Effects of ERalpha overexpression on female reproduction in mice

Recently, we generated transgenic mice in which ERalpha can be inducibly overexpressed in reproductive tissues (ERalpha overexpressors). These mice were used to test the hypothesis that prenatal and postnatal ERalpha overexpression reduces female fertility. To do so, litter sizes, ovulation, follicle numbers, uterine histology, implantation sites, and hormone levels were compared in ERalpha overexpressors and controls. The data indicate that ERalpha overexpressors have reduced fertility compared to controls and that the reduced fertility is not due to reduced ovulatory capacity, altered levels of estradiol, FSH, and LH, or impaired follicular growth. ERalpha overexpressors, however, had a higher number of apoptotic cells in the endometrial epithelium and a reduced number of implantation sites compared to controls. Thus, the increased number of apoptotic cells and reduced number of implantation sites observed in ERalpha overexpressing uteri compared to controls may, in part, account for the reduced litter size produced by ERalpha overexpressing females.     

The level of BCR-ABL1 kinase activity before treatment does not identify chronic myeloid leukemia patients who fail to achieve a complete cytogenetic response on imatinib

Imatinib is currently the first line therapy for newly diagnosed patients with chronic myeloid leukemia. However, 20–25% of patients do not achieve durable complete cytogenetic responses. The mechanism underlying this primary resistance is unknown, but variations in BCR-ABL1 kinase activity may play a role and can be investigated by measuring the autophosphorylation levels of BCR-ABL1 or of a surrogate target such as Crkl. In this study we used flow cytometry to investigate the in vitro inhibition of Crkl phosphorylation by imatinib in CD34⁺ cells in diagnostic samples from two groups of patients distinguished by their cytogenetic response. No difference in inhibition of Crkl phosphorylation was observed in the two groups. The observation that increasing the dose of imatinib in vivo did not increase the level of cytogenetic response in some non-responders suggests that in at least a proportion of patients imatinib resistance may be due to activation of BCR-ABL1-independent pathway.     

Estimation of infarct size using transthoracic Doppler echocardiographic measurement of coronary flow reserve in infarct related and reference coronary artery

Background

Patients in chronic phase of myocardial infarction (MI) have decreased coronary flow reserve (CFR) in infarct related artery (IRA) that is proportional to the extent of microvascular/myocardial damage. We proposed a novel model for the assessment of microvascular damage and infarct size using Doppler echocardiography evaluation of CFRs of the IRA (LAD) and reference artery (RCA).

Methods

Our study included 34 consecutive patients (28 men, mean age 50 ± 11 years) with first anterior STEMI and single vessel disease successfully treated with primary PCI. All patients underwent SPECT MPI for the assessment of infarct size (expressed as a percentage of myocardium with fixed perfusion abnormalities) and CFR evaluation of LAD and RCA. CFR derived percentage of microvascular damage (CFR PMD) was calculated as: CFR PMD = (CFR RCA − CFR LAD) / (CFR RCA − 1) × 100 (%).

Results

CFR PMD correlated significantly with all parameters evaluating the severity of myocardial damage including: peak CK activity (r = 0.632, p < 0.001), WMSI (r = 0.857, p < 0.001), ejection fraction (r = − 0.820, p < 0.001), left ventricular end diastolic (r = 0.757, p < 0.001) and end systolic volume (r = 0.794, p < 0.001). Most importantly, CFR PMD (22 ± 17%) correlated significantly with infarct size by SPECT MPI (21 ± 17%) (r = 0.874, p < 0.001).

Conclusions

CFR PMD derived from the proposed model was significantly related to echocardiographic and enzymatic parameters of infarct size, as well as to myocardial damage assessed by SPECT MPI in patients with successfully reperfused first anterior STEMI.     

A comparison of the antinociceptive and temperature responses to morphine and fentanyl derivatives in rats

In addition to producing antinociception, opioids exert profound effects on body temperature. This study aimed at comparing antinociceptive and hyperthermic responses between two groups of μ-opioid receptor agonists: fentanyl (4-anilinopiperidine-type) and morphine (phenanthrene-type) derivatives in rats. Analgesic activity was assessed by tail immersion test and the body temperature by insertion of a thermometer probe into the colon. Fentanyl (F), (±)-cis-3-methyl fentanyl (CM), (±)-cis-3-carbomethoxy fentanyl (C), (±)trans-3-carbomethoxy fentanyl (T) and (±)-cis-3 butyl fentanyl (B) produced dose-dependent increase in antinociception and hyperthermia. The relative order of analgesic potency was: CM(11.27)>F(1)>C(0.35)≥T(0.11)≥B(0.056). Similar to this, the relative order of hyperthermic potency was: CM(8.43)>F(1)>C(0.46)≥T(0.11)≥B(0.076). Morphine (M), oxycodone (O), thebacon (T) and 6,14-ethenomorphinan-7-methanol, 4,5-epoxy-6-fluoro-3-hydroxy-α,α,17-trimethyl-, (5α,7α) (E) also produced dose-dependent increase in antinociception and hyperthermia. Among morphine derivatives the relative order of analgesic potency was: E(56)>O(5)≥T(2.6)>M(1), and similar to this, the relative order of hyperthermic potency was: E(37)>O(3)≥T(2.3)>M(1). Morphine (phenanthrene-type) and fentanyl (4-anilinopiperidine-type) derivatives produced hyperthermia in rats at doses about 2 times lower, and 6–11 times higher, than their median antinociceptive doses, respectively. This study is first to identify difference between these two classes of opioid drugs in their potencies in producing hyperthermia. Further studies are needed to clarify the significance of these findings.     

Unbiased entropy estimates in stress: a parameter study

This study proposes a method for obtaining a stable working point that enables the unbiased estimates of the approximate entropy and the sample entropy. Pattern length, normalized threshold, time delay and tines series length are levels of freedom that are considered. Pulse interval signals used for the experiment are recorded from laboratory animals with different likelihood of developing cardiovascular disease--normal and borderline hypertensive rats--exposed to the acute and to the chronic stress. It is shown that the threshold level is the major source of the instability, and that the generally accepted and widely used methods for a threshold choice may lead to an incorrect psychological interpretation. A method for the threshold level correction is proposed.     

Arsenic occurrence in drinking water supply systems in ten municipalities in Vojvodina Region, Serbia

Vojvodina, a northern region of Serbia, belongs to the Pannonian Basin, whose aquifers contain high concentrations of arsenic. This study represents arsenic levels in drinking water in ten municipalities in Serbia. Around 63% of all water samples exceeded Serbian and European standards for arsenic in drinking water. Large variations in arsenic were observed among supply systems. Arsenic concentrations in public water supply systems in Vojvodina were much higher than in other countries in the Pannonian Basin.