Psoriasis is a chronic skin auto-inflammatory and systemic disorder. Novel treatments are needed to solve a plethora of cases refractory to current treatment regimens. N-bromotaurine (TauNH-Br), a natural taurine oxidizing derivative produced by inflammatory cells, has anti-inflammatory, antiproliferative, and antimicrobial properties. This evidence prompted us to use TauNH-Br as a local agent for treatment of therapy-refractory psoriasis. Two pustular-plaque psoriasis cases, unresponsive to systemic and local treatments, one with localized lesions and one with generalized lesions, were selected. Both applications primarily indicated a sufficient curative activity of 1% TauNH-Br in psoriasis lesions. Moreover, TauNH-Br co-administration with taurine and a novel olive oil formulation cut in half the time needed for TauNH-Br alone to cause the same regression of equivalent psoriasis plaque lesions in the same patient. Importantly, all adverse effects of TauNH-Br (erythema, itching, bleeding) could be minimized by the combination therapy. Periods of 2-7 weeks to achieve almost complete regression with this formulation were remarkably short as compared to conventional treatment regimens that both patients had followed previously. Of note, there was no relapse within 3 months of monitoring. Combination formulations containing TauNH-Br and olive oil could become an advantageous topical medication for treatment of psoriasis.
DNA polymerase ζ (Pol ζ) is a specialized Pol that is involved in translesion DNA synthesis (TLS), in particular, in the extension of primer DNA after bypassing DNA lesions. Previously, we established human cells that express a variant form of Pol ζ with an amino acid change of leucine 2618 to methionine (L2618M) in the catalytic subunit REV3L (DNA Repair, 45, 34-43, 2016). This amino acid change made the cells more sensitive to the mutagenicity of benzo[a]pyrene diol epoxide (BPDE). In this study, we embedded BPDE-N2-guanine at a defined position in the supF gene on the shuttle plasmid and introduced it to REV3 L2618M cells or the wild-type (WT) cells to examine how far Pol ζ L2618M extends the primer DNA after bypassing the lesion. The adduct induced primarily G to T and G to C at the adducted site in both cell lines, but generated additional sequence changes such as base substitutions, deletions and additions in the extension patch much more often in REV3 L2618M cells than in the WT cells. Mutations in the extension patch in REV3 L2618M cells occurred most often within 10 bps from the adducted site. Then, the number of mutations gradually decreased and no mutations were observed between 30 and 40 bps from the lesion. We concluded that human Pol ζ L2618M and perhaps WT Pol ζ extend the primer DNA up to approximately 30 bps from the lesion in vivo. The possibility of involvement of Pol ζ L2618M in the insertion step of TLS is discussed.
Coronavirus disease 2019 (COVID-19) was first officially diagnosed in the city of Wuhan, China in January 2020. In reality, the disease was identified in December 2019 in the same city where patients began showing symptoms of pneumonia of unidentified origin. Very soon the disease became a global pandemic due to the suppression of information in the country of origin and inadequate testing for the COVID-19 virus. Currently, > 101 million people have been found positive for this virus and > 2.17 million people have died. There are no signs that COVID-19 is slowing down. This deadly virus affects multiple vital organs (lungs, heart, nervous system, blood, and immune system), yet its exact mechanism of pathophysiology remains obscure. Depending on the viral load, sick people often show symptoms of fever, cough, shortness of breath, coagulopathy, cardiac abnormalities, fatigue, and death. Great strides have been made in COVID-19 testing, thereby allowing timely therapeutic intervention. Currently, vaccines are on the market from Pfizer, Moderna and Astra Zeneca with limited supply. Phase III clinical trials are also underway from other manufacturers. In the current scenario, nutraceuticals and other phyto-mineral supplements appear to be promising alternative solutions for the prevention and treatment of COVID-19.
Chitosan is a deacetylated derivative of chitin obtained from the exoskeleton of shellfish, including crab, lobster, crayfish, and shrimp. Chitin can also be obtained from edible mushrooms. Chitosan and its derivatives are used in a number of health conditions, such as hypertension, obesity, high cholesterol, Crohn disease, insomnia, wound healing, periodontal disease, dry eye disease, cancer, and many others. Unique physicochemical/rheological properties of chitosan (absorption, solution stability, biodegradability, biocompatibility, nonimmunogenic activity, and nontoxicity) make them versatile for a myriad of applications in drug-delivery systems, enzyme immobilization, bioadhesive materials, vaccines, etc. These compounds also exert antimicrobial and antifungal effects, thereby having applications in agriculture and food industries. Nanoparticles (NPs) of chitosan and its derivatives offer superior results over non-NPs of chitosan in many biomedical and pharmaceutical applications. Chitosan has been approved for use in the United States, Italy, Japan, Finland, and many other countries.
Objectives: To examine the efficacy and safety of a proprietary nutraceutical formulation BVP-01 to manage the clinical signs of osteoarthritis (OA) in dogs using a blinded placebo-controlled study.Introduction: Currently, every fifth dog suffers from OA. OA dogs are usually treated with non-steroidal anti-inflammatory drugs (NSAIDS), but because of their serious side effects, nutraceuticals are used as alternative medicine.Methods: Dogs were selected from 5 primary accession clinics in New Zealand, and evaluated for clinical signs of OA.Dogs with mild OA were randomly allocated into three Groups: Group 1, BVP-01, Group 2, Placebo for six weeks followed by BVP-01 for next six weeks; Group 3, BVP-01 and Rimadyl (R).Group 4, severe OA dogs were treated with the same medication protocol as Group 3. The dogs were supplemented for 12 weeks.During weeks 7-12, Groups 2, 3 and 4 received BVP-01.The owners assessed the dogs weekly for pain and activity.At 0, 6 and 12 weeks the dogs were clinically examined and were videoed for subsequent kinematic analysis.Results: Of 74 dogs accepted into the trial, clinical and owner data on 71 dogs and kinematic data on 58 dogs were obtained.Supplementation of dogs with BVP-01 +R (Group 3) resulted in a significant improvement in owner-assessed activity and pain scores at weeks 2 and 3. Supplementation with BVP-01 (Group 1) provided a comparable significant improvement at weeks 9 and 10.Clinical assessment identified that lameness grade was worse in Group 4 at weeks 0, 6 and 12. Groups 1, 2 and 3 had significant improvement in articular pain scores at week 6.Kinematic analysis identified an improvement in limb range of motion at week 12 for Group 3 (p=0.055)and there was a trend for improvement in Group 1 (p=0.079).Conclusions And Clinical Relevance: BVP-01 offers an alternative to NSAIDs for the management of mild OA signs in dogs.
Nutrition is the epic centre of human activities and is a key player of changing and evolving patho-physiological state. Nutritional substances can modify metabolism and specific biological functions. Nutritional deficiencies results in to diseased states thus limiting the performance. A meaningful gain in sport, besides extensive practice, is depends on other factors too, like psychological, social and nutritional supplements. However use of exogenous substances as supplements to enhance the sport activities may be dangerous and may come under the preview of banned or illegal substances to disease prone conditions. In such situation biomolecule found itself in the body with known beneficial markers may be best suited .Such agents may act as pharmaconutrients with further potentiating and protection of organs with induced stress of exercise and numerous sports activities. Human body contains significant amount of sulphur in Free State and also in combined state, in shape of sulphur amino acids(SAA) one such SAA is Taurine ;chemically recognise as 2 Amino Ethane Sulfonic Acid.
In this world of competition, maintaining product quality is an important criterion of companies. Six Sigma is a tool which is used to reduce the rejections and improve quality. This paper describes the implementation of Six Sigma on a production line. The production line manufactures camshafts, facing an elevated rejection rate. The DMAIC (Define Measure Analysis Improve Control) methodology assists to minimize the number of rejections. The rejected camshaft is either send to scrap or for rework. To unravel the source of defects, Six Sigma provides a statistical approach to comprehend the root cause of defects. By deducing possible reasons for defects, it is easy to perceive the source of all variations. By implementing Six Sigma the quality level of production line has been improved.
Hyaluronic acid (also known as hyaluronan or hyaluronate) is naturally found in many tissues and fluids, but more abundantly in articular cartilage and synovial fluid (SF). Hyaluronic acid (HA) content varies widely in different joints and species. HA is a non-sulfated, naturally occurring nonprotein glycosaminoglycan (GAG), with distinct physico-chemical properties, produced by synoviocytes, fibroblasts, and chondrocytes. HA has an important role in the biomechanics of normal SF, where it is partially responsible for lubrication and viscoelasticity of the SF. The concentration of HA and its molecular weight (MW) decline as osteoarthritis (OA) progresses with aging. For that reason, HA has been used for more than four decades in the treatment of OA in dogs, horses and humans. HA produces anti-arthritic effects via multiple mechanisms involving receptors, enzymes and other metabolic pathways. HA is also used in the treatment of ophthalmic, dermal, burns, wound repair, and other health conditions. The MW of HA appears to play a critical role in the formulation of the products used in the treatment of diseases. This review provides a mechanism-based rationale for the use of HA in some disease conditions with special reference to OA.
Osteoarthritis (OA) is an inflammatory joint disease characterized by chronic and progressive degradation of the articular cartilage, osteophyte formation, thickening and sclerosis of the subchondral bone, bone marrow lesions, hypertrophy of bone at the margin, synovitis, and fibrosis. OA is a degenerative joint disease of the entire joint and surrounding muscles. Multiple etiologies, underlying mechanisms, and molecular pathways are involved in the pathophysiology of OA. Currently, clinical tools to diagnose the early changes of OA that occur in the articular cartilage are lacking. Although inflammation, pain, and lameness are hallmarks of OA, detection of semiquantitative and quantitative biomarkers in synovial fluid, serum, and urine aid in the diagnosis of OA at various stages. A large number of biomarkers have been identified for indicating cartilage breakdown or enzymes that cause cartilage degeneration, and they are commonly employed in determining disease onset, severity, progression, prognosis, and therapeutic modalities. Obviously, MRI confirms the cartilage and/or bone damage in OA, but that occurs in later stages. In such scenarios, circulatory biochemical markers and surrogate end points play pivotal roles in detecting early disease onset and prevent progression of OA by choosing an appropriate disease-modifying OA drug or complementary alternative medicine. This chapter describes the pathophysiology of OA in brief, classification of OA biomarkers, and biomarkers of inflammation, pain, and cartilage degeneration/loss associated with OA.