Social Cognition Impairments in Patients with Multiple Sclerosis and Comparison with Imaging Studies, Disease Duration and Grade of Disability

Cognitive impairments in multiple sclerosis (MS) are heterogeneous and their rate varies between 43% and 70%. A less studied aspect of cognition is social cognition, which is not a uniform theoretical construct. It includes emotion perception, prosody, empathy, theory of mind (ToM) and assessment of mood. In addition to progressive physical disability, social cognitive impairments are a reason for job loss in 24–80% of patients with MS, increased divorce rate, dissolution of partnerships and social communication difficulties

Molecular-genetic diagnosis of a Bulgarian family with multiple endocrine neoplasia, type IIA

INTRODUCTION: Multiple Endocrine Neoplasia (MEN) is a rare autosomal dominant disease with frequency 1:30 000 and it is classified in 3 subtypes: MEN 2A (Sipple syndrome), familial medullary thyroid carcinoma (FMTC), MEN 2B. The MEN 2A subtype constitutes approximately 70%-80% of cases of MEN 2. The onset age of the MEN 2A is prior to age 35 years. MEN 2A has an increased risk for parathyroid hyperplasia or adenoma. The clinical diagnosis is suspected when at least 2 specific endocrine tumors are detected in one patient or close relatives (MTC, pheochromocytoma, parathyroid adenomas). MTC is suspected in case of increased serum levels of calcitonin. The biochemical phenotype of MTC is revealed between age 5 and 25 (mean age 15 years). The tumor formation in the neck area is between age of 15 and 20 (2). Although there is controversy surrounding the definition of CCH, its utility to identify or confirm MEN 2 has been essentially replaced by RET (REarranged during Transfection) protooncogene testing. This allows the early surgery interventions, proper genetic counseling and prenatal diagnostics.MATERIAL AND METHODS: We report on a Caucasian male with complains of general weakness and weight loss (10 kg for 2 month). The patient`s mother has been diagnosed at 47 as bilateral pheochromocytomas and struma nodosa and died at age of 51. In the index patient abdominal ultrasound examination with biopsy of adrenal glands and histological analysis revealed pheochromocytoma on the right side; elevated plasma calcitonin concentration and US scan with biopsy of thyroid tissue detected medular thyroid cancer. The index patient has two elder brothers - it turned out that one of them had been surgically treated for medular thyroid cancer in the past; bilateral pheocromocytomas were detected in the family screening process.RESULTS AND CONCLUSION: MEN 2A diagnosis was suspected and we performed sequencing of RET protooncogene. The genetic analysis of the family affected members revealed c.1902C>G, p.Cys634Trp heterozygous mutation. Unfortunately, two kids in the families of 2 of the brothers have also inherited the mutation. All adult family members were offered genetic counseling. The standard therapy and the prophylactic thyroidectomy include the surgical removal of the thyroid gland, followed by parathyroid gland autotransplantation. In case codon 634 mutation the surgery is recommended before age of 5 years. All affected relatives are going through monitoring for residual disease. The screening protocol includes plasma levels of calcitonin. The stimulation tests are more sensitive than calcitonin measurements alone so they are recommended

Dendritic cells and TNF-Related apoptosis inducing ligand (TRAIL) represent new possibilities for sepsis treatment

Sepsis refers to a generalized inflammatory response of the organism to an infection or to bacterial products in circulation, rather than the development of an infection per se. Despite recent advances in clinical practice and overall medical care, sepsis remains a great health care problem and is still the most common cause of death in critically ill patients with infection. We suppose that during the course of sepsis the expression of TRAIL in different organs correlates with acute mortality and further development of multiple organ dysfunction syndrome (MODS). It is expected that dendritic cells (DCs) might become targets for apoptotic processes in a result of elevated TRAIL expression. This hypothesis is a bias for detailed investigations for in vivo studies in animal models and for in vitro studies of septic patients

Serum Leptin and Resistin Levels in Knee Osteoarthritis—Clinical and Radiologic Links: Towards Precise Definition of Metabolic Type Knee Osteoarthritis

Obesity is considered a major risk factor for the development and progression of knee osteoarthritis (OA). Apart from the mechanical effect of obesity via increase in mechanical overload of weight-bearing joints, an association with hand OA has been observed. There has been increasing interest in the role of adipokines in the pathogenesis of OA in the recent years. It has been suggested that their systemic effects link obesity and OA. In this regard, the aim of the current study was measurement and analysis of serum levels of leptin and resistin in patients with knee OA with different body mass index (BMI). Seventy-three patients with primary symptomatic knee OA at the age between 35 and 87 years (mean age 66 years) were included in the study (67 women and 6 men). The patients were from 2nd to 4th radiographic stage according to Kellgren–Lawrence scale. 43 patients were with concomitant obesity (BMI ≥ 30 kg/m2, mean values 38.34 ± 8.20) and 30 patients with BMI < 30 kg/m2 (mean values 25.07 ± 2.95). Eleven individuals with different BMIs, including cases with obesity but without radiographic knee OA, were examined as a control group. Serum levels of leptin and resistin were measured via ELISA method. In patients with knee OA and BMI ≥ 30 kg/m2, serum levels of leptin (39.546 ± 12.918 ng/mL) were significantly higher as compared with healthy individuals (15.832 ± 16.531 ng/mL, p < 0.05) and the patients with low BMI (p < 0.05). In patients with BMI < 30 kg/m2 the levels of leptin (13.010 ± 10.94 ng/mL) did not differ significantly from the respective values in the control group (p = 0.48). Serum levels of resistin were also higher in knee OA patients in comparison with healthy controls, but the difference was statistically significant only for patients with high BMI (2.452 ± 1.002 ng/mL in the group with BMI ≥ 30 kg/m2; 2.401 ± 1.441 ng/mL in patients with BMI < 30 kg/m2; 1.610 ± 1.001 ng/mL in the control group, p < 0.05). A correlation was found between the serum levels of leptin and radiographic stage of OA, i.e., higher leptin levels were present in the more advanced 3rd and 4th radiographic stage, while for resistin a correlation was observed in the patient subgroup with BMI < 30 kg/m2. Serum leptin and resistin levels and clinical characteristics were analyzed in patients with different clinical forms of OA. Novel clinical correlations have been found in the current study in patients with isolated knee OA vs. cases with presence of other disease localizations. It has been observed that patients with isolated knee OA were significantly younger and had higher BMI as compared with cases in whom OA is combined with other localizations i.e., spondyloarthritis ± presence of hip OA and with generalized OA. This supports the hypothesis that presence of obesity promotes earlier development of knee OA as an isolated localization of the disease in younger patients before appearance of osteoarthritic changes at other sites. The levels of leptin and resistin in isolated knee OA were also higher. Serum levels of leptin and resistin in combination with patients’ clinical characteristics suggest existence of different clinical and laboratory profile through which more precise definition of metabolic phenotype of knee OA would be possible. Considering the fact that obesity is a modifiable risk factor that has an impact on progression of knee OA, different approaches to influence obesity may offer potential for future disease-modifying therapeutic interventions

Disease-Modifying Potential of Metformin and Alendronate in an Experimental Mouse Model of Osteoarthritis

Osteoarthritis (OA) is the most common degenerative joint disease causing progressive damages of the cartilage and subchondral bone, synovial inflammation, and severe pain. Despite the complex pathomorphological changes that occur in OA, the approach to different forms of OA is standardized. The global results from pharmacological treatment are not satisfactory. Hence, this study aimed to explore the effects of metformin, alendronate, and their combination on OA development and progression in mice with collagenase-induced osteoarthritis (CIOA). Female ICR (CD-2) mice were randomized to five groups: control group, CIOA untreated, CIOA + metformin, CIOA + alendronate, and CIOA + metformin + alendronate. OA was induced by the intra-articular (i.a.) injection of collagenase. OA phenotype was analyzed by flow cytometry (bone marrow cell differentiation), ELISA (serum levels of the adipokines leptin and resistin), and histology (pathological changes of the knee joint). Treatment with metformin, alendronate, or their combination inhibited the expression of RANK and RANKL on osteoblasts and osteoclasts obtained by ex vivo cultivation of bone marrow cells in mineralization or osteoclastogenic media. In addition, metformin treatment was effective for the attenuation of fibroblast differentiation, but not of mesenchymal stem cells (MSCs), while alendronate had an opposite effect. The combination of metformin and alendronate had a suppressive effect on both MSCs and fibroblasts differentiation. Treatment with metformin, alendronate, and their combination decreased serum concentrations of leptin and resistin in the chronic phase of arthritis. The histopathological examination showed that compared with the untreated CIOA group (OA score 9), the groups treated with metformin (OA score 4) or alendronate (OA score 6) had lower scores for cartilage changes. Metformin combined with alendronate significantly decreased the degree of cartilage degeneration (OA score 2), suggesting that this combination might be a useful approach for the treatment of OA patients

Changes in the Subchondral Bone, Visfatin, and Cartilage Biomarkers after Pharmacological Treatment of Experimental Osteoarthritis with Metformin and Alendronate

Subchondral bone that has intense communication with the articular cartilage might be a potential target for pharmacological treatment in the early stages of osteoarthritis (OA). Considering the emerging data about the role of adipokines in the pathogenesis of OA, the administration of drugs that influence their level is also intriguing. Metformin and alendronate were administered in mice with collagenase-induced OA (CIOA) as a monotherapy and in combination. Safranin O staining was used for the assessment of changes in subchondral bone and articular cartilage. Before and after treatment, serum levels of visfatin and biomarkers of cartilage turnover (CTX-II, MMP-13, and COMP) were assessed. In the current study, the combined administration of alendronate and metformin in mice with CIOA led to the protection against cartilage and subchondral bone damage. In mice with CIOA, metformin led to a decrease in visfatin level. In addition, treatment with metformin, alendronate, or their combination lowered the level of cartilage biomarkers (CTX-II and COMP), while the level of MMP-13 was not influenced. In conclusion, personalized combination treatment in OA according to clinical phenotype, especially in the early stages of the disease, might lead to the identification of a successful disease-modifying therapeutic protocol in OA

Hemocyanins from Helix and Rapana Snails Exhibit in Vitro Antitumor Effects in Human Colorectal Adenocarcinoma

Hemocyanins are oxygen-transporting glycoproteins in the hemolymph of arthropods and mollusks that attract scientific interest with their diverse biological activities and potential applications in pharmacy and medicine. The aim of the present study was to assess the in vitro antitumor activity of hemocyanins isolated from marine snail Rapana venosa (RvH) and garden snails Helix lucorum (HlH) and Helix aspersa (HaH), as well the mucus of H. aspersa snails, in the HT-29 human colorectal carcinoma cell line. The effects of the hemocyanins on the cell viability and proliferation were analyzed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and the alterations in the tumor cell morphology were examined by fluorescent and transmission electron microscopy. The results of the MTT assay showed that the mucus and α-subunit of hemocyanin from the snail H. aspersa had the most significant antiproliferative activity of the tested samples. Cytomorphological analysis revealed that the observed antitumor effects were associated with induction of apoptosis in the tumor cells. The presented data indicate that hemocyanins and mucus from H. aspersa have an antineoplastic activity and potential for development of novel therapeutics for treatment of colorectal carcinoma

Antitumor Activity of Bioactive Compounds from Rapana venosa against Human Breast Cell Lines

This study is the first report describing the promising antitumor activity of biologically active compounds isolated from the hemolymph of marine snail Rapana venosa—a fraction with Mw between 50 and 100 kDa and two structural subunits (RvH1 and RvH2), tested on a panel of human breast cell lines—six lines of different molecular subtypes of breast cancer MDA-MB-231, MDA-MB-468, BT-474, BT-549, SK-BR-3, and MCF-7 and the non-cancerous MCF-10A. The fraction with Mw 50–100 kDa (HRv 50–100) showed good antitumor activity manifested by a significant decrease in cell viability, altered morphology, autophagy, and p53 activation in treated cancer cells. An apparent synergistic effect was observed for the combination of HRv 50–100 with cis-platin for all tested cell lines. The combination of HRv 50–100 with cisplatin and/or tamoxifen is three times more effective compared to treatment with classical chemotherapeutics alone. The main proteins in the active fraction, with Mw at ~50 kDa, ~65 kDa, ~100 kDa, were identified by MALDI-MS, MS/MS analyses, and bioinformatics. Homology was established with known proteins with antitumor potential detected in different mollusc species: peroxidase-like protein, glycoproteins Aplysianin A, L-amino acid oxidase (LAAO), and the functional unit with Mw 50 kDa of RvH. Our study reveals new perspectives for application of HRv 50–100 as an antitumor agent used alone or as a booster in combination with different chemotherapies

A Generalized Net Model of the Prostate Gland’s Functioning

Over the last 20 years, many Generalized Net (GN) models of the ways of functioning of the different systems and organs in the human body and models related to the description of biomedical processes in living organisms have been constructed. In this paper, a GN model of the prostate gland’s functioning was developed, as a continuation of the previous research. The model provides the possibility to trace the logical relations of the interactions of the prostate gland and various individual organs in the human body. The model shows the possibility for the existence of currently unknown feedback loops