Dysregulation of the immuno-inflammatory response, as seen in sepsis, may culminate in host cell and organ damage. Lipopolysaccharide from Gram-negative bacterial cell walls induces gene activation and subsequent inflammatory mediator expression. Gene activation is regulated by a number of transcription factors at the nuclear level, of which nuclear factor kappaB appears to have a central role. The redox (reduction-oxidation) cellular balance is important for normal cellular function, including transcription factor regulation. In sepsis, a state of severe oxidative stress is encountered, with host endogenous antioxidant defences overcome. This has implications for cellular function and the regulation of gene expression. This review gives an overview of the mechanisms by which transcription factor activation and inflammatory mediator overexpression occur in sepsis, together with the events surrounding the state of oxidative stress encountered and the effects on the host's antioxidant defences. The effect of oxidative stress on transcription factor regulation is considered, together with the role of antioxidant repletion in transcription factor activation and in sepsis in general. Other interventions that may modulate transcription factor activation are also highlighted.

BackgroundThe anabolic response to progressive resistance exercise training (PRET) in haemodialysis patients is unclear. This pilot efficacy study aimed to determine whether high-intensity intradialytic PRET could reverse atrophy and consequently improve strength and physical function in haemodialysis patients. A second aim was to compare any anabolic response to that of healthy participants completing the same program.MethodsIn a single blind controlled study, 23 haemodialysis patients and 9 healthy individuals were randomly allocated to PRET or an attention control (SHAM) group. PRET completed high-intensity exercise leg extensions using novel equipment. SHAM completed low-intensity lower body stretching activities using ultra light resistance bands. Exercises were completed thrice weekly for 12 weeks, during dialysis in the haemodialysis patients. Outcomes included knee extensor muscle volume by magnetic resonance imaging, knee extensor strength by isometric dynamometer and lower body tests of physical function. Data were analysed by a per protocol method using between-group comparisons.ResultsPRET elicited a statistically and clinically significant anabolic response in haemodialysis patients (PRET—SHAM, mean difference [95 % CI]: 193[63 to 324] cm3) that was very similar to the response in healthy participants (PRET—SHAM, 169[−41 to 379] cm3). PRET increased strength in both haemodialysis patients and healthy participants. In contrast, PRET only enhanced lower body functional capacity in the healthy participants.ConclusionsIntradialytic PRET elicited a normal anabolic and strength response in haemodialysis patients. The lack of a change in functional capacity was surprising and warrants further investigation.

This guideline is written primarily for doctors and nurses working in dialysis units and related areas of medicine in the UK, and is an update of a previous version written in 2009. It aims to provide guidance on how to look after patients and how to run dialysis units, and provides standards which units should in general aim to achieve. We would not advise patients to interpret the guideline as a rulebook, but perhaps to answer the question: “what does good quality haemodialysis look like?”The guideline is split into sections: each begins with a few statements which are graded by strength (1 is a firm recommendation, 2 is more like a sensible suggestion), and the type of research available to back up the statement, ranging from A (good quality trials so we are pretty sure this is right) to D (more like the opinion of experts than known for sure). After the statements there is a short summary explaining why we think this, often including a discussion of some of the most helpful research. There is then a list of the most important medical articles so that you can read further if you want to – most of this is freely available online, at least in summary form.A few notes on the individual sections: This section is about how much dialysis a patient should have. The effectiveness of dialysis varies between patients because of differences in body size and age etc., so different people need different amounts, and this section gives guidance on what defines “enough” dialysis and how to make sure each person is getting that. Quite a bit of this section is very technical, for example, the term “eKt/V” is often used: this is a calculation based on blood tests before and after dialysis, which measures the effectiveness of a single dialysis session in a particular patient.This section deals with “non-standard” dialysis, which basically means anything other than 3 times per week. For example, a few people need 4 or more sessions per week to keep healthy, and some people are fine with only 2 sessions per week – this is usually people who are older, or those who have only just started dialysis. Special considerations for children and pregnant patients are also covered here.This section deals with membranes (the type of “filter” used in the dialysis machine) and “HDF” (haemodiafiltration) which is a more complex kind of dialysis which some doctors think is better. Studies are still being done, but at the moment we think it’s as good as but not better than regular dialysis.This section deals with fluid removal during dialysis sessions: how to remove enough fluid without causing cramps and low blood pressure. Amongst other recommendations we advise close collaboration with patients over this.This section deals with dialysate, which is the fluid used to “pull” toxins out of the blood (it is sometimes called the “bath”). The level of things like potassium in the dialysate is important, otherwise too much or too little may be removed. There is a section on dialysate buffer (bicarbonate) and also a section on phosphate, which occasional...

No abstract