The influence of SARS-COV-2 pandemic in the pharmaceutical service in ALBANIA.

Objective: In the second year of the COVID-19 pandemic, the role of the pharmacists was confirmed as central at the territorial level. The purpose of this study was to assess knowledge, attitudes, and practices of pharmacists in Albania, critical changes in the Albanian pharmaceutical market during the COVID-19 pandemic and evaluate factors influencing the quality of the pharmaceutical service. Methods: A nationwide survey was conducted, using an online questionnaire targeting Albanian pharmacists during 2021. Results: Most of the respondents were females (86.2%), belonged to the 30-39 age group (51.7%) and worked in community pharmacies (73%). Although most of the respondents did participate in training courses (62.8%), only about 38% of them had good knowledge about COVID-19 (score 5/8). Moreover, the level of knowledge increases the possibility to apply the rules. 65% of the pharmacists who were very afraid of getting infected with COVID -19, stated that they followed the WHO rules compared to 37 % of those who were not afraid. Regarding the medicines offered, 64% of the respondents claimed that there have been difficulties in ensuring the adequate medicines during the pandemic. Furthermore, although 61% of the pharmacists declared that the price of medicines during the pandemic has not changed, 58% of them thought that the revenues of all pharmaceutical sectors have risen. Conclusion: From this study it is concluded that although the pharmacists in Albania have demonstrated strength, professionality, and commitment to offer pharmaceutical service to the highest level, they faced numerous challenges during this difficult time. In the future, the pharmacist's role can be extended in the community to provide successful medical service and their collaboration within and between pharmacists and physicians is essential.

The influence of SARS-COV-2 pandemic in the pharmaceutical service in ALBANIA

Objective: In the second year of the COVID-19 pandemic, the role of the pharmacists was confirmed as central at the territorial level. The purpose of this study was to assess knowledge, attitudes, and practices of pharmacists in Albania, critical changes in the Albanian pharmaceutical market during the COVID-19 pandemic and evaluate factors influencing the quality of the pharmaceutical service. Methods: A nationwide survey was conducted, using an online questionnaire targeting Albanian pharmacists during 2021. Results: Most of the respondents were females (86.2%), belonged to the 30-39 age group (51.7%) and worked in community pharmacies (73%). Although most of the respondents did participate in training courses (62.8%), only about 38% of them had good knowledge about COVID-19 (score 5/8). Moreover, the level of knowledge increases the possibility to apply the rules. 65% of the pharmacists who were very afraid of getting infected with COVID -19, stated that they followed the WHO rules compared to 37 % of those who were not afraid. Regarding the medicines offered, 64% of the respondents claimed that there have been difficulties in ensuring the adequate medicines during the pandemic. Furthermore, although 61% of the pharmacists declared that the price of medicines during the pandemic has not changed, 58% of them thought that the revenues of all pharmaceutical sectors have risen. Conclusion: From this study it is concluded that although the pharmacists in Albania have demonstrated strength, professionality, and commitment to offer pharmaceutical service to the highest level, they faced numerous challenges during this difficult time. In the future, the pharmacist’s role can be extended in the community to provide successful medical service and their collaboration within and between pharmacists and physicians is essential. (AU)

Selective Inhibitors of Histone Deacetylase 10 (HDAC-10).

Histone acetylation balance is one epigenetic mechanism controlling gene expression associated with disease progression. It has been observed that histone deacetylase 10 (HDAC-10) isozyme contributes to the chemotherapy resistance; in addition, the poor clinical outcome observed in patients with aggressive solid tumors, such as neuroblastoma, has been associated with its overexpression. Moreover, HDAC-10 selective inhibition suppresses the autophagic response, thus providing an improved risk-benefit profile compared to cytotoxic cancer chemotherapy drugs. On these bases, HDAC-10 is becoming an emerging target for drug design. Due to the rapid progress in the development of next-generation HDAC inhibitors, this review article aims to provide an overview on novel selective or dual HDAC-8/10 inhibitors, as new leads for cancer chemotherapy, able to avoid the severe side-effects of several actual approved "pan" HDAC inhibitors. A literature search was conducted in MedLine, PubMed, Caplus, SciFinder Scholar databases from 2015 to the present. Since the disclosure that the HDAC-6 inhibitor Tubastatin A was able to bind HDAC-10 efficiently, several related analogues were synthesized and tested. Both tricyclic (25-30) and bicyclic (31-42) derivatives were considered. The best pharmacological profile was shown by 36 (HDAC-10 pIC50 = 8.4 and pIC50 towards Class I HDACs from 5.2-6.4). In parallel, based on the evidence that high levels of HDAC-8 are a marker of poor prognosis in neuroblastoma treatment, dual HDAC-8/10 inhibitors were designed. The hydroxamic acid TH34 (HDAC-8 and 10 IC50 = 1.9 µM and 7.7 µM, respectively) and the hybrid derivatives 46d, 46e and 46g were the most promising both in terms of potency and selectivity. Literature surveys indicate several structural requirements for inhibitory potency and selectivity towards HDAC-10, e.g., electrostatic and/or hydrogen bond interactions with E274 and complementarity to the P(E,A) CE motif helix.

Romidepsin (FK228), A Histone Deacetylase Inhibitor and its Analogues in Cancer Chemotherapy.

BACKGROUND: Human HDACs represent a group of enzymes able to modify histone and non-histone proteins, which interact with DNA to generate chromatin. The correlation between irregular covalent modification of histones and tumor development has been proved over the last decades. Therefore, HDAC inhibitors are considered as potential drugs in cancer treatment. Romidepsin (FK228), Belinostat (PXD-101), Vorinostat (SAHA), Panobinostat (LBH-589) and Chidamide were approved by FDA as novel antitumor agents. OBJECTIVE: The aim of this review article is to highlight the structure-activity relationships of several FK228 analogues as HDAC inhibitors. In addition, the synergistic effects of a dual HDAC/PI3K inhibition by some derivatives have been investigated. MATERIALS AND METHODS: PubMed, MEDLINE, CAPLUS, SciFinder Scholar database were considered by selecting articles which fulfilled the objectives of this review, dating from 2015 till present time. RESULTS: HDAC inhibitors have a significant role in cancer pathogenesis and evolution. Class I HDAC isoforms are expressed in many tumor types, therefore, potent and selective Class I HDAC inhibitors are of great interest as candidate therapeutic agents with limited side effects. By structurebased optimization, several FK228 analogues [15 (FK-A5), 22, 23 and 26 (FK-A11)] were identified, provided with significant activity against Class I HDAC enzymes and dose dependent antitumor activity. Compound 26 was recognized as an interesting HDAC/PI3K dual inhibitor (IC50 against p110α of 6.7 µM while for HDAC1 inhibitory activity IC50 was 0.64 nM). CONCLUSION: Romidepsin analogues HDAC inhibitors have been confirmed as useful anticancer agents. In addition, dual HDAC/PI3K inhibition showed by some of them exhibited synergistic effects in inducing apoptosis in human cancer cells. Further studies on FK228 analogues may positively contribute to the availability of potent agents in tumor treatment.