Synthesis and Potential Applications of Lipid Nanoparticles in Medicine

Currently, carriers of active ingredients in the form of particles of a size measured in nanometers are the focus of interest of research centers worldwide. So far, submicrometer emulsions, liposomes, as well as microspheres, and nanospheres made of biodegradable polymers have been used in medicine. Recent studies show particular interest in nanoparticles based on lipids, and at the present time, are even referred to as the “era of lipid carriers”. With the passage of time, lipid nanoparticles of the so-called first and second generation, SLN (Solid Lipid Nanoparticles) and nanostructured lipid carriers and NLC (Nanostructured Lipid Carriers), respectively, turned out to be an alternative for all imperfections of earlier carriers. These carriers are characterized by a number of beneficial functional properties, including, among others, structure based on lipids well tolerated by the human body, high stability, and ability to carry hydro- and lipophilic compounds. Additionally, these carriers can enhance the distribution of the drug in the target organ and alter the pharmacokinetic properties of the drug carriers to enhance the medical effect and minimize adverse side effects. This work is focused on the current review of the state-of-the-art related to the synthesis and applications of popular nanoparticles in medicine, with a focus on their use, e.g., in COVID-19 vaccines.     

Sarcoidosis of the paranasal sinuses

European Archives of Oto-Rhino-Laryngology - Sarcoidosis is a chronic disease, which predominantly affects the lung. Since sinonasal sarcoidosis is rare, little is known about the sarcoidosis...     

Retroperitoneal fibrosis,a rare entity with urorenal and vascular subtypes – preliminary data

IntroductionRetroperitoneal fibrosis (RPF) is a rare disease associated with the formation of hard inflammatory and fibrous tissue in the retroperitoneum. Taking into consideration the fact that RPF is a rare disease with different subtypes, we compared the basal clinical and biochemical characteristics of the vascular and urorenal subtypes.Patients and methodsFrom January 2005 until December 2021, 27 patients were identified as vascular subtype (18 males) and 11 as urorenal subtype (9 males).ResultsPatients with a primary urorenal origin had significantly worse kidney function as reflected by serum creatinine and eGFR (both p < 0.001); they also had higher serum cholesterol (p < 0.01). Hypertension, diabetes, hyperlipidemia and nicotinism were significantly more prevalent in vascular subtype (all p < 0.001).ConclusionVascular subtype is more prevalent in our study with more cardiovascular risk factor present. Due to the diversity of symptoms, diagnosis of RPF becomes a challenge for specialists as well as therapy.     

Increased plasma levels of brain-derived neurotrophic factor in patients with long-term bipolar disorder

Recent data indicate that neurotrophins may play a role in the physiopathology of bipolar disorder (BD) and may be useful as biomarkers of the disease. The aim of this study was to evaluate the plasma concentrations of brain-derived neurotrophic factor (BDNF) in BD patients, and to correlate their levels with clinical parameters. BDNF was measured in plasma from 53 BD type I subjects (34 during mania and 19 during euthymia) and 38 healthy controls by enzyme-linked immuno-sorbent assay (ELISA). Patients were assessed by a structured clinical interview (Mini-plus), Young mania and Hamilton depression rating scales. Plasma BDNF levels were significantly increased in patients with mania (P ≤ 0.001) and euthymia (P ≤ 0.001) when compared with controls, but did not correlate with any clinical parameters. BDNF concentration was higher in BD patients with 10 or more years of disease. BDNF plasma levels were increased in BD patients, mainly in those with a longer course of disease. In line with previous studies, it is conceivable that BDNF may play a role in the pathophysiology of BD.     

Synthesis and biological properties of S-adamantylated heterocyclic compounds

A series of new S-adamantylated compounds were prepared by adamanlyl cation attack on the thiol group. The biological activity of new compounds as the inducers of TNF-alpha in genetically modified mouse melanoma cells is presented.     

Determinants of occupational disability following a low back injury: a critical review of the literature

The aim of this research was to determine prognostic indicators of work disability in occupational back pain as reported in the literature, by systematically searching the research literature, assessing the methodological quality of the research, and synthesizing the findings into a concise summary. An article was considered eligible for review if research participants had an injury of the back, the article was based on original research, published in English, and involved a cohort with back pain less than 6 months post injury with at least one follow up assessment. Each article was independently reviewed by two blinded reviewers using 19 appraisal criteria for methodological quality of prognostic studies. Nineteen studies met the methodological standard to be included. Time since onset, demographic factors, functional disability, psychological distress, pain reports, previous episodes, and work environment were identified as important prognostic factors. Most studies compartmentalized the factors they considered. What is needed is a comprehensive multivariate biopsychosocial job-related model of work disability.     

Synthesis and pharmacological activity of new carbonyl derivatives of 1-aryl-2-iminoimidazolidine: part 2. Synthesis and pharmacological activity of 1,6-diaryl-5,7(1H)dioxo-2,3-dihydroimidazo[1,2-a][1,3,5]triazines

Synthesis and pharmacological activity of 1,6-diaryl-5,7(1H)dioxo-2,3-dihydroimidazo-[1,2-a][1,3,5]triazines (C) are presented. The title compounds were obtained from 1-arylimidazolinurea derivatives in cyclization reaction with difunctional carbonyl reagents--phosgene (method I) or carbonyldiimidazole (CDI) (method II). Their molecular structures were confirmed by the X-ray analysis of 1-phenyl-6-(4-chlorophenyl)-5,7(1H)-dioxo-2,3-dihydroimidazo[1,2-a][1,3,5]triazine (C2) crystals. Compounds C exhibited significant depressive action on the central nervous system (CNS) of the laboratory animals, correlated with very low acute toxicity (LD(50) > 2000 mg kg(-1) i.p.), and showed antinociceptive activity in behavioural models. Reversion of this effect by small dose of naloxone (5 mg kg(-1)) can suggest opioid-like mechanism of antinociception produced by these and other carbonyl derivatives of 1-aryl-2-iminoimidazolidine. Additionally, an effect on the serotonin neurotransmission pathway was also observed. The receptor mechanism of activity for investigated compounds was confirmed only for the opioid mu receptor in binding affinity assay test. Same tests performed for the serotonin 5-HT(2) and benzodiazepine BZD receptors showed no affinity for tested compounds. The opioid-like and serotonergic activities are similar to these described earlier for chain carbonyl 1-aryl-2-iminoimidazolidine derivatives containing urea moiety, mainly due to similar chemical structure, although compounds C are not able to adopt any of the higher energy conformations of urea derivatives. Rigid location of aromatic ring (Ar') at N6, acting as a spacer blocking any direct access to the carbonyl groups (e.g. through the hydrogen bonding), could be responsible for lack of affinity toward 5-HT(2) expressed in the binding assay test.