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The aim of this study was to develop a suitable clotrimazole (CLT)-loaded mucoadhesive vaginal gel (CLT-MVG) for topical applications in vaginal candidiasis. Ten CLT-MVG formulations were prepared, consisting of mixtures of acid polyacrylic (Carbopol 940) and polyethene oxides, Sentry Polyox WSRN 1105 or 750, according to an experimental D-optimal design, and CLT was suspended at a ratio of 1%. The prepared CLT-MVG formulations were studied in vitro, and the formulation containing Carbopol 940 0.89% combined with PEO 1105 1.39% was identified with the optimal rheological and in vitro bioadhesion properties, ensuring the prolonged release of CLT, with a similarity factor greater than 50, indicating dissolution profile similarity for three batches of the optimized formulation. This optimized formulation showed a pH in the tolerance range, and an adequate ex vivo mucoadhesion time, while the FT-IR studies revealed no interactions between the excipients and CLT. The microscopic analysis identified a mean particle size of suspended CLT of 5.24 ± 0.57 μm. The in vitro antifungal activity of the optimized formulation was tested on twenty strains of Candida albicans and proved to be better compared to a marketed clotrimazole preparation, showing a greater inhibition effect ( p < 0.05). The optimized formulation could be a good candidate for the local treatment of vaginal mycosis.

Background: Mental disorders can have a significant impact on patients' life, including economic, social and individual consequences, and psychotropic medication is essential to treat these conditions. Psychotropic drug utilization studies contribute to a clearer picture of the management of these conditions. Data published from Romania on this topic is limited. The present study aims to characterize the utilization patterns of anxiolytics, antidepressants (ADs), and antipsychotics (APs) in Romania during 1998-2018. Methods: Drug utilization data were provided by Management Center for Documentation, Information and Marketing (CEGEDIM) Romania and quantitative data for each psychotropic medicine were converted to total defined daily doses (DDDs) and to DDD/1000inhabitants/day (DDD/TID). The total use of medicines in DDD/TID was computed in order to obtain the drug utilization 90% (DU90%) segment. Results: An increasing trend in total utilization of psychotropic medicines in Romania started in 2004. Anxiolytics use was predominant until 2013 and the yearly anxiolytic use over the entire study period remained between 10 and 15 DDD/TID. Diazepam lost popularity over time in detriment of the utilization of other anxiolytic benzodiazepines, such as alprazolam and lorazepam. ADs utilization markedly increased during the study period (the average annual growth rate was 13.66% starting 1999). Selective serotonin reuptake inhibitors (SSRIs) became present on the 2008 DU90% and was the dominant class of ADs, with sertraline being the most prescribed, followed by escitalopram and paroxetine. APs utilization showed an increasing trend from 2003 until 2018. Atypical APs became present on the 2008 DU90%, while typical APs were no longer included in the 2018 DU90%. Among atypical APs, olanzapine was the main agent prescribed, and starting 2010 was followed by quetiapine and risperidone. The uptake of APs long-acting formulations became more evident during the last analyzed years (2015-2018). Conclusion: We observed an increasing utilization of APs and a more prominent increase in ADs utilization in Romania during 1998-2018. The anxiolytic prescribing remained nearly stable during this time. Further research can bring more information on the various factors influencing psychotropic utilization in Romania., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Iaru, Bucsa, Farcas, Pop, Cristina, Armean, Brumboiu, Vostinaru and Mogosan.)

Coumarins are a family of benzopyrones largely distributed in the natural kingdom, being present in the seeds, fruits, flowers, or roots of various plant species. Natural coumarin compounds are found in significant concentrations in some herbs or spices used as nutraceuticals, but they are also present in cosmetics or household products, due to their pleasant odor. Therefore, an accidental exposure to high doses of coumarins, could lead to the development of harmful effects in some patients. This review summarizes the latest published data from preclinical and clinical studies with natural coumarins, focused on the investigation of general and specific toxicity, with the aim of a better understanding of the safety profile of these valuable compounds. Regulatory aspects concerning the use of natural coumarins in several world regions are also reviewed., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Heghes, Vostinaru, Mogosan, Miere, Iuga and Filip.)

Although the human eye is an easily accessible sensory organ, it remains a challenge for drug administration due to the presence of several anatomical and physiological barriers which limit the access of drugs to its internal structures. Molecular imprinting technology may be considered the avant-garde approach in advanced drug delivery applications and, in particular, in ocular therapy. In fact, molecularly imprinted polymers hold the promise to compensate for the current shortcomings of the available arsenal of drug delivery systems intended for ocular therapy. The present manuscript aims to review the recent advances, the current challenges and most importantly to raise awareness on the underexplored potential and future perspectives of molecularly imprinted polymer-based drug delivery systems intended for the treatment of eye diseases.

Propolis is a resinous mixture with a complex chemical composition, produced by honeybees and stingless bees from a variety of vegetal sources. In the last decades, propolis was extensively researched, multiple studies confirming its anti-inflammatory, antioxidant, antimicrobial, and wound-healing properties. More recently, due to an exponential increase in the number of patients with metabolic diseases, there is also a growing interest in the study of antidiabetic, antihyperlipidemic, and anti-obesity effects of propolis. The aim of this review was to evaluate the potential role of propolis in the prevention and treatment of metabolic diseases like diabetes mellitus, dyslipidemia, and obesity. The preclinical in vivo and in vitro pharmacological models investigating antidiabetic, antihyperlipidemic, and anti-obesity effects of propolis were reviewed with a focus on the putative mechanisms of actions of several chemical constituents. Additionally, the available clinical studies and an evaluation of the safety profile of propolis were also presented.

The antitussive, antioxidant, and anti-inflammatory effects of a walnut ( Juglans regia L.) septum extract (WSE), rich in bioactive compounds were investigated using the citric acid aerosol-induced cough experimental model in rodents. Wistar male rats were treated orally for three days with distilled water (control), codeine (reference), and WSE in graded doses. On the third day, all rats were exposed to citric acid aerosols, the number of coughs being recorded. Each animal was sacrificed after exposure, and blood and lung tissue samples were collected for histopathological analysis and the assessment of oxidative stress and inflammatory biomarkers. The results of the experiment showed a significant antitussive effect of WSE, superior to codeine. This activity could be due to cellular protective effect and anti-inflammatory effect via the stimulation of the antioxidant enzyme system and the decrease of IL-6 and CXC-R1 concentration in the lung tissue of WSE-treated animals. The antioxidant and anti-inflammatory effects of WSE were confirmed by biochemical assays and histopathological analysis. This is the first scientific study reporting the antitussive effect of walnut septum, a new potential source of non-opioid antitussive drug candidates, and a valuable bioactive by-product that could be used in the treatment of respiratory diseases.

Metabolic diseases like diabetes mellitus or dyslipidemia have a complex etiology characterized by the interference of genetic predisposition and environmental factors like diet or lifestyle. Over time they can cause significant vascular complications, leading to dysfunction or failure of key organs (brain, heart), with possible fatal consequences or a severe reduction of life quality. Although current authorized drugs may successfully control blood glucose or cholesterol level, their use is often associated with severe side effects, therefore the development of new drug candidates is necessary for a better management of metabolic diseases. Among potential new drug sources, aromatic plants rich in essential oils like Melissa officinalis L., Mentha x piperita L., Cuminum cyminum L. or Pistacia lentiscus L. var. chia are very promising due to their diverse chemical composition and multiple mechanisms of action. This review describes a series of recent experimental studies investigating antidiabetic and hypolipemic effects of essential oils extracted from several aromatic plant species with an ethnopharmacological relevance in the Balkan peninsula. The pharmacological models used in the studies together with the putative mechanisms of action of the main constituents are also detailed. The presented data clearly sustain a potential administration of the studied essential oils for the prevention and treatment of metabolic diseases. Further research is needed in order to ascertain the therapeutic importance of these findings., (Copyright © 2020 Heghes, Filip, Vostinaru, Mogosan, Miere, Iuga and Moldovan.)

Antioxidant dietary intervention is considered a potential strategy in delaying age-related dysfunctions. In this study of 56 days, we assessed the antioxidant effects of walnut kernel (WK) and walnut septum extract (WSE) in a D-galactose (D-gal)-induced aging model and in a naturally aged rat model. Young Wistar rats, treated with D-gal (1200 mg/week), and old rats received daily WK or WSE added to the feed. After 8 weeks, blood, liver, and brain samples were collected and hematological, biochemical, oxidative stress biomarkers, histological, and immunohistochemical analyses were performed. Moreover, acetylcholinesterase activity was investigated in brain homogenates. The outcomes demonstrated significant improvement in cellular antioxidant activity and/or decrease of reactive oxygen species, advanced glycation end products, nitric oxide, malondialdehyde, or increase of glutathione after WK or WSE intake in both models. Additionally, WSE showed hypoglycemic effect, and both WK and WSE lowered acetylcholinesterase activity. Both diets could protect neurons against the induced senescence and could reverse the pathological conditions in the physiological aged brain. Thus, dietary supplementation with WK or WSE can maintain the liver and brain health and reduce the risk of age-related diseases, as well as delaying the onset of aging processes.

The antispasmodic effect of drugs is used for the symptomatic treatment of cramping and discomfort affecting smooth muscles from the gastrointestinal, billiary or genitourinary tract in a variety of clinical situations.The existing synthetic antispasmodic drugs may cause a series of unpleasant side effects, and therefore the discovery of new molecules of natural origin is an important goal for the pharmaceutical industry. This review describes a series of recent studies investigating the antispasmodic effect of essential oils from 39 plant species belonging to 12 families. The pharmacological models used in the studies together with the mechanistic discussions and the chemical composition of the essential oils are also detailed. The data clearly demonstrate the antispasmodic effect of the essential oils from the aromatic plant species studied. Further research is needed in order to ascertain the therapeutic importance of these findings., Competing Interests: The authors declare no conflict of interest.

Cataracts are responsible for half of the world blindness, surgery being the only viable treatment. Lutein, a naturally occurring carotenoid in the eye, has the potential to reduce cataract progression by protecting the eye from photo-oxidative stress. To restore the eye's natural line of defense against photo-oxidative stress, a formulation was developed using zein and poly(lactic-co-glycolic acid) nanoparticles (NPs) embedded in an optimized bioadhesive thermosensitive gel for the delivery of lutein via topical application. Cataracts were induced in Crl:WI rats via selenite injection at 13 days post-partum, followed by 7 days of treatment with free lutein or lutein-loaded NPs administered orally or topically. Cataract severity was significantly reduced in rats treated with topical applications of lutein-loaded NPs compared to the positive control, while no significant differences were observed in rats treated with other lutein formulations including oral and topically applied free lutein., (Copyright © 2018 Elsevier Inc. All rights reserved.)

This work was aimed at correlating the chemotype of three Mentha species cultivated in Romania with an in vivo study of the anti-inflammatory and antinociceptive effects of essential oils. The selected species were Mentha piperita L. var. pallescens (white peppermint), Mentha spicata L. subsp. crispata (spearmint), and Mentha suaveolens Ehrh. (pineapple mint). Qualitative and quantitative analysis of the essential oils isolated from the selected Mentha species was performed by gas chromatography coupled with mass spectrometry (GC-MS). The anti-inflammatory activity of the essential oils was determined by the rat paw edema test induced by λ-carrageenan. The antinociceptive effect of the essential oils was evaluated by the writhing test in mice, using 1% ( v / v ) acetic acid solution administered intraperitonealy and by the hot plate test in mice. The results showed a menthol chemotype for M. piperita pallescens , a carvone chemotype for M. spicata, and a piperitenone oxide chemotype for M. suaveolens . The essential oil from M. spicata L. (EOMSP) produced statistically significant and dose-dependent anti-inflammatory and antinociceptive effects.

Recently, a series of thiazolo arene ruthenium complexes were found to be highly cytotoxic in vitro, on both cisplatin-sensitive and cisplatin-resistant ovarian cancer cells. The most active compound of the series, [(η(6)-p-cymene)Ru(L)Cl]Cl (L = 1-(2-(2-(3-chlorobenzylidene)hydrazinyl)-4-methylthiazol-5-yl)ethanone), was selected for an in vivo study in order to assess its safety profile. The ruthenium complex was administered to female Crl:WI rats orally, by gastric intubation and intraperitoneal injection. The hematological parameters and the histopathological changes in liver, kidneys, spleen and brain were investigated after a 14-days treatment. The substance was very well tolerated orally, with a LD50 value of over 2000 mg/kg body weight. Symptoms were observed only in the first day after intraperitoneal administration of the highest dose, with a LD50 value between 300 and 2000 mg/kg bw. The hematological profile was not modified at any of the tested doses, after both oral and intraperitoneal acute administration. Structural modifications (moderate lymphocytolysis) were identified only in the spleen at the highest tested dose. In conclusion, the thiazolo arene ruthenium complex was very well tolerated orally and had a low acute toxicity after intraperitoneal administration in Crl:WI rats The results justify further investigation to determine the in vivo therapeutic potential of this promising ruthenium complex., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Background: It is generally recognized that adverse drug reactions (ADRs) represent a major concern of health systems in terms of early recognition, proper management and prevention. The aims of this study were to identify the most frequent ADRs recognized by the attending physicians, study their nature and target these ADRs in order to take future preventive measures., Methods: A prospective study was conducted over a 12-month period in an internal medicine department using stimulated spontaneous reporting for identifying ADRs. All ADRs reported by physicians were followed up to the patient's discharge and evaluated by an independent group of pharmacologists. Causality, severity and preventability were assessed., Results: Of the 1854 admissions, 112 ADRs in 94 patients (5.07%) were validated from the total of 118 ADRs reported. The overall incidence of serious ADRs in the hospitalized patients was 4.7%. According to the MedDRA classification, the most frequent ADRs affected the gastrointestinal system, followed by metabolic and vascular systems. The drugs most frequently involved were cardiovascular agents, anticoagulants and NSAIDs. Drug interactions were responsible for 25.9% of ADRs. According to the selected preventability scale, 40.18% ADRs were classified as 'potentially preventable' and 9.82% 'definitely preventable'. Most of the ADRs were 'type A' reactions and as such could have been avoided simply by adjusting the doses or by avoiding drug interactions., Conclusions: Serious ADRs in hospitalized patients are common and often preventable. Preventing strategies should target drug prescription. Adequate training regarding pharmacology and optimization of drug therapy might help reduce ADRs' morbidity and mortality., (Copyright (c) 2010 European Federation of Internal Medicine. Published by Elsevier B.V. All rights reserved.)