Pharmacotherapeutic Efficacy Research Articles

Anticancer effects of emetine against cisplatin resistant pancreatic cancer cells via activation of Cyto-c/Caspase-9/Caspase-3/Bax/Bad axis

This investigation examines the potential pharmacotherapeutic efficacy of emetine, a natural alkaloid, against pancreatic ductal carcinoma, utilizing the PaCa3 cell line as a model. Employing a multifaceted approach, the study explores emetine's impact on cell viability, clonogenic potential, and apoptotic pathways, unravelling its molecular mechanisms. Additionally, an in-vivo assessment is conducted to evaluate emetine's antitumor efficacy against PaCa3 xenografts. Under standard conditions, PaCa3 cells were treated with varying emetine concentrations and subjected to MTT, clonogenic, DAPI, AO/EB, Annexin V-FITC/PI, and Western blot assays. In-vivo experiments involved the administration of emetine to female nude mice with PaCa3 xenografts, with subsequent measurement of tumor weight and volume. Statistical analyses included Tukey-test and ANOVA. Emetine demonstrated a significant and dose- and time-dependent cytotoxic effect on PaCa3 cells, reducing viability from 98% to 8% (***p<0.001). Clonogenic assay indicated a substantial inhibition of colony formation. DAPI staining revealed nuclear chromatin condensation, while AO/EB staining indicated heightened apoptosis. Annexin V-FITC/PI assay exhibited a dose-dependent decrease in normal cell viability and an increase in apoptotic events. Western blot analysis showcased concentration-dependent downregulation of anti-apoptotic Bcl-2 and upregulation of pro-apoptotic markers. In-vivo experiments illustrated a dose-dependent reduction in tumor weight (5 g to 1.6 g) and volume (2400 mm³ to 844 mm³) with emetine treatment. In conclusion, emetine emerges as a potent anticancer agent against pancreatic ductal carcinoma, exhibiting cytotoxicity, clonogenic inhibition, and apoptotic induction in PaCa3 cells. The in-vivo study further highlights its promising therapeutic potential, laying the groundwork for future clinical studies in pancreatic cancer treatment.

HEPATOPROTECTIVE EFFECT OF GOLDEN VOLODUSHKA (BUPLEURUM AUREUM L.) HERB EXTRACT OF DRY IN EXPERIMENTAL TOXIC HEPATITIS IN RATS

Introduction. The search for new medicines, including those of plant origin, for the treatment of diseases of the hepatobiliary system is relevant and timely. A promising source for the development of hepatoprotective drugs is golden volodushka (Bupleurum aureum L.). To date, a large evidence base has been accumulated for the biochemical study of this plant, its pharmacological activity has been scien-tifically proven. Good stocks of golden volodushka in the wild, the simplicity of its harvesting and the possibility of cultivation were noted. The VILAR State Medical University has developed a method for obtaining volodushka golden herb extract of dry. Aim. The study of the pharmacotherapeutic efficacy of volodushka golden (Bupleurum aureum L.) herb extract of dry in case of liver damage under experimental conditions. Material and methods. In the studies, white non-linear male rats with a body weight of 180-200 g were used. Volodushka extract was studied at doses of 50 and 100 mg/kg. The comparison drug was silimar at a dose of 100 mg/kg. Experimental CCl4 – induced hepatitis in rats was caused by a single subcutaneous injection of 50% carbon tetrachloride oil solution one hour after the last administration of the studied extract and the comparison drug. After 48 hours, blood was taken from the tail vein of rats, serum was obtained and its biochemical analysis was carried out. Next, the rats eu-thanized in a CO2 chamber and the liver extracted for pathophysiological evaluation. Tetracycline hepatitis was caused by intragastric administration of tetracycline to animals at a dose of 500 mg/kg. Then, after 48 hours, blood was taken from the animals, serum was obtained and its biochemical analysis was carried out. Results. Volodushka golden grass dry extract on a model of carbon tetrachloride hepatitis exhibits a hepatoprotective effect, which is confirmed by a comparative pathophysiological study and a study of the activity of enzyme markers of the morphofunctional state of the liver in rat blood serum. In the tetracycline hepatitis model, the studied extract also has a hepatoprotective effect, which is confirmed by biochemical studies. Conclusions. Studies of volodushka extract in conditions of experimental liver lesions have shown that the studied extract in experimental therapeutic doses has a pronounced hepatoprotective effect and is promising for the creation of a herbal medicine for the prevention and treatment of diseases of the digestive system.

CO115 The Interpretation and Grading of Evidence Derived From Interim Analyses for the Assessment of the Pharmacotherapeutic Efficacy of Medicines

CO115 The Interpretation and Grading of Evidence Derived From Interim Analyses for the Assessment of the Pharmacotherapeutic Efficacy of Medicines

Pharmacotherapeutic efficacy of the use of pelargonium sidovid root extract in the prevention and treatment of respiratory diseases

Relevance in research infectious and inflammatory diseases of the upper respiratory tract caused by high prevalence, variability of clinical manifestations and severity of the disease with the risk of developing complications. Respiratory diseases are a cause of functional and morphological disorders of the respiratory tract mucosa which is a protective barrier against various damaging agents. It is necessary to use complex drugs that preserve and restore the physiological activity of the mucous membrane as much as possible. In this regard, there is a great interest of plant medical product (extract of the roots of pelargonium sidovid is the chief active ingredient) which causes stimulation of nonspecific protective mechanisms, the beating frequency of the cilia of the ciliated epithelium, the activity of NK cells, phagocytes, modulation of the synthesis of interferon and proinflammatory cytokines, the expression of adhesive molecules, chemotaxis. We can notice moderate direct antibacterial and antiviral properties of extract. The pharmacotherapeutic efficacy of the plant medical product containing an extract of pelargonium sidovid roots was analysed in our research to treatment of respiratory diseases. There is a literature review about efficacy and safety preparations containing liquid extract of pelargonium sidovid roots. The extract effectiveness is confirmed by the results of clinical investigation: children and adults are digest the drug, greatly facilitates the course of diseases, prevents the development of complications, and reduces the duration of acute respiratory infections. Extract of the roots of pelargonium sidovid is easy to use and dosage. All these properties make it possible to include this medical product in the complex therapy of inflammatory diseases of the respiratory tract.

HIV gp120 impairs nucleus accumbens neuroimmune function and dopamine D3 receptor-mediated inhibition of cocaine seeking in male rats

Cocaine Use Disorders (CUDs) are associated with an increased risk of human immunodeficiency virus (HIV) infection. Cocaine and the HIV envelope protein gp120 each induce distinct deficits to mesocorticolimbic circuit function and motivated behavior; however, little is known regarding how they interact to dysregulate these functions or how such interactions impact pharmacotherapeutic efficacy. We have previously shown that the selective, weak partial agonist of the dopamine D3 receptor (D3R), MC-25-41, attenuates cocaine-seeking behavior in male rats. Here, we sought to characterize changes in striatal neuroimmune function in gp120-exposed rats across abstinence from operant access to cocaine (0.75 mg/kg, i.v.) or sucrose (45 mg/pellet), and to examine the impact of gp120 exposure on MC-25-41-reduced cocaine seeking. After establishing a history of cocaine or sucrose self-administration, rats received intracerebroventricular gp120 infusions daily the first 5 days of abstinence and were sacrificed either on day 6 or after 21 days of forced abstinence and a cue-induced cocaine seeking test. We demonstrated that MC-25-41 treatment attenuated cue-induced cocaine seeking among control rats but not gp120-exposed rats. Moreover, postmortem analysis of nucleus accumbens (NAc) core neuroimmune function indicated cocaine abstinence- and gp120-induced impairments, and the expression of several immune factors within the NAc core significantly correlated with cocaine-seeking behavior. We conclude that cocaine abstinence dysregulates striatal neuroimmune function and interacts with gp120 to inhibit the effectiveness of a D3R partial agonist in reducing cocaine seeking. These findings highlight the need to consider comorbidities, such as immune status, when evaluating the efficacy of novel pharmacotherapeutics.

The effect of the composition of Soderm®-Forte gel and the new injectable form of Rexod® on pathology findings in gingival tissue in experimental periodontitis in rats

Introduction: Periodontitis is the most important problem of modern dentistry. The development of new medicines and treatment regimens for patients with periodontal complex lesions is a strategic direction of modern pharmacology and dentistry. In this view, pride of place goes to morphological research, which allows not only to study the effect of drugs on pathomorphological changes in periodontal tissues, but also to estimate their therapeutic effectiveness. Aim of the study: to determine the nature of the effect of the composition of Soderm®-Forte gel and the new injectable form of Rexod® on the pathology findings in gingival tissue of rats with experimental periodontitis.
 Materials and methods: Experimental periodontitis (EP) was induced in rats by ligature method. The study was per­formed according to the following algorithm: animals with intact periodontium; animals with untreated EP; animals with EP treated with traditional drug therapy (TDT); animals with EP treated with combinations of TDT with Soder­m®-Forte gel and TDT with Soderm®-Forte gel and the new injectable form (NIF) of Rexod®. For pathomorphological examination, biopsy specimen was taken from the gingival margin of the lower incisors. The ImageJ software was used for computer morphometry.
 Results and discussion: Examination of the gum samples revealed moderate therapeutic effects of the TDT. The com­binations of TDT with Soderm®-Forte gel and, to a greater extent, TDT with Soderm®-Forte gel and the NIF of Rexod® showed high pharmacotherapeutic efficacy, manifested in rapid regeneration of the gingival tissues.
 Conclusion: The combination of TDT, Soderm®-Forte gel and the NIF of Rexod® shows the most beneficial effect on the pathological processes in the gum. The pharmacotherapeutic effect of the studied combination promotes the earliest regeneration of damaged gum tissues and reduces the risk of persistent pathology changes in them.

Pharmacotherapeutic efficacy on noninvasive fibrosis progression in nonalcoholic fatty liver disease: a systematic review and network meta-analysis.

Fibrosis impacts long-term outcomes among patients with nonalcoholic fatty liver disease (NAFLD). Due to well-documented flaws associated with liver biopsy, there has been a recent emphasis on prioritizing noninvasive testing over liver biopsy for the assessment of fibrosis. A comprehensive systematic review and frequentist random effects network meta-analysis was performed among randomized controlled trials reporting pharmacologic intervention in NAFLD. The primary endpoint was the absolute change in liver stiffness measurement (LSM) via elastography. Secondary endpoints included changes in noninvasive serologic tests including APRI, fibrosis-4 index, NAFLD fibrosis score, enhanced liver fibrosis (ELF) and FibroTest (FibroSure in the USA). Forty-five randomized controlled trials enrolling 6932 patients were identified for this network meta-analysis. Across the primary endpoint, firsocostat, semaglutide, montelukast, cilofexor plus firsocostat, obeticholic acid and diacerein (change in LSM via vibration controlled transient elastography), in addition to lubiprostone and pemafibrate (change in LSM via magnetic resonance elastography) were found to be the most effective and statistically significant treatment interventions. Similarly, the following interventions were determined to be most effective as compared to placebo among secondary endpoints: saroglitazar, lubiprostone, and obeticholic acid (change in APRI); saroglitazar, semaglutide, firsocostat and cilofexor plus firsocostat (change in ELF); obeticholic acid and belapectin [change in FibroTest/FibroSure]. This is the first systematic review and network meta-analysis reporting pharmacologic efficacy in the progression of fibrosis based on noninvasive testing among patients with NAFLD. Semaglutide, obeticholic acid, firsocostat, cilofexor plus firsocostat and lubiprostone were found to be the most effective treatments based on their consistent efficacy reproduced across multiple endpoints, both via elastography and noninvasive blood tests.

The protective effects of Esculentoside A through AMPK in the triple transgenic mouse model of Alzheimer's disease

BackgroundNeurofibrillary tangles comprising hyperphosphorylated tau are vital factors associated with the pathogenesis of Alzheimer's disease (AD). The elimination or reduction of hyperphosphorylated and abnormally aggregated tau is a valuable measure in AD therapy. Esculentoside A (EsA), isolated from Phytolacca esculenta, exhibits pharmacotherapeutic efficacy in mice with amyloid beta-induced AD. However, whether EsA affects tau pathology and its specific mechanism of action in AD mice remains unclear. PurposeTo investigate the roles and mechanisms of EsA in cognitive decline and tau pathology in a triple transgenic AD (3 × Tg-AD) mouse model. MethodsEsA (5 and 10 mg/kg) was administered via intraperitoneal injection to 8-month-old AD mice for eight consecutive weeks. Y-maze and novel object recognition tasks were used to evaluate the cognitive abilities of mice. Potential signaling pathways and targets in EsA-treated AD mice were assessed using quantitative proteomic analysis. The NFT levels and hippocampal synapse numbers were investigated using Gallyas-Braak silver staining and transmission electron microscopy, respectively. Western blotting and immunofluorescence assays were used to measure the expression of tau-associated proteins. ResultsEsA administration attenuated memory and recognition deficits and synaptic damage in AD mice. Isobaric tags for relative and absolute quantitation proteomic analysis of the mouse hippocampus revealed that EsA modulated the expression of some critical proteins, including brain-specific angiogenesis inhibitor 3, galectin-1, and Ras-related protein 24, whose biological roles are relevant to synaptic function and autophagy. Further research revealed that EsA upregulated AKT/GSK3β activity, in turn, inhibited tau hyperphosphorylation and promoted autophagy to clear abnormally phosphorylated tau. In hippocampus-derived primary neurons, inhibiting AMP-activated protein kinase (AMPK) activity through dorsomorphin could eliminate the effect of EsA, as revealed by increased tau hyperphosphorylation, downregulated activity AKT/GSK3β, and blocked autophagy. ConclusionsTo our knowledge, this study is the first to demonstrate that EsA attenuates cognitive decline by targeting the pathways of both tau hyperphosphorylation and autophagic clearance in an AMPK-dependent manner and it shows a high reference value in AD pharmacotherapy research.

Evaluation of the Pharmacotherapeutic Efficacy of Cycloartane Glycosides in Comparison to Lovastatin in Rabbits with Experimental Atherosclerosis

Evaluation of the Pharmacotherapeutic Efficacy of Cycloartane Glycosides in Comparison to Lovastatin in Rabbits with Experimental Atherosclerosis

Pharmacotherapy of knemidocoptosis in budgerigars

The article presents a study of the pharmacotherapeutic efficacy of drugs of etiotropic action Ivermikol drops and Aversectin ointment for cnemidocoptosis in budgerigars. Treatment was directed to the study of etiotropic therapy of acaricidal drugs in relation to the causative agents of invasion in sick birds and in the environment. Extensibility and intensity (EE and IE) of the drugs were assessed on the 6th, 22nd and 36th days after the treatment. A study group of budgies suffering from knemidocoptosis was given the following treatment regimen: ivermicol drops, chlorhexidine and Perlen multivitamized grain mixture for food. According to the treatment, on the 6th day in budgies, the extensibility was 0 %. On the 22nd day of treatment in 4 parrots during microscopic examination of scrapings from the affected areas, Knemidocoptes mites were found. Thus, the extensibility of ivermicol drops was 33.3 %. On the 36th day, the extensibility of the treatment of parrots with ivermicol drops was 100 %. Thus, the results obtained make it possible to recommend the indicated scheme for the treatment of ornamental birds for knemidocoptosis. Thuse of the treatment of sick budgerigars according to a different scheme (aversectin ointment, chlorhexidine and multivitamized Perlen grain mixture for nutrition) also proved to be effective. However, on the 22nd day of treatment, microscopic examination of scrapings from the affected areas revealed Knemidokoptes mites in 5 parrots, thus, the extensibility of aversectin ointment was 16.7 %. On the 36th day of treatment in parrots of the control group, which were treated with aversectin ointment, the EE of treatment was 66 %, since 2 out of 6 parrots remained sick, which required further treatment. The dynamics of the EE and IE of ivermicol drops and avesectin ointments on the 6th, 22nd, and 36th days of the study indicate the highest therapeutic efficacy of ivermicol drops. Thus, the use of ivermicol drops as a means of etiotropic action in the cinemidocoptosis of budgerigars is effective. Key words: scabies, treatment, knemidocoptosis, parrots, Cnemidocoptes pilae, acaricidalpreparations, ivermicoldrops, aversectinointment.

Ефективність і патогенетичне обґрунтування застосування вілдагліптину у хворих на цукровий діабет 2-го типу

Актуальність. Інгібітори дипептидилпептидази 4-го типу (ДПП-4), маючи інкретинову активність, впливають на основні патогенетичні механізми цукрового діабету (ЦД) 2-го типу. Вілдагліптин є інноваційним препаратом класу інгібіторів ДПП-4 з унікальними характеристиками фармакокінетики, ефективність і безпека якого вивчалися в плацебо-контрольованих дослідженнях. Мета дослідження: вивчення фармакотерапевтичної ефективності, безпеки й переносимості препарату Гліптар виробництва ПАТ «Київмедпрепарат» (Україна) у терапії хворих на ЦД 2-го типу. Матеріали та методи. У дослідження було включено 49 пацієнтів із ЦД 2-го типу. До включення в дослідження хворі отримували монотерапію метформіном у дозі не менше за 1000 мг на добу принаймні упродовж останніх шести місяців. Тривалість перебігу ЦД 2-го типу в середньому становила 6,2 ± 1,8 року. Пацієнти сформували дві групи для подальшого спостереження. 29 пацієнтам, які до цього часу отримували препарати метформіну в дозі до 2000 мг/добу, був додатково призначений препарат Гліптар (вілдагліптин) у дозі 50 мг двічі на добу. Пацієнти другої групи (n = 20) продовжували прийом метформіну двічі на день в дозі 2000 мг/добу. Результати. Через 12 тижнів у хворих першої групи на тлі терапії метформіном у поєднанні з вілдагліптином рівень НbА1с вірогідно знизився до 6,42 ± 0,21 %, глікемія натще — до 6,14 ± 0,22 ммоль/л, глікемія постпрандіальна — до 8,63 ± 0,23 ммоль/л. На тлі комбінованого лікування у хворих на ЦД 2-го типу відзначалися зниження маси тіла на 1,18 кг, а також тенденція до зниження індексу маси тіла з 31,49 ± 1,08 кг/м2 до 29,98 ± 0,76 кг/м2. Рівень імунореактивного інсуліну становив після лікування в першій групі 14,08 ± 1,83 мкОд/мл (при початковому 21,11 ± 2,03 мкОд/мл), індекс HOMA-IR — 3,14 ± 0,21 (проти початкового 6,28 ± 1,42). Вірогідне зниження показників вуглеводного обміну, інсулінорезистентності можна оцінювати як позитивну динаміку завдяки комбінованому лікуванню. Висновки. З огляду на отримані переваги подвійної терапії в лікуванні хворих на ЦД 2-го типу відповідно до загальноприйнятої покрокової терапії на другому етапі пацієнтам, які отримують метформін і не досягли цільового глікемічного контролю, доцільно призначати препарат вілдагліптину. Комбінована терапія вілдагліптином у поєднанні з метформіном забезпечує комплексну дію на чинники ризику серцево-судинних захворювань у вигляді запобігання розвитку гіперінсулінемії та зниження інсулінорезистентності.

Oral drug delivery for immunoengineering.

The systemic pharmacotherapeutic efficacy of immunomodulatory drugs is heavily influenced by its route of administration. A few common routes for the systemic delivery of immunotherapeutics are intravenous, intraperitoneal, and intramuscular injections. However, the development of novel biomaterials, in adjunct to current progress in immunoengineering, is providing an exciting area of interest for oral drug delivery for systemic targeting. Oral immunotherapeutic delivery is a highly preferred route of administration due to its ease of administration, higher patient compliance, and increased ability to generate specialized immune responses. However, the harsh environment and slow systemic absorption, due to various biological barriers, reduces the immunotherapeutic bioavailability, and in turn prevents widespread use of oral delivery. Nonetheless, cutting edge biomaterials are being synthesized to combat these biological barriers within the gastrointestinal (GI) tract for the enhancement of drug bioavailability and targeting the immune system. For example, advancements in biomaterials and synthesized drug agents have provided distinctive methods to promote localized drug absorption for the modulation of local or systemic immune responses. Additionally, novel breakthroughs in the immunoengineering field show promise in the development of vaccine delivery systems for disease prevention as well as combating autoimmune diseases, inflammatory diseases, and cancer. This review will discuss current progress made within the field of biomaterials and drug delivery systems to enhance oral immunotherapeutic availability, and how these new delivery platforms can be utilized to deliver immunotherapeutics for resolution of immune‐related diseases.

Gut microbiota specifically mediates the anti-hypercholesterolemic effect of berberine (BBR) and facilitates to predict BBR’s cholesterol-decreasing efficacy in patients

IntroductionGut microbiota has been implicated in the pharmacological activities of many natural products. As an effective hypolipidemic agent, berberine (BBR)’s clinical application is greatly impeded by the obvious inter-individual response variation. To date, little evidence exists on the causality between gut microbes and its therapeutic effects, and the linkage of bacteria alterations to the inter-individual response variation. ObjectivesThis study aims to confirm the causal role of the gut microbiota in BBR’s anti-hyperlipidemic effect and identify key bacteria that can predict its effectiveness. MethodsThe correlation between gut microbiota and BBR’s inter-individual response variation was studied in hyperlipidemic patients. The causal role of gut microbes in BBR’s anti-hyperlipidemic effects was subsequently assessed by altered administration routes, co-treatment with antibiotics, fecal microbiota transplantation, and metagenomic analysis. ResultsThree-month clinical study showed that BBR was effectively to decrease serum lipids but displayed an obvious response variation. The cholesterol-lowering but not triglyceride-decreasing effect of BBR was closely related to its modulation on gut microbiota. Interestingly, the baseline levels of Alistipes and Blautia could accurately predict its anti-hypercholesterolemic efficiency in the following treatment. Causality experiments in mice further confirmed that the gut microbiome is both necessary and sufficient to mediate the lipid-lowering effect of BBR. The absence of Blautia substantially abolished BBR's cholesterol-decreasing efficacy. ConclusionThe gut microbiota is necessary and sufficient for BBR’s hyperlipidemia-ameliorating effect. The baseline composition of gut microbes can be an effective predictor for its pharmacotherapeutic efficacy, providing a novel way to achieve personalized therapy.

A multivariate comparative clinical pharmacotherapeutic efficacy and chronopharmacovigilance assessment study of ofloxacin, one of the commonplace, TGFβ1 inducing and telomerase impairing fluoroquinolones, in treating acute gastroenteritis, chronic obstructive pulmonary disease, new drug-sensitive tuberculosis, recurrent mixed cutaneous infections, and post-surgical refractory wound infections, among the global patients, with heterogenous pharmacogeographic and pharmacogenomic constitution

Background: Ofloxacin has an inhibitory effect on DNA gyrase, DNA topoisomerase IV and IL-1α, IL-6, IL-8, TNFa; and a superinducing effect on IL-2. Ofloxacin has profound bactericidal, anti-tubercular, anti-leprotic, anti-viral including anti-coronavirus, anti-fungal, anti-protozoal, comedolytic, anti-comedogenic, anti-inflammatory, immunomodulatory, and anti-malignant: pro-apoptotic and anti-proliferative potential, including TGFb1 targeted G2 phase cell cycle arrest and telomerase activity impairment. Objectives of the study were a comparative clinical pharmacotherapeutic efficacy and chronopharmacovigilance assessment study, of ofloxacin, one of the commonplace TGFb1 inducing and telomerase impairing fluoroquinolones, in treating heterogenous global patients, suffering from different diseases.Methods: A prospective, multivariate study of 100 patients, allotted into group A (acute gastroenteritis) =20, group B (chronic obstructive pulmonary disease) =20, group C (new drug-sensitive tuberculosis) =20, group D (recurrent mixed cutaneous infections) =20, and group E (post-surgical refractory wound infections) =20, was prescribed ofloxacin 200-400 mg twice daily, according to required prescribed regimens. A comparative pharmacotherapeutic efficacy assessment was made from the complete recovery time-periods, including the residual recovery time-periods. The chronopharmacovigilance assessment was made by adverse effects occurrence monitoring during treatment period or follow-up, with an Adverse Event Case Report Form. Results: The residual recovery time-periods, in group A=0 days, group B=2 days, group E=3 days, group D=3 days, and group C=7 days. Adverse effects were not statistically significant, with a predictable chronopharmacovigilance illustration.Conclusions: The pharmacotherapeutic efficacy of ofloxacin was more for treating group A, followed by group B, followed by group E and group D, and finally followed by group C. Ofloxacin was safe, without any pharmacogenomic or pharmacogeographic heterogeneity related fluctuation.

Micronized Resveratrol Shows Anticonvulsant Properties in Pentylenetetrazole-Induced Seizure Model in Adult Zebrafish.

Epilepsy affects 50 million people around the world, and the patients experience cognitive, psychological and social consequences. Despite the considerable quantity of antiepileptic drugs available, 30% of patients still suffer in seizure. Therefore, the advance in therapeutic alternatives is mandatory. Resveratrol has been attracting the attention of many researchers because of its pharmacological potential. However, despite its neuroprotective and anti-epileptic effects, clinical resveratrol use is impaired by its low bioavailability. Here, we applied the supercritical fluid micronization technology (SEDS) to overcome this deficit, and investigated the anticonvulsant potential of micronized resveratrol in a PTZ-induced seizure model in adult zebrafish (Danio rerio). SEDS permits obtaining significantly reduced particle size with a fine size distribution in comparison with the starting material. It can improve the pharmacotherapeutic efficacy. Our data showed that micronized resveratrol decreased the occurrence of the tonic-clonic seizure stage and slowed the development of the seizures in a similar manner of diazepam. Non-processed resveratrol was not able to protect the animals. Furthermore, diazepam decreased the locomotion and exploratory behavior. Differently from diazepam, the micronized resveratrol did not induce behavioral adverse events. In addition, our data showed that the PTZ-induced seizures increased the c-fos transcript levels following the neural excitability. However, the increase in c-fos levels was prevented by micronized resveratrol. In conclusion, our results demonstrate that the micronized resveratrol shows anticonvulsant effect, like the classical antiepileptic drug diazepam in a PTZ-induced seizure model. Excitingly, different from diazepam, micronized resveratrol did not provoke behavioral adverse events.

Modern opportunities for treatment and prevention of NSAID-induced enteropathies

Nonsteroidal anti-inflammatory drugs (NSAIDs) are currently actively used in real clinical practice and everyday life with a wide range of pathological conditions and diseases, and are part of the medicinal arsenal of doctors of various specialties. Along with high pharmacotherapeutic efficacy according to the main indications, a whole range of various complications is associated with the use of NSAIDs. Of particular relevance is the negative specific effect of NSAIDs on the mucous membrane of the gastrointestinal tract. The problem of NSAID gastropathy is widely discussed in the literature, which is largely due to the possibilities of its prevention and treatment using proton pump inhibitors. For a long time, much less attention was paid to the issues of NSAID-dependent bowel damage, which may be associated with less instrumental diagnostic capabilities of these lesions and the lack of effective means for their prevention and treatment. The review presented addresses the pathogenesis, clinical features and diagnosis of NSAID enteropathy. Proton pump inhibitors effectively prevent the development of dyspepsia, erosion and ulcers, as well as gastrointestinal bleeding when taking NSAIDs at the level of the upper gastrointestinal tract, but they are ineffective in preventing and treating NSAID enteropathy. A new approach is the use of rebamipide, which has proven its clinical effectiveness in the prevention of NSAID-mediated Lesions in the upper and Lower gastrointestinal tract. Currently, rebamipid is included in the recommendations of the leading specialized communities in Russia and is recommended not only for the prevention and treatment of NSAIDs induced gastrointestinal lesions, but also as part of the complex therapy of peptic ulcer and anti-heLicobacter therapy. The review reviewed studies showing the efficacy and safety of rebamipide for the treatment and prevention of NSAID enteropathy.

Hepatoprotective activity of Ficus semicordata Buch.-Ham. ex Sm. leaves aqueous extract on D-galactosamine induced toxicity in HepG2 cell line

The leaves of Ficus semicordata Buch-Ham.ex Sm., locally in North India is referred to as Bhumi udumbara have been reported for their traditional use to cure jaundice and various liver ailments. Despite its extensive usage in northeastern states of India, there is a lack of scientific substantiation on the safety and pharmacotherapeutic efficacy. The present study was carried out to evaluate the hepatoprotective activity of F. semicordata (FS) leaves aqueous extract on HepG2 cell line to validate its ethnic claim in the management of liver disorders. D-galactosamine induced HepG2 cell toxicity model was used to evaluate its hepatoprotective activity. The cells were treated with different concentrations of aqueous extracts and dexamethasone as a standard. MTT assay was performed to determine the % inhibition of hepatotoxicity. The result indicates that the toxicity induced by D-galactosamine is reduced by FS aqueous extract group which is better when compared with the standard drug. This study revealed the hepatoprotective potential of F. semicordata on HepG2 cell line.

ДОСЛІДЖЕННЯ ГІПОЛІПІДЕМІЧНОЇ ДІЇ ПРИ КУРСОВОМУ ПРИЗНАЧЕННІ ЕКСТРАКТІВ ТРАВИ Verbena officinalis L.

Мета роботи. Дослідження впливу екстрактів трави Verbena officinalis L. на рівень ліпідів в крові піддослідних тварин на моделі атеросклеротичної гіперліпідемії. Матеріали і методи. Дослідження впливу екстрактів трави Verbena officinalis L. на рівень фракцій ліпідів у крові піддослідних білих щурів проводили в умовах тритонової моделі гіперліпідемії. Про фармакотерапевтичну ефективність досліджуваних екстрактів робили висновок на основі біохімічних, морфологічних та гістологічних показників. Результати й обговорення. Отримані результати вивчення біохімічних показників крові щурів свідчать, що при курсовому, протягом 10 днів, введенні стандартизованих екстрактів трави Verbena officinalis L. тваринам із модельованою тритоном WR-1339 атеросклеротичною гіперліпідемією, спостерігалося зниження рівня ліпідного складу крові. Висновки. В результаті вивчення динаміки біохімічних показників крові щурів із атеросклеротичною гіперліпідемією, змодельованою тритоном WR-1339, при курсовому призначенні екстрактів із трави Verbena officinalis L. встановлено, що застосування екстрактів зменшує рівень ліпідів крові, а саме загальних ліпідів, β-ліпопротеїнів, тригліцеролів, загального холестеролу, а також показників загального протеїну, сечовини, АлАТ і АсАТ. Найбільш виражену дію проявляє водно-спиртовий екстракт трави Verbena officinalis L.

Фармако-математичний аналіз залежності «структура – активність» координаційних сполук германію за синдрому тривалого розчавлювання

Мета дослідження – провести комплексний порівняльний фармако-математичний аналіз ефективності координаційних сполук германію з біолігандами у посткомпресійному періоді на підставі результатів скринінгу потенційних засобів фармакотерапії наслідків синдрому тривалого розчавлювання (СТР). Експериментальною моделлю ендотоксикозу посттравматичного генезу був патологічний процес, який розвивався у тварин у результаті розчавлювання м’яких тканин задніх кінцівок протягом 5 год у спеціальному приладі з манометричним контролем тиску. Кількісними критеріями фармакотерапевтичної ефективності досліджуваних сполук в умовах ендотоксикозу на тлі СТР були концентрація кінцевих продуктів перекисного окиснення ліпідів (ПОЛ), що реагують з 2-тіобарбітуровою кислотою (ТБК-реактанти) у гомогенаті печінки щурів і рівень молекул середньої маси (МСМ) у сироватці крові щурів. Кореляційні залежності «структура – активність» проводили за методом найменших квадратів. За результатами скринінгової серії досліджень потенційних засобів фармакотерапії наслідків СТР проведений комплексний фармако-математичний аналіз активності координаційних сполук германію з біолігандами. Показано, що ефективна детоксикація організму за умов СТР притаманна сполукам германію з комплексним органічним аніоном – (Мігу-4-6,8,9). Максимальну здатність зменшувати вміст універсальних маркерів ендогенної інтоксикації проявила сполука (Мігу-6), у разі введення якої рівень МСМ знижується в 2 рази, а концентрація ТБК-реактантів знижується в 4,4 разу порівняно з контрольною групою. Показано, що між концентрацією ТБК-реактантів у гомогенаті печінки щурів і вмістом МСМ у сироватці крові щурів існує залежність, коефіцієнти кореляції (детермінації) якої змінюються в незначному ступені за порівняння різних груп без тіотриазоліну та таких, що містять і тіотриазолін, зокрема, коефіцієнт лінійної кореляції для групи А та групи А1 становить 0,986 і 0,908 відповідно. Отримані дані вказують на правильність вибору тіотриазоліну як препарату порівняння за умов екстремального стану, що вивчається, та можуть бути фармако-математичним обґрунтуванням доцільності його використання на етапі клінічних досліджень. Залежність показників МСМ і ТБК-реактантів від кількості акцепторів та донорів водневого зв'язку, дипольного моменту, енергій ван-дер-ваальсових та електростатичних взаємодій характеризується показниками – коефіцієнтами кореляції та детермінації (rxy, R2) різного рівня. Для показника МСМ найхарактернішим є зв'язок з акцепторами водневого зв'язку (rxy = 0,931, група С), тоді як для показника ТБК-реактантів зв'язок з акцепторами водневого зв'язку характеризується значенням rxy на рівні 0,481 (група С).

Cerebrospinal Fluid Proteomics For Identification Of α2-Macroglobulin As A Potential Biomarker To Monitor Pharmacological Therapeutic Efficacy In Dopamine Dictated Disease States Of Parkinson's Disease And Schizophrenia.

AimParkinson’s disease and schizophrenia are clinical end points of dopaminergic deficit and excess, respectively, in the mid-brain. In accordance, current pharmacological interventions aim to restore normal dopamine levels, the overshooting of which culminates in adverse effects which results in psychotic symptoms in Parkinson’s disease and extra-pyramidal symptoms in schizophrenia. Currently, there are no laboratory assays to assist treatment decisions or help foresee these drug side-effect outcomes. Therefore, the aim was to discover a protein biomarker that had a varying linear expression across the clinical dopaminergic spectrum.Materials and methodsiTRAQ-based proteomic experiments along with mass spectrometric analysis was used for comparative proteomics using cerebrospinal fluid (CSF). CSF fluid was collected from 36 patients with Parkinson’s disease, 15 patients with urological diseases that served as neurological controls, and seven schizophrenic patients with hallucinations. Validation included ELISA and pathway analysis to highlight the varying expression and provide plausible molecular pathways for differentially expressed proteins in the three clinical phenotypes.ResultsProtein profiles were delineated in CSF from Parkinson’s disease patients, neurological control and schizophrenia, respectively. Ten of the proteins that were identified had a linear relationship across the dopaminergic spectrum. α-2-Macroglobulin showed to be having high statistical significance on inter-group comparison on validation studies using ELISA.ConclusionsNon-gel-based proteomic experiments are an ideal platform to discover potential biomarkers that can be used to monitor pharmaco-therapeutic efficacy in dopamine-dictated clinical scenarios. α-2 Macroglobulin is a potential biomarker to monitor pharmacological therapy in Parkinson’s disease and schizophrenia.