Evaluating pyrene toxicity on Arctic key copepod species Calanus hyperboreus

Calanus hyperboreus is a key species in the Arctic regions because of its abundance and role in the Arctic food web. Exploitation of the off shore oil reserves along Western Greenland is expected in the near future, and it is important to evaluate the acute and chronic effects of oil emissions to the ecosystem. In this study C. hyperboreus females were exposed to concentrations of 0, 0.1, 1, 10 and 100 nM pyrene and saturated concentrations measured to ~300 nM. Daily quantification of egg and faecal pellet production showed significant decreases in the pellet production, while the egg production was unaffected. The hatching success was also unaffected, although the total reproductive output was reduced with increased pyrene concentrations. Accumulation of pyrene in the copepods was higher in feeding than starving females and only trace amounts of the phase I metabolite 1-hydroxypyrene, were found. Lowered reproductive output, reduced grazing, and reduced ability to metabolize pyrene suggest that oil contamination may constitute a risk to C. hyperboreus recruitment, energy transfer in the food web and transfer of pyrene to higher trophic levels.     

Endothelial Cell Death and Intimal Foam Cell Accumulation in the Coronary Artery of Infected Hypercholesterolemic Minipigs

Apoptosis of endothelial cells (ECs) has been suggested to play a role in atherosclerosis. We studied the synergism of hypercholesterolemia with Chlamydia pneumoniae and influenza virus infections on EC morphology and intimal changes in a minipig model. The coronary artery was excised at euthanasia (19 weeks of age) and serial sections were processed for the detection of EC apoptosis, histology, and transmission electron microscopy (TEM) studies. There was a significantly higher number of TUNEL-positive ECs in infected compared to noninfected groups [0.2942 % (interquartile ranges (IR), 0.2941; n?=?26) versus 0 % (IR, 0; n?=?12), p?<?0.01]. Caspase-3 staining was negative. Cholesterol diet together with infections induced widening of the subendothelial space and appearance of increased numbers of foam cells. TEM revealed degenerative changes in cytoplasmic organelles and signs of EC necrosis. In conclusion, infection leads to an increase in coronary EC death and seems to exacerbate cholesterol-induced intimal thickening and foam cell accumulation.     

Serum concentrations of Anti-Müllerian Hormone (AMH) in 95 patients with Klinefelter syndrome with or without cryptorchidism

Aim: Anti‐Müllerian hormone (AMH) is produced by foetal Sertoli cells at the time of sexual differentiation and is responsible for the regression of the Müllerian ducts in the male foetus. AMH is a testis‐specific marker of diagnostic value in infants with ambiguous genitalia or with bilateral cryptorchidism. However, little is known about AMH in boys and adult men with normal or abnormal gonadal function. We therefore aimed at determining circulating AMH concentrations in patients with 47,XXY Klinefelter syndrome (KS) with or without cryptorchidism. Methods: AMH was determined in 95 47,XXY patients aged 0.2–64.5 years, of which 12 patients had a history of cryptorchidism. Results: AMH was within the normal range in boys with Klinefelter syndrome until puberty. The pubertal decline was delayed, especially in patients with a history of cryptorchidism. AMH was below ?2 SD in 85% of adult KS. Conclusion: AMH secretion in patients with 47,XXY KS was within normal limits during mini‐puberty and until puberty. Thereafter, AMH declined to subnormal levels in all patients. We hypothesize that this decline was a result of the hyalinization of seminiferous tubules in relation to puberty, rather than caused by disrupted regulatory mechanisms at the level of the pituitary–gonadal axis.     

A randomized,comparative pilot study of azithromycin versus benzathine penicillin G for treatment of early syphilis

BACKGROUND: Penicillin is the only medication currently recommended for treatment of early syphilis in non-penicillin-allergic patients. Preliminary data suggest that azithromycin may be effective for syphilis therapy. STUDY DESIGN: This was a randomized, comparative pilot study of intramuscular injections of benzathine penicillin G and two oral azithromycin regimens for treatment of syphilis. METHODS: We randomly assigned patients with early syphilis to treatment with either intramuscular injections of 2.4 million units of benzathine penicillin G or azithromycin administered orally, either as a single 2.0-g dose or as two 2.0-g doses given 1 week apart. Serological response to therapy was evaluated at 3, 6, 9, and 12 months following therapy. Participants whose rapid plasma reagin (RPR) test became nonreactive or whose RPR titer decreased > or =2 dilutions were classified as responding to therapy. When serological tests did not show a response to therapy, the treatment was classified as a failure if RPR titers increased > or =2 dilutions. Nonresponders were those whose serologic titers remained within +/-1 dilution of the initial RPR titer. RESULTS: Cumulative response rates were as follows: benzathine penicillin G, 86% (12 of 14); azithromycin, 2.0-g single dose, 94% (16 of 17); and azithromycin, two 2.0-g doses given 1 week apart, 83% (24 of 29). Therapy failed for one patient treated with benzathine penicillin and one patient treated with the two-dose azithromycin regimen, whereas in six patients the clinical manifestations of infection resolved but there was no serological response. CONCLUSION: Oral therapy with 2.0 g of azithromycin as a single dose or as two doses 1 week apart is a promising alternative to therapy with benzathine penicillin G for syphilis and should be studied further.     

Determination of NAT2 acetylation status in the Greenlandic population

N-acetyltransferase 2 (NAT2) is a well-studied phase II xenobiotic metabolizing enzyme relevant in drug metabolism and cancerogenesis. NAT2 activity is largely determined by genetic polymorphisms in the coding region of the corresponding gene. We investigated NAT2 acetylation status in 1556 individuals from Greenland based on four different single nucleotide polymorphism (SNP) panels and the tagging SNP rs1495741. There was good concordance between the NAT2 status inferred by the different SNP combinations. Overall, the fraction of slow acetylators was low with 17.5 % and varied depending on the degree of Inuit ancestry; in individuals with <50 % Inuit ancestry, we observed more than 25 % slow acetylators reflecting European ancestry. Greenland has a high incidence of tuberculosis, and individual dosing of isoniazid according to NAT2 status has been shown to improve treatment and reduce side effects. Our findings could be a first step in pharmacogenetics-based tuberculosis therapy in Greenland.     

Monoclonal gammopathy of undetermined significance and risk of venous thromboembolism

Background: Patients with multiple myeloma are at increased risk of venous thromboembolism (VTE), but little information is available on VTE risk in patients with the precursor condition monoclonal gammopathy of undetermined significance (MGUS). Objective: To evaluate the risk of VTE and its impact on mortality in patients with MGUS. Patients and Methods: We identified 1610 patients with MGUS and no prior diagnosis of VTE during the 1978–2005 period in North Jutland County, Denmark. We used the Danish Central Population Registry to select 16 100 general population comparison cohort members with no prior VTE diagnosis, matched with the MGUS patients by age, sex, and comorbidity. Follow‐up data on VTE incidence in the two groups were obtained from the Danish National Patient Registry covering all Danish hospitals. Time‐varying Cox regression analysis was used to compute the incidence rate ratio (IRR) of VTE and the mortality rate ratio (MRR) for MGUS patients who developed VTE compared to MGUS patients without VTE. Results: In the MGUS cohort, 50 VTE events were identified during 12 594 person‐years (PY) of follow‐up, corresponding to an incidence rate of 4.0 VTEs/1000 PY. The IRR for VTE among MGUS patients compared to the comparison cohort was 1.37 (95% confidence interval (CI): 1.00–1.88). Of the 50 MGUS patients with VTE, one was later diagnosed with malignant transformation. The adjusted MRR for MGUS patients with VTE compared to MGUS patients without VTE was 1.94 (95% CI: 1.36–2.77). Conclusions: MGUS is a risk factor for VTE, and VTE is a marker for increased mortality among MGUS patients.     

The JAK2V617F allele burden and STAT3- and STAT5 phosphorylation in myeloproliferative neoplasms: early prefibrotic myelofibrosis compared with essential thrombocythemia, polycythemia vera and myelofibrosis

Early prefibrotic myelofibrosis (early PMF) is a diagnosis that clinically and histologically mimic essential thrombocythemia (ET), but is important to distinguish from ET, polycythemia vera (PV) and primary myelofibrosis (PMF) due to its different prognosis and clinical evolution. In this study, we assessed the allele burden of JAK2V617F in bone marrow biopsies from patients with these chronic myeloproliferative neoplasms. We correlated our findings with the amount of phosphorylated STAT3 (P-STAT3) and STAT5 (P-STAT5) in megakaryocyte nuclei in the bone marrow. The JAK2V617F allele burden was significantly higher in patients with PV (median: 50.99, range: 23.08-97.29, p < 0.01 and p < 0.01) and PMF (median: 44.13, range: 33.61-92.17, p < 0.05 and p < 0.01) compared with a low allele burden in ET (median: 23.465, range: 8.67-47.92) and early PMF (median: 25.68, range: 0.61-49.13) respectively. In addition, we found a significantly higher phosphorylation of STAT5 and STAT3 in the JAK2V617F positive group than in the negative group. There was no positive correlation between increasing JAK2V617F allele burden and the amount of P-STAT3 and P-STAT5. However, we found low values of P-STAT5 in bone marrow biopsies from patients with ETJAK2V617F+ as compared with patients with early PMFJAK2V617F+. Although this difference was statistically significant, larger studies are needed to firmly support this conclusion.