Analgesic properties of the dry combined extract BNO 1016 in leukotriene depended hyperalgesia.

Combined dry extract BNO 1016 is a herbal drug commonly used for rhinosinusitis therapy. It is known that a significant role in rhinosinusitis pathogenesis is played by an inflammatory reaction in maxillary sinuses of the nasal cavity. At the initial stage of any inflammation the largest impact is caused by leukotrienes. Major chronic rhinosinusitis (CRS) according to the guideline EPOS-2020 include facial pain as clinical diagnostic criteria for rhinosinusitis. Therefore, it is reasonable to study the analgesic effects of the combined dry extract BNO 1016 on the model of zymozan- induced hyperalgesia. The tested drug is the combined dry extract BNO 1016 ("Bionorica SE", Germany) at different dose levels. The reference drug is ibuprofen. Leukotriene hyperalgesia was induced by subplantar injection of zymozan into the paw of Wistar rats. Pain threshold was evaluated with Ugo-Basil analgesimeter and analgesic activity was calculated together with mean effective dose (ED50) with help of the Probit Analysis. The highest analgesic activity was observed at a dose level of 500 mg/kg of BNO 1016 during all time-points of the experiment and reached 169.5% 3h after hyperalgesia onset. The analgesic activity of BNO 1016 at doses of 50 mg/kg in 1h, 2h, 3h after induction hyperalgesia, 150 mg/kg and 500 mg/ kg was credibly higher than that of Ibuprofen at all time-points of the experiment. Based on the experimental data, the index of ED50 for analgesic activity of BNO 1016 was calculated with Probit Analysis. The combined dry extract BNO 1016 shows a high level of analgesic activity in the leukotriene-depended hyperalgesia model, which is very promising for the improvement of treatment of patients with CRS, but additional preclinical and clinical researches are reasonable.

N-Acetylglucosamine is the most effective glucosamine derivative for the treatment of membranous nephropathy in rats.

Nephroprotective drug development for optimizing treatment of chronic kidney disease (CKD) is an important task of pharmaceutical science. Our study evaluated nephroprotective properties of the two glucosamine derivatives N-acetylglucosamine and glucosamine hydrochloride in a 3-week-long parenteral and oral daily administration at doses of 50 mg/kg in rats with doxorubicin nephropathy. Nephroprotective activity (NA) was evaluated by determining the functional state of the kidneys, the level of azotemia and the activity of free-radical processes in the renal tissue. The results show a significant increase in renal excretory function, normalization of nitrogen metabolism and a decline of free-radical processes under the influence of both studied amino sugars in rats with doxorubicin nephropathy. I. m. route of administration yielded the highest efficacy for both amino sugars with the highest level of NA (83.3%) shown by N-acetylglucosamine. Thus N-acetylglucosamine in i. m. injections has the highest NA among the glucosamine derivatives, and is a promising agent for CKD treatment.

Diclocor is superior to diclofenac sodium and quercetin in normalizing biochemical parameters in rats with collagen-induced osteoarthritis.

OBJECTIVE: The aim of the present study was to investigate anti-inflammatory activity of Diclocor in the setting of collagen-induced osteoarthritis in rats in comparison with its active monocomponents-diclofenac sodium and quercetin. METHODS: The study was conducted on the model of collagen-induced osteoarthritis and included measurement of sialic acids, glycoproteins, C-reactive protein, prostaglandin E2, 6-keto-prostaglandin F1α, thromboxane B2, and leukotriene B4. Lastly, morphologic study with morphometry was also performed. RESULTS: Diclocor is superior to quercetin and diclofenac sodium by the degree of pharmacological effect on some of the studied parameters. The differences between the values were statistically significant. CONCLUSION: Diclocor is a promising corrector of inflammatory and destructive joint diseases. Owing to the presence of both diclofenac sodium and quercetin in its composition, Diclocor exhibits a complex mechanism of anti-inflammatory action affecting cyclooxygenase and lipoxygenase ways of arachidonic acid biotransformation.

[Effect of glucosamine hydrochloride in combination with paracetamol on chondrocyte apoptosis under conditions of systemic steroidal arthritis development in rats].

The effect of a combination of glucosamine hydrochloride with paracetamol on the apoptosis of chondrocytes in the articular cartilage of rats with experimental steroidal dystrophy (osteoarthritis) has been studied by hystochemical methods. Untreated control rats are characterized by a significant increase in the fraction of chondrocytes involved in the processes of apoptosis. The treatment of animals by a combination of glucosamine hydrocloride with paracetamol substantially reduced the percentage of apoptic chondrocytes. The pronounced antiapoptic effect of the investigated combination differed but little from the effect of glucosamine hydrochloride alone, but significantly exceeded the antiapoptic activity of paracetamol.

[Nonantibiotic properties of macrolides and their role in modulation of the inflammatory reaction].

Macrolides is one of the most interesting and promising classes of antibiotics, which occupy one of the first places in the world in the frequency of clinical use. In recent years, new facts have reported about specific features of the mechanism of action and pharmacodynamics of macrolides, in particular, with respect to their anti-inflammatory effect. Unfortunately, many therapists and pharmacists are not familiar with recent advanced in the clinical and pharmacological evidence concerning extra-antibiotic properties characteristic of some macrolides. Macrolides increase defensive mechanisms of the body against infection at the first stage of their action and suppress inflammation at the next stages, which leads to faster resolution of a disease. The immunomodulating properties of macrolides are also discussed and require further investigation. Good prospects are related with combined therapy, in which antibiotics are used jointly with drugs potentiating their extra-antibiotic effect and overwhelming negative effects on the body. This approach will significantly improve the efficiency of therapy, reduce the risk of side effects, and reduce the cost of treatment.

[The influence of paracetamol on the parameters of connective tissue metabolism during experimental osteoarthrosis].

We present results of the biochemical investigation of changes in the metabolism and accumulation of articular cartilage matrix macromolecules and the inflammatory tests in experimental animals with corticosteroidal dystrophy of connective tissues after the therapy by paracetamol in low doses, which corresponded to a standard mean therapeutic dose MTD= 40 mg/kg, 1/2 MTD = 20 mg/kg, 1/4 MTD = 10 mg/kg, and 1/8 MTD = 5 mg/kg, in comparison to the effect of glucosamine hydrochloride treatment in a dose of 50 mg/kg. It is established that paracetamol in low doses exhibits a moderate chondroprotective effect and stimulates the articular cartilage reparative regeneration under conditions of corticostereoidal dystrophy of connective tissues. The most pronounced chondroprotective effect of paracetamol was observed in doses of 1/4 MTD and 1/8 MTD (10 and 5 mg/kg, respectively), but not in the case of MTD. At the same time, the antiinflammatory properties of paracetamol in all doses were insufficiently pronounced.

[The influence of experimental therapy on the dynamics of endogenous glucosamine content in laboratory animals with nephropathy].

The effects of glucosamine hydrochloride, glucosamine sulfate, N-acetylglucosamine, glucosamine pentaacetate, and combinations of glucosamine hydrochloride and N-acetylglucosamine with diclofenac sodium on the endogenous glucosamine (aminosugar) content in the blood and kidney of rats with experimental nephropathy have been studied. The development of inflammatory and destructive processes in kidneys is accompanied by an increase in the aminosugar content in the blood serum and the corresponding decrease in renal tissues. This fact can be used as a nonspecific diagnostic criterion for the level of kidney damage and for the efficacy of pharmacotherapy. Normalization of these indices in the case of successful therapy was observed, which was most pronounced upon the administration of glucosamine hydrochloride, N-acetylglucosamine, and their combinations with diclofenac sodium.

[Paracetamol: advantages and drawbacks in the treatment of dystrophic destructive lesions in connective tissues].

The advantages and drawbacks of using paracetamol in the treatment of dystrophic and destructive lesions in connective tissues are considered.

[Experimental study of the effect of glucosamine hydrochloride on metabolic and repair processes in connective tissue structures]. / Eksperimental'noe izuchenie vliianiia gliukozamina gidrokhlorida na metabolicheskie i reparativnye protsessy v soedinitel'notkannykh strukturakh.

The effects of glucosamine hydrochloride on the metabolic and repair processes were studied on a model of post-traumatic osteoarthrosis in the articular cartilage and on a model of post-traumatic keratitis in the cornea. The administration of glucosamine hydrochloride stimulated repair and favored inhibition of dystrophic post-traumatic processes in the connective-tissue structures. It is suggested that a probable mechanism of the drug action consists in stimulation of the synthesis of glucosaminoglycanes and collagen.

[Effects of rumalon and arteparon correcting metabolism in the connective tissue on the functional state of the liver in toxic hepatitis]. / Vliianie korrektorov metabolizma soedinitel'noi tkani rumalona i arteparona na funktsional'noe sostoianie pecheni v usloviiakh toksicheskogo gepatita.

Effects of the connective tissue metabolism correctors rumalon (a glycosaminoglycane peptide complex) and arteparon (glucosamine sulfate) on the cholepoietic and absorption-excretion functions of liver were studied on a model of toxic liver damage. Rumalon exhibits pronounced anticholelithiasis and cholagogic properties and improves the absorption-excretion liver function. Arteparon produced no cholagogic action, inhibited the elimination of bromosulfalein, and showed no anticholelithiasis activity. The difference in the pharmacological effects of two drugs is related to their structural distinctions and the differing characteristics of aglycons and anions entering into their compositions.

[Radioprotective effect of a new pharmaceutical "glucosuccine"]. / Radioprotektornoe deistvie novogo farmakologicheskogo sredstva "gliukosuktsin".

The experiments on 6-Gy irradiated rats have revealed that the new biologically active substance. Glucosuccine has a radioprotective effect which depends upon the route of administration. The agent was demonstrated to produce a profound radioprotective rather than therapeutical effects. Its administration for 30 days proved to be less effective than its triple use prior to and following irradiation.

[An experimental study of suikrepan]. / Eksperimental'noe izuchenie suikrepana.

Acute, subacute, and chronic experiments were performed to examine the toxicity, specific action, analgetic, and physicochemical properties of suicrepan derived from the porcine duodenal mucosa and the hormone secretin contained in it. Suicrepan was found to be an effective pancreatic extrasecretory function stimulant, by showing therapeutical benefits in experimental pancreatitis and analgesic effects. The drug was demonstrated to display a low toxicity.

[The effect of the amino sugar glucosamine on the endogenous intoxication processes in pulmonary edema in rats]. / Vliianie aminosakhara gliukozamina na sostoianie protsessov éndotoksikoza pri oteke legkikh u krys.

The effects of glycosamine aminosugar on the processes of endotoxicosis and lipid peroxidation were thoroughly studied in rats with toxic pulmonary edema. There was a glycosamine-induced decrease in markers of endotoxicosis, such as medium-weight molecular peptides and malonic dialdehyde in serum and lung tissue. Administration of exogenous glucosamine resulted in its incorporation into the membranes of target organs, connective tissue and normalized the levels of endogenous N-acetyl-glucosamine, which finally determined antitoxic and antioxidative properties in this aminosugar.

[Antihypoxic effect of glucosamine in acute hypoxic states in mice]. / Antygipoksychnyi efect gliukozaminu pry gostrykh gipoksychnykh stanakh organizmu myshei.

The preventive glucosamine injection causes an increase in the survival of mice with acute hypobaric hypoxia. The injection of glucosamine, combined with sodium hydroxybutyrate greatly increased their antihypoxic activities.

[The influence of glucosamine on the antiexudative effect of nonsteroidal anti-inflammatory agents]. / Vliianie gliukozamina na antiékssudativnyi éffekt nesteroidnykh protivovospalitel'nykh svoistv.

The study of the antiexudative activities of voltaren, indomethacin and piroxicam in combination with glucosamine on the model of carrageenan inflammation showed that the combination makes it possible to decrease the effective doses of nonsteroidal anti-inflammatory drugs by 2-2.7 times with the preservation of the pronounced antiexudative activity. A diverse influence of aminosugar on the anti-inflammatory effect of nonsteroidal anti-inflammatory drugs depending on the sequence and routes of administration is connected with their membrane mechanisms and metabolic features of amino sugar.

[The efficacy of glucosamine in treating complicated hyperreactive experimental myocardial infarct]. / Effektivnost' gliukozamina v lechenii oslozhnennogo giperreaktovnogo éksperimental'nogo infarkta miokarda.

The effect of glucosamine hydrochloride on the course of complicated hyperreactive myocardial infarction in dogs was studied. Glucosamine contributed to the restoration of reactivity in the animals. The reactivity became corresponding for normoreactive myocardial infarction. Glucosamine normalized carbohydrate and protein metabolism in the necrosis zone, cAMP and cGMP and also their ratio that led to healing by postinfarction scar, and in none of the cases the heart aneurysm developed. The optimizing healing of hyperreactive myocardial infarction under the influence of glucosamine is mediated through the mechanisms of reactivity and the regulation of metabolic processes.

[The liver-protective properties of D-glucosamine]. / Gepatozashchitnye svoistva D-gliukozamina.

The antioxidant and membrane-stabilizing activities of D-glucosamine were studied on two models of toxic liver damage. When administered in a dose of 50 mg/kg, D-glucosamine was found to prevent the development of the hepatocyte cytolysis syndrome, to normalize the cholate- and glycogen-synthetic functions of the liver. D-glucosamine exhibited a significant anabolic effect that also supplemented its hepatoprotective activity.

[Physiologic importance of glucosamine]. / Fiziologicheskoe znachenie glikozamina.

The paper reviews the present state of the problem on the physiological importance of D-(+)-glucosamine, an amino sugar. Glucosamine is shown to be a component of many biological important systems widely spread in nature. It is a part of the connective tissues, membranes, lipopolysaccharides and mucopolysaccharides and participates in detoxic function of the liver and kidneys. The data from literature reviewed permit concluding that glucosamine and its derivatives are potentially useful and possess antiinflammatory, liver-defending, antihypoxic and other pharmacological activities.