Acta Pharmaceutica最新文献

This study aimed to elucidate the characteristics and pharmacokinetics of orally disintegrating tablets (ODTs) containing coenzyme Q10 (CoQ10) granules prepared by spray drying, hot-melting, and wet granulation. The hardness and disintegration times of CoQ10-ODTs containing 5 % crospovidone were 61.6-81.8 N and < 30 s, respectively; these values indicate that the as-prepared ODTs were adequate for clinical use. The hardness and disintegration times of all ODTs did not change significantly after a 28-day storage period at 30 °C/10 % relative humidity (RH), but storage under high temperature and humidity affected their characteristics. The dissolution and pharmacokinetics of CoQ10-ODTs showed that ODTs prepared using the spray-drying method had the highest dissolution and absorbability among the CoQ10-ODTs tested. These results provide useful information for the preparation of ODTs using CoQ10.

The effects of 3R,16S-2-hydroxyethyl apovincaminate (HEAPO, RGH-10885) compared with those of two cholinesterase inhibitors, donepezil and galantamine, were examined in naïve Wistar rats using standard active and passive avoidance tests. The active avoidance test (shuttle box) and two passive avoidance tests (step-through and step-down) were performed according to the experimental design. There were 10 groups of rats (n = 8) and the substances studied were applied orally before each testing session. In the active avoidance test, the number of conditioned stimuli (avoidances), unconditioned stimuli (escapes) and intertrial crossings were observed. In step-down and step-through passive avoidance tests, the latencies of reactions were observed. All the studied compounds showed positive effects in the learning and memory tests, compared to the controls. It was concluded that HEAPO, donepezil and galantamine had a memory-enhancing effect in active and passive avoidance tests.

This century's most serious catastrophe, COVID-19, has been dubbed "the most life-threatening disaster ever". Asthmatic persons are even more prone to COVID-19's complex interplay with the underlying inflammatory condition. In order to protect themselves against COVID-19, asthmatic patients must be very vigilant in their usage of therapeutic techniques and drugs (e.g., bronchodilators, 5-lipoxygenase inhibitors), which may be accessed to deal with mild, moderate, and severe COVID-19 indications. People with asthma may have more severe COVID-19 symptoms, which may lead to a worsening of their condition. Several cytokines were found to be elevated in the bronchial tracts of patients with acute instances of COVID-19, suggesting that this ailment may aggravate asthma episodes by increasing inflammation. The intensity of COVID-19 symptoms is lessened in patients with asthma who have superior levels of T-cells. Several antibiotics, antivirals, antipyretics, and anti-inflammatory drugs have been suggested to suppress COVID-19 symptoms in asthmatic persons. Furthermore, smokers are more likely to have aggravated repercussions in COVID-19 infection. Being hospitalized to critical care due to COVID-19, needing mechanical breathing, and suffering from serious health repercussions, are all possible outcomes for someone who has previously smoked. Smoking damages airways and alveoli, which significantly raises the risk of COVID-19-related health complications. Patients with a previous record of smoking are predisposed to severe COVID-19 disease symptoms that essentially require a combination of bronchodilators, mucolytics, antivirals, and antimuscarinic drugs, to cope with the situation. The present review discusses the care and management of asthmatic and smoker patients in COVID-19 infection.

Nitric oxide (NO) participates in processes such as endothelium-dependent vasodilation and neurotransmission/neuromodulation. The role of NO in epilepsy is controversial, attributing it to anticonvulsant but also proconvulsant properties. Clarification of this dual effect of NO might lead to the development of new antiepileptic drugs. Previous results in our laboratory indicated that this contradictory role of NO in seizures could depend on the nitric oxide synthase (NOS) isoform involved, which could play opposite roles in epileptogenesis, one of them being proconvulsant but the other anticonvulsant. The effect of convulsant drugs on neuronal NO (nNO) and endothelial NO (eNO) levels was investigated. Considering the distribution of neuronal and endothelial NOS in neurons and astrocytes, resp., primary cultures of neurons and astrocytes were used as a study model. The effects of convulsant drugs pentylenetetrazole, thiosemicarbazide, 4-aminopyridine and bicuculline on NO levels were studied, using a spectrophotometric method. Their effects on NO levels in neurons and astrocytes depend on the concentration and time of treatment. These convulsant drugs caused an increase in nNO, but a decrease in eNO was proportional to the duration of treatment in both cases. Apparently, nNO possesses convulsant properties mediated by its effect on the glutamatergic and GABAergic systems, probably through GABA_A receptors. Anticonvulsant properties of eNO may be the consequence of its effect on endothelial vasodilation and its capability to induce angiogenesis. Described effects last as seizures do. Considering the limitations of these kinds of studies and the unexplored influence of inducible NO, further investigations are required.

The activation of the monocyte-macrophage system and the damage to the renal and pancreatic tissue are common complications in patients with diabetes induced by hyper-glycemia. This study aimed to evaluate the effect and mechanism of butyrate (NaB), a metabolite of intestinal flora, on inhibiting the inflammatory response of human monocyte-macrophages (THP-1 cells) induced by high glucose and the damage of pancreatic and renal tissue in diabetic mice. The results showed that high concentration glucose significantly up-regulated the expressions of IL-1β, TNF-α, and NLRP3 in THP-1 cells and mouse spleen, and that NaB could inhibit the overexpression of those genes. The abundance of Beclin-1, LC3B and reactive oxygen species (ROS) in THP-1 cells is increased due to the high glucose concentration, and NaB can inhibit the genes responsible for upregulating the expression. In diabetic mice, vacuolar degeneration of renal tubules was observed. Then we observed that some of the epithelial cells of the renal tubules were exfoliated and some formed tubules. NaB could alleviate these pathological lesions, but NaB cannot alleviate pancreatic injury. Our results indicated that NaB could be used for the prevention and adjuvant treatment of diabetic kidney injury.

Voltage-gated K⁺ (K_v) channels play a role in the cellular processes of various cancer cells, including lung cancer cells. We previously identified and reported a salivary protein from the Xenopsylla cheopis, FS48, which exhibited inhibitory activity against K_v1.1-1.3 channels when assayed in HEK 293T cells. However, whether FS48 has an inhibitory effect on cancer cells expressing Kv channels is unclear. The present study aims to reveal the effects of FS48 on the K_v channels and the NCI-H460 human lung cancer cells through patch clamp, MTT, wound healing, transwell, gelatinase zymography, qRT-PCR and WB assays. The results demonstrated that FS48 can be effective in suppressing the K_v currents, migration, and invasion of NCI-H460 cells in a dose-dependent manner, despite the failure to inhibit the proliferation. Moreover, the expression of K_v1.1 and K_v1.3 mRNA and protein were found to be significantly reduced. Finally, FS48 decreases the mRNA level of MMP-9 while increasing TIMP-1 mRNA level. The present study highlights for the first time that blood-sucking arthropod saliva-derived protein can inhibit the physiological activities of tumour cells via the Kv channels. Furthermore, FS48 can be taken as a hit compound against the tumour cells expressing K_v channels.

Malaria is a serious worldwide medical issue that results in substantial annual death and morbidity. The availability of treatment alternatives is limited, and the rise of resistant parasite types has posed a significant challenge to malaria treatment. To prevent a public health disaster, novel antimalarial agents with single-dosage therapies, extensive curative capability, and new mechanisms are urgently needed. There are several approaches to developing antimalarial drugs, ranging from alterations of current drugs to the creation of new compounds with specific targeting abilities. The availability of multiple genomic techniques, as well as recent advancements in parasite biology, provides a varied collection of possible targets for the development of novel treatments. A number of promising pharmacological interference targets have been uncovered in modern times. As a result, our review concentrates on the most current scientific and technical progress in the innovation of new antimalarial medications. The protein kinases, choline transport inhibitors, dihydroorotate dehydrogenase inhibitors, isoprenoid biosynthesis inhibitors, and enzymes involved in the metabolism of lipids and replication of deoxyribonucleic acid, are among the most fascinating antimalarial target proteins presently being investigated. The new cellular targets and drugs which can inhibit malaria and their development techniques are summarised in this study.

The current meta-analysis searched the literature connected to different tranquilizers used to treat elderly people and assessed it in terms of dose, types of outcomes and adverse effects, to determine a safe and acceptable tranquilizer and its optimal dose. A systematic literature review was undertaken for randomized controlled trials, case-control, retrospective and prospective studies on the use of tranquilizers in elderly patients, using PubMed, Ebsco, SCOPUS and Web of Science. PICOS criteria were used to select studies, and pertinent event data was collected. This meta-analysis includes 16 randomized control trials spanning the years 2000 to 2022, using the data from 2224 patients. The trials that were included used various tranquilizers such as diazepam, alprazolam, temazepam and lorazepam, and indicated high treatment efficacy and low adverse effects. With a p-value of 0.853 for Egger's test and 0.13 for Begg's test, the current meta-analysis shows a minimal probability of publication bias. A recent meta-analysis supports the use of tranquilizers in older people to treat sleeplessness, epilepsy or anxiety, but only at modest doses, because large doses are harmful and produce numerous withdrawal symptoms.

Stagnation in novelties of osteosarcoma (OS) treatment indicates the need for new therapeutic methods. OS cancer stem cells (OS-CSC) are taught to have the ability to self-renew and develop mechanisms of anticancer drug resistance, and this is why it is difficult to eradicate them. Their metabolism has been recognized as a potential target of therapeutic action. Ascorbic acid (AA) is considered to act pro-oxidative against OS-CSC in vitro by oxidative effect and by inhibition of glycolysis. This study examined an in vitro impact of AA on OS-CSC metabolism isolated from patients' biopsies, with the aim of better understanding of OS-CSC metabolism and the action of AA on OS-CSC. OS-CSC were isolated using a sphere culture system and identified as stem cells using Hoechst 33342 exclusion assay. Determination of the dominant type of metabolism of OS-CSC, parental OS cells, human mesenchymal stem cells (hMSC) and U2OS OS lineage before and after AA treatment was done by Seahorse XF (Agilent). Cytotoxicity of high-dose AA was confirmed by the MTT test and was proven for all the examined cell types as well as HEK293. Seahorse technology showed that OS-CSC can potentially use both glycolysis and oxidative phosphorylation (OXPHOS), and can turn to glycolysis and slow metabolic potential in unfavorable conditions such as incubation in AA.

A good therapeutic alliance is relevant for healthcare providers exposed to patients' suffering, especially since patients and physicians may understand the painful experience differently. Our aim was to explore the impact of therapeutic alliance on analgesic outcomes in a real-world interdisciplinary pain unit (PU). A cross-sectional observational study was conducted on outpatients (n = 69) using opioids on a long-term basis for the treatment of chronic non-cancer pain, where clinical pharmacologists and pharmacists advised patients about their opioid treatment. Responses to the patient-doctor relationship questionnaire (PDRQ), sociodemographic and clinical information (pain level, quality of life and hospital use) were collected, whereas pharmacology data (analgesic prescription, adverse events, and compliance) were obtained from electronic health records. Patients were predominantly middle-aged (75 % women, 72 % retired), experiencing moderate pain (VAS 40-70 mm) on average, and under a high morphine equianalgesic dosage (95 ± 88 mg per day, mainly tapentadol or fentanyl). Patients with better PDRQ outcomes, and therefore better therapeutic alliance, showed lower pain intensity than patients with worse PDRQ outcomes (pain intensity: high scores 60 ± 47 mm and medium scores 60 ± 45 mm vs. low scores 80 ± 75 mm, p < 0.01). Along with this, pain intensity was lower when patients affirmed that, thanks to the health-care providers, they "gained new insight", "felt better", or "felt content with their doctor's treatment". What´s more, patients who affirmed "I benefit from the treatment" experienced increased pain relief (benefit 40 ± 30 vs. non-benefit 19 ± 26 mm, p = 0.010) and improved quality of life (benefit 33 ± 25 vs. non-benefit 18 ± 16 mm, p = 0.031). However, there was a percentage of patients who did not fully understand the provided information, which is something to be taken into account to improve in clinical routine. Therapeutic alliance supported by pharmacist experts on pain management can be an effective strategy to improve analgesic outcomes. Further efforts are needed to improve communication strategies for pain management. Future directions of research should include the analysis of the role of the pharmacist in poly-professional consultations as related to the advice of patients about their medication, and the mutual trust with the patients.