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INTRODUCTION: Antibiotics are one of the great advances in medicine. But overusing them has led to resistant bacteria (bacteria that are harder to treat). The current study foresees better non-toxic antimicrobial substances (conventional antibiotics) that insist to consider medicinal plants and animal-derived products, which have better antibiotics without any side effects. The goal of this in-vitro study was to evaluate the antimicrobial activity of cotton balls incorporated with Musa paradisiaca and chitosan. MATERIALS AND METHODS: Musa paradisiaca, chitosan, and gentamicin-reinforced cotton balls were considered in three groups namely Group 1, Group 2, and Group 3, which tested against the strains of Staphylococcus aureus, Escherichia coli, Actinomyces israelii, Streptococcus mutans, andBacteroides fragilis. For the present study, pre-sterilized cotton balls were taken and then soaked with Banana peel extract and soluble chitosan solution at different concentrations of 500 µg/ml, 250 µg/ml, 100 µg/ml, and 50 µg/ml under aseptic conditions and were dried at 50° overnight. The same incorporation method was followed for a 10mg/ml concentration of gentamicin, which was used as a positive control group. RESULTS: In this current study, the banana peel extract, soluble chitosan, and gentamicin exhibited antimicrobial activity against all the tested microorganisms. In the well diffusion method, at the concentration of 500 µg/ml and 250 µg/ml, chitosan and banana peel extract were comparatively better than the positive control group (gentamicin) at a higher concentration of 10 mg/ml. CONCLUSION: From the results of the present study, a lower concentration of the testing group (soluble chitosan and banana peel extract) exhibited a better effect when compared to a higher concentration of gentamicin. Hence, chitosan and banana peel extract impregnated cotton could be preferred for routine clinical scenarios like wounds, extractions sockets, and during any short intraoperative surgical procedures periodontal surgery, where it can provide maximal antimicrobial effects without the side effects of antibiotics.
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Peripheral neurons that sense glucose relay signals of glucose availability to integrative clusters of neurons in the brain. However, the roles of such signalling pathways in the maintenance of glucose homoeostasis and their contribution to disease are unknown. Here we show that the selective activation of the nerve plexus of the hepatic portal system via peripheral focused ultrasound stimulation (pFUS) improves glucose homoeostasis in mice and rats with insulin-resistant diabetes and in swine subject to hyperinsulinemic-euglycaemic clamps. pFUS modulated the activity of sensory projections to the hypothalamus, altered the concentrations of metabolism-regulating neurotransmitters, and enhanced glucose tolerance and utilization in the three species, whereas physical transection or chemical blocking of the liver-brain nerve pathway abolished the effect of pFUS on glucose tolerance. Longitudinal multi-omic profiling of metabolic tissues from the treated animals confirmed pFUS-induced modifications of key metabolic functions in liver, pancreas, muscle, adipose, kidney and intestinal tissues. Non-invasive ultrasound activation of afferent autonomic nerves may represent a non-pharmacologic therapy for the restoration of glucose homoeostasis in type-2 diabetes and other metabolic diseases.
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Diabetes Mellitus Experimental , Glucose , Animais , Diabetes Mellitus Experimental/terapia , Glucose/metabolismo , Homeostase , Hipotálamo/metabolismo , Fígado/metabolismo , Camundongos , Ratos , SuínosRESUMO
OBJECTIVES: Musculoskeletal pain and fatigue are common features in systemic lupus erythematosus (SLE). The cholinergic anti-inflammatory pathway is a physiological mechanism diminishing inflammation, engaged by stimulating the vagus nerve. We evaluated the effects of non-invasive vagus nerve stimulation in patients with SLE and with musculoskeletal pain. METHODS: 18 patients with SLE and with musculoskeletal pain ≥4 on a 10 cm Visual Analogue Scale were randomised (2:1) in this double-blind study to receive transcutaneous auricular vagus nerve stimulation (taVNS) or sham stimulation (SS) for 4 consecutive days. Evaluations at baseline, day 5 and day 12 included patient assessments of pain, disease activity (PtGA) and fatigue. Tender and swollen joint counts and the Physician Global Assessment (PGA) were completed by a physician blinded to the patient's therapy. Potential biomarkers were evaluated. RESULTS: taVNS and SS were well tolerated. Subjects receiving taVNS had a significant decrease in pain and fatigue compared with SS and were more likely (OR=25, p=0.02) to experience a clinically significant reduction in pain. PtGA, joint counts and PGA also improved. Pain reduction and improvement of fatigue correlated with the cumulative current received. In general, responses were maintained through day 12. Plasma levels of substance P were significantly reduced at day 5 compared with baseline following taVNS but other neuropeptides, serum and whole blood-stimulated inflammatory mediators, and kynurenine metabolites showed no significant change at days 5 or 12 compared with baseline. CONCLUSION: taVNS resulted in significantly reduced pain, fatigue and joint scores in SLE. Additional studies evaluating this intervention and its mechanisms are warranted.
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Fadiga/terapia , Lúpus Eritematoso Sistêmico/complicações , Dor Musculoesquelética/terapia , Estimulação Elétrica Nervosa Transcutânea/métodos , Estimulação do Nervo Vago/métodos , Adulto , Idoso , Método Duplo-Cego , Fadiga/imunologia , Feminino , Humanos , Pessoa de Meia-Idade , Dor Musculoesquelética/imunologia , Medição da Dor , Projetos Piloto , Resultado do TratamentoRESUMO
BACKGROUND: The present study aims to assess and compare the reduction in salivary Mutans Streptococci counts after chewing Xylitol, herbal and placebo gums among high school children. METHODS: The study was conducted among 72 school children (12-15 years) from 3 randomly selected schools (blocks). Xylitol, herbal and placebo gums were randomly allocated to 3 blocks. Subjects were instructed to chew one pellet four times a day for 21 days. The mean reduction in salivary Streptococcus mutans count was assessed. RESULTS: The 100% Xylitol sweetened chewing gum "Xylitol"has shown statistically significant reduction in salivary Mutans Streptococci colony forming units at the end of 21 days (P < 0.01). The reduction was not statistically significant in herbal and placebo chewing gum. CONCLUSIONS: Hundred percentage Xylitol sweetened chewing gum was found to be more effective in reducing salivary Mutans Streptococci count when compared to herbal and placebo chewing gums.
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Dopamina/metabolismo , Eletroacupuntura/métodos , Sepse/terapia , Nervo Vago/imunologia , Animais , MasculinoRESUMO
The inflammasome regulates the release of caspase activation-dependent cytokines, including interleukin (IL)-1ß, IL-18 and high-mobility group box 1 (HMGB1). By studying HMGB1 release mechanisms, here we identify a role for double-stranded RNA-dependent protein kinase (PKR, also known as EIF2AK2) in inflammasome activation. Exposure of macrophages to inflammasome agonists induced PKR autophosphorylation. PKR inactivation by genetic deletion or pharmacological inhibition severely impaired inflammasome activation in response to double-stranded RNA, ATP, monosodium urate, adjuvant aluminium, rotenone, live Escherichia coli, anthrax lethal toxin, DNA transfection and Salmonella typhimurium infection. PKR deficiency significantly inhibited the secretion of IL-1ß, IL-18 and HMGB1 in E. coli-induced peritonitis. PKR physically interacts with several inflammasome components, including NOD-like receptor (NLR) family pyrin domain-containing 3 (NLRP3), NLRP1, NLR family CARD domain-containing protein 4 (NLRC4), absent in melanoma 2 (AIM2), and broadly regulates inflammasome activation. PKR autophosphorylation in a cell-free system with recombinant NLRP3, apoptosis-associated speck-like protein containing a CARD (ASC, also known as PYCARD) and pro-caspase-1 reconstitutes inflammasome activity. These results show a crucial role for PKR in inflammasome activation, and indicate that it should be possible to pharmacologically target this molecule to treat inflammation.
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Proteína HMGB1/metabolismo , Inflamassomos/metabolismo , eIF-2 Quinase/metabolismo , Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Trifosfato de Adenosina/farmacologia , Animais , Antígenos de Bactérias/farmacologia , Proteínas Reguladoras de Apoptose/metabolismo , Toxinas Bacterianas/farmacologia , Proteínas Adaptadoras de Sinalização CARD/metabolismo , Proteínas de Ligação ao Cálcio/metabolismo , Proteínas de Transporte/metabolismo , Linhagem Celular , Células Cultivadas , Cristalinas/metabolismo , Escherichia coli/imunologia , Escherichia coli/fisiologia , Infecções por Escherichia coli/imunologia , Infecções por Escherichia coli/metabolismo , Feminino , Proteína HMGB1/sangue , Humanos , Inflamassomos/agonistas , Interleucina-18/sangue , Interleucina-1beta/sangue , Interleucina-6/análise , Interleucina-6/sangue , Macrófagos Peritoneais/efeitos dos fármacos , Macrófagos Peritoneais/metabolismo , Masculino , Proteínas de Membrana/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Proteína 3 que Contém Domínio de Pirina da Família NLR , Proteínas NLR , Peritonite/metabolismo , Fosforilação , RNA de Cadeia Dupla/imunologia , RNA de Cadeia Dupla/farmacologia , Rotenona/farmacologia , Infecções por Salmonella/imunologia , Infecções por Salmonella/metabolismo , Salmonella typhimurium/imunologia , Salmonella typhimurium/fisiologia , Transfecção , Ácido Úrico/farmacologia , eIF-2 Quinase/antagonistas & inibidores , eIF-2 Quinase/deficiência , eIF-2 Quinase/genéticaRESUMO
PURPOSE: The aim of the present study was to assess and compare the antibacterial effect of garlic extract with those of chlorhexidine and negative control mouthwashes against Streptococcus mutans. MATERIALS AND METHODS: The present study was carried out in two phases. In Phase 1, the zone of inhibition of various concentrations of garlic extract against S. mutans was determined using the cup and plate method. The minimum concentration at which a zone of inhibition appeared was further employed to prepare a mouthwash that was used in Phase 2. This phase included 45 dental students whose baseline salivary S. mutans level was assessed. They were randomly divided into three groups: '1' representing students using garlic extract mouthwash (garlic extract + water + sorbitol + spearmint oil), '2' representing those using chlorhexidine (0.2%) mouthwash and '3' representing those using a negative control (water + sorbitol + spearmint oil). All of the subjects were advised to use 10 ml of the assigned mouthwash once daily after their last meal for a duration of 7 days. On day 8, the post-treatment salivary S. mutans counts were assessed, and the data were analysed and compared by performing appropriate statistical tests. RESULTS: Phase 1: the 3% concentration was the minimum concentration at which a zone of inhibition was observed. Phase 2: a reduction in post-test S. mutans counts in all three groups was found. The mean difference that was observed in the garlic extract group was 5.23 x 105 CFU/ml, in the chlorhexidine group 2.63 x 105 CFU/ml and in the negative control group 1.18 x 105 CFU/ml. The differences among all three groups were statistically significant (P < 0.05) and that between the negative control and the garlic group was highly significant (P < 0.001). CONCLUSIONS: Garlic extract is effective against S. mutans when tested both in vitro and in vivo. As S. mutans is one of the primary aetiological organisms in dental caries development (Loesche, 1986), and in the present study garlic extract has been shown to be effective against S. mutans, garlic extract mouth rinse might be used as an effective remedy in the prevention of dental caries.
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Anti-Infecciosos Locais/uso terapêutico , Clorexidina/uso terapêutico , Alho , Antissépticos Bucais/uso terapêutico , Extratos Vegetais/uso terapêutico , Saliva/microbiologia , Streptococcus mutans/efeitos dos fármacos , Adolescente , Adulto , Carga Bacteriana , Técnicas Bacteriológicas , Química Farmacêutica , Feminino , Aromatizantes/química , Humanos , Masculino , Mentha spicata , Testes de Sensibilidade Microbiana , Antissépticos Bucais/química , Extratos Vegetais/administração & dosagem , Óleos de Plantas/química , Sorbitol/química , Edulcorantes/química , Adulto JovemRESUMO
OBJECTIVE: High mobility group box chromosomal protein 1 (HMGB-1) is a DNA binding nuclear protein that can be released from dying cells and activated myeloid cells. Extracellularly, HMGB-1 promotes inflammation. Clinical and experimental studies demonstrate that HMGB-1 is a pathogenic factor in chronic arthritis. Mice with combined gene deficiency for DNase II and IFNRI spontaneously develop chronic, destructive polyarthritis with many features shared with rheumatoid arthritis. DNase II is needed for macrophage degradation of engulfed DNA. The aim of this study was to evaluate a potential pathogenic role of HMGB-1 in this novel murine model. METHODS: The course of arthritis, assessed by clinical scoring and histology, was studied in DNase II(-/-) × IFNRI(-/-) mice, in comparison with heterozygous and wild-type mice. Synovial HMGB-1 expression was analyzed by immunohistochemistry. Serum levels of HMGB-1 were determined by Western immunoblotting and enzyme-linked immunosorbent assay (ELISA), and anti-HMGB-1 autoantibodies were detected by ELISA. Macrophage activation was studied by immunostaining for intracellular interleukin-1ß and HMGB-1. HMGB-1 was targeted with truncated HMGB-1-derived BoxA protein, acting as a competitive antagonist, with intraperitoneal injections every second day for 5 weeks. RESULTS: DNase II(-/-) × IFNRI(-/-) mice developed symmetric polyarthritis with strong aberrant cytosolic and extracellular HMGB-1 expression in synovial tissue, in contrast to that observed in control animals. Increased serum levels of HMGB-1 and HMGB-1 autoantibodies were recorded in DNase II(-/-) × IFNRI(-/-) mice, both prior to and during the establishment of disease. Systemic HMGB-1-specific blockade significantly ameliorated the clinical disease course, and a protective effect on joint destruction was demonstrated by histologic evaluation. CONCLUSION: HMGB-1 is involved in the pathogenesis of this spontaneous polyarthritis, and intervention with an HMGB-1 antagonist can mediate beneficial effects.
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Artrite/imunologia , Artrite/metabolismo , Domínios HMG-Box/imunologia , Proteína HMGB1/imunologia , Proteína HMGB1/metabolismo , Animais , Artrite/prevenção & controle , Artrite Experimental/imunologia , Artrite Experimental/metabolismo , Artrite Experimental/prevenção & controle , Autoanticorpos , Endodesoxirribonucleases/deficiência , Proteína HMGB1/antagonistas & inibidores , Camundongos , Camundongos Knockout , Proteínas Recombinantes/imunologia , Proteínas Recombinantes/farmacologiaRESUMO
OBJECTIVE: Electrical vagus nerve stimulation inhibits proinflammatory cytokine production and prevents shock during lethal systemic inflammation through an alpha7 nicotinic acetylcholine receptor (alpha7nAChR)-dependent pathway to the spleen, termed the cholinergic anti-inflammatory pathway. Pharmacologic alpha7nAChR agonists inhibit production of the critical proinflammatory mediator high mobility group box 1 (HMGB1) and rescue mice from lethal polymicrobial sepsis. Here we developed a method of transcutaneous mechanical vagus nerve stimulation and then investigated whether this therapy can protect mice against sepsis lethality. DESIGN: Prospective, randomized study. SETTING: Institute-based research laboratory. SUBJECTS: Male BALB/c mice. INTERVENTIONS: Mice received lipopolysaccharide to induce lethal endotoxemia or underwent cecal ligation and puncture to induce polymicrobial sepsis. Mice were then randomized to receive electrical, transcutaneous, or sham vagus nerve stimulation and were followed for survival or euthanized at predetermined time points for cytokine analysis. MEASUREMENTS AND MAIN RESULTS: Transcutaneous vagus nerve stimulation dose-dependently reduced systemic tumor necrosis factor levels during lethal endotoxemia. Treatment with transcutaneous vagus nerve stimulation inhibited HMGB1 levels and improved survival in mice with polymicrobial sepsis, even when administered 24 hrs after the onset of disease. CONCLUSIONS: Transcutaneous vagus nerve stimulation is an efficacious treatment for mice with lethal endotoxemia or polymicrobial sepsis.