrunken with sucrose, proton fluxes mediated by the Jacobs-Stewart cycle contribute to dissipation of the increased outward Cl concentration gradient. With maximally inhibitory concentrations of ethoxzolamide, a residual proton efflux of 2 mu eq/g Hb.min is insensitive to manipulation of the membrane potential with valinomycin, but is completely inhibited by DIDS. The ethoxzolamide-insensitive apparent proton efflux may be driven against the electrochemical gradient, and is thus consistent with HCl cotransport (or Cl/OH exchange). The data are consistent with predictions of equations describing nonideal osmotic and ionic equilibria of human red blood cells. Thus osmotic equilibration after shrinkage of human red blood cells by hypertonic sucrose occurs in two time-resolved steps: rapid equilibration of water followed by slower equilibration of chloride and protons (or hydroxide). Under our experimental conditions, about two-thirds of the osmotically induced apparent proton efflux is mediated by the Jacobs-Stewart cycle, with the remainder being consistent with mediation via DIDS-sensitive HCl cotransport (or Cl/OH exchange).

scholarly journals The Intrapericardial Delivery of Extracellular Vesicles from Cardiosphere-Derived Cells Stimulates M2 Polarization during the Acute Phase of Porcine Myocardial Infarction

2019 ◽  
Vol 16 (3) ◽  
pp. 612-625 ◽  
Author(s):  
Esther López ◽  
Rebeca Blázquez ◽  
Federica Marinaro ◽  
Verónica Álvarez ◽  
Virginia Blanco ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Extracellular Vesicles ◽  
Acute Phase ◽  
Peripheral Blood ◽  
Cardiac Tissue ◽  
Troponin I ◽  
Pathological Condition ◽  
Experimental Conditions ◽  
Inflammatory Phase ◽  
Arginase 1

AbstractAcute myocardial infarction triggers a strong inflammatory response in the affected cardiac tissue. New therapeutic tools based on stem cell therapy may modulate the unbalanced inflammation in the damaged cardiac tissue, contributing to the resolution of this pathological condition. The main goal of this study was to analyze the immunomodulatory effects of cardiosphere-derived cells (CDCs) and their extracellular vesicles (EV-CDCs), delivered by intrapericardial administration in a clinically relevant animal model, during the initial pro-inflammatory phase of an induced myocardial infarction. This effect was assessed in peripheral blood and pericardial fluid leukocytes from infarcted animals. Additionally, cardiac functional parameters, troponin I, hematological and biochemical components were also analyzed to characterize myocardial infarction-induced changes, as well as the safety aspects of these procedures. Our preclinical study demonstrated a successful myocardial infarction induction in all animals, without any reported adverse effect related to the intrapericardial administration of CDCs or EV-CDCs. Significant changes were observed in biochemical and immunological parameters after myocardial infarction. The analysis of peripheral blood leukocytes revealed an increase of M2 monocytes in the EV-CDCs group, while no differences were reported in other lymphocyte subsets. Moreover, arginase-1 (M2-differentiation marker) was significantly increased in pericardial fluids 24 h after EV-CDCs administration. In summary, we demonstrate that, in our experimental conditions, intrapericardially administered EV-CDCs have an immunomodulatory effect on monocyte polarization, showing a beneficial effect for counteracting an unbalanced inflammatory reaction in the acute phase of myocardial infarction. These M2 monocytes have been defined as “pro-regenerative cells” with a pro-angiogenic and anti-inflammatory activity.

scholarly journals Potential Implications of Citrulline and Quercetin on Gut Functioning of Monogastric Animals and Humans: A Comprehensive Review

Nutrients ◽  
2021 ◽  
Vol 13 (11) ◽  
pp. 3782
Author(s):  
Victoria Anthony Uyanga ◽  
Felix Kwame Amevor ◽  
Min Liu ◽  
Zhifu Cui ◽  
Xiaoling Zhao ◽  
...  
Keyword(s):  
Gut Microbiota ◽  
Dietary Supplements ◽  
Intestinal Inflammation ◽  
Rapid Development ◽  
Gut Health ◽  
Bioactive Substances ◽  
Beneficial Effects ◽  
Intestinal Integrity ◽  
Gut Homeostasis ◽  
Immunomodulatory Properties

The importance of gut health in animal welfare and wellbeing is undisputable. The intestinal microbiota plays an essential role in the metabolic, nutritional, physiological, and immunological processes of animals. Therefore, the rapid development of dietary supplements to improve gut functions and homeostasis is imminent. Recent studies have uncovered the beneficial effects of dietary supplements on the immune response, microbiota, gut homeostasis, and intestinal health. The application of citrulline (a functional gut biomarker) and quercetin (a known potent flavonoid) to promote gut functions has gained considerable interest as both bioactive substances possess anti-inflammatory, anti-oxidative, and immunomodulatory properties. Research has demonstrated that both citrulline and quercetin can mediate gut activities by combating disruptions to the intestinal integrity and alterations to the gut microbiota. In addition, citrulline and quercetin play crucial roles in maintaining intestinal immune tolerance and gut health. However, the synergistic benefits which these dietary supplements (citrulline and quercetin) may afford to simultaneously promote gut functions remain to be explored. Therefore, this review summarizes the modulatory effects of citrulline and quercetin on the intestinal integrity and gut microbiota, and further expounds on their potential synergistic roles to attenuate intestinal inflammation and promote gut health.

scholarly journals Evaluation of Small Molecular Polypeptides from the Mantle of Pinctada Martensii on Promoting Skin Wound Healing in Mice

Molecules ◽  
2019 ◽  
Vol 24 (23) ◽  
pp. 4231 ◽  
Author(s):  
Faming Yang ◽  
Xiaoming Qin ◽  
Ting Zhang ◽  
Haisheng Lin ◽  
Chaohua Zhang
Keyword(s):  
Amino Acids ◽  
Wound Healing ◽  
Transforming Growth Factor ◽  
Skin Wound ◽  
Inflammatory Factor ◽  
Bioactive Substances ◽  
Skin Wound Healing ◽  
Proliferative Phase ◽  
Pinctada Martensii ◽  
Inflammatory Phase

Skin wound healing, especially chronic wound healing, is a common challenging clinical problem. It is urgent to broaden the sources of bioactive substances that can safely and efficiently promote skin wound healing. This study aimed to observe the effects of small molecular peptides (SMPs) of the mantle of Pinctada martensii on wound healing. After physicochemical analysis of amino acids and mass spectrometry of SMPs, the effect of SMPs on promoting healing was studied through a whole cortex wound model on the back of mice for 18 consecutive days. The results showed that SMPs consisted of polypeptides with a molecular weight of 302.17–2936.43 Da. The content of polypeptides containing 2–15 amino acids accounted for 73.87%, and the hydrophobic amino acids accounted for 56.51%. Results of in vitro experimentation showed that SMPs possess a procoagulant effect, but no antibacterial activity. Results of in vivo experiments indicated that SMPs inhibit inflammatory response by secretion of anti-inflammatory factor IL-10 during the inflammatory phase; during the proliferative phase, SMPs promote the proliferation of fibroblasts and keratinocytes. The secretion of transforming growth factor-β1 and cyclin D1 accelerates the epithelialization and contraction of wounds. In the proliferative phase, SMPs effectively promote collagen deposition and partially inhibit superficial scar hyperplasia. These results show that SMPs promotes dermal wound healing in mice and have a tremendous potential for development and utilization in skin wound healing.

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