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1.
Clin Rheumatol ; 37(4): 1065-1074, 2018 Apr.
Article in English | MEDLINE | ID: mdl-29520673

ABSTRACT

The classification of anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) remains controversial. The main objective of this study was to define the respective values of ANCA serotype-based classification, clinicopathological classification, and histopathological classification in predicting patient and renal outcomes in a Spanish cohort of patients with ANCA with specificity for myeloperoxidase, MPO-ANCA, versus ANCA with specificity for proteinase 3, PR3-ANCA. Two hundred and forty-five patients with ANCA-AAV and biopsy-proven renal involvement diagnosed between 2000 and 2104 were recruited in 12 nephrology services. Clinical and histologic data, renal outcomes, and mortality were analyzed. We applied the Chapel Hill Consensus Conference definition with categories for granulomatosis with the polyangiitis (GPA) and microscopic polyangiitis (MPA), the classification based on ANCA specificity, and the histopathological classification proposed in 2010. Eighty-two percent were MPO-ANCA positive and 18.0% PR3-ANCA positive. Altogether, 82.9% had MPA and 17.1% GPA. The median follow-up was 43.2 months (0.1-169.3). Neither ANCA-based serological nor clinical classification was predictive of renal outcomes or patient survival on bivariate or multivariate Cox regression analysis. Histopathological classification was found to predict development of end-stage renal disease (p = 0.005) in Kaplan-Meier analysis. ANCA specificity was more predictive of relapse than clinicopathological classification in multivariate analysis (HR 2.086; 95% CI 1.046-4.158; p = 0.037). In our Spanish cohort, a majority of patients had an MPO-ANCA-AAV. A classification based on ANCA specificity has a higher predictive value for relapse occurrence and could be used for decision-making with respect to induction treatment and maintenance therapies.


Subject(s)
Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis/physiopathology , Antibodies, Antineutrophil Cytoplasmic/immunology , Kidney/physiopathology , Adult , Aged , Aged, 80 and over , Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis/immunology , Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis/pathology , Female , Humans , Kidney/immunology , Kidney/pathology , Male , Middle Aged , Myeloblastin/immunology , Retrospective Studies , Spain , Young Adult
2.
Am J Transplant ; 17(3): 733-743, 2017 03.
Article in English | MEDLINE | ID: mdl-27496082

ABSTRACT

Kidney transplants from living donors (LDs) have a better outcome than those from deceased donors (DDs). Different factors have been suggested to justify the different outcome. In this study, we analyzed the infiltration and phenotype of monocytes/macrophages and the expression of inflammatory and fibrotic markers in renal biopsy specimens from 94 kidney recipients (60 DDs and 34 LDs) at baseline and 4 months after transplantation. We evaluated their association with medium- and long-term renal function. At baseline, inflammatory gene expression was higher in DDs than in LDs. These results were confirmed by the high number of CD68-positive cells in DD kidneys, which correlated negatively with long-term renal function. Expression of the fibrotic markers vimentin, fibronectin, and α-smooth muscle actin was more elevated in biopsy specimens from DDs at 4 months than in those from LDs. Gene expression of inflammatory and fibrotic markers at 4 months and difference between 4 months and baseline correlated negatively with medium- and long-term renal function in DDs. Multivariate analysis point to transforming growth factor-ß1 as the best predictor of long-term renal function in DDs. We conclude that early macrophage infiltration, sustained inflammation, and transforming growth factor-ß1 expression, at least for the first 4 months, contribute significantly to the difference in DD and LD transplant outcome.


Subject(s)
Graft Rejection/etiology , Graft Survival/immunology , Inflammation/etiology , Kidney Transplantation/adverse effects , Macrophages/immunology , Tissue Donors , Tissue and Organ Procurement/methods , Adult , Cadaver , Delayed Graft Function , Female , Follow-Up Studies , Glomerular Filtration Rate , Graft Rejection/pathology , Humans , Inflammation/pathology , Kidney Failure, Chronic/surgery , Kidney Function Tests , Male , Middle Aged , Prognosis , Prospective Studies , Risk Factors
3.
Expert Opin Pharmacother ; 17(10): 1363-73, 2016 Jul.
Article in English | MEDLINE | ID: mdl-27156578

ABSTRACT

INTRODUCTION: Chronic kidney disease-mineral and bone disorders (CKD-MBD) are associated with costly complications and dismal hard-outcomes. AREAS COVERED: In two comprehensive articles we review contemporary and future pharmacological options for treatment of phosphate (P) imbalance (part 1) and hyperparathyroidism (this part 2), taking into account CKD-accelerated cardiovascular calcification (CVC) processes. EXPERT OPINION: Improvements in CKD-MBD require an integral approach, addressing all three components of the CKD-MBD triad. Here, initial guidance to control hyperparathyroidism is provided, taking into account the presence/absence of CVC. We include also measures for patients at risk of adynamic bone disease or suffering from calciphylaxis. Many epidemiological studies (relating to vitamin D) and thorough analyses of recent randomized clinical trials (of cinacalcet) point towards benefits of attempting to improve biochemical parameters while trying to, at least, avoid progression of CVC by more rational use of intestinal P-binders and low-dose vitamin D derivatives and/or calcimimetics. This approach does not seem to be far away from significantly improving hard-outcomes, at least in the dialysis population. The availability of new drugs and the performance of randomized clinical trials should ultimately lead to define earlier, clearer, and more cost-effective patient stratification and biochemical targets with consequent significant clinical improvements.


Subject(s)
Bone Diseases, Metabolic/drug therapy , Hyperparathyroidism, Secondary/drug therapy , Renal Insufficiency, Chronic/drug therapy , Cinacalcet/therapeutic use , Disease Progression , Humans , Minerals/metabolism , Phosphates/metabolism , Randomized Controlled Trials as Topic , Renal Dialysis , Vitamin D/therapeutic use
4.
Expert Opin Pharmacother ; 17(9): 1247-58, 2016 Jun.
Article in English | MEDLINE | ID: mdl-27156993

ABSTRACT

INTRODUCTION: Chronic kidney disease-mineral and bone disorders (CKD-MBD), involving a triad of laboratory and bone abnormalities, and tissue calcifications, are associated with dismal hard-outcomes. AREAS COVERED: In two comprehensive articles, we review contemporary and future pharmacological options for treatment of phosphate (P) imbalance (this part 1) and hyperparathyroidism (part 2), taking into account CKD-accelerated atheromatosis/atherosclerosis and/or cardiovascular calcification (CVC) processes. EXPERT OPINION: Improvements in CKD-MBD require an integral approach, addressing all three components of the CKD-MBD triad. Individualization of treatment with P-binders and combinations of anti-parathyroid agents may improve biochemical control with lower incidence of undesirable effects. Isolated biochemical parameters do not accurately reflect calcium or P load or bone activity and do not stratify high cardiovascular risk patients with CKD. Initial guidance is provided on reasonable therapeutic strategies which consider the presence of CVC. This part reflects that although there is not an absolute evidence, many studies point to the need to improve P imbalance while trying to, at least, avoid progression of CVC by restriction of Ca-based P-binders if economically feasible. The availability of new drugs (i.e. inhibitors of intestinal transporters), and studies including early CKD should ultimately lead to clearer and more cost/effective clinical targets for CKD-MBD.


Subject(s)
Bone Diseases/drug therapy , Cardiovascular Diseases/prevention & control , Hyperparathyroidism/drug therapy , Phosphates/metabolism , Renal Insufficiency, Chronic/drug therapy , Vascular Calcification/prevention & control , Bone Diseases/complications , Bone Diseases/metabolism , Calcimimetic Agents/therapeutic use , Calcium/metabolism , Cardiovascular Diseases/complications , Cardiovascular Diseases/metabolism , Disease Progression , Humans , Hyperparathyroidism/complications , Hyperparathyroidism/metabolism , Minerals/metabolism , Parathyroid Hormone/metabolism , Phosphates/deficiency , Renal Insufficiency, Chronic/complications , Renal Insufficiency, Chronic/metabolism , Risk Factors , Vascular Calcification/chemically induced
5.
PLoS One ; 11(4): e0151997, 2016.
Article in English | MEDLINE | ID: mdl-27055262

ABSTRACT

INTRODUCTION: The instrumented-Timed-Up-and-Go test (iTUG) provides detailed information about the following movement patterns: sit-to-walk (siwa), straight walking, turning and walk-to-sit (wasi). We were interested in the relative contributions of respective iTUG sub-phases to specific clinical deficits most relevant for daily life in Parkinson's disease (PD). More specifically, we investigated which condition-fast speed (FS) or convenient speed (CS)-differentiates best between mild- to moderate-stage PD patients and controls, which parameters of the iTUG sub-phases are significantly different between PD patients and controls, and how the iTUG parameters associate with cognitive parameters (with particular focus on cognitive flexibility and working memory) and Health-Related-Quality of Life (HRQoL). METHODS: Twenty-eight PD participants (65.1 ± 7.1 years, H&Y stage 1-3, medication OFF state) and 20 controls (66.1 ± 7.5 years) performed an iTUG (DynaPort®, McRoberts BV, The Netherlands) under CS and FS conditions. The PD Questionnaire 39 (PDQ-39) was employed to assess HRQoL. General cognitive and executive functions were assessed using the Montreal Cognitive Assessment and the Trail Making Test. RESULTS: The total iTUG duration and sub-phases durations under FS condition differentiated PD patients slightly better from controls, compared to the CS condition. The following sub-phases were responsible for the observed longer total duration PD patients needed to perform the iTUG: siwa, turn and wasi. None of the iTUG parameters correlated relevantly with general cognitive function. Turning duration and wasi maximum flexion velocity correlated strongest with executive function. Walking back duration correlated strongest with HRQoL. DISCUSSION: This study confirms that mild- to moderate-stage PD patients need more time to perform the iTUG than controls, and adds the following aspects to current literature: FS may be more powerful than CS to delineate subtle movement deficits in mild- to moderate-stage PD patients; correlation levels of intra-individual siwa and wasi parameters may be interesting surrogate markers for the level of automaticity of performed movements; and sub-phases and kinematic parameters of the iTUG may have the potential to reflect executive functioning and HRQoL aspects of PD patients.


Subject(s)
Cognition , Gait Disorders, Neurologic/physiopathology , Parkinson Disease/physiopathology , Quality of Life , Aged , Algorithms , Biomechanical Phenomena , Case-Control Studies , Cross-Sectional Studies , Female , Humans , Male , Middle Aged , Netherlands , Postural Balance , Prospective Studies , Time Factors
6.
Case Rep Dermatol ; 8(3): 333-340, 2016.
Article in English | MEDLINE | ID: mdl-28461812

ABSTRACT

BACKGROUND: Omega-3 fatty acids (O3FA) have been used to treat IgA nephropathy (IgAN) but not cutaneous IgA vasculitis (IgAV). CASE REPORT: A 47-year-old female was referred for cutaneous vasculitis. She had a 24-year history of flares of palpable purpura, arthralgia associated with hematuria, and proteinuria. We diagnosed cutaneous IgAV associated with IgAN. We administered prednisone at doses ranging from 10 to 45 mg/day to control the flares. To reduce prednisone exposure, different therapeutic strategies (colchicine, diphenhydramine, hydroxyzine, azathioprine, benzathine penicillin, and mycophenolate mofetil) were applied without success. After 11 years, therapy with O3FA capsules containing 460 mg eicosapentaenoic acid and 380 mg of docosahexaenoic acid t.i.d. was introduced, allowing the prednisone to be stopped 2 years later. When the dose of O3FA was decreased to 1 capsule on alternate days, the cutaneous flares reappeared, but they were again controlled when the patient took 1 O3FA capsule daily. CONCLUSIONS: O3FA can be useful to control cutaneous IgAV.

8.
Curr Vasc Pharmacol ; 12(2): 313-23, 2014 Mar.
Article in English | MEDLINE | ID: mdl-23713879

ABSTRACT

The activation of vitamin D receptors (VDR) - (including activation by 25-hydroxyvitamin D) - seems to have not only mineral-metabolism beneficial effects but also important extra-skeletal actions. Paricalcitol is a synthetic vitamin D2 agonist of the VDR approved for the prevention and treatment of secondary hyperparathyroidism associated with chronic kidney disease (CKD). As a result of its selectivity, paricalcitol provides a wider therapeutic window for PTH suppression, minimizing deleterious effects of high serum calcium and/or phosphate concentrations. Paricalcitol also shares, and sometimes improves pleiotropic vitamin-D related systemic effects. For instance, paricalcitol has been repeatedly shown to decrease calcium and phosphate deposition in vessels and to decrease the expression of osteogenic factors preventing the active transformation of smooth muscle vascular cells into osteoblast-like cells in experimental models. In patients, paricalcitol has been associated with improved survival of dialysis patients and it may improve residual albuminuria in diabetic patients. Consequently, paricalcitol may enhance the standard of care in these high-risk patients. Although it seems reasonable to use these potential advantages to guide the individual and integral management of the complex CKD-mineral and bone disorder, it is necessary to recognize that many of these observations have not been proven nor confirmed in prospective clinical trials.


Subject(s)
Ergocalciferols/therapeutic use , Animals , Calcium/metabolism , Ergocalciferols/pharmacology , Heart/drug effects , Humans , Hyperparathyroidism, Secondary/drug therapy , Kidney/drug effects , Phosphates/metabolism , Receptors, Calcitriol/physiology , Renal Insufficiency, Chronic/drug therapy
9.
Eur J Neurol ; 21(2): 361-3, 2014 Feb.
Article in English | MEDLINE | ID: mdl-23834483

ABSTRACT

BACKGROUND AND PURPOSE: Exome sequencing analysis has recently identified a nonsense mutation in fused in sarcoma (FUS) segregating with essential tremor (ET) within a large French-Canadian family. Further characterization of FUS resulted in the identification of additional mutations in ET patients; however, their pathogenicity still remains to be confirmed. The role of FUS in an independent cohort of ET patients from Canada was evaluated. METHODS: The entire coding sequence of FUS in 217 patients diagnosed with ET was analyzed and two missense variants in 219 healthy controls were genotyped by Sanger sequencing. RESULTS: Sequencing of FUS identified a previously reported non-pathogenic mutation p.G174_G175del in one ET patient and two healthy controls, and a novel p.R377W in one patient with family history of disease. This mutation is highly conserved and strongly predicted to be damaging by in silico analysis. CONCLUSION: This study has identified a novel FUS p.R377W substitution in ET patients. Additional genotyping studies in a large number of ET patients and controls are necessary to conclusively define its pathogenicity.


Subject(s)
Essential Tremor/genetics , Genetic Predisposition to Disease , Genotype , RNA-Binding Protein FUS/genetics , Adult , Aged , Aged, 80 and over , Female , Genetic Association Studies , Genetic Variation , Humans , Male , Middle Aged
10.
Clin Exp Immunol ; 175(2): 323-31, 2014 Feb.
Article in English | MEDLINE | ID: mdl-24134783

ABSTRACT

Macrophages are involved in the development and progression of kidney fibrosis. The aim of this study was to analyse the phenotype of circulating monocytes and their ability to predict kidney allograft dysfunction in living kidney transplant recipients. Whole blood samples from 25 kidney recipients and 17 donors were collected at five time-points. Monocyte phenotype was analysed by flow cytometry, and interleukin (IL)-10 and soluble CD163 by enzyme-linked immunosorbent assay. One week after transplantation, surface CD163 and IL-10 levels increased significantly from baseline [2·99 ± 1·38 mean fluorescence intensity (MFI) to 5·18 ± 2·42 MFI for CD163; 4·5 ± 1·46 pg/ml to 6·7 ± 2·5 pg/ml for IL-10]. This CD163 increase correlated with 4-month creatinine levels (r = 0·4394, P = 0·04). However, soluble CD163 decreased significantly from baseline at 1 week (797·11 ± 340·45 ng/ml to 576·50 ± 293·60 ng/ml). CD14(+) CD16(-) monocytes increased at 4 months and correlated positively with creatinine levels at 12 and 24 months (r = 0·6348, P = 0·002 and r = 0·467, P = 0·028, respectively) and negatively with Modification of Diet in Renal Disease (MDRD) at 12 months (r = 0·6056, P = 0·003). At 4 months, IL-10 decreased significantly (P = 0·008) and correlated positively with creatinine at 2 years (r = 0·68, P = 0·010) and with CD14(+) CD16(-) monocytes at 4 months (r = 0·732, P = 0·004). At 24 h, levels of human leucocyte antigen D-related declined from 12·12 ± 5·99 to 5·21 ± 3·84 and CD86 expression decreased from 2·76 ± 1·08 to 1·87 ± 0·95. Both markers recovered progressively until 12 months, when they decreased again. These results indicate that monitoring monocytes could be a promising new prognostic tool of graft dysfunction in renal transplant patients.


Subject(s)
Allografts/immunology , Kidney Transplantation , Monocytes/immunology , Primary Graft Dysfunction/pathology , Allografts/cytology , Antigens, CD/metabolism , Antigens, Differentiation, Myelomonocytic/metabolism , B7-2 Antigen/metabolism , Creatinine/metabolism , Female , Fibrosis , HLA-DR Antigens/metabolism , Humans , Immunosuppressive Agents/therapeutic use , Inflammation/immunology , Interleukin-10/blood , Interleukin-10/metabolism , Kidney/pathology , Lipopolysaccharide Receptors/metabolism , Macrophages/immunology , Male , Middle Aged , Mycophenolic Acid/analogs & derivatives , Mycophenolic Acid/therapeutic use , Phenotype , Prednisone/therapeutic use , Prospective Studies , Receptors, Cell Surface/metabolism , Receptors, IgG/metabolism , Spain , Tacrolimus/therapeutic use
11.
Int J Tuberc Lung Dis ; 17(4): 520-5, 2013 Apr.
Article in English | MEDLINE | ID: mdl-23485386

ABSTRACT

SETTING: The Dominican Republic is a high-incidence area for multidrug-resistant tuberculosis (MDR-TB; 6.6% of initial cases). Standardised treatment regimens for MDR-TB may be a potential solution. OBJECTIVE: To present the effectiveness of standard regimens under routine national conditions. DESIGN: We reviewed all MDR-TB patients treated under routine conditions from 29 August 2006 to 30 June 2010, showing interim and final outcomes. Patients were treated with regimens that were standardised or individualised based on previously received second-line anti-tuberculosis drugs. RESULTS: Population description and culture conversion data are reported for the 289 MDR-TB patients. The median patient age was 31 years. Most had failed first-line treatment (72.6%). Culture negativity was obtained within 4 months (median 2 months) in 78.6%. Among the 150 patients treated between 2006 and 2008, 74% had favourable results on standardised and 66% on individualised regimens (P = 0.211). The efficacy of the standardised and individualised regimens was respectively 92.8% and 81% (P = 0.056). The relapse rate was approximately 1%. A median of five drug side effects occurred per patient. More than 2 months to culture conversion and bilateral cavitation on chest X-ray were found to be unfavourable outcome risk factors. CONCLUSIONS: Standardised MDR-TB regimens may be effective at the national level, even in resource-poor settings.


Subject(s)
Antitubercular Agents/therapeutic use , Drug Resistance, Multiple, Bacterial , Tuberculosis, Multidrug-Resistant/drug therapy , Adult , Antitubercular Agents/adverse effects , Developing Countries , Dominican Republic/epidemiology , Drug Therapy, Combination , Female , Health Resources , Humans , Incidence , Male , Microbial Sensitivity Tests , Mycobacterium tuberculosis/drug effects , Mycobacterium tuberculosis/isolation & purification , Predictive Value of Tests , Program Evaluation , Proportional Hazards Models , Retrospective Studies , Time Factors , Treatment Outcome , Tuberculosis, Multidrug-Resistant/diagnosis , Tuberculosis, Multidrug-Resistant/epidemiology
12.
Med Teach ; 34(1): e29-45, 2012.
Article in English | MEDLINE | ID: mdl-22250693

ABSTRACT

BACKGROUND: Problem-Based Learning (PBL) is a whole-curriculum concept. AIM: This study aimed to compare learning preferences and strategies between physical therapy students taught by PBL and those receiving conventional lectures on massage therapy, trauma physical therapy, and electrotherapy, hydrotherapy, and thermotherapy. METHODS: This quasi-experimental study included 182 male and female students on physical therapy diploma courses at three universities in Andalusia (Spain). The Canfield Learning Skills Inventory (CLSI) was used to assess learning strategies and the Approaches to Study Skills Inventory for Students (ASSIST) to analyze study preferences. RESULTS: At the end of the academic year 2009/10, physical therapy students taught by PBL considered the most important learning strategies to be group work, study organization, relationship of ideas, and academic results. In comparison to conventionally taught counterparts, they considered that PBL reduced lack of purpose, memorizing without relating, the law of minimum effort, and fear of failure. Among these PBL students, the most highly rated study preferences were: organization of course tasks, cordial interaction with the teacher, learning by reading and images, and direct hands-on experience. CONCLUSION: For these physical therapy students, PBL facilitates learning strategies and study preferences in comparison to conventional teaching.


Subject(s)
Biomedical Technology/education , Physical Therapists/education , Problem-Based Learning , Female , Humans , Male , Spain , Surveys and Questionnaires , Young Adult
13.
Gerokomos (Madr., Ed. impr.) ; 21(2): 62-65, jun. 2010. tab
Article in Spanish | IBECS | ID: ibc-87542

ABSTRACT

El aumento de la esperanza de vida, acompañadade una crisis en el cuidado informal, ha provocadoque aumenten el número de ingresos residenciales.Esta situación lleva consigo que la persona viva el duelode forma distinta atendiendo al escenario donde sedesarrolle, bien sea la familia o la institución.El objetivo fundamental de esta investigación esdescribir las diferencias existentes entre el dueloatendiendo al lugar donde se desarrolla. En concreto,una residencia de ancianos versus la familia.Concluyendo, cabe destacar que existen clarasdiferencias entre vivir el duelo en una institucióncerrada y en el seno familiar (AU)


The rise of the life expectancy, accompanied by a crisis inthe informal care has caused that increase the residentialincome number. This situation takes with him that theliving person the mourning, in a different way payingattention to the stage where it takes place whether thefamily or the institution. The primary goal of thisinvestigation is to describe gaps between the mourningpaying attention to the place where it takes place.Specifically a nursing home versus family. Concludingwe must emphasize that are clear differences betweenliving the mourning in a closed institution and thefamiliar breast (AU)


Subject(s)
Humans , Aged , Homes for the Aged , Family/psychology
15.
J Bacteriol ; 186(16): 5384-91, 2004 Aug.
Article in English | MEDLINE | ID: mdl-15292139

ABSTRACT

Gluconacetobacter diazotrophicus is an endophyte of sugarcane frequently found in plants grown in agricultural areas where nitrogen fertilizer input is low. Recent results from this laboratory, using mutant strains of G. diazotrophicus unable to fix nitrogen, suggested that there are two beneficial effects of G. diazotrophicus on sugarcane growth: one dependent and one not dependent on nitrogen fixation. A plant growth-promoting substance, such as indole-3-acetic acid (IAA), known to be produced by G. diazotrophicus, could be a nitrogen fixation-independent factor. One strain, MAd10, isolated by screening a library of Tn5 mutants, released only approximately 6% of the amount of IAA excreted by the parent strain in liquid culture. The mutation causing the IAA(-) phenotype was not linked to Tn5. A pLAFR3 cosmid clone that complemented the IAA deficiency was isolated. Sequence analysis of a complementing subclone indicated the presence of genes involved in cytochrome c biogenesis (ccm, for cytochrome c maturation). The G. diazotrophicus ccm operon was sequenced; the individual ccm gene products were 37 to 52% identical to ccm gene products of Escherichia coli and equivalent cyc genes of Bradyrhizobium japonicum. Although several ccm mutant phenotypes have been described in the literature, there are no reports of ccm gene products being involved in IAA production. Spectral analysis, heme-associated peroxidase activities, and respiratory activities of the cell membranes revealed that the ccm genes of G. diazotrophicus are involved in cytochrome c biogenesis.


Subject(s)
Bacterial Proteins/genetics , Cytochromes c/genetics , Gluconacetobacter/genetics , Indoleacetic Acids/metabolism , Mutation , Bacterial Proteins/physiology , Cell Membrane/metabolism , Cytochromes c/biosynthesis , DNA Transposable Elements , DNA, Bacterial/chemistry , DNA, Bacterial/isolation & purification , Escherichia coli/genetics , Genes, Bacterial , Genetic Complementation Test , Gluconacetobacter/metabolism , Molecular Sequence Data , Mutagenesis, Insertional , Nitrogen Fixation/genetics , Operon , Peroxidases/analysis , Sequence Analysis, DNA , Sequence Homology , Spectrum Analysis
16.
J Bacteriol ; 181(22): 6987-95, 1999 Nov.
Article in English | MEDLINE | ID: mdl-10559164

ABSTRACT

The characteristics of the respiratory system of Acetobacter diazotrophicus PAL5 were investigated. Increasing aeration (from 0.5 to 4.0 liters of air min(-1) liter of medium(-1)) had a strong positive effect on growth and on the diazotrophic activity of cultures. Cells obtained from well-aerated and diazotrophically active cultures possessed a highly active, membrane-bound electron transport system with dehydrogenases for NADH, glucose, and acetaldehyde as the main electron donors. Ethanol, succinate, and gluconate were also oxidized but to only a minor extent. Terminal cytochrome c oxidase-type activity was poor as measured by reduced N, N,N,N'-tetramethyl-p-phenylenediamine, but quinol oxidase-type activity, as measured by 2,3,5,6-tetrachloro-1,4-benzenediol, was high. Spectral and high-pressure liquid chromatography analysis of membranes revealed the presence of cytochrome ba as a putative oxidase in cells obtained from diazotrophically active cultures. Cells were also rich in c-type cytochromes; four bands of high molecular mass (i.e., 67, 56, 52, and 45 kDa) were revealed by a peroxidase activity stain in sodium dodecyl sulfate-polyacrylamide gel electrophoresis. KCN inhibition curves of respiratory oxidase activities were biphasic, with a highly resistant component. Treatment of membranes with 0.2% Triton X-100 solubilized c-type cytochromes and resulted in a preparation that was significantly more sensitive to cyanide. Repression of diazotrophic activity in well-aerated cultures by 40 mM (NH(4))(2)SO(4) caused a significant decrease of the respiratory activities. It is noteworthy that the levels of glucose dehydrogenase and putative oxidase ba decreased 6. 8- and 10-fold, respectively. In these cells, a bd-type cytochrome seems to be the major terminal oxidase. Thus, it would seem that glucose dehydrogenase and cytochrome ba are key components of the respiratory system of A. diazotrophicus during aerobic diazotrophy.


Subject(s)
Acetobacter/metabolism , Nitrogen Fixation , Oxygen Consumption , Acetobacter/growth & development , Culture Media , Cytochromes/metabolism , Electron Transport , Heme/metabolism , Oxidation-Reduction , Potassium Cyanide/pharmacology , Quaternary Ammonium Compounds/pharmacology , Temperature
17.
Compend Contin Educ Dent ; 18(4): 325-6, 328, 330 passim; quiz 336, 1997 Apr.
Article in English | MEDLINE | ID: mdl-9452541

ABSTRACT

The high incidence of allergic reactions to some common dental antibiotics, primarily topical penicillins, has led to general concerns about all topical antibiotics. The development of resistant bacterial strains and efforts to reserve key antibiotics for life-threatening infections have also limited topical use of antibiotics. Delivery technologies providing for site-specific drug delivery have renewed interest in the use of topical antimicrobials to treat adult periodontitis. Topical tetracycline has an extremely low sensitizing potential and is not one of the antibiotics reserved by the medical community for use in life-threatening situations. Despite tetracycline's widespread dermatologic use and increasing use in adjunctive treatment of adult periodontitis, the incidence of allergic response to topical tetracycline is very low. Also, it is unlikely to cause resistance when used locally for short durations--particularly at the high per-site concentrations achieved with tetracycline periodontal fiber. Studies with tetracycline fiber showed no significant change in the tetracycline susceptibility of gram-negative periodontal microorganisms.


Subject(s)
Anti-Bacterial Agents/adverse effects , Drug Hypersensitivity/etiology , Tetracycline Resistance , Tetracycline/adverse effects , Administration, Topical , Adult , Anti-Bacterial Agents/administration & dosage , Gram-Negative Bacteria/drug effects , Humans , Periodontitis/drug therapy , Periodontitis/microbiology , Tetracycline/administration & dosage
18.
J Periodontal Res ; 31(8): 540-4, 1996 Nov.
Article in English | MEDLINE | ID: mdl-8971652

ABSTRACT

Actisite (tetracycline hydrochloride) periodontal fiber is a 23 cm monofilament containing 12.7 mg tetracycline HCl homogeneously dispersed in a polymer. This product is indicated as an adjunct to scaling and root planing to reduce pocket depth and bleeding on probing in patients with adult periodontitis. The sustained-release system, placed in the periodontal pocket for 10 d, releases the antibiotic through mechanisms of diffusion and osmosis. A study was conducted in 13 patients with moderate to severe adult periodontitis to evaluate the amount of tetracycline HCl released during therapy (based on residual drug content). Fibers placed in the pocket remained in place for an average of 9 d. Each patient had 1-4 teeth treated with fiber therapy. At the termination of therapy samples from 29 teeth were retrieved and analyzed. The amount of matrix polymer was used as an internal standard for the quantitation of tetracycline, eliminating any uncertainties with respect to recovery or contamination. An average of 31% (SD 9%) of the tetracycline HCl content was released from the fiber during the treatment period. No single fiber had less than 50% of the original drug remaining. The study demonstrated that a substantial amount of the tetracycline remains in the Actisite fiber at removal (about 70%), which indicates that substantial drug concentrations are maintained in the pocket for the duration of treatment.


Subject(s)
Anti-Bacterial Agents/therapeutic use , Periodontitis/drug therapy , Tetracycline/therapeutic use , Administration, Topical , Adult , Aged , Anti-Bacterial Agents/administration & dosage , Anti-Bacterial Agents/analysis , Anti-Bacterial Agents/chemistry , Chromatography, High Pressure Liquid , Combined Modality Therapy , Delayed-Action Preparations , Dental Scaling , Diffusion , Drug Carriers , Female , Gingival Hemorrhage/drug therapy , Gingival Hemorrhage/therapy , Humans , Male , Middle Aged , Osmosis , Periodontal Pocket/drug therapy , Periodontal Pocket/therapy , Periodontitis/therapy , Polyvinyls/analysis , Polyvinyls/chemistry , Root Planing , Tetracycline/administration & dosage , Tetracycline/analysis , Tetracycline/chemistry
19.
Can J Microbiol ; 42(3): 294-8, 1996 Mar.
Article in English | MEDLINE | ID: mdl-8868238

ABSTRACT

The purification and characterization of AAT1, one of two aromatic amino acid aminotransferase (EC 2.6.1.57) in Azospirillum brasilense, is described. Purified AAT1 had a subunit mass of 33 kDa and a nondenatured molecular mass of 66 kDa, suggesting a dimeric structure. Other properties include a pI of 5.04, an optimum temperature of 45 degrees C, and optimum pH of 8.5. AAT1 utilized all aromatic amino acids, the L-tryptophan derivatives such as L-5-methyl tryptophan and L-flour-tryptophan, and L-histidine. The apparent Km values for L-tyrosine, L-phenylalanine, and L-tryptophan were 0.19, 0.43, and 1.05 mM, respectively. The enzyme was competive inhibited by indole-3-pyruvic acid with a Ki of 0.17 mM.


Subject(s)
Azospirillum brasilense/enzymology , Transaminases/isolation & purification , Transaminases/metabolism
20.
J Clin Periodontol ; 22(11): 824-9, 1995 Nov.
Article in English | MEDLINE | ID: mdl-8550857

ABSTRACT

To evaluate the relative efficacy of a non-degradable osmotic slow-release dosage form containing 6.6 mg cetylpyridinium chloride (MOTS [Mucosal Oral Therapeutic System] CPC) to inhibit new plaque formation and gingivitis, a single-blind, randomised, parallel group pilot study was set up. 52 healthy volunteers were assigned to receive one of the following treatments for 18 days of non-brushing: holding 1 MOTS CPC 2 x daily for 2 h intra-orally, or rinsing 30 s with 15 ml Peridex 2 x daily, or dissolve Cepacol (each 1.6 mg CPC) lozenges 2 x daily unsupervised. Before the test period, the subjects received a thorough tooth cleaning followed by tooth polishing 1 x a week for 3 weeks to achieve clinical gingival health. After the start of therapy, the subjects were examined at day 4, 7 (+/- 2), 14 (+/- 2) and 18 (2 +/-). Relative efficacy was assessed by the modified Navy plaque index, the Quigley and Hein index, the planimetric plaque index, as well as the papillary marginal gingival index. There was an increase in both plaque formation and gingivitis over the 18 +/- 2 day period of nonbrushing for all subjects in the study. Peridex was the most effective in inhibiting plaque and gingivitis formation over that period of time. There was no difference between MOTS CPC and Cepacol at any time point in plaque accumulation and gingivitis intensity. Peridex was considered more convenient than MOTS CPC. Cepacol resulted in more staining at 18 days than MOTS CPC and Peridex.


Subject(s)
Anti-Infective Agents, Local/therapeutic use , Cetylpyridinium/therapeutic use , Dental Plaque/prevention & control , Adolescent , Adult , Anti-Infective Agents, Local/administration & dosage , Anti-Infective Agents, Local/adverse effects , Cetylpyridinium/administration & dosage , Cetylpyridinium/adverse effects , Chlorhexidine/administration & dosage , Chlorhexidine/adverse effects , Chlorhexidine/analogs & derivatives , Chlorhexidine/therapeutic use , Delayed-Action Preparations , Dental Plaque/microbiology , Dental Plaque Index , Dental Prophylaxis , Drug Tolerance , Female , Gingivitis/prevention & control , Humans , Male , Mouthwashes , Periodontal Index , Pilot Projects , Single-Blind Method , Tablets
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