Pharmacological Substances Research Articles

Antimicrobial activity of a novel Spanish propolis against planktonic and sessile oral Streptococcus spp

Increased bacterial resistance to traditional antimicrobial agents has prompted the use of natural products with antimicrobial properties such as propolis, extensively employed since ancient times. However, the chemical composition of propolis extracts is extremely complex and has been shown to vary depending on the region and season of collection, due to variations in the flora from which the pharmacological substances are obtained, being therefore essential for their antimicrobial activity to be checked before use. For this purpose, we evaluate the in vitro antimicrobial and anti-biofilm activity of a new and promising Spanish ethanolic extract of propolis (SEEP) on Streptococcus mutans and Streptococcus sanguinis, responsible, as dominant ‘pioneer’ species, for dental plaque. Results reveal that S. sanguinis is more sensitive to SEEP, slowing and retarding its growth considerably with lower concentrations than those needed to produce the same effect in S. mutans. SEEP presents concentration- and time-dependent killing activity and, furthermore, some of the subinhibitory concentrations employed increased biofilm formation even when bacterial growth decreased. Mono and dual-species biofilms were also inhibited by SEEP. Findings obtained clearly show the relevance of using biofilm and subinhibitory concentration models to determine optimal treatment concentrations.

Deep learning with language models improves named entity recognition for PharmaCoNER

BackgroundThe recognition of pharmacological substances, compounds and proteins is essential for biomedical relation extraction, knowledge graph construction, drug discovery, as well as medical question answering. Although considerable efforts have been made to recognize biomedical entities in English texts, to date, only few limited attempts were made to recognize them from biomedical texts in other languages. PharmaCoNER is a named entity recognition challenge to recognize pharmacological entities from Spanish texts. Because there are currently abundant resources in the field of natural language processing, how to leverage these resources to the PharmaCoNER challenge is a meaningful study.MethodsInspired by the success of deep learning with language models, we compare and explore various representative BERT models to promote the development of the PharmaCoNER task.ResultsThe experimental results show that deep learning with language models can effectively improve model performance on the PharmaCoNER dataset. Our method achieves state-of-the-art performance on the PharmaCoNER dataset, with a max F1-score of 92.01%.ConclusionFor the BERT models on the PharmaCoNER dataset, biomedical domain knowledge has a greater impact on model performance than the native language (i.e., Spanish). The BERT models can obtain competitive performance by using WordPiece to alleviate the out of vocabulary limitation. The performance on the BERT model can be further improved by constructing a specific vocabulary based on domain knowledge. Moreover, the character case also has a certain impact on model performance.

Improving deep learning method for biomedical named entity recognition by using entity definition information

BackgroundBiomedical named entity recognition (NER) is a fundamental task of biomedical text mining that finds the boundaries of entity mentions in biomedical text and determines their entity type. To accelerate the development of biomedical NER techniques in Spanish, the PharmaCoNER organizers launched a competition to recognize pharmacological substances, compounds, and proteins. Biomedical NER is usually recognized as a sequence labeling task, and almost all state-of-the-art sequence labeling methods ignore the meaning of different entity types. In this paper, we investigate some methods to introduce the meaning of entity types in deep learning methods for biomedical NER and apply them to the PharmaCoNER 2019 challenge. The meaning of each entity type is represented by its definition information.Material and methodWe investigate how to use entity definition information in the following two methods: (1) SQuad-style machine reading comprehension (MRC) methods that treat entity definition information as query and biomedical text as context and predict answer spans as entities. (2) Span-level one-pass (SOne) methods that predict entity spans of one type by one type and introduce entity type meaning, which is represented by entity definition information. All models are trained and tested on the PharmaCoNER 2019 corpus, and their performance is evaluated by strict micro-average precision, recall, and F1-score.ResultsEntity definition information brings improvements to both SQuad-style MRC and SOne methods by about 0.003 in micro-averaged F1-score. The SQuad-style MRC model using entity definition information as query achieves the best performance with a micro-averaged precision of 0.9225, a recall of 0.9050, and an F1-score of 0.9137, respectively. It outperforms the best model of the PharmaCoNER 2019 challenge by 0.0032 in F1-score. Compared with the state-of-the-art model without using manually-crafted features, our model obtains a 1% improvement in F1-score, which is significant. These results indicate that entity definition information is useful for deep learning methods on biomedical NER.ConclusionOur entity definition information enhanced models achieve the state-of-the-art micro-average F1 score of 0.9137, which implies that entity definition information has a positive impact on biomedical NER detection. In the future, we will explore more entity definition information from knowledge graph.

Natural products as drugs source in the Ecuador´s essential medicines list

This paper presents the analysis of the origin of 391 active ingredients (AIs) of the 9th list of essential medicines in Ecuador, using the system proposed by Newman and Cragg with certain modifications. The AIs of natural origin represent 54.2% of the list and have greater importance in the categories H, R and B of the Anatomical, Therapeutic and Chemical classification system for pharmacological substances and medicines. In addition, the influence of natural products was analyzed in the categories with the highest amount of IAs J, L and N, as well as in category C, which is associated with the main cause of death in Ecuador.

Construction of a "Bacteria-Metabolites" Co-Expression Network to Clarify the Anti-Ulcerative Colitis Effect of Flavonoids of Sophora flavescens Aiton by Regulating the "Host-Microbe" Interaction.

Ulcerative colitis (UC) is considered an immune disease, which is related to the dysbiosis of intestinal microbiota and disorders of the host immune system and metabolism. Sophora flavescens Aiton has been used for the clinical treatment of UC in China and East Asia for thousands of years. It has many traditional prescriptions and modern preparations, and its curative effects are definite. We are the first to report that the flavonoids in Sophora flavescens (S. flavescens) Aiton EtOAc extract (SFE) could potentially attenuate the dextran sodium sulfate–induced UC in mice, which changed the current understanding of considering alkaloids as the only anti-UC pharmacological substances of S. flavescens Aiton. Based on the 16S rRNA gene sequencing and metabolomic analysis, it was found that the anti-UC effects of SFE were due to the regulation of gut microbiota, reversing the abnormal metabolisms, and regulation of the short-chain fatty acids synthesis. Notably, according to the interaction networks of specific bacteria and “bacteria and metabolites” co-expression network, the SFE could enrich the abundance of the commensal bacterium Lactobacillus, Roseburia, norank_f__Muribaculaceae, Anaerotruncus, Candidatus_Saccharimona, and Parasutterella, which are proposed as potentially beneficial bacteria, thereby playing vital roles in the treatment of UC.

Methodological aspects of creation of patient-derived tumor xenografts

High rates of cancer incidence and mortality from malignant neoplasms remains an urgent health problem. The development of the most effective therapeutic algorithms is required to improve the survival of cancer patients. An important condition for the discovery of new anticancer drugs and their translation into clinical practice involves the ability to model tumor growth, reproduce the characteristics of human disease, and evaluate measurable effects of pharmacological substances in laboratory facilities. Xenograft models established by direct implantation of fresh tumor tissue samples from individual patients into immunodeficient mice are considered suitable for both preclinical trials and for solving fundamental problems in oncology. The review highlights the significance of patient-derived xenograft models as a platform with high predictive value and the prerequisites that make them the preferred tool for research in cancer biology. The most important methodological aspects in the creation of these models are considered. Methods for obtaining and preparing biological tumor samples for xenotransplantation are discussed. The significance of the immune status, as well as the phenotypic and genetic characteristics of recipient animals, is described. The article presents the limitations of animal models associated with their immunodeficiency status and ways to overcome them. The principles for choosing xenotransplantation sites (heterotopic and orthotopic) and their advantages and disadvantages are discussed. In conclusion, we emphasize the need to continue the work on optimizing PDX (Patient-Derived Xenograft) models to overcome their limitations and to obtain the most reliable and valuable research results in oncology.

Antimicrobial Polymer-Based Hydrogels for the Intravaginal Therapies-Engineering Considerations.

The review is focused on the hydrogel systems dedicated to the intravaginal delivery of antibacterial, antifungal and anti-Trichomonas vaginalis activity drugs for the treatment of gynaecological infections. The strategies for the enhancement of the hydrophobic drug solubility in the hydrogel matrix based on the formation of bigel systems and the introduction of nano- and microparticles as a drug reservoir are presented. Hydrogel carriers of natural and synthetic pharmacological substances, drug-free systems displaying antimicrobial activity thanks to the hydrogel building elements and systems combining the antimicrobial activity of both drug and polymer building components are distinguished. The design of hydrogels facilitating their administration and proper distribution in the vaginal mucosa and the vagina based on thermoresponsive systems capable of gelling at vaginal conditions and already-cross-linked injectable systems after reaching the yield stress are discussed. In addition, the mechanisms of hydrogel bioadhesion that regulate the retention time in the vagina are indicated. Finally, the prospects for the further development of hydrogel-based drug carriers in gynaecological therapies are highlighted.

Modern clinical and physiological bases of super microsurgery. The view of a physiologist and surgeons

This paper is a retrospective analysis of the long-term work of a large group of Russian scientists representing various Medical Institutions of St. Petersburg (in the past years of Leningrad) in the period from the 70s of the XX century to the present in the field of theoretical clinical lymphology. We aimed to discuss critical studies of a group of anatomists, in the sphere of the structure of lymphangions and lymph nodes in health and lymphedema of the lower extremities in humans. Experimental data of physiologists are presented, which made it possible for the first time to substantiate the functional mechanisms of active lymph transport in health and in lymphedema of the lower extremities. In addition, there are some results of testing biopsy specimens with various pharmacological agents and vasoactive substances. At last, there is an example of the clinical use of theoretical knowledge in the tactics of choice and expediency of surgical treatment of lymph drainage disorders in patients is given.

MATHEMATICAL MODEL FOR THE INVESTIGATION OF HYPOXIC STATES IN THE HEART MUSCLE AT VIRAL DAMAGE

The main complications of organism damaged by SARS-CoV-2 virus are various cardiovascular system lesions. As a result, the secondary tissue hypoxia is developed and it is relevant to search the means for hypoxic state alleviation. Mathematical modeling of this process, followed by the imitation of hypoxic states development, and subsequent correction of hypoxia at this model may be one of the directions for investigations. Aim. The purpose of this study was to construct mathematical models of functional respiratory and blood circulatory systems to simulate the partial occlusion of blood vessels during viral infection lesions and pharmacological correction of resulting hypoxic state. Methods. Methods of mathematical modeling and dynamic programming were used. Transport and mass exchange of respiratory gases in organism, partial occlusion of blood vessels and influence of antihypoxant were described by the systems of ordinary nonlinear differential equations. Results. Mathematical model of functional respiratory system was developed to simulate pharmacological correction of hypoxic states caused by the complications in courses of viral infection lesions. The model was based on the theory of functional systems by P. K. Anokhin and the assumption about the main function of respiratory system. The interactions and interrelations of individual functional systems in organism were assumed. Constituent parts of our model were the models of transport and mass exchange of respiratory gases in organism, selforganization of respiratory and blood circulatory systems, partial occlusion of blood vessels and the transport of pharmacological substance. Conclusions. The series of computational experiments for averaged person organism demonstrated the possibility of tissue hypoxia compensation using pharmacological substance with vasodilating effect, and in the case of individual data array, it may be useful for the development of strategy and tactics for individual patient medical treatment.

The past and present research at the University of Sydney’s Discipline of Orthodontics

The University of Sydney’s Discipline of Orthodontics has been actively pursuing research in the areas of root resorption, sleep apnea, magnets in orthodontics, implants, acceleration of orthodontic tooth movement (OTM), and remote monitoring (RM). Our research has shed light on many specific factors that influence orthodontically induced inflammatory root resorption (OIIRR). We also explored the effects of some of the most discussed acceleration interventions on OTM and OIIRR, such as vibration, micro-osteoperforations, piezocision, low-level laser therapy, light emitting diode, light amplification by stimulated emission of radiation, and pharmacological substances. Further, we have researched into maximizing orthopedic treatment outcomes of maxillary deficient children with use of intraoral force application with utilization of miniscrew-assisted rapid palatal expander. We are currently trialing use of RM to facilitate orthodontic services in the public dental clinics.

β-patchoulene protects against non-alcoholic steatohepatitis via interrupting the vicious circle among oxidative stress, histanoxia and lipid accumulation in rats

Non-alcoholic steatohepatitis (NASH), an extreme progressive subtype of metabolic associated fatty liver disease, is well characterized by hepatic steatosis, injury and inflammation. It causes irreversible hepatic damage and there are no approved interventions for it. β-PAE, a representatively pharmacological active substance isolated from Pogostemon cablin, has been indicated to alleviate hepatic steatosis and injury through modulating lipid metabolism in rats with simple steatosis. However, its protection against NASH remains unclear. Here, this study explored the potential effect of β-PAE against high-fat diet-induced NASH in rats. The results displayed that β-PAE significantly reduced the gains of body weight and epididymal adipose tissue, liver index and attenuated liver histological damages in NASH rats. It also markedly alleviated hepatic inflammation by inhibiting NLRP3 inflammasome activation. In NASH, the active NLRP3 inflammasome is caused by hepatic lipid abnormal accumulation-induced oxidative stress. Excessive oxidative stress results in hepatic histanoxia, which exacerbates lipid metabolism disorders by elevating CD36 to suppress AMPK signalling pathways. Moreover, the lipid accumulation led by lipid metabolism dysfunction intensifies oxidative stress. A vicious circle is formed among oxidative stress, histanoxia and lipid accumulation, eventually, but β-PAE effectively interrupted it. Interestingly, soluble CD36 (sCD36) was tightly associated not only with hepatic steatosis and injury but also with inflammation. Collectively, β-PAE exerted a positive effect against NASH by interrupting the vicious circle among oxidative stress, histanoxia and lipid accumulation, and sCD36 may be a promising non-invasive tool for NASH diagnosis.

Identification and characterization of quinoline alkaloids from the root bark of Dictamnus dasycarpus and their metabolites in rat plasma, urine and feces by UPLC/Qtrap-MS and UPLC/Q-TOF-MS

Quinoline alkaloids are the main bioactive and potentially toxic constituents in the root bark of Dictamnus dasycarpus Turcz. (BXP), a widely used traditional Chinese medicine for the treatment of skin inflammation, eczema and rubella. However, the comprehensive analysis of the chemical components and metabolites of quinoline alkaloids remain unclear. In this study, an integrated strategy by combining UPLC/Q-TOF-MS and UPLC/Qtrap-MS was established to comprehensively profile the quinoline alkaloids from BXP and their metabolites in rat plasma, urine and feces. Q-TOF-MS (MSE mode), Qtrap-MS (EMS, MIM, pMRM and NL mode) were performed for acquiring more precursor ions and clearer precursor product ions. A step-by-step manner based on the diagnostic fragment ions (DFIs), in-house database, ClogP value and dipole moment (μ) was proposed to overcome the complexities due to the similar fragmentation behaviors of the quinoline alkaloids. As a result, a total of 73 quinoline alkaloids were unambiguously or tentatively identified. Among them, 4 furoquinolines, 10 dihydrofuroquinolines, 2 pyranoquinolinones, 4 dihydropyranoquinolinones and 9 quinol-2-ones were characterized in BXP for the first time. Moreover, a total of 98 BXP-related constituents (including 57 prototypes and 41 metabolites) were detected in rat plasma, urine and feces. The metabolic pathways included phase I reactions (O-demethylation, hydroxylation and 2,3-olefinic epoxidation) and phase II reactions (conjugation with glucuronide, sulfate and N-acetylcysteine). In conclusion, the integrated strategy with the proposed stepwise manner is suitable for rapid identifying and characterizing more extensive quinoline alkaloids of BXP in vitro and in vivo. Moreover, the results will be helpful for revealing the pharmacological effective substances or toxic substances of BXP and provide a solid basis for further research.

Approaches to modeling pulmonary embolism and chronic thromboembolic pulmonary hypertension in rodents and medium-sized laboratory animals

Pulmonary embolism (PE) is the third most common cardiovascular disease. It is still associated with high hospital mortality, as well as with the development of acute and chronic complications. Treatment and prevention of PE and its complications requires high-tech approaches aimed at improving the prognosis of patients. In this regard, experimental studies aimed at studying the pathogenesis, improving diagnostic methods and searching for new pharmacological substances for the prevention and treatment of PE are in demand from the point of view of clinical practice. Considering the current trends in preclinical research, experimental work on rodents — mice, rats, hamsters, as well as on medium-sized laboratory animals (rabbits) is becoming more and more common. The use of these animal species is ethically acceptable and economically viable. The choice of a specific type of animal and a method for modeling PE is primarily determined by the objectives of the study. This article provides an overview of the main approaches to modeling PE, as well as discusses the advantages and disadvantages of each method. Special attention is paid to the modeling of chronic thromboembolic pulmonary hypertension (CTEPH) as one of the most dangerous complications of PE. The work analyzed publications from 1978 to 2020, in which PE was simulated in rodents and medium laboratory animals.

Stretchable electrical cell-substrate impedance sensor platform for monitoring cell monolayers under strain

Stretchable microelectrodes paired with an ultra-elastic substrate can be used for electrical sensing of mechanically stretched cells and cell monolayers. Here, we present the development of a cell-stretching platform with thin-film interdigitated microelectrodes. Up to 35 % cyclic stretch are feasible with a novel interlaced meander design connected to the microelectrodes and using Poly(dimethylsiloxane) (PDMS) with a Young’s modulus of 50 kPa as an ultra-elastic substrate. Reliable electrical contacting of the microelectrodes under stretch was achieved by perforation of the contact pads. The novel platform enables label-free, real-time electrical cell-substrate impedance (ECIS) monitoring of cell monolayers. Proof-of-concept experiments indicated that electrical impedance of Madin-Darby canine kidney (MDCK) cell monolayers increased sharply by uniaxial mechanical strain above 20 %. For comparison, human alveolar basal epithelial adenocarcinoma (A549) cell monolayers, which are known to lack mature cell junctions, showed a continuous decrease of electrical impedance over the whole applied strain range of 35 %. The data reveal that impedance changes upon stretching depend on epithelial cell types and existence of tight cellular junctions. The system provides the basis for reliable continuous long-term monitoring of electrical properties of cell monolayers under strain by electrical impedance spectroscopy, e.g., to monitor epithelial permeability changes in real time and under label-free conditions to screen the influence of pharmacological substances.

Quality Control of Protein Supplements: A Review

The growing consumer awareness regarding health and fitness has been leading to a huge rise in the consumption of nutritional supplements and, consequently, to an increase in concerns about their quality. In this sense, one of the most consumed products is protein supplements and, despite being safer than other types of supplements, there are several studies showing incompatibilities between what is present on the labels and their actual content. Therefore, this review is focused on gathering information about the problems arising from poor manufacturing practices and inadequate quality control of sport protein supplements. These issues are mainly related to three aspects: reduction of the supplements’ nutritional value, the presence of pharmacological substances, and contamination with microorganisms or toxic metals. Regarding the first aspect, reports about the “classic” addition of nitrogen-rich compounds to mask the protein content measured by the Kjeldahl method were discussed, as well as recent topics such as the addition of cheaper proteins to produce an “undetectable” adulteration in whey protein supplements. With respect to the presence of pharmacological compounds, it is a finding that is not very common in protein supplements; however, even trace amounts of foreign substances in this type of product may cause adverse effects to consumers, and, in the case of an elite athlete, may result in doping. Finally, we discuss about the contamination with microorganisms and toxic metals, this latter being a subject that should be further explored due to few studies in the literature.

Behavioral analysis of anxiolytic action of phenazepam in conditions of an acute psychogenic stress (predator presentation) in Danio rerio

We studied the effect of benzodiazepine anxiolytic phenazepam after the predator presentation to Danio rerio. The test of novelty was used: the fish was placed first in a beaker with a dissolved pharmacological substance (or H2O) and then into a novel tank for 6 min, where the trajectory, the path length, the number of movements to the upper part of the novel tank, the number and time of the pattern of freezing were measured. It is shown that, in response to the novelty of tank, the fish are reacted by submerging to the bottom, increasing the frizing, and reducing the number of movements to the upper half of the novel tank. After phenazepam administration, the fish were not only in the lower, but also in the upper part of the novel tank. The average path length did not change significantly in the range of doses used. The number and time of the frizing, as well as the time spent in the lower part of the novel tank, decreased more than 2 times compared to the control group of animals and showed a dose-dependent effect. The number of movements to the upper part of the novel tank for the experiment increased significantly from 1 in the control to 57 after phenazepam in a dose of 1 mg/l. At the same time, the number of movements of fish to the upper part of the novel tank significantly increased more than 2 times from 3th min of the experiment with the use of phenazepam in a dose of 1 mg/l. Predator presentation (Hypsophrys nicaraguensis) caused an increase in the number of freezing (temporary immobilization) and a decrease in the length of the trajectory of movement in the novel tank as compared with the Danio rerio control group. Phenazapam at a dose of 1 mg/l removed the effects of a predator, while exhibiting a typical effect: the number of movements to the upper part of the tank during the experiment significantly increased to 30; the time at the bottom of the tank was halved. It was concluded that the novelty stress test and the test with a predator are highly sensitive for studying anxiety-phobic reactions in Danio rerio.

Effect of Wnt pathway inhibitor on ovarian cancer tumors.

e15010 Background: Ovarian cancer (OC) is the fourth most common cancer in women aged 40-54 years. Despite advances in cancer research, no existing methods provide effective early diagnosis and treatment of OC, so the search for new medications is an urgent task. The effectiveness of the XAV-939 pharmacological substance, which inhibits the Wnt signaling pathway, was studied in an orthotopic patient-derived xenograft of human ovarian cancer. Methods: A PDX model was created in 20 female immunodeficient Balb/c Nude mice. A tumor fragment was implanted into the ovary, and the ovary was transposed under the skin to better visualize the xenograft growth. When the average tumor volume was 67.4 mm3, animals were divided into 4 groups: group 1 – controls (n = 5); group 2 – animals receiving paclitaxel (n = 5); group 3 – animals with XAV-939 (n = 5); group 4 – animals with combined paclitaxel+XAV-939 (n = 5). The control group received the carrier substance, and the test substances were administered at 10 mg/kg; the substances were administered intraperitoneally twice a week for 22 days. The tumor growth was assessed throughout the experiment by measuring its linear dimensions (length and width), and the volume and tumor growth index were calculated. The data were statistically processed using Microsoft Excel and STATISTICA 10. The Mann-Whitney nonparametric test was used to assess the differences between the control and experimental groups. Results: No statistically significant differences were observed in the indices of tumor growth between groups 2 (paclitaxel) and 1 (control), and groups 3 (XAV-939) and 1 (control). However, the difference was statistically significant between groups 4 (paclitaxel+XAV-939) and 1 (control). The tumor growth inhibition index was calculated at the end of the experiment. It was maximal in group 4 (paclitaxel+XAV-939) – 67.78%; in groups 2 (paclitaxel) and 3 (XAV-939), it was 21.39% and 30.33%, respectively. Conclusions: An orthotopic PDX model of ovarian cancer was generated, and the activity of XAV-939 towards the OC xenograft was studied; the greatest efficacy of the preparation was noted in combination with paclitaxel.

Susceptibility of animal species to experimental SARS-CoV-2 (Coronaviridae: Coronavirinae: Betacoronavirus; Sarbecovirus) infection

Due to the new coronavirus infection pandemic, the global scientific community has been forced to change the direction of the most research, focusing on vaccine development as well as the search for new antiviral drugs totreat COVID-19. The choice of experimental models, timeframe and approaches for evaluating drugs and vaccines under development is crucial for the development of effective measures to prevent and control this disease.The purpose of this review was to summarize the relevant data concerning the susceptibility of laboratory animals to SARS-CoV-2. This paper describes the most virus-susceptible animal species that can be used to reproduce coronavirus infection, stressing the main advantages and disadvantages of each of them.According to the latest data, small rodents (Rodentia) and non-human primates (Strepsirrhini) are commonly used in the scientific community to model coronavirus infection. The viral load in the upper and lower parts of the respiratory system, clinical symptoms of infection (weight loss, body temperature and general health status), pathomorphological picture in target organs and the production of antibodies after infection are considered to the main markers of pathology. Despite the vast amount of data, none of the described models of SARS-CoV-2 infection may be considered a gold standard, since they do not reproduce all spectrum of morphological and pathogenetic mechanisms of infection, and do not fully reflect the clinical picture observed in patients in human population.Based on the analyzed literature data, we suppose that Syrian hamster (Mesocricetus auratus) and mice (Muridae) expressing the angiotensin converting enzyme receptor 2 (ACE2) are the most suitable animal species for their use in experiments with SARS-CoV-2 infection. The development of neutralizing antibodies makes it possible to evaluate the efficacy of vaccines, while the course and severity of symptoms infection makes the use of mice and hamsters especially popular for screening pharmacological substances with antiviral mechanism of action, when their administration can prevent or slow the disease progression.

The Use Of Kretek Herbs For Cigarette Addicts In View Of Islamic Law

‘There are differences of opinion among the ulama regarding smoking which led to the emergence of two groups in it, namely those who do not forbid it (allow smoking) and those who firmly say that smoking is haram. However, the phenomenon in the field shows that even though the prohibition of smoking has been loudly voiced, the smoking rate in Indonesia, in particular, is increasing. Therefore, herbal cigarettes are a solution for heavy smokers. Herbal cigarettes are a cylinder of paper measuring approximately 70 to 120 mm long containing tobacco ingredients and several active ingredients which are said to have beneficial pharmacological substances and effects for the body. Although in fact heavy smokers find it difficult to switch from previous cigarettes to herbal cigarettes, herbal cigarettes themselves can be said to be a solution so that smokers switch to cigarettes with lower toxic levels. Herbal cigarettes are a solution to efforts to make heavy smokers reduce their cigarette addiction or even hopefully quit eventually”.

Original compound with anticonvulsant activity in the treatment of alcoholism

IntroductionOriginal compound ortho-fluorobenzonal, a barbiturate derivative, is shown to reveal strong anticonvulsant activity by means increasing GABA-mediation. Disturbance of GABA(A) -receptors functions play an essential role in both alcoholism and epilepsy pathogenesis.Objectives Taking into account the presence of GABA(A)-receptors on the lymphocytes surface and involvement of immune system in alcoholism pathogenesis, we investigated ortho-fluorobenzonal effects on the immune and nervous systems functional activities in mice with chronic alcohol exposure to find new perspective pharmacological substances in the treatment of alcoholism.Methods(CBAxC57Bl/6) F1 male mice with 6-month 10% ethanol exposure were undergoing intragastric administration of original compound ortho-fluorobenzonal for 10 days. Animal’s alcohol consumption, behavior and immune parameters were estimated.ResultsIt was found that ethanol daily consumption decreased sharply starting from 2 days of ortho-fluorobenzonal administration and led to the cessation of ethanol consumption by the 4 day in mice with chronic alcohol exposure. Pronounced changes in motor and exploratory activities in “open field” test was registered in long-term alcoholized mice after 10- day course ortho-fluorobenzonal administration. The above behavioral changes were recorded against the brain cytokines synthesis modulation. We have shown also the modulation by ortho-fluorobenzonal of immune system functional activity, in particular, significant cellular and humoral immune response stimulation, estimated by the relative number of antibody forming cells and reaction of delayed-type hypersensitivity respectively.ConclusionsOriginal compound ortho-fluorobenzonal has a positive neuroimmunomodulation effect that manifests itself in the correction of iimmune and behavior disorders caused by the chronic ethanol exposure, therefore, this compound is promising in the therapy of alcoholismDisclosureNo significant relationships.