BPC 157, L-NAME, L-Arginine, NO-Relation, in the Suited Rat Ketamine Models Resembling "Negative-Like" Symptoms of Schizophrenia.

We attempted throughout the NO-system to achieve the particular counteraction of the ketamine-induced resembling "negative-like" schizophrenia symptoms in rats using pentadecapeptide BPC 157, and NO-agents, NG-nitro-L-arginine methylester (L-NAME), and/or L-arginine, triple application. This might be the find out the NO-system organized therapy (i.e., simultaneously implied NO-system blockade (L-NAME) vs. NO-system over-stimulation (L-arginine) vs. NO-system immobilization (L-NAME+L-arginine)). The ketamine regimen (intraperitoneally/kg) included: 3 mg (cognitive dysfunction, novel object recognition test), 30 mg (anxiogenic effect (open field test) and anhedonia (sucrose test)), and 8 mg/3 days (social withdrawal). Medication (mg/kg intraperitoneally) was L-NAME (5), L-arginine (100), and BPC 157 (0.01), alone and/or together, given immediately before ketamine (L-NAME, L-arginine, and combination) or given immediately after (BPC 157 and combinations). BPC 157 counteracted ketamine-cognition dysfunction, social withdrawal, and anhedonia, and exerted additional anxiolytic effect. L-NAME (antagonization, social withdrawal) and L-arginine (antagonization, cognitive dysfunction, anhedonia) both included worsening cognitive dysfunction, anhedonia, and anxiogenic effect (L-NAME), social withdrawal, and anxiogenic effect (L-arginine). Thus, ketamine-induced resembling "negative-like" schizophrenia symptoms were "L-NAME non-responsive, L-arginine responsive" (cognition dysfunction), "L-NAME responsive, L-arginine non-responsive" (social withdrawal), "L-NAME responsive, L-arginine responsive, opposite effect" (anhedonia) and "L-NAME responsive, L-arginine responsive, parallel effect" (both anxiogening). In cognition dysfunction, BPC 157 overwhelmed NO-agents effects. The mRNA expression studies in brain tissue evidenced considerable overlapping of gene overexpression in healthy rats treated with ketamine or BPC 157. With the BPC 157 therapy applied immediately after ketamine, the effect on Nos1, Nos2, Plcg1, Prkcg, and Ptgs2 (increased or decreased expression), appeared as a timely specific BPC 157 effect on ketamine-specific targets.

Greener Is Better: First Approach for the Use of Natural Deep Eutectic Solvents (NADES) to Extract Antioxidants from the Medicinal Halophyte Polygonum maritimum L.

In this study, natural deep eutectic solvents (NADES) formed by choline chloride (ChCl), sucrose, fructose, glucose, and xylose, were used to extract antioxidants from the halophyte Polygonum maritimum L. (sea knotgrass) and compared with conventional solvents (ethanol and acetone). NADES and conventional extracts were made by an ultrasound-assisted procedure and evaluated for in vitro antioxidant properties by the radical scavenging activity (RSA) on the 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical, oxygen radical absorbance capacity (ORAC), and copper chelating activity (CCA). Samples were profiled by liquid chromatography (LC)-electrospray ionization (ESI)-QTOF-MS analysis. ChCl:fructose was more efficient in the DPPH assay, than the acetone extract. ChCl:sucrose and ChCl:fructose extracts had the highest ORAC when compared with the acetone extract. NADES extracts had higher CCA, than the acetone extract. The phenolic composition of the NADES extracts was less complex than the conventional extracts, but the proportions of major antioxidants, such as flavonols and flavan-3-ols, were similar in all the solvents. Myricitrin was the major flavonoid in all of the samples, while gallic acid was the main phenolic acid in the conventional extracts and present in a greater amount in ChCl:fructose. Results suggest that NADES containing ChCl and sucrose/fructose can replace conventional solvents, especially acetone, in the extraction of antioxidants from sea knotgrass.

Brain-gut Axis and Pentadecapeptide BPC 157: Theoretical and Practical Implications.

BACKGROUND: Brain-gut interaction involves, among others, peptidergic growth factors which are native in GI tract and have strong antiulcer potency and thus could from periphery beneficially affect CNS-disorders. We focused on the stable gastric pentadecapeptide BPC 157, an antiulcer peptidergic agent, safe in inflammatory bowel disease trials and now in multiple sclerosis trial, native and stable in human gastric juice. METHODS: Review of our research on BPC 157 in terms of brain-gut axis. RESULTS: BPC 157 may serve as a novel mediator of Robert's cytoprotection, involved in maintaining of GI mucosa integrity, with no toxic effect. BPC 157 was successful in the therapy of GI tract, periodontitis, liver and pancreas lesions, and in the healing of various tissues and wounds. Stimulated Egr-1 gene, NAB2, FAK-paxillin and JAK-2 pathways are hitherto implicated. Initially corresponding beneficial central influence was seen when BPC 157 was given peripherally and a serotonin release in particular brain areas, mostly nigrostriatal, was changed. BPC 157 modulates serotonergic and dopaminergic systems, beneficially affects various behavioral disturbances that otherwise appeared due to specifically (over)stimulated/damaged neurotransmitters systems. Besides, BPC 157 has neuroprotective effects: protects somatosensory neurons; peripheral nerve regeneration appearent after transection; after traumatic brain injury counteracts the otherwise progressing course, in rat spinal cord compression with tail paralysis, axonal and neuronal necrosis, demyelination, cyst formation and rescues tail function in both short-terms and long-terms; after NSAIDs or insulin overdose or cuprizone encephalopathies were attenuated along with GI, liver and vascular injuries. CONCLUSION: BPC 157, a gastric peptide, may serve as remedy in various CNS-disorders.

SAPHO syndrome: a review.

INTRODUCTION: Synovitis-acne-pustulosis-hyperostosis-osteitis (SAPHO) is an acronym for various osteoarticular and dermatological manifestations that can appear in the same patient. It is a rare syndrome, but since its awareness has increased, there have been more and more such reports in the literature. AIMS: The objectives of this review are to summarize the current state of knowledge on pediatric and adult-onset SAPHO syndrome, and to discuss treatment strategies that should be considered. RESULTS: The SAPHO syndrome can affect patients of any age, and its etiology is still not known. The syndrome has its cognizable radiological characteristics that are most important in making the diagnosis. There are several diagnostic criteria as well, but they need further validation. No standard treatment protocols are available and current treatment options are not evidenced-based due to the rarity of the syndrome. Therapy is empirical and aimed at easing pain and modifying the inflammatory process. It includes nonsteroidal anti-inflammatory drugs (NSAIDs) as the first-line agents. Antibiotics, corticosteroids, disease-modifying anti-rheumatic drugs, biologicals targeting tumor necrosis factor alpha or interleukin-1, and bisphosphonates have all been used with variable success. Surgery is reserved to treat complications. Even though it is a disease with good long-term prognosis, its treatment remains a challenge and the results are known to be disappointing, especially with the skin component of the disease. CONCLUSION: It is expected that these patients present at the time of diagnosis and the treatment should be as early, effective, and safe as possible in order to prevent osteoarticular progression and to limit the adverse events associated with pharmacological drugs.

Mutation in the type II collagen gene (COL2AI) as a cause of primary osteoarthritis associated with mild spondyloepiphyseal involvement.

OBJECTIVE: To define the clinical, radiologic and molecular characteristics of a patient with early progressive osteoarthritis and mild spondyloepiphyseal dysplasia. METHODS: We describe an 18-year-old girl with early progressive osteoarthritis and mild spondyloepiphyseal dysplasia. The index case underwent a physical examination, anthropometric measurements and radiologic and laboratory studies. DNA of the patient and her only living parent (mother) was sequenced for the type II collagen gene (COL2A1). RESULTS: Mild scoliosis was noticed in the proband at the age of 13 years. At the same age, she began to have arthralgia in almost all the joints and osteoarthritis progressed fast, necessitating a hip, knee and ankle prosthesis at the age of 18 years. She was eumorphic with no ocular or hearing abnormalities. Molecular testing of the COL2A1 gene revealed a p.Gly204Val mutation. The mutation was absent in the healthy mother. CONCLUSION: This patient provides further proof that an early osteoarthritic phenotype can be caused by a mutation in the COL2A1 gene.

Anti-neutrophil cytoplasmic antibody positivity in five children with systemic lupus erythematosus--what is the importance of this finding?

Juvenile systemic lupus erythematosus (JSLE) is a systemic autoimmune chronic disease that can affect any part of the body. It is characterized by the formation of antibodies against nuclear antigens. Vasculitis may be found in SLE, but it scarcely complies with anti-neutrophil cytoplasmic antibodies (ANCA)-associated vasculitis (AAV) criteria. We report five cases of severe JSLE associated with AAV diagnosed between 1991 and 2013 in three university-based tertiary care centers. The patients (3 girls and 2 boys, aged 12 to 17) presented with a severe clinical picture and the following features: cytopenia (n=5), autoimmune hepatitis (n=3), lupus nephritis (n=1), pancreatitis (n=1), secondary antiphospholipid syndrome (n=2), impending respiratory failure (n=2), and gastrointestinal bleeding (n=1). All patients were proteinase 3 (PR3) ANCA positive, while two of them were myeloperoxidase (MPO) and PR3 ANCAs positive at the same time. They were treated with corticosteroids and immunosuppressive drugs. Remission of the disease was achieved in three patients. The course of the disease was worsening in two patients and we included rituximab (anti-CD20) in therapy. All of our patients presented as the most severe SLE patients, who must be diagnosed as soon as possible and treated very intensively. Since the comorbidity of JSLE and AAV occurs very rarely in children, presentation of such patients, their clinical pictures, treatment, and the course of the diseases are experiences that can be of great help.