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1.
J Eur Acad Dermatol Venereol ; 2022 Nov 25.
Article in English | MEDLINE | ID: mdl-36433688

ABSTRACT

BACKGROUND: PD-1 antibodies and BRAF+MEK inhibitors are widely used for adjuvant therapy of fully resected high-risk melanoma. Little is known about treatment efficacy outside of phase III trials. This real-world study reports on clinical outcomes of modern adjuvant melanoma treatment in specialized skin cancer centers in Germany, Austria and Switzerland. METHODS: Multicenter, retrospective study investigating stage III-IV melanoma patients receiving adjuvant nivolumab (NIV), pembrolizumab (PEM) or dabrafenib+trametinib (D+T) between 1/2017 and 10/2021. The primary endpoint was 12-month recurrence free survival (RFS). Further analyses included descriptive and correlative statistics, and a multivariate linear-regression machine learning model to assess the risk of early melanoma recurrence. RESULTS: 1198 patients from 39 skin cancer centers from Germany, Austria and Switzerland were analyzed. The vast majority received anti PD-1 therapies (n=1003). 12-month RFS for anti PD-1 and BRAF+MEK inhibitor treated patients were 78.1% and 86.5% respectively (hazard ratio [HR] 1.998 [95%CI 1.335-2.991]; p=0.001). There was no statistically significant difference in overall survival in anti PD-1 (95.8%) and BRAF+MEK inhibitor (96.9%) treated patients (p>0.05) during the median follow-up of 17 months. Data indicates that anti PD-1 treated patients who develop immune-related adverse events (irAEs) have lower recurrence rates compared to patients with no irAEs (HR 0.578 [95%CI 0.443-0.754], p=0.001). BRAF mutation status did not affect overall efficacy of anti PD-1 treatment (p>0.05). In both, anti PD-1 and BRAF+MEK inhibitor treated cohorts, data did not show any difference in 12-month RFS and 12-month OS comparing patients receiving total lymph node dissection versus sentinel lymph node biopsy only (p>0.05). The recurrence prediction model reached high specificity but only low sensitivity with an AUC=0.65. No new safety signals were detected. Overall, recorded numbers and severity of adverse events were lower than reported in pivotal phase III trials. CONCLUSIONS: Despite recent advances in adjuvant melanoma treatment, early recurrence remains a significant clinical challenge. This study shows that total lymph node dissection does not reduce the risk of early melanoma recurrence and should only be considered in selected patients. Data further highlight that variables collected during clinical routine are unlikely to allow for a clinically relevant prediction of individual recurrence risk.

3.
Life Sci ; 287: 120128, 2021 Dec 15.
Article in English | MEDLINE | ID: mdl-34774874

ABSTRACT

Glioblastoma is the most frequent and malignant brain tumor. The median survival for this disease is approximately 15 months, and despite all the available treatment strategies employed, it remains an incurable disease. Preclinical and clinical research have shown that the resistance process related to DNA damage repair pathways, glioma stem cells, blood-brain barrier selectivity, and dose-limiting toxicity of systemic treatment leads to poor clinical outcomes. In this context, the advent of drug delivery systems associated with localized treatment seems to be a promising and versatile alternative to overcome the failure of the current treatment approaches. In order to bypass therapeutic tumor resistance mechanisms, more effective combinatorial therapies should be identified, such as the use of cytotoxic drugs combined with the inhibition of DNA damage response (DDR)-related targets. Additionally, critical reasoning about the delivery approach and administration route in brain tumors treatment innovation is essential. The outcomes of future experimental studies regarding the association of delivery systems, alternative treatment routes, and DDR targets are expected to lead to the development of refined therapeutic interventions. Novel therapeutic approaches could improve the life's quality of glioblastoma patients and increase their survival rate.


Subject(s)
Antineoplastic Agents/administration & dosage , Brain Neoplasms/drug therapy , DNA Damage/drug effects , Drug Delivery Systems/trends , Drug Development/trends , Glioblastoma/drug therapy , Animals , Antineoplastic Agents/metabolism , Blood-Brain Barrier/drug effects , Blood-Brain Barrier/metabolism , Brain Neoplasms/metabolism , DNA Damage/physiology , Drug Delivery Systems/methods , Drug Development/methods , Glioblastoma/metabolism , Humans
4.
Schmerz ; 35(6): 391-400, 2021 Dec.
Article in German | MEDLINE | ID: mdl-33877413

ABSTRACT

BACKGROUND, OBJECTIVES: Deficits in the quality of pain management in hospitals have been described for years. The aim of this study was to assess structures and processes of pain management in departments for internal medicine in German hospitals. MATERIALS AND METHODS: Data were collected using a standardized telephone interview (non-university hospital departments) on a randomized sample of hospitals (circa 1/3 of hospitals); all German departments of university hospitals were invited to participate and questioned separately using an online questionnaire (SurveyMonkey®). RESULTS: Data from 139 non-university departments (response rate: 21%) and 33 university hospital departments (only 21 questionnaires were fully answered, response rate 17 and 11%, respectively) were collected. Of 619 non-university hospital departments contacted, 441 explicitly refused to participate in the survey, most often on the grounds that there was no interest in pain management. Pain was regularly recorded as an independent parameter during the medical visit in 89% of the non-university hospital and 96% of the university hospital departments; written standardized treatment protocols for pain therapy were available in 57% of the non-university hospital departments (54% university hospital departments). In 76% of the non-university hospitals departments (100% university hospital departments), an acute pain service was also available for patients of internal medicine departments for co-treatment. Written cooperation agreements were less common (35% non-university hospital departments, 18% university hospital departments). CONCLUSION: The described implementation of pain management was satisfying in the participating departments. However, in consideration of the low participation and high rejection of participation due to explicit disinterest in the topic, the results should be critically assessed and presumably characterized by a significant positive bias.


Subject(s)
Pain Clinics , Pain Management , Hospitals, University , Humans , Internal Medicine , Pain Measurement , Surveys and Questionnaires
5.
J Eur Acad Dermatol Venereol ; 35(5): e312-e314, 2021 May.
Article in English | MEDLINE | ID: mdl-33587787
6.
Braz. j. biol ; 80(2): 266-272, Apr.-June 2020. tab, graf
Article in English | LILACS (Americas) | ID: biblio-1132372

ABSTRACT

Abstract The treatment of choice for chronic atrophic candidiasis (CAC), also known as denture stomatitis, is topical antifungal therapy. This study aimed to isolate, identify, and assess the antifungal susceptibility of Candida species from mucosal sites in denture wearers with a diagnosis of CAC and determine the prevalence of associated variables. The sample consisted of 44 patients wearing complete or partial dentures who had a clinical diagnosis of CAC. Using sterile cotton swabs, specimens were collected from the oral mucosa of all patients and grown at 30ºC for 48 h in CHROMagar Candida, as a means of isolating and screening the species. The complementary identification of the species was performed using the VITEK 2 automated system (BioMérieux), as well as the determination of their susceptibility to antifungal agents. Data were analyzed using the chi-square test. STATA 13.1 was used for statistical analysis (α = 5%). Of 44 patients with CAC, 33 (75%) had lesions classified as Newton type II. Yeasts were isolated in 38 cases. The most prevalent species was Candida albicans. None of the isolates were resistant to the antifungals tested. Our findings suggest that current indications for antifungal agents are appropriate. Also, antifungal susceptibility testing and proper fungal identification can help dentists to determine the optimal course of treatment for CAC.


Resumo O tratamento de escolha para candidíase atrófica crônica (CAC), também conhecida como estomatite protética, é a terapia antifúngica tópica. Este estudo teve como objetivo isolar, identificar e avaliar a susceptibilidade antifúngica de espécies de Candida de locais mucosos em portadores de prótese com diagnóstico de CAC e determinar a prevalência de variáveis associadas. A amostra consistiu em 44 pacientes portadores de próteses completas ou parciais que tiveram um diagnóstico clínico de CAC. Usando swab estéril, foram coletados espécimes da mucosa oral de todos os pacientes e cultivados a 30ºC durante 48 h em CHROMagar Candida, como forma de isolamento e triagem das espécies. A identificação complementar das espécies foi realizada no sistema automatizado VITEK 2 (BioMérieux), bem como a determinação da susceptibilidade delas a agentes antifúngicos. Os dados foram analisados usando o teste do qui-quadrado. O STATA 13.1 foi utilizado para análise estatística (α = 5%). Dos 44 pacientes com CAC, 33 (75%) apresentaram lesões classificadas como Newton tipo II. As leveduras foram isoladas em 38 casos. A espécie mais prevalente foi Candida albicans. Nenhum dos isolados foi resistente aos antifúngicos testados. Nossas descobertas sugerem que as indicações atuais para os agentes antifúngicos são apropriadas. Além disso, testes de susceptibilidade antifúngicos e identificação fúngica adequada podem ajudar os dentistas a determinar o curso ótimo de tratamento para CAC.


Subject(s)
Humans , Candida , Candidiasis, Oral , Candida albicans , Microbial Sensitivity Tests , Antifungal Agents
8.
Braz J Biol ; 80(2): 266-272, 2020.
Article in English | MEDLINE | ID: mdl-31291399

ABSTRACT

The treatment of choice for chronic atrophic candidiasis (CAC), also known as denture stomatitis, is topical antifungal therapy. This study aimed to isolate, identify, and assess the antifungal susceptibility of Candida species from mucosal sites in denture wearers with a diagnosis of CAC and determine the prevalence of associated variables. The sample consisted of 44 patients wearing complete or partial dentures who had a clinical diagnosis of CAC. Using sterile cotton swabs, specimens were collected from the oral mucosa of all patients and grown at 30ºC for 48 h in CHROMagar Candida, as a means of isolating and screening the species. The complementary identification of the species was performed using the VITEK 2 automated system (BioMérieux), as well as the determination of their susceptibility to antifungal agents. Data were analyzed using the chi-square test. STATA 13.1 was used for statistical analysis (α = 5%). Of 44 patients with CAC, 33 (75%) had lesions classified as Newton type II. Yeasts were isolated in 38 cases. The most prevalent species was Candida albicans. None of the isolates were resistant to the antifungals tested. Our findings suggest that current indications for antifungal agents are appropriate. Also, antifungal susceptibility testing and proper fungal identification can help dentists to determine the optimal course of treatment for CAC.


Subject(s)
Candida , Candidiasis, Oral , Antifungal Agents , Candida albicans , Humans , Microbial Sensitivity Tests
9.
J Nucl Cardiol ; 26(2): 541-542, 2019 04.
Article in English | MEDLINE | ID: mdl-28865068
11.
Internist (Berl) ; 58(6): 621-625, 2017 Jun.
Article in German | MEDLINE | ID: mdl-28235985

ABSTRACT

We report about a 58-year-old man with a chronic and treatment-naive hepatitis C virus (HCV) infection of genotype 1b, who had undergone autologous stem cell transplantation twice due to multiple myeloma. Subsequently, a high-level viremic reactivation of an occult hepatitis B virus (HBV) infection and also a reverse seroconversion was observed. Furthermore, a sustained spontaneous remission of HCV infection was seen. Antiviral therapy of HBV infection was initiated with tenofovir. Seven months after therapy initiation, the patient acquired an "anti-HBc-only" status. Antiviral therapy with tenofovir is still continued. The patient is in a good clinical condition.


Subject(s)
Hepatitis B virus/physiology , Hepatitis B/drug therapy , Hepatitis C/therapy , Multiple Myeloma/therapy , Stem Cell Transplantation , Antiviral Agents/therapeutic use , Hepacivirus , Hepatitis B/immunology , Humans , Male , Middle Aged , Remission, Spontaneous , Tenofovir/therapeutic use , Virus Activation
12.
Int J Sports Med ; 37(5): 347-53, 2016 May.
Article in English | MEDLINE | ID: mdl-26859644

ABSTRACT

Metabolic syndrome (MetS) and type 2 diabetes mellitus (T2DM) are associated with macro- and microcirculatory complications that reduce physical performance. Wearing compression garments to potentially optimize hemodynamics has been discussed. This study investigates the effects of wearing compression stockings on physical performance-related variables in type 2 diabetic men with metabolic syndrome (n=9, 57±12 years, BMI: 36±4 kg/m(2)). Participants served as their own controls in a randomized 3*3 crossover study wearing below-knee stockings with either compression (24 or 30 mmHg ankle pressure) or no compression. Venous pooling and lower limb oxygenation profiles were determined with near-infrared spectroscopy and arterial oxygen saturation was determined using a pulse oxymeter. Measurements were performed in the supine lying position, during standing, following 10 tiptoe exercises and after submaximal intensity cycling. In addition, lactate and erythrocyte deformability were analyzed in capillary blood pre- and post-exercise. Erythrocyte deformability was analyzed using a laser-assisted optical rotational red cell analyzer. No significant differences in any variables when wearing different compression or regular stockings were evident at any point of measurement. This study did not reveal any beneficial effects of wearing compression stockings at rest and during acute bouts of moderately intense exercise in this particular patient group.


Subject(s)
Diabetes Mellitus, Type 2/therapy , Exercise Test , Hemodynamics , Metabolic Syndrome/therapy , Stockings, Compression , Aged , Cross-Over Studies , Erythrocyte Deformability , Humans , Lactic Acid/blood , Leg , Male , Middle Aged , Oximetry , Oxygen Consumption , Rest , Spectroscopy, Near-Infrared , Venous Insufficiency/therapy
13.
Braz. J. Biol. ; 2019.
Article in English | VETINDEX | ID: vti-742405

ABSTRACT

Abstract The treatment of choice for chronic atrophic candidiasis (CAC), also known as denture stomatitis, is topical antifungal therapy. This study aimed to isolate, identify, and assess the antifungal susceptibility of Candida species from mucosal sites in denture wearers with a diagnosis of CAC and determine the prevalence of associated variables. The sample consisted of 44 patients wearing complete or partial dentures who had a clinical diagnosis of CAC. Using sterile cotton swabs, specimens were collected from the oral mucosa of all patients and grown at 30ºC for 48 h in CHROMagar Candida, as a means of isolating and screening the species. The complementary identification of the species was performed using the VITEK 2 automated system (BioMérieux), as well as the determination of their susceptibility to antifungal agents. Data were analyzed using the chi-square test. STATA 13.1 was used for statistical analysis ( = 5%). Of 44 patients with CAC, 33 (75%) had lesions classified as Newton type II. Yeasts were isolated in 38 cases. The most prevalent species was Candida albicans. None of the isolates were resistant to the antifungals tested. Our findings suggest that current indications for antifungal agents are appropriate. Also, antifungal susceptibility testing and proper fungal identification can help dentists to determine the optimal course of treatment for CAC.


Resumo O tratamento de escolha para candidíase atrófica crônica (CAC), também conhecida como estomatite protética, é a terapia antifúngica tópica. Este estudo teve como objetivo isolar, identificar e avaliar a susceptibilidade antifúngica de espécies de Candida de locais mucosos em portadores de prótese com diagnóstico de CAC e determinar a prevalência de variáveis associadas. A amostra consistiu em 44 pacientes portadores de próteses completas ou parciais que tiveram um diagnóstico clínico de CAC. Usando swab estéril, foram coletados espécimes da mucosa oral de todos os pacientes e cultivados a 30ºC durante 48 h em CHROMagar Candida, como forma de isolamento e triagem das espécies. A identificação complementar das espécies foi realizada no sistema automatizado VITEK 2 (BioMérieux), bem como a determinação da susceptibilidade delas a agentes antifúngicos. Os dados foram analisados usando o teste do qui-quadrado. O STATA 13.1 foi utilizado para análise estatística ( = 5%). Dos 44 pacientes com CAC, 33 (75%) apresentaram lesões classificadas como Newton tipo II. As leveduras foram isoladas em 38 casos. A espécie mais prevalente foi Candida albicans. Nenhum dos isolados foi resistente aos antifúngicos testados. Nossas descobertas sugerem que as indicações atuais para os agentes antifúngicos são apropriadas. Além disso, testes de susceptibilidade antifúngicos e identificação fúngica adequada podem ajudar os dentistas a determinar o curso ótimo de tratamento para CAC.

14.
Braz. J. Biol. ; 80(2): 266-272, 2020. tab, graf
Article in English | VETINDEX | ID: vti-28655

ABSTRACT

The treatment of choice for chronic atrophic candidiasis (CAC), also known as denture stomatitis, is topical antifungal therapy. This study aimed to isolate, identify, and assess the antifungal susceptibility of Candida species from mucosal sites in denture wearers with a diagnosis of CAC and determine the prevalence of associated variables. The sample consisted of 44 patients wearing complete or partial dentures who had a clinical diagnosis of CAC. Using sterile cotton swabs, specimens were collected from the oral mucosa of all patients and grown at 30ºC for 48 h in CHROMagar Candida, as a means of isolating and screening the species. The complementary identification of the species was performed using the VITEK 2 automated system (BioMérieux), as well as the determination of their susceptibility to antifungal agents. Data were analyzed using the chi-square test. STATA 13.1 was used for statistical analysis ( = 5%). Of 44 patients with CAC, 33 (75%) had lesions classified as Newton type II. Yeasts were isolated in 38 cases. The most prevalent species was Candida albicans. None of the isolates were resistant to the antifungals tested. Our findings suggest that current indications for antifungal agents are appropriate. Also, antifungal susceptibility testing and proper fungal identification can help dentists to determine the optimal course of treatment for CAC.(AU)


O tratamento de escolha para candidíase atrófica crônica (CAC), também conhecida como estomatite protética, é a terapia antifúngica tópica. Este estudo teve como objetivo isolar, identificar e avaliar a susceptibilidade antifúngica de espécies de Candida de locais mucosos em portadores de prótese com diagnóstico de CAC e determinar a prevalência de variáveis associadas. A amostra consistiu em 44 pacientes portadores de próteses completas ou parciais que tiveram um diagnóstico clínico de CAC. Usando swab estéril, foram coletados espécimes da mucosa oral de todos os pacientes e cultivados a 30ºC durante 48 h em CHROMagar Candida, como forma de isolamento e triagem das espécies. A identificação complementar das espécies foi realizada no sistema automatizado VITEK 2 (BioMérieux), bem como a determinação da susceptibilidade delas a agentes antifúngicos. Os dados foram analisados usando o teste do qui-quadrado. O STATA 13.1 foi utilizado para análise estatística ( = 5%). Dos 44 pacientes com CAC, 33 (75%) apresentaram lesões classificadas como Newton tipo II. As leveduras foram isoladas em 38 casos. A espécie mais prevalente foi Candida albicans. Nenhum dos isolados foi resistente aos antifúngicos testados. Nossas descobertas sugerem que as indicações atuais para os agentes antifúngicos são apropriadas. Além disso, testes de susceptibilidade antifúngicos e identificação fúngica adequada podem ajudar os dentistas a determinar o curso ótimo de tratamento para CAC.(AU)


Subject(s)
Candida , Antifungal Agents , Candidiasis , Stomatitis , Disease Susceptibility
15.
Chirurg ; 83(2): 153-62, 2012 Feb.
Article in German | MEDLINE | ID: mdl-21678103

ABSTRACT

BACKGROUND: Emergency treatment and resuscitation within hospitals are managed by so-called medical emergency teams (MET). The present study examined the circumstances, number, initial treatment and further hospital course of in-hospital emergency cases at a level 1 university hospital. METHODS: A retrospective study of in-hospital emergencies on the surgical wards of a university hospital including all non-intensive care areas from January 2007 to June 2010 was carried out. A self-developed documentation protocol which was introduced in 2006 was used by the MET to document general patient characteristics and details of the emergency treatment. These data included the place where the emergency situation arose, the patient's assignment to a surgical discipline, a detailed description of the emergency situation, the effectiveness of basic life support measures as well as the further hospital course of the patient. RESULTS: A total of 235 emergency cases were documented within the study period of 3.5 years. The frequency of in-hospital emergencies was 4/1,000 admitted patients per year. Cardiac arrest was encountered in 31,5%. Out of all patients 54,5% were admitted to an intensive care unit. CONCLUSION: The tasks of a MET at a surgical university hospital go beyond mere cardiopulmonary resuscitation. Emergency cases within the full spectrum of perioperative complications are encountered. Further multicenter studies with standardized protocols are required to analyze the management of German in-hospital emergencies.


Subject(s)
Documentation/statistics & numerical data , Emergency Medical Services/statistics & numerical data , Hospitals, University/statistics & numerical data , Perioperative Care/statistics & numerical data , Perioperative Period/statistics & numerical data , Surgery Department, Hospital/statistics & numerical data , Adolescent , Adult , Aged , Aged, 80 and over , Cardiopulmonary Resuscitation/statistics & numerical data , Child , Child, Preschool , Databases, Factual/statistics & numerical data , Female , Germany , Heart Arrest/epidemiology , Heart Arrest/therapy , Humans , Intensive Care Units/statistics & numerical data , Male , Middle Aged , Patient Admission/statistics & numerical data , Young Adult
16.
Schweiz Arch Tierheilkd ; 151(12): 597-603, 2009 Dec.
Article in English | MEDLINE | ID: mdl-19946851

ABSTRACT

In this retrospective study, the results of 3'527 eye examinations in 6 different breeds affected with Collie Eye Anomaly (CEA) over a period of 8 years (1999 - 2007) are described. CEA was divided into three main ophthalmoscopic features, a) choroidal hypoplasia (CRH), b) CRH and coloboma and c) coloboma alone. Of the 101 Smooth Collies 8.9 % showed signs of CRH, whereas 36.9 % of Rough Collies were affected with CRH, 2.8 % with CRH and coloboma and 0.38 % with coloboma alone. Choroidal hypoplasia was present in 13.1 %, CRH and coloboma in 1.8 % and coloboma alone in 0.2 % of the Shetland Sheepdogs. Only one Australian Shepherd dog had CRH, while 0.7 % of the Border Collies were affected with CRH. None of the Nova Scotia Duck Tolling Retrievers were affected with CEA. There were no statistically significant differences in the occurrence of CEA between males and females, nor was there any relation between coat colors. Significant differences could be shown between dogs younger or older than 8 weeks at first examination. CEA was more often diagnosed in dogs younger than 8 weeks within the Rough Collie and Shetland Sheepdog.


Subject(s)
Dog Diseases/epidemiology , Dogs/anatomy & histology , Eye Abnormalities/veterinary , Animals , Coloboma/epidemiology , Coloboma/veterinary , Eye Abnormalities/epidemiology , Female , Incidence , Male , Retrospective Studies , Sex Characteristics , Switzerland/epidemiology
17.
Pacing Clin Electrophysiol ; 24(5): 789-95, 2001 May.
Article in English | MEDLINE | ID: mdl-11388097

ABSTRACT

QT dispersion has been suggested and disputed as a risk marker for ventricular arrhythmias after myocardial infarction. Delayed ventricular activation after myocardial infarction may affect arrhythmic risk and QT intervals. This study determined if delayed activation as assessed by (1) QRS duration in the 12-lead ECG and by (2) late potentials in the signal-averaged ECG affects QT dispersion and its ability to assess arrhythmic risk after myocardial infarction. QT duration, JT duration, QT dispersion, and JT dispersion were compared to QRS duration in the 12-lead ECG and to late potentials in the signal-averaged ECG recorded in 724 patients 2-3 weeks after myocardial infarction. Prolonged QRS duration (> 110 ms) and high QRS dispersion increased QT and JT dispersion by 12%-15% (P < 0.05). Presence of late potentials, in contrast, did not change QT dispersion. Only the presence of late potentials (n = 113) was related to arrhythmic events during 6-month follow-up. QT dispersion, JT dispersion, QRS duration, and QRS dispersion were equal in patients with (n = 29) and without arrhythmic events (QT disp 80 +/- 7 vs 78 +/- 1 ms, JT disp 80 +/- 6 vs 79 +/- 2 ms, mean +/- SEM, P > 0.2). In conclusion, prolonged QRS duration increases QT dispersion irrespective of arrhythmic events in survivors of myocardial infarction. Presence of late potentials, in contrast, relates to arrhythmic events but does not affect QT dispersion. Therefore, QT dispersion may not be an adequate parameter to assess arrhythmic risk in survivors of myocardial infarction.


Subject(s)
Arrhythmias, Cardiac/etiology , Arrhythmias, Cardiac/physiopathology , Electrocardiography , Myocardial Infarction/physiopathology , Aged , Heart Rate/physiology , Humans , Male , Middle Aged , Myocardial Infarction/complications , Prognosis , Prospective Studies , Risk Assessment , Signal Processing, Computer-Assisted , Ventricular Dysfunction, Left/etiology , Ventricular Dysfunction, Left/physiopathology
18.
Biochemistry ; 40(9): 2964-71, 2001 Mar 06.
Article in English | MEDLINE | ID: mdl-11258908

ABSTRACT

Aminoglycoside nucleotidyltransferases catalyze the transfer of a nucleoside monophosphoryl group from a nucleotide to a hydroxyl group of an aminoglycoside antibiotic. Kanamycin nucleotidyltransferase [ANT (4',4' ')-I] from Staphylococcus aureus confers resistance to numerous aminoglycosides with a 4' or 4' ' hydroxyl group in the equatorial position. The synthesis of m-nitrobenzyl triphosphate, a new substrate of kanamycin nucleotidyltransferase, is reported. The kanamycin nucleotidyltransferase catalyzed reaction of kanamycin A with m-nitrobenzyl triphosphate is 2 orders of magnitude slower than that with ATP. The MALDI-TOF spectra of the purified products of both reactions revealed that kanamycin A was modified only at one position. The regiospecificity of the reaction catalyzed by kanamycin nucleotidyltransferase of kanamycin A with either ATP or m-nitrobenzyl triphosphate was determined directly by one- and two-dimensional hetero- and homonuclear NMR techniques. The site of the modification was unambiguously assigned to the 4' hydroxyl of kanamycin A; thus, the products formed are 4'-(adenosine-5'-phosphoryl)-kanamycin A and 4'-(m-nitrobenzyl phosphoryl)-kanamycin A. This eliminates the uncertainty concerning the point of modification since this could not be determined from the crystal structure of the enzyme with bound MgAMPCPP and kanamycin A [Pedersen, L. C., Benninig, M. M., and Holden, H. M. (1995) Biochemistry 34, 13305-13311].


Subject(s)
Nucleotidyltransferases/metabolism , Staphylococcus aureus/enzymology , Adenosine Monophosphate/analogs & derivatives , Adenosine Triphosphate/analogs & derivatives , Adenosine Triphosphate/chemistry , Adenosine Triphosphate/isolation & purification , Kanamycin/analogs & derivatives , Kanamycin/chemistry , Kanamycin/isolation & purification , Kinetics , Nucleotidyltransferases/chemistry , Protein Conformation , Substrate Specificity
19.
Revista da Faculdade de Odontología. Porto Alegre;37(1): 15-17,
in Portuguese | URUGUAIODONTO | ID: odn-14435
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