RESUMO
BACKGROUND: Hypertension is a global health concern that is best managed at the primary care level. In low- and middle-income countries (LMICs) facing resource constraints, collaboration between well-prepared entry-level advanced practice nurses (APNs) and physicians (medical doctors [MDs]) can enhance the care of patients with primary hypertension. OBJECTIVE: The purpose of this study was to evaluate the effectiveness of collaborative entry-level APNs in primary hypertension management, including patient knowledge, physiological and behavioral outcomes, consultation length, and patient satisfaction. METHODS: Sixty-three eligible patients were randomly assigned to either an entry-level APN intervention group or a control group with MDs. Three master's-prepared nurses, trained in hypertension management, acted as entry-level APNs, following the Joint National Committee guidelines in collaboration with a physician. The control group underwent standard clinic consultations. After 1 month, a mixed analysis of variance was used to assess intervention effectiveness, examining both between-groups and within-groups outcomes. RESULTS: Both groups shared similar sociodemographic and baseline characteristics. Significant improvements in blood pressure, body mass index, knowledge, self-management, and medication adherence were found at the 1-month follow-up, with no significant differences in outcomes or patient satisfaction between the entry-level APN and MD groups. However, clinical consultation time was significantly longer for entry-level APNs than for MDs. CONCLUSIONS: Collaborative entry-level APNs managing primary hypertension are comparable with MD care; however, larger, longer trials are essential for a thorough assessment. Strengthening the development of entry-level advanced practice nursing roles in low- and middle-income countries is crucial for addressing service gaps in primary hypertension and other chronic diseases.
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Prática Avançada de Enfermagem , Hipertensão , Humanos , Hipertensão/enfermagem , Hipertensão/tratamento farmacológico , Feminino , Masculino , Pessoa de Meia-Idade , Satisfação do Paciente , Adulto , Idoso , Atenção Primária à SaúdeRESUMO
BACKGROUND: Nursing students experience higher stress and burnout compared to students in other health professions, with a prevalence rate of as high as 20%. More recently, they have been affected by changes in nursing education due to the COVID-19 pandemic, such as requirements for social isolation and distance learning. Although there are existing studies on interventions that address academic burnout among nursing students, there is no synthesis of randomized trials on this topic. AIM: This study aimed to systematically synthesize studies of interventions for academic burnout among nursing students. METHODS: A systematic search for randomized controlled trials was performed in PubMed, CINAHL, CENTRAL, Web of Science, and Scopus. Eligibility criteria were based on study directness in relation to the Patient, Intervention, Comparison, and Outcome (PICO) question. Two review authors independently screened articles for inclusion, collected data from the included studies, and performed risk of bias assessments using the Cochrane Risk of Bias Tool 2.0. A narrative synthesis was performed. This review was registered a priori in PROSPERO (CRD42022350196). RESULTS: Six papers were included in this review. Various interventions were studied: Qigong exercises, progressive muscle relaxation, autogenic therapy and laughter therapy, didactic behavioral sessions focusing on personal and professional development, and coping skills enhancement. The effects of these interventions on academic burnout, depression, and stress among nursing students were short term and their benefits over time remain uncertain. LINKING EVIDENCE TO ACTION: Progressive muscle relaxation and cognitive behavioral interventions demonstrated short-term positive effects on academic burnout, depression, and stress among nursing students. These findings may support the development of individual-level and organizational-level initiatives for nursing students aimed to lessen or prevent academic burnout. Large-scale, high-quality studies on the effect of interventions on academic burden in various settings and cultures are needed.
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Esgotamento Profissional , COVID-19 , Estudantes de Enfermagem , Humanos , Pandemias , Esgotamento Profissional/terapia , Adaptação PsicológicaRESUMO
BACKGROUND: The Atopic Dermatitis (AD) TREATgermany registry was initiated by the German Society for Dermatology (DDG) in 2011 to evaluate the 'real-life' situation of health care for patients with AD. OBJECTIVES: Interim data analysis on baseline characteristics as well as current and prescribed systemic treatments of the TREATgermany registry patients. METHODS: Patients (≥18 years) with moderate-to-severe AD [objective (o)SCORAD > 20], or with current or previous anti-inflammatory systemic treatment for AD within 24 months, were included and are followed up over at least 24 months. To assess clinical signs, the eczema area severity index (EASI, 0-72), the oSCORAD (0-83) and the Investigator Global Assessment (IGA; 6-point scale) were used. The disease severity was globally scored by the patients [Patient Global Assessment (PGA); six-step Likert scale]. Disease symptoms were assessed by the patient-oriented eczema measure (POEM, 0-28) and numeric rating scales (NRS, 0-10). Health-related quality of life was measured using the dermatological life quality index (DLQI, 0-30). RESULTS: A total of 612 patients were recruited across 32 sites between 06/2016 and 01/2019 (mean age: 42.6 ± 14.2 years; mean oSCORAD: 40.8 ± 16.3). The mean POEM score was 16.3 ± 7.5. Pruritus was rated highest among subjective symptoms (NRS: 5.4 ± 2.7). The mean DLQI value was 11.3 ± 7.5. The frequency of arterial hypertension was lower (20.8%) compared with the general population, whilst this was higher for depression (10%). More than 60% of the patients had received systemic glucocorticosteroids, and 36.8% had received cyclosporine A prior to inclusion. Dupilumab was the leading substance documented as either 'current' (12.1%) or 'prescribed' (31.4%) at baseline. CONCLUSIONS: These 'real-life' data clearly demonstrate the substantial disease burden. Most of TREATgermany patients were already treated with or prescribed dupilumab at baseline. Moreover, current findings indicate the urgent need for further alternative agents in order to achieve a perceptible improvement of quality of life of patients with moderate-to-severe AD.
Assuntos
Dermatite Atópica , Eczema , Adulto , Dermatite Atópica/tratamento farmacológico , Humanos , Pessoa de Meia-Idade , Qualidade de Vida , Sistema de Registros , Índice de Gravidade de DoençaRESUMO
BACKGROUND: Dry skin is a frequent and multifaceted condition which can be associated with skin irritation, itch, patient discomfort and manifest skin disease. In spite of being frequent, little is known about the epidemiology of dry skin in the population. OBJECTIVE: To determine the prevalence of dry skin in the German adult population. METHODS: Data of 48 630 employed persons were assessed on a cross-sectional level in whole-body examinations by experienced dermatologists during company-based skin screenings conducted in 343 German companies. Next to the current dermatologic findings, age, gender, allergies, atopic diseases and the skin type were assessed. RESULTS: In total, n = 14 300 persons (29.4%) were rated as having xerotic skin. Older age but not gender was associated with xerosis. In the regression analyses controlling for age and gender, dry skin was a significant predictor for: axillary dermatitis (OR: 4.51; CI 2.70-7.54), atopic eczema (OR: 3.99; CI 3.42-4.65), exsiccation eczema (OR: 2.96; CI 2.40-3.65), psoriasis (OR: 1.57; CI 1.38-1.78), plantar warts (OR: 1.42; CI 1.26-1.60), seborrhoeic dermatitis (OR: 1.28; CI 1.16-1.42) and atopic disposition (OR: 1.17; CI 1.12-1.22). CONCLUSION: Dry skin is a frequent condition in the adult general population and needs special attention. Known risk factors may facilitate identifying patients at risk for deterioration.
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Dermatopatias/epidemiologia , Adulto , Fatores Etários , Estudos Transversais , Dermatite Atópica/epidemiologia , Dermatite Seborreica/epidemiologia , Feminino , Alemanha/epidemiologia , Humanos , Hipersensibilidade/epidemiologia , Masculino , Pessoa de Meia-Idade , Prevalência , Psoríase/epidemiologia , Verrugas/epidemiologiaRESUMO
BACKGROUND: Hereditary angioedema (HAE) with normal C1-INH (HAEnCI) may be linked to specific mutations in the coagulation factor 12 (FXII) gene (HAE-FXII) or functional mutations in other genes that are still unknown. We sought to identify and characterize a hitherto unknown type of HAE with normal C1-INH and without mutation in the F12 gene. METHODS: The study comprised analysis of whole-exome sequencing, Sanger sequencing, and clinical data of patients. RESULTS: We detected a mutation in the plasminogen (PLG) gene in patients with HAEnCI. The mutation c.988A>G was located in exon 9 leading to the missense mutation p.Lys330Glu (K330E) in the kringle 3 domain of the PLG protein. The mutation was identified by next-generation sequencing in 14 patients with HAEnCI belonging to 4 of 7 families. Family studies revealed that this type of HAE was transmitted as an autosomal dominant trait. The PLG gene mutation was present in all studied symptomatic patients and was also found in 9 of 38 index patients from 38 further families with HAEnCI. Most patients had swelling of face/lips (78.3%) and tongue (78.3%). A total of 331 of all 3.795 tongue swellings (8.7%) were associated with dyspnea, voice changes, and imminent asphyxiation. Two women died by asphyxiation due to a tongue swelling. CONCLUSIONS: Hereditary angioedema with a mutation in the PLG gene is a novel type of HAE. It is associated with a high risk of tongue swellings.
Assuntos
Angioedemas Hereditários/genética , Mutação/genética , Plasminogênio/genética , Adolescente , Adulto , Idoso , Criança , Pré-Escolar , Feminino , Alemanha , Humanos , Masculino , Pessoa de Meia-Idade , Mutação de Sentido Incorreto/genética , Sequenciamento do Exoma/métodos , Adulto JovemRESUMO
BACKGROUND: Clinical registries may provide high-quality evidence on the use and effectiveness of therapeutic interventions under real-life conditions. Adults with moderate-to-severe atopic eczema (atopic dermatitis [AD]) are enrolled into TREATgermany and prospectively followed over at least 2 years. This paper analyses the association between dermatological quality of life and work limitations. MATERIALS AND METHODS: Treatment modalities and a broad set of physician- and patient-reported outcome measures are documented using validated instruments to assess clinical disease severity (EASI [Eczema Area and Severity Index], objective SCORAD [objective-SCORing Atopic Dermatitis]), quality of life (DLQI [Dermatology Life Quality Index]), symptoms (POEM [Patient-oriented Eczema Measure]), global disease severity, as well as patient satisfaction and work limitations including presenteeism (WLQ [Work Limitation Questionnaire]). From 06/2016 until 12/2017, 241 individuals (mean age 43⯱ 15 years, 38.6% female) were enrolled at 19 recruitment centers; 69% of the patients were employed. RESULTS: Employed persons had DLQI and WLQ scores of 10.6⯱ 6.9 points and 17.7⯱ 18.1%, respectively. Mean presenteeism was substantial accounting for 9.2%. With coefficients of 0.39 and 0.33 WLQ and presenteeism scores significantly correlate with DLQI (pâ¯< 0.000). Bootstrapped regression models showed that the limitations in coping with work requirements increase by 1.7% as DLQI increases by one point. Lower quality of life due to AD is most strongly associated with limitations in the area of physical and performance requirements in general. Presenteeism increases by 0.5% as DLQI increases by one point. CONCLUSION: Moderate-to-severe AD has substantial adverse economic impact with mean productivity loss of patients of almost 10%. Future analyses from TREATgermany will address the impact of innovative treatment modalities on quality of life and work productivity of patients with moderate-to-severe AD.
Assuntos
Competência Clínica , Dermatite Atópica , Eczema , Sistema de Registros , Adulto , Dermatite Atópica/terapia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Qualidade de Vida , Índice de Gravidade de DoençaRESUMO
PURPOSE: The objective of the study was to clarify whether driving abstinence should be recommended when patients are discharged from hospital after unicompartmental knee arthroplasty (UKA). We tested the hypotheses that there are differences in the peri-operative course of brake response time in patients undergoing right-sided (1) or left-sided (2) UKA. Additionally, we tested whether brake response time is significantly influenced by pain (3), driving experience (4) or age (5). METHODS: In 43 patients undergoing UKA, brake response time was measured with a custom-made driving simulator pre-operatively and 1 and 6 weeks after UKA. Patients' visual analogue scales for knee pain and their self-reported driving experience were also assessed. RESULTS: In patients with right-sided UKA, brake response time changed from 786 (261) ms pre-operatively to 900 (430) ms 1 week post-operatively (p = 0.029). At 6 weeks post-operatively, brake response time had returned to 712 (139) ms, which was deemed to be an insignificant change from the pre-operative reference benchmark. When surgery was performed on the contralateral left side, no effect was found onto the right side's brake response time. Knee pain and driving experience were significantly correlated with brake response time. No such correlations were found between brake response time and age. CONCLUSIONS: On the basis of the current findings, it is concluded that brake response time returns to pre-operative levels 6 weeks after UKA surgery. Therefore, it is proposed that driving be abstained from for that period.
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Artroplastia do Joelho , Condução de Veículo , Osteoartrite do Joelho/fisiopatologia , Osteoartrite do Joelho/cirurgia , Tempo de Reação , Idoso , Artralgia/diagnóstico , Artralgia/fisiopatologia , Feminino , Humanos , Articulação do Joelho/fisiopatologia , Articulação do Joelho/cirurgia , Masculino , Pessoa de Meia-Idade , Educação de Pacientes como Assunto , Período Pós-Operatório , Recuperação de Função FisiológicaRESUMO
Hereditary angioedema due to C1 inhibitor (C1 esterase inhibitor) deficiency (types I and II HAE-C1-INH) is a rare disease that usually presents during childhood or adolescence with intermittent episodes of potentially life-threatening angioedema. Diagnosis as early as possible is important to avoid ineffective therapies and to properly treat swelling attacks. At a consensus meeting in June 2011, pediatricians and dermatologists from Germany, Austria, and Switzerland reviewed the currently available literature, including published international consensus recommendations for HAE therapy across all age groups. Published recommendations cannot be unconditionally adopted for pediatric patients in German-speaking countries given the current approval status of HAE drugs. This article provides an overview and discusses drugs available for HAE therapy, their approval status, and study results obtained in adult and pediatric patients. Recommendations for developing appropriate treatment strategies in the management of HAE in pediatric patients in German-speaking countries are provided.Conclusion Currently, plasma-derived C1 inhibitor concentrate is considered the best available option for the treatment of acute HAE-C1-INH attacks in pediatric patients in German-speaking countries, as well as for short-term and long-term prophylaxis.
Assuntos
Proteína Inibidora do Complemento C1/uso terapêutico , Inativadores do Complemento/uso terapêutico , Angioedema Hereditário Tipos I e II/tratamento farmacológico , Adolescente , Adulto , Androgênios/uso terapêutico , Anti-Inflamatórios não Esteroides/uso terapêutico , Antifibrinolíticos/uso terapêutico , Áustria , Bradicinina/análogos & derivados , Bradicinina/uso terapêutico , Criança , Proteínas Inativadoras do Complemento 1/uso terapêutico , Progressão da Doença , Alemanha , Humanos , Peptídeos/uso terapêutico , Proteínas Recombinantes/uso terapêutico , SuíçaRESUMO
AIM: To analyse the performance of HbA(1c) in diagnosing Type 2 diabetes based on fasting plasma glucose and/or 2-h plasma glucose measurements after a 75-g oral glucose tolerance test. METHODS: This is a study of diagnostic test accuracy in individuals referred to the Clinical Pathology Department for oral glucose tolerance testing. After fasting overnight, HbA(1c), fasting plasma glucose and 2-h plasma glucose were measured. The receiver operating characteristic curve was used to evaluate the diagnostic performance of HbA(1c). RESULTS: Four hundred and ninety-eight subjects (195 male, mean age 56 years) were enrolled and 115 (23.1%) were diagnosed with diabetes according to glucose-based methods and only 56 (11.2%) individuals were identified by HbA(1c) ≥ 6.5% (48 mmol/mol) (sensitivity 20.9%, specificity 95.3%). There is poor agreement between the newly recommended criterion and the current glucose-based diagnostic criteria (κ = 0.217; P < 0.001), probably because the diagnostic methods identify different populations of patients. Adding a glucose-based method into an algorithm, as proposed by the UK Department of Health, improved HbA(1c) performance. CONCLUSIONS: HbA(1c) ≥ 6.5% (48 mmol/mol) showed limited sensitivity to diabetes diagnosis, although with high specificity. The results suggest that this cut-off point would not be enough to diagnose diabetes. Its use as the sole diabetes diagnostic test should be interpreted with caution to assure the correct classification of diabetic individuals.
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Glicemia/metabolismo , Diabetes Mellitus Tipo 2/diagnóstico , Teste de Tolerância a Glucose/métodos , Hemoglobinas Glicadas/metabolismo , Diabetes Mellitus Tipo 2/epidemiologia , Diabetes Mellitus Tipo 2/metabolismo , Jejum , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Padrões de Referência , Sensibilidade e Especificidade , Reino Unido/epidemiologiaRESUMO
Cushing's syndrome is a state of cortisol excess, possibly from a tumor in the pituitary gland, the adrenal gland, or an ectopic nonpituitary ACTH-secreting source. The first form, pituitary in origin, was originally described by Harvey Cushing, MD, and was labeled as Cushing's disease. Long-term therapy with glucocorticoids also can lead to iatrogenic Cushing's syndrome.
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Síndrome de ACTH Ectópico/diagnóstico , Adenoma/fisiopatologia , Síndrome de Cushing/diagnóstico , Síndrome de Cushing/etiologia , Síndrome de Cushing/terapia , Glucocorticoides/efeitos adversos , Hipófise/fisiopatologia , Adolescente , Humanos , Masculino , Filipinas , Resultado do TratamentoRESUMO
We report on the preparation of 4-aza-5,6-dimethylbenzimidazolylcobamide and 5,6-dimethyl-7-azabenzimidazolylcobamide. These vitamin B12-analogs were required as reference compounds for comparison with a corrinoid previously isolated in small amounts for Eubacterium limosum grown in the presence of 4(5)-aminoimidazole. 4(7)-Aza-5,6-dimethylbenzimidazole was synthesized from N-1-benzyl-4-nitroimidazole which was reduced to N-1-benzyl-4-aminoimidazole and condensed with 1-dimethylamino-2-methylbutan-3-one to yield N-1-benzyl-4-aza-5,6-dimethylbenzimidazole. The benzyl group of this compound was split off by catalytic hydrogenation to form 4(7)-aza-5,6-dimethylbenzimidazole. 4(7)-Aza-5,6-dimethylbenzimidazole was transformed by a growing culture of Propionibacterium shermanii into 4-aza-5,6-dimethylbenzimidazolylcobamide and 5,6-dimethyl-7-azabenzimidazolylcobamide. Both vitamin B12-analogs were almost as active as Vitamin B12 in a growth test with the vitamin B12-dependent Escherichia coli-mutant DSM 4261.
Assuntos
Cobamidas/síntese química , Escherichia coli/efeitos dos fármacos , Vitamina B 12/análogos & derivados , Vitamina B 12/síntese química , Cobamidas/química , Cobamidas/farmacologia , Escherichia coli/genética , Escherichia coli/crescimento & desenvolvimento , Eubacterium/metabolismo , Indicadores e Reagentes , Espectroscopia de Ressonância Magnética , Espectrometria de Massas , Estrutura Molecular , Vitamina B 12/farmacologiaRESUMO
The 5,6-dimethylbenzimidazole unit of vitamin B12 is formed from riboflavin via FMN in aerobic and some aerotolerant bacteria. Thereby C-1' of the ribityl side chain gets C-2 of 5,6-dimethylbenzimidazole. Experiments with homogenates of Propionibacterium shermanii on the fate of C-atoms 2' to 5' of the ribityl side chain of riboflavin in this transformation are reported. It was found that [5'-3H]riboflavin leads to radioactive sugar phosphates. These were isolated, dephosphorylated, and separated. Thus 3H-D-fructose and 3H-D-glucose were detected. The degradation of 3H-D-glucose revealed that 14 per cent of the total radioactivity was located in C-1, and 86 per cent in C-6. This indicates that during 5,6-dimethylbenzimidazole biosynthesis a three carbon unit is formed from the ribityl side chain of riboflavin.
Assuntos
Benzimidazóis/metabolismo , Propionibacterium/metabolismo , Riboflavina/metabolismo , Biotransformação , Frutose/metabolismo , Glucose/metabolismo , Marcação por Isótopo/métodos , Técnica de Diluição de Radioisótopos , Riboflavina/síntese química , TrítioRESUMO
Autoimmune diseases can initially present as chronic urticaria. We describe the course of a patient with hypocomplementemic urticarial vasculitis syndrome (HUVS) as well as his successful treatment with high-dose intravenous immunoglobulins (IVIG). HUVS was diagnosed clinically and confirmed by histology and laboratory studies. After only one cycle with IVIG (2 g/kg) all HUVS symptoms were significantly decreased.
Assuntos
Angioedema/tratamento farmacológico , Doenças Autoimunes/tratamento farmacológico , Complemento C1q/deficiência , Complemento C3/deficiência , Complemento C4/deficiência , Imunoglobulinas Intravenosas/administração & dosagem , Lúpus Eritematoso Sistêmico/tratamento farmacológico , Vasculite Leucocitoclástica Cutânea/tratamento farmacológico , Adulto , Angioedema/diagnóstico , Angioedema/imunologia , Angioedema/patologia , Doenças Autoimunes/diagnóstico , Doenças Autoimunes/imunologia , Doenças Autoimunes/patologia , Biópsia , Diagnóstico Diferencial , Seguimentos , Humanos , Infusões Intravenosas , Lúpus Eritematoso Sistêmico/diagnóstico , Lúpus Eritematoso Sistêmico/imunologia , Lúpus Eritematoso Sistêmico/patologia , Masculino , Pele/patologia , Vasculite Leucocitoclástica Cutânea/diagnóstico , Vasculite Leucocitoclástica Cutânea/imunologia , Vasculite Leucocitoclástica Cutânea/patologiaRESUMO
Under microaerophilic conditions Salmonella typhimurium LT2 synthesizes cobalamin, during which 5,6-dimethylbenzimidazole is formed from riboflavin. We report here that in an anoxic environment S. typhimurium did not form cobalamin, but rather adenylcobamide, 2-methyladenylcobamide, and cobyric acid. This indicated that S. typhimurium, like other microorganisms that synthesize 5,6-dimethylbenzimidazole from riboflavin, requires oxygen for the formation of the cobalamin base.
Assuntos
Cobamidas/metabolismo , Salmonella typhimurium/metabolismo , Vitamina B 12/metabolismo , Anaerobiose , Riboflavina/metabolismo , Salmonella typhimurium/crescimento & desenvolvimentoRESUMO
A phospholipid mixture was isolated from bovine vesicle tissue. This phospholipid preparation contained the following prostaglandin precursor fatty acids: 4.7 percent 5,8,11-eicosatrienoic acid, 9.1 percent 5,8,11,14-eicosatetraenoic acid and 0.9% 5,8,11,14,17-eicosapentaenoic acid. With this phospholipid preparation as substrate phospholipase activity could be detected in different fractions of bovine seminal vesicle cells. The highest phospholipase activity was found in the microsomal fraction, less in the mitochondria and essentially no activity in the cytosol. With a microsome preparation (acetone powder) of bovine seminal vesicles the influence of certain effectors on the phospholipase activity was investigated. Prostaglandins E2 and F2alpha (10(-5) M) showed 19 and 41 percent inhibition, DB-c-AMP (2 times 10(-9) M) 54%, c-AMP (10(-9) M) 22%, epinephrine (10(-4) M) 60%, testosterone (10(-5) M) 25% inhibition of the phospholipase activity. Whereas ethanol exhibits also a strong inhibition on the phospholipase activity, it shows a pronounced activation of the prostaglandin synthetase.
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Oxigenases de Função Mista/metabolismo , Fosfolipases/metabolismo , Prostaglandina-Endoperóxido Sintases/metabolismo , Prostaglandinas/biossíntese , Glândulas Seminais/metabolismo , Animais , Bovinos , AMP Cíclico/farmacologia , Citosol/metabolismo , Epinefrina/farmacologia , Etanol/farmacologia , Masculino , Microssomos/metabolismo , Mitocôndrias/metabolismo , Norepinefrina/farmacologia , Prostaglandinas E/farmacologia , Glândulas Seminais/efeitos dos fármacos , Testosterona/farmacologiaRESUMO
Two hitherto unknown vitamin B-12 factors were isolated from sewage sludge. They were degraded with cerous hydroxide to cobinamide and the corresponding nucleoside. The nucleosides were further split with dilute hydrochloric acid to the bases and D-ribose. The structure of the two bases was found to be 2-methylsulfinyladenine and 2-methylsulfonyladenine. This was revealed by mass, infrared and nuclear magnetic resonance spectroscopy, and by comparison with the synthetic compounds. On addition of the synthetic bases to fermentations with Propionibacterium acidi-propionici the vitamin B-12 factors containing the corresponding base were formed. They were identical with the 2-methylsulfonyladenylcobamide and 2-methylsulfonyladenylcobamide originally isolated from sewage sludge.