Delayed and persistent suppression of bronchoconstriction by trypsin in the airway lumen.

Mucosal trypsin, a protease-activated receptor (PAR) stimulant, may have an endogenous bronchoprotective role on airway smooth muscle. To test this possibility the effects of lumenal trypsin on airway tone in segments of pig bronchus were tested. Bronchial segments from pigs were mounted in an organ chamber containing Kreb's solution. Contractions were assessed from isovolumetric lumen pressure induced by acetylcholine (ACh) or carbachol added to the adventitia. Trypsin, added to the airway lumen (300 microg x mL(-1)), had no immediate effect on smooth muscle tone but suppressed ACh-induced contractions after 60 min, for at least 3 h. Synthetic activating peptides (AP) for PAR1, PAR2 or PAR3 were without effect, but PAR4 AP caused rapid, weak suppression of contractions. Lumenal thrombin was without effect and did not prevent the effects of trypsin. Effects of trypsin were reduced by N(omega)-nitro-L-arginine methyl ester but not indomethacin. Trypsin, thrombin and PAR4 AP released prostaglandin E2. Adventitially, trypsin, thrombin and PAR4 AP (but not PAR2 AP) relaxed carbachol-toned airways after <3 min. The findings of this study show that trypsin causes delayed and persistent bronchoprotection by interacting with airway cells accessible from the lumen. The signalling mechanism may involve nitric oxide synthase but not prostanoids or protease-activated receptors.     

Late results with biograft in peripheral arterial surgery

A total of 106 vascular reconstructions below the inguinal ligament including axillo-femoral and femoro-femoral bypasses were performed using 137 Dardik's human umbilical veins. The indication for surgery was limb salvage in 29%. The distal anastomosis was done with the popliteal artery above the knee in 53 cases, below the knee in 31, and with a tibial artery in 1. The axillo-femoral bypass was performed in 21 cases, and femoro-femoral bypass in 32. The accumulated graft patency rates of femoro-popliteal bypass at 1 yr./3 yrs./5 yrs. were 93%/75%/75%, those of femoro-femoral bypass were 85%/85%/85%, and those of axillo-femoral bypass were 54%/27%/27%. No special risk factor influencing patency rate was found from this study. In long term period, graft aneurysm was observed in 3 cases. It is concluded that the human umbilical vein is the graft material of choice for femoro-popliteal or femoro-femoral bypass when the saphenous vein is not available, and the careful follow-up is important because of the risk of graft aneurysm.     

Mild gentamicin nephrotoxicity reduces the progression of chronic adriamycin nephrosis

SUMMARY: The effect of mild acute tubular injury on the progression of tubulointerstitial fibrosis was studied in pair-fed uninephrectomized male Wistar rats with established adriamycin nephrosis ( n = 34). Rats were stratified into three groups according to endogenous creatinine clearance (CrCl), proteinuria (Upr) and body weight (BW): (i) group 1 (Fe, n = 12) received a single intraperitoneal injection of ferric nitrilotriacetate (5 mg Fe/kg BW); (ii) group 2 (G, n = 10) three daily subcutaneous injections of gentamicin (60 mg/kg BW) and; (iii) group 3 (C, n = 12) saline injections. Serial CrCl (day 2, day 5, weeks 2, 4, 6 and 8) and renal histology (week 8) were examined following administration of nephrotoxin. CrCl was reduced on d2 (Fe: 0.78 ± 0.23 mL/min; mean ± SD) and day 5 (G: 0.91 ± 0.36 mL/min) as compared with C (1.22 ± 0.12 mL/min; P <0.05). There was no change in the serum creatinine and functional recovery occurred by d5 (Fe) and week 2 (G). Upr decreased transiently in G at week 2 (G: 482 ± 208 mg/day vs C: 716 ± 233; P = 0.05) despite similar food intake, baseline Upr and CrCl. At week 8, CrCl in Fe (0.84 ± 0.40 mL/min) was similar to C (0.84 ± 0.58 mL/min), whereas in G it remained stable (1.27 ± 0.39 mL/min; P <0.05). By morphometric analysis, mean relative interstitial volume (RIV) and glomerulosclerosis (GS) in Fe (RIV: 28.5 ± 13.4%; GS: 10.3 ± 12.3%) was no different to C (RIV: 24.5 ± 12.5%; GS: 20.9 ± 20.0%), whereas both parameters were reduced in G (RIV: 14.1 ± 8.1%; GS: 4.0 ± 4.8%; P <0.05). Mild gentamicin nephrotoxicity therefore reduced the progression of adriamycin nephrosis. the mechanism of this finding is unclear, but it may relate to altered glomerular and tubular cell handling of protein.     

Do ethnicity and gender have an impact on pain thresholds in minor dermatologic procedures?

Background and Objectives: The perception of pain is a personal experience influenced by many factors, including genetic, ethnic and cultural issues. Understanding these perceptions is especially important in dermatologic patients undergoing minor surgical operations and who often differ in their pain response to surgical treatments. Little is known about how these differences affect the perception of experimental pain. The purpose of this study was to determine experimental pain perception differences in three distinct East Asian ethnic populations.
Methods: Pain thresholds were examined with a psychophysical computerized quantitative thermal sensory testing device (TSA 2001) in healthy volunteers recruited from three different Asian ethnic groups. Using the methods of limits, experimental pain perception threshold was measured on the forehead and volar aspect of the forearm in 49 healthy subjects. The measurements were then repeated after skin barrier perturbation with adhesive tape stripping of the stratum corneum. All three ethnic groups were analyzed separately with respect to age, gender educational level and skin type.
Results: A total of 20 Chinese, 14 Malay and 15 Indian subjects completed the study. Thermal pain thresholds were similar in all three ethnic groups before and after tape strippings. No significant differences were noted between genders.
Conclusions: Using quantitative sensory thermal testing, we demonstrated that no significant differences in pain occur between different races and genders.