Perinatal stimulation and adaptation of the neonate

The present report describes psychobiological studies of behavior around the time of birth. An adaptive, ecological perspective is presented in which stimulation of the fetus and newborn is purported to instigate adaptive postpartum behavior. Studies describing the perinatal sensory environment are reviewed, with a consideration of emergent sensory function of the fetus. It is asserted that afferent input associated with parturition perturbs the fetus and neonate, producing a general arousal state that facilitates breathing, suckling, and early learning. The view developed herein is that perinatal sensory input induces and canalizes the newborn's behavior, thereby regulating adaptive postpartum function. Deviations in afferent input may alter ontogenetic trajectories and compromise developmental outcome by reducing availability of conditions necessary for adequate postpartum adaptation.     

Doxorubicin induces cardiomyocyte dysfunction via a p38 MAP kinase-dependent oxidative stress mechanism

Doxorubicin, an anthracycline used for cancer therapy, is known to elicit an irreversible cardiotoxicity. Several mechanisms were postulated for its cardiac toxicity including generation of reactive oxygen species (ROS). This study was designed to determine the acute effect of doxorubicin on cardiac mechanical and intracellular Ca(2+) properties in isolated ventricular myocytes. Contractile properties of male adult rat ventricular myocytes were analyzed including peak shortening (PS), time-to-PS (TPS), time-to-90% relengthening (TR(90)) and maximal velocity of shortening/relengthening (+/-dL/dt). Intracellular Ca(2+) transients and generation of ROS were measured with fura-2 and fluoroprobe 5-(6)-chloromethyl-2',7'-dichlorodihydrofluorescein diacetate, respectively. Acute (5 min) incubation of myocytes with doxorubicin (10(-9)-10(-4)M) significantly prolonged TPS, TR(90) and intracellular Ca(2+) transient decay rate without affecting PS, +/-dL/dt, resting intracellular Ca(2+) levels and electrically triggered intracellular Ca(2+) rise. Interestingly, the doxorubicin-induced prolongation of TPS and TR(90) was ablated by treatment of the antioxidant Vitamin C (100 microM) or the p38 MAP kinase inhibitor SB203580 (10 microM). Both Vitamin C and SB203580 unmasked a doxorubicin-induced positive response in PS. Vitamin C itself enhanced basal +/-dL/dt, whereas, SB203580 unmasked a doxorubicin-induced positive response of +/-dL/dt. The doxorubicin-induced response of intracellular Ca(2+) transients was essentially unaffected by Vitamin C. The role of ROS in doxorubicin-induced cardiac contractile response was confirmed with the ability of doxorubicin to enhance ROS generation, which was prevented by Vitamin C and SB203580. These data provide evidence that doxorubicin impairs cardiac contractile property in single myocytes through an oxidative stress-mediated pathway.     

What do cancer survivors believe causes cancer? (United States)

Objective: To describe cancer survivors beliefs about the causes of prostate, colorectal or breast cancers.Methods: A survey of beliefs about cancer causation was completed by 670 cancer survivors (416 with breast cancer, 165 with prostate cancer and 89 with colorectal cancer) enrolled in a population-based study in Colorado. Categorical analysis was used to describe associations between participants beliefs about the cause of their cancer type, both in themselves and in others, and personal characteristics, including gender, age, and familial cancer risk.Results: Cancer survivors most frequently reported genetic factors, smoking, environmental factors (e.g., pollutants or occupation), and psychosocial factors (e.g., stress) as causing their type of cancer. Respondents underestimated the importance of behavioral factors that are known to be associated with increased cancer risk, such as obesity and physical inactivity, while overestimating the importance of stress and environmental pollution.Conclusions: Cancer survivors beliefs about what causes cancer are substantially different than those of experts. Because those affected by cancer should be well informed about the causes of cancer, educational efforts are needed, especially regarding the importance of factors that can be modified to reduce cancer risk.     

A full flora, but not monocolonization by Escherichia coli or lactobacilli, supports tolerogenic processing of a fed antigen

Fed protein undergoes processing and coupling to major histocompatibility complex (MHC) II molecules during passage through the intestinal epithelium, generating a tolerogenic form of the antigen in serum. Transfer of this factor to naïve animals induces tolerance in the recipient. In this study, we investigate what impact colonization with Gram-positive (Lactobacillus plantarum) or Gram-negative (Escherichia coli) bacteria has on tolerogenic processing in the gut. Germ-free (GF), monocolonized or conventional mice were fed ovalbumin (OVA), and their serum was collected and transferred to naïve conventional recipients that were tested for delayed-type hypersensitivity against OVA after parenteral immunization. A transferable tolerogenic factor was produced by conventional mice, but not by mice that were germ free or monocolonized with either E. coli or L. plantarum. Conventional, but neither GF nor monocolonized mice showed upregulation of MHCII expression in the epithelium of small intestine. The results suggest that a complex intestinal microflora is needed to support oral tolerance development.