ABSTRACT:We report complete transection of major muscle and the systemic peptide treatment that induces healing of quadriceps muscle promptly and then maintains the healing with functional restoration. Initially, stable gastric pentadecapeptide BPC 157 (GEPPPGKPADDAGLV, M.W. 1419, PL-10, PLD-116, PL 14736 Pliva, Croatia; in trials for inflammatory bowel disease; wound treatment; no toxicity reported; effective alone without carrier) also superiorly accelerates the healing of transected Achilles tendon. Regularly, quadriceps muscle completely transected transversely 1.0 cm proximal to patella presents a definitive defect that cannot be compensated in rat. BPC 157 (10 mg, 10 ng, 10 pg/kg) is given intraperitoneally, once daily; the first application 30 min posttransection, the final 24 h before sacrifice. It consistently improves muscle healing throughout the whole 72-day period. Improved are: (i) biomechanic (load of failure increased); (ii) function (walking recovery and extensor postural thrust/motor function index returned toward normal healthy values); (iii) microscopy/immunochemistry [i.e., mostly muscle fibers connect muscle segments; absent gap; significant desmin positivity for ongoing regeneration of muscle; larger myofibril diameters on both sides, distal and proximal (normal healthy rat-values reached)]; (iv) macroscopic presentation (stumps connected; subsequently, atrophy markedly attenuated; finally, presentation close to normal noninjured muscle, no postsurgery leg contracture). Thus, posttransection healing-consistently improved-may suggest this peptide therapeutic application in muscle disorders. ß

BPC 157, at all investigated intervals, given locally or intraperitoneally, accelerated post-injury muscle healing and also helped to restore the full function.

The aim of this study was to determine flow-induced dilatation (FID) and the role of oxidative stress/antioxidative capacity in isolated, pressurized middle cerebral arteries (MCAs) of high salt (HS)-fed rats. Healthy male Sprague-Dawley rats (11 weeks old) were fed low salt (0.4% NaCl; LS group) or high salt (4% NaCl; HS group) diets for 1 week. Reactivity of MCAs in response to stepwise increases in pressure gradient (Δ10-Δ100 mmHg) was determined in the absence or presence of the superoxide dismutase (SOD) mimetic TEMPOL and/or the nitric oxide synthases (NOS) inhibitor N(ω) -nitro-l-arginine methyl ester (l-NAME). mRNA levels of antioxidative enzymes, NAPDH-oxidase components, inducible (iNOS) and endothelial nitric oxide synthases (eNOS) were determined by quantitative real-time PCR. Blood pressure (BP), antioxidant enzymes activity, oxidative stress in peripheral leukocytes, lipid peroxidation products and the antioxidant capacity of plasma were measured for both groups. FID was reduced in the HS group compared to the LS group. The presence of TEMPOL restored dilatation in the HS group, with no effect in the LS group. Expression of glutathione peroxidase 4 (GPx4) and iNOS in the HS group was significantly decreased; oxidative stress was significantly higher in the HS group compared to the LS group. HS intake significantly induced basal reactive oxygen species production in the leukocytes of mesenteric lymph nodes and splenocytes, and intracellular production after stimulation in peripheral lymph nodes. Antioxidant enzyme activity and BP were not affected by HS diet. Low GPx4 expression, increased superoxide production in leukocytes, and decreased iNOS expression are likely to underlie increased oxidative stress and reduced nitric oxide bioavailability, leading to impairment of FID in the HS group without changes in BP values.

Key pointsr Recent studies have shown that some of the deleterious effects of a high-salt (HS) diet are independent of elevated blood pressure and are associated with impaired endothelial function.r Increased generation of cyclo-oxygenase (COX-1 and COX-2)-derived vasoconstrictor factors and endothelial activation may contribute to impaired vascular relaxation during HS loading.r The present study aimed to assess the regulation of microvascular reactivity and to clarify the role of COX-1 and COX-2 in normotensive subjects on a short-term HS diet.r The present study demonstrates the important role of COX-1 derived vasoconstrictor metabolites in regulation of microvascular blood flow during a HS diet.r These results help to explain how even short-term HS diets may impact upon microvascular reactivity without changes in blood pressure and suggest that a vasoconstrictor metabolite of COX-1 could play a role in this impaired tissue blood flow. AbstractThe present study aimed to assess the effect of a 1-week high-salt (HS) diet on the role of cyclo-oxygenases (COX-1 and COX-2) and the vasoconstrictor prostaglandins, thromboxane A 2 (TXA 2 ) and prostaglandin F 2α (PGF 2α ), on skin microcirculatory blood flow, as well as to detect its effect on markers of endothelial activation such as soluble cell adhesion molecules. Young women (n = 54) were assigned to either the HS diet group (N = 30) (ß14 g day -1 NaCl ) or low-salt (LS) diet group (N = 24) (<2.3 g day -1 NaCl ) for 7 days. Post-occlusive reactive hyperaemia (PORH) in the skin microcirculation was assessed by laser Doppler flowmetry. Plasma renin activity, plasma aldosterone, plasma and 24 h urine sodium and potassium, plasma concentrations of TXB 2 (stable TXA 2 metabolite) and PGF 2α , soluble cell adhesion molecules and blood pressure were measured before and after the diet protocols. One HS diet group subset received 100 mg of indomethacin (non-selective COX-1 and COX-2 inhibitor), and another HS group subset received 200 mg of celecoxib (selective COX-2 inhibitor) before repeating laser Doppler flowmetry measurements. Blood pressure was unchanged after the HS diet, although it significantly reduced after the LS diet. Twenty-four hour urinary sodium was increased, and plasma renin activity and plasma aldosterone levels were decreased after the HS diet. The HS diet significantly impaired PORH and increased TXA 2 but did not change PGF 2α levels. Indomethacin restored microcirculatory blood flow and reduced TXA 2 . By contrast, celecoxib decreased TXA 2 levels but had no significant effects on blood flow. Restoration of of PORH by indomethacin during a HS diet suggests an important role of COX-1 derived vasoconstrictor metabolites in the regulation of microvascular blood flow during HS intake.

The effects of consumption of n-3 polyunsaturated fatty acids (n-3 PUFAs) enriched hen eggs on endothelium-dependent and endothelium-independent vasodilation in microcirculation, and on endothelial activation and inflammation were determined in young healthy individuals. Control group (N = 21) ate three regular hen eggs/daily (249 mg n-3 PUFAs/day), and n-3 PUFAs group (N = 19) ate three n-3 PUFAs enriched hen eggs/daily (1053 g n-3 PUFAs/day) for 3 weeks. Skin microvascular blood flow in response to iontophoresis of acetylcholine (AChID; endothelium-dependent) and sodium nitroprusside (SNPID; endothelium-independent) was assessed by laser Doppler flowmetry. Blood pressure (BP), body composition, body fluid status, serum lipid and free fatty acids profile, and inflammatory and endothelial activation markers were measured before and after respective dietary protocol. Results: Serum n-3 PUFAs concentration significantly increased, AChID significantly improved, and SNPID remained unchanged in n-3 PUFAs group, while none was changed in Control group. Interferon-γ (pro-inflammatory) significantly decreased and interleukin-10 (anti-inflammatory) significantly increased in n-3 PUFAs. BP, fat free mass, and total body water significantly decreased, while fat mass, interleukin-17A (pro-inflammatory), interleukin-10 and vascular endothelial growth factor A significantly increased in the Control group. Other measured parameters remained unchanged in both groups. Favorable anti-inflammatory properties of n-3 PUFAs consumption potentially contribute to the improvement of microvascular endothelium-dependent vasodilation in healthy individuals.