RESUMO
Our aim was to investigate the occurrence of bacteremia associated with removal of a semirigid osteosynthesis plate and an adjacent third molar. Ten patients with fixed mandibular angle fracture were bacteriologically sampled from the second molar's distal gingival pocket, from the third molar's extraction socket and from the osteosynthesis plate. Blood samples from the ante-cubital vein were taken 10 times until 30 min postoperatively. Established culture, isolation and identification methods for the bacterial species were used. Bacteremia was detected in 60% of the subjects, most frequently 1.5 min after removal of the plate (20%) and 1.5 and 5 min after extraction of the tooth (20%), but also 10 min (10%) and 30 min (10%) postoperatively. 13 different bacterial species or groups were isolated, mean 2.5 +/- 1.9 per bacteremia-positive subject. The majority (85%) were anaerobes with Actinomyces, Campylobacter and Lactobacillus species predominating. In all the blood culture-positive cases the corresponding species was also recovered from one or more of the oral samples. These results show that oral surgical procedures are associated with a high frequency of longstanding anaerobic bacteremia, which could be harmful in patients at risk.
Assuntos
Bacteriemia/etiologia , Remoção de Dispositivo/efeitos adversos , Fraturas Mandibulares/cirurgia , Extração Dentária/efeitos adversos , Adulto , Bactérias Anaeróbias/isolamento & purificação , Placas Ósseas , Feminino , Fixação Interna de Fraturas , Humanos , Técnicas de Fixação da Arcada Osseodentária , Masculino , Dente Serotino/cirurgiaRESUMO
Our aim was to investigate bacteremia caused by surgical extraction of partly erupted mandibular third molars. From 16 young adults, bacterial samples were taken from the third-molar pericoronal pocket and post-operatively from the extraction socket, and blood samples were drawn from the ante-cubital vein up to 30 min after surgery. Of the subjects, 88% had detectable bacteremia-50% 1 min after the incision, 44% immediately after extraction. The respective percentages at 10, 15, and 30 min were 44%, 25%, and 13%. Blood cultures contained 31 species (74% anaerobes), with 3.9 +/- 2.6 species isolated per subject. Most prevalent were the anaerobes Prevotella, Eubacterium, and Peptostreptococcus sp. and the aerobes viridans-group streptococci and Streptococcus milleri group. Any species found in the blood was also isolated from the mouth, from 93% of the pericoronal pockets and from 43% of the extraction sockets. Surgical dental extraction clearly causes bacteremia of a high frequency and lasting longer than thus far assumed.
Assuntos
Bacteriemia/microbiologia , Bactérias Anaeróbias/classificação , Dente Serotino/cirurgia , Extração Dentária , Adulto , Infecções por Bacteroidaceae/microbiologia , Eubacterium/isolamento & purificação , Feminino , Bolsa Gengival/microbiologia , Infecções por Bactérias Gram-Positivas/microbiologia , Humanos , Masculino , Dente Serotino/microbiologia , Peptostreptococcus/isolamento & purificação , Prevotella/isolamento & purificação , Infecções Estreptocócicas/microbiologia , Streptococcus milleri (Grupo)/isolamento & purificação , Fatores de Tempo , Extração Dentária/efeitos adversos , Alvéolo Dental/microbiologia , Estreptococos Viridans/isolamento & purificaçãoRESUMO
OBJECTIVES: The authors carried out clinical, histopathologic, immunocytochemical, electrophysiologic, and imaging investigations and molecular genetic analysis in seven patients with distal myopathy belonging to a Finnish family. RESULTS: The disease showed autosomal dominant inheritance. Age at onset ranged from 32 to 45 years. The first symptoms for referral were clumsiness with the hands and frequent stumbling from a steppage gait. Muscle weakness was characterized by early involvement of the small muscles of the hands, gluteus medium, and both anterior and posterior muscle compartments of the legs. The disease progressed to involve other intrinsic muscles of the hands, as well as the forearm muscles, triceps and infraspinatus, and proximal lower limbs. Asymmetry of muscle involvement was common. EMG showed myopathic features, serum CK was normal or slightly elevated, and muscle biopsy showed many rimmed vacuoles and dystrophic changes. There was no evidence of linkage to Welander distal myopathy or tibial muscular dystrophy loci. CONCLUSION: These patients may have a distinct distal myopathy. Genome-wide scan is undertaken in order to identify the disease locus.
Assuntos
Distrofias Musculares/diagnóstico , Distrofias Musculares/genética , Fenótipo , Adulto , Idade de Início , Idoso , Biópsia , Creatina Quinase/sangue , Progressão da Doença , Eletrodiagnóstico , Família , Feminino , Finlândia/etnologia , Genes Dominantes , Ligação Genética , Mãos/fisiopatologia , Humanos , Perna (Membro)/fisiopatologia , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Debilidade Muscular/etiologia , Debilidade Muscular/fisiopatologia , Músculo Esquelético/diagnóstico por imagem , Músculo Esquelético/patologia , Distrofias Musculares/complicações , Linhagem , Tomografia Computadorizada por Raios XRESUMO
The authors carried out a clinical, laboratory and muscle computed tomographgy CT follow-up study of 18-21 years on two sisters affected by quadriceps myopathy (QM). The onset in the fourth decade was a weakness in the thighs. During the follow-up study, the patients showed only vasti muscles involvement, normal creatine kinase (CK) levels, myopathic muscle biopsy and electromyography (EMG) and normal membrane protein expression on immunocytochemical analysis. Therefore, all muscle pathologies known to have quadriceps involvement as a leading feature have been ruled out. We conclude that our patients have pure QM with probable autosomal recessive inheritance.
Assuntos
Doenças Musculares/diagnóstico , Biópsia/métodos , Creatina Quinase/sangue , Eletromiografia/métodos , Feminino , Seguimentos , Humanos , Microscopia Eletrônica , Pessoa de Meia-Idade , Músculo Esquelético/diagnóstico por imagem , Músculo Esquelético/metabolismo , Músculo Esquelético/patologia , Músculo Esquelético/ultraestrutura , Doenças Musculares/genética , Condução Nervosa/fisiologia , Radiografia , Irmãos , Tomógrafos ComputadorizadosRESUMO
Matrilysin is a matrix metalloproteinase expressed in exocrine and mucosal epithelium in many human tissues. Immunohistochemical staining showed that matrilysin is expressed in suprabasal cells of junctional epithelium facing the teeth and in epithelial cell rests of Malassez. No matrilysin expression was seen in the periodontal pocket tissue. In a tissue culture model mimicking junctional epithelium, matrilysin expression was also observed in suprabasal epithelial cells. Of 13 anaerobic oral bacterial species tested, F. nucleatum, F. necrophorum, P. endodontalis, and P. denticola stimulated matrilysin expression in porcine periodontal ligament epithelial cells from 2.5- to 5.7-fold, compared with untreated cells. The enzyme was localized in intracytoplasmic vesicles that also reacted with antibodies against lysosomal membrane protein h-lamp-1. The results indicate that matrilysin may play an important role in the normal physiology of junctional epithelium.
Assuntos
Inserção Epitelial/enzimologia , Metaloproteinase 7 da Matriz/biossíntese , Ligamento Periodontal/enzimologia , Adolescente , Adulto , Animais , Bactérias Anaeróbias/imunologia , Northern Blotting , Células Cultivadas , Vesículas Citoplasmáticas/enzimologia , Células Epiteliais/enzimologia , Feminino , Regulação Enzimológica da Expressão Gênica , Humanos , Imuno-Histoquímica , Masculino , Mucosa Bucal/enzimologia , Ligamento Periodontal/citologia , Suínos , Regulação para CimaRESUMO
Axial myopathy (AM) is a rare neuromuscular disorder characterised by selective involvement of the spinal muscles with a bent spine and/or drooping head as leading clinical features. We here report the results of clinical, histopathological, MRI, molecular genetics and electrophysiological investigations carried out on six patients affected by pure axial myopathy. Symptoms appeared within an age range of 35 to 56 years. The first symptoms were difficulty in keeping the trunk and head in an upright position. Both bent spine and dropped head were reduced in a supine position. The disease was slowly progressive. Muscle strength examination and muscle imaging revealed involvement of the spinal and neck extensor muscles only. Serum CK was normal to slightly increased. EMG and muscle biopsy specimens obtained from spinal muscles showed an advanced chronic myopathic pattern. We conclude that axial myopathy may be much more common than previously thought, because gradual progression of cervical kyphosis may often be explained as a feature of normal ageing or as an associated sign of several neurological disorders and vertebral degeneration diseases.
Assuntos
Músculo Esquelético/patologia , Músculo Esquelético/fisiopatologia , Doenças Musculares/patologia , Doenças Musculares/fisiopatologia , Curvaturas da Coluna Vertebral/etiologia , Coluna Vertebral/fisiopatologia , Idoso , Creatina Quinase/sangue , Eletromiografia , Feminino , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Contração Muscular/fisiologia , Fibras Musculares Esqueléticas/patologia , Atrofia Muscular/patologia , Atrofia Muscular/fisiopatologia , Postura/fisiologia , Curvaturas da Coluna Vertebral/patologia , Curvaturas da Coluna Vertebral/fisiopatologia , Coluna Vertebral/patologiaRESUMO
BACKGROUND: Acetaldehyde is a local carcinogen in the digestive tract in humans. Atrophic gastritis leads to microbial colonization of the stomach, which could enhance microbial production of acetaldehyde from ethanol. The aim of the study was to study microbial ethanol metabolism and acetaldehyde production in the stomach of achlorhydric atrophic gastritis patients. METHODS: For the in vivo study, glucose or ethanol was infused via a nasogastric tube to the stomach of seven achlorhydric atrophic gastritis patients and five healthy controls. Gastric juice samples for ethanol and acetaldehyde determinations and microbial analysis were obtained at 30 and 60 min after the infusions. For the in vitro study, gastric juice samples from 14 atrophic gastritis patients and 16 controls were obtained during gastroscopy, whereafter the samples were incubated for 2 h with 1% ethanol at 37 degrees C and acetaldehyde was determined. RESULTS: Minor endogenous ethanol and acetaldehyde concentrations were detected after glucose infusion in the gastric juice of four atrophic gastritis patients. After ethanol infusion, the mean intragastric acetaldehyde level of the atrophic gastritis patients was 4.5-fold at 30 min and 6.5-fold at 60 min compared to controls. In vitro, the difference between the study groups was even higher, 7.6-fold. A vast selection of oral bacterial species and some Enterobacteriaceae and yeasts were presented in the gastric juice of atrophic gastritis patients. CONCLUSIONS: Microbial ethanol metabolism leads to high intragastric acetaldehyde levels after ethanol drinking in achlorhydric atrophic gastritis patients. This could be one of the factors responsible for enhanced gastric cancer risk among atrophic gastritis patients.
Assuntos
Acetaldeído/metabolismo , Acloridria/microbiologia , Etanol/farmacologia , Mucosa Gástrica/microbiologia , Gastrite Atrófica/microbiologia , Bactérias Gram-Negativas/crescimento & desenvolvimento , Bactérias Gram-Positivas/crescimento & desenvolvimento , Adulto , Estudos de Casos e Controles , Feminino , Suco Gástrico/metabolismo , Mucosa Gástrica/metabolismo , Gastrite Atrófica/metabolismo , Glucose/farmacologia , Bactérias Gram-Negativas/isolamento & purificação , Bactérias Gram-Positivas/isolamento & purificação , Humanos , Masculino , Pessoa de Meia-Idade , Valores de Referência , Medição de Risco , Sensibilidade e EspecificidadeRESUMO
In humans, low peak bone mass is a significant risk factor for osteoporosis. We report that LRP5, encoding the low-density lipoprotein receptor-related protein 5, affects bone mass accrual during growth. Mutations in LRP5 cause the autosomal recessive disorder osteoporosis-pseudoglioma syndrome (OPPG). We find that OPPG carriers have reduced bone mass when compared to age- and gender-matched controls. We demonstrate LRP5 expression by osteoblasts in situ and show that LRP5 can transduce Wnt signaling in vitro via the canonical pathway. We further show that a mutant-secreted form of LRP5 can reduce bone thickness in mouse calvarial explant cultures. These data indicate that Wnt-mediated signaling via LRP5 affects bone accrual during growth and is important for the establishment of peak bone mass.
Assuntos
Densidade Óssea/genética , Anormalidades do Olho/genética , Olho/embriologia , Osteoblastos/metabolismo , Osteoporose/genética , Receptores de LDL/fisiologia , Fator de Crescimento Transformador beta , Proteínas de Peixe-Zebra , Proteínas Adaptadoras de Transdução de Sinal , Adulto , Animais , Animais não Endogâmicos , Proteína Morfogenética Óssea 2 , Proteínas Morfogenéticas Ósseas/farmacologia , Células COS , Criança , Pré-Escolar , Chlorocebus aethiops , Cromossomos Humanos Par 11/genética , Meios de Cultivo Condicionados/farmacologia , DNA Complementar/genética , Proteínas Desgrenhadas , Feminino , Genes Recessivos , Heterozigoto , Humanos , Proteínas Relacionadas a Receptor de LDL , Proteína-5 Relacionada a Receptor de Lipoproteína de Baixa Densidade , Masculino , Mesoderma/citologia , Camundongos , Camundongos Endogâmicos C57BL , Técnicas de Cultura de Órgãos , Fosfoproteínas/genética , Fosfoproteínas/fisiologia , Proteínas/genética , Proteínas/fisiologia , Proteínas Proto-Oncogênicas/genética , Proteínas Proto-Oncogênicas/fisiologia , Receptores de LDL/deficiência , Receptores de LDL/genética , Proteínas Recombinantes de Fusão/fisiologia , Proteínas Recombinantes , Transdução de Sinais , Crânio/citologia , Especificidade da Espécie , Células Estromais/citologia , Células Estromais/efeitos dos fármacos , Síndrome , Transfecção , Proteínas Wnt , Proteína Wnt-5a , Proteína Wnt2 , Proteína Wnt3 , Proteína Wnt4RESUMO
PURPOSE: Despite greatly improved dental health in industrialized countries, severe odontogenic infections still occasionally lead to hospitalization. The aim of the present study was to determine whether what symptoms, signs, or laboratory parameters on hospital admission were associated with the need for treatment in the intensive care unit (ICU). PATIENTS AND METHODS: Over an 18-month period, 100 consecutive patients (59 male, 41 female) were included in the study. Twenty percent of the patients required ICU treatment because of cardiorespiratory problems or severe complications of their infection. Both ICU and non-ICU patients were examined clinically and blood samples were taken and studied in respect to several parameters associated with infection, including C-reactive protein (CRP) levels. The findings were analyzed statistically for differences between the groups. RESULTS: No particular anamnestic background variable was associated with the need for intensive care. However, a particularly high CRP level on admission was found to be associated with a more severe course of the infection. CONCLUSIONS: This study showed that determination of CRP levels may be useful in clinical decision-making in patients with severe odontogenic infections.
Assuntos
Cuidados Críticos , Infecção Focal Dentária/fisiopatologia , Adulto , Análise de Variância , Sedimentação Sanguínea , Proteína C-Reativa/análise , Distribuição de Qui-Quadrado , Feminino , Fibrinogênio/análise , Infecção Focal Dentária/sangue , Infecção Focal Dentária/complicações , Cardiopatias/fisiopatologia , Hospitalização , Humanos , Contagem de Leucócitos , Pneumopatias/fisiopatologia , Masculino , Admissão do Paciente , Fatores de Risco , Estatística como Assunto , Infecções Estreptocócicas/fisiopatologiaRESUMO
We studied exercise-induced changes in the adenosine triphosphate (ATP), phosphocreatine (PCr), and lactate levels in the skeletal muscle of mitochondrial patients and patients with McArdle's disease. Needle muscle biopsy specimens for biochemical measurement were obtained before and immediately after maximal short-term bicycle exercise test from 12 patients suffering from autosomal dominant and recessive forms of progressive external ophthalmoplegia and multiple deletions of mitochondrial DNA (adPEO, arPEO, respectively), five patients with mitochondrial encephalomyopathy with lactic acidosis and stroke-like episodes (MELAS) 3243 A-->G point mutation, and four patients with McArdle's disease. Muscle ATP and PCr levels at rest or after exercise did not differ significantly from those of the controls in any patient group. In patients with mitochondrial disease, muscle lactate tended to be lower at rest and increase more during exercise than in controls, the most remarkable rise being measured in patients with adPEO with generalized muscle symptoms and in patients with MELAS point mutation. In McArdle patients, the muscle lactate level decreased during exercise. No correlation was found between the muscle ATP and PCr levels and the respiratory chain enzyme activity.
Assuntos
Trifosfato de Adenosina/metabolismo , Exercício Físico/fisiologia , Doença de Depósito de Glicogênio Tipo V/fisiopatologia , Ácido Láctico/metabolismo , Miopatias Mitocondriais/fisiopatologia , Músculo Esquelético/metabolismo , Fosfocreatina/metabolismo , Adulto , Idoso , DNA Mitocondrial/genética , Transporte de Elétrons/fisiologia , Enzimas/metabolismo , Teste de Esforço , Deleção de Genes , Genes Dominantes , Genes Recessivos , Doença de Depósito de Glicogênio Tipo V/metabolismo , Humanos , Síndrome MELAS/metabolismo , Síndrome MELAS/fisiopatologia , Masculino , Pessoa de Meia-Idade , Miopatias Mitocondriais/metabolismo , Oftalmoplegia/genética , Oftalmoplegia/metabolismo , Oftalmoplegia/fisiopatologia , Aptidão FísicaRESUMO
BACKGROUND: Acetaldehyde is a known local carcinogen in the digestive tract in humans. Bacterial overgrowth in the hypochlorhydric stomach enhances production of acetaldehyde from ethanol in vivo after alcohol ingestion. Therefore, microbially produced acetaldehyde may be a potential risk factor for alcohol-related gastric and cardiac cancers. This study was aimed to investigate which bacterial species and/or groups are responsible for acetaldehyde formation in the hypochlorhydric human stomach and to characterize their alcohol dehydrogenase (ADH) enzymes. METHODS: After 7 days of treatment with 30 mg of lansoprazole twice a day, a gastroscopy was performed on eight volunteers to obtain hypochlorhydric gastric juice. Samples were cultured and bacteria were isolated and identified; thereafter, their acetaldehyde production capacity was measured gas chromatographically by incubating intact bacterial suspensions with ethanol at 37 degrees C. Cytosolic ADH activities, Km values, and protein concentration were determined spectrophotometrically. RESULTS: Acetaldehyde production of the isolated bacterial strains (n = 51) varied from less than 1 to 13,690 nmol of acetaldehyde/10(9) colony-forming units/hr. ADH activity of the strains that produced more than 100 nmol of acetaldehyde/10(9) colony-forming units/hr (n = 23) varied from 3.9 to 1253 nmol of nicotinamide adenine dinucleotide per minute per milligram of protein, and Km values for ethanol ranged from 0.65 to 116 mM and from 0.5 to 3.1 M (high Km). There was a statistically significant correlation (r = 0.64, p < 0.001) between ADH activity and acetaldehyde production from ethanol in the tested strains. The most potent acetaldehyde producers were Neisseria and Rothia species and Streptococcus salivarius, whereas nearly all Stomatococcus, Staphylococcus, and other Streptococcus species had a very low capacity to produce acetaldehyde. CONCLUSIONS: This study demonstrated that certain bacterial species or groups that originate from the oral cavity are responsible for the bulk of acetaldehyde production in the hypochlorhydric stomach. These findings provide new information with the respect to the local production of carcinogenic acetaldehyde in the upper digestive tract of achlorhydric human subjects.
Assuntos
Acetaldeído/metabolismo , Acloridria/microbiologia , Álcool Desidrogenase/metabolismo , Bactérias Aeróbias/metabolismo , Depressores do Sistema Nervoso Central/farmacocinética , Etanol/farmacocinética , Acloridria/induzido quimicamente , Adulto , Suco Gástrico/metabolismo , Humanos , Masculino , Estatísticas não ParamétricasRESUMO
BACKGROUND: Acute appendicitis is the most common surgical emergency in childhood. However, the pathogenesis and detailed microbiology are obscure. OBJECTIVE: To determine in detail the bacterial etiology of appendicitis in children in relation to the histologic tissue pathology. STUDY DESIGN: Tissue samples obtained at surgery from 41 children with suspected acute appendicitis were examined histologically and by culture for aerobic and anaerobic bacteria. The patients were analyzed according to histopathologic and clinical findings. RESULTS: Aerobic and anaerobic species were isolated from 40 of 41 (98%) samples; on average, 14.1 isolates per specimen (10.4 anaerobes and 3.7 aerobes). Specimens from patients with gangrenous appendices yielded significantly higher numbers of anaerobic isolates per specimen than did specimens from patients with healthy appendices (11.7 vs. 7.7; P < 0.01). Bacteria belonging to the Bacteroides fragilis group were the most frequently isolated anaerobic microorganisms (95%). Other organisms frequently isolated in all histology groups were Peptostreptococcus micros (66%), Bilophila wadsworthia (63%), Fusobacterium nucleatum (44%), Eggerthella lenta (44%) and a hitherto undescribed bile-resistant, pigment-producing Gram-negative rod (41%). Of the aerobes Escherichia coli (88%) and Streptococcus anginosus group (former Streptococcus "milleri" group) organisms (61%) were the most frequent findings. CONCLUSIONS: The shift from histologically normal toward gangrenous appendices was clearly associated with markedly elevated anaerobic bacterial counts in terms of species. The unusually high frequencies of B. wadsworthia (75%) and the hitherto undescribed bile-resistant, pigment-producing Gram-negative rod (56%) in gangrenous appendices represent unique and different findings from those reported in adults.
Assuntos
Apendicite/microbiologia , Bactérias/isolamento & purificação , Adolescente , Apendicite/patologia , Bactérias Aeróbias/isolamento & purificação , Bactérias Anaeróbias/isolamento & purificação , Criança , Pré-Escolar , Feminino , Humanos , Lactente , MasculinoRESUMO
BACKGROUND: Acetaldehyde, produced locally in the digestive tract, has recently been shown to be carcinogenic in humans. AIM: To examine the effect of iatrogenic hypochlorhydria on intragastric acetaldehyde production from ethanol after a moderate dose of alcohol, and to relate the findings to the changes in gastric flora. METHODS: Eight male volunteers ingested ethanol 0.6 g/kg b.w. The pH, acetaldehyde level and microbial counts of the gastric juice were then determined. The experiment was repeated after 7 days of lansoprazole 30 mg b.d. RESULTS: The mean (+/- S.E.M.) pH of the gastric juice was 1.3 +/- 0.06 and 6.1 +/- 0.5 (P < 0.001) before and after lansoprazole, respectively. This was associated with a marked overgrowth of gastric aerobic and anaerobic bacteria (P < 0. 001), by a 2.5-fold (P=0.003) increase in gastric juice acetaldehyde level after ethanol ingestion, and with a positive correlation (r=0. 90, P < 0.001) between gastric juice acetaldehyde concentration and the count of aerobic bacteria. CONCLUSIONS: Treatment with proton pump inhibitors leads to hypochlorhydria, which associates with intragastric overgrowth of aerobic bacteria and microbially-mediated acetaldehyde production from ethanol. Since acetaldehyde is a local carcinogen in the concentrations found in this study, long-term use of gastric acid secretory inhibitors is a potential risk-factor for gastric and cardiac cancers.
Assuntos
Acetaldeído/metabolismo , Acloridria/induzido quimicamente , Antiulcerosos/efeitos adversos , Etanol/metabolismo , Mucosa Gástrica/efeitos dos fármacos , Mucosa Gástrica/metabolismo , Omeprazol/análogos & derivados , 2-Piridinilmetilsulfinilbenzimidazóis , Adulto , Bactérias/crescimento & desenvolvimento , Suco Gástrico/metabolismo , Mucosa Gástrica/microbiologia , Humanos , Concentração de Íons de Hidrogênio , Lansoprazol , Masculino , Omeprazol/efeitos adversos , Inibidores da Bomba de PrótonsRESUMO
The pathogenetic mechanisms behind alcohol-associated carcinogenesis in the upper digestive tract remain unclear, as alcohol is not carcinogenic. However, there is increasing evidence that a major part of the tumour-promoting action of alcohol might be mediated via its first, toxic and carcinogenic metabolite acetaldehyde. Acetaldehyde is produced from ethanol in the epithelia by mucosal alcohol dehydrogenases, but much higher levels derive from microbial oxidation of ethanol by the oral microflora. In this study we investigated factors that might alter the composition and quantities of the oral microflora and, consequently, influence microbial acetaldehyde production. Information about dental health, smoking habits, alcohol consumption and other factors was obtained by a questionnaire from 326 volunteers with varying social backgrounds and health status, e.g. oral cavity malignancy. Paraffin-induced saliva was collected and the microbial production of acetaldehyde from ethanol was measured. Smoking and heavy drinking were the strongest factors increasing microbial acetaldehyde production. Whether poor dental status may alter local acetaldehyde production from ethanol remained unanswered. Bacterial analysis revealed that mainly gram-positive aerobic bacteria and yeasts were associated with higher acetaldehyde production. Increased local microbial salivary acetaldehyde production due to ethanol among smokers and heavy drinkers could be a biological explanation for the observed synergistic carcinogenic action of alcohol and smoking on upper gastrointestinal tract cancer. It offers a new microbiological approach to ethanol-associated carcinogenesis at these anatomic sites.
Assuntos
Acetaldeído/toxicidade , Bactérias/metabolismo , Etanol/efeitos adversos , Fungos/metabolismo , Neoplasias Bucais/etiologia , Saliva/microbiologia , Fumar/efeitos adversos , Acetaldeído/análise , Acetaldeído/metabolismo , Adulto , Idoso , Contagem de Colônia Microbiana , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Saliva/química , Saliva/metabolismoRESUMO
Hereditary gelsolin-related amyloidosis (AGel amyloidosis) is a systemic disorder caused by a G654A or G654T mutation in the gene coding for gelsolin, an actin-modulating protein. Altered platelet shape change has been demonstrated in gelsolin-deficient knock-out mice, but this has not been studied in humans with gelsolin deficiency. We measured platelet shape change, characterized by maximal decrease in light transmission (D) and reaction time (T), and aggregation, associated with stimulation of platelets with different agonists in platelet rich plasma, as well as coagulation factor VIII and ristocetin cofactor activities in 20 patients, 10 healthy sibs and 20 healthy control subjects. Statistically significant alterations of parameters describing platelet shape change (D, T) were observed after stimulation with adenosine diphosphate and collagen in patients when compared to healthy subjects, but not in maximal aggregation responses, platelet counts, coagulation factor VIII or ristocetin cofactor activity levels. Patients had more haemostatic derangements. Our results suggest that, in addition to amyloid deposition, the G654A gelsolin gene defect causes altered gelsolin-mediated cellular mechanisms, which may contribute, e.g., to bleeding tendency in AGel amyloidosis patients.
Assuntos
Amiloidose/sangue , Amiloidose/genética , Plaquetas/patologia , Gelsolina/genética , Mutação Puntual , Adulto , Idoso , Amiloidose/complicações , Animais , Plaquetas/efeitos dos fármacos , Estudos de Casos e Controles , Tamanho Celular , Colágeno/farmacologia , Fator VIII/metabolismo , Feminino , Hemorragia/sangue , Hemorragia/etiologia , Hemorragia/genética , Humanos , Técnicas In Vitro , Masculino , Camundongos , Pessoa de Meia-Idade , Agregação Plaquetária , Fator de von Willebrand/metabolismoRESUMO
Muscle-eye-brain disease belongs to congenital muscular dystrophies with central nervous system abnormalities. The etiology of MEB is still unknown, but abnormal immunoreactivity for laminin-2 has been reported. To evaluate disease progression in muscle tissue, 32 biopsy specimens from 17 muscle-eye-brain patients were analysed. The samples of four patients were studied by immunohistochemical techniques and by quantitative Western blotting. The samples showed a great variation in the muscle pathology. Regenerative fibers and mild fiber size variation were present in over 60%. At infancy, necrotic and regenerative fibers were common, while fat infiltration was the most prominent finding in the age group over five years. In quantitative studies, the amount of laminin alpha 2 chain was clearly reduced to 10-20% of normal. In contrast, laminin beta 2 chain was overexpressed in the Western blotting studies. These findings may reflect a yet unidentified primary disturbance in the basement membrane composition and function.
Assuntos
Proteínas do Citoesqueleto/metabolismo , Proteínas de Membrana/metabolismo , Músculos/metabolismo , Músculos/patologia , Distrofias Musculares/metabolismo , Distrofias Musculares/patologia , Adolescente , Adulto , Idoso , Western Blotting , Distroglicanas , Distrofina/metabolismo , Feminino , Humanos , Imuno-Histoquímica , Laminina/metabolismo , Masculino , Glicoproteínas de Membrana/metabolismo , Pessoa de Meia-Idade , Distrofias Musculares/congênitoRESUMO
BACKGROUND: Many human colonic facultative anaerobic and aerobic bacteria are capable of alcohol dehydrogenase (ADH)-mediated ethanol oxidation. In this bacteriocolonic pathway for ethanol oxidation intracolonic ethanol is first oxidized by bacterial ADHs to acetaldehyde, which is further oxidized by either colonic mucosal or bacterial aldehyde dehydrogenases to acetate. The produced acetaldehyde is a highly toxic and carcinogenic agent. This study was aimed to investigate the ethanol oxidation capability and acetaldehyde formation of Escherichia coli IH 50546 and IH 50817. These intestinal E. coli strains expressed either high (IH 50546) or low (IH 50817) ADH activity. METHODS: Strains were cultured for 48 h on agar plates supplemented with ethanol under aerobic, microaerobic (6% O2), and anaerobic conditions. RESULTS: Under aerobic conditions both E. coli strains oxidized ethanol. The ethanol consumption rates (ECR) were 1.046+/-0.025 mM/h and 0.367+/-0.148 mM/h with IH 50546 and IH 50817, respectively. In the case of IH 50546 this was associated with significant acetaldehyde production (418+/-13 microM), suggesting ADH-mediated ethanol oxidation. Under microaerobic conditions only IH 50546 was able to oxidize ethanol (ECR, 0.498+/-0.074 mM/h) and to produce acetaldehyde (up to 440+/-76 microM) to significant extents. Under anaerobic conditions both strains fermented glucose to ethanol. CONCLUSIONS: This study experimentally shows the potential of certain bacteria representing normal human colonic flora to produce acetaldehyde under various atmospheric conditions that may prevail in different parts of the GI tract. This bacterial adaptation may be an essential feature of the bacteriocolonic pathway to produce toxic and carcinogenic acetaldehyde from either endogenous or exogenous ethanol.
Assuntos
Acetaldeído/metabolismo , Álcool Desidrogenase/metabolismo , Enterobacteriaceae/enzimologia , Escherichia coli/enzimologia , Etanol/metabolismo , Oxirredução , Bactérias Aeróbias/enzimologia , Bactérias Aeróbias/fisiologia , Bactérias Anaeróbias/enzimologia , Bactérias Anaeróbias/fisiologia , Fermentação/fisiologia , Humanos , Mucosa Intestinal/microbiologia , Mucosa Intestinal/fisiologiaRESUMO
BACKGROUND: Acetaldehyde, the first metabolite of alcohol, has been proposed to be the carcinogenic substance behind ethanol-related oral cancers. High levels of acetaldehyde are formed from ethanol in saliva by the oral flora, but so far the role of certain microbial species responsible for this phenomenon is not known. Yeasts are common commensals of the oral cavity that have alcohol-oxidizing enzymes, thus providing a potential source of acetaldehyde from ethanol. The aim of this study was to examine the contribution of oral yeasts to the production of ethanol-derived acetaldehyde in the oral cavity. METHODS: Fifty-five saliva samples were divided into two groups, high and low, based on the in vitro salivary acetaldehyde production capacity from ethanol. Yeasts were isolated and identified from these samples, and their acetaldehyde production capacity was determined gas chromatographically by incubating intact cells with ethanol at the physiological pH of 7.4. RESULTS: Yeast colonization was found in 78% of the high acetaldehyde-producing salivas, compared with 47% in the low acetaldehyde-producing salivas (p = 0.026). Among carriers, the density of yeasts was higher in the high than in low acetaldehyde producers (p = 0.025). Candida albicans was the main species isolated (88% of all oral isolates). Moreover, C. albicans strains isolated from the high acetaldehyde-producing salivas formed significantly higher acetaldehyde levels from ethanol than C. albicans strains from low-acetaldehyde-producing salivas (73.1 nmol ach/10e6 colony-forming units vs. 43.2 nmol ach/10e6 colony-forming units, p = 0.035). CONCLUSIONS: This study shows that some C. albicans strains have a marked capacity to produce toxic and carcinogenic acetaldehyde from ethanol in vitro. Because the in vitro production of salivary acetaldehyde has been previously shown to correlate with in vivo acetaldehyde production, our finding could be an important microbial pathogenetic factor underlying cancer of the oral cavity associated with ethanol drinking.
Assuntos
Acetaldeído/metabolismo , Candida albicans/metabolismo , Etanol/metabolismo , Saliva/metabolismo , Consumo de Bebidas Alcoólicas/efeitos adversos , Consumo de Bebidas Alcoólicas/metabolismo , Humanos , Neoplasias Bucais/metabolismo , Neoplasias Bucais/microbiologia , Fumar/efeitos adversos , Fumar/metabolismoRESUMO
OBJECTIVES: The aim of the study was to evaluate the biochemical causes of recurrent rhabdomyolysis in Finland. MATERIAL AND METHODS: We examined 22 patients with recurrent rhabdomyolysis, and 26 patients with one episode of rhabdomyolysis or other symptoms compatible with metabolic myopathy. Muscle histopathology and activities of phosphorylase (PHRL) (total and active), phosphofructokinase (PFK), carnitine palmitoyltransferase (CPT) and myoadenylate deaminase (MAD) were studied. The limit of enzyme deficiency was defined as enzyme activity less than 5% of the mean of the control subjects. RESULTS: We found 4 patients with muscle PHRL deficiency, 1 patient with PFK deficiency and 1 patient with evidence of phosphorylase kinase deficiency. One patient had Becker's muscle dystrophy, 2 patients had unspecified dystrophies, 1 patient had Miyoshi myopathy, and 1 patient had a form of mitochondrial encephalomyopathy (MELAS). CONCLUSION: Enzyme defects were found in 23% of the patients with recurrent rhabdomyolysis. Other muscle diseases, muscular dystrophies or myopathies, were detected in 18% of these patients, emphasizing the value of clinical and histopathological examination of patients with previous rhabdomyolysis.
Assuntos
Músculo Esquelético/enzimologia , Rabdomiólise/enzimologia , AMP Desaminase/biossíntese , Adolescente , Adulto , Biópsia , Carnitina O-Palmitoiltransferase/biossíntese , Carnitina O-Palmitoiltransferase/deficiência , Creatina Quinase/sangue , Exercício Físico/fisiologia , Teste de Esforço , Feminino , Antebraço/irrigação sanguínea , Humanos , Isquemia/sangue , Isquemia/diagnóstico , Masculino , Pessoa de Meia-Idade , Músculo Esquelético/patologia , Fosfofrutoquinase-1/biossíntese , Fosforilase Quinase/biossíntese , Fosforilase Quinase/deficiência , Fosforilases/biossíntese , Fosforilases/deficiência , Recidiva , Rabdomiólise/etiologia , Rabdomiólise/patologiaRESUMO
Ingested ethanol is transported to the colon via blood circulation, and intracolonic ethanol levels are equal to those of the blood ethanol levels. In the large intestine, ethanol is oxidized by colonic bacteria, and this can lead to extraordinarily high acetaldehyde levels that might be responsible, in part, for ethanol-associated carcinogenicity and gastrointestinal symptoms. It is believed that bacterial acetaldehyde formation is mediated via microbial alcohol dehydrogenases (ADHs). However, almost all cytochrome-containing aerobic and facultative anaerobic bacteria possess catalase activity, and catalase can, in the presence of hydrogen peroxide (H2O2), use several alcohols (e.g., ethanol) as substrates and convert them to their corresponding aldehydes. In this study we demonstrate acetaldehyde production from ethanol in vitro by colonic contents in a reaction catalyzed by both bacterial ADH and catalase. The amount of acetaldehyde produced by the human colonic contents was proportional to the ethanol concentration, the amount of colonic contents, and the length of incubation time, even in the absence of added nicotinamide adenine dinucleotide or H2O2. The catalase inhibitors sodium azide and 3-amino-1,2,4-triazole (3-AT) markedly reduced the amount of acetaldehyde produced from 22 mM ethanol in a concentration dependent manner compared with the control samples (0.1 mM sodium azide to 73% and 10 mM 3-AT to 67% of control). H2O2 generating system [beta-D(+)-glucose + glucose oxidase] and nicotinamide adenine dinucleotide induced acetaldehyde formation up to 6- and 5-fold, respectively, and together these increased acetaldehyde formation up to 11-fold. The mean supernatant catalase activity was 0.53+/-0.1 micromol/min/mg protein after the addition of 10 mM H2O2, and there was a significant (p < 0.05) correlation between catalase activity and acetaldehyde production after the addition of the hydrogen peroxide generating system. Our results demonstrate that colonic contents possess catalase activity, which probably is of bacterial origin, and indicate that in addition to ADH, part of the acetaldehyde produced in the large intestine during ethanol metabolism can be catalase dependent.