Genetic hyperferritinaemia and reticuloendothelial iron overload associated with a three base pair deletion in the coding region of the ferroportin gene (SLC11A3)

Iron overload may predominantly involve parenchymal or reticuloendothelial cells, the prototype of parenchymal iron overload being HFE-related genetic haemochromatosis. We studied a family with autosomal dominant hyperferritinaemia in whom the proband showed selective iron accumulation in the Kupffer cells on liver biopsy. Analysis of L and H ferritin genes excluded mutations responsible for hereditary hyperferritinaemia/cataract syndrome or similar translational disorders. Sequence analysis of the ferroportin gene (SLC11A3) in four individuals with hyperferritinaemia singled out a three base pair deletion in a region that contains four TTG repeats. This mutation removes a TTG unit from 780 to 791, and predicts the loss of one of three sequential valine residues 160-162. Denaturing high performance liquid chromatography can be used for its detection. SLC11A3 polymorphism analysis indicates that this probably represents a recurrent mutation due to slippage mispairing. Affected individuals may show marginally low serum iron and transferrin saturation, and young women may have marginally low haemoglobin concentration levels. Serum ferritin levels are directly related to age, but are 10-20 times higher than normal. Heterozygosity for the ferroportin Val 162 deletion represents the prototype of selective reticuloendothelial iron overload, and should be taken into account in the differential diagnosis of hereditary or congenital hyperferritinaemias.     

The effect of cannabis on oxidative stress and neurodegeneration induced by intrastriatal rotenone injection in rats

We investigated the effect of cannabis treatment on the development of oxidative stress and nigrostriatal cell injury induced by intrastriatal rotenone injection in rats. Rotenone was injected into the right striatum at a concentration of 5 mM (3 μl/rat). The control rats received the vehicle (DMSO). Subsequently, the effect of Cannabis sativa extract treatment on rotenone toxicity was evaluated. Starting on the second day of rotenone injection, rats were treated with C. sativa extract (5, 10, or 15 mg/kg) (expressed as Δ⁹-tetrahydrocannabinol) subcutaneously (s.c.) once daily for 30 days. Biochemical markers of oxidative stress, malondialdehyde (MDA), reduced glutathione (GSH), nitric oxide, paraoxonase 1 (PON1) activity, catalase activity, as well as tumor necrosis factor alpha (TNF-α), were determined in different brain areas after 30 days of rotenone treatment. Histopathology and immunohistochemical expression of tyrosine hydroxylase (TH), capase 3, and inducible nitric oxide synthase (iNOS) were also performed. Results showed that intrastriatal injection of rotenone resulted in increased brain oxidative stress in the cerebral cortex, striatum, hippocampus, midbrain, and cerebellum. MDA increased by 41.4–70 %, nitric oxide increased by 48.3–77.5 %, while GSH decreased by 25.0–34.2 %. PON1 and catalase activities decreased by 43.0–60.8 % and by 14.2–36 %, respectively, in these areas. Striatal TNF-α increased by 638.9 % of control value after rotenone injection. Rotenone induced motor deficits (decreased rearing activity). Rotenone caused marked nigrostriatal neurodegeneration, decreased TH immunoreactivity, and increased both iNOS and caspase 3 immunoreactivities in the striatum. Cannabis decreased brain oxidative stress and nitric oxide release induced by intrastriatal rotenone in several brain areas. Cannabis also decreased the elevated TNF-α in the striatum. Cannabis did not protect against the immunohistochemical changes in the striatum and substantia nigra or against neuronal degeneration induced by rotenone treatment. Collectively, these results indicated that the administration of cannabis did not protect against nigrostriatal damage caused by intrastriatal rotenone.     

Third-Generation-Cephalosporin-Resistant Klebsiella pneumoniae Isolates from Humans and Companion Animals in Switzerland: Spread of a DHA-Producing Sequence Type 11 Clone in a Veterinary Setting

Characterization of third-generation-cephalosporin-resistant Klebsiella pneumoniae isolates originating mainly from one human hospital (n = 22) and one companion animal hospital (n = 25) in Bern (Switzerland) revealed the absence of epidemiological links between human and animal isolates. Human infections were not associated with the spread of any specific clone, while the majority of animal infections were due to K. pneumoniae sequence type 11 isolates producing plasmidic DHA AmpC. This clonal dissemination within the veterinary hospital emphasizes the need for effective infection control practices.     

The Early Cognitive Development of Children at High Risk of Developing an Eating Disorder

Diagnosis of an eating disorder (ED) has been associated with differences in cognition. Recent evidence suggests that differences may be present prior to onset. Children at familial high risk for ED show cognitive differences at ages 8–10 years. Research is required to investigate differences in cognitive development at various time points. This is the first study to investigate cognitive development in children at high risk at 18 months (Griffiths Mental Development Scale; n = 982) and 4 years old (Wechsler Preschool and Primary Scale of Intelligence—Revised; n = 582), in comparison with children not at risk, using a general population sample, the Avon Longitudinal Study of Parents and Children. Children of women with lifetime anorexia nervosa revealed difficulties in social understanding, visual‐motor function, planning and abstract reasoning. Cognitive differences observed here have also been observed in clinical groups. This suggests difficulties may be present prior to onset, potentially affecting risk status for development of ED. Findings contribute to an understanding of aetiology, and design of prevention/intervention strategies. Copyright © 2013 The Authors. European Eating Disorders Review published by John Wiley & Sons Ltd.     

The Relationship Between Renal Resistive Index,Arterial Stiffness,and Atherosclerotic Burden: The Link Between Macrocirculation and Microcirculation

The renal resistive index (RRI) measured by Doppler sonography is a marker of microvascular status that can be generalized to the whole of the arterial tree. Its association with large‐vessel dysfunction, such as arterial stiffness or the atherosclerotic burden, can help to establish physiopathological associations between macrocirculation and microcirculation. The authors conducted a cross‐sectional study of hypertensive patients (n=202) and a healthy control group (n=16). Stiffness parameters, atherosclerotic burden, and determination of the RRI in both kidneys were performed. The average RRI was 0.69±0.08 and was significantly greater in patients with diabetes and chronic kidney disease. Renal resistive index positively correlated with age, creatinine, and albuminuria. Positive correlations were found with arterial stiffness parameters (pulse wave velocity, ambulatory arterial stiffness index, and 24‐hour pulse pressure), as well as atherosclerotic burden and endothelial dysfunction measured as asymmetric dimethylarginine in serum. In the multivariate analysis, independent factors for increased RRI were age, renal function, 24‐hour diastolic blood pressure, and arterial stiffness. The authors concluded that there is an independent association between renal hemodynamics and arterial stiffness. This, together with the atherosclerotic burden and endothelial dysfunction, suggests that there is a physiopathologic relationship between macrovascular and microvascular impairment.