Just to follow up on our discussion about handwashing--it's known that handwashing in child care centers helps to decrease illness/absenteeism, but this was a RCT (randomly controlled trial) to look at children in child care and the effect of good hand hygiene (and alcohol-based sanitizers) at home.
A randomized, controlled trial of a multifaceted intervention including alcohol-based hand sanitizer and hand-hygiene education to reduce illness transmission in the home.
Sandora TJ, Taveras EM, Shih MC, Resnick EA, Lee GM, Ross-Degnan D, Goldmann DA.
Division of Infectious Diseases, Children's Hospital Boston, Harvard Medical School, Boston, MA, USA. thomas.sandora@childrens.harvard.edu
OBJECTIVE: Good hand hygiene may reduce the spread of infections in families with children who are in out-of-home child care. Alcohol-based hand sanitizers rapidly kill viruses that are commonly associated with respiratory and gastrointestinal (GI) infections. The objective of this study was to determine whether a multifactorial campaign centered on increasing alcohol-based hand sanitizer use and hand-hygiene education reduces illness transmission in the home. METHODS: A cluster randomized, controlled trial was conducted of homes of 292 families with children who were enrolled in out-of-home child care in 26 child care centers. Eligible families had > or =1 child who was 6 months to 5 years of age and in child care for > or =10 hours/week. Intervention families received a supply of hand sanitizer and biweekly hand-hygiene educational materials for 5 months; control families received only materials promoting good nutrition. Primary caregivers were phoned biweekly and reported respiratory and GI illnesses in family members. Respiratory and GI-illness-transmission rates (measured as secondary illnesses per susceptible person-month) were compared between groups, adjusting for demographic variables, hand-hygiene practices, and previous experience using hand sanitizers. RESULTS: Baseline demographics were similar in the 2 groups. A total of 1802 respiratory illnesses occurred during the study; 443 (25%) were secondary illnesses. A total of 252 GI illnesses occurred during the study; 28 (11%) were secondary illnesses. The secondary GI-illness rate was significantly lower in intervention families compared with control families (incidence rate ratio [IRR]: 0.41; 95% confidence interval [CI]: 0.19-0.90). The overall rate of secondary respiratory illness was not significantly different between groups (IRR: 0.97; 95% CI: 0.72-1.30). However, families with higher sanitizer usage had a marginally lower secondary respiratory illness rate than those with less usage (IRR: 0.81; 95% CI: 0.65-1.09). CONCLUSIONS: A multifactorial intervention emphasizing alcohol-based hand sanitizer use in the home reduced transmission of GI illnesses within families with children in child care. Hand sanitizers and multifaceted educational messages may have a role in improving hand-hygiene practices within the home setting.
24 September 2009
22 September 2009
The role of Killer T cells in adipose tissue inflammation
A number of good posts have gone up in recent weeks detailing the now well established connection between systematic insulin resistance and a state of chronic low grade inflammation in adipose tissue. ElhamV495K and explore in more detail the vast web of cytokine and chemokine interactions involved between adipose tissue and the invasive macrophages (predominantly M1) that accompany (cause?) this chronic inflammation; both do a good job, as well, of highlighting the difficulty of unraveling the cause and effect nature of this incredibly complex system.
In light of our lecture today on T cell development, I thought I'd add another piece to the puzzle: the role of CD3+CD8+CD4- cells (otherwise known as Killer T cells or CTL) in the development of obesity related adipose tissue inflammation and insulin resistance.
In both diet induced obese mice (DIO) and the leptin deficient ob/ob mice, the adipose tissue stromal vascular fraction has much higher levels of both macrophages and CTLs, and much lower levels of Helper T cells (defined by being CD3+CD4+CD8-). Furthermore, the increase in CTLs can be seen as early as 6 weeks on a high fat diet, while the increase in macrophages lags, not differing from control mice until 10 weeks. The presence of CTLs actually turns out to be necessary for initiation and maintence of macrophage recruitment: by regularly injecting mice with a CD8 antibody, the majority of M1 macrophage infiltration and many of the metabolic effects of DIO can be prevented (in young mice) or ameliorated (in mice with already established cronic inflammation).
Prior to reading this finding, the chronic inflammation associated with DIO looked, to me, very much like the innate immune response we learned about in our first class: damaged peripheral tissue releasing cytokines and chemokines, recruiting phagocytic white blood cells. However, this finding shows that the inflammation is actually directly tied to and reliant on the adaptive immune response. While the infiltrating CTLs are not monoclonal, as might be expected in a traditional "vs. self" autoimmune response, they do have preferential expression of two variable region receptor minigenes, suggesting that they are being activated by some epitope or family of epitopes in the adipose tissue (neither CTLs or adipose tissue alone will recruit macrophages, but lean adipose tissue combined with these CTLs is sufficient for M1 recruitment and activation).
Hopefully, this addition of another cell type to the already complicated of story of adipose tissue inflammation will help to unravel the series of events linking obesity to metabolic disease.
In light of our lecture today on T cell development, I thought I'd add another piece to the puzzle: the role of CD3+CD8+CD4- cells (otherwise known as Killer T cells or CTL) in the development of obesity related adipose tissue inflammation and insulin resistance.
In both diet induced obese mice (DIO) and the leptin deficient ob/ob mice, the adipose tissue stromal vascular fraction has much higher levels of both macrophages and CTLs, and much lower levels of Helper T cells (defined by being CD3+CD4+CD8-). Furthermore, the increase in CTLs can be seen as early as 6 weeks on a high fat diet, while the increase in macrophages lags, not differing from control mice until 10 weeks. The presence of CTLs actually turns out to be necessary for initiation and maintence of macrophage recruitment: by regularly injecting mice with a CD8 antibody, the majority of M1 macrophage infiltration and many of the metabolic effects of DIO can be prevented (in young mice) or ameliorated (in mice with already established cronic inflammation).
Prior to reading this finding, the chronic inflammation associated with DIO looked, to me, very much like the innate immune response we learned about in our first class: damaged peripheral tissue releasing cytokines and chemokines, recruiting phagocytic white blood cells. However, this finding shows that the inflammation is actually directly tied to and reliant on the adaptive immune response. While the infiltrating CTLs are not monoclonal, as might be expected in a traditional "vs. self" autoimmune response, they do have preferential expression of two variable region receptor minigenes, suggesting that they are being activated by some epitope or family of epitopes in the adipose tissue (neither CTLs or adipose tissue alone will recruit macrophages, but lean adipose tissue combined with these CTLs is sufficient for M1 recruitment and activation).
Hopefully, this addition of another cell type to the already complicated of story of adipose tissue inflammation will help to unravel the series of events linking obesity to metabolic disease.
Toll: An awesome gene.
In our first session we discussed the Toll-like receptors (TLRs) and were not sure about the correct origin/translation of 'Toll'. Below is an excerpt of an article describing the name-giving event and I will give my own interpretation of the sentence exclaimed by Nuesslein-Volhard following the excerpt.
Hansson GK, Edfeldt K.
Arterioscler Thromb Vasc Biol. 2005 Jun;25(6):1085-7. No abstract available.
PMID: 15923538 [PubMed - indexed for MEDLINE]
Toll to be paid at the gateway to the vessel wall.
"[...] Christiane Nüsslein-Volhard of the Max Planck Institute in Tübingen
analyzed mutations in fruit flies. In 1985, she saw a weird-looking fly
larva in which the ventral portion of the body was underdeveloped. Her
spontaneous comment was "Das war ja toll!" meaning "That was weird!" and she
coined the name Toll for the mutated gene. The protein product of the Toll
gene was found to cause ventralization, and normal functional activity of
Toll is necessary for dorsoventral polarity in the fly. The discovery of
Toll was one in a series of discoveries of genes controlling early
embryogenesis, which led to a Nobel prize for Nüsslein-Volhard in
1995.[...]"
'Toll' in old German means 'crazy', but 'toll' changed the meaning over time and today it is used similar to the English 'great', 'awesome' or 'cool'. I am sure that Nuesslein-Volhard, being a modern woman of the 1980's, exclaimed "That was [is?] awesome!" because she knew that this discovery would greatly enhance her career :-).
Hansson GK, Edfeldt K.
Arterioscler Thromb Vasc Biol. 2005 Jun;25(6):1085-7. No abstract available.
PMID: 15923538 [PubMed - indexed for MEDLINE]
Toll to be paid at the gateway to the vessel wall.
"[...] Christiane Nüsslein-Volhard of the Max Planck Institute in Tübingen
analyzed mutations in fruit flies. In 1985, she saw a weird-looking fly
larva in which the ventral portion of the body was underdeveloped. Her
spontaneous comment was "Das war ja toll!" meaning "That was weird!" and she
coined the name Toll for the mutated gene. The protein product of the Toll
gene was found to cause ventralization, and normal functional activity of
Toll is necessary for dorsoventral polarity in the fly. The discovery of
Toll was one in a series of discoveries of genes controlling early
embryogenesis, which led to a Nobel prize for Nüsslein-Volhard in
1995.[...]"
'Toll' in old German means 'crazy', but 'toll' changed the meaning over time and today it is used similar to the English 'great', 'awesome' or 'cool'. I am sure that Nuesslein-Volhard, being a modern woman of the 1980's, exclaimed "That was [is?] awesome!" because she knew that this discovery would greatly enhance her career :-).
Let a neutrophil hot pursuit put a smile on your face :)
http://www.youtube.com/watch?v=VAhM9OxZDkU . put on your headphones :)
Other cool Vids :
http://www.youtube.com/watch?v=cL9KY_ECzfo&feature=related pathogen binding on macrophage
http://www.youtube.com/watch?v=lrYlZJiuf18&feature=fvw Ab immune response
http://www.youtube.com/watch?v=I9zSe0qmXGw&feature=related Neutrophil moving to the site of infection
http://www.youtube.com/watch?v=KiLJl3NwmpU&feature=response_watch cytokine release
Other cool Vids :
http://www.youtube.com/watch?v=cL9KY_ECzfo&feature=related pathogen binding on macrophage
http://www.youtube.com/watch?v=lrYlZJiuf18&feature=fvw Ab immune response
http://www.youtube.com/watch?v=I9zSe0qmXGw&feature=related Neutrophil moving to the site of infection
http://www.youtube.com/watch?v=KiLJl3NwmpU&feature=response_watch cytokine release
21 September 2009
Adiponectin: The good adipokine
Or is it? Produced by small adipocytes, adiponectin has been known through the AMPK signaling pathway to increase glucose sensitivity, promote fatty acid catabolism and also to have energy conserving effects. Many have linked adiponectin to inflammation due to its inverse relationship with proinflammatory cytokines in metabolic syndrome, T2D and obesity.
These roles are only applicable in metabolic dysfunction. New evidence suggests that levels of the 'good' cytokine increase in other inflammatory disease states such as rheumatoid arthritis, chrohn's disease and others. It's relationship to other proinflammatory cytokines in the classic chronic inflammation seem to be synergistic. Instead of suppressing adiponectin, TNF a actually enhances its proinflammatory functions in these other disease states. Adiponectin is also in much higher concentration in general than other cytokines suggesting many different roles. In fact, the adipokine seems to serve different roles even in the same tissues depending on other mediators as seen in the visceral adipose tissue of Chron's disease. The diverse roles of adiponectin open a whole new area of study which could lead to better understanding of to the roles of adipose in inflammatory states.
http://www.ncbi.nlm.nih.gov/pubmed/18061654
These roles are only applicable in metabolic dysfunction. New evidence suggests that levels of the 'good' cytokine increase in other inflammatory disease states such as rheumatoid arthritis, chrohn's disease and others. It's relationship to other proinflammatory cytokines in the classic chronic inflammation seem to be synergistic. Instead of suppressing adiponectin, TNF a actually enhances its proinflammatory functions in these other disease states. Adiponectin is also in much higher concentration in general than other cytokines suggesting many different roles. In fact, the adipokine seems to serve different roles even in the same tissues depending on other mediators as seen in the visceral adipose tissue of Chron's disease. The diverse roles of adiponectin open a whole new area of study which could lead to better understanding of to the roles of adipose in inflammatory states.
http://www.ncbi.nlm.nih.gov/pubmed/18061654
Red, Hot, Painful, and Dangerous
Inflammation is a good thing and it works really hard to keep us healthy. Whenever we are hurt or infected it comes to the rescue kicking the intruders butt and stays around afterwards to help our tissues repair. However, like all good things too much can be a bad thing.
Our hero inflammation might actually be hurting us. Metabolic syndrome- loosely defined has having three of the five components: obesity, hypertension, dyslipidemia, insulin resistance, and atherosclerosis- appears to be partly caused by inflammation. All of the evidence points to inflammation.
Lets take a step back and be health detectives for a second. We know inflammation is designed to be good for us and obviously does not cause obesity so how is such a good thing involved in such a bad syndrome? A few of the best theories are as follows:
1) Obesity causes increased adiposity. In the obese state the adipocytes produce proinflammatory adipokines that cause insulin resistance as a means to put themselves on a diet. These adipokines along with increased numbers of M1 macrophages in the adiposity are responsible for increased systemic inflammation causing atherosclerosis and other bad things.
2) Inflammation causes insulin resistance as a means to provide the immune system with more energy during a pathogenic assault. Extrapolating from this statement I assume the following; this mechanism was under selective pressure and through divergence the acute insulin resistance became synonymous with acute pathogenic assault (like an alarm) and thus acute inflammation. During times of increased glucose levels the body gets confused and thinks it is under attack and causes insulin resistance even if the immunocompetent cells do not need extra energy.
3) Obesity increases lipolysis releasing Free Fatty Acids into the blood stream. Free Fatty Acids bind to TLRs causing cytokine release resulting in systemic inflammation.
These are just a few that I thought explained how a good thing can accidentally do bad things. Maybe inflammation is still our hero after all and it is trying to keep us healthy even if we are not. Maybe our bad lifestyle choices are what is really causing metabolic syndrome and inflammation is just getting a bad rap.
-Randy. I read 12 additional articles to find this information which also happens to be the number of beers Dr. Zoe Cohen has after 495k. Just kidding we all know Dr. Cohen probably rides her bicycle for 12 miles after class.
P.S. CRP was once especially useful for measuring acute inflammation because of a cheap, easy, and inexpensive laboratory technique. Take a plasma sample, if the subject has acute inflammation CRP in the sample will slow the sedimentation rate. So with some experience one can tell if a subject has acute inflammation based on if their plasma sedimentation’s rate is slower or faster.
Subscribe to:
Posts (Atom)