Chitosan Soft Matter Vesicles Loaded with Acetaminophen as Promising Systems for Modified Drug Release.

Our study was designed to acquire, characterize and evaluate the biocompatibility of novel lipid vesicles loaded with acetaminophen (APAP) and coated with chitosan (CS). We investigated the in vitro and in vivo drug release kinetics from these systems, and we conducted assessments for both in vitro hemocompatibility and in vivo biocompatibility. For the in vivo biocompatibility evaluation, the mice were randomly divided into four groups of six animals and were treated orally as follows: control group: 0.1 mL/10 g body weight of double-distilled water; CS group: 0.1 mL/10 g body weight 1% CS solution; APAP group: 150 mg/kg body weight APAP; APAP-v group: 150 mg/kg body weight APAP-loaded lipid vesicles. The impact of APAP-v on various hematological, biochemical, and immune parameters in mice were assessed, and the harvested tissues were subjected to histopathological examination. The innovative formulations effectively encapsulating APAP within soft vesicles exhibited reasonable stability in solution and prolonged drug release in both in vitro and in vivo studies. The in vitro hemolysis test involving APAP-loaded vesicles revealed no signs of damage to red blood cells. The mice treated with APAP-v showed neither significant variances in hematological, biochemical, and immune parameters, nor structural changes in the examined organ samples, compared to the control group. APAP-v administration led to prolonged drug release. We can conclude that the APAP-v are innovative carrier systems for modifying drug release, making them promising candidates for biomedical applications.

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.

Zinc Chloride Enhances the Antioxidant Status, Improving the Functional and Structural Organic Disturbances in Streptozotocin-Induced Diabetes in Rats.

Background and Objectives: Diabetes mellitus (DM) is a complex disease affecting the whole metabolic balance of the body and resulting in multiple organ complications: cardiovascular, neuronal, renal, etc. Our study focuses on investigating the effect of zinc chloride (Zn) on certain blood parameters suggestive for assessing the metabolic disturbances, the liver and kidney function, the oxidative stress and the immune defense capacity in experimental-induced DM with streptozotocin (STZ) and cholesterol in rats. Materials and Methods: The animals were assigned to three groups, as follows: Group 1 (Control): buffer citrate solution 0.1 mL/100 g body; Group 2 (STZ): 20 mg/kg body STZ and fat diet (10 g cholesterol/100 g diet); Group 3 (STZ+Zn): 20 mg/kg body STZ + 5 mg/kg body Zn chloride and the same fat diet. DM was induced by administering STZ in a single take daily, for three consecutive days, Zn and citrate buffer were administered orally for a month. The protocol was approved by the Ethics Committee of the University 'Grigore T Popa' Iasi, in agreement with the International Regulations about the handling of laboratory animals. Results: The use of STZ in rats fed with cholesterol was correlated with important weight gain, hyperglycemia, the intensification of the transaminases activity and the increase in serum alkaline phosphatase, cholesterol, triglyceride, urea, creatinine and in malondialdehyde. Conclusions: The treatment with Zn resulted in weight loss and a decrease in blood sugar in diabetic rats. Supplementation with Zn notably reduced oxidative stress, preserved the pancreatic architecture and restored the liver and kidney function and structure in STZ-induced DM in rats.

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.

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.

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.

A Novel Symbiotic Beverage Based on Sea Buckthorn, Soy Milk and Inulin: Production, Characterization, Probiotic Viability, and Sensory Acceptance.

Nowadays, vegan consumers demand that food products have more and more properties that contribute to the prevention of some diseases, such as lower fat content, increased mineral content (calcium, iron, magnesium, and phosphorus), pleasant flavor, and low calorie values. Therefore, the beverage industry has tried to offer consumers products that include probiotics, prebiotics, or symbiotics with improved flavor and appearance and beneficial effects on health. The possibility of producing beverages based on soy milk with sea buckthorn syrup or sea buckthorn powder supplemented with inulin and fermented with the Lactobacillus casei ssp. paracasei strain was examined. The aim of this study was to obtain a novel symbiotic product that exploits the bioactive potential of sea buckthorn fruits. Tests were carried out in the laboratory phase by fermenting soy milk, to which was added sea buckthorn syrup (20%) or sea buckthorn powder (3%) and inulin in proportions of 1% and 3%, with temperature variation of fermentation (30 and 37 °C). During the fermentation period, the survivability of prebiotic bacteria, pH, and titratable acidity were measured. The storage time of beverages at 4 °C ± 1 °C was 14 days, and the probiotic viability, pH, titratable acidity, and water holding capacity were determined. Novel symbiotic beverages based on sea buckthorn syrup or powder, inulin, and soy milk were successfully obtained using the Lactobacillus casei ssp. paracasei strain as a starter culture. Moreover, the inulin added to the novel symbiotic beverage offered microbiological safety and excellent sensory attributes as well.

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.

Immunologic and nonimmunologic sclerodermal skin conditions - review.

Scleroderma-like cutaneous lesions have been found in many pathological conditions and they have the clinical appearance of sclerotic or scleroatrophic lesions. Affected skin biopsies described histopathological changes similar to those of scleroderma located strictly on the skin or those of systemic sclerosis. These skin lesions can be found in inflammatory diseases with autoimmune substrate (generalized morphea, chronic graft versus host disease, eosinophilic fasciitis), tissue storage diseases (scleredema, scleromyxedema, nephrogenyc systemic fibrosis, systemic amyloidosis), metabolic diseases (porphyrya cutanea tarda, phenylketonuria, hypothyroidism, scleredema diabeticorum), progeroid syndromes. Given the multiple etiologies of sclerodermal lesions, a correct differential diagnosis is necessary to establish the appropriate treatment.

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.

Once-Daily Abrocitinib for the Treatment of Moderate-to-Severe Atopic Dermatitis in Adults and Adolescents Aged 12 Years and Over: A Short Review of Current Clinical Perspectives.

Atopic dermatitis (AD) is a chronic inflammatory skin disorder with high prevalence and a complex pathophysiology. This relapsing and remitting skin disorder has many negative consequences on the patient's quality of life and that of his family. Until now, moderate-to-severe AD treatment was a symptomatic one, using skin emollients, topical corticosteroids, phototherapy, antihistamines and systemic drugs - immune suppressants and other systemic treatments (dupilumab). Starting from 2021, abrocitinib, a Janus kinase-1 inhibitor, was approved for the treatment of moderate-to-severe cases of AD in Europe, in adults. Multiple phase three studies (JADE MONO-1 [NCT03349060]; JADE MONO-2 [NCT03575871]; JADE TEEN [NCT03796676]; JADE COMPARE; GOODERHAM; JADE EXTEND) have yielded positive results in adults and adolescents suffering from this disease, with efficacy, a good tolerance, safe profile, and with generally mild side effects. The positive results were obtained even starting from the first stages of the oral drug administration. The low frequency of side effects and the advantage of having an orally administered medication makes abrocitinib an important additional tool for the treatment of moderate-to-severe forms of AD.

Paraclinical Aspects in Systemic Sclerosis.

Systemic sclerosis (SSc) is a chronic inflammatory disease with an autoimmune substrate that affects the skin and a large number of internal organs. The chronic inflammatory process is sustained by a wide range of cytokines and chemokines, which are discharged by inflammatory cells, with fibrosis and nail bed vascular changes (disorganized vasculature architecture with microhemorrhages, megacapillaries and areas without capillaries). Confocal microscopy contributes to the understanding of the molecular mechanism involved in chronic inflammation and mainly targets the field of research. Coherent optical tomography, capillaroscopy, and skin biopsy are useful for the differential diagnosis of SSc with other sclerodermoid syndromes. The immunological profile is a classification criterion for SSc and directs the diagnosis to the two subsets of the disease. Multisystemic damage requires evaluation with the help of a set of investigations specific to each affected organ, such as: diffusing capacity for carbon monoxide, forced vital capacity, 6-minute walk test, high-resolution computed tomography standard and reduced sequential, cardiac ultrasound and right cardiac catheterization. The current possibilities of diagnosis, treatment and monitoring are permanently adapting to new medical discoveries.

Hearing Loss Secondary to Systemic Sclerosis Vasculopathy: Case Study with a Short Review.

Systemic sclerosis (SSc) is a collagenosis with a substrate of chronic inflammation, which is determined by autoimmunity. The pathogenesis of this disease involves microvasculopathy (small vessel pathology) followed by excessive cutaneous and visceral fibrosis. Although acoustic and vestibular impairment is not classified as being a secondary pathology of SSc, several studies have identified cases of SSc that associate hearing loss and especially vertigo and tinnitus. This paper presents data from the medical literature that have identified vestibular and auditory symptoms among patients with SSc, associating the clinical case presentation of a patient suffering from SSc, which is associated with hearing loss. The need for additional studies on larger groups of patients is underlined, in order to clarify the impact of vasculopathy and fibrosis on the acoustic and vestibular analyzer in patients with SSc.

CREST Syndrome in Systemic Sclerosis Patients - Is Dystrophic Calcinosis a Key Element to a Positive Diagnosis?

Introduction: CREST syndrome is a clinical entity associated with systemic sclerosis, which meets at least three of the five clinical features: calcinosis, Raynaud's phenomenon, esophageal dysmotility, sclerodactyly, and telangiectasia. Three of these clinical features (Raynaud's phenomenon, sclerodactyly and esophageal dysmotility) are often present in classical subsets of SSc: limited and diffuse, and their presence in association does not define CREST syndrome. Calcinosis seems to be less common in SSc and its association with other clinical features is characteristic of CREST syndrome. Therefore, it can be appreciated that calcinosis is the key element of CREST syndrome. Methods: This study included a number of 37 candidates with SSc, diagnosed with the help of the American College of Rheumatology (ACR)/European League Against Rheumatism (EULAR) 2013 criteria. Results and Discussions: These three elements (calcinosis, Raynaud's phenomenon, esophageal dysmotility) were recorded both in the limited subset of SSc, but especially in the subset of diffuse SSc, contrary to the data in the literature. Conclusion: We appreciate that CREST syndrome is a clinical entity that can overlap with both subsets of SSc. Given the divergent views of the authors on the classification of CREST syndrome, future studies may contribute to a reassessment of SSc classification.

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.

Violent death in a rare peroxisomal disease--Zellweger syndrome.

Peroxisomal diseases are rare (1:50,000), genetically determined disorders (autosomal recessive), systemic, multiorgan illnesses with prominent involvement of the nervous system, caused either by the failure to form or to maintain the peroxisome, or by a defect in the function of a single or multiple peroxisomal enzymes. Peroxisomes contain approximately 50 enzymes which are responsible for many metabolic reactions, and play an important role in the oxidation of saturated very-long-chain fatty acids (VLCFA). The authors present the case of a Romanian boy, who died at the age of 1.6 of one of the peroxisomal diseases-Zellweger syndrome. Newborn infants with Zellweger syndrome have a typical dysmorphic facies, neonatal seizures, profound hypotonia, and eye abnormalities. Major abnormalities are present in the liver (fibrotic), kidney (cortical cysts), and brain (lipid-laden macrophages and histiocytes in cortical and periventricular areas, demyelination, centrosylvian polymicrogyria and pachygyria)-cerebro-hepato-renal syndrome (CHRS) (Zellweger). Infants with Zellweger syndrome rarely live more than a few months, but in this case the survival was longer, and the cause of death was not directly the peroxisomal disease but a violent cause of death-mechanical asphyxia with tracheo-bronchial food aspiration. The authors present the results of investigations carried out during the child's life, but also data collected at the autopsy and hystopathological postnecroptic investigations. By presenting this case, the authors wish to bring to your attention a rare pathology in forensic practice by the paradox of finding a common violent cause of death, asphyxia with food aspiration, in a rare metabolic-genetic disease, which is usually fatal by itself.