Polymorphisms in gene encoding TRPV1-receptor involved in pain perception are unrelated to chronic pancreatitis

Background  

The major clinical feature in chronic pancreatitis is pain, but the genetic basis of pancreatic pain in chronic pancreatitis is poorly understood. The transient receptor potential vanilloid receptor 1 (TRPV1) gene has been associated with pain perception, and genetic variations in TRPV1 may modify the presence and phenotype of chronic pancreatitis. The aim of our study was to investigate the genetic variation of TRPV1 in Dutch patients with chronic pancreatitis and healthy controls.     

Pain and musculoskeletal pain syndromes in adolescents

The presence of musculoskeletal pain was evaluated in adolescents. Pain was reported by 40% of respondents, benign joint hypermobility syndrome by 10%, myofascial syndrome by 5%, tendonitis by 2%, and fibromialgia by 1%. Logistical regression analysis indicated that sex and age were predictive of pain.     

Laparoscopic tension-free repair of anterior abdominal wall incisional and ventral hernias with an intraperitoneal Gore-Tex mesh: prospective study and review of the literature

BACKGROUND: Recurrence rates after repair of incisional and ventral hernias range from 18% to 52%. Prosthetic open repair has decreased this rate, but the wide fascial dissection it requires increases the complication rate. Laparoscopic repair is a safe and effective alternative. PATIENTS AND METHODS: A prospective study was performed including 86 patients (63 women and 23 men) with a mean age of 54 years (range 29-79 years) having incisional or ventral hernias who underwent laparoscopic repair in our institution between July 1994 and October 2001. The majority of the patients were obese with a mean body mass index of 31.7 kg/m2. The abdominal wall defect size ranged from 2 X 1 cm to 20 X 13 cm. In all cases, a Gore-Tex mesh (Dual Mesh, W.L. Gore & Associates, Flagstaff, AZ, USA) was used in sizes ranging from 10 X 15 cm to 20 X 30 cm. RESULTS: Nineteen repairs were performed for recurrent hernias (12 incisional and 7 ventral). The mean operative time was 110.3 minutes (range 50-240 minutes). There was one open conversion (1.2%), one intraoperative complication (1.2%), and no deaths. There were no wound or mesh infections. Immediate postoperative complications occurred in 9 patients (10.6%) and late complications occurred in 16 patients (18.8%). The average hospital stay was 4.8 days (range 2-19 days). During a mean follow-up of 37 months (range 6-73 months), there were 6 hernia recurrences (7%). CONCLUSION: Laparoscopic repair of incisional hernia and ventral hernia appears to be safe, especially with the use of Gore-Tex mesh, and is proving to be effective as it decreases pain, complications, hospital stay, and recurrences.     

Distinct chaperone mechanisms can delay the formation of aggresomes by the myopathy-causing R120G alphaB-crystallin mutant

A familial form of desmin-related myopathy (DRM) is associated with a missense mutation (R120G) in alphaB-crystallin (alphaB) and is characterized by intracellular desmin aggregation. Because alphaB is a molecular chaperone that participates in the assembly of desmin filaments, it has been suggested that the desmin aggregation might be due to the loss of alphaB function. We report here that alphaBR120G has indeed impaired in vivo function and structure as reflected by a highly reduced capacity to protect cells against heat shock and by an abnormal supramolecular organization even in cells not expressing desmin. In many cells, alphaBR120G accumulated in inclusion bodies that had characteristics of aggresomes concentrating around the centrosome following a microtubule-facilitated process. Three distinct chaperone mechanisms could reduce or even prevent the formation of the alphaBR120G aggresomes. Wild-type alphaB and Hsp27 prevented aggresome formation by co-oligomerizing with alphaBR120G. Hsp70 with its co-chaperone Hdj-1 or Chip-1 but not a mutant of Chip-1 lacking ubiquitin ligase activity, reduced the frequency of aggresome formation likely by targeting alphaBR120G for degradation. Finally, HspB8 interacted only transiently with alphaB but nonetheless rescued the alphaBR120G oligomeric organization, suggesting that it acted as a true chaperone assisting in the folding of the mutant protein. Hence, the formation of inclusion bodies in alphaBR120G-mediated DRM is probably due to the misfolding of alphaBR120G per se and can be delayed or prevented by expression of the wild type alphaB allele or other molecular chaperones, thereby explaining the adult onset of the disease.     

Biological activity of designed photolabile metal nitrosyls: light-dependent activation of soluble guanylate cyclase and vasorelaxant properties in rat aorta

The biological and pharmacological utility of nitric oxide (NO) has led to the development of many classes of NO-donor compounds as both research tools and therapeutic agents. Many donors currently in use rely on thermal decomposition or bioactivation for the release of NO. We have developed several photolabile metal-nitrosyl donors that release NO when exposed to either visible or UV light. Herein, we show that these donors are capable of activating the primary "NO receptor", soluble guanylate cyclase (sGC), in a light-dependent fashion leading to increases in cGMP. Moreover, we demonstrate that these donors are capable of eliciting light-dependent increases of cGMP in smooth muscle cells and vasorelaxation of rat aortic smooth muscle tissue, all effects that are attributed to activation of sGC. The potential utility of these compounds as drugs and/or research tools is discussed.