Cancer treatments can have significant cardiovascular adverse effects that can cause cardiomyopathy and heart failure with reduced survival benefit and considerable decrease in the use of ...antineoplastic therapy. The purpose of this study is to assess the role of TLR2 and TLR4 gene expression as an early marker for the risk of doxorubicin-induced cardiomyopathy in correlation with early diastolic dysfunction in patients treated with doxorubicin. Our study included 25 consecutive patients who received treatment with doxorubicin for hematological malignancies (leukemia, lymphomas or multiple myeloma), aged 18-65 years, with a survival probability>6 months and with left ventricular ejection fraction>50%. Exclusion criteria consisted of the following: previous anthracycline therapy, previous radiotherapy, history of heart failure or chronic renal failure, atrial fibrillation, and pregnancy. In all patients, in fasting state, a blood sample was drawn for the assessment of TLR2 and TLR4 gene expression. Gene expression was assessed by quantitative reverse transcription PCR (qRT-PCR) using blood collection, RNA isolation, cDNA reverse transcription, qRT-PCR and quantification of the relative expression. At enrollment, all patients were evaluated clinically; an ECG and an echocardiography were performed. The average amount of gene expression units was 0.113 for TLR4 (range 0.059-0.753) and 0.218 for TLR2 (range 0.046-0.269). The mean mRNA extracted quantity was 113 571 ng/μl. As for the diastolic function parameters, criteria for diastolic dysfunction were present after 6 months in 16 patients (64%). In these patients, the mean values for TLR4 were 0.1198625 and for TLR2 were 0.16454 gene expression units. As for the diastolic function parameters, criteria for diastolic dysfunction were present after 6 months in 16 patients (64%). In these patients, the mean value for TLR2 was 0.30±0.19 and for TLR4 was 0.15±0.04. The corresponding values for the patients who did not develop diastolic dysfunction were 0.16±0.07 for TLR2 (P=0.01) and 0.11±0.10 for TLR4 (P=0.2). Our study suggests that TLR4 and TLR2 expression is higher in patients under doxorubicin therapy who develop diastolic dysfunction. This may suggest a predisposition to myocardial involvement, a higher sensitivity to doxorubicin cardiac effects.
Childbirth may cause the most severe pain some women experience in their lifetime. Epidural analgesia is an effective form of pain relief during labour and is considered to be the reference standard. ...Traditionally epidural analgesia has been delivered as a continuous infusion via a catheter in the epidural space, with or without the ability for the patient to supplement the analgesia received by activating a programmable pump to deliver additional top-up doses, known as patient-controlled epidural analgesia (PCEA). There has been interest in delivering maintenance analgesic medication via bolus dosing (automated mandatory bolus - AMB) instead of the traditional continuous basal infusion (BI); recent randomized controlled trials (RCTs) have shown that the AMB technique leads to improved analgesia and maternal satisfaction.
To assess the effects of automated mandatory bolus versus basal infusion for maintaining epidural analgesia in labour.
We searched CENTRAL, MEDLINE, Embase, the World Health Organization International Clinial Trials Registry Platform (WHO-ICTRP) and ClinicalTrials.gov on 16 January 2018. We screened the reference lists of all eligible trials and reviews. We also contacted authors of included studies in this field in order to identify unpublished research and trials still underway, and we screened the reference lists of the included articles for potentially relevant articles.
We included all RCTs that compared the use of bolus dosing AMB with continuous BI for providing pain relief during epidural analgesia for labour in women.
We used the standard methodological procedures expected by Cochrane. Our primary outcomes were: risk of breakthrough pain with the need for anaesthetic intervention; risk of caesarean delivery; risk of instrumental delivery. Secondary outcomes included: duration of labour; local anaesthetic consumption. We used GRADE to assess the certainty of evidence for each outcome.
We included 12 studies with a total of 1121 women. Ten studies enrolled healthy nulliparous women only and two studies enrolled healthy parous women at term as well. All studies excluded women with complicated pregnancies. There were variations in the technique of initiation of epidural analgesia. Seven studies utilized the combined spinal epidural (CSE) technique, and the other five studies only placed an epidural catheter without any intrathecal injection. Seven studies utilized ropivacaine: six with fentanyl and one with sufentanil. Two studies used levobupivacaine: one with sufentanil and one with fentanyl. Three used bupivacaine with or without fentanyl. The overall risk of bias of the studies was low.AMB probably reduces the risk of breakthrough pain compared with BI for maintaining epidural analgesia for labour (from 33% to 20%; risk ratio (RR) 0.60; 95% confidence interval (CI) 0.39 to 0.92, 10 studies, 797 women, moderate-certainty evidence). AMB may make little or no difference to the risk of caesarean delivery compared to BI (15% and 16% respectively; RR 0.92; 95% CI 0.70 to 1.21, 11 studies, 1079 women, low-certainty evidence).AMB may make little or no difference in the risk of instrumental delivery compared to BI (12% and 9% respectively; RR 0.75; 95% CI 0.54 to 1.06, 11 studies, 1079 women, low-certainty evidence). There is probably little or no difference in the mean duration of labour with AMB compared to BI (mean difference (MD) -10.38 min; 95% CI -26.73 to 5.96, 11 studies, 1079 women, moderate-certainty evidence). There is probably a reduction in the hourly consumption of local anaesthetic with AMB compared to BI for maintaining epidural analgesia during labour (MD -1.08 mg/h; 95% CI -1.78 to -0.38, 12 studies, 1121 women, moderate-certainty evidence). Five out of seven studies reported an increase in maternal satisfaction with AMB compared to BI for maintaining epidural analgesia for labour; however, we did not pool these data due to their ordinal nature. Seven studies reported Apgar scores, though there was significant heterogeneity in reporting. None of the studies showed any significant difference between Apgar scores between groups.
There is predominantly moderate-certainty evidence that AMB is similar to BI for maintaining epidural analgesia for labour for all measured outcomes and may have the benefit of decreasing the risk of breakthrough pain and improving maternal satisfaction while decreasing the amount of local anaesthetic needed.
The 50S subunit of the ribosome catalyzes the peptidyl-transferase reaction of protein synthesis. We have generated X-ray crystallographic electron density maps of the large ribosomal subunit from ...Haloarcula marismortui at various resolutions up to 9 angstrom using data from crystals that diffract to 3 angstrom. Positioning a 20 angstrom resolution EM image of these particles in the crystal lattice produced phases accurate enough to locate the bound heavy atoms in three derivatives using difference Fourier maps, thus demonstrating the correctness of the EM model and its placement in the unit cell. At 20 angstrom resolution, the X-ray map is similar to the EM map; however, at 9 angstrom it reveals long, continuous, but branched features whose shape, diameter, and right-handed twist are consistent with segments of double-helical RNA that crisscross the subunit.
The 50S subunit of the ribosome catalyzes the peptidyl-transferase reaction of protein synthesis. We have generated X-ray crystallographic electron density maps of the large ribosomal subunit from
...Haloarcula marismortui at various resolutions up to 9 Å using data from crystals that diffract to 3 Å. Positioning a 20 Å resolution EM image of these particles in the crystal lattice produced phases accurate enough to locate the bound heavy atoms in three derivatives using difference Fourier maps, thus demonstrating the correctness of the EM model and its placement in the unit cell. At 20 Å resolution, the X-ray map is similar to the EM map; however, at 9 Å it reveals long, continuous, but branched features whose shape, diameter, and right-handed twist are consistent with segments of double-helical RNA that crisscross the subunit.
Abstract An increase in activity of the pituitary–gonadal axis (PG-axis) and gonadal development are essential for the onset of spawning migration of chum salmon from the Bering Sea. In the Bering ...Sea, fish with larger body sizes initiated gonadal development and commenced spawning migration to the natal river by the end of summer. We thus hypothesized that insulin-like growth factor-I (IGF-I), a somatotropic signal that interacts with the PG-axis, can be one of such factors responsible for the onset of migration, and examined changes in plasma levels and hepatic expression of IGF-I gene in oceanic and homing chum salmon in 2001–2003. The plasma IGF-I levels and corresponding body sizes in maturing adults, which had developing gonads, were significantly higher than those in immature fish in all years examined. Such increase in the plasma IGF-I levels in maturing fish was observed even in the Gulf of Alaska during February 2006, while coincident increase was not observed in the hepatic amounts of IGF-I mRNA. In autumn, the plasma IGF-I levels in homing adults decreased during upstream migration in the Ishikari River-Ishikari bay water system in Hokkaido, Japan. In conclusion, the plasma IGF-I levels increased with gonadal development when chum salmon migrated from the winter Gulf of Alaska to the summer Bering Sea. Circulating IGF-I may interact with the PG-axis and promote gonadal development that is inseparable from the onset of spawning migration. Circulating IGF-I levels were thereafter lowered in accordance with final maturation during upstream migration in the breeding season.
Abstract Pacific salmon migrate from ocean through the natal river for spawning. Information on expression of genes encoding osmoregulatory hormones and migratory behavior is important for ...understanding of molecular events that underlie osmoregulation of homing salmon. In the present article, regulation of gene expression for osmoregulatory hormones in pre-spawning salmon was briefly reviewed with special reference to neurohypophysial hormone, vasotocin (VT), and pituitary hormones, growth hormone (GH) and prolactin (PRL). Thereafter, we introduced recent data on migratory behavior from SW to FW environment. In pre-spawning chum salmon, the hypothalamic VT mRNA levels increased in the males, while decreased in the females with loss of salinity tolerance when they were kept in SW. The amounts of GH mRNA in the pituitary decreased during ocean migration prior to entrance into FW. Hypo-osmotic stimulation by SW-to-FW transfer did not significantly affect the amount of PRL mRNA, but it was elevated in both SW and FW environments along with progress in final maturation. Behaviorally, homing chum salmon continued vertical movement between SW and FW layers in the mouth of the natal river for about 12 h prior to upstream migration. Pre-spawning chum salmon in an aquarium, which allowed fish free access to SW and FW, showed that individuals with the lower plasma testosterone (T) and higher estradiol-17β (E2) levels spent longer time in FW when compared with the SW fish. Taken together, neuroendocrine mechanisms that underlie salt and water homeostasis and migratory behavior from SW to FW may be under the control of the hypothalamus-pituitary-gonadal axis in pre-spawning salmon.
Fragestellung:
Aromatasehemmer sind der Standard der endokrinen Therapie des Hormonrezeptor positiven, postmenopausalen Mammakarzinoms. Vor kurzem konnte gezeigt werden, dass der BMI signifikant die ...Effektivität von Anastrozol bei Brustkrebspatientinnen beeinflusst. In dieser prospektiven Studie haben wir untersucht, ob unterschiedliche Veränderungen der Serumhormonspiegel von normalgewichtigen und übergewichtigen Patientinnen während der endokrinen Therapie mit einem Aromatasehemmer ursächlich für diesen Einfluss des BMI sind.
Methode:
54 postmenopausale Hormonrezeptor positive Brustkrebspatientinnen wurden in diese prospektive Studie eingeschlossen. BMI sowie Serumhormonspiegel (FSH, LH, Östradiol, Insulin, und SHBG) wurden unmittelbar vor Beginn der Therapie mit einem Aromatasehemmer sowie 3 Monate später gemessen. Ebenso wurde ein Fragebogen bezüglich spezifischer Nebenwirkungen vor und nach 3 Monaten Therapie ausgefüllt.
Ergebnisse:
10 normalgewichtige und 44 übergewichtige Brustkrebspatientinnen mit einem Durchschnittsalter von 67 Jahren wurden eingeschlossen. Die Serum-Östradiolspiegel waren überwiegend unter der Nachweisgrenze sowohl vor als auch nach 3 monatiger Therapie mit dem Aromatasehemmer. Somit wurden LH und FSH als hochsensitive Surrogatparameter für die Serum-Östradiol Spiegel herangezogen. Übergewichtige Patientinnen hatten signifikant niedrigere LH und FSH Spiegel als normalgewichtige Patientinnen sowohl vor Beginn der Therapie (p=0,029 und p=0,012) als auch nach 3 monatiger Therapie mit dem Aromatasehemmer (p=0,032 und p=0,007). LH und FSH Spiegel stiegen nach 3 monatiger Therapie mit dem Aromatasehemmer bei normalgewichtigen aber nicht bei übergewichtigen Patientinnen an.
Es konnte kein Unterschied im Hinblick auf Nebenwirkungen zwischen normalgewichtigen und übergewichtigen Patientinnen festgestellt werden.
Schlussfolgerung:
Unterschiedliche Veränderungen der Serumhormonspiegel während der endokrinen Therapie mit Aromatasehemmern scheinen für den klinischen Einfluss des BMI auf die Effektivität der Aromatasehemmer verantwortlich zu sein.
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