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Chemotherapy-induced cardiotoxicity is a major cause of morbidity and mortality in cancer survivors. Myocardial dysfunction is one of the most frequent problems of chemotherapy, with highly important unfavorable effects on the prognosis in the short and long term. Its association with malignant pathology influences the compliance with specific oncological therapy and the healing process as well. Therefore, the myocardial dysfunction is becoming a reason for expanded morbidity and even early mortality for this category of patients. Our study demonstrates that cytostatics in the anthracycline class, especially Doxorubicin with a cumulative dose of more than 400 mg/m2, their association with "targeted" molecular therapies and Cyclophosphamide, along with the co-existence of cardiovascular risk factors such as hypertension and dyslipidemia, can affect longitudinal myocardial mechanics, which can be studied and tracked by decreasing the LSsubendo echocardiographic parameter in the first 12 months of cytostatic treatment. After the 6th dose of chemotherapy, approximately 50% of the patients under study had pathological changes in LSsubendo, and after the 8th treatment this number rose to 88%. In our study we demonstrated that the reduction in GLS between the two evaluated moments, pre-treatment and after 12 months, was influenced by the treatment with anthracyclines, with Doxorubicin administered in a cumulative dose > 400 mg/m2, with the association of cytostatic classes consisting of: anthracyclines, "targeted" molecular therapies, and cyclophosphamide, and by the coexistence of hypertension and dyslipidemia. Our results on the variation of GLS and LSsubendo at 12 months of the research for patients with hematological neoplasia are consistent with other data in literature, with myocardial deformity parameters changing early during cytostatic specific treatment, thus preceding a decline in LVEF. An early diagnosis of myocardial dysfunction is feasible by using longitudinal deformation criterion (parameters) assessed by 2D speckle tracking echocardiography.

Skin tags, also known as fibroepithelial polyps (FPs) or acrochordons, are soft, pigmented excrescences, with a prevalence of 50–60% in the population, occurring especially in the fourth decade of life. To date, FPs have been efficiently eliminated using minimum invasive methods such as surgical removal, cauterization, laser irradiation, and cryosurgery. Over-the-counter treatments are also of interest for patients due to their non-invasive character, but their clinical efficiency has not been clearly demonstrated. This study was designed in order to evaluate the efficacy of a modern-pharmaceutical-formulation-type poloxamer-based binary hydrogel, having Origanum vulgare L. essential oil (OEO-PbH) as an active ingredient in the management of FPs. The formulation has been shown to possess good qualities in terms of stability and sterility. Non-invasive measurements revealed changes in some physiological skin parameters. An increase in transepidermal water loss (TEWL) and erythema index was noted, while skin surface water content (SWC) decreased during eight weeks of treatment. The macroscopic evaluation revealed that the FPs dried and shrunk after topical treatment with OEO-PbH. Clinically, patients presented a lowering of the number of lesions on the treated area of 20–30% after one month of treatment and around 50% after the second month. Histopathological examination suggests that topical treatment with OEO-PbH may induce histological changes in the epidermis, dermis, and fibrovascular cores of FPs, including a loss of thickness, reduced size and number of blood vessels, and low cellularity. These changes may contribute to the observed reduction in size of FPs after treatment with OEO-PbH.

Liana Suciu,1 Maria Suciu,1 Mirela Voicu,1 Raluca Mureșan,2 Florina Viorica Pârv,3 Valentina Buda,1 Carmen Cristescu1 1Department of Pharmacology and Clinical Pharmacy, Faculty of Pharmacy, University of Medicine and Pharmacy Victor Babeș, Timisoara, Romania; 2Department of Mathematics, Faculty of Mathematics and Informatics, West University, Timisoara, Romania; 3Department of Cardiology, Faculty of Medicine, University of Medicine and Pharmacy Victor Babeș, Timișoara, RomaniaCorrespondence: Maria Suciu; Mirela VoicuDepartment of Pharmacology and Clinical Pharmacy, Faculty of Pharmacy, University of Medicine and Pharmacy Victor Babeș, Eftimie Murgu Square, No. 1-3, Timișoara, RomâniaTel +40723319050; +40745763424Email suciu.maria@umft.ro; mavoicu@yahoo.comPurpose: Romania has a high prevalence of hypertension (45.1% in 2016). Whether this is attributable to a low rate of treatment adherence—which can aggravate the pathology and reduce patients’ quality of life (QoL)—is unknown. To address this point, the present study investigated the factors that influence short- and long-term adherence and QoL in patients with arterial hypertension using a specially designed questionnaire.Patients and Methods: The study enrolled 289 patients at different stages of hypertension with or without comorbidities. The diagnosis of hypertension was established by the cardiologist, and treatment regimens were communicated by patients to the clinical pharmacist who administered the questionnaire, which comprised 7 domains with variable numbers of items.Results: The majority of surveyed patients (57.43%) considered that their capacity for effort was decreased because of their hypertension, with 65.05% reporting that they were affected by symptoms associated with high blood pressure (eg, headache and dizziness). Most patients (71.28%) understood the consequences of discontinuing their medication and the severe complications of hypertension, and 69.55% indicated that they would not stop treatment if they experienced side effects. For 53.28% of patients, social activity was significantly affected by their condition. Only 47.05% of patients underwent regular mandatory medical examinations and 55.36% periodically monitored their blood pressure at home. A regression analysis revealed correlations between specific questionnaire items and patient characteristics.Conclusion: Nonpharmacologic factors that were shown to influence patients’ adherence to treatment and QoL included the level of health education and knowledge of disease complications, self-monitoring of hypertension, and consultation with medical and pharmaceutical healthcare providers regarding hypertension and its treatment.Keywords: arterial hypertension, quality of life, adherence, medication

In the last decades, both animal and human studies have neglected female subjects with the aim of evading a theorized intricacy of feminine hormonal status. However, clinical experience proves that pharmacological response may vary between the two sexes since pathophysiological dissimilarities between men and women significantly influence the pharmacokinetics and pharmacodynamics of drugs. Sex-related differences in central nervous system (CNS) medication are particularly challenging to assess due to the complexity of disease manifestation, drugs’ intricate mechanisms of action, and lack of trustworthy means of evaluating the clinical response to medication. Although many studies showed contrary results, it appears to be a general tendency towards a certain sex-related difference in each pharmacological class. Broadly, opioids seem to produce better analgesia in women especially when they are administered for a prolonged period of time. On the other hand, respiratory and gastrointestinal adverse drug reactions (ADRs) following morphine therapy are more prevalent among female patients. Regarding antidepressants, studies suggest that males might respond better to tricyclic antidepressants (TCAs), whereas females prefer selective serotonin reuptake inhibitors (SSRI), probably due to their tolerance to particular ADRs. In general, studies missed spotting any significant sex-related differences in the therapeutic effect of antiepileptic drugs (AED), but ADRs have sex variations in conjunction with sex hormones’ metabolism. On the subject of antipsychotic therapy, women appear to have a superior response to this pharmacological class, although there are also studies claiming the opposite. However, it seems that reported sex-related differences regarding ADRs are steadier: women are more at risk of developing various side effects, such as metabolic dysfunctions, cardiovascular disorders, and hyperprolactinemia. Taking all of the above into account, it seems that response to CNS drugs might be occasionally influenced by sex as a biological variable. Nonetheless, although for each pharmacological class, studies generally converge to a certain pattern, opposite outcomes are standing in the way of a clear consensus. Hence, the fact that so many studies are yielding conflicting results emphasizes once again the need to address sex-related differences in pharmacological response to drugs.

Since the prevalence of heart failure (HF) increases with age, HF is now one of the most common reasons for the hospitalization of elderly people. Although the treatment strategies and overall outcomes of HF patients have improved over time, hospitalization and mortality rates remain elevated, especially in developed countries where populations are aging. Therefore, this paper is intended to be a valuable multidisciplinary source of information for both doctors (cardiologists and general physicians) and pharmacists in order to decrease the morbidity and mortality of heart failure patients. We address several aspects regarding pharmacological treatment (including new approaches in HF treatment strategies [sacubitril/valsartan combination and sodium glucose co-transporter-2 inhibitors]), as well as the particularities of patients (age-induced changes and sex differences) and treatment (pharmacokinetic and pharmacodynamic changes in drugs; cardiorenal syndrome). The article also highlights several drugs and food supplements that may worsen the prognosis of HF patients and discusses some potential drug–drug interactions, their consequences and recommendations for health care providers, as well as the risks of adverse drug reactions and treatment discontinuation, as an interdisciplinary approach to treatment is essential for HF patients.

pigenin (API) is a phytocompound belonging to the subclass of flavones that can be found in both functional foods as well as medicinal plants. Recent studies have assigned API antioxidant, anti-inflammatory, anti-spasmodic, anti-viral, anti-thrombotic, anti-angiogenic and chemopreventive potential in vitro on various cell lines and/or in experimental animal models. Apigenin-7-O-glucoside (API-7) is one of its main glycosides and can be commonly found in chamomile flowers, parsley, celery. The aim of this study was to evaluate the in vitro anti-proliferative and pro-apoptotic effects of API and its glycoside (apigenin-7-O-glucoside) against HeLa human cervical cancer cells. Results have shown that in the set experimental conditions both the aglycone as well as the heteroside elicit antiproliferative and pro-apoptotic potential against the screened cell line, the aglycone being more active than the heteroside.

Background Rational use of medications and monitoring of prescriptions in elderly patients is important to decrease the number and duration of hospitalizations, emergency medical consultations, mortality, as well as medical costs. Purpose To identify potentially inappropriate medications (PIMs) and potential prescription omissions (PPOs), and determine their prevalence based on the Screening Tool of Older Persons' potentially inappropriate Prescriptions (STOPP) v2 criteria and Screening Tool to Alert doctors to Right Treatment (START) v2 criteria for patients aged >65 years. Methods This cross-sectional study was conducted in two rural counties in Romania based on electronic prescriptions for chronic conditions (EPCCs) issued from 30 days to 90 days by a specialist or general practitioner. Collected EPCCs were evaluated by an interdisciplinary team of specialists based on 26 STOPP v2 criteria and 10 START v2 criteria. Results PIM prevalence was 25.80% and PPO prevalence was 41.72% for 646 EPCCs. The mean age of patients was 75 years and the mean number of drugs per EPCC was four. The most frequently identified PIMs were treatment duration (6.65%), theophylline administration (5.72%), drug indication (4.64%), cyclo-oxygenase-2 non-steroidal anti-inflammatory drugs (1.39%), and zopiclone prescription (0.77%). Statins (24.76%), beta-blockers (8.04%), and beta-2 agonist/antimuscarinic bronchodilators (5.88%) were the most frequently identified PPOs. Conclusion PPOs were more prevalent than PIMs for elderly populations living in the two rural counties in Romania we studied. Health practitioners (family physicians, specialists, and pharmacists) should focus on prophylactic and curative considerations when prescribing agents to decrease the morbidity and mortality of elderly rural Romanian patients.

Purpose This study aimed to assess the serum levels of intracellular adhesion molecule (sICAM-1), and vascular cell adhesion molecule (sVCAM-1), in the first psychotic episode schizophrenia (SZ) patients, before and after six months of antipsychotic treatment. Patients and methods The study included 50 patients with a first hospitalization for SZ and 50 healthy control subjects that were patient-matched regarding age, gender, body mass index and smoking status. The evaluation included the presence of cardiovascular risk factors, measurements of systolic and diastolic blood pressure, body mass index, smoking status, ankle-brachial index, carotid intima-media thickness, and echocardiography. The Brief Psychiatric Rating Scale (BPRS) score was calculated for the patients. The plasma levels of fasting glucose, total cholesterol, LDL-cholesterol, HDL-cholesterol, triglycerides, sICAM-1 and sVCAM-1 were determined at baseline in all subjects and after six months of antipsychotic treatment. Thirty patients (60%) were treated with olanzapine and 20 (40%) with risperidone. Results The average age of patients experiencing their first episode of SZ was 29.7±6.6 years, and 23 (46%) were men. The initial sICAM-1 levels of the patients were lower than those of the control group (P Conclusion In the patients experiencing an FEP of SZ, the levels of sICAM-1 were lower, while the levels of sVCAM-1 were higher than in the healthy control subjects. The antipsychotics used in the treatment of schizophrenia increased sICAM-1 and decreased sVCAM. The baseline level of sVCAM-1 was an independent predictor of a BPRS score >120 at baseline.

Background and Objectives: The present study demonstrates that apart from the well-known toxicity of liposoluble vitamins, some hydrosoluble vitamins may also exert toxicity, thus, routine supplementation with vitamins or ingestion of fortified foods should not be considered harmless. The study addresses the possible correlations between the physico-chemical properties and the side effects of vitamins when taken in high doses or for a too long a period. Materials and Methods: The FAFDrugs4.0 computational tool was used for computational assessment of the ADMET profile of several hydro- and liposoluble vitamins. Results: ADMET analysis revealed the following major data: vitamin B3 and B13 showed reduced structural complexity, thus, a relative toxicological potential may be exerted. Vitamins B1 and B7 were found to have good oral absorption and thus good bioavailability, while Vitamin B3 was found to have decreased oral absorption. In addition, all of the liposoluble vitamins reflected higher complexity, much greater than most of the potentially therapeutically-proven compounds. Conclusions: The present study emphasizes the importance between the physico-chemical properties of vitamins and their possible toxicological impact.

Four alcoholic extracts from Romanian Cruciferous species—cabbage, acclimatized broccoli, black radish and cauliflower—were obtained in a microwave field. The extracts showed good and symmetric antioxidant activity (0.97–1.13 mmol/L TE) and good phenolic content (1001–1632 mg GAE/L). For the HPLC method, the limit of detection (LOD), limit of quantitation (LOQ) and recovery degree were established. The small values of LOD and LOQ indicated a great fit of data. The HPLC method achieved satisfactory quantitative recoveries in the range of 96%–122%, except for the lowest sinigrin concentration (8.774 µg/mL). The presence of metals in the studied extracts falls within the allowed limits. The four Cruciferous extracts showed good and slightly asymmetric antibacterial activities against some Gram-positive and Gram-negative bacteria, including strains with known resistance to antibiotics. Moreover, greater inhibitory effects were exhibited against Gram-negative bacteria. Asymmetrically, no inhibition was observed on the fungal strains. Therefore, the present results may suggest that some alcoholic extract formulas of cabbage and black radish (presenting good antibacterial activity) might be helpful in the antimicrobial fight and could be successfully used on selected cases and strains.

Background Thrombospondin-1 (TSP-1) is a matricellular functional protein of the extracellular matrix. As it is not constitutively present extracellularly, its secretion is enhanced in several situations, namely injury, chronic pathology, tissue remodeling, angiogenesis, and aging. Over the last decade, TSP-1 has been reported to be involved in complex and opposing biological effects on vasculature in the context of NO signaling. Several studies have reported high patient TSP-1 plasma levels, indicating that the protein can potentially serve as a prognostic marker for pulmonary arterial hypertension. Materials and methods Here, we aimed to quantify TSP-1 serum levels in hypertensive patients with endothelial dysfunction before and after one year of treatment with Perindopril (an antihypertensive drug with vasoprotective properties). Results After one year of treatment, TSP-1 levels increased in hypertensive patients compared to baseline (T0: 8061.9 ± 3684.80 vs T1: 15380±5887 ng/mL, p

Background Bacterial multidrug resistance currently poses an increasingly serious threat, with important clinical consequences regarding treatment options. In 2017, the WHO released a global list of resistant bacteria, identifying multidrug-resistant (MDR) Gram-negative bacteria such as carbapenem-resistant Enterobacteriaceae, Pseudomonas aeruginosa or Acinetobacter baumannii, extended-spectrum cephalosporin-resistant Enterobacteriaceae as critical priorities for developing new strategies of treatment. Purpose The novelty presented in this study refers to the evaluation of the volatile oil obtained from the leaves of Mentha×piperita L., on MDR strains from hospitalized patients. Material and methods The essential oil was extracted by steam distillation and tested on six reference bacterial strains and also on the MDR strains collected from patients of the "Pius Brinzeu" Emergency Clinical County Hospital Timișoara. The in vitro antibacterial activity was evaluated by agar disk diffusion method and microdilution method. Results Testing the antibacterial activity of peppermint oil on both reference strains and isolated MDR strains from hospitalized patients demonstrated its bactericidal effect. Minimum inhibitory concentration (MIC) was lower (20 mg/mL) for Staphylococcus aureus, Escherichia coli and Proteus mirabilis and higher (40 mg/mL) for Klebsiella pneumoniae, Pseudomonas aeruginosa and Acinetobacter baumannii strains. Minimum bactericidal concentration (MBC) was equal to MIC, with the exception of Pseudomonas aeruginosa strains, where MBC was the double of MIC. Conclusion The present study highlights the bactericidal activity of Mentha×piperita L. essential oil on all tested MDR or extensively drug-resistant Gram-positive and Gram-negative strains of Staphylococcus aureus, Escherichia coli, Klebsiellapneumoniae, Proteus mirabilis, Pseudomonas aeruginosa and Acinetobacter baumannii. This oil may be a therapeutic option in the near future for many infectious diseases produced by MDR bacteria.

The present study was conducted in order to evaluate the biological activity of thyme aqueous extract as compared to the silver nanoparticles obtained on it on four different cancer lines: non-melanoma skin cancer (A431 cell line), melanoma skin cancer (A375cell line), hormone dependent breast cancer (MCF-7 cell line), and non-hormone dependent breast cancer (MDA-MB-231 cell line). Of particular importance in the study of biological activity is the chemical composition. Formulas rich in compounds of classes like those of flavonoids are recognized for their efficacy and important antioxidant effect. The extract tested at various concentrations ranging from 10-1000 �g/mL exhibited a pronounced effect only on MCF-7 cells at the highest concentration tested and regarding the biosynthesized silver nanoparticles, the effect can be noted even at 1 � M also only in the case of MCF-7 cells.

Purpose: Endoglin is a transmembrane glycoprotein which plays an important role in maintaining cardiovascular homeostasis. One of its forms, soluble endoglin (sEng), a molecule with antiangiogenic properties, has been found overexpressed in patients suffering from hypercholesterolemia, diabetes mellitus and hypertension, and is proposed as a marker of endothelial damage. Accordingly, we aimed to quantify the efficacy of various antihypertensive regimens on sEng levels, in hypertensive patients with endothelial dysfunction. Patients and methods: 323 patients were enrolled, and there were 99 patients with normal blood pressure values, 106 hypertensive patients under chronic treatment with different types of antihypertensive molecules (beta blockers, calcium channel blockers, and diuretics) in monotherapy, and 118 hypertensive patients under chronic treatment with perindopril. sEng plasma levels were quantified and were correlated with classical methods of assessing the endothelial damage. Results: Patients under chronic treatment with perindopril had lower sEng plasma levels compared with the other group of hypertensive patients under different regimens of antihypertensive treatment (sEng: 4.73±1.39 versus 5.63±2.33, p

Cardiovascular diseases represent the main cause of morbidity and mortality worldwide. Obesity, sedentary life style, diet, smoking and stress are the principal inducers of hypertension, endothelium dysfunction and insulin resistance in the developed countries. The latest in vitro and in vivo studies on different type of extracts obtained from black-fruited Aronia highlight its excellent cardioprotective actions for the prevention and treatment of cardiovascular and metabolic disorders. So, this chapter aims to bring an up-to-date regarding the antioxidant, anti-inflammatory, anti-atherosclerotic, antiplatelet, blood pressure, glucose and lipid reduction properties of black-fruited Aronia, as a possible new therapeutic strategy for the primary and secondary prevention of cardiovascular pathologies.

One of the most important class of natural compounds with successful preclinical results in the management of cancer is the flavonoids. Due to the plethora of biological activities, apigenin (4 ′ ,5,7 trihydroxyflavone) is a main representant of the flavone subclass. Although the antiproliferative and antiangiogenic effects of apigenin were studied on a significant number of human and murine melanoma cell lines, in order to complete the data existing in the literature, the aim of this study is to evaluate the in vitro effect of apigenin on SK-MEL-24 human melanoma cell line as well as in vivo on tumor angiogenesis using the aforementioned cell line on the chorioallantoic membrane assay. Results have shown that in the range of tested doses, the phytocompound presents significant antiproliferative, cytotoxic, and antimigratory potential at 30 μM, respectively, 60 μM. Moreover, the phytocompound in both tested concentrations limited melanoma cell growth and migration and induced a reduced angiogenic reaction limiting melanoma cell development.

Populus nigra L. (Salicaceae family) is one of the most popular trees that can be found in deciduous forests. Some particularities that characterize the Populus genus refer to the fact that it includes more than 40 species, being widespread especially in Europe and Asia. Many residues, parts of this tree can be used as a bioresource for different extracts as active ingredients in pharmaceuticals next to multiple benefits in many areas of medicine. The present review discusses the latest findings regarding the phytochemical composition and the therapeutic properties of Populus nigra L. buds. The vegetal product has been described mainly to contain phenolic compounds (phenols, phenolic acids and phenylpropanoids), terpenoids (mono and sesquiterpenoids), flavones (e.g., apigenol and crysin), flavanones (e.g., pinocembrin and pinostrombin), caffeic/ferulic acids and their derivates, and more than 48 phytocompounds in the essential oils. The resinous exudates present on the buds have been the major plant source used by bees to form propolis. Several studies depicted its antioxidant, anti-inflammatory, antibacterial, antifungal, antidiabetic, antitumor, hepatoprotective, hypouricemic properties and its effects on melanin production. All these lead to the conclusion that black poplar buds are a valuable and important source of bioactive compounds responsible for a wide range of therapeutic uses, being a promising candidate as a complementary and/or alternative source for a large number of health problems. The aim of the review is to gather the existing information and to bring an up to date regarding the phytochemical and therapeutic uses of Populus nigra L. buds.

Oenothera biennis L. (OB), also commonly known as evening primrose, belongs to the Onagraceae family and has the best studied biological activity of all the members in the family. In therapy, the most frequently used type of extracts are from the aerial part, which are the fatty oils obtained from the seeds and have a wide range of medicinal properties. The aim of this study was to evaluate the phytochemical composition and biological activity of OB hydroalcoholic extract and to provide directions for the antimicrobial effect, antiproliferative and pro-apoptotic potential against A375 melanoma cell line, and anti-angiogenic and anti-inflammatory capacity. The main polyphenols and flavonoids identified were gallic acid, caffeic acid, epicatechin, coumaric acid, ferulic acid, rutin and rosmarinic acid. The total phenolic content was 631.496 &micro, gGAE/mL of extract and the antioxidant activity was 7258.67 &mu, molTrolox/g of extract. The tested extract had a mild bacteriostatic effect on the tested bacterial strains. It was bactericidal only against Candida spp. and S. aureus. In the set of experimental conditions, the OB extract only manifested significant antiproliferative and pro-apoptotic activity against the A375 human melanoma cell line at the highest tested concentration, namely 60 &mu, g/mL. The migration potential of A375 cells was hampered by the OB extract in a concentration-dependent manner. Furthermore, at the highest tested concentration, the OB extract altered the mitochondrial function in vitro, while reducing the angiogenic reaction, hindering compact tumor formation in the chorioallantoic membrane assay. Moreover, the OB extract elicited an anti-inflammatory effect on the experimental animal model of ear inflammation.

The aim of this work was to assess the impact of an excipient in a pharmaceutical formulation containing candesartan cilexetil over the decomposition of the active pharmaceutical ingredient and to comparatively investigate the kinetics of degradation during thermolysis in an oxidative atmosphere under controlled thermal stress. To achieve this, the samples were chosen as follows: pure candesartan cilexetil and a commercial tablet of 32 mg strength. As a first investigational tool, Universal attenuated total reflection Fourier transform infrared (UATR-FTIR) spectroscopy was chosen in order to confirm the purity and identity of the samples, as well as to check if any interactions took place in the tablet between candesartan cilexetil and excipients under ambient conditions. Later on, samples were investigated by thermal analysis, and the elucidation of the decomposition mechanism was achieved solely after performing an in-depth kinetic study, namely the use of the modified non-parametric kinetics (NPK) method, since other kinetic methods (American Society for Testing and Materials&mdash, ASTM E698, Friedman and Flynn&ndash, Wall&ndash, Ozawa) led to inadvertencies. The NPK method suggested that candesartan cilexetil and the tablet were degraded by the contribution of two steps, the main being represented by chemical degradation and the secondary being a physical transformation. The excipients chosen in the formulation seemed to have a stabilizing effect on the decomposition of the candesartan cilexetil that was incorporated into the tablet, relative to pure active pharmaceutical ingredient (API), since the apparent activation energy for the decomposition of the tablet was 192.5 kJ/mol, in comparison to 154.5 kJ/mol for the pure API.

The influence of excipients on the stability of sodium levothyroxine pentahydrate (LTSS) under ambient conditions and thermal stress was evaluated. Since LTSS is a synthetic hormone with a narrow therapeutic index, the interactions of LTSS with excipients can lead to a drastic diminution of therapeutic activity. Ten commonly used pharmaceutical excipients with different roles in solid formulations were chosen as components for binary mixtures containing LTSS, namely, starch, anhydrous lactose, D-mannitol, D-sorbitol, gelatin, calcium lactate pentahydrate, magnesium stearate, methyl 2-hydroxyethyl cellulose (Tylose), colloidal SiO2 (Aerosil) and talc. As investigational tools, universal attenuated total reflectance- Fourier transform infrared spectroscopy UATR-FTIR spectroscopy and thermal analysis were chosen and used as follows: UATR-FTIR spectra were drawn up for samples kept under ambient conditions, while thermoanalytical tools (TG/DTG/HF data) were chosen to evaluate the inducing of interactions during thermal stress. The corroboration of instrumental results led to the conclusion that LTSS is incompatible with lactose, mannitol and sorbitol, and these excipients should not be considered in the development of new generic solid formulations.

Cannabis sativa L. is a plant long used for its textile fibers, seed oil, and oleoresin with medicinal and psychoactive properties. It is the main source of phytocannabinoids, with over 100 compounds detected so far. In recent years, a lot of attention has been given to the main phytochemicals present in Cannabis sativa L., namely, cannabidiol (CBD) and Δ9-tetrahydrocannabinol (THC). Compared to THC, CBD has non-psychoactive effects, an advantage for clinical applications of anti-tumor benefits. The review is designed to provide an update regarding the multi-target effects of CBD in different types of cancer. The main focus is on the latest in vitro and in vivo studies that present data regarding the anti-proliferative, pro-apoptotic, cytotoxic, anti-invasive, anti-antiangiogenic, anti-inflammatory, and immunomodulatory properties of CBD together with their mechanisms of action. The latest clinical evidence of the anticancer effects of CBD is also outlined. Moreover, the main aspects of the pharmacological and toxicological profiles are given.

Background and Aims: Romania is among the countries with the lowest life expectancy in the European Union, the leading cause of death being represented by cardiovascular disorders (ischemic heart disease and stroke). Thus, we aimed to identify the possible prescribing problems of drugs administered as a chronic treatment in the elderly based on the current international recommendations of appropriate prescribing.

The European Commission’s 2019 report regarding the state of health profiles highlighted the fact that Romania is among the countries with the lowest life expectancy in the European Union. Therefore, the objectives of the present study were to assess the current prescription habits of general physicians in Romania related to medicines taken by the elderly population for chronic conditions in both urban and rural setting and to discuss/compare these practices with the current international recommendations for the elderly (American—Beers 2019 criteria and European—STOPP/START v.2, 2015 criteria). A total of 2790 electronic prescriptions for chronic pathologies collected from 18 community pharmacies in the western part of Romania (urban and rural zones) were included. All medicines had been prescribed by general physicians. We identified the following situations of medicine overuse: 15% of the analyzed prescriptions involved the use of nonsteroidal anti-inflammatory drugs (NSAIDs) for &gt, 2 weeks, 12% involved the use of a proton-pump inhibitor (PPI) for &gt, 8 weeks, theophylline was the bronchodilator used as a monotherapy in 3.17% of chronic obstructive pulmonary disease cases, and zopiclone was the hypnotic drug of choice for 2.31% of cases. Regarding the misuse of medicines, 2.33% of analyzed prescriptions contained an angiotensin-converting enzyme (ACE) inhibitor and an angiotensin II receptor blocker (ARB) for patients with renal failure in addition to vitamin K antagonists (AVKs) and NSAIDs in 0.43% of cases. Prescriptions for COX2 NSAIDs for periods longer than 2 weeks for patients with cardiovascular disorders accounted for 1.33% of prescriptions, and trihexyphenidyl was used as a monotherapy for patients with Parkinson’s disease in 0.18% of cases. From the included medical prescriptions, 32.40% (the major percent of 2383 prescriptions) had two potentially inappropriate medications (PIMs). Rural zones were found to be risk factor for PIMs. Decreasing the chronic prescription of NSAIDs and PPIs, discontinuing the use of hypnotic drugs, and avoiding potentially harmful drug–drug associations will have long term beneficial effects for Romanian elderly patients.

Background Bacterial multidrug resistance currently poses an increasingly serious threat, with important clinical consequences regarding treatment options. In 2017, the WHO released a global list of resistant bacteria, identifying multidrug-resistant (MDR) Gram-negative bacteria such as carbapenem-resistant Enterobacteriaceae, Pseudomonas aeruginosa or Acinetobacter baumannii, extended-spectrum cephalosporin-resistant Enterobacteriaceae as critical priorities for developing new strategies of treatment. Purpose The novelty presented in this study refers to the evaluation of the volatile oil obtained from the leaves of Mentha×piperita L., on MDR strains from hospitalized patients. Material and methods The essential oil was extracted by steam distillation and tested on six reference bacterial strains and also on the MDR strains collected from patients of the “Pius Brînzeu” Emergency Clinical County Hospital Timișoara. The in vitro antibacterial activity was evaluated by agar disk diffusion method and microdilution method. Results Testing the antibacterial activity of peppermint oil on both reference strains and isolated MDR strains from hospitalized patients demonstrated its bactericidal effect. Minimum inhibitory concentration (MIC) was lower (20 mg/mL) for Staphylococcus aureus, Escherichia coli and Proteus mirabilis and higher (40 mg/mL) for Klebsiella pneumoniae, Pseudomonas aeruginosa and Acinetobacter baumannii strains. Minimum bactericidal concentration (MBC) was equal to MIC, with the exception of Pseudomonas aeruginosa strains, where MBC was the double of MIC. Conclusion The present study highlights the bactericidal activity of Mentha×piperita L. essential oil on all tested MDR or extensively drug-resistant Gram-positive and Gram-negative strains of Staphylococcus aureus, Escherichia coli, Klebsiellapneumoniae, Proteus mirabilis, Pseudomonas aeruginosa and Acinetobacter baumannii. This oil may be a therapeutic option in the near future for many infectious diseases produced by MDR bacteria.

Minodora Andor,1,* Liana Dehelean,2,* Ana-Maria Romosan,2,* Valentina Buda,3 Gabriela Radu,1 Florina Caruntu,1 Aurora Bordejevic,1 Minodora Marinela Manea,4 Ion Papava,2 Cristina Ana Bredicean,2 Radu Stefan Romosan,2 Mirela Tomescu1 1Medical Semiology II, Department of Internal Medicine I, “Victor Babeş” University of Medicine and Pharmacy, Timişoara, Romania; 2Discipline of Psychiatry, Department of Neurosciences, “Victor Babeş” University of Medicine and Pharmacy, Timisoara, Romania; 3Pharmacology and Clinical Pharmacology, 2nd Department, “Victor Babeş” University of Medicine and Pharmacy, Timişoara, Romania; 4Department of Psychology, Medical Education, “Iuliu HaÅ£ieganu” University of Medicine and Pharmacy, Cluj-Napoca, Romania *These authors contributed equally to this work and thus share first authorship Purpose: This research article assesses the cardiovascular impact of long-term injectable antipsychotic therapy on patients diagnosed with schizophrenia spectrum disorders. In our study, we attempted to quantify the potential causes of cardiovascular damage, assess cardiovascular parameters, and correlate them with the time elapsed from the onset of the psychosis until the initiation of injectable antipsychotic therapy, as well as the duration of long-acting therapy, and finally, to compare two of the most utilized long-acting injectable (LAI) medications (olanzapine vs risperidone).Patients and methods: This cross-sectional study recruited 64 patients of 2 outpatient clinics undergoing treatment with LAI antipsychotics for schizophrenic spectrum disorder. The study reports outpatients’ clinical data, laboratory blood sample findings, routine echocardiography, as well as speckle tracking echocardiography.Results: Among patients with longer durations of pre-long-acting antipsychotic treatment, body mass indices, mitral velocity wave values (E and A waves), and the global longitudinal strain (GLS) measurements significantly correlated with patients’ myocardial contractility. The study also found that GLS was significantly lower in the group in which pre-LAI duration was prolonged, and was not influenced by the duration of LAI treatment. Furthermore, patients receiving olanzapine showed significantly improved myocardial contractility as measured by the aforementioned parameters, in comparison with patients treated with risperidone.Conclusion: The results of our study indicate that patients suffering from schizophrenia and who are left untreated or poorly treated for a longer period of time may develop myocardial impairment. The changes may be both secondary to a high prevalence of cardiovascular risk factors and may also be generated by the disease per se. The group who received olanzapine demonstrated improved results for a longer period of time without proper medication. Keywords: schizophrenic patients, speckle tracking echocardiography, myocardial dysfunction

Black chokeberry fruits possess a wide range of biological activities, among which the most important that are frequently mentioned in the literature are their antioxidant, anti-inflammatory, anti-proliferative, and antimicrobial properties. The present paper reports, for the first time, the encapsulation of the ethanolic extract of Aronia melanocarpa L. fruits into two mesoporous silica-type matrices (i.e., pristine MCM-41 and MCM-41 silica decorated with zinc oxide nanoparticles). The aim of this work was to evaluate the antiradicalic capacity, the antimicrobial potential, and the effects on the cell viability on a cancer cell line (i.e., A375 human melanoma cell line) versus normal cells (i.e., HaCaT human keratinocytes) of black chokeberry extract loaded on silica-type matrices in comparison to that of the extract alone. The ethanolic polyphenolic extract obtained by conventional extraction was characterized by high-performance liquid chromatography with a photodiode array detector (HPLC&ndash, PDA) and spectrophotometric methods. The extract was found to contain high amounts of polyphenols and flavonoids, as well as good radical scavenging activity. The extract-loaded materials were investigated by Fourier transform infrared spectroscopy, N2 adsorption&ndash, desorption isotherms, thermal analysis, and radical scavenger activity on solid samples. The black chokeberry extract, both free and loaded onto mesoporous silica-type matrices, exhibited a significant antioxidant capacity. Antibacterial activity was recorded only for Gram-positive bacteria, with a more potent antibacterial effect being observed for the extract loaded onto the ZnO-modified MCM-41 silica-type support than for the free extract, probably due to the synergistic effect of the ZnO nanoparticles that decorate the pore walls of silica. The cellular viability test (i.e., MTT assay) showed dose- and time-dependent activity regarding the melanoma cell line. The healthy cells were less affected than the cancer cells, with all tested samples showing good cytocompatibility at doses of up to 100 &micro, g/mL. Improved in vitro antiproliferative and antimigratory (i.e., scratch assay) potential was demonstrated through the loading of black chokeberry extract into mesoporous silica-type matrices, and the screened samples exhibited low selectivity against the tested non-tumor cell line. Based on presented results, one can conclude that mesoporous silica-type matrices are good hosts for black chokeberry extract, increasing its antioxidant, antibacterial (on the screened strains), and in vitro antitumor (on the screened cell line) properties.

This paper presents the results obtained after studying the thermal stability and decomposition kinetics of perindopril erbumine as a pure active pharmaceutical ingredient as well as a solid pharmaceutical formulation containing the same active pharmaceutical ingredient (API). Since no data were found in the literature regarding the spectroscopic description, thermal behavior, or decomposition kinetics of perindopril, our goal was the evaluation of the compatibility of this antihypertensive agent with the excipients in the tablet under ambient conditions and to study the effect of thermal treatment on the stability of perindopril erbumine. ATR-FTIR (Attenuated Total Reflectance Fourier Transform Infrared) spectroscopy, thermal analysis (thermogravimetric mass curve (TG—thermogravimetry), derivative thermogravimetric mass curve (DTG), and heat flow (HF)) and model-free kinetics were chosen as investigational tools. Since thermal behavior is a simplistic approach in evaluating the thermal stability of pharmaceuticals, in-depth kinetic studies were carried out by classical kinetic methods (Kissinger and ASTM E698) and later with the isoconversional methods of Friedman, Kissinger-Akahira-Sunose and Flynn-Wall-Ozawa. It was shown that the main thermal degradation step of perindopril erbumine is characterized by activation energy between 59 and 69 kJ/mol (depending on the method used), while for the tablet, the values were around 170 kJ/mol. The used excipients (anhydrous colloidal silica, microcrystalline cellulose, lactose, and magnesium stearate) should be used in newly-developed generic solid pharmaceutical formulations, since they contribute to an increased thermal stability of perindopril erbumine.

Ephedra alata Decne. belongs to the Ephedraceae family. It is a species of Ephedra that grows mostly in the desert. Today, the main importance of Ephedra species in the medical field is due to the presence of the alkaloids derived from phenyl-alanine, which act on the sympathetic nervous system as a sympathomimetic. The aim of this study was to conduct a phytochemical characterization of the hydroalcoholic extract of the aerial part of Ephedra alata Decne., which is indigenous to Tunis, that involves the total phenolic content, individual phenolic content, and antioxidant activity as well as a biological screening for the evaluation of the antimicrobial, antifungal, antiproliferative, pro-apoptotic, and cytotoxic potential against the MCF-7 breast cancer cell line. The results show that the hydroalcoholic extract contains polyphenolic phytocompounds (156.226 ± 0.5 mgGAE/g extract) and elicits antioxidant activity (7453.18 ± 2.5 μmol Trolox/g extract). The extract acted as a bacteriostatic agent against all tested bacterial strains, but was bactericidal only against the Gram-positive cocci and Candida spp. In the set experimental parameters, the extract presents antiproliferative, pro-apoptotic, and cytotoxic potential against the MCF-7 human breast cancer cell line.

Thrombospondin-1 (TSP-1) is a potent endogenous inhibitor of both physiological and pathological angiogenesis, widely studied as a target in drug development for treating cancer. Several studies performed in the cardiovascular field on TSP-1 are contradictory, the role of TSP-1 in the physiopathology of cardiovascular disorders (CVDs) being, for the moment, incompletely understood and may be due to the presence of several domains in its structure which can stimulate many cellular receptors. It has been reported to inhibit NO-mediated signaling and to act on the angiogenesis, tissue perfusion, endothelial cell proliferation, and homeostasis, so we aimed to quantify the effect Perindopril has on TSP-1 plasma levels in hypertensive patients with endothelial dysfunction in comparison with other antihypertensive drugs, such as beta blockers, calcium channel blockers, and diuretics, in a chronic treatment. As a conclusion, patients under treatment with Perindopril had increased plasma levels of TSP-1 compared with other hypertensive patients and with the control group. The results of this study confirms the pleiotropic properties of Perindopril: anti-proliferative, anti-inflammatory, with effects showed by quantifying a single biomarker: TSP-1.

BACKGROUND AND AIMS: Adverse drug reactions are responsible for approximatively 20% of hospital admissions in geriatric units. In Romania, around 18% of the total population is represented by people > 65 years old, the main cause of death being represented by atherosclerotic complications: myocardial infarction and stroke. Thus, we aimed to identify potentially inappropriate associations of drugs that can increase the iatrogenic events in elderly, leading to increased mortality. METHODS: This retrospective study included 2790 chronic electronic prescriptions, issued by physicians (between January 2018 and March 2019) and collected from 18 community pharmacies in Romania. The collected prescriptions were screen by a team of specialists (including cardiologist, nephrologist, generalist and clinical pharmacist) based on the Beers 2019 Criteria and the current European guidelines for each major pathology. RESULTS: 2.33% for prescriptions had an ACE inhibitor associated with an ARB, followed by “The Triple Whammy” therapy (associations of RAAS inhibitors + diuretics + NSAIDs) in 2% of cases, COX2 NSAIDs were prescribed as a chronic treatment in patients associating cardiovascular disorders (>2weeks) in 1.33% of cases, 1.15% of prescriptions has an RAAS inhibitor associated with an NSAID and 0.43% of cases had an AVK associated with an NSAID. CONCLUSIONS: Our study highlights an increased prescription of drug associations having a high risk of acute kidney injury (functional renal failure) and cardiovascular complications. Thus, the study draws attention to the urgent need for appropriate pharmacological treatment in order to also decrease the iatrogenic risk, in a population where the leading cause of death is represented by atherosclerotic complications.