Hi researcher,

Thanks for your reply.

It's interesting that you report high Cl levels. The studies I've been reading don't support this as a general thing. One study found an association with higher Cl and slower disease progression. I'd like to explore this association with bradykinin which you suggest. Are you taking an ACE inhibitor by any chance? Does the side effect of those drugs, which increase bradykinin levels, explain the coughing side-effect of these drugs? Is it due to increased TRPV1 signalling? Dr McCandless" mention of sneezing has me wonder whether this is an area to look at. I thought I'd read somewhere that ACE inhibitors were protective in ALS. This study looks interesting "Effect of kinin B(2) receptor ablation on skeletal muscle development and myostatin gene expression"

Mary

Evidence that enhanced nasal reactivity to bradykinin in patients with symptomatic allergy is mediated by neural reflexes☆☆☆★★★
Journal of Allergy and Clinical Immunology, Volume 97, Issue 6, Pages 1252-1263
M.RICCIO

Abstract
OBJECTIVE: The aim of this study was to determine whether allergic inflammation induces nasal hyperreactivity to bradykinin by enhancing neuronal responsiveness. METHODS: We compared the response to localized, unilateral nasal challenge with bradykinin in patients with perennial allergic rhinitis and nonallergic subjects, and in patients with seasonal allergic rhinitis challenged in and out of season. Weights of secretions from each nostril were recorded, and levels of albumin and lactoferrin in secretions recovered from each nostril were assayed. Contralateral administration of atropine (0.32 mg) was used to evaluate the role of cholinergic reflexes in nasal hyperresponsiveness to bradykinin. RESULTS: In patients with symptomatic allergy, bradykinin induced greater symptom scores than in asymptomatic atopic or nonallergic control subjects. Moreover, bradykinin caused sneezing in a majority of patients with symptomatic allergy but in none of the asymptomatic atopic or nonallergic control subjects. Only patients with symptomatic allergy showed dose-dependent bilateral increases in secretion weights and levels of the serous glandular marker, lactoferrin. In contrast, bradykinin induced similar increases in ipsilateral, but not contralateral, levels of albumin in all patient populations. Atropine inhibited contralateral secretion and lactoferrin production (p < 0.05) in patients with symptomatic allergy. CONCLUSION: The induction of sneezing and of atropine-inhibitable contralateral glandular secretion demonstrates that allergic inflammation causes nasal hyperreactivity to bradykinin, at least in part, by enhancing neuronal responsiveness. (J ALLERGY CLIN IMMUNOL 1996;97:1252-63.)

Lung. 2009 Nov 30. [Epub ahead of print]

Neuropeptides. 2009 Dec 30. [Epub ahead of print]

Effect of kinin B(2) receptor ablation on skeletal muscle development and myostatin gene expression.
de Picoli Souza K, Batista EC, Silva ED, Reis FC, Silva SM, Araujo RC, Luz J, Santos EL, Pesquero JB.

School of Environmental and Biological Science, Federal University of Grande Dourados, Rodovia Dourados - Itahum, Km 12, 79804-970 Dourados, MS, Brazil.

Bradykinin (BK) is an active peptide that binds to the kinin B(2) receptor and induces biological events during the development and adult life. In this study we aimed to investigate the effect of kinin B(2) receptor ablation in the postnatal skeletal muscle development and body composition in adult life. For studies of skeletal muscle development, control (C57Bl6 - WT) and B(2) receptor knockout mice (B(2)(-/-)) were sacrificed at 15, 30 and 90days after birth, the gastrocnemius skeletal muscle was weighed and myostatin gene expression evaluated by real time PCR. For energy balance determination, data from control and B(2)(-/-) at 90 and 120days were collected by calorimetric method. Body composition at 120days was determined by chloroform-methanol (total body fat) and Lowry-modified method (total body protein). The results show that B(2)(-/-) have significantly increased total body weight at 15, 30 and 90days of life, when compared to WT. The weight of the gastrocnemius skeletal muscle was also significantly increased at 30 and 90days of life. Body composition analyses revealed that B(2)(-/-) mice exhibit more total corporal protein and less total corporal fat. Energy balance revealed that B(2)(-/-) have increased metabolizable energy intake and energy expenditure when compared to control mice, resulting in a lower energy gain. Interestingly, myostatin mRNA expression was significantly decreased in 15 and 30days old B(2)(-/-) mice and after icatibant treatment of WT adult mice for 5days. In conclusion, together our results show that kinin B(2) receptor deletion increases lean mass, reduces fat mass and improves metabolism efficiency in mice. The mechanism involved in this phenotype could be related to the reduction of myostatin gene expression during postnatal life. Copyright © 2009 Elsevier Ltd. All rights reserved.

PMID: 20045188 [PubMed - as supplied by publisher]

Neurochem Res. 2003 May;28(5):711-4.

Influence of temocapril on cultured ventral spinal cord neurons.
Iwasaki Y, Ichikawa Y, Igarash O, Ikeda K, Kino****a M.

Fourth Department of Internal Medicine, Toho University Ohashi Hospital, 2-17-6 Ohashi Meguro-Ku, Tokyo 153-8515, Japan. yaso@med.toho-u.ac.jp

Temocapril, a angiotensin-converting enzyme (ACE) inhibitor, was tested for neurotrophic activity in primary explant cultures of ventral spinal cord of fetal rats (VSCC). Temocapril had a remarkable effect on neurite outgrowth with a 4.2- to 5.1-fold increased over that of control VSCC at their effective concentrations. In temocapril-treated VSCC, choline acetyltransferase (ChAT) activity was also increased 2.4-3.2 times over that of control at 10(-9) and 10(-8) M, respectively. Our data suggest that temocapril is a candidate for neurotrophic factors on spinal motor neurons in vitro. A possible therapeutic role for temocapril in damaged motor neurons, such as in motor neuropathy and amyotrophic lateral sclerosis, remains to be defined.

PMID: 12716021 [PubMed - indexed for MEDLINE]

http://ntp.niehs.nih.gov/index.cfm?objectid=070AC403-B110-CA79-3A23AF79DE7B752A
14-WEEK STUDY IN MICE

Groups of 10 male and 10 female mice were exposed to 2-butoxyethanol by inhalation at concentrations of 0, 31, 62.5, 125, 250, or 500 ppm, 6 hours per day, 5 days per week for 14 weeks. Two male and two female mice exposed to 500 ppm died and two males and two females were killed moribund during the first 2 weeks of the study. Final mean body weights of 125, 250, and 500 ppm male mice were significantly less than those of the chamber controls. Clinical findings were observed only in 500 ppm males and females that died or were killed moribund and included abnormal breathing, red urine stains, and lethargy. Hematologic evaluation indicated an anemia that was characterized as normocytic, normochromic, and regenerative in mice exposed to 62.5 ppm or greater; the anemia was more pronounced in females. Liver weights of males exposed to 500 ppm were significantly greater than the chamber controls. In mice either dying early or killed moribund, there were inflammation, necrosis, and ulceration of the forestomach; mediastinal pleura and peritoneal inflammation associated with the forestomach lesions; liver necrosis; renal tubule degeneration; atrophy of the spleen, thymus, and mandibular and mesenteric lymph nodes; and degeneration of the testis. Exposure-related increases in the incidences of hematopoietic cell proliferation and hemosiderin pigmentation of the spleen, Kupffer cell hemosiderin pigmentation of the liver, inflammation and epithelial hyperplasia of the forestomach, and renal tubule hemosiderin pigmentation occurred in male and/or female mice surviving to the end of the study.