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1.
Toxicol Appl Pharmacol ; 330: 1-8, 2017 09 01.
Article in English | MEDLINE | ID: mdl-28673684

ABSTRACT

Non-alcoholic steatohepatitis (NASH) is a form of non-alcoholic fatty liver disease (NAFLD) characterized by steatosis, inflammation, and fibrosis often associated with metabolic syndrome. Fibroblast growth factor 15 (FGF15), an endocrine factor mainly produced in the distal part of small intestine, has emerged to be a critical factor in regulating bile acid homeostasis, energy metabolism, and liver regeneration. We hypothesized that FGF15 alters the development of each of the listed features of NASH. To test this hypothesis, four-week old male Fgf15-/- and their corresponding wild-type (WT) mice were fed either a high fat diet (HFD) or a control chow diet for six months. The results confirmed that HFD feeding for six months in WT mice recapitulated human NASH phenotype, including macrovesicular steatosis, inflammation, and fibrosis. Whereas FGF15 deficiency had no effect on the severity of liver steatosis or inflammation, it was associated with decreased liver fibrosis. Furthermore, FGF15 deficiency resulted in abnormal bile acid homeostasis, increased insulin resistance, increased HFD-induced serum triglycerides, decreased inductions of hepatic cholesterol content by HFD, and altered gene expression of lipid metabolic enzymes. These data suggest that FGF15 improves lipid homeostasis and reduces bile acid synthesis, but promotes fibrosis during the development of NASH.


Subject(s)
Diet, High-Fat/adverse effects , Fibroblast Growth Factors/deficiency , Non-alcoholic Fatty Liver Disease/pathology , Animals , Bile Acids and Salts/metabolism , Cholesterol/metabolism , Hepatitis/pathology , Homeostasis/genetics , Insulin Resistance , Liver/metabolism , Liver Cirrhosis/pathology , Male , Mice , Mice, Inbred C57BL , Mice, Knockout , Non-alcoholic Fatty Liver Disease/etiology , Triglycerides/blood
3.
Appl Microbiol Biotechnol ; 52(1): 85-90, 1999 Jul.
Article in English | MEDLINE | ID: mdl-10461374

ABSTRACT

The present work describes investigations on the bacterial degradation of the alicyclic molecule cyclododecane. It represents a structure where the initial degradative steps have to be similar to a "subterminal" attack as there is no "terminal" part of the molecule. We were able to show that the gram-positive bacterium Rhodococcus ruber CD4 DSM 44394 oxidizes cyclododecane to the corresponding alcohol and ketone, the latter being subject to ring fission by a Baeyer-Villiger oxygenase. This key enzyme is an NADPH- and O2-dependent flavoprotein with a substrate specificity for bigger rings. The further metabolism of the resulting lactone gives rise to an omega-hydroxyalkanoic acid that is susceptible to common beta-oxidation. Due to its alicyclic character and its ring size, cyclododecane is comparable to aliphatic bridge components that are an important element in the coal texture. They contribute to the three-dimensional coal structure and thus could serve as a valuable target for the oxidative abilities of R. ruber CD4 to reduce the molecular mass of coal.


Subject(s)
Hydrocarbons, Alicyclic/metabolism , Rhodococcus/metabolism , Biodegradation, Environmental , Hydrocarbons, Alicyclic/chemistry , Oxidation-Reduction , Oxygenases/metabolism , Rhodococcus/enzymology , Rhodococcus/growth & development
4.
Scand J Infect Dis ; 31(6): 539-42, 1999.
Article in English | MEDLINE | ID: mdl-10680981

ABSTRACT

This study includes 80 patients (38 children and 42 adults) who contracted aseptic meningitis in the summer of 1996 in Fribourg, Switzerland. Virological studies revealed an enteroviral infection in 65 out of 70 (93%) investigated patients. In 47 out of the 53 cases (89%) where a precise virus could be identified, the causative agent was an Echovirus 30. More than 50 patients lived in an area within a 5-km radius. The patients presented with the classic symptoms and signs of aseptic meningitis. In contrast, polymorphonuclear leukocytes predominated in the cerebrospinal fluid in the first 24 h and 32% of the cases had a left shift in their peripheral blood smear. The patients' age did not influence white blood cell count, the proportion of polymorphonuclear leukocytes or protein concentration in the cerebrospinal fluid. Thirty-three patients (41%) received antibiotic treatment, and 38 patients (48%) left the hospital within 24 h. Only 2 neuroradiological procedures and 1 electroencephalographic recording were performed. The outcome was favourable in all patients.


Subject(s)
Disease Outbreaks , Echovirus Infections/epidemiology , Meningitis, Viral/epidemiology , Adolescent , Adult , Child , Child, Preschool , Echovirus Infections/drug therapy , Echovirus Infections/virology , Female , Humans , Infant , Infant, Newborn , Length of Stay , Leukocyte Count , Male , Meningitis, Viral/drug therapy , Meningitis, Viral/virology , Middle Aged , Switzerland/epidemiology
5.
J Clin Microbiol ; 36(9): 2408-12, 1998 Sep.
Article in English | MEDLINE | ID: mdl-9705364

ABSTRACT

Enteroviruses (EV) are among the most common causes of aseptic meningitis. Standard diagnostic techniques are often too slow and lack sensitivity to be of clinical relevance. EV RNA can be detected within 5 h by a commercially available reverse transcription-PCR (RT-PCR) test kit. Cerebrospinal fluid (CSF) samples from 68 patients presenting with aseptic meningitis during a summer outbreak in Switzerland were examined in parallel with cell culture and commercial RT-PCR. RT-PCR was positive in all 16 CSF specimens positive by cell culture (100%). In addition, 42 of 52 (80%) CSF samples negative by cell culture were PCR positive. In 26 of these 42 (62%) patients, viral culture from other sites (throat swab or stool) was also positive. The CSF virus culture took 3 to 7 days to become positive. Echovirus 30 was the type most often isolated in this outbreak. The sensitivity of CSF RT-PCR based on clinical diagnosis during this aseptic meningitis outbreak in patients with negative bacterial culture results was 85%, i.e., considerably higher than the sensitivity of CSF virus culture (24%). We conclude that this commercial RT-PCR assay allows a positive diagnosis with minimal delay and may thus influence clinical decisions.


Subject(s)
Disease Outbreaks , Enterovirus Infections/cerebrospinal fluid , Enterovirus Infections/virology , Enterovirus/isolation & purification , Meningitis, Viral/cerebrospinal fluid , Meningitis, Viral/virology , Adolescent , Adult , Child , Child, Preschool , Enterovirus Infections/epidemiology , Female , Humans , Infant , Male , Meningitis, Viral/epidemiology , Polymerase Chain Reaction/methods , Switzerland
6.
Praxis (Bern 1994) ; 85(16): 517-9, 1996 Apr 16.
Article in French | MEDLINE | ID: mdl-8657995

ABSTRACT

A patient presenting with acute left-knee arthritis was diagnosed as having articular chondrocalcinosis. Routine laboratory tests motivated by a history of muscular cramps and weakness revealed hypokalemia and hypomagnesemia. Further investigations showed Bartter's syndrome. The characteristics of Bartter's syndrome and chondrocalcinosis and the relationship between the two diseases are developed.


Subject(s)
Bartter Syndrome/complications , Chondrocalcinosis/etiology , Knee Joint , Adult , Bartter Syndrome/diagnosis , Humans , Hypokalemia/etiology , Magnesium Deficiency/etiology , Male , Muscle Cramp/etiology
7.
J Rheumatol ; 20(3): 510-1, 1993 Mar.
Article in English | MEDLINE | ID: mdl-8478860

ABSTRACT

The term "iliopsoas sign" has different meanings in the medical literature. Among musculoskeletal disorders, iliopsoas bursitis is probably the most common cause of this clinical sign. Here we report an unexpected vascular pathology in a young man. The only clinical manifestation on examination was an iliopsoas sign.


Subject(s)
Posture/physiology , Psoas Muscles/physiopathology , Adult , Bursitis/complications , Bursitis/diagnosis , Bursitis/physiopathology , Diagnosis, Differential , Humans , Male
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