Biomedicine represents one of the main study areas for dendrimers, which have proven to be valuable both in diagnostics and therapy, due to their capacity for improving solubility, absorption, bioavailability and targeted distribution. Molecular cytotoxicity constitutes a limiting characteristic, especially for cationic and higher-generation dendrimers. Antineoplastic research of dendrimers has been widely developed, and several types of poly(amidoamine) and poly(propylene imine) dendrimer complexes with doxorubicin, paclitaxel, imatinib, sunitinib, cisplatin, melphalan and methotrexate have shown an improvement in comparison with the drug molecule alone. The anti-inflammatory therapy focused on dendrimer complexes of ibuprofen, indomethacin, piroxicam, ketoprofen and diflunisal. In the context of the development of antibiotic-resistant bacterial strains, dendrimer complexes of fluoroquinolones, macrolides, beta-lactamines and aminoglycosides have shown promising effects. Regarding antiviral therapy, studies have been performed to develop dendrimer conjugates with tenofovir, maraviroc, zidovudine, oseltamivir and acyclovir, among others. Furthermore, cardiovascular therapy has strongly addressed dendrimers. Employed in imaging diagnostics, dendrimers reduce the dosage required to obtain images, thus improving the efficiency of radioisotopes. Dendrimers are macromolecular structures with multiple advantages that can suffer modifications depending on the chemical nature of the drug that has to be transported. The results obtained so far encourage the pursuit of new studies.
The prevalence of diabetes mellitus (DM) rises constantly each year worldwide. Because of that, the funds allocated for the DM treatment have increased over time. Regarding the number of DM cases, Romania is among the top ten countries in Europe. Based on the National Diabetes Programme (NDP), antidiabetic drugs and other expenditures (Self-monitoring blood glucose (SMBG) test, HbA1c, insulin pumps/insulin pumps supplies) are free of charge. This programme has undergone many changes in drugs supply, in the last two decades: re-organizing the NDP, authorization of new molecules with high prices (e.g., SGLT-2 inhibitors, etc.) or new devices (e.g., insulin pumps, etc.) The main purpose of this study is to identify and analyse the impact of the DM costs on the Romanian health budget and to highlight the evolution of these costs. A retrospective longitudinal research on the official data regarding the DM costs from 2000 to 2017 was performed. The DM funds (DMF) were adjusted with the inflation rate. In this period, the average share of DMF in the total funds allocated for health programmes was 21.3 ± 3.4%, and DMF average growth rate was 25.4% (r = 0.488, p = 0.047). On the other hand, the DMF increased more than 14 times, in spite of the patients’ number having increased only about 2.5 times. Referring to the structure of DMF, the mean value of the antidiabetic drugs cost was of 96,045 ± 67,889 thousand EUR while for other expenditures it was of 11,530 ± 7922 thousand EUR (r = 0.945, p < 0.001). Between 2008 and 2017, the total DMF was 181,252 ± 74,278 thousand EUR/year. Moreover, the average patients’ number was 667,384 ± 94,938 (r = 0.73, p = 0.016), and the cost of treatment was 215 ± 36 EUR/patient/year. Even if the cost is rising, the correct and optimal treatment is a main condition for the diabetic patient’s health and for the prevention of its complications, which have multiple socio-economic repercussions.
Currently, the efficacy of antibiotics is severely affected by the emergence of the antimicrobial resistance phenomenon, leading to increased morbidity and mortality worldwide. Multidrug-resistant pathogens are found not only in hospital settings, but also in the community, and are considered one of the biggest public health concerns. The main mechanisms by which bacteria develop resistance to antibiotics include changes in the drug target, prevention of entering the cell, elimination through efflux pumps or inactivation of drugs. A better understanding and prediction of resistance patterns of a pathogen will lead to a better selection of active antibiotics for the treatment of multidrug-resistant infections.
Nowadays, humanity is confronted with one of the most difficult challenges. Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) was identified for the first time in Hubei, China in December 2019 and produced the COVID-19 pandemic, a devastating disease that led to many complications and deaths. The authorities and the global healthcare system have been alerted regarding the prevention and treatment of this pathology. Even though worldwide quarantine was declared, health care professionals, including pharmacists, have been at the frontline in this war. Since the beginning of the pandemic, the authorities relied on the involvement of the community, hospital, or clinical pharmacists in offering support to the entire population. Also, the authorities implemented measures for emergency authorization of the vaccines, or the drugs used in COVID-19 treatment. In order to facilitate the population’s access to healthcare services, the authorities have established regulations regarding, the extension of prescriptions by pharmacists, working hours, prevention of shortages and price-increase, drive-thru services, etc. However, several countries have taken financial measures to support the pharmacies’ activity. At the same time, pharmaceutical associations elaborated guidelines for the protection of pharmacists and patients alike. Additionally, the pharmacies have come to support the health system and patients by adapting pharmaceutical care to the new needs like preparation and supply of disinfectants, patient care, information, and counseling, especially to COVID-19 patients, as well as the implementation of home drugs-delivery systems. The important roles played by pharmacists were to perform COVID-19 tests and further vaccines, as well as to combat the abundance of misinformation and fake news. The clinical and hospital pharmacy services have also been adapted. Strengthening the role of the pharmacist in the medical team was important for the purpose of providing correct and complete information regarding drugs used in the COVID-19 pathology. In all these activities, pharmacists needed creativity and professionalism, but also the support of pharmacy owners and managers. With this crisis, pharmaceutical care has entered a new phase, demonstrating the ability of pharmacists to be competent and accessible providers of public health. Based on this information, we conducted a narrative review whose purpose was to identify the impact of the authorities’ decisions on pharmaceutical practice, the involvement of professional associations, and the responsibilities of the pharmacy owners and management. On the other hand, we performed a global assessment on the pharmaceutical care services provided by community pharmacists as well as by clinical or hospital pharmacists during the COVID-19 pandemic.
This study aimed to evaluate the comparative biological effects of Polygonum aviculare L. herba (PAH) extract and quercetin-entrapped liposomes on doxorubicin (Doxo)-induced toxicity in HUVECs. HUVECs were treated with two formulations of liposomes loaded with PAH extract (L5 and L6) and two formulations of liposomes loaded with quercetin (L3 prepared with phosphatidylcholine and L4 prepared with phosphatidylserine). The results obtained with atomic force microscopy, zeta potential and entrapment liposome efficiency confirmed the interactions of the liposomes with PAH or free quercetin and a controlled release of flavonoids entrapped in all the liposomes. Doxo decreased the cell viability and induced oxidative stress, inflammation, DNA lesions and apoptosis in parallel with the activation of Nrf2 and NF-kB. Free quercetin, L3 and L4 inhibited the oxidative stress and inflammation and reduced apoptosis, particularly L3. Additionally, these compounds diminished the Nrf2 and NF-kB expressions and DNA lesions, principally L4. PAH extract, L5 and L6 exerted antioxidant and anti-inflammatory activities, reduced γH2AX formation and inhibited extrinsic apoptosis and transcription factors activation but to a lesser extent. The loading of quercetin in liposomes increased the cell viability and exerted better endothelial protection compared to free quercetin, especially L3. The liposomes with PAH extract had moderate efficiency, mainly due to the antioxidant and anti-inflammatory effects and the inhibition of extrinsic apoptosis.
The aim of this study was to determine the variability of several chemical compounds and the antioxidant and antimicrobial activities of eight types of berries harvested from two different geographical regions in the same year. The analyses were performed on bilberry, black currant, gooseberry, red currant, raspberry, sea buckthorn, strawberry and sour cherry, which were handpicked during the summer of 2019, in the same periods when they are typically harvested for consumer purposes. Total anthocyanins content (TAC), total flavonoids content (TFC), total polyphenolic compounds (TPC), determination of the Ferric-Reducing Antioxidant Power (FRAP), determination of the DPPH free radical scavenging assay (RSA), determination of nine phenolic compounds by HPLC-UV assay and antimicrobial activity were determined for undiluted hydroalcoholic extracts of all the studied berries. The results showed that the berries from Romania were richer in antioxidant compounds than the berries from Russia. The TPC content varied between 4.13–22.2 mg GAE/g d.w., TFC between 3.33–8.87 mg QE/g d.w. and TAC between 0.13–3.94 mg/g d.w. The highest variability was determined for TPC. Regarding the antioxidant activity assessed by FRAP assay, values were between 6.02–57.23 µmols TE/g d.w. and values for the RSA method between 18.44–83.81%. From the eight types of berries analyzed, bilberries and raspberries had the highest antioxidant activity considering both regions and both determination methods. Not only the type, but also the environmental and cultivation conditions in which the berries grow, can lead to variations in their chemical composition. The extracted polyphenolic compounds from the studied berries showed antibacterial properties on pathogens, such as Escherichia coli, Bacillus subtilis and Staphyloccocus aureus. The inhibitory action on Salmonella typhi and fungi Candida albicans and Aspegillus niger was absent to very low. The antimicrobial activity of the hydroalcoholic extracts was dependent on the provenance of the berries, too.
Statins are included in the category of high-frequency prescription drugs, and their use is on an upward trend worldwide. In 2012, the FDA issued a warning about possible cognitive adverse drug reactions (ADRs) related to statins, some of which are listed in the Summary of Product Characteristics, but there are still concerns about their potential risk of psychiatric events. The aim of this research was to investigate spontaneous reports containing psychiatric ADRs associated with statins by analyzing the EudraVigilance (EV) database. From January 2004 to July 2021, a total of 8965 ADRs were reported for the Systems Organ Class (SOC) “psychiatric disorders”, of which 88.64% were registered for atorvastatin (3659), simvastatin (2326) and rosuvastatin (1962). Out of a total of 7947 individual case safety reports (ICSRs) of the 3 statins mentioned above, in 36.3% (2885) of them, statins were considered the only suspected drug, and in 42% (3338), no other co-administered drugs were mentioned. Moreover, insomnia has been reported in 19.3% (1536) of cases, being the most frequent adverse reaction. A disproportionality analysis of psychiatric ADRs was performed. The Reporting Odds Ratio (ROR) and 95% confidence interval (95% CI) were calculated for simvastatin, atorvastatin and rosuvastatin compared with antiplatelets and antihypertensive drugs. The reporting probability for most ADRs of these statins compared to antiplatelets was higher. The reporting probability for insomnia, nightmares and depression produced by statins compared to antihypertensive drugs was also higher. The results of this analysis augment the existing data about a possible correlation between the administration of statins and the occurrence of psychiatric side effects.
The aim of this study was to describe and analyze epidemiological and clinical features of children screened for COVID-19 at Sibiu Pediatric Clinical Hospital during the first 9 months (March–November) of coronavirus disease pandemic in Romania. A total of 203 pediatric patients with a confirmed diagnosis of COVID-19 were included in the study. The median age of the patients was 121 (IQR 18–181) months and 52.22% had mild clinical type with pneumonia, 35.47% were moderate cases, 3.94% severe cases, 0.99% critically ill cases and 7.39% were asymptomatic. The most common symptoms were fever (n = 130, 64.03%), nasal congestion (n = 138, 67.98%), cough (n = 128, 63.05%) followed by sore throat (n = 64, 31.52%), rhinorrhea (n = 63, 31.03%), fatigue (n = 57, 28.07%), headache (n = 47, 23.15%), diarrhea (n = 39, 19.21%), vomiting (n = 32, 15.76%), myalgia (n = 24, 11.82%), abdominal pain (n = 22, 10.83%). A higher proportion of infants with severe or critical disease was encountered with lymphopenia (n = 9, 90%), neutrophilia (n = 5, 50%), leukocytosis (n = 5, 50%) compared with asymptomatic infants (n = 10, 66.67%, n = 1, 6.67%, n = 3, 20%) or mild (n = 53, 50%, n = 19, 17.92%, n = 15, 14.15%) and moderate (n = 37, 51.39%, n = 9, 12.50%, n = 6, 8.33%) cases (p = 0.095, p = 0.042, p = 0.034). Pediatric patients generally had mild or moderate type of COVID-19, and the critically ill cases were rare. In our study, frequent symptoms were observed in both the systemic and respiratory systems, ear, nose and throat system, and less from gastrointestinal system, central nervous system or ocular system. Additionally, there is an increase in liver and myocardial enzyme levels with an increase in disease severity. Understanding the clinical and laboratory characteristics of pediatric patients is important for diagnosis, management and effective control of the disease.
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