Anxiolytic-like Activity, Antioxidant Properties, and Facilitatory Effects on the Short-Term Memory Retention of Molsidomine in Rats.

Compelling evidence indicates that nitric oxide (NO) exerts a significant influence on the central nervous system, participates in the modulation of neurotransmitter release, contributes to the regulation of cognitive functions, and plays a crucial role in modulating various aspects of neural activity. We aimed to explore the influence of two NO donors, molsidomine (MSD) and V-pyrro/NO, on the innate spontaneous psychomotor abilities and short-term memory in rats. Using an actimeter test, the locomotor activity, stress-sensitive behavior, and anxiety level were investigated. The influence on the animal`s cognitive functions was evaluated usingthe Y-maze test to assess the spontaneous alternation percentage, number of arms visited, number of alternations, and the preference index. Four distinct groups of five white male Wistar rats were exposed to the intraperitoneal treatments as follows: Control batch-0.3 mL/100 g of body weight saline solution, Mg batch-200 mg/kbwof magnesium chloride, MSD batch-1 mg/kbw of molsidomine, and V-pyrro/NO batch-5 mg/kbwof V-pyrro/NO. The intraperitoneal administration of MSD resulted in a significant reduction in spontaneous behavior and exploratory skills but was less pronounced than the positive control drug, magnesium chloride. Conversely, treatment with V-pyrro/NO led to only a slight decrease in horizontal movements during the actimeter test. MSD administration, but not V-pyrro/NO, notably increased the rate of spontaneous alternation in the Y-maze test. Additionally, the use of MSD resulted in an increase in the blood level of brain-derived neurotrophic factor and the intensification of the antioxidant enzymes, superoxide dismutase, and glutathione peroxidase activity. In our experimental setup, we demonstrated that MSD exposure led to a decrease in spontaneous behavior, showed anxiolytic effects and antioxidant activity, and improved spatial memory acquisition in rats.

Chronic Administration of Ion Channel Blockers Impact Microglia Morphology and Function in a Murine Model of Alzheimer's Disease.

As the population ages, a high prevalence of multimorbidity will affect the way physicians need to think about drug interactions. With microglia's important involvement in the pathology and progression of Alzheimer's disease (AD), understanding whether systemically administered drugs intended for other affections could impact microglia function, already impacted by the presence of beta-amyloid, is important. The aim of this study was to evaluate morphological changes of microglia, using in vivo 2-photon laser scanning microscopy, in a murine model of AD under systemic administration of sodium or calcium ion channel blockers in order to establish potential effects that these drugs might have on microglia under neuro-inflammatory conditions. A total of 30 mice (age 14-16 weeks, weight 20-25 g) were used, with 25 APP randomly divided into three groups. The remaining animals were CX3CR1GFP/GFP male mice (n = 5) used as WT controls. After baseline behavior testing, all animals received daily intraperitoneal injections for 30 days according to the assigned group [WT (n = 5), Control (n = 5), Carbamazepine (n = 10), and Verapamil (n = 10)]. The results showed that the Verapamil treatment improved short-term memory and enhanced exploratory behavior in APP mice. The Carbamazepine treatment also improved short-term memory but did not elicit significant changes in anxiety-related behavior. Both Verapamil and Carbamazepine reduced the surveillance speed of microglia processes and changed microglia morphology in the cortex compared to the Control group. Due to their complex molecular machinery, microglia are potentially affected by drugs that do not target them specifically, and, as such, investigating these interactions could prove beneficial in our management of neurodegenerative pathologies.

The Role of the Prognostic Inflammatory and Nutritional Index (PINI) in the Evolution of Patients with Chronic Kidney Disease and Other Pathologies.

BACKGROUND: Protein-energy loss and inflammation are the main risk factors in the occurrence of complications in hemodialysis patients. The Prognostic Inflammatory and Nutritional Index (PINI) is a simple, inexpensive test to identify the early onset of inflammation and malnutrition in hemodialysis patients, critically ill subjects and those with malignancies. METHODS: A systemic review of English literature was conducted on the topic published between 1985 and 2022. A focused and sensitive search strategy was applied to the PUBMED database to identify relevant scientific articles in English. Once articles were identified, a detailed quality and bias assessment was performed. Two independent researchers analyzed the detailed data extraction. RESULTS: PINI proved to be a sensitive, powerful, low-cost and simple test. PINI has been useful in assessing evolution and prognostics in clinical care, with values above one being associated with a high risk of mortality and morbidity. It is useful in cases with surgical and postoperative complications, long hospitalization, as well as increased associated expenses. CONCLUSIONS: This is the first review of the literature on the above-mentioned topic (PINI) and is a valuable candidate for validating prognosis in patients with different pathologies.

Synthesis, Characterization and Biocompatibility Evaluation of Novel Chitosan Lipid Micro-Systems for Modified Release of Diclofenac Sodium.

The purpose of our study was the obtaining, characterization and biocompatibility estimation of novel carrier systems for diclofenac. Diclofenac is a potent nonsteroidal anti-inflammatory drug with frequent gastrointestinal side effects, impairing the quality of the patient's life. Original diclofenac-loaded micro-vesicles coated with chitosan were prepared and physico-chemical analyzed. We investigated their in vitro hemocompatibility and in vivo biocompatibility in rats. The animals were treated orally as follows: group 1 (Control): distilled water 0.3 mL/100 g body weight; Group 2 (CHIT): 0.3 mL/100 g body weight 0.5% chitosan solution; Group 3 (DCF): 15 mg/kg body weight diclofenac; Group 4 (DCF-ves): lipid vesicles loaded with diclofenac 15 mg/kg body weight. Blood samples were collected for assessing: red blood cells, hemoglobin, hematocrit and leukocyte formula. A series of specific parameters of the liver and kidney function, some markers of immune defense, as well as the activity of some enzymes involved in oxidative processes, were also investigated. At the end of the experiment, the animals were sacrificed and fragments of liver, kidney and stomach were collected for histopathological examination. No blood hemolysis was evidenced by the in vitro test with the administration of diclofenac vesicles. The animals treated with diclofenac lipid vesicles stabilized with chitosan did not display any notable differences in their hematological and biochemical profile compared to control animals. These data correlated with the histological results, which showed the absence of architectural changes in the examined tissues. Biological in vitro and in vivo evaluation revealed that the microvesicles containing diclofenac are biocompatible, with potential to be used as delivery systems to modify the drug release, thus making them an attractive candidate for biomedical applications.

Insights into the Relationship between Pentraxin-3 and Cancer.

Although cancer can be cured if detected early and treated effectively, it is still a leading cause of death worldwide. Tumor development can be limited by an appropiate immune response, but it can be promoted by chronic extensive inflammation through metabolic dysregulation and angiogenesis. In the past decade, numerous efforts have been made in order to identify novel candidates with predictive values in cancer diagnostics. In line with this, researchers have investigated the involvement of pentraxin-3 (PTX-3) in cellular proliferation and immune escape in various types of cancers, although it has not been clearly elucidated. PTX-3 is a member of the long pentraxin subfamily which plays an important role in regulating inflammation, innate immunity response, angiogenesis, and tissue remodeling. Increased synthesis of inflammatory biomarkers and activation of different cellular mechanisms can induce PTX-3 expression in various types of cells (neutrophils, monocytes, lymphocytes, myeloid dendritic cells, fibroblasts, and epithelial cells). PTX-3 has both pro- and anti-tumor functions, thus dual functions in oncogenesis. This review elucidates the potential usefulness of PTX-3 as a serum biomarker in cancer. While future investigations are needed, PTX-3 is emerging as a promising tool for cancer's diagnosis and prognosis, and also treatment monitoring.

Diagnostic Accuracy of Machine-Learning Models on Predicting Chemo-Brain in Breast Cancer Survivors Previously Treated with Chemotherapy: A Meta-Analysis.

We performed a meta-analysis of chemo-brain diagnostic, pooling sensitivities, and specificities in order to assess the accuracy of a machine-learning (ML) algorithm in breast cancer survivors previously treated with chemotherapy. We searched PubMed, Web of Science, and Scopus for eligible articles before 30 September 2022. We identified three eligible studies from which we extracted seven ML algorithms. For our data, the χ2 tests demonstrated the homogeneity of the sensitivity's models (χ2 = 7.6987, df = 6, p-value = 0.261) and the specificities of the ML models (χ2 = 3.0151, df = 6, p-value = 0.807). The pooled area under the curve (AUC) for the overall ML models in this study was 0.914 (95%CI: 0.891-0.939) and partial AUC (restricted to observed false positive rates and normalized) was 0.844 (95%CI: 0.80-0.889). Additionally, the pooled sensitivity and pooled specificity values were 0.81 (95% CI: 0.75-0.86) and 0.82 (95% CI: 0.76-0.86), respectively. From all included ML models, support vector machine demonstrated the best test performance. ML models represent a promising, reliable modality for chemo-brain prediction in breast cancer survivors previously treated with chemotherapy, demonstrating high accuracy.

Magnesium Potentiates the Vortioxetine's Effects on Physical Performances and Biological Changes in Exercise-Induced Stress in Rats.

Background and objectives: Vortioxetine (VRT) is a relatively new selective serotonin reuptake inhibitor (SSRI) antidepressant and serotonin receptor modulator, approved for the treatment of major depression and generalized anxiety disorder. Depression has been linked with psychomotor disengagement, oxidative stress burden and decreased blood levels of brain-derived neurotrophic factor (BDNF). In our study we performed the experimental investigation of VRT, magnesium and of their association on the rats' endurance capacity, motor behavior and blood biological disturbances in rats subjected to forced exercise in treadmill test. Materials and Methods: The substances were administered orally for 14 consecutive days, as follows: group 1 (control): distilled water 0.3 mL/100 g body; group 2 (Mg): magnesium chloride 200 mg/kg body; group 3 (VRT): VRT 20 mg/kg body; group 4 (VRT+Mg): VRT 20 mg/kg body + magnesium chloride 200 mg/kg body. Magnesium was used as positive control substance with known effects in treadmill test. The consequences of VRT treatment on glucose, cortisol, BDNF and oxidative stress biomarkers (superoxide-dismutase, malondialdehyde, glutathione-peroxidase, lactate dehydrogenase) were also assessed. Results and conclusions: The use of VRT resulted in an improvement in motor capacity and an increase of the rats' endurance to physical effort. The administration of VRT increased the serum BDNF levels and reduced the oxidative stress in rats subjected to physical effort. The association of magnesium potentiated the effects of VRT on physical performances, the antioxidant activity and the decreasing in serum stress markers in treadmill test in rats.

Screening performance of C-reactive protein for active pulmonary tuberculosis in HIV-positive patients: A systematic review with a meta-analysis.

Background: Tuberculosis (TB) is the leading infectious cause of mortality worldwide. In the last years, resistant strains of the etiological agent, Mycobacterium tuberculosis, have emerged, thus demanding more triage tests to identify active pulmonary TB (PTB) patients and to evaluate their disease severity. Therefore, acute-phase reaction serum tests are required for monitoring TB patients, among WHO symptom screening recommendations. C-reactive protein (CRP) is a non-specific inflammatory biomarker that has been recently proposed for TB screening and can be quantitatively analyzed through cost-effective point-of-care assays. A previous meta-analysis found CRP to be highly sensitive and moderately specific for active PTB with confirmed HIV infection. Methods: We performed a meta-analysis update of diagnostic tests, pooling sensitivities, and specificities in order to assess the accuracy of CRP as a potential test for the screening of HIV-associated PTB in outpatients. We searched MEDLINE, Web of Science, and SCOPUS for eligible articles before 19 October 2021. Results: We identified 13 eligible studies with HIV-positive patients with PTB. At a CRP threshold of 10 mg/L, CRP pooled sensitivity was 87% (76%-93%) and pooled specificity was 67% (49%-81%), with an area under the curve (AUC) of 0.858. Using a CRP threshold of 8 mg/L, pooled sensitivity was 82% (72%-89%) and pooled specificity was 82% (67%-92%), with an AUC of 0.879. We found that CRP has a high sensitivity in the screening of PTB in HIV-positive outpatients, consistent with findings reported previously. Conclusions: Regardless of pooled specificity, better results were found using the CRP threshold of 8 mg/L as a test screening of PTB, meeting the need of further approaching specific TB diagnostic methods and reducing resource consumption.

The Use of Chitosan-Coated Nanovesicles in Repairing Alcohol-Induced Damage of Liver Cells in Mice.

Background and Objectives In the past few decades, the studies concerning the natural polysaccharide chitosan have been centered on a new direction: its hepatoprotective action. The aim of our study was to evaluate the influence of previously designed chitosan lipid vesicles on the liver damage induced by alcohol consumption in mice. Materials and Methods The study involved the oral administration of substances in one daily dose as follows: Group 1 (control): water; Group 2 (control alcohol): 5% alcohol in water; Group 3 (CHIT): 0.1 mL/10 g body weight chitosan solution in animals treated with alcohol; Group 4 (CHIT-ves): 0.1 mL/10 g body chitosan vesicles in animals treated with alcohol; Group 5 (AcA): 200 mg/kg body ascorbic acid in animals treated with alcohol. In order to evaluate liver damage after alcohol consumption, the following hematological parameters were tested: the activity of alanine aminotransferase, aspartate aminotransferase and lactate dehydrogenase; serum values of urea and creatinine; the phagocytic capacity of polymorphonuclear neutrophilsin peripheral blood;serum opsonic capacity;bactericidal capacity of peritoneal macrophages; and the activity of malondialdehyde, glutathione peroxidase, superoxide dismutase and lactate dehydrogenase. Results and Conclusions The treatment with chitosan vesicles decreased liver enzyme activity and reduced the oxidative stress disturbances in alcoholic mice, thus repairing the hepatic functional and structural damages. These beneficial activities of chitosan vesicles were comparable with ascorbic acid effects in alcoholic mice.

Mycobacterium tuberculosis and Pulmonary Rehabilitation: From Novel Pharmacotherapeutic Approaches to Management of Post-Tuberculosis Sequelae.

Tuberculosis (TB) is still a worldwide public health burden, as more than 1.3 million deaths are expected to be reported in 2021. Even though almost 20 million patients have completed specific anti-TB treatment and survived in 2020, little information is known regarding their pulmonary sequelae, quality of life, and their need to follow rehabilitation services as researchers shifted towards proper diagnosis and treatment rather than analyzing post-disease development. Understanding the underlying immunologic and pathogenic mechanisms during mycobacterial infection, which have been incompletely elucidated until now, and the development of novel anti-TB agents could lead to the proper application of rehabilitation care, as TB sequelae result from interaction between the host and Mycobacterium tuberculosis. This review addresses the importance of host immune responses in TB and novel potential anti-TB drugs' mechanisms, as well as the assessment of risk factors for post-TB disease and usefulness of guidance and optimization of pulmonary rehabilitation. The use of rehabilitation programs for patients who successfully completed anti-tuberculotic treatment represents a potent multifaceted measure in preventing the increase of mortality rates, as researchers conclude that a patient with a TB diagnosis, even when properly completing pharmacotherapy, is threatened by a potential life loss of 4 years, in comparison to healthy individuals. Dissemination of pulmonary rehabilitation services and constant actualization of protocols could strengthen management of post-TB disease among under-resourced individuals.

The Analysis of Chitosan-Coated Nanovesicles Containing Erythromycin-Characterization and Biocompatibility in Mice.

Nanoantibiotics have proved improved pharmacokinetic characteristics and antimicrobial features. Recent studies have shown non-toxicity, non-immunogenicity, antioxidant, anti-hyperlipidemic, and hepatocyte protective actions, among other advantages of chitosan-based nanoparticles. The purpose of our study was the structural analysis of novel chitosan-coated vesicles entrapping erythromycin (ERT) and the assessment of their biocompatibility in mice. According to the group in which they were randomly assigned, the mice were treated orally with one of the following: distilled water; chitosan; ERT; chitosan vesicles containing ERT. Original nanosystems entrapping ERT in liposomes stabilized with chitosan were designed. Their oral administration did not produce sizeable modifications in the percentages of the leukocyte formula elements, of some blood constants useful for evaluating the hepatic and renal function, respectively, and of some markers of oxidative stress and immune system activity, which suggests a good biocompatibility in mice. The histological examination did not reveal significant alterations of liver and kidney architecture in mice treated with chitosan liposomes entrapping ERT. The results indicate the designed liposomes are a promising approach to overcome disadvantages of conventional ERT treatments and to amplify their benefits and can be further studied as carrier systems.

Pharmacist's Perspectives on Administering a COVID-19 Vaccine in Community Pharmacies in Four Balkan Countries.

Community pharmacists expanded their roles and engaged in vaccination services in many countries around the world, but not in Balkan countries. This research aimed to assess the perceptions of pharmacists on involvement in the coronavirus disease (COVID-19) vaccine administration in four Balkan countries (Albania, Bulgaria, Romania, and Serbia). A cross-sectional survey was conducted using an online questionnaire that was distributed to community pharmacists across these countries between February and March 2021. A total of 636 community pharmacists were included in the analysis of the survey. The willingness to administer vaccines for COVID-19 (or other vaccines well established in the practice, like a flu vaccine) in community pharmacies is significantly different among the countries: the pharmacists from Albania were more willing to administer vaccines. The factors associated with the eagerness to vaccinate are almost the same among the countries: the lack of training in the faculty classes and the lack of a special place where to administer vaccines. Additional significant factors were found in Bulgaria (pharmacists from independent pharmacies wanted more than the pharmacists working in chain pharmacies to administer vaccines) and in Serbia (male pharmacists agreed more with administering vaccines than female pharmacists). Further national reforms are needed for adopting the expanding role of community pharmacists.

Assessment of the In Vivo Release and Biocompatibility of Novel Vesicles Containing Zinc in Rats.

This paper is focused on the in vivo release and biocompatibility evaluation in rats of some novel systems entrapping zinc chloride in lipid vesicles. The particles were prepared by zinc chloride immobilization inside lipid vesicles made using phosphatidylcholine, stabilized with 0.5% chitosan solution, and dialyzed for 10 h to achieve a neutral pH. The submicrometric systems were physico-chemically characterized. White Wistar rats, assigned into four groups of six animals each, were treated orally with a single dose, as follows: Group I (control): deionized water 0.3 mL/100 g body weight; Group II (Zn): 2 mg/kg body weight (kbw) zinc chloride; Group III (LV-Zn): 2 mg/kbw zinc chloride in vesicles; Group IV (LVC-Zn): 2 mg/kbw zinc chloride in vesicles stabilized with chitosan. Haematological, biochemical, and immune parameters were assessed after 24 h and 7 days, and then liver fragments were collected for histopathological examination. The use of zinc submicrometric particles-especially those stabilized with chitosan-showed a delayed zinc release in rats. No substantial changes to blood parameters, plasma biochemical tests, serum complement activity, or peripheral neutrophils phagocytic capacity were noted; moreover, the tested substances did not induce liver architectural disturbances. The obtained systems provided a delayed release of zinc, and showed good biocompatibility in rats.

Crosstalk between vitamin D axis, inflammation and host immunity mechanisms: A prospective study.

Tuberculosis (TB) remains a public health burden, after many years at attempts for its eradication. Vitamin D (VD) status has been suggested to be related to TB susceptibility because it has the ability to regulate multiple axes of the innate and adaptive host immune response. VD mediates cathelicidin (LL-37) synthesis, a cationic bactericidal peptide, through the expression of vitamin D receptor (VDR). Host innate defense mechanisms include autophagy and apoptosis of alveolar macrophages. The present study aimed to assess the relationship between VD status, inflammation and host defense mechanisms before and after two months of first-line anti-TB pharmacotherapy. The study included newly diagnosed individuals with pulmonary TB without co-morbidities (HIV infection, diabetes, cancer) and without VD supplementation or other therapies interfering with VD serum levels. We measured serum levels of 25-hydroxyvitamin D (25-(OH)-D), the major circulating form of vitamin D, VDR, LL-37, beclin-1 (an autophagy marker) and M30 (an apoptosis biomarker) before and after two months of anti-TB treatment. Individuals presented lower levels of 25-(OH)-D before receiving first-line anti-TB treatment (T0) in comparison with its plasmatic levels after two-months of therapy (T2). At T2, patients were divided in two subgroups according the results of sputum-culture conversion. After two-months of therapy, decreased values of LL-37, beclin-1 and M30 were observed in the culture-negative patients compared to the culture-positive patients. Control of anti-TB treatment outcome could be improved by appraisal of VD status and host defense mechanisms such as autophagy and apoptosis.

Biocompatibility and Pharmacological Effects of Innovative Systems for Prolonged Drug Release Containing Dexketoprofen in Rats.

The present study reports on the in vivo biocompatibility investigation and evaluation of the effects of liposomes containing dexketoprofen in somatic sensitivity in rats. METHOD: The liposomes were prepared by entrapping dexketoprofen in vesicular systems stabilized with chitosan. The in vivo biocompatibility was evaluated after oral administration in white Wistar rats: Group I (DW): distilled water 0.3 mL/100 g body weight; Group II (DEX): dexketoprofen 10 mg/kg body weight (kbw); Group III (nano-DEX): liposomes containing dexketoprofen 10 mg/kbw. Blood samples were collected from caudal lateral vein one day and seven days after the substance administration, to assess the eventual hematological, biochemical, and immunological changes. The investigation of somatic pain reactivity was performed using the hot plate test, to count the latency time response evoked by the thermal paws' noxious stimulation. RESULTS: Original liposomes entrapping dexketoprofen, with mean size of 680 nm and good stability, were designed. Laboratory analysis indicated no substantial variances between the three treated groups. The treatment with liposomes containing dexketoprofen resulted in a prolongation of the latency time response, statistically significant in the interval between 90 min and 10 h, in the hot plate test. CONCLUSIONS: The use of liposomes with dexketoprofen proved a good in vivo biocompatibility in rats and prolonged analgesic effects in the hot plate test.

Evaluation of prognostic significance of hematological profiles after the intensive phase treatment in pulmonary tuberculosis patients from Romania.

We evaluated in this cohort study the predictive ability of 23 peripheral blood parameters and ratios for treatment outcomes after the 2-month intensive phase in patients with PTB. In 63 patients out of 90 that turned culture negative, a significant decrease in white blood cell count, neutrophils, monocyte, hemoglobin, platelet, plateletcrit, erythrocyte sedimentation rate, MLR, NLR, PLR and SII values after anti-TB therapy compared to pretreatment was observed (p <0.001). Logistic regression analysis generated a model of predictors consisting of nine covariates. Spearman's correlation analysis revealed significant positive correlations between NLR with NEU (r = 0.79, p<0.01), SII with NEU (r = 0.846, p<0.01), PLT with SII (r = 0.831, p<0.01), PLT with PCT (r = 0.71, p<0.01) and MPV with P-LCR (r = 0,897, p<0.01) in 63 patients out of 90 that turned culture negative after 2 months of treatment. ROC curve analysis indicated that all areas under the curve (AUC) revealed no statistically significant results, except lymphocyte for culture conversion. In summary, here we observed a set of hematological parameters that declined significantly as the disease was treated in patients that turned culture negative. Despite some limitations, our findings are useful for further studies aiming to identify hematological profiles that could predict the treatment outcome.

Influence of COVID-19 on Health-Related Quality of Life and the Perception of Being Vaccinated to Prevent COVID-19: An Approach for Community Pharmacists from Romania and Bulgaria.

Community pharmacists are essential front-line health workers, involved in relieving the COVID-19 burden. Their health-related quality of life status needs to be assessed, as lower levels could affect their functioning. In order to evaluate the current status of community pharmacists' quality of life from Romania and Bulgaria during the COVID-19 pandemic, and to identify factors associated with their decision on being vaccinated to prevent COVID-19, an online survey involving 395 community pharmacists was conducted from 15th July 2020 to 15th August 2020. The 15D instrument was used for quality-of-life assessment. The pharmacists' recommendations for vitamin C and D intake during the COVID-19 pandemic were also analyzed in order to promote future training programs for community pharmacists. Descriptive statistics, comparative analyses between pharmacists from Romania and Bulgaria, and multiple correlation analyses were performed on the collected data. Significant differences were observed for the level of quality of life between the two groups of pharmacists according to their age; smaller values, directly correlated with their age (total 15D score and age: Spearman r = 0.168, p = 0.022), were obtained for Bulgarian pharmacists regarding sleeping, usual activities, mental function, discomfort and symptoms, depression, distress. The perception of being vaccinated did not differ between Romanian and Bulgarian pharmacists, as almost 50% agreed to vaccination (p = 0.7542). Their willingness to vaccinate was correlated with vitamin D usage (p = 0.0134), rather than with vitamin C (p = 0.4157). No other significant associations were found between willingness to get vaccinated to prevent COVID-19 and other characteristics (age, gender, income, quality-of-life markers). Evidence-based interventions are required to enhance the health-related quality of life of community pharmacists involved in the first line of the COVID-19 pandemic.

Evaluation of Antinociceptive Effects of Chitosan-Coated Liposomes Entrapping the Selective Kappa Opioid Receptor Agonist U50,488 in Mice.

Background and Objectives: The selective kappa opioid receptor agonist U50,488 was reported to have analgesic, cough suppressant, diuretic and other beneficial properties. The aim of our study was to analyze the effects of some original chitosan-coated liposomes entrapping U50,488 in somatic and visceral nociceptive sensitivity in mice. Materials and Methods: The influence on the somatic pain was assessed using a tail flick test by counting the tail reactivity to thermal noxious stimulation. The nociceptive visceral estimation was performed using the writhing test in order to evaluate the behavioral manifestations occurring as a reaction to the chemical noxious peritoneal irritation with 0.6% acetic acid (10 mL/kbw). The animals were treated orally, at the same time, with a single dose of: distilled water 0.1 mL/10 gbw; 50 mg/kbw U50,488; 50 mg/kbw U50,488 entrapped in chitosan-coated liposomes, according to the group they were randomly assigned. Results: The use of chitosan-coated liposomesas carriers for U50,488 induced antinociceptive effects that began to manifest after 2 h, andwere prolonged but with a lower intensity than those caused by the free selective kappa opioid in both tests. Conclusion: In this experimental model, the oral administration of nanovesicles containing the selective kappa opioid agonist U50,488 determined a prolonged analgesic outcome in the tail flick test, as well as in the writhing test.

Immunological approaches and therapy in burns (Review).

Burns have become an important public health problem in the last two decades, with just over a quarter of a million deaths annually. Major burns are accompanied by a strong inflammatory response, which will most often lead to systemic response inflammatory syndrome, followed by sepsis and finally induce multiple organ failure. The main mechanism involved in wound healing after burns is the inflammatory process, characterized by the recruitment of myeloid and T cells and by the involvement of numerous cytokines, chemokines, complement fractions, as well as various growth factors. Inflammasomes, protein-based cytosolic complexes, activated during metabolic stress or infection, play a role in modulating and improving the defense capacity of the innate immune system. Nucleotide-binding domain and leucine-rich repeat protein 3 (NLRP3) inflammasome has been studied predominantly and several hypotheses have been issued. Restoring the balance between the pro-inflammatory response and the anti-inflammatory activity is the key element to effective therapy in burns. Severe burns require nutritional support and pharmacotherapy not only for burn area but for different pathological complications of burn injury. In-depth research is required to find new ways to modulate the defense capacity, to prevent the complications of abnormal immune response and to treat burn injuries efficiently.