Characteristics of heart failure with a preserved ejection fraction in black South African patients.

Background: Heart failure with a preserved ejection fraction (HFpEF) is common in the elderly (≥75 years) and associated with arterial stiffness. The mean age of HFpEF presentation is lower (40-55 years) in sub-Saharan Africa. No clinical study has been conducted on HFpEF in identifying and characterising this phenotype at a younger age, moreover in a South African black population where the risk of HFpEF is two times higher than in other ethnic groups. This study investigated the characteristics of HFpEF in a black South African population, the biochemical markers that predict HFpEF and cardiac structural changes in this HF phenotype. Methods: Sixty-six participants with HFpEF and 213 controls were enrolled. All participants gave informed consent and completed a standardised questionnaire. Echocardiographic, anthropometric, central haemodynamic measurements, pulse wave velocity (PWV) and biomarker analysis were done. Results: The mean age of HFpEF participants was 54.88 ± 13.51 years. Most of the participants (76 %) were between 20 and 64 years, while only 24 % were older. HFpEF participants were hypertensive, and more obese with increased incidence of alcohol consumption. PWV was increased in HFpEF (9.97 ± 2.78 m/s) when compared to participants without HFpEF (6.11 ± 2.18 m/s), p < 0.0001. There were no significant associations between central haemodynamic parameters, N-terminal pro B-type natriuretic peptide (NT-proBNP) (p = 0.9746), and galectin-3 (p = 0.2166). NT-proBNP, but not galectin-3, was associated with left ventricular hypertrophy (p = 0.0002) and left atrial diameter (p = 0.0005). Conclusion: HFpEF in South Africa is predominant in obese young to middle-age individuals with arterial stiffness and who consume alcohol regularly. NT-proBNP could be used to diagnose HFpEF, however, should be interpreted with caution in populations with a high prevalence of obesity.

Treatment-specific risk of subsequent malignant neoplasms in five-year survivors of diffuse large B-cell lymphoma.

BACKGROUND: The introduction of rituximab significantly improved the prognosis of diffuse large B-cell lymphoma (DLBCL), emphasizing the importance of evaluating the long-term consequences of exposure to radiotherapy, alkylating agents and anthracycline-containing (immuno)chemotherapy among DLBCL survivors. METHODS: Long-term risk of subsequent malignant neoplasms (SMNs) was examined in a multicenter cohort comprising 2373 5-year DLBCL survivors treated at ages 15-61 years in 1989-2012. Observed SMN numbers were compared with expected cancer incidence to estimate standardized incidence ratios (SIRs) and absolute excess risks (AERs/10 000 person-years). Treatment-specific risks were assessed using multivariable Cox regression. RESULTS: After a median follow-up of 13.8 years, 321 survivors developed one or more SMNs (SIR 1.5, 95% CI 1.3-1.8, AER 51.8). SIRs remained increased for at least 20 years after first-line treatment (SIR ≥20-year follow-up 1.5, 95% CI 1.0-2.2, AER 81.8) and were highest among patients ≤40 years at first DLBCL treatment (SIR 2.7, 95% CI 2.0-3.5). Lung (SIR 2.0, 95% CI 1.5-2.7, AER 13.4) and gastrointestinal cancers (SIR 1.5, 95% CI 1.2-2.0, AER 11.8) accounted for the largest excess risks. Treatment with >4500 mg/m2 cyclophosphamide/>300 mg/m2 doxorubicin versus ≤2250 mg/m2/≤150 mg/m2, respectively, was associated with increased solid SMN risk (hazard ratio 1.5, 95% CI 1.0-2.2). Survivors who received rituximab had a lower risk of subdiaphragmatic solid SMNs (hazard ratio 0.5, 95% CI 0.3-1.0) compared with survivors who did not receive rituximab. CONCLUSION: Five-year DLBCL survivors have an increased risk of SMNs. Risks were higher for survivors ≤40 years at first treatment and survivors treated with >4500 mg/m2 cyclophosphamide/>300 mg/m2 doxorubicin, and may be lower for survivors treated in the rituximab era, emphasizing the need for studies with longer follow-up for rituximab-treated patients.

A comparative study of ochratoxin A-induced apoptosis in hamster kidney and HeLa cells.

Ochratoxin A (OA), produced by strains of Aspergillus and Penicillium, at a dose of 20 micrograms/ml caused nuclear and nucleolar changes characteristic of apoptosis in hamster kidney (HaK) and HeLa cells. However, the morphological and biochemical lesions were not identical in the two cell types. In HaK cells micronuclei formation in prophase and interphase cells predominated but in HeLa cells apoptotic body formation was more prevalent. Indirect immunofluorescence indicated that nucleolar morphology was affected in both cell types with segregation of the fibrillar and granular components of the nucleolus present after 24 hr exposure. [35S]Methionine incorporation into SDS-PAGE-separated proteins was decreased after continuous exposure for 24 hr, but after only 3 hr exposure, the synthesis of three proteins was markedly increased in HaK (approximately 39, 90, and 180 kDa) and HeLa (approximately 40, 92, and 150 kDa) cells. Enhanced early synthesis of proteins was more pronounced in HaK cells in the G1-phase and in HeLa cells in the S-phase. Internucleosomal DNA breaks, characteristic of apoptosis, were present in G1 and S-phase HaK cells exposed to OA. In contrast, DNA of very high molecular weight was seen in synchronized HeLa cells. The results indicate that OA may activate different cellular processes involved in the degradation of DNA in HaK and HeLa cells.

Purification and characterization of a novel heparinase.

A unique heparinase was isolated from a recently discovered Gram-negative soil bacterium. The enzyme (heparinase III) was purified by hydroxylapatite chromatography, chromatofocusing, and gel permeation chromatography. The enrichment was 48x, and the specific activity of catalytically pure heparinase was 127 IU/mg of protein. Similar to the heparinase I from Flavobacterium heparinum, heparinase III also degrades heparin to mainly disaccharide fragments. It is specific for heparin and also breaks down heparan sulfate, but not hyaluronic acid and chondroitin sulfate. Heparinase III, however, differs markedly from heparinase I in several other aspects: it has a higher molecular mass (94 versus 43 kDa), pI (9.2 versus 8.5), its Km and kcat are different, and it has a higher energy of activation (15.6 versus 6.3 kcal/mol). Optimal activity was also found at higher pH (7.6 versus 6.5) and temperature (45 versus 37 degrees C). Furthermore, the amino acid composition of heparinase III is quite different from that of heparinase I.