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1.
Environ Epigenet ; 4(2): dvy011, 2018 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-29992049

RESUMO

Epigenetic modifications, of which DNA methylation is the most stable, are a mechanism conveying environmental information to subsequent generations via parental germ lines. The paternal contribution to adaptive processes in the offspring might be crucial, but has been widely neglected in comparison to the maternal one. To address the paternal impact on the offspring's adaptability to changes in diet composition, we investigated if low protein diet (LPD) in F0 males caused epigenetic alterations in their subsequently sired sons. We therefore fed F0 male Wild guinea pigs with a diet lowered in protein content (LPD) and investigated DNA methylation in sons sired before and after their father's LPD treatment in both, liver and testis tissues. Our results point to a 'heritable epigenetic response' of the sons to the fathers' dietary change. Because we detected methylation changes also in the testis tissue, they are likely to be transmitted to the F2 generation. Gene-network analyses of differentially methylated genes in liver identified main metabolic pathways indicating a metabolic reprogramming ('metabolic shift'). Epigenetic mechanisms, allowing an immediate and inherited adaptation may thus be important for the survival of species in the context of a persistently changing environment, such as climate change.

2.
Aliment Pharmacol Ther ; 42(9): 1037-50, 2015 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-26307025

RESUMO

BACKGROUND: Hiccups are familiar to everyone, but remain poorly understood. Acute hiccups can often be terminated by physical manoeuvres. In contrast, persistent and intractable hiccups that continue for days or months are rare, but can be distressing and difficult to treat. AIM: To review the management of hiccups, including a systematic review of reported efficacy and safety of pharmacological treatments. METHODS: Available articles were identified using three electronic databases in addition to hand searching of published articles. Inclusion criteria were any reports of pharmaceutical therapy of 'hiccup(s)', 'hiccough(s)' or 'singultus' in English or German. RESULTS: Treatment of 341 patients with persistent or intractable hiccups was reported in 15 published studies. Management was most effective when directed at the underlying condition. An empirical trial of anti-reflux therapy may be appropriate. If the underlying cause is not known or not treatable, then a range of pharmacological agents may provide benefit; however, systematic review revealed no adequately powered, well-designed trials of treatment. The use of baclofen and metoclopramide are supported by small randomised, placebo-controlled trials. Observational data suggest that gabapentin and chlorpromazine are also effective. Baclofen and gabapentin are less likely than standard neuroleptic agents to cause side effects during long-term therapy. CONCLUSIONS: This systematic review revealed no high quality data on which to base treatment recommendations. Based on limited efficacy and safety data, baclofen and gabapentin may be considered as first line therapy for persistent and intractable hiccups, with metoclopramide and chlorpromazine in reserve.


Assuntos
Aminas/uso terapêutico , Baclofeno/uso terapêutico , Clorpromazina/uso terapêutico , Ácidos Cicloexanocarboxílicos/uso terapêutico , Soluço/tratamento farmacológico , Soluço/fisiopatologia , Metoclopramida/uso terapêutico , Ácido gama-Aminobutírico/uso terapêutico , Anticonvulsivantes/uso terapêutico , Antipsicóticos/uso terapêutico , Benzamidas/uso terapêutico , Agonistas dos Receptores de GABA-B/uso terapêutico , Gabapentina , Soluço/etiologia , Soluço/terapia , Humanos , Ensaios Clínicos Controlados Aleatórios como Assunto , Resultado do Tratamento
8.
Infection ; 37(4): 370-3, 2009 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-19390780

RESUMO

A 53-year old immunocompetent Swiss female is described who developed severe meningoencephalitis due to infection with Cryptococcus gattii 13 months following exposure on Vancouver Island, Canada. Diagnosis was based on cerebrospinal fluid (CSF) examination, i.e., positive India-ink staining, positive latex particle agglutination, and positive culture. Species identification was performed by growth on L-canavanine-glycine-bromthymol blue medium and by sequencing of the intergenic and internal transcribed spacer regions of the rRNA genes. After initial therapy with fluconazole by which the patient did not improve, therapy was changed to amphotericin B and flucytosine and later to high-dose fluconazole and amphotericin B. Despite long-term treatment and external drainage of the CSF, the patient's condition improved only slowly. The patient was discharged after 132 days of hospitalization.


Assuntos
Criptococose/diagnóstico , Cryptococcus/isolamento & purificação , Meningoencefalite/microbiologia , Anfotericina B/uso terapêutico , Antifúngicos/uso terapêutico , Líquido Cefalorraquidiano/microbiologia , Criptococose/tratamento farmacológico , Criptococose/microbiologia , Criptococose/cirurgia , Cryptococcus/genética , Meios de Cultura/química , DNA Fúngico/química , DNA Fúngico/genética , DNA Espaçador Ribossômico/química , DNA Espaçador Ribossômico/genética , Drenagem , Feminino , Fluconazol/uso terapêutico , Flucitosina/uso terapêutico , Humanos , Meningoencefalite/tratamento farmacológico , Meningoencefalite/cirurgia , Pessoa de Meia-Idade , Dados de Sequência Molecular , Filogenia , Análise de Sequência de DNA , Suíça , Viagem
10.
Infection ; 35(5): 364-6, 2007 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-17721739

RESUMO

We describe a case of cerebral aspergillosis which was successfully treated with a combination of caspofungin and voriconazole. The patient remains in remission 18 months after stopping antifungal treatment. We discuss primary and salvage therapy of invasive aspergillosis with focus on cerebral involvement. Since historical data showed a fatal outcome in most cases, amphotericin B does not cross the blood brain barrier while voriconazole does, we chose a combination of voriconazole plus caspofungin as primary therapy.


Assuntos
Antifúngicos/uso terapêutico , Equinocandinas/uso terapêutico , Encefalite/tratamento farmacológico , Encefalite/microbiologia , Neuroaspergilose/complicações , Neuroaspergilose/tratamento farmacológico , Pirimidinas/uso terapêutico , Triazóis/uso terapêutico , Adulto , Caspofungina , Quimioterapia Combinada , Humanos , Lipopeptídeos , Masculino , Voriconazol
11.
Ultrastruct Pathol ; 30(1): 53-8, 2006.
Artigo em Inglês | MEDLINE | ID: mdl-16517470

RESUMO

Conidiobolus coronatus is a major insect pathogen belonging to the fungal order Entomophthorales, causing a rare subcutaneous infection of the nasofacial region, resulting in swelling of predominantly the nose, mouth, and perinasal tissue. Later in the course of the infection firm, painless, subcutaneous nodules develop that are attached to the underlying tissues but not to the skin. No morphological studies are available in the literature on the morphology of C. coronatus in vivo and all morphological studies have been conducted on in vitro cultures. Here the authors report on the ultrastructural pathology as seen with a scanning electron microscope (SEM) of villous conidia of C. coronatus, detected in a 37-year-old woman who presented to the casualty department at Pretoria Academic Hospital, South Africa with left-sided facial pain and headache. The diagnosis of C. coronatus was confirmed by LightCycler real-time flourescence PCR technique. Research shows that typically diagnosis of the pathogen is established only on histological examination, and in over 85% of cases cultures for the causative organism is negative. This pathogen has not previously been found in a blood sample and the authors present for the first time the morphology of C. coronatus in blood using the SEM.


Assuntos
Sangue/parasitologia , Conidiobolus/isolamento & purificação , Esporos Fúngicos/isolamento & purificação , Zigomicose/diagnóstico , Adulto , Conidiobolus/patogenicidade , Conidiobolus/ultraestrutura , DNA Fúngico/análise , Evolução Fatal , Feminino , Humanos , Microscopia Eletrônica de Varredura/métodos , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Esporos Fúngicos/genética , Esporos Fúngicos/ultraestrutura , Zigomicose/sangue , Zigomicose/genética
12.
QJM ; 97(11): 717-27, 2004 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-15496528

RESUMO

BACKGROUND: The desert horned vipers (Cerastes cerastes and C. gasperettii) are the most familiar snakes of the great deserts of North Africa and the Middle East, including the plains of Iraq. They are responsible for many human snake bites. In Western countries, they are popular among exotic-snake keepers. AIM: To investigate mechanisms of life-threatening envenoming and treatment. DESIGN: Clinical investigation. METHODS: Clinical and laboratory studies with measurement of serum venom antigen concentrations by enzyme immunoassay. RESULTS: Two men bitten while handling captive Saharan horned vipers (Cerastes cerastes) in Europe developed extensive local swelling and life-threatening systemic envenoming, characterized by coagulopathy, increased fibrinolysis, thrombocytopenia, micro-angiopathic haemolytic anaemia and acute renal failure. The clinical picture is explicable by the presence in C. cerastes venom of several thrombin-like, Factor-X-activating, platelet-aggregating, haemorrhagic and nephrotoxic components. In one case, prophylactic use of subcutaneous epinephrine may have contributed to intracranial haemorrhage. The roles in treatment of heparin (rejected) and specific antivenom (recommended) are discussed. DISCUSSION: Cerastes cerastes is capable of life-threatening envenoming in humans. Optimal treatment of envenoming is by early administration of specific antivenom, and avoidance of ineffective and potentially-dangerous ancillary methods.


Assuntos
Injúria Renal Aguda/etiologia , Transtornos da Coagulação Sanguínea/etiologia , Mordeduras de Serpentes/complicações , Viperidae , Adulto , Animais , Antivenenos/uso terapêutico , Hemólise/efeitos dos fármacos , Humanos , Masculino , Pessoa de Meia-Idade , Mordeduras de Serpentes/tratamento farmacológico , Venenos de Víboras/imunologia
13.
Eur J Clin Microbiol Infect Dis ; 22(9): 558-60, 2003 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-12938011

RESUMO

In the study presented here a LightCycler real-time PCR system was used for the diagnosis of fungal infections from clinical tissue samples. Nine specimens were investigated from six patients with suspected or proven invasive fungal infections. Seven of nine samples were positive in a broad-range fungal PCR assay. In four samples, Aspergillus fumigatus was detected both by a species-specific hybridization assay as well as by sequencing of amplification products. In addition, the broad-range fungal PCR assay and PCR sequencing detected and identified, respectively, the following organisms in the specimens noted: Candida albicans in a culture-negative liver biopsy, Histoplasma capsulatum in a bone marrow sample, and Conidiobolus coronatus in a facial soft tissue specimen. Real-time PCR is a promising tool for the diagnosis of invasive fungal infections in human tissue samples and offers some advantages over culture methods, such as rapid analysis and increased sensitivity.


Assuntos
Fungemia/diagnóstico , Fungos/isolamento & purificação , Micoses/diagnóstico , Reação em Cadeia da Polimerase Via Transcriptase Reversa/métodos , Aspergillus fumigatus/isolamento & purificação , Sequência de Bases , Candida albicans/isolamento & purificação , DNA Fúngico/análise , Feminino , Fungemia/microbiologia , Histoplasma/isolamento & purificação , Humanos , Hibridização In Situ , Masculino , Microscopia Eletrônica , Dados de Sequência Molecular , Micoses/microbiologia , Estudos de Amostragem , Sensibilidade e Especificidade , Fatores de Tempo
14.
Dtsch Med Wochenschr ; 128(25-26): 1395-8, 2003 Jun 20.
Artigo em Alemão | MEDLINE | ID: mdl-12813673

RESUMO

HISTORY AND ADMISSION FINDINGS: A 69-year-old man had a history of chronic abdominal pain and intermittent fever for more than 10 years. Due to acute epigastric pain and intermittent fever with night sweat for one week he was admitted for further investigation. On physical examination there was tenderness in the right upper and lower epigastrium without a palpable mass. INVESTIGATIONS: Laboratory figures showed signs of inflammation with a CRP of 103 mg/l. Leucocyte counts were normal without left shift. CT and MRI scans showed a sharp-edged mass of 10 x 8 cm in diameter in the retroperitoneal area with big vessels running through it. Laparoscopic biopsy confirmed the suspected diagnosis of retractile mesenteritis. TREATMENT AND COURSE: Under therapy with oral progesterone (Utrogestan 1 x 100 mg/d) and prednisone (Prednison 1 x 50 mg/d) there was fast symptomatic relief. A CT scan 2 months after initial diagnosis showed clear regression of the tumor. CONCLUSION: Retractile mesenteritis is a rare cause of chronic abdominal pain with variable symptoms. Its aetiology is unknown. In case of bowel ischemia a surgical approach is preferred, milder forms may be treated with immunosuppressive agents as well as oral progesterone. Progesterone has exhibited positive effects on fatty tissue with successful treatment in desmoid tumors and retroperitoneal fibrosis. Here in we could demonstrate its safe and efficient use in a patient with retractile mesenteritis.


Assuntos
Dor Abdominal/etiologia , Anti-Inflamatórios/uso terapêutico , Mesentério , Peritonite/diagnóstico , Prednisona/uso terapêutico , Progesterona/uso terapêutico , Administração Oral , Idoso , Biópsia/métodos , Doença Crônica , Diagnóstico Diferencial , Humanos , Masculino , Mesentério/diagnóstico por imagem , Mesentério/patologia , Peritonite/tratamento farmacológico , Peritonite/patologia , Tomografia Computadorizada por Raios X
15.
Infection ; 31(2): 86-91, 2003 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-12682813

RESUMO

BACKGROUND: DNA of Tropheryma whipplei, the etiologic agent of Whipple's disease, has recently been detected in the saliva of healthy subjects. In this pilot study we searched for the habitat of T. whipplei within the oral cavity. MATERIALS AND METHODS: Samples from different oral sites were obtained from periodontically healthy volunteers, patients with progressive periodontitis and Chinese subjects with necrotizing ulcerative gingivitis or gingivitis. Quantitative real-time PCR was performed using T. whippleispecific primers, human beta-globin-specific primers to control for tissue DNA extraction and PCR reaction and broad-range eubacterial primers to control for bacterial DNA extraction. T. whipplei specificity of multiple amplicons was confirmed by sequencing. The detection limit of the method was 10 ag of T. whipplei DNA, corresponding to one to five bacteria under reference assay conditions. RESULTS: T. whipplei was found in the oral cavity of four out of ten healthy individuals from hospital staff and in three out of nine periodontitis patients, but in none of the individuals from China. All positive samples derived from subgingival and gingival sulcus plaque containing between 10(3) and 5 x 10(5) cells ml(-1) of plaque suspension, whereas saliva, smooth surface plaque and samples from the tongue or cheeks were negative. CONCLUSION: Our results suggest that T. whipplei colonizes the human body via the oral cavity and that bacterial plaques of the gingival crevice and the gingival sulcus/pocket may serve as a natural primary habitat.


Assuntos
Actinomycetales/isolamento & purificação , Placa Dentária/microbiologia , Gengiva/microbiologia , Gengivite/microbiologia , Periodontite/microbiologia , Actinomycetales/genética , Actinomycetales/crescimento & desenvolvimento , Adulto , Estudos de Coortes , DNA Bacteriano/análise , Placa Dentária/epidemiologia , Meio Ambiente , Estudos Epidemiológicos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Reação em Cadeia da Polimerase/métodos , Temperatura
17.
Eur J Clin Pharmacol ; 57(4): 321-6, 2001 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-11549211

RESUMO

This report describes a 57-year-old female patient with chronic lumbago, who died from the sequelae of acute liver failure induced by nimesulide medication. Nimesulide is a non-steroidal anti-inflammatory drug (NSAID) which preferentially inhibits cyclo-oxygenase 2 and has been associated with a total of 13 reported cases of severe liver injury including our case. On the basis of the literature reports, the following features of nimesulide-associated hepatotoxicity were identified: female sex (84% of cases), age (mean age 62 years), jaundice as a primary manifestation (90%) and the absence of peripheral blood eosinophilia. The average duration of therapy of the published cases was 62 days (range 7-180 days). Based on spontaneous reports to the World Health Organization, nimesulide induces a high proportion of severe adverse hepatic reactions compared with other NSAIDs registered in Switzerland. Hepatotoxicity thus represents an important risk factor of nimesulide usage.


Assuntos
Anti-Inflamatórios não Esteroides/efeitos adversos , Doença Hepática Induzida por Substâncias e Drogas/etiologia , Sulfonamidas/efeitos adversos , Doença Hepática Induzida por Substâncias e Drogas/diagnóstico , Evolução Fatal , Feminino , Humanos , Pessoa de Meia-Idade
18.
Dtsch Med Wochenschr ; 126(28-29): 809-11, 2001 Jul 13.
Artigo em Alemão | MEDLINE | ID: mdl-11499262

RESUMO

HISTORY AND ADMISSION FINDINGS: A 23-year-old woman was hospitalized with headache, malaise and somnolence 11 hours after ingestion of A2 (benzylpiperazine), 7 hours after ingestion of ecstasy (MDMA), and large volume of fluids. On admission she had bradycardia (heart rate 48/min), hypertension (blood pressure 154/95 mm Hg), and reduced consciousness with diminished tendon reflexes and non-reacting pupils (Glasgow Coma Score 6). INVESTIGATIONS: Serum sodium was markedly decreased (115 mmol/l [normal 135-145]) with low plasma osmolality (246 mosm/kg [normal 280-300]). Other laboratory findings were within normal limits. TREATMENT AND COURSE: The patient had severe hypervolaemic hypotonic hyponatraemia. 40 minutes after admission she seized twice and was intubated. Brain CT scan showed massive cerebral oedema with beginning tonsillar herniation. Serum sodium concentration returned to normal within 38 hours, but the patient deteriorated neurologically with increasing tonsillar herniation detected in a second brain CT scan. The patient died 57 hours after admission. CONCLUSION: 13 cases of MDMA-associated severe hyponatraemia are reported. Intake of fluids after MDMA ingestion may lead to potentially fatal hypervolaemic hypotonic hyponatraemia with cerebral oedema. Symptoms appear about 8 hours (range 4-18) after MDMA ingestion. Even low doses of MDMA and fluids may lead to a serious outcome. The only risk factor is female gender. Measurement of serum sodium and brain CT scan is recommended in all patients with altered mental status after MDMA consumption.


Assuntos
Edema Encefálico/induzido quimicamente , Alucinógenos/intoxicação , Hiponatremia/induzido quimicamente , N-Metil-3,4-Metilenodioxianfetamina/intoxicação , Piperazinas/intoxicação , Adulto , Evolução Fatal , Feminino , Humanos , Drogas Ilícitas/intoxicação , Fatores de Risco , Fatores Sexuais , Sódio/sangue , Transtornos Relacionados ao Uso de Substâncias/diagnóstico , Transtornos Relacionados ao Uso de Substâncias/mortalidade , Tomografia Computadorizada por Raios X , Intoxicação por Água/induzido quimicamente
20.
Swiss Med Wkly ; 131(5-6): 81-3, 2001 Feb 10.
Artigo em Inglês | MEDLINE | ID: mdl-11383230

RESUMO

Reactive hypoglycaemia is a rare disease which occurs postprandially in everyday life involving blood glucose levels below 2.5 to 2.8 mmol/l. We report on a 66-year-old patient who developed symptomatic reactive hypoglycaemia due to late dumping syndrome 10 years after oesophagectomy with cervical anastomosis. A 75 g sucrose load revealed a plasma glucose level of 9.4 mmol/l after one hour, followed by symptomatic hypoglycaemia with a plasma glucose level of 1.8 mmol/l after three hours. Concomitantly, high concentrations of insulin (3216 pmol/l at a glucose level of 9.4 mmol/l and 335 pmol/l at a glucose level of 1.8 mmol/l) and glucagon-like peptide 1 (GLP-1) (375 pmol/l at a glucose level of 9.4 mmol/l and 85 pmol/l at a glucose level of 1.8 mmol/l) were measured. While the patient was under treatment with acarbose, another sucrose load did not provoke symptomatic hypoglycaemia (plasma glucose nadir of 4.6 mmol/l after two hours). Insulin and GLP-1 levels increased much less, to peak levels of 375 pmol/l and 75 pmol/l respectively, after one hour when plasma glucose was 6.8 mmol/l. We conclude that in patients with reactive hypoglycaemia due to gastrointestinal surgery, acarbose decreases rapid glucose absorption associated with hyperglycaemia and GLP-1 secretion, and thus diminishes excessive insulin release. Acarbose is therefore a successful treatment modality for reactive hypoglycaemia due to late dumping syndrome.


Assuntos
Acarbose/administração & dosagem , Síndrome de Esvaziamento Rápido/tratamento farmacológico , Esofagectomia , Hipoglicemia/tratamento farmacológico , Complicações Pós-Operatórias/tratamento farmacológico , Idoso , Glicemia/metabolismo , Síndrome de Esvaziamento Rápido/complicações , Humanos , Hipoglicemia/etiologia , Masculino , Complicações Pós-Operatórias/etiologia
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