Alexandria University

Ankara University

Devi Ahilya University, Indore

Dr. Harisingh Gour University

University of Bonn

Universidade do Vale do Itajaí (Univali)

University of Iceland

University of Balochistan

ISF College of Pharmacy

National Institute of Health Sciences, Japan

Akademickie Centrum Komputerowe CYFRONET AGH

Lanzhou University

National Institute of Biomedical Innovation

Kobe Gakuin University

University of Salzburg

B. S. Anangpuria Educational Institutes

University of Greifswald

Martin Luther University Halle-Wittenberg

University of Oslo

Istanbul University

University of Lille Nord de France

University of Porto

University of Florida

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Comenius University Bratislava

Freie Universität Berlin

DiePharmazie is one of the world's leading pharmaceutical journals. As a peer-reviewed scientific journal, DiePharmazie is regularly indexed in Current Contents/Life Sciences, Excerpta Medica, Analytical Abstracts, International Pharmaceutical Abstracts, Beilstein Current Facts in Chemistry, Chemical Engineering and Biotechnology Abstracts (CEABA) and Science Citation Index. The journal DiePharmazie publishes reviews, experimental studies, letters to the editor, as well as book reviews. The following fields of pharmacy are covered: Pharmaceutical and medicinal chemistry, pharmaceutical analysis and drug control, pharmaceutical technolgy, biopharmacy (biopharmaceutics, pharmacokinetics, biotransformation), experimental and clinical pharmacology, pharmaceutical biology (pharmacognosy), history of pharmacy.

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The relationship between large conductance calcium activated potassium channel (BKCa) and vascular lesions in type 2 diabetes mellitus (T2DM) was investigated by observing vascular reactivity of thoracic aorta and mesenteric artery and the current changes of BKCa in vascular smooth muscle cells (VSMCs). The thoracic aorta and mesenteric artery of T2DM rats were isolated, the whole cell perforated patch clamp experiment and single channel patch clamp experiment of acute enzyme separation of thoracic aorta and mesenteric artery smooth muscle cells were performed to measure the membrane capacitance and the amplitude of macro current. And the vascular ring experiment was performed to observe the change of relaxation percentage. The results showed that the amplitude of BKCa current in vascular smooth muscle cells of diabetic rats was higher than that of the control group. The channel current had outward rectifying characteristics. BKCa is related to vascular reactivity and smooth muscle relaxation in T2DM rats. The opening probability of BKCa in VSMCs of diabetic rats was significantly increased. This study suggests that BKCa may be a new target for diabetic vascular disease.

Changes of BKCA current and vascular reactivity in vascular smooth muscle of thoracic aorta and mesenteric artery in type 2 diabetic rats

T cell immunoglobulin and mucin domain-1 (TIM-1) is a transmembrane glycoprotein and has been reported as an molecular mechanism of allergic diseases. This study aimed to explore the effects of anti-TIM-1 monoclonal antibodies (anti-TIM1) on the development of allergic asthma. Female C57BL/6 mice were induced and challenged with ovalbumin (OVA) and received subsequent intranasal administration of anti-TIM1. The airway resistance of all mice was evaluated using a Buxco PFT system. Flow cytometry was used to detect the expression of TIM-1 in peripheral blood mononuclear cells. The level of cytokine production in the bronchial alveolar lavage fluid and serum was determined using ELISA. Mucous cells were observed using Alcian blue and periodic acid-Schiff staining. In addition, B-cell lymphoma gene 2(BCL2), T-box transcription factor (T-bet), GATA binding protein-3(GATA3), signal transducer and activator of transcription (STAT) 1, STAT6 were analyzed by western blot analysis. Their corresponding mRNA expression levels were determined by quantitative PCR. The mRNA expression level of Mucin 5AC in the lung tissues was also detected using quantitative RT-PCR. The results showed that the intranasal administration of anti-TIM1 ameliorated airway inflammation and hyperresponsiveness in an acute model of asthma. Following administration of anti-TIM1, both the mRNA and protein levels of T-bet were upregulated, while those of BCL2 and GATA3 were downregulated. Moreover, the phosphorylation levels of STAT1 and STAT6 were increased. Taken together, these findings demonstrated that intranasal administration of anti-TIM1 ameliorated allergic lung inflammation and remodeling in mouse models of asthma by repairing both the STAT1 and STAT6 pathways.

Anti-TIM1 suppresses airway inflammation and hyperresponsiveness via the STAT6 /STAT1 pathways in mice with allergic asthma

Background: Patients with prostate cancer often develop resistance to androgen deprivation therapy, a condition called castration-resistant prostate cancer (CRPC). Enzalutamide (MDV3100) can prolong the survival of patients with CRPC after chemotherapy, but ∼50% of patients eventually relapse and develop resistance to MDV3100. Thus, it is necessary to explore new treatment methods to improve the therapeutic effect of MDV3100. Tyrosine kinases play an essential role in the pathogenesis of CRPC. Methods: MTT assay was used to detect the inhibitory effects of MDV3100 and tyrosine kinase inhibitor on prostate cancer cells. CompuSyn version 1.0 was used to calculate the combination index (CI) values using the Chou-Talalay method. Clone formation and EdU assay were used to detect the effect of afatinib combined with MDV3100 on the proliferation of 22Rv1 cells. RT-qPCR and Western blot were used to explore the mechanism of drug combination. The aim of the present study was to determine the effects of several tyrosine kinase inhibitors (TKIs) when used in combination with MDV3100 in vitro. Results: The results demonstrated that TKIs combined with MDV3100 exerted a synergistic effect on a variety of PCa cells. Afatinib combined with MDV3100 could suppress the proliferation and migration of 22RV1 cells, as well as cause their cell cycle arrest and apoptosis. Mechanistically, afatinib effectively reduced the protein expression levels of HER2 and HER3 and inhibited EGFR phosphorylation, thereby enhancing the effect of MDV3100 and suppressing CRPC. Conclusions: These findings suggested that afatinib treatment improved the effect of MDV3100 on 22RV1 cells, highlighting this drug as a potential therapeutic strategy for patients with CRPC.

Enhanced antitumor efficacy by combining afatinib with MDV3100 in castration-resistant prostate cancer

Mental health disorders such as stress, anxiety, depression and insomnia caused by COVID-19 have attracted worldwide attention. Traditional Chinese medicines (TCMs) have been proven to be a safe and effective option for treating mental health disorders. Recently, after assessing its efficacy and safety fully, the Netherlands Medicines Evaluation Board approved XiaoYao Tablets as a traditional herbal medicinal product (THMP), indicated for an alternative self-care for patients in Europe to relieve the symptoms of mental stress and exhaustion. Despite the fact that TCMs have gradually become one of the therapeutic choices worldwide, to-date, only a few TCMs have been successfully registered in the European Union (EU) as THMPs, and XiaoYao Tablets is the first successfully registered combination TCM from China. In this article, traditional use efficacy and clinical safety of XiaoYao Tablets in the treatment of mental health disorders were summarized and analyzed from the perspective of traditional use registration (TUR). Additionally a safety evolution pathway of combination TCMs was established. This article will not only seek to enhance our understanding about traditional use efficacy and clinical safety of XiaoYao Tablets, but also summarize the experience of XiaoYao Tablets as the first successfully registered combination TCM from China, which could serve as role model for the others to overcome registration difficulties in the EU.

Traditional use and safety evaluation of combination Traditional Chinese Medicine in European registration: with XiaoYao Tablets as an example

A capillary electrophoretic method for the chiral separation and quantification of mitiglinide (MTG) enantiomers is described (less than 9.5 min) with resolution value Rs = 5.25 and with excellent peak shapes after performing the dynamically coating for the bare fused capillary. The study aims to develop and validate a novel and simple method for the separation and quantification of MTG enantiomers using CE after dynamic coating the capillary wall using the hydroxyethyl cellulose (HEC) coating agent. Dynamic coating procedure of the capillary inner surface is conducted via rapid flushes using 0.1 M sodium hydroxide, water, and aqueous solution containing HEC, and hydroxypropyl-γ-cyclodextrin (HP-γ-CD). Besides buffer was used for the dynamic coating process in addition to its use as the separation medium. When the dynamic coating was used, peak symmetry was improved. A bare fused-silica capillary was used throughout the separation after being coated using HEC dissolved in the background electrolyte (BGE) of 50 mM Na₂HPO₄ - 1 M H₃PO₄ solution; pH 8.5; containing 25 25 mg mL-1 of each HP-γ-CD and HEC. The dynamic coating procedure achieved an improvement in migration time as well as peak area precision. The adsorbed coating agent showed slight interactions with MTG, providing efficient separation with outstanding durability and reproducibility at slightly alkaline conditions (pH 8.5). Acceptable validation criteria for selectivity, linearity, precision, and accuracy were also studied. The newly developed method was effectively applied to the assay of enantiomers of MTG in pharmaceutical formulations. Additionally, it was proven to have the advantages of being simple, rapid, and accurate.

A novel and simple dynamic coating capillary electrophoresis method for the chiral separation and quantification of mitiglinide enantiomers using hydroxyethyl cellulose as a dynamic coating agent

The Artemisia plant which grows in most desert areas of the world, One of the important plants at all times, as it has been scientifically and practically proven to be non-toxic, By taking it orally, whether in powder or solution form by humans, And using chemical statements and measurements of chemical devices for its alcoholic and aqueous extract, it contains A wide range of compounds, most of which are anti-oxidants. It helped to use it extensively in the industrial field in the form of pesticides, and in the medical field in the prevention and treatment of parts of the digestive system, increasing the activity of the enzymes of the heart, liver, pancreas. In addition to containing a group of chemical elements that lead to an increase in the effectiveness of these enzymes, As well as to combat cancer cells using the alcoholic extract from it, and because of the presence of phenols in its composition, it was used as anti-bacterials. The most important thing is that it is used in some countries of the African continent to treat some cases of the Corona epidemic. In European countries, it is currently being studied and developed for use in the treatment of Corona, because of its ease of access, simplicity of production, licenses when selling and the absence of side effects when using it, and this helped the world to eliminate the global pandemic.

Study applications extract of plant various Artemisia in the medical field: Review

Origanum vulgare L. essential oil possesses a wide spectrum of biological activities. Nanoencapsulation of O. vulgare essential oil into liposomes seems to be a promising strategy to maintain and improve these biological properties. This research was carried out to develop a suitable liposomal formulation for the effective encapsulation of O. vulgare essential oil in order to improve the antioxidant and cytotoxic activities. The characterization of liposomal nanocarriers was conducted in terms of size, zeta potential, and encapsulation efficiency. An MTT assay was used to assess the cytotoxic activity of the prepared and characterized O. vulgare essential oil liposomes in MCF-7 cancer cell lines. Antioxidant activity was determined by assessing DPPH scavenging activity. O. vulgare essential oil exerted cytotoxic activity with an IC50 of 50 μg/ml. The essential oil of O. vulgare was effectively encapsulated in liposomes, with no significant change observed among the formulations. The antioxidant activity was significantly enhanced after encapsulating the essential oil in liposomes. Origanum vulgare essential-oil-loaded Phospholipon 90H liposomes demonstrated considerably increased cytotoxic activity against MCF-7 cells, whereas Lipoid S100 liposomes showed no significant differences from the non-encapsulated essential oil. Phospholipon 85G liposomes had the least cytotoxic impact. As a result, liposomes containing O. vulgare essential oil may be promising nanocarriers for the development of anticancer agents.

Nanoencapsulation of Origanum vulgare essential oil into liposomes with anticancer potential

The aim of the present study was to survey adverse drug events (ADEs) in patients with bipolar disorders and identify risk factors using the Japanese Adverse Drug Event Report (JADER) database, a spontaneous reporting system. Data on patients with bipolar disorders were extracted from the JADER database. The Medical Dictionary for Regulatory Activities (MedDRA) preferred terms (PT) and standardized MedDRA queries (SMQ) were used to define ADEs. A multiple logistic regression analysis was performed to identify risk factors for ADEs. A total of 8653 reports of 1108 types of ADEs (PT) were registered in data collected on 3521 patients with bipolar disorders. Rash (PT) was the most frequently reported in 549 patients, followed by drug eruption (PT) in 387, fever (PT) in 364, toxicity to various agents (PT) in 291, and Stevens-Johnson syndrome (PT) in 261. Among 24 ADEs (PT) that were reported in more than 50 patients, lamotrigine was associated with increased risks of 13 ADEs (PT), followed by carbamazepine with increased risks of 8 ADEs (PT). The majority of these ADEs belonged to hypersensitivity (SMQ) or hepatic disorder (SMQ). Lithium carbonate was associated with increased risks of rash (PT), drug interaction (PT), and tubulointerstitial diseases (SMQ). All antipsychotics increased the adjusted odds ratio for neuroleptic malignant syndrome (PT). The risk of hyperglycemia/new onset diabetes mellitus (SMQ) was increased by olanzapine, quetiapine fumarate, and risperidone. We are presenting the profiles of ADEs in patients with bipolar disorders using the JADER database, and propose risk factors for 19 ADEs (PT) and 4 ADEs (SMQ).

Analysis of adverse drug events in patients with bipolar disorders using the Japanese Adverse Drug Event Report database

Caffeine and Camellia sinensis (green tea) has been known to have positive effect on memory. The present study investigated the possible effect of caffeine and green tea co-administration on oxidative stress markers, inflammatory marker and acetylcholine esterase activity in scopolamine-induced memory loss in female Swiss mice. Memory behavioral tests using Y-maze and Morris water maze was carried out, followed by oxidative stress biomarkers, acetylcholinesterase activity and Tumor Necrosis Factor alpha (TNF-α) evaluation from the mice brain tissues after caffeine and green tea administration. Scopolamine administered intraperitoneally at a dose of 1mg/kg Body Weight (BW) for 7 days significantly reduced the percent alternation of the mice in Y-maze thus, increased acetylcholinesterase activity and increased TNF-α level. However, caffeine administered orally at a dose 50mg/kg BW and green tea administered orally at a dose of 60mg/kg BW increased the percent alternation significantly, reduced acetylcholinesterase activity and reduced the TNF alpha level significantly. Oxidative stress markers evaluated GSH and MDA, showed no significant difference across all groups. These findings showed scopolamine has a deteriorating effect on cognition by increasing acetylcholinesterase activities thus mopping out acetylcholine at a faster rate. However, caffeine and green tea singly and in combination restored cognition, reduced acetylcholinesterase activity and restored TNF-α level. The neuroprotective effect of caffeine and green tea was compared to that of Donepezil, an established cognition enhancing drug and the effect was agonistic. The ability of caffeine and green tea to reduce acetylcholinesterase activity could be the mechanism for the ability to enhance memory. The ability of these compounds in restoring TNF alpha level also further potentiates their neuroprotective capability.

Caffeine and Camellia sinensis enhance cognition and decrease acetylcholinesterase activity in scopolamine-induced memory loss in female Swiss mice

To explore potential indoleamine 2,3-dioxygenase 1 (IDO1) inhibitors, we designed a series of compounds incorporating urea and 1,2,3-triazole structures. IDO1 enzymatic activity experiments with the synthesized compounds were used to verify their molecular-level activity; for instance, the half maximal inhibitory concentration value of compound 3c was 0.07 μM. Our research has yielded a series of novel IDO1 inhibitors which may be beneficial in the development of drugs targeting IDO1 for cancer treatment.

Novel Compounds with Promising IDO1 Inhibitory Activity As New Cancer Drug Candidates: Derivatives Of N, N'-diphenylurea Linked With 1,2,3-triazole

The Town Hall Pharmacy (Raeapteek) in the Town Hall Square of Tallinn, Estonia (N59°26'16.001'' E24°44'45.412'') was first mentioned in historical records on 8 April 1422. To our best knowledge, the Raeapteek is the oldest community pharmacy in Europe which has operated on the same premises since the beginning. There are several hypotheses about the actual opening time of Raeapteek: it is possible that the pharmacy was operating on the square of the Tallinn Town Hall as early as in 1415, 1420, 1392 or even in 1248. In the territory of present-day Estonia, two pharmacies (in Tartu first mentioned in 1430) were already in business in less than 200 kilometres from each other before community pharmacies were opened in Russia, Sweden, Finland, Norway, Denmark, Lithuania, and other cities. The Raeapteek played an essential role in the establishment of the current Estonian History Museum, the Estonian Pharmaceutical Factory, K. C. Fick's faience manufactory and other dignified institutions had their beginning at the pharmacy. Now, the pharmacy functions hand-in-hand with the museum which is supported by the city of Tallinn.

600 Years of Town Hall Pharmacy (raeapteek) in Tallinn, Estonia

The current conflict between Russia and Ukraine increased concerns in the German population of a release of radioactive substances, e.g.radioactive iodine. A high dose of potassium iodide (PI) may prevent accumulation of radioactive iodine in the thyroid gland. Therefore, the German government keeps a sufficient quantity of PI in stock for public supply in case of an emergency. We investigated ambulatory drug dispensing rates of PI and found that the total dispensing of PI (statutory health insurance (SHI), private health insurance (PHI), and overthe-counter (OTC)) increased by 106% from February to March 2022. Changes in PI dispensing were mainly due to an increase in OTC sales, where PI as an antidote showed a sevenfold increase from around 930 packages (February 2022) to 6,500 packages (March 2022), while SHI and PHI dispensing remained relatively low. Furthermore, we investigated whether these changes in dispensing raised the number of suspected adverse drug reactions (ADR). We found no increase of ADR reports related to the use of PI-containing medicinal products between February and September 2022, neither in our national pharmacovigilance nor in the European EudraVigilance database. The data suggest that the mere possibility of a nuclear disaster in Ukraine raised the demand of PI in Germany. Thus, timely and proactive information and reassurance of the public of supply reliability by the Government in a case of a nuclear emergency could be helpful in preventing potential drug shortages and unfounded concern.

Increased Demand for Pharmaceutical Drugs Containing Potassium Iodide In Connection with the Russia-Ukraine Conflict

The professor of pharmacy, Johann Georg Noel Dragendorff (1836-1898) is primarily known in the history of pharmacy as a pharmacognosist and forensic chemist, so far he has been less described as a toxicologist. He worked for 30 years (1864-1894) at the University of Dorpat (Tartu) in Estonia, and had been invited from Germany, developing here one of the pharmaceutical research centers in all of Europe. Dr. Dragendorff supervised 90 theses of Master of Pharmacy and 87 theses of Doctor of Medicine in Tartu/Dorpat. Dragendorff's supervised master's theses reveal his particular interest in phytochemistry. Of the 87 doctoral dissertations supervised by Dragendorff, are related to forensic chemistry (26 works), and toxicology with pharmacology (21). This work introduces Dragen-dorff as a toxicologist, discusses the theses supervised by him and his textbooks. Dragendorff's development as a toxicologist was logical considering his extensive scientific activities and the drugs characteristic of the 19 th century. These, especially alkaloids and mercury preparations, are introduced in more detail in this study.

Professor Georg Dragendorff (1836-1898) as a Toxicologist

Physiologic changes due to aging, pregnancy, nutritional status, drug interactions, and can affect pharmacokinetics and pharmacodynamics of antiepileptic drugs. In this review article, the interactions between phenytoin and herbs recorded in the literature were summarized according to the Medline database (via PubMed). Our results revealed that, changes in phenytoin's bioavailability were reported for co-administration of herbs or herbal extracts. An increase in phenytoin blood levels was established with Piper nigrum, Mentat, and Lipidum sativum in in vitro and/or in vivo studies. In contrast, herbphenytoin interactions led to sub-therapeutic levels of phenytoin in other cases with herbs such as Cannabis, Ginkgo biloba, Morinda citrifolia, Nigella sativa, and Trigonella foenum graceum. In addition, the findings of other pharmcodynamic experiments showed that various herbs, including Zizyphus jujube, Terminalia chebula, Curcuma longa L, and Centella asiatica, improved the pharmacological impact of phenytoin. To reduce the patients' health risks, health professionals involved in their treatment are expected to be thoroughly educated about the interactions between phenytoin and medicinal plants.

Phenytoin's Pharmacological Interactions with Medicinal Herbs: A Review

Delivery of free amino acids into and through the stratum corneum of the skin using micro emulsions and microemulsion-based hydrogels: Formulation, characterization, and ex-vivo permeation studies

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