Munchausen by internet: current research and future directions.

The Internet has revolutionized the health world, enabling self-diagnosis and online support to take place irrespective of time or location. Alongside the positive aspects for an individual's health from making use of the Internet, debate has intensified on how the increasing use of Web technology might have a negative impact on patients, caregivers, and practitioners. One such negative health-related behavior is Munchausen by Internet

The effect of enteral and parenteral feeding on secretion of orexigenic peptides in infants

<p>Abstract</p> <p>Background</p> <p>The feeding in the first months of the life seems to influence the risks of obesity and affinity to some diseases including atherosclerosis. The mechanisms of these relations are unknown, however, the modification of hormonal action can likely be taken into account. Therefore, in this study the levels of ghrelin and orexin A - peripheral and central peptide from the orexigenic gut-brain axis were determined.</p> <p>Methods</p> <p>Fasting and one hour after the meal plasma concentrations of ghrelin and orexin were measured in breast-fed (group I; n = 17), milk formula-fed (group II; n = 16) and highly hydrolyzed, hypoallergic formula-fed (group III; n = 14) groups, age matched infants (mean 4 months) as well as in children with iv provision of nutrients (glucose - group IV; n = 15; total parenteral nutrition - group V; n = 14). Peptides were determined using EIA commercial kits.</p> <p>Results</p> <p>Despite the similar caloric intake in orally fed children the fasting ghrelin and orexin levels were significantly lower in the breast-fed children (0.37 ± 0.17 and 1.24 ± 0.29 ng/ml, respectively) than in the remaining groups (0.5 ± 0.27 and 1.64 ± 0.52 ng/ml, respectively in group II and 0.77 ± 0.27 and 2.04 ± 1.1 ng/ml, respectively, in group III). The postprandial concentrations of ghrelin increased to 0.87 ± 0.29 ng/ml, p < 0.002 and 0.76 ± 0.26 ng/ml, p < 0.01 in groups I and II, respectively as compared to fasting values. The decrease in concentration of ghrelin after the meal was observed only in group III (0.47 ± 0.24 ng/ml). The feeding did not influence the orexin concentration. In groups IV and V the ghrelin and orexin levels resembled those in milk formula-fed children.</p> <p>Conclusion</p> <p>The highly hydrolyzed diet strongly affects fasting and postprandial ghrelin and orexin plasma concentrations with possible negative effect on short- and long-time effects on development. Also total parenteral nutrition with the continuous stimulation and lack of fasting/postprandial modulation might be responsible for disturbed development in children fed this way.</p

Differential Regional Immune Response in Chagas Disease

Following infection, lymphocytes expand exponentially and differentiate into effector cells to control infection and coordinate the multiple effector arms of the immune response. Soon after this expansion, the majority of antigen-specific lymphocytes die, thus keeping homeostasis, and a small pool of memory cells develops, providing long-term immunity to subsequent reinfection. The extent of infection and rate of pathogen clearance are thought to determine both the magnitude of cell expansion and the homeostatic contraction to a stable number of memory cells. This straight correlation between the kinetics of T cell response and the dynamics of lymphoid tissue cell numbers is a constant feature in acute infections yielded by pathogens that are cleared during the course of response. However, the regional dynamics of the immune response mounted against pathogens that are able to establish a persistent infection remain poorly understood. Herein we discuss the differential lymphocyte dynamics in distinct central and peripheral lymphoid organs following acute infection by Trypanosoma cruzi, the causative agent of Chagas disease. While the thymus and mesenteric lymph nodes undergo a severe atrophy with massive lymphocyte depletion, the spleen and subcutaneous lymph nodes expand due to T and B cell activation/proliferation. These events are regulated by cytokines, as well as parasite-derived moieties. In this regard, identifying the molecular mechanisms underlying regional lymphocyte dynamics secondary to T. cruzi infection may hopefully contribute to the design of novel immune intervention strategies to control pathology in this infection

A Research Agenda for Helminth Diseases of Humans: Health Research and Capacity Building in Disease-Endemic Countries for Helminthiases Control

Capacity building in health research generally, and helminthiasis research particularly, is pivotal to the implementation of the research and development agenda for the control and elimination of human helminthiases that has been proposed thematically in the preceding reviews of this collection. Since helminth infections affect human populations particularly in marginalised and low-income regions of the world, they belong to the group of poverty-related infectious diseases, and their alleviation through research, policy, and practice is a sine qua non condition for the achievement of the United Nations Millennium Development Goals. Current efforts supporting research capacity building specifically for the control of helminthiases have been devised and funded, almost in their entirety, by international donor agencies, major funding bodies, and academic institutions from the developed world, contributing to the creation of (not always equitable) North–South “partnerships”. There is an urgent need to shift this paradigm in disease-endemic countries (DECs) by refocusing political will, and harnessing unshakeable commitment by the countries' governments, towards health research and capacity building policies to ensure long-term investment in combating and sustaining the control and eventual elimination of infectious diseases of poverty. The Disease Reference Group on Helminth Infections (DRG4), established in 2009 by the Special Programme for Research and Training in Tropical Diseases (TDR), was given the mandate to review helminthiases research and identify research priorities and gaps. This paper discusses the challenges confronting capacity building for parasitic disease research in DECs, describes current capacity building strategies with particular reference to neglected tropical diseases and human helminthiases, and outlines recommendations to redress the balance of alliances and partnerships for health research between the developed countries of the “North” and the developing countries of the “South”. We argue that investing in South–South collaborative research policies and capacity is as important as their North–South counterparts and is essential for scaled-up and improved control of helminthic diseases and ultimately for regional elimination

A Quantitative Study of the Mechanisms behind Thymic Atrophy in Gαi2-Deficient Mice during Colitis Development

Mice deficient for the G protein subunit Gαi2 spontaneously develop colitis, a chronic inflammatory disease associated with dysregulated T cell responses. We and others have previously demonstrated a thymic involution in these mice and an aberrant thymocyte dynamics. The Gαi2−/− mice have a dramatically reduced fraction of double positive thymocytes and an increased fraction of single positive (SP) thymocytes. In this study, we quantify a number of critical parameters in order to narrow down the underlying mechanisms that cause the dynamical changes of the thymocyte development in the Gαi2−/− mice. Our data suggest that the increased fraction of SP thymocytes results only from a decreased number of DP thymocytes, since the number of SP thymocytes in the Gαi2−/− mice is comparable to the control littermates. By measuring the frequency of T cell receptor excision circles (TRECs) in the thymocytes, we demonstrate that the number of cell divisions the Gαi2−/− SP thymocytes undergo is comparable to SP thymocytes from control littermates. In addition, our data show that the mature SP CD4+ and CD8+ thymocytes divide to the same extent before they egress from the thymus. By estimating the number of peripheral TREC+ T lymphocytes and their death rate, we could calculate the daily egression of thymocytes. Gαi2−/− mice with no/mild and moderate colitis were found to have a slower export rate in comparison to the control littermates. The quantitative measurements in this study suggest a number of dynamical changes in the thymocyte development during the progression of colitis

A case report and brief review of the literature on bilateral retinal infarction following cardiopulmonary bypass for coronary artery bypass grafting

Postoperative visual loss is a devastating perioperative complication. The commonest aetiologies are anterior ischaemic optic neuropathy (AION), posterior ischaemic optic neuropathy (PION), and central retinal artery occlusion (CRAO). These appear to be related to certain types of operation, most commonly spinal and cardiac bypass procedures; with the rest divided between: major trauma causing excessive blood loss; head/neck and nasal or sinus surgery; major vascular procedures (aortic aneurysm repair, aorto-bifemoral bypass); general surgery; urology; gynaecology; liposuction; liver transplantation and duration of surgery. The non-surgical risk factors are multifactorial: advanced age, prolonged postoperative anaemia, positioning (supine v prone), alteration of venous drainage of the retina, hypertension, smoking, atherosclerosis, hyperlipidaemia, diabetes, hypercoagulability, hypotension, blood loss and large volume resuscitation. Other important cardiac causes are septic emboli from bacterial endocarditis and emboli caused by atrial myxomata. The majority of AION cases occur during CPB followed by head/neck surgery and prone spine surgery. CPB is used to allow coronary artery bypass grafting on a motionless heart. It has many side-effects and complications associated with its use and we report here a case of bilateral retinal infarction during routine coronary artery bypass grafting in a young male patient with multiple risk factors for developing this complication despite steps to minimise its occurrence

The Action Mechanism of the Myc Inhibitor Termed Omomyc May Give Clues on How to Target Myc for Cancer Therapy

Recent evidence points to Myc – a multifaceted bHLHZip transcription factor deregulated in the majority of human cancers – as a priority target for therapy. How to target Myc is less clear, given its involvement in a variety of key functions in healthy cells. Here we report on the action mechanism of the Myc interfering molecule termed Omomyc, which demonstrated astounding therapeutic efficacy in transgenic mouse cancer models in vivo. Omomyc action is different from the one that can be obtained by gene knockout or RNA interference, approaches designed to block all functions of a gene product. This molecule – instead – appears to cause an edge-specific perturbation that destroys some protein interactions of the Myc node and keeps others intact, with the result of reshaping the Myc transcriptome. Omomyc selectively targets Myc protein interactions: it binds c- and N-Myc, Max and Miz-1, but does not bind Mad or select HLH proteins. Specifically, it prevents Myc binding to promoter E-boxes and transactivation of target genes while retaining Miz-1 dependent binding to promoters and transrepression. This is accompanied by broad epigenetic changes such as decreased acetylation and increased methylation at H3 lysine 9. In the presence of Omomyc, the Myc interactome is channeled to repression and its activity appears to switch from a pro-oncogenic to a tumor suppressive one. Given the extraordinary therapeutic impact of Omomyc in animal models, these data suggest that successfully targeting Myc for cancer therapy might require a similar twofold action, in order to prevent Myc/Max binding to E-boxes and, at the same time, keep repressing genes that would be repressed by Myc

Pharmacogenetics: data, concepts and tools to improve drug discovery and drug treatment

Variation in the human genome is a most important cause of variable response to drugs and other xenobiotics. Susceptibility to almost all diseases is determined to some extent by genetic variation. Driven by the advances in molecular biology, pharmacogenetics has evolved within the past 40 years from a niche discipline to a major driving force of clinical pharmacology, and it is currently one of the most actively pursued disciplines in applied biomedical research in general. Nowadays we can assess more than 1,000,000 polymorphisms or the expression of more than 25,000 genes in each participant of a clinical study – at affordable costs. This has not yet significantly changed common therapeutic practices, but a number of physicians are starting to consider polymorphisms, such as those in CYP2C9, CYP2C19, CYP2D6, TPMT and VKORC1, in daily medical practice. More obviously, pharmacogenetics has changed the practices and requirements in preclinical and clinical drug research; large clinical trials without a pharmacogenomic add-on appear to have become the minority. This review is about how the discipline of pharmacogenetics has evolved from the analysis of single proteins to current approaches involving the broad analyses of the entire genome and of all mRNA species or all metabolites and other approaches aimed at trying to understand the entire biological system. Pharmacogenetics and genomics are becoming substantially integrated fields of the profession of clinical pharmacology, and education in the relevant methods, knowledge and concepts form an indispensable part of the clinical pharmacology curriculum and the professional life of pharmacologists from early drug discovery to pharmacovigilance