Hemochromatosis gene mutations may affect the survival of patients with myelodysplastic syndrome

Objectives: The recent availability of potent oral iron chelators is renewing an interest in the assessment of the possible impact of HFE genetics in MDS.

Methods: Thirty six newly diagnosed patients with MDS were studied for parameters of iron metabolism in addition to C282Y and H63D mutations of the HFE gene.

Results: Mutations were present in 11 out of 36 patients (31%), which were not different from our general population and were equally distributed among MDS subtypes. Mutated patients had higher ferritin levels (P?=?0.039) and lower TIBC (P?=?0.018). Ferritin was found to be higher for the untransfused mutated patients (P?=?0.017), but not for transfusion-dependent patients in whom ferritin levels correlated significantly with the number of blood units received (P?=?0.04). There was no difference in the number of blood units received between the mutated and wild type patients. A new observation made was that the mutated patients had a lower overall survival in addition to a poorer leukemia free survival (LFS) (P?=?0.004 and P?=?0.003, respectively).

Discussion: The HFE gene mutations are not more frequent in MDS patients. Iron overload in mutated patients was higher but there was no correlation found using supportive therapy for anemia. The effect of mutations on survival could be mediated by changes in iron metabolism.

Conclusion: The HFE genotype may predict MDS prognosis and there is a need for further studies. It remains a challenging question if HFE mutated MDS patients should be considered for potent iron chelation therapy.     

Scaling behaviour of VO2 in athletes and untrained individuals

OBJECTIVE: The present study analysed the allometric relationship (MR = a . M(b)) between human metabolic rate (MR), ranging from resting to maximal metabolic conditions, and body mass (M ), both in athletes of different specialization and untrained individuals. SUBJECTS AND METHODS: Two hundred and seventy male athletes and 43 untrained men performed a continuous incremental test to volitional exhaustion on a motorized treadmill. Metabolic rate (i.e. VO2) was measured during resting (VO2REST), sub-maximal (walking at 5 km h(-1) VO2WALK; running at 7.5 km h(-1) VO2RUN; ventilatory anaerobic threshold VO2VT) and maximal exercise conditions (maximum oxygen uptake VO2MAX). RESULTS: A significant difference (p < 0.001) in the MR-body mass relationships between athletes and controls was found. For the control group, the mass exponent b exhibited a non-significant (p = 0.37) increase with increasing metabolic demand (b = 0.69, 0.76, 0.76, 0.84, and 0.89, for VO2REST, VO2WALK, VO2RUN, VO2VT, and VO2MAX, respectively). In contrast, the corresponding mass exponent for the athletic group significantly (p < 0.01) decreased when moving from resting to maximal metabolic conditions (b = 0.98, 0.88, 0.80, 0.69, and 0.67). CONCLUSION: These results indicate that the recently proposed allometric cascade model may be valid in describing the scaling behaviour of MR in untrained individuals, but not in athletes of different specialization.     

The relevance of multidrug resistance-associated P-glycoprotein expression in the treatment response of B-cell chronic lymphocytic leukemia

BACKGROUND AND OBJECTIVES: The aim of this study was to determine whether expression of P-glycoprotein (Pgp) is an intrinsic feature of B-lymphocytes in B-cell chronic lymphocytic leukemia (B-CLL) and how it correlates with hematologic indices and tumor load in the disease. Furthermore, the change of Pgp expression under cytotoxic treatment and its correlation to treatment outcome were studied. DESIGN AND METHODS: In 42 B-CLL patients, of whom 13 were sequentially monitored, expression of extracellular (MRK-16) and intracellular (C-219) Pgp epitopes on peripheral blood lymphocytes was determined by flow cytometry analysis and quantified by ratio of the mean fluorescence (RMF) in flow cytometry analysis. RESULTS: Median RMF values in B-CLL patients were higher than in age-matched controls. Pgp expression did not correlate with any of the hematologic features or clinical stage of the disease. Patients who received some type of cytoreductive treatment prior to the study had lower Pgp values for both measured epitopes (median RMF for C-219 and MRK-16 of 1.99 and 2.03 in comparison to those of non-treated patients: 3.11 and 2.88, respectively). In 13 patients monitored during treatment the decrease in RMF was noted after treatment with chlorambucil, with RMF values for both Pgp epitopes decreasing in responders. This was in contrast to unchanged or even increased RMF values in those patients who did not respond to therapy. INTERPRETATION AND CONCLUSIONS: Our study confirms the importance of quantitative evaluation of Pgp expression by flow cytometry. At the clinical level, cross-sectional, single test evaluation of Pgp is of limited value whereas sequential follow-up values correlate with treatment response.     

Binding of cystatin C to Alzheimer's amyloid beta inhibits in vitro amyloid fibril formation

The colocalization of cystatin C, an inhibitor of cysteine proteases, with amyloid beta (Abeta) in parenchymal and vascular amyloid deposits in brains of Alzheimer's disease (AD) patients may reflect cystatin C involvement in amyloidogenesis. We therefore sought to determine the association of cystatin C with Abeta. Immunofluorescence analysis of transfected cultured cells demonstrated colocalization of cystatin C and beta amyloid precursor protein (betaAPP) intracellularly and on the cell surface. Western blot analysis of immunoprecipitated cell lysate or medium proteins revealed binding of cystatin C to full-length betaAPP and to secreted betaAPP (sbetaAPP). Deletion mutants of betaAPP localized the cystatin C binding site within betaAPP to the Abeta region. Cystatin C association with betaAPP resulted in increased sbetaAPP but did not affect levels of secreted Abeta. Analysis of the association of cystatin C and Abeta demonstrated a specific, saturable and high affinity binding between cystatin C and both Abeta(1-42) and Abeta(1-40). Notably, cystatin C association with Abeta results in a concentration-dependent inhibition of Abeta fibril formation.     

The effect of delayed anti-NMDAR encephalitis recognition on disease outcome

Anti-NMDA receptor encephalitis is an acute form of brain inflammation that is potentially lethal but has a high probability for recovery with treatment. Although the clinical picture of anti-NMDAR encephalitis is usually recognizable due to its relatively well-known symptoms, the disorder can sometimes present itself in an unpredictable and atypical way. In this case report, we wish to present the influence of different delay times prior to the establishment of diagnosis. Thus, our first patient was diagnosed with anti-NMDAR encephalitis 4 years after the initial symptoms, the second one after 8 years, and the third one after 13 months. The outcomes of the three presented patients indicate the importance of being aware of many clinical presentations of this disorder, as its early diagnosis greatly affects the outcome and may reduce permanent damage, especially in cognitive functions.     

The Effect of Tobacco Use on Oral Health and Dental Readiness in the Croatian Army

ABSTRACT

This study examined tobacco use as a risk factor in the development of periodontal disease as dental emergency and dental readiness among soldiers. A total of 884 soldiers were followed: 650 recruits and 234 professional active veterans. They were categorized into dental readiness classes, and questionnaires were completed about tobacco use. Overall, 62.7% of soldiers reported current smoking, with a higher prevalence of smokers among recruits. The results showed a significant difference in smokers vs. non-smokers in dental readiness, supragingival/subgingival calculus, gingivitis, and Class 3 dental fittnes. More recruits (63.8%) smoked than veterans (59.4%), but greater prevalence of daily cigarette smoking and duration of smoking habits was found among veterans. In both groups, soldiers who smoked were characterized by a higher percentage of periodontal health problems and decreased combat readiness compared to soldiers who did not smoke. This indicates a need for oral health prevention program, and cigarette smoking and cessation programs.