interesting study

I saw this in Men's Health. I chased down the article. I think it's interesting to say the least. Hard to say if this affects guys on AAS.

Edit to add: nevermind.. It was anti inflammatory drugs that had a negative impact on muscle growth.. I'm losing my mind

ok andy since you are on the hunt now, how about the implications for Ketotifen?

jb

Seems to be the case for KETO that it can be beneficial in this anti-muscle wasting endeavor
HD

Ketotifen, an anti-histamine approved in Europe, is also a TNF inhibitor that may be useful in AIDS-related wasting. Studies report that the drug has potent anti-inflammatory activity and reduces edema, rashes and allergy-associated dermatitis. It may have activity against ulcerative colitis. A study of Ketotifen for eosinophilic gastroenteritis, a wasting syndrome of unknown cause, reported substantial weight gains.2 A number of studies note that the drug's chief side effects are appetite stimulation and weight gain. German studies report that Ketotifen reduces TNF secretions from peripheral white blood cells of people with HIV.3,4 A pilot study of Ketotifen in people with AIDS was presented at the Ninth International AIDS Conference in 1993.5 Another study using Ketotifen in combination with oxymetholone was also reported at the conference (see combination therapy section below).

In the monotherapy study, eight people with HIV and elevated TNF were treated with Ketotifen for three months. TNF levels decreased on therapy and increased after treatment discontinuation. Patients gained a mean of about six pounds on treatment, and lean body mass also increased significantly. Both weight and lean body mass decreased after going off therapy.

The Germans believe the suppression of TNF is Ketotifen's mechanism of action, but the drug may simply be treating malabsorption by virtue of its anti-inflammatory activity in the gut. To our knowledge, there are no ongoing studies of Ketotifen by itself, which is unfortunate as the drug is extremely safe. Dose-ranging studies might find greater activity at higher doses. At present, the drug's maker, Sandoz, has no plans of marketing the drug in the US. It is available through the PWA Health Group in New York.

Gold star to huge deep. this is available thru the CEM store and i can vouch that it works

jb

Re: interesting study

Posted by: jboldman

any thoughts on this?

jb

Horm Res. 2007;67 Suppl 1:64-70. Epub 2007 Feb 15. Links
How proinflammatory cytokines may impair growth and cause muscle wasting.Thissen JP.
Diabetes and Nutrition Unit, School of Medicine, Universite Catholique de Louvain, Brussels, Belgium.

Background: Cytokines, such as tumor necrosis factor (TNF)-alpha, interleukin (IL)-1beta and IL-6, that are released in response to injury are thought to inhibit growth and cause muscle wasting, at least in part by inhibiting anabolic hormones such as insulin-like growth factor I (IGF-I). Because critical illness in humans is accompanied by high circulating concentrations of growth hormone (GH), which is the main stimulus for IGF-I production by the liver, resistance to GH is thought to contribute to the IGF-I decline observed in catabolic diseases. While TNF-alpha seems to cause GH resistance mainly through downregulation of liver GH receptor expression, IL-6 may inhibit the GH-stimulated Janus kinase and signal transducer and activator of transcription pathways by induction of suppressors of cytokine signaling proteins. Elevations in circulating IGF binding protein-1 levels, as observed in many catabolic situations, may play a role in the decline in muscle mass by decreasing the rate of protein synthesis in skeletal muscle. Furthermore, the increase in local muscle cytokines produced during inflammation makes the muscle GH-resistant and reduces its own IGF-I production. Finally, not only decreased IGF-I production by muscle, but also decreased muscle sensitivity to the anabolic effects of IGF-I, may contribute to muscle wasting observed in response to severe stress. Conclusions: Taken together, proinflammatory cytokines may contribute to the growth retardation and muscle wasting that occur after injury by impairing the GH/IGF-I axis at several levels. Copyright (c) 2007 S. Karger AG, Basel.

sure

Peptides. 2006 Dec;27(12):3269-75.

Angiotensin II induces NF-kappaB activation in HUVEC via the p38MAPK pathway.

Guo RW, Yang LX, Li MQ, Liu B, Wang XM.

Department of Cardiology, Kunming General Hospital of Chengdu Military Area, Yunnan 650032, China.

Angiotensin II (Ang II) is the main active peptide of the renin-angiotensin system (RAS), producing a number of inflammatory mediators that lead to endothelial dysfunction and the progression of atherosclerosis. Ang II-induced NF-kappaB nuclear translocation plays a pivotal role in this response. This study examines the NF-kappaB activation mechanism elicited by Ang II in human umbilical vein endothelial cells (HUVEC). Electrophoretic mobility shift assays and Western blotting revealed that Ang II, signaling via AT(1), produces a time-dependent increase in NF-kappaB DNA binding and IkappaBalpha degradation. These results also demonstrate that Ang II leads to MAPK phosphorylation and p38MAPK pathway-induced NF-kappaB activation. Furthermore, AT(1) is required for p38MAPK phosphorylation induced by Ang II. This study provides evidence that Ang II elicits NF-kappaB activation via the p38MAPK pathway in HUVEC.

Br J Cancer. 2005 Feb 28;92(4):711-21.

NF-kappaB mediates proteolysis-inducing factor induced protein degradation and expression of the ubiquitin-proteasome system in skeletal muscle.

Wyke SM, Tisdale MJ.

Pharmaceutical Sciences Research Institute, Aston University, Birmingham B4 7ET, UK.

Loss of skeletal muscle in cancer cachexia has a negative effect on both morbidity and mortality. The role of nuclear factor-kappaB (NF-kappaB) in regulating muscle protein degradation and expression of the ubiquitin-proteasome proteolytic pathway in response to a tumour cachectic factor, proteolysis-inducing factor (PIF), has been studied by creating stable, transdominant-negative, muscle cell lines. Murine C(2)C(12) myoblasts were transfected with plasmids with a CMV promoter that had mutations at the serine phosphorylation sites required for degradation of I-kappaBalpha, an NF-kappaB inhibitory protein, and allowed to differentiate into myotubes. Proteolysis-inducing factor induced degradation of I-kappaBalpha, nuclear accumulation of NF-kappaB and an increase in luciferase reporter gene activity in myotubes containing wild-type, but not mutant, I-kappaBalpha proteins. Proteolysis-inducing factor also induced total protein degradation and loss of the myofibrillar protein myosin in myotubes containing wild-type, but not mutant, plasmids at the same concentrations as those causing activation of NF-kappaB. Proteolysis-inducing factor also induced increased expression of the ubiquitin-proteasome pathway, as determined by 'chymotrypsin-like' enzyme activity, the predominant proteolytic activity of the beta-subunits of the proteasome, protein expression of 20S alpha-subunits and the 19S subunits MSS1 and p42, as well as the ubiquitin conjugating enzyme, E2(14k), in cells containing wild-type, but not mutant, I-kappaBalpha. The ability of mutant I-kappaBalpha to inhibit PIF-induced protein degradation, as well as expression of the ubiquitin-proteasome pathway, confirms that both of these responses depend on initiation of transcription by NF-kappaB.

Atherosclerosis. 2006 Nov 14;

Angiotensin II induces IL-6 expression...............

for IL 6:

Quercetin.

---------------------------

NF-kB is transcription factor which induces the expression of many genes that participate in inflamatory response

. Last edited by oswaldosalcedo on 02-24-2007 at 06:05 PM

Diabetes. 2007 Feb 7

Visceral fat adipokine secretion is associated with systemic inflammation in obese humans.

Fontana L, Eagon JC, Trujillo ME, Scherer PE, Klein S.

Center for Human Nutrition, Washington University School of Medicine, St. Louis, Missouri, USA.

Although excess visceral fat is associated with non-infectious inflammation, it is not clear whether visceral fat is simply associated with, or actually causes metabolic disease in humans. To evaluate the hypothesis that visceral fat promotes systemic inflammation by secreting inflammatory adipokines into the portal circulation that drains visceral fat, we determined adipokine arteriovenous concentration differences across visceral fat, by obtaining portal vein and radial artery blood samples, in 25 extremely obese subjects (body mass index [BMI] 54.7+/-12.6 kg/m(2)) during gastric bypass surgery at Barnes-Jewish Hospital in St.Louis, MO. Mean plasma IL-6 concentration was approximately 50 % greater in portal vein than in radial artery in obese subjects (P=0.007). Portal vein IL-6 concentration correlated directly with systemic C-reactive protein concentrations (r=0.544, p=0.005). Mean plasma leptin concentration was approximately 20% lower in portal vein than in radial artery in obese subjects (P=0.0002). Plasma TNFalpha, resistin, MCP-1, and adiponectin concentrations were similar in portal vein and radial artery in obese subjects. These data suggest that visceral fat is an important site for IL-6 secretion, and provide a potential mechanistic link between visceral fat and systemic inflammation in persons with abdominal obesity.

I saw this in Men's Health. I chased down the article. I think it's interesting to say the least. Hard to say if this affects guys on AAS.

Edit to add: nevermind.. It was anti inflammatory drugs that had a negative impact on muscle growth.. I'm losing my mind

O.S., those are some good posts, good info, thanks,
HD

Posted by: jboldman

 

.

at your service!

J Nutr. 2004 Oct;134(10):2673-7.

Expression of interleukin-6 is greater in preadipocytes than in adipocytes of 3t3-L1 cells and C57BL/6J and ob/ob mice.

Harkins JM, Moustaid-Moussa N, Chung YJ, Penner KM, Pestka JJ, North CM, Claycombe KJ.

Department of Food Science and Human Nutrition, Michigan State University, East Lansing, MI 48824, USA.

Inflammation plays a major role in the development of chronic diseases such as cardiovascular disease and Type 2 diabetes. Further, it was demonstrated that obese animals and humans have significantly higher levels of circulating proinflammatory cytokines, such as interleukin-6 (IL-6). The aim of this study was to determine whether adipose tissue could be a major source of circulating IL-6 in leptin-deficient obese (ob/ob) mice by comparing the expression of IL-6 in different tissues of ob/ob mice. Our secondary goal was to determine whether preadipocytes are the source of adipose tissue IL-6. The ob/ob mice had higher levels of plasma IL-6 (P < 0.05) and adipose tissue IL-6 mRNA (P < 0.05) compared with lean mice. Interestingly, IL-6 mRNA levels of liver and spleen were not different between ob/ob and lean mice, whereas adipose tissue IL-6 mRNA levels were higher in the ob/ob mice compared with lean mice (P < 0.05). In addition, we showed that IL-6 secretion from the adipose tissue stromal vascular fraction cells was higher than that from fully differentiated adipocytes (P < 0.001). We further demonstrated that 3T3-L1 preadipocytes had significantly higher levels of lipopolysaccharide (LPS)-stimulated IL-6 mRNA and IL-6 secretion than differentiated 3T3-L1 adipocytes. Taken together, these data suggest that adipose tissue and preadipocytes from the adipose tissue stromal vascular fraction may contribute significantly to the increased plasma IL-6 levels in ob/ob mice.