One of the best ways to fight acne is through acne awareness and in taking the right steps to prevent it from forming in the first place. However, regardless of the efforts to prevent its formation, there is still a good chance that a person will suffer acne throughout their lifetime. How severe it becomes [...]
IntroductionExperimental streptococcal cell wall (SCW)-induced arthritis is characterized by two successive phases of the disease. The acute phase occurs early and is associated with an inflammatory process and neutrophil infiltration into the synovium. The second chronic phase is related to effector T cell activation and the dysregulation of macrophage function. Creation of an immunomodulatory environment has been attributed to apoptotic cells themselves, apoptotic cell uptake by phagocytes as well as a lesser sensitivity of phagocytes capturing apoptotic bodies to activation. Therefore we evaluated the potential of apoptotic cell injection to influence the course of inflammation in SCW-induced arthritis in rats.
Methods:
Rat apoptotic thymocytes were injected i.p. (2.10e8) in addition to an arthritogenic dose of systemic SCW in LEW female rats. Control rats received SCW immunization and PBS. Rats were then followed for arthritis occurrence and circulating cytokine detection. At sacrifice, regulatory T cells (Treg) and macrophages were analyzed.
Results:
Apoptotic cell injection profoundly suppressed joint swelling and destruction typically observed during the acute and chronic phases of SCW-induced arthritis. Synovial inflammatory cell infiltration and bone destruction were also markedly suppressed. Ex vivo experiments revealed reduced levels of tumor necrosis factor (TNF) in cultures of macrophages from rats challenged with SCW in the presence of apoptotic thymocytes as well as reduced macrophage response to lipo-polysaccharide (LPS). Moreover, apoptotic cell injection induced higher Foxp3+ Tregs in the lymphoid organs, especially in the draining lymph nodes.
Conclusions:
Our data indicate that apoptotic cells modulate macrophage function and result in Treg generation/increase. This may be involved in inhibition of inflammation and amelioration of arthritis. This highlights and confirms previous studies showing that in vivo generation of Tregs using apoptotic cell injection may be a useful tool to prevent and treat inflammatory autoimmune responses.
Background:
Depression and elevated depression symptoms are more prevalent in patients with type 2 diabetes than in those without diabetes and are associated with adverse health outcomes and increased total healthcare utilization. There is, however, a lack of evidence on (cost-) effectiveness of treatment options for minor and mild-major depression in patients with type 2 diabetes. In this paper we describe the design and methods of the economic evaluation, which will be conducted alongside the MIND-DIA trial (Cognitive behaviour therapy in elderly type 2 diabetes patients with minor or mild-major depression). The objective of the economic evaluation (MIND-DIA CEA) is to examine incremental cost-effectiveness of a diabetes-specific cognitive behaviour group therapy (CBT) as compared to intensified treatment as usual (TAU) and to a guided self-help group intervention (SH).
Methods:
A total number of 315 patients (aged 65-85) will be included in the study and followed for 15 months. During this period data on health sector costs, patient costs and societal productivity/time costs will be collected in addition to clinical data. Person-years free of moderate/severe major depression, quality adjusted life years (QALYs), and cumulative costs will be estimated for each arm of the trial (CBT, TAU and SH). To determine cost-effectiveness of the CBT, differences in costs and effects between the CBT group and TAU/SH group will be calculated.DiscussionCBT is a potentially effective treatment option to improve quality of life and to avoid the onset of a moderate/severe major depression in elderly patients with type 2 diabetes and minor or mild-major depression. This hypothesis will be evaluated in the MIND-DIA trial. Based on these results the associated economic evaluation will provide additional evidence on the cost-effectiveness of CBT in this target population. Methodological strengths and weaknesses of the planned economic evaluation are discussed.Trial registrationThe MIND-DIA study has been registered at the Current Controlled Trials Register (ISRCTN58007098).
Background:
Creatine synthesis takes place predominately in the kidney and liver via a two-step process involving AGAT (L-arginine:glycine amidinotransferase) and GAMT (guanidinoacetate methyltransferase). Creatine is taken into cells via the creatine transporter (CrT), where it plays an essential role in energy homeostasis, particularly for tissues with high and fluctuating energy demands. Very little is known of the fetal requirement for creatine and how this may change with advancing pregnancy and into the early neonatal period. Using the spiny mouse as a model of human perinatal development, the purpose of the present study was to comprehensively examine the development of the creatine synthesis and transport systems.
Results:
The estimated amount of total creatine in the placenta and brain significantly increased in the second half of pregnancy, coinciding with a significant increase in expression of CrT mRNA. In the fetal brain, mRNA expression of AGAT increased steadily across the second half of pregnancy, although GAMT mRNA expression was relatively low until 34 days gestation (term is 38-39 days). In the fetal kidney and liver, AGAT and GAMT mRNA and protein expression were also relatively low until 34-37 days gestation. Between mid-gestation and term, neither AGAT or GAMT mRNA or protein could be detected in the placenta.
Conclusions:
Our results suggest that in the spiny mouse, a species where, like the human, considerable organogenesis occurs before birth, there appears to be a limited capacity for endogenous creatine synthesis until approximately 0.9 of pregnancy. This implies that a maternal source of creatine, transferred across the placenta, may be essential until the creatine synthesis and transport system matures in preparation for birth. If these results also apply to the human, premature birth may increase the risk of creatine deficiency.
I have noted since publication of our paper [Brabin BJ, et al. Monitoring and evaluation of malaria in pregnancy - developing a rational basis for control. Malar J. 2008, 7(Suppl 1):S6] that my surname is incorrect. My surname has been spelt incorrectly as Wasame as it is actually spelt Warsame.