Hippocampus-based behavioral,structural, and molecular dynamics across the estrous cycle

The activity of neurons in the rodent hippocampus contributes to diverse behaviors, with the activity of ventral hippocampal neurons affecting behaviors related to anxiety and emotion regulation, and the activity of dorsal hippocampal neurons affecting performance in learning- and memory-related tasks. Hippocampal cells also express receptors for ovarian hormones, estrogen and progesterone, and are therefore affected by physiological fluctuations of those hormones that occur over the rodent estrous cycle. In this review, we discuss the effects of cycling ovarian hormones on hippocampal physiology. Starting with behavior, we explore the role of the estrous cycle in regulating hippocampus-dependent behaviors. We go on to detail the cellular mechanisms through which cycling estrogen and progesterone, through changes in the structural and functional properties of hippocampal neurons, may be eliciting these changes in behavior. Then, providing a basis for these cellular changes, we outline the epigenetic, chromatin regulatory mechanisms through which ovarian hormones, by binding to their receptors, can affect the regulation of behavior- and synaptic plasticity-related genes in hippocampal neurons. We also highlight an unconventional role that chromatin dynamics may have in regulating neuronal function across the estrous cycle, including in sex hormone-driven X chromosome plasticity and hormonally-induced epigenetic priming. Finally, we discuss directions for future studies and the translational value of the rodent estrous cycle for understanding the effects of the human menstrual cycle on hippocampal physiology and brain disease risk.     

Association of SV40 with human tumours

SV40 was discovered as a contaminant of poliovirus vaccines that were inadvertently administered to millions of people in Europe and the United States between 1955 and 1963. Shortly afterwards, SV40 was proven to be oncogenic in rodents and capable of transforming human and animal cells in vitro. The possibility that SV40 might cause tumours in humans thus became a subject of scientific and public interest and scrutiny. However, largely due to a lack of significant epidemiological evidence, interest in assessing SV40's potential carcinogenic role in humans diminished. Recently, many laboratories have reported the presence of SV40-like DNA in a high proportion of human mesotheliomas, ependymomas and osteosarcoma (the three main types of tumours caused by virus in hamsters), renewing the question whether SV40 might be a human tumour virus. Molecular data from these studies are reviewed to re-evaluate the potential role of SV40 as a human carcinogen.     

Multicatheter hybrid breast brachytherapy: a potential alternative for patients with inadequate skin distance

PurposeThe purpose of this study was to determine whether the ClearPath (CP) multicatheter hybrid device was able to achieve acceptable dosimetry in patients in whom the proximity of the breast surgical cavity to the skin precluded treatment with intracavitary MammoSite (MS) brachytherapy.Methods and materialsThe study consisted of 11 patients who had the MS catheter placed and who were subsequently not treated due to inadequate skin distance. A phantom scan of the CP multicatheter hybrid device was superimposed on the MS CT scan and a dosimetric comparison was performed.ResultsThe median MS balloon size, diameter, and minimum skin distance were 40 cc, 4.1 cm, and 5 mm, respectively. The D₉₀, V₁₀₀, V₁₅₀, and V₂₀₀ with MS vs. CP were 95.29% vs. 97.06%, 88.8% vs. 91.3%, 35.7% vs. 38.0%, and 9.4% vs. 9.6%, respectively. The median maximum skin dose was 5.5 Gy vs. 3.9 Gy (p <.0001). The median dose homogeneity index (DHI) was 0.60 vs. 0.59 (p = .09). The median maximum rib, heart, and lung dose were 2.17 Gy vs. 2.18 Gy, 2.17 Gy vs. 2.18 Gy, and 0.50 Gy vs. 0.56 Gy, respectively.ConclusionThe hybrid CP catheter reduced the skin dose significantly without compromising the planning target volume coverage, DHI, or dose to other critical organs. The use of this device has the potential to increase the applicability of accelerated partial breast brachytherapy (APBI) in patients with a surgical cavity close to skin compared with balloon brachytherapy.     

Transforming growth factor β2 induced pleurodesis is not inhibited by corticosteroids

BACKGROUND: Talc and tetracyclines induce pleurodesis by directly injuring the pleura. The injury results in intense inflammation which subsequently leads to fibrosis. Corticosteroids can inhibit talc pleurodesis by reducing the inflammatory process. We hypothesised that transforming growth factor beta2 (TGFbeta2), a fibrogenic cytokine with immunomodulatory functions, could induce effective pleurodesis without generating significant pleural inflammation and therefore remain effective despite co-administration of corticosteroids. METHODS: Thirty rabbits were divided into two groups. Rabbits in the steroid group received weekly intramuscular injections of triamcinolone diacetate (0.8 mg/kg). Ten rabbits in each group were given 5.0 microg TGFbeta2 intrapleurally via a chest tube while the remaining five received 1.7 microg TGFbeta2. Pleurodesis was graded macroscopically after 14 days from 1 (none) to 8 (>50% symphysis). RESULTS: TGFbeta2 produced excellent pleurodesis at both 5.0 microg and 1.7 microg doses. The pleural effusions produced after the injection were low in all inflammatory markers. No significant differences were seen between the steroid group and controls in macroscopic pleurodesis scores (7.2 (1.3) v 7.1 (1.2)), levels of inflammatory markers in the pleural fluids (leucocyte 1107 (387)/mm(3) v 1376 (581)/mm(3); protein 3.1 (0.3) mg/dl v 2.9 (0.3) mg/dl, and LDH 478 (232) IU/l v 502 (123) IU/l), and the degree of microscopic pleural fibrosis and pleural inflammation. CONCLUSIONS: TGFbeta2 can induce effective pleurodesis and remains effective in the presence of high dose parenteral corticosteroids.