Numerical assessment of radiation binary targeted therapy for HER-2 positive breast cancers: advanced calculations and radiation dosimetry

In our previous publication (Mundy et al 2006 Phys. Med. Biol. 51 1377) we have described the theoretical assessment of our novel approach in radiation binary targeted therapy for HER-2 positive breast cancers and summarized the future directions in this area of research. In this paper we advanced the numerical analysis to show the detailed radiation dose distribution for various neutron sources in combination with the required boron concentration and allowed radiation skin doses. We once again proved the feasibility of the concept and will use these data and conclusions to start with the experimental verifications.     

Biological evaluation of selected 3,4‐dihydro‐2(1H)‐quinoxalinones and 3,4‐dihydro‐1,4‐benzoxazin‐2‐ones: Molecular docking study

In order to investigate new potential therapeutically active agents, we investigated the biological properties of two small libraries of quinoxalinones and 1,4‐benzoxazin‐2‐ones. The results obtained showed that compounds 5 , 9–11 have good cytotoxic activity against HeLa cells where the lowest IC₅₀ value (10.46 ± 0.82 μM/mL) was measured for compound 10 . Additionally, the most active compounds ( 5 , 9 – 11 ) showed much better selectivity for MRC‐5 cells (up to 17.4) compared to cisplatin. In vitro evaluation of the inhibition of the enzyme α‐glucosidase showed that compounds 10 and 11 exert significant inhibition of the enzyme at 52.54 ± 0.09 and 40.09 ± 0.49 μM, respectively. Competitive experiments with ethidium bromide (EB) indicated that all tested compounds have affinity to displace EB from the EB‐DNA complex through intercalation, suggesting good competition with EB (K_sv = (3.1 ± 0.2), (5.1 ± 0.1), (5.6 ± 0.2), and (6.3 ± 0.2) × 10³ M^?1). A molecular docking study was also performed to better understand the binding modes and to conclude the structure–activity relationships of the synthesized compounds.

     

Seroepidemiology of hepatitis E in patients on haemodialysis in Croatia

International Urology and Nephrology - Data on the seroprevalence of hepatitis E virus (HEV) in heamodialysis (HD) patients are conflicting, ranging from 0 to 44%. The aim of this study was to...     

Overexpression of oxytocin receptors in the hypothalamic PVN increases baroreceptor reflex sensitivity and buffers BP variability in conscious rats

Background and Purpose

The paraventricular nucleus (PVN) of the hypothalamus is an important integrative site for neuroendocrine control of the circulation. We investigated the role of oxytocin receptors (OT receptors) in PVN in cardiovascular homeostasis.

Experimental Approach

Experiments were performed in conscious male Wistar rats equipped with a radiotelemetric device. The PVN was unilaterally co-transfected with an adenoviral vector (Ad), engineered to overexpress OT receptors, and an enhanced green fluorescent protein (eGFP) tag. Control groups: PVN was transfected with an Ad expressing eGFP alone or untransfected, sham rats (Wt). Recordings were obtained without and with selective blockade of OT receptors (OTX), during both baseline and stressful conditions. Baroreceptor reflex sensitivity (BRS) and cardiovascular short-term variability were evaluated using the sequence method and spectral methodology respectively.

Key Results

Under baseline conditions, rats overexpressing OT receptors (OTR) exhibited enhanced BRS and reduced BP variability compared to control groups. Exposure to stress increased BP, BP variability and HR in all rats. In control groups, but not in OTR rats, BRS decreased during stress. Pretreatment of OTR rats with OTX reduced BRS and enhanced BP and HR variability under baseline and stressful conditions. Pretreatment of Wt rats with OTX, reduced BRS and increased BP variability under baseline and stressful conditions, but only increased HR variability during stress.

Conclusions and Implications

OT receptors in PVN are involved in tonic neural control of BRS and cardiovascular short-term variability. The failure of this mechanism could critically contribute to the loss of autonomic control in cardiovascular disease.     

Unrelated stem cell transplantation in multiple myeloma after a reduced-intensity conditioning with pretransplantation antithymocyte globulin is highly effective with low transplantation-related mortality

We investigated the feasibility of unrelated stem cell transplantation in 21 patients with advanced stage II/III multiple myeloma after a reduced-intensity conditioning regimen consisting of fludarabine (150 mg/m(2)), melphalan (100-140 mg/m(2)), and antithymocyte globulin (ATG; 10 mg/kg on 3 days). The median patient age was 50 years (range, 32-61 years). All patients had received at least one prior autologous transplantation, in 9 cases as part of an autologous-allogeneic tandem protocol. No graft failure was observed. At day 40 complete donor chimerism was detected in all patients. Grade II to IV acute graft-versus-host disease (GVHD) was seen in 8 patients (38%), and severe grade III/IV GVHD was observed in 4 patients (19%). Six patients (37%) developed chronic GVHD, but only 2 patients (12%) experienced extensive chronic GVHD. The estimated probability of nonrelapse mortality at day 100 was 10% and at 1 year was 26%. After allografting, 40% of the patients achieved a complete remission, and 50% achieved a partial remission, resulting in an overall response rate of 90%. After a median follow-up of 13 months, the 2-year estimated overall and progression-free survival rates are 74% (95% CI, 54%-94%) and 53% (95% CI, 29%-87%), respectively. A shorter progression-free survival was seen in patients who already experienced relapse to prior autograft (26% versus 86%, P =.04). Dose-reduced conditioning with pretransplantation ATG followed by unrelated stem cell transplantation provides durable engraftment and donor chimerism, reduces substantially the risk of transplant-related organ toxicity, and induces high remission rates.     

Chlamydia pneumoniae infections in patients with community-acquired pneumonia in Slovenia

It is well known that Chlamydia pneumoniae is an important respiratory pathogen. In this study, the prevalence of specific antibodies to C. pneumoniae in hospitalized patients with community-acquired pneumonia (943 adult females, 990 adult males and 185 children) was evaluated over a period of 7 y (1993-99). Two serum samples were obtained from all of the patients: 1 on admission and the other 3 weeks later. The specimens were tested for C. pneumoniae IgG, IgM and IgA antibodies by means of a microimmunofluorescence test. Acute infection with C. pneumoniae was determined in 9.4% of females and 13.1% of males. In children and adolescent patients, the microimmunofluorescence test showed recent infection in 8.6% of cases, with the highest prevalence occurring in the 11-15 y age group. The highest prevalence of C. pneumoniae pneumonia was found in 1995 and 1999: 15.4% and 13.6% respectively. The results obtained showed that C. pneumoniae is persistently present in the population of Slovenia.     

Egg consumption and carotid atherosclerosis in the Northern Manhattan Study

Background

The evidence supporting recommendations to limit intake of cholesterol rich foods is inconclusive. We aimed to examine the association between egg consumption and carotid atherosclerosis phenotypes, and the association with clinical vascular events in a prospective, urban, multi-ethnic population.

Methods and results

The Northern Manhattan Study is a population based cohort to determine stroke incidence, risk factors and prognosis. A sub-cohort of 1429 NOMAS participants with both carotid ultrasounds and comprehensive dietary information was evaluated (mean ± SD age of participants 65.80 ± 8.80, 40% male, 18% white, 20% black, 60% Hispanic). The association between egg consumption and carotid intima media thickness (cIMT) was assessed with linear regression. Logistic and quantile regression was used to examine the association between egg consumption and carotid plaque presence, thickness, and area. The relation between egg consumption and clinical vascular events (N = 2669) was examined with Cox models. The mean total cIMT was 0.91 ± 0.08 mm and 58% had carotid plaque present. Increasing egg consumption was inversely associated with cIMT, plaque presence, thickness, and area, in models adjusted for demographics, vascular risk factors and diet. For every additional egg consumed per week, the risk of plaque decreased by 11% (95% CI 3%–18%). No association was detected between egg consumption and risk of clinical vascular outcomes, over a mean follow up of 11 years and after adjustment for covariates.

Conclusions

Frequency of egg consumption in the low to moderate range was inversely related to several markers of carotid atherosclerosis. No association with clinical vascular events, including stroke, was detected. Our findings do not support current vascular health guidelines suggesting the extreme limitation or avoidance of egg consumption due to its cholesterol content.