ABSTRACT
Teicoplanin (Teico) is an antimicrobial agent that spontaneously forms micelles in aqueous media. In this work, we characterized the physicochemical properties of nanoparticles formed by the interaction of Teico with Amphotericin B (AmB). Teico-AmB micelles structure spontaneously in aqueous media, with a particle size of 70-100 nm and a zeta potential of -28 mV. Although the characterization of these nanostructures yielded satisfactory results, in vitro cytotoxicity tests showed high toxicity. Based on this, adding cholesterol to the formulation was evaluated to try to reduce the toxicity of the drug. These Teico-AmB-Chol nanostructures have a larger size, close to 160 nm, but a lower polydispersity index. They also showed strongly negative surface charge and were more stable than Teico-AmB, remaining stable for at least 20 days at 4 °C and 25 °C and against centrifugation, dilution, freezing, lyophilization and re-suspension processes with a recovery percentage of AmB greater than 95%, maintaining their initial size and zeta potential. These Teico-AmB-Chol micelles show lower cytotoxic effect and higher biological activity than Teico-AmB, even than Amfostat® and Ambisome® formulations. These two new nanoparticles, with and without Chol, are discussed as potential formulations able to improve the antifungal therapeutic efficiency of AmB.
Subject(s)
Amphotericin B , Nanoparticles , Amphotericin B/toxicity , Amphotericin B/chemistry , Micelles , Teicoplanin , Antifungal Agents/toxicity , Antifungal Agents/chemistry , Nanoparticles/chemistryABSTRACT
2020 will be remembered worldwide for the outbreak of Coronavirus disease (COVID-19), which quickly spread until it was declared as a global pandemic. The main protease (Mpro) of SARS-CoV-2, a key enzyme in coronavirus, represents an attractive pharmacological target for inhibition of SARS-CoV-2 replication. Here, we evaluated whether the anti-inflammatory drug Ibuprofen, may act as a potential SARS-CoV-2 Mpro inhibitor, using an in silico study. From molecular dynamics (MD) simulations, we also evaluated the influence of ionic strength on the affinity and stability of the Ibuprofen-Mpro complexes. The docking analysis shows that R(-)Ibuprofen and S(+)Ibuprofen isomers can interact with multiple key residues of the main protease, through hydrophobic interactions and hydrogen bonds, with favourable binding energies (-6.2 and -5.7 kcal/mol, respectively). MM-GBSA and MM-PBSA calculations confirm the affinity of these complexes, in terms of binding energies. It also demonstrates that the ionic strength modifies significantly their binding affinities. Different structural parameters calculated from the MD simulations (120 ns) reveal that these complexes are conformational stable in the different conditions analysed. In this context, the results suggest that the condition 2 (0.25 NaCl) bind more tightly the Ibuprofen to Mpro than the others conditions. From the frustration analysis, we could characterize two important regions (Cys44-Pro52 and Linker loop) of this protein involved in the interaction with Ibuprofen. In conclusion, our findings allow us to propose that racemic mixtures of the Ibuprofen enantiomers might be a potential treatment option against SARS-CoV-2 Mpro. However, further research is necessary to determinate their possible medicinal use.Communicated by Ramaswamy H. Sarma.
Subject(s)
COVID-19 Drug Treatment , Sodium Chloride , Coronavirus 3C Proteases , Cysteine Endopeptidases/chemistry , Humans , Ibuprofen/pharmacology , Molecular Docking Simulation , Molecular Dynamics Simulation , Peptide Hydrolases/chemistry , Protease Inhibitors/chemistry , SARS-CoV-2 , Viral Nonstructural Proteins/chemistryABSTRACT
The polyethers yessotoxin (YTX) and okadaic acid (OA) are two marine algal toxins frequently associated as edible shellfish contaminants. Seafood contamination by these compounds, also at low concentrations and for a long period of time, can increase the possibility of their simultaneous and repeated ingestion, with possible synergistic toxic effects. Thus, in vivo toxicity by repeated oral exposure to a combination of fixed doses of YTX and OA (1 mg YTX/kg and 0.185 mg OA/kg, daily for 7 days) was investigated in mice, in comparison to that of each toxin alone. No mortality, signs of toxicity, diarrhea or hematological changes was induced by the toxins co-administration or by the single toxins. Light microscopy revealed changes at gastric level (multifocal subacute inflammation, erosions and epithelial hyperplasia) in 2/5 mice co-administered with the toxins. In animals dosed only with OA, epithelial hyperplasia of forestomach and slight focal subacute inflammation of its submucosa were noted. No changes were induced by the treatment with YTX. Ultrastructural analysis of the heart revealed some cardiomyocytes with "loose packing" of myofibrils and aggregated rounded mitochondria in mice co-administered with the toxins or with YTX; OA-treated mice showed only occasional mitochondrial assemblage and dilated sarcomeres. Thus, the combined oral doses of YTX (1 mg/kg/day) and OA (0.185 mg/kg/day) did not exert cumulative or additive toxic effects in mice, in comparison to the single toxins.
Subject(s)
Marine Toxins/toxicity , Okadaic Acid/toxicity , Oxocins/toxicity , Animals , Female , Heart/drug effects , Marine Toxins/administration & dosage , Mice , Mice, Inbred Strains , Mollusk Venoms , Myocardium/ultrastructure , Okadaic Acid/administration & dosage , Oxocins/administration & dosage , Toxicity Tests , Transaminases/bloodABSTRACT
Respuestas mediadas por IgE juegan un papel fundamental en los pacientes alérgicos, con intolerancia alimentaria. Sin embargo, la asociación de anticuerpos IgG e IgA específicos para alimentos con la evolución clínica de los pacientes alérgicos es aún materia de controversia. En este estudio investigamos si anticuerpos IgG e IgA específicos para carne de vaca pueden coexistir con anticuerpos IgE de la misma especificidad en pacientes alérgicos y examinamos su relevancia clínica en los diferentes contextos alérgicos. Anticuerpos IgE, IgG e IgA específicos para carne de vaca se determinaron por enzimoinmunoensayo (ELISA) en una poblaciónde pacientes alérgicos (N = 125), clasificados en pacientes con asma, alergias en piel y alergias gastrointestinales, así como en sujetos control (N = 80). Se determinaron además, anticuerpos IgE específicos para frutas cítricas, tomate, leche de vaca, huevo de gallina y trigo. La carne de vaca fue el alimento más alergénico en toda la población, no sólo para la IgE (57,6%, p <0,001), sino también para los isotipos IgG e IgA (53,6% y 34,0% respectivamente, P <0,001).Anticuerpos IgE, IgG e IgA se presentaron con mayor frecuencia en el suero de las tres poblaciones : asma, alergias en piel y gastrointestinales en comparación con los sueros de sujetos controles (P<0,001). Sorprendentemente, los isotipos IgG e IgA se detectaron de manera significativa, incluso en ausencia de IgE, en las trescondiciones alérgicas. Todos los pacientes alérgicos, incluyendo aquéllos que presentaban sólo anticuerpos IgG e IgA, mejoraron sus síntomas significativamente y disminuyeron sus niveles de anticuerpos específicos para carne de vaca en respuesta a una dieta de exclusión de carne vacuna...
IgE-mediated responses play a pivotal role in allergic patients with food intolerance. However, the association of food-specific IgG and IgA antibodies with the clinical outcome of allergic patients is still a matter of controversy. In this study we investigate the possibility that beef-specific IgG and IgA antibodies may coexist with beef-specific IgE antibodies in food allergic patients and determine their clinical relevance indifferent allergic contexts. Beef-specific IgE, IgG and IgA antibodies were determined by enzymoimmunoassay (ELISA) in a population of allergic patients(n=125) divided into patients with asthma, skin disease or gastrointestinal disorders and in control subjects (n=80). IgE specificfor citric fruits, tomato, cow ́s milk, eggs hen ́s and wheat was also determined. Beef was the predominant antigenic food in the whole population, not only for IgE (57.6%; P<0.001), but also for IgG and IgA isotypes (53.6% and 34.0% respectively, P<0.001). Beef-specific IgE, IgG and IgA antibodies increased significantly in patients with asthma, gastrointestinal and skin allergic disorders compared to sera from control subjects (P<0.001). Remarkably, IgG and IgA isotypes were significantly detected, even in the absence of IgE, in the three allergic pathologies. All allergic patients, including those showing only IgG and IgA antibodies, significantly ameliorated their symptoms and diminished the levels of beef-specific antibodies in response to a cow meat exclusion diet. ..
Subject(s)
Humans , Male , Female , Asthma , Food Hypersensitivity , Gastrointestinal Diseases , Immunoglobulin A , Immunoglobulin E , Immunoglobulin G , MeatABSTRACT
Respuestas mediadas por IgE juegan un papel fundamental en los pacientes alérgicos, con intolerancia alimentaria. Sin embargo, la asociación de anticuerpos IgG e IgA específicos para alimentos con la evolución clínica de los pacientes alérgicos es aún materia de controversia. En este estudio investigamos si anticuerpos IgG e IgA específicos para carne de vaca pueden coexistir con anticuerpos IgE de la misma especificidad en pacientes alérgicos y examinamos su relevancia clínica en los diferentes contextos alérgicos. Anticuerpos IgE, IgG e IgA específicos para carne de vaca se determinaron por enzimoinmunoensayo (ELISA) en una poblaciónde pacientes alérgicos (N = 125), clasificados en pacientes con asma, alergias en piel y alergias gastrointestinales, así como en sujetos control (N = 80). Se determinaron además, anticuerpos IgE específicos para frutas cítricas, tomate, leche de vaca, huevo de gallina y trigo. La carne de vaca fue el alimento más alergénico en toda la población, no sólo para la IgE (57,6%, p <0,001), sino también para los isotipos IgG e IgA (53,6% y 34,0% respectivamente, P <0,001).Anticuerpos IgE, IgG e IgA se presentaron con mayor frecuencia en el suero de las tres poblaciones : asma, alergias en piel y gastrointestinales en comparación con los sueros de sujetos controles (P<0,001). Sorprendentemente, los isotipos IgG e IgA se detectaron de manera significativa, incluso en ausencia de IgE, en las trescondiciones alérgicas. Todos los pacientes alérgicos, incluyendo aquéllos que presentaban sólo anticuerpos IgG e IgA, mejoraron sus síntomas significativamente y disminuyeron sus niveles de anticuerpos específicos para carne de vaca en respuesta a una dieta de exclusión de carne vacuna...(AU)
IgE-mediated responses play a pivotal role in allergic patients with food intolerance. However, the association of food-specific IgG and IgA antibodies with the clinical outcome of allergic patients is still a matter of controversy. In this study we investigate the possibility that beef-specific IgG and IgA antibodies may coexist with beef-specific IgE antibodies in food allergic patients and determine their clinical relevance indifferent allergic contexts. Beef-specific IgE, IgG and IgA antibodies were determined by enzymoimmunoassay (ELISA) in a population of allergic patients(n=125) divided into patients with asthma, skin disease or gastrointestinal disorders and in control subjects (n=80). IgE specificfor citric fruits, tomato, cow ́s milk, eggs hen ́s and wheat was also determined. Beef was the predominant antigenic food in the whole population, not only for IgE (57.6%; P<0.001), but also for IgG and IgA isotypes (53.6% and 34.0% respectively, P<0.001). Beef-specific IgE, IgG and IgA antibodies increased significantly in patients with asthma, gastrointestinal and skin allergic disorders compared to sera from control subjects (P<0.001). Remarkably, IgG and IgA isotypes were significantly detected, even in the absence of IgE, in the three allergic pathologies. All allergic patients, including those showing only IgG and IgA antibodies, significantly ameliorated their symptoms and diminished the levels of beef-specific antibodies in response to a cow meat exclusion diet. ..(AU)
Subject(s)
Humans , Male , Female , Immunoglobulin G , Immunoglobulin A , Immunoglobulin E , Food Hypersensitivity , Meat , Asthma , Gastrointestinal DiseasesABSTRACT
BACKGROUND: We report herein a novel strategy for the preparation of protein-based nanodelivery vehicles for hydrophobic active pharmaceutical ingredients. METHODS: The procedure consisted of three steps, ie, exposure of hydrophobic residues of a protein to a pH-induced partial unfolding: interaction between hydrophobic residues on the protein and the hydrophobic active pharmaceutical ingredient, and a final step where the structure of the protein was reversed to a native-like state by returning to neutral pH. As proof of concept, the interaction of paclitaxel with partially unfolded states of human serum albumin was evaluated as a potential method for the preparation of water-soluble complexes of the taxane with albumin. RESULTS: We found that paclitaxel readily binds to pH-induced partially unfolded albumin, leading to the formation of optically clear water-soluble complexes. The complexes thus formed were more stable in solution when the albumin native state was at least partially restored by neutralization of the solution to a pH around 7. It was also observed that the hydrodynamic radius of human serum albumin was only slightly increased after the cycle of pH changes, remaining in a monomeric state with a size according to paclitaxel binding. Furthermore, paclitaxel binding did not affect the overall exposure of charged groups of human serum albumin, as evaluated by its interaction with an ionic exchange resin. CONCLUSION: The in vitro biological activity of the complexes formed was qualitatively equivalent to that of a Cremophor(®)-based formulation.
Subject(s)
Paclitaxel/administration & dosage , Paclitaxel/chemistry , Serum Albumin/chemistry , Cell Line, Tumor , Chromatography, Ion Exchange , Drug Stability , Humans , Hydrogen-Ion Concentration , Hydrophobic and Hydrophilic Interactions , Nanoparticles/chemistry , Nanoparticles/ultrastructure , Osmolar Concentration , Particle Size , Pharmaceutical Vehicles/administration & dosage , Pharmaceutical Vehicles/chemistry , Polyethylene Glycols/chemistry , Protein Unfolding , Serum Albumin/administration & dosage , Solubility , TemperatureABSTRACT
The acute oral toxicity of a new palytoxin congener, 42-hydroxy-palytoxin (42-OH-PLTX), was investigated in female CD-1 mice. The toxin (300-1697 µg/kg), administered by gavage, induced scratching, jumping, respiratory distress, cyanosis, paralysis and death of mice, with an LD50 of 651 µg/kg (95% confidence limits: 384-1018 µg/kg) within 24 h. Hematoclinical analyses showed increased plasma levels of lactate dehydrogenase and aspartate-aminotransferase at doses of 600 µg/kg and above, as well as of alanine-aminotransferase, creatine phosphokinase and potassium ions at ≥ 848 µg/kg. Histology revealed inflammatory lesions in the non-glandular area of the stomach of mice that survived up to 24 h after gavage (424-1200 µg/kg). Although no histological alterations were seen in skeletal and cardiac muscles, changes in some plasma biomarkers (creatine phosphokinase, lactate dehydrogenase) suggested involvement of these tissues in 42-OH-PLTX oral toxicity, in agreement with epidemiological data on seafood poisonings ascribed to palytoxins. Complete recovery of the tissue and hematological changes was observed two weeks post-exposure. Furthermore, 42-OH-PLTX induced in vitro delayed erythrocyte hemolysis at concentrations similar to those of PLTX (EC50 = 7.6 and 13.2 x 10⻹² M, respectively). This hemolysis could be completely neutralized by a monoclonal anti-PLTX antibody. The in vivo data, together with the in vitro data recorded for 42-OH-PLTX, seem to indicate Na+/K+-ATPase as one of the key cellular targets of this toxin.
Subject(s)
Cnidarian Venoms/toxicity , Pyrans/toxicity , Stomach/pathology , Administration, Oral , Animals , Antibodies, Monoclonal , Biomarkers/blood , Chromatography, Liquid , Cnidarian Venoms/administration & dosage , Female , Hemolysis/drug effects , Histological Techniques , Lethal Dose 50 , Mass Spectrometry , Mice , Pyrans/administration & dosageABSTRACT
IgE-mediated responses play a pivotal role in allergic patients with food intolerance. However, the association of food-specific IgG and IgA antibodies with the clinical outcome of allergic patients is still a matter of controversy. In this study we investigate whether beef-specific IgG and IgA antibodies may coexist with beef-specific IgE antibodies in food-allergic patients and examined their clinical relevance in different allergic settings. Beef-specific IgE, IgG and IgA antibodies were determined by solid-phase enzymoimmunoassay (ELISA) in a population of allergic patients (N=125) classified into patients with asthma, skin disease or gastrointestinal disorders, as well as in control subjects (N=80). IgE antibodies specific for citric fruits, tomato, cows milk, chickens egg and wheat were also determined. Beef was the predominant allergenic food in the whole population, not only for IgE (57.6 percent; P less than 0.001), but also for IgG and IgA isotypes (53.6 percent and 34.0 percent, respectively, P less than 0.001). Beef-specific IgE, IgG and IgA antibodies increased significantly in sera from patients with asthma, gastrointestinal disorders and skin allergy compared to sera from control subjects (P less than 0.001). Remarkably, IgG and IgA isotypes were significantly detected, even in the absence of IgE, in the three allergic conditions. All allergic patients, including those showing only IgG and IgA antibodies, significantly ameliorated their symptoms, and their levels of beef-specific antibodies were considerably reduced in response to a cow meat exclusion diet. While patients with gastrointestinal or skin allergic diseases were capable of tolerating beef following an established period of diet exclusion, asthmatic patients experienced a relapse of symptoms and showed a considerable increase in IgE, IgG and IgA-specific antibodies when re-challenged with a beef-enriched diet. Thus, beef-specific IgG and IgA antibodies coexist with IgE antibodies in sera from allergic patients and are significantly associated with the clinical course of allergic disorders, particularly asthma.
Subject(s)
Hypersensitivity/immunology , Immunoglobulins/blood , Meat/adverse effects , Adult , Animals , Cattle , Diet , Female , Food Hypersensitivity/immunology , Humans , Immunoglobulin A/blood , Immunoglobulin E/blood , Immunoglobulin G/blood , Male , Middle AgedABSTRACT
The acute oral toxicity of palytoxin (PLTX), a highly toxic compound associated with seafood intoxication in tropical and subtropical areas, was investigated in mice. After gavage administration (300-1697 microg/kg) to groups of five female CD-1 mice, signs of toxicity and lethality were recorded for 24 h. The LD(50) was 767 microg/kg (95% confidence limits: 549-1039 microg/kg) and the main symptoms observed were scratching, jumping, respiratory distress and paralysis. Hematoclinical analyses showed increased levels of creatine phosphokinase and lactate dehydrogenase at doses of 600 microg/kg and above, and aspartate transaminase at 848 microg/kg and above. Histological analysis revealed acute inflammation of the forestomach in mice surviving up to 24h after administration (424-1200 microg/kg). Other histological alterations were observed in the liver and pancreas, while cardiac and skeletal muscle cells revealed only ultrastructural alterations visible by transmission electron microscopy. Ultrastructural and hematoclinical findings suggest an involvement of skeletal and/or cardiac muscle as targets of PLTX, according to the observed human symptoms. A NOEL of 300 microg/kg can be estimated from this acute oral toxicity study.
Subject(s)
Acrylamides/toxicity , Administration, Oral , Animals , Cnidarian Venoms , Creatine Kinase/metabolism , Creatinine/metabolism , Dose-Response Relationship, Drug , Female , Kidney/pathology , Kidney/ultrastructure , L-Lactate Dehydrogenase/metabolism , Lethal Dose 50 , Liver/pathology , Liver/ultrastructure , Mice , Microscopy, Electron, Transmission , Muscle, Skeletal/pathology , Muscle, Skeletal/ultrastructure , Myocardium/pathology , Myocardium/ultrastructure , Survival Analysis , Transaminases/metabolismABSTRACT
Latex, a polyisoprene (PI) hydrophobic elastomer, was evaluated in vitro and in vivo as a matrix for intravaginal steroid hormone delivery. Matrices containing hormone were prepared by swelling latex in chloroform that contained soluble progesterone (P4). In vitro studies demonstrate that P4 release from PI follows a zero order model during at least 100 h and depends on initial load up to 10 mg cm(-2). The release of P4 from a PI matrix was found to be two times faster than from a polydimethylsiloxane (PDMS) matrix. FT-IR and X-ray powder diffraction analysis of P4 polymorphs show that when nucleated in PDMS, the hormone crystallizes only in alpha-form while in latex, crystallizes as a mixture of alpha- and beta-form. In vivo studies show that devices with a PI matrix containing 0.5 g of P4 are effective to reach plasma levels above 1 ng ml(-1) that are needed to synchronize estrous in cattle. Altogether, the results show that PI, a vulcanized polymer with a carbon-carbon backbone, can be used as a new matrix for the intravaginal administration of progesterone with improved release profile than silicone and that the matrix can influence the crystalline state of the hormone.
Subject(s)
Drug Carriers , Fertility Agents, Female/administration & dosage , Latex/chemistry , Progesterone/administration & dosage , Administration, Intravaginal , Animals , Cattle , Chemistry, Pharmaceutical , Crystallization , Crystallography, X-Ray , Dimethylpolysiloxanes/chemistry , Drug Compounding , Estrus Synchronization/drug effects , Female , Fertility Agents, Female/blood , Fertility Agents, Female/chemistry , Fertility Agents, Female/pharmacokinetics , Ovariectomy , Powder Diffraction , Progesterone/blood , Progesterone/chemistry , Progesterone/pharmacokinetics , Solubility , Spectroscopy, Fourier Transform Infrared , Technology, Pharmaceutical/methodsABSTRACT
High temperature vulcanizing silicone elastomers have been widely used in controlled delivery systems of steroid hormones with the aim of controlling estrous cycle in livestock. This paper reports experiments conducted to evaluate the possibility of using room temperature vulcanizing (RTV) silicone elastomers for the intravaginal administration of progesterone to cattle. In vitro studies showed that RTV silicones and high-temperature vulcanizing silicone release progesterone at a similar rate. Y-shaped inserts made of different polymers were designed as supports of RTV silicone sheaths to test the in vivo release of progesterone. Field evaluation showed that RTV silicone sheaths containing 0.75 g of progesterone were at least as effective at estrous synchronization as commercially available intravaginal inserts.
Subject(s)
Cattle/physiology , Dimethylpolysiloxanes , Drug Delivery Systems/veterinary , Estrus Synchronization/methods , Progesterone/administration & dosage , Administration, Intravaginal , Animals , Delayed-Action Preparations , Drug Delivery Systems/methods , Female , Male , Pregnancy , Progesterone/blood , Random AllocationABSTRACT
Bacterial mediastinitis after orthotopic heart transplantation (OHT) is well described in the literature. However, little information has been published on fungal mediastinitis in this population. We describe a man with Aspergillus fumigatus mediastinitis diagnosed 10 weeks after OHT. The patient was treated with voriconazole. The literature on Aspergillus mediastinitis is also reviewed.
Subject(s)
Aspergillosis/diagnosis , Aspergillus fumigatus/isolation & purification , Heart Transplantation , Mediastinitis/diagnosis , Mediastinitis/microbiology , Antifungal Agents/therapeutic use , Aspergillosis/drug therapy , Drug Administration Schedule , Humans , Male , Middle Aged , Opportunistic Infections/drug therapy , Opportunistic Infections/microbiology , Pyrimidines/administration & dosage , Pyrimidines/therapeutic use , Triazoles/administration & dosage , Triazoles/therapeutic use , VoriconazoleABSTRACT
BACKGROUND: Infective endocarditis is a known complication of cardiac transplantation. However, published information has been limited to case reports and small case series. METHODS: Cardiac transplantation has been performed at Temple University Hospital since 1983. We identified transplant patients with ICD-9 codes for endocarditis or bacteremia. A diagnosis of endocarditis required fulfillment of the Duke criteria and presence of a vegetation. Clinical and microbiologic data were collected. Demographic and survival information were compared with heart transplant recipients without endocarditis. We reviewed all previously published cases using a MEDLINE search. RESULTS: Ten of 659 heart transplant recipients had endocarditis (1.5%, 187 cases per 100,000 person years). Mitral and tricuspid valves were involved predominantly. No patient had aortic valve infection. Patients with tricuspid valve infection had a greater median number of endomyocardial biopsies (n=23) than those with mitral valve infection (n=9, P=0.10). The major pathogens were Staphylococcus aureus (4 cases) and Aspergillus fumigatus (3 cases). Factors associated with S. aureus infection were new hemodialysis catheters, cellulitis, and a contaminated donor organ. All patients with A. fumigatus had antecedent cytomegalovirus viremia and disseminated fungal infection, including endophthalmitis. Endocarditis-related mortality was 80%. Median survival after transplant was 1.4 years in patients with endocarditis, compared with 9.3 years in other heart transplant recipients (P<0.001). CONCLUSIONS: Endocarditis is substantially more common in heart transplant recipients than in general populations. Frequent central venous catheter access and multiple endomyocardial biopsies appear to predispose to infection. Aspergillus is a common pathogen and endocarditis follows infection elsewhere. The prognosis of post-cardiac transplant endocarditis is poor.
Subject(s)
Endocarditis/etiology , Heart Transplantation/adverse effects , Adult , Aged , Aspergillosis/etiology , Endocarditis/microbiology , Endocarditis/mortality , Endocarditis, Bacterial/etiology , Female , Humans , Male , Middle Aged , Retrospective StudiesABSTRACT
In this work we evaluated the efficacy and safety of a bread formulation containing chitosan in dyslipidemic type 2 diabetic subjects. For this purpose a total of 18 patients were allowed to incorporate to their habitual diets 120 g/day of bread containing 2% (wt/wt) chitosan (chitosan group, n= 9) or standard bread (control group, n= 9). Before the study and after 12 weeks on the modified diet, the following parameters were evaluated: body weight, plasma cholesterol, high-density lipoprotein (HDL)-cholesterol, low-density lipoprotein (LDL)-cholesterol, triglyceride, and hemoglobin A(1c) (HbA(1c)). Compared with the control group, the patients receiving chitosan-containing bread decreased their mean levels of LDL-cholesterol and significantly increased their mean levels of HDL-cholesterol at the end of the study. There were no significant differences in the body weight, serum triglyceride, and HbA(1c). These results suggest that chitosan incorporated into bread formulations could improve the lipoprotein balance similar to typical biliary salts trappers, increasing the HDL- and lowering the LDL-cholesterol, without changing the triglyceride levels. These results warrant further studies over a longer period of time to evaluate if a persistent improvement in levels of lipoproteins can be attained with this strategy.
Subject(s)
Bread , Chitin/analogs & derivatives , Chitin/administration & dosage , Cholesterol, HDL/blood , Cholesterol, LDL/blood , Diabetes Mellitus, Type 2/diet therapy , Hyperlipidemias/diet therapy , Blood Glucose/metabolism , Body Weight/drug effects , Chitin/adverse effects , Chitosan , Diabetes Mellitus, Type 2/blood , Diabetes Mellitus, Type 2/complications , Food Additives/pharmacology , Food Additives/therapeutic use , Glycated Hemoglobin/analysis , Humans , Hyperlipidemias/blood , Hyperlipidemias/complications , Treatment Outcome , Triglycerides/bloodABSTRACT
We evaluated the in vitro capacity of high and low molecular weight chitosans (HMWCh and LMWCh) to inhibit the adherence of strains of S. mutans obtained from the American Type Culture Collection (ATCC,25175) to artificial saliva-coated hydroxiapatite beads. The effect of these biopolymers was assessed in terms of pH, ionic force, minimum inhibitory concentration (MIC) and antibacterial activity. The results show that HMWCh is modified by a rise in pH (7.0) and ionic strength. The induced conformational changes lead to the formation of rigid meshes capable of aggregating and entrapping S. mutans. This process is associated to the properties of HMWCh. LMWCh gave rise to smaller aggregates that exhibited a comparatively reduced interaction capacity. The MIC for HMWCh was 0.5 g% and evidenced the bacteriostatic action of the aggregates. We conclude that HMWCh would exert an inhibitory effect on the process of specific adsorption of S. mutans to saliva-coated hydroxiapatite beads.
Subject(s)
Bacterial Adhesion/drug effects , Chitin/analogs & derivatives , Chitin/pharmacology , Streptococcus mutans/drug effects , Chitin/chemistry , Chitosan , Durapatite , Hydrogen-Ion Concentration , Microbial Sensitivity Tests , Molecular Weight , Osmolar Concentration , SalivaABSTRACT
We evaluated the in vitro capacity of high and low molecular weight chitosans (HMWCh and LMWCh) to inhibit the adherence of strains of S. mutans obtained from the American Type Culture Collection (ATCC,25175) to artificial saliva-coated hydroxiapatite beads. The effect of these biopolymers was assessed in terms of pH, ionic force, minimum inhibitory concentration (MIC) and antibacterial activity. The results show that HMWCh is modified by a rise in pH (7.0) and ionic strength. The induced conformational changes lead to the formation of rigid meshes capable of aggregating and entrapping S. mutans. This process is associated to the properties of HMWCh. LMWCh gave rise to smaller aggregates that exhibited a comparatively reduced interaction capacity. The MIC for HMWCh was 0.5 g
and evidenced the bacteriostatic action of the aggregates. We conclude that HMWCh would exert an inhibitory effect on the process of specific adsorption of S. mutans to saliva-coated hydroxiapatite beads.
ABSTRACT
We evaluated the in vitro capacity of high and low molecular weight chitosans (HMWCh and LMWCh) to inhibit the adherence of strains of S. mutans obtained from the American Type Culture Collection (ATCC,25175) to artificial saliva-coated hydroxiapatite beads. The effect of these biopolymers was assessed in terms of pH, ionic force, minimum inhibitory concentration (MIC) and antibacterial activity. The results show that HMWCh is modified by a rise in pH (7.0) and ionic strength. The induced conformational changes lead to the formation of rigid meshes capable of aggregating and entrapping S. mutans. This process is associated to the properties of HMWCh. LMWCh gave rise to smaller aggregates that exhibited a comparatively reduced interaction capacity. The MIC for HMWCh was 0.5 g
and evidenced the bacteriostatic action of the aggregates. We conclude that HMWCh would exert an inhibitory effect on the process of specific adsorption of S. mutans to saliva-coated hydroxiapatite beads.
ABSTRACT
The present clinical study was performed to comparatively assess the therapeutic effect of Low and High Molecular Weight Chitosan (LMWCh and HMWCh), hexetidine, triclosan. Plaque index, saliva buffering capacity and bacteriological controls for S. mutans and lactobacilli, were performed. The plaque and bacterial indices revealed statistically significant differences between groups. Buffering capacity was similar using, hexetidine, and triclosan, whereas it was maximum in 100% of the patients in the LMWCh and HMWCh groups. Only 0.5% HMWCh induced low activity of S. mutans in 100% of the patients and caused complete inhibition of lactobacilli growth. No changes were observed in the profile of salivary proteins. The present clinical study confirms the therapeutic efficacy of the chitosan as a bacteriostatic agent.
Subject(s)
Anti-Infective Agents, Local/administration & dosage , Chitin/analogs & derivatives , Chitin/administration & dosage , Dental Plaque/drug therapy , Hexetidine/administration & dosage , Triclosan/administration & dosage , Adolescent , Adult , Chitosan , Colony Count, Microbial , Dental Plaque/microbiology , Double-Blind Method , Female , Humans , Lactobacillus/drug effects , Male , Molecular Weight , Mouthwashes/pharmacology , Mouthwashes/therapeutic use , Saliva/microbiology , Streptococcus mutans/drug effectsABSTRACT
The present clinical study was performed to comparatively assess the therapeutic effect of Low and High Molecular Weight Chitosan (LMWCh and HMWCh), hexetidine, triclosan. Plaque index, saliva buffering capacity and bacteriological controls for S. mutans and lactobacilli, were performed. The plaque and bacterial indices revealed statistically significant differences between groups. Buffering capacity was similar using, hexetidine, and triclosan, whereas it was maximum in 100
of the patients in the LMWCh and HMWCh groups. Only 0.5
HMWCh induced low activity of S. mutans in 100
of the patients and caused complete inhibition of lactobacilli growth. No changes were observed in the profile of salivary proteins. The present clinical study confirms the therapeutic efficacy of the chitosan as a bacteriostatic agent.
ABSTRACT
The present clinical study was performed to comparatively assess the therapeutic effect of Low and High Molecular Weight Chitosan (LMWCh and HMWCh), hexetidine, triclosan. Plaque index, saliva buffering capacity and bacteriological controls for S. mutans and lactobacilli, were performed. The plaque and bacterial indices revealed statistically significant differences between groups. Buffering capacity was similar using, hexetidine, and triclosan, whereas it was maximum in 100
of the patients in the LMWCh and HMWCh groups. Only 0.5
HMWCh induced low activity of S. mutans in 100
of the patients and caused complete inhibition of lactobacilli growth. No changes were observed in the profile of salivary proteins. The present clinical study confirms the therapeutic efficacy of the chitosan as a bacteriostatic agent.
