Auxiliary Drugs Research Articles

Robotic Actuation-Mediated Quantitative Mechanogenetics for Noninvasive and On-Demand Cancer Therapy.

Cell mechanotransduction signals are important targets for physical therapy. However, current physiotherapy heavily relies on ultrasound, which is generated by high-power equipment or amplified by auxiliary drugs, potentially causing undesired side effects. To address current limitations, a robotic actuation-mediated therapy is developed that utilizes gentle mechanical loads to activate mechanosensitive ion channels. The resulting calcium influx precisely regulated the expression of recombinant tumor suppressor protein and death-associated protein kinase, leading to programmed apoptosis of cancer cell line through caspase-dependent pathway. In stark contrast to traditional gene therapy, the complete elimination of early- and middle-stage tumors (volume ≤ 100mm3) and significant growth inhibition of late-stage tumor (500mm3) are realized in tumor-bearing mice by transfecting mechanogenetic circuits and treating daily with quantitative robotic actuation in a form of 5min treatment over the course of 14days. Thus, this massage-derived therapy represents a quantitative strategy for cancer treatment.

Determining knowledge of antimicrobial therapy in senior medical students (results of the KANT-IV project)

Objective. To determine the level of basic knowledge of 5–6-year medical students in the issues of appropriate antimicrobial therapy. Materials and Methods. A multicenter questionnaire survey with analysis of results – stage of KANT project (full name of the project – «Physicians’ (Students’) knowledge in antimicrobials usage») conducted in 2020-2023. Results. A total of 277 students in 6 regions of Russia were surveyed. The average level of correct answers for the whole questionnaire amounted to 42.2%, taking into account the extended analysis of sub-items questions #8,9 – 42.6%. The respondents were best able to answer the questionnaire questions about the choice of time interval during which the effectiveness of antimicrobial therapy is assessed (average level of completeness of the answer – 90.6%); the choice of the most rational action when diagnosing acute tonsillitis or pharyngitis at the appointment (average level of completeness of the answer – 57.8%); indication of the regimen of different AMD (average level of completeness of the answer – 55.2%). The worst results were recorded when answering the following questions: justification of the situation of prolongation of antimicrobial therapy (AMT) for more than 5-7 days in a patient with positive clinical dynamics in the treatment of outpatient pneumonia (average level of completeness of the answer – 19.5%), indication of AMD of choice in the therapy of various infections (average level of completeness of the answer – 22.9%), prescription of auxiliary drugs to the justified prescription of AMD in the treatment of respiratory tract infections (average level of completeness of the answer – 21.3%). Conclusions. Having researched the results of this study, we can conclude that the level of knowledge of senior medical students in rational antibiotic therapy is quite low. In this regard, according to the authors, it is necessary to allocate an additional number of academic hours in the disciplines of «Pharmacology», «Clinical Pharmacology», specialized therapeutic disciplines, to optimize the educational program, as well as to provide students with modern sources of information that relate to the topic of rational antimicrobial therapy.

Determining knowledge of antimicrobial therapy in practitioners (results of the KANT-IV project)

Objective. To determine the level of knowledge of doctors on the rational use of antimicrobial drugs in clinical practice and to compare with data of the previous stage of the study and results obtained from students in a parallel project. Materials and Methods. A multicenter questionnaire survey of practitioners with analysis of results – stage of KANT project (full name of the project – «Physicians’ (Students’) knowledge in antimicrobials usage») conducted in 2020–2023. Results. A total of 336 participants were surveyed in 5 centers (10 Russian regions: Belgorod, Novosibirsk, Rostov, Voronezh, Lipetsk, Sakhalin, Primorsky, Krasnodar, and Krasnoyarsk regions, Republic of Tatarstan). The average level of correct answers (LCA) for the whole questionnaire was 47.5% (taking into account the extended analysis of sub-items questions No. 8 and 9 – 46.8%). Doctors showed the best results in answering questions about the time interval during which the effectiveness of antimicrobial therapy is evaluated (LCA – 84.2%); about choosing the most rational action if antimicrobial therapy (AMT) has a positive clinical effect, but requires a long course of therapy (LCA – 72.6%); selection of rational diagnostic/treatment action in the diagnosis of acute tonsillitis or pharyngitis, in a case where etiologic diagnosis is required (LCA – 63.1%). The worst results were recorded in answering to the following questions: indication of the antimicrobial drug of choice in the treatment of various infections (LCA – 29.1%); the choice of auxiliary drugs in addition to the justified appointment of antimicrobial drugs in the treatment of bacterial infections of the respiratory tract for the entire period of the disease or in certain phases (LCA – 26.6% – 35.1%); indication of a combination of antimicrobial drugs that is irrational to prescribe in clinical practice due to a similar mechanism and/or spectrum of activity against pathogens (LCA – 24.4%). Significant differences were found between centers in a number of questions, between physicians in KANT-III and KANT-IV projects (p < 0.001), and between physicians and students in a parallel project (KANT-IV students, LCA – 42.6%, p < 0.001). Conclusions. An unsatisfactory level of physicians’ knowledge of AMT and choice of adjuvant agents, as well as appropriateness of antimicrobial combination was found. The authors believe there is a need for making more efforts in areas of increasing physicians’ compliance to clinical recommendations, expertise and quality control of pharmacotherapy, recruitment of clinical pharmacologists; to optimize the educational process in universities, to expand the scope and availability of additional educational programs within the system of continuous education, as well as to train physicians in using modern sources of scientific medical information.

A structural atlas of druggable sites on Nav channels

ABSTRACT Voltage-gated sodium (Nav) channels govern membrane excitability by initiating and propagating action potentials. Consistent with their physiological significance, dysfunction, or mutations in these channels are associated with various channelopathies. Nav channels are thereby major targets for various clinical and investigational drugs. In addition, a large number of natural toxins, both small molecules and peptides, can bind to Nav channels and modulate their functions. Technological breakthrough in cryo-electron microscopy (cryo-EM) has enabled the determination of high-resolution structures of eukaryotic and eventually human Nav channels, alone or in complex with auxiliary subunits, toxins, and drugs. These studies have not only advanced our comprehension of channel architecture and working mechanisms but also afforded unprecedented clarity to the molecular basis for the binding and mechanism of action (MOA) of prototypical drugs and toxins. In this review, we will provide an overview of the recent advances in structural pharmacology of Nav channels, encompassing the structural map for ligand binding on Nav channels. These findings have established a vital groundwork for future drug development.

Suppressive stroma-immune prognostic signature impedes immunotherapy in ovarian cancer and can be reversed by PDGFRB inhibitors

BackgroundAs the most lethal gynecologic cancer, ovarian cancer (OV) holds the potential of being immunotherapy-responsive. However, only modest therapeutic effects have been achieved by immunotherapies such as immune checkpoint blockade. This study aims to propose a generalized stroma-immune prognostic signature (SIPS) to identify OV patients who may benefit from immunotherapy.MethodsThe 2097 OV patients included in the study were significant with high-grade serous ovarian cancer in the III/IV stage. The 470 immune-related signatures were collected and analyzed by the Cox regression and Lasso algorithm to generalize a credible SIPS. Correlations between the SIPS signature and tumor microenvironment were further analyzed. The critical immunosuppressive role of stroma indicated by the SIPS was further validated by targeting the major suppressive stroma component (CAFs, Cancer-associated fibroblasts) in vitro and in vivo. With four machine-learning methods predicting tumor immune subtypes, the stroma-immune signature was upgraded to a 23-gene signature.ResultsThe SIPS effectively discriminated the high-risk individuals in the training and validating cohorts, where the high SIPS succeeded in predicting worse survival in several immunotherapy cohorts. The SIPS signature was positively correlated with stroma components, especially CAFs and immunosuppressive cells in the tumor microenvironment, indicating the critical suppressive stroma-immune network. The combination of CAFs’ marker PDGFRB inhibitors and frontline PARP inhibitors substantially inhibited tumor growth and promoted the survival of OV-bearing mice. The stroma-immune signature was upgraded to a 23-gene signature to improve clinical utility. Several drug types that suppress stroma-immune signatures, such as EGFR inhibitors, could be candidates for potential immunotherapeutic combinations in ovarian cancer.ConclusionsThe stroma-immune signature could efficiently predict the immunotherapeutic sensitivity of OV patients. Immunotherapy and auxiliary drugs targeting stroma could enhance immunotherapeutic efficacy in ovarian cancer.

Effect of Betanin, the Major Pigment of Red Beetroot (Beta vulgaris L.), on the Activity of Recombinant Human Cytochrome P450 Enzymes.

Most of the currently available drugs are derived from natural sources, but they are used only after extensive chemical modifications to improve their safety and efficacy. Natural products are used in health supplements and cosmetic preparations and have been used as auxiliary drugs or alternative medicines. When used in combination with conventional drugs, these herbal products are known to alter their pharmacokinetics and pharmacodynamics, reducing their therapeutic effects. Moreover, herb-drug interactions (HDIs) may have serious side effects, which is one of the major concerns in health practice. It is postulated that HDIs affect the pathways regulating cytochrome P450 enzymes (CYPs). Betanin, the chief pigment of red beetroot (Beta vulgaris L.), has various types of pharmacological activity, such as anti-inflammatory, antioxidant, and anticancer effects. However, the potential risk of HDIs for betanin has not yet been studied. Thus, we aimed to predict more specific HDIs by evaluating the effects of betanin on CYPs (CYP1A2, CYP2B6, CYP2C9, CYP2C19, CYP2D6, and CYP3A4), the major phase I metabolic enzymes, using fluorescence-/luminescence-based assays. Our results showed that betanin inhibited CYP3A4 activity in a dose-dependent manner (IC50 = 20.97 µΜ). Moreover, betanin acted as a competitive inhibitor of CYP3A4, as confirmed by evaluating Lineweaver-Burk plots (Ki value = 19.48 µΜ). However, no significant inhibitory effects were observed on other CYPs. Furthermore, betanin had no significant effect on CYP1A2, CYP2B6, or CYP2C9 induction in HepG2 cells. In conclusion, betanin acted as a competitive inhibitor of CYP3A4, and thus it should be used cautiously with other drugs that require metabolic enzymes as substrates. Additional in vivo studies and clinical trials are needed to further elucidate the HDIs of betanin.

Evaluation of α-Glucosidase Inhibition and Antihyperglycemic Activity of Extracts Obtained from Leaves and Flowers of Rumex crispus L.

Among antihyperglycemic drugs used for treating diabetes, α-glucosidase inhibitors generate the least adverse effects. This contribution aimed to evaluate the potential antidiabetic activity of Rumex crispus L. by testing its in vitro α-glucosidase inhibition and in vivo antihyperglycemic effects on rats with streptozotocin (STZ)-induced diabetes. Better inhibition of α-glucosidase was found with the methanol extract versus the n-hexane and dichloromethane extracts. The methanol extract of the flowers (RCFM) was more effective than that of the leaves (RCHM), with an IC50 of 7.3 ± 0.17 μg/mL for RCFM and 112.0 ± 1.23 μg/mL for RCHM. A bioactive fraction (F89s) also showed good α-glucosidase inhibition (IC50 = 3.8 ± 0.11 μg/mL). In a preliminary study, RCHM and RCFM at 150 mg/kg and F89s at 75 mg/kg after 30 days showed a significant effect on hyperglycemia, reducing glucose levels (82.2, 80.1, and 84.1%, respectively), and improved the lipid, renal, and hepatic profiles of the rats, comparable with the effects of metformin and acarbose. According to the results, the activity of R. crispus L. may be mediated by a diminished rate of disaccharide hydrolysis, associated with the inhibition of α-glucosidase. Thus, R. crispus L. holds promise for the development of auxiliary drugs to treat diabetes mellitus.

Study on the awareness and its influencing factors of patients with pulmonary tuberculosis on preferential policies for tuberculosis prevention and treatment in Shandong, China.

We investigated the awareness and its influencing factors of patients with pulmonary tuberculosis on preferential policies for tuberculosis prevention and treatment in Shandong, China. A total of 858 patients with pulmonary tuberculosis between January 1, 2018 and September 30, 2019 were surveyed with questionnaires. The basic information (age, sex, education level, family financial situation, disease and diagnosis and treatment, etc), policy awareness, and satisfaction survey status, etc of these 858 tuberculosis patients were collected and analyzed with SPSS software (Chicago, IL) The awareness of tuberculosis patients on preferential policies for tuberculosis prevention and treatment was acceptable with awareness rate of 75.17% (645/858), but their satisfaction with the current policies was not ideal. Debt status and total household assets were the influencing factors of awareness (P < .01). Patients with pulmonary tuberculosis expected to get more free items and lower-cost auxiliary drugs. Patients with pulmonary tuberculosis have different levels of awareness on preferential policies for tuberculosis prevention and treatment. Therefore, targeted promotion of preferential policies for tuberculosis prevention and treatment and different management methods for different patients are of great significance to the treatment of tuberculosis epidemics.

Ameliorative effect of Berberidis radix polysaccharide selenium nanoparticles against carbon tetrachloride induced oxidative stress and inflammation.

Berberidis radix polysaccharide (BRP) extracted as capping agents was applied to prepare BRP-selenium nanoparticles (BRP-SeNPs) in the redox reaction system of sodium selenite and ascorbic acid. The stability and characterization of BRP-SeNPs were investigated by physical analysis method. The results revealed that BRP were tightly wrapped on the surface of SeNPs by forming C-O⋯Se bonds or hydrogen bonding interaction (O-H⋯Se). BRP-SeNPs presented irregular, fragmented and smooth surface morphology and polycrystalline nanoring structure, and its particle size was 89.4nm in the optimal preparation condition. The pharmacologic functions of BRP-SeNPs were explored in vitro and in vivo. The results showed that BRP-SeNPs could heighten the cell viabilities and the enzyme activity of GSH-Px and decrease the content of MDA on H2O2-induced AML-12 cells injury model. In vivo tests, the results displayed that BRP-SeNPs could increase the body weight of mice, promote the enzyme activity like SOD and GSH-Px, decrease the liver organ index and the hepatic function index such as ALT, AST, CYP2E1, reduce the content of MDA, and relieve the proinflammation factors of NO, IL-1β and TNF-α in CCl4-induced mice injury model. Liver tissue histopathological studies corroborated the improvement of BRP-SeNPs on liver of CCl4-induced mice. The results of Western blot showed that BRP-SeNPs could attenuate oxidant stress by the Nrf2/Keap1/MKP1/JNK pathways, and downregulate the proinflammatory factors by TLR4/MAPK pathway. These findings suggested that BRP-SeNPs possess the hepatoprotection and have the potential to be a green liver-protecting and auxiliary liver inflammation drugs.

Auxiliary Pain Killer Drugs: Versatile Medications for Pain Management

The Article Abstract is not available.

A mathematical model of reward-mediated learning in drug addiction.

Substances of abuse are known to activate and disrupt neuronal circuits in the brain reward system. We propose a simple and easily interpretable dynamical systems model to describe the neurobiology of drug addiction that incorporates the psychiatric concepts of reward prediction error, drug-induced incentive salience, and opponent process theory. Drug-induced dopamine releases activate a biphasic reward response with pleasurable, positive "a-processes" (euphoria, rush) followed by unpleasant, negative "b-processes" (cravings, withdrawal). Neuroadaptive processes triggered by successive intakes enhance the negative component of the reward response, which the user compensates for by increasing drug dose and/or intake frequency. This positive feedback between physiological changes and drug self-administration leads to habituation, tolerance, and, eventually, to full addiction. Our model gives rise to qualitatively different pathways to addiction that can represent a diverse set of user profiles (genetics, age) and drug potencies. We find that users who have, or neuroadaptively develop, a strong b-process response to drug consumption are most at risk for addiction. Finally, we include possible mechanisms to mitigate withdrawal symptoms, such as through the use of methadone or other auxiliary drugs used in detoxification.

Object Oriented Programming Untuk Sistem Informasi Pencatatan Hutang Dalam Pengadaan Obat Pada Rsud X

In the drug procurement process, there is no specific record of debt by the Pharmacy section or by the Finance Sector. The records that are trying to be done are like payment receipts from the Finance Sector paying invoices from the drug industry that have provided drugs to the Pharmacy Section. So that the financial sector in managing debt as well as in recognizing debt and the maturity of debt payments of each supplier. With these obstacles, the RSUD requires an Information System for Recording Debts in Procurement of Auxiliary Drugs for the Pharmaceutical Sector and the Financial Sector in recording Debts, especially in the procurement of Drugs. This data system uses object-oriented programming with a SQL Server database to create an information system that can speed up the forest recording process in drug procurement&#x0D; &#x0D; Keywords: Object Oriented Programing, hutang, RSUD

Management and Control Platform of Auxiliary Drugs Based on Big Data

In recent years, with the introduction of national, provincial and municipal policies, rules and regulations, and the introduction of big data technology, drug control personnel have further increased their awareness of data. However, in practice, how to carefully control drugs and make full use of big data technology to improve the level of control has become a new confusion for drug control personnel. Therefore, the purpose of this paper is to study the platform of auxiliary drug control based on big data. Based on the actual situation of drug use, this paper analyzes the main problems in the process of drug control, and designs an auxiliary drug control platform based on big data. The auxiliary drug management and control platform based on big data proposed in this paper can collect data in real time, comprehensively analyze all kinds of information, and realize intelligent management and improve the efficiency of each specific application scenario. In this paper, through the research of drug use management and control platform, doctors can get scientific guidance in formulating drug use plan, and the efficiency of drug query is improved by about 80% compared with the traditional plan. At the same time, the drug use plan can be improved in time according to the patient’s illness development in the process of drug use, which promotes the rational and standardized clinical application of drugs.

Metabolic diversity as a reason for unsuccessful detoxification from benzodiazepines: the rationale for serum BZD concentration monitoring.

Many harms secondary to benzodiazepine (BZD) dependence force users towards detoxification treatment. However, even strongly motivated patients tolerate the process badly or experience early relapse. The detoxification procedure has not yet been standardized. The objective of this paper is to examine the hypothesis that faulty detoxification routines may have caused some failures. The detoxification approaches found in the literature were compared stage by stage. The review was used to identify possible common, across-the-board systematic errors. The presented literature review confirms that the widespread divergence in the BZD metabolism rate is effectively neglected during detoxification routines. Without laboratory measurements, these differences, additionally interfered with by auxiliary drugs, undermine not only the scheduled but even the symptom-driven procedures. An initial substitution with a long-acting BZD, although recommended, may lead to over-accumulation. This excess, varying between patients and incompatible with the current tapering stage, may lead to repeated overestimation of the patient's adjustments to reduced doses. Consequently, the patient's good clinical presentation at withdrawal, resulting in a conclusion of detoxification, may actually reflect a persistently high serum BZD concentration. The low-concentration stage, if shifted past the end of treatment, exposes patients to unexpected, unassisted withdrawal crises. With laboratory feedback, these crises, unlike the symptoms related to deficient re-adaptation mechanisms, could be prevented. Moreover, by minimizing the high-concentration phase, time can be saved for properly assisted low-concentration challenges. A customized detoxification procedure driven not only by the intensity of withdrawal symptoms but also by serum BZD monitoring may prevent some failures. As the standard regimen, it would make detoxification from BZDs more reliable and effective.

Збереження протимікробної активності метаболітних комплексів Lactobacillus rhamnosus та Saccharomyces boulardii після кріоконсервування

The paper demonstrates an antimicrobial effect of metabolite complexes of Lactobacillus rhamnosus GG and Saccharomyces boulardii, obtained by own method, after 6 months’ storage in a frozen state (−23 ± 1ºС) in respect of Staphylococcus aureus, Staphylococcus haemoliticus, Enterococcus faecalis, Corynebacterium xerosis with multidrug resistance. Increase in diameters of growth inhibition zones (by (3.0 ± 0.4)–(6.1 ± 0.3) mm) for all the investigated pathogens under the influence of metabolite complexes (freshly obtained and after storage) with azithromycin has been proven. No significant difference in antimicrobial activity of antibacterial agents with freshly obtained complexes and after storage at (−23 ± 1)°C was found. The expediency of using the chosen storage method to design the brand new products as well as development of ‘auxiliary drugs’ for antibiotics was confirmed.

Use of Andrographis paniculata (Burm. f.) Nees for Treating Hepatitis

Andrographis paniculata (Burm. f.) Nees (APN) is a medicinal plant widely used in Asian countries. APN is used for its anti-inflammatory and antiviral properties. Previous studies did not clarify its pathway to treat hepatitis under the next generation of natural antibiotics. No definite trend has found expression in the multi-component Chinese medicine (MCCM). Besides, the research and development of a particular component in APN can not cover the most pharmacological effects of APN treating hepatitis. Based on the current information biology data, this review found that the intersection number of APN and hepatitis were 1,016 from 3,922 APN PPI targets and 1,818 hepatitis targets, respectively, according to current data. The filtered prediction outcome suggests that the MCCM of APN treating hepatitis were wogonin, oroxylin A, and andrographolide, which accounted for more than 95% of the compound contribution index of APN treating hepatitis. The predicated primary related pathways were the Notch, thyroid hormone, hepatitis B, and prolactin signalling pathways. This review serves to summarize the current research on APN to indicate a specific research direction to determine the pharmacological mechanism of APN and the interaction between drug targets and disease targets, laying a foundation for the subsequent development of its MCCM, new drugs, and auxiliary drugs.

Rational antimicrobial chemotherapy: assessment of the level of basic knowledge of general practitioners. Final results of the KANT project

Introduction: The irrational use of medicines leads to a decrease in the quality of care, an increase in treatment costs and side effects. In the case of antibacterial drugs, in addition to all the above-mentioned consequences, their improper use can lead to an aggravation of the existing and quite challenging problem of our time – the growth of antibiotic resistance among pathogenic microorganisms.&#x0D; The aim of the study: to determine the level of basic knowledge of medical specialists in the field of a rational use of antimicrobial drugs (AMD).&#x0D; Materials and methods: The study was based on an analysis of an anonymous multicenter survey in the framework of the KANT project (the full name of the project is “Physicians’ (Students’) Knowledge of Antimicrobials Usage”). It was conducted in 2018–2019 in 10 major centers of Russia.&#x0D; Results and iscussion: According to the results of the study, the respondents showed a low level of knowledge of the rational use of antibacterial drugs. The best results are obtained for questions No.1 (time interval for evaluating the effectiveness of the initial antimicrobial therapy (AMT)), No.2 (rationality and period of AMD change with a positive clinical effect), and No.9 (determining the mode of using the proposed drugs), whereas the worst results were obtained for questions No.3 (determining irrational combinations of AMD), No.4 (determining a situation requiring a long course of AMT), and No.7 (choosing auxiliary drugs for bacterial respiratory infections).&#x0D; Conclusion: The results obtained in the study indicate the need for additional educational activities among health professionals.

Ulinastatin alleviates cerebral ischemia-reperfusion injury in rats by activating the Nrf-2/HO-1 signaling pathway.

BackgroundUlinastatin, a urinary trypsin inhibitor, is one of the widely used auxiliary drugs in the rescue of acute circulatory failure. This study aims to explore the protective mechanisms of ulinastatin on cerebral ischemia-reperfusion (I/R) injury.MethodsA cerebral MCAO was established with middle cerebral artery occlusion (MCAO) in Sprague Dawley (SD) rats. Western blotting was employed to show protein expression. Oxidative stress markers [reactive oxygen species (ROS), superoxide dismutase (SOD), malondialdehyde (MDA), and glutathione (GSH)] and inflammatory cytokines (IL-6, IL-1β, and IL-18) were analyzed to show oxidative stress and inflammation. Hematoxylin and eosin (HE) and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) and triphenyltetrazolium chloride (TTC) staining were applied to show brain injury.ResultsHE, TUNEL and TTC staining indicated that ulinastatin significantly ameliorated cerebral I/R injury and reduced apoptotic cells in the MCAO brain tissue. Ulinastatin also reduced the MCAO-induced expression of intercellular adhesion molecule 1(ICAM-1)/caspase-3. Additionally, the highly expressed ROS, MDA and inflammatory cytokines (IL-6, IL-1β and IL-18) were significantly suppressed, and the inhibited SOD and GSH were recovered with ulinastatin treatment. Consequently, the expression of nuclear factor erythroid-2-related factor 2 (Nrf2)/heme oxygenase-1 (HO-1) (which was significantly inhibited by MCAO) was re-activated by ulinastatin and/or TBHQ (an Nrf-2 activator), and treatment with ML-385 (an Nrf-2 inhibitor) blocked the inhibition of apoptosis, inflammation, and oxidative stress by ulinastatin. Our results indicate that the Nrf-2/HO-1 signaling pathway may be involved in the pharmacological mechanism of ulinastatin in cerebral I/R injury.ConclusionsUlinastatin protected against inflammation and oxidative stress in cerebral I/R injuries via activation of the Nrf-2/HO-1 signaling pathway.

Similarities and differences between Ginkgo biloba and Panax notoginseng in treatment of ischemic cerebrovascular disease

Ginkgo biloba and Panax notoginseng are both herb medicines for cerebrovascular disease, and play an active role in treating ischemic cerebrovascular disease(ICVD). Their mechanisms of action include antioxidant stress, nerve protection, vascular protection. According to the comparative study of literatures, G. biloba has a certain protective effect from the early stage of free radical formation throughout the whole process of causing cell inflammation and apoptosis in antioxidant stress; while P. notoginseng has mainly anti-inflammatory, anti-apoptosis effects. In the nerve protection and repair of nerve damage caused by glutamate, both could promote neurogenesis, repair damaged axons and protect nerve cells. In addition, G. biloba could also relieve neurotoxicity caused by glutamate damage, while P. notoginseng have a unique effect in repairing blood-brain barrier(BBB) and blood vessel regeneration. In clinic, they are used as auxiliary drugs in combination with thrombolytic therapy, and play curative effects in alleviating inflammation, eliminating edema, improving the cure rate and the prognosis. For cerebral diseases caused by chronic cerebral hypoperfusion, G. biloba could reduce inflammation and improve cognition. In addition, G. biloba could protect neurocyte by adjusting the secretion of dopamine in vivo, and has a certain effect on antidepressant diseases, which however needs further studies.

Sequential analysis for median effective dose of Dexmedetomidine in upper limb Lidocaine intravenous regional anesthesia

ABSTRACT Background Auxiliary drugs augment the effect of local anesthetic in intravenous regional anesthesia (IVRA). The aim of our study was to estimate the median effective dose (ED50) of Dexmedetomidine in elective upper limb Lidocaine 0.5% IVRA. Method A prospective, double-blind, sequential study using modified Dixon’s up and down method. Thirty patients scheduled for minor upper limb surgeries were recruited in the Study, however, we ended up analyzing data of 26 patients due to protocol violation. The first patient in this sequential trial was randomly selected and received a mixed solution of 0.5% lidocaine and 0.4 µg/kg of dexmedetomidine, with 0.1 µg/kg dose interval. If IVRA outcome was satisfactory, the dose went down for the next patient by 0.1 µg/kg. Vice versa, if the outcome was unsatisfactory, the dexmedetomidine dose was stepped up by 0.1 µg/kg. Sensory and motor block onset, recovery times, hemodynamic variables, surgical and tourniquet VAS scores and time to first analgesic request were recorded. Results The series of patient responses to IVRA was satisfactory in 11 patients (42.3%) and unsatisfactory in 15 patients (57.6%) due to either surgical pain in 6 patients or tourniquet pain in the remaining 9 patients. In patients with satisfactory response to IVRA, intraoperative and postoperative mean arterial pressure and heart rate, compared with baseline (just prior to inflating the proximal cuff) measurement, showed no statistically significant differences (P = 0.754 and 0.324, respectively). Intergroup comparison of Patients with unsatisfactory response to IVRA time to first analgesic request showed no statistical difference (P > 0.05). Conclusion the ED 50 of Dexmedetomidine (95% confidence interval, CI) as adjuvant for satisfactory 0.5% lidocaine IVRA was 0.7 µg/kg (0.6–0.8).