Burn injury has a systemic effect on reinnervation of skin and restoration of nociceptive function

Burn injury can lead to abnormal sensory function at both the injury and at distant uninjured sites. Here, we used a mouse model to investigate return of nociceptive function and reinnervation of the skin at the wound and uninjured distant sites following a 3% total burn surface area full‐thickness burn injury. We have previously shown that topical application of zinc‐metallothionein‐IIA (Zn₇‐MT‐IIA) accelerates healing following burn injury, and here, we investigated the potential of Zn₇‐MT‐IIA to enhance reinnervation and sensory recovery. In all burn‐injured animals, there was a significant reduction in nociceptive responses (Semmes–Weinstein filaments) at locations near and distant to the wound up to 8 weeks following injury. Cutaneous nerve reinnervation (assessed using protein gene product 9.5 immunohistochemistry) of the wound center was slow in the epidermis but rapid in the dermis. In the dermis, nerves subsequently degenerated both at the wound center and in distant uninjured areas. In contrast, epidermal nerve densities in the distant uninjured areas returned to normal, uninjured levels. Zn₇‐MT‐IIA did not influence return of nociceptive function nor reinnervation. We conclude that burn injury compromises nociceptive function and nerve regeneration both at the injury site and systemically; thus, therapies in addition to Zn₇‐MT‐IIA should be explored to return normal sensory function.     

Effects of Growth Hormone Administration on Bone Mineral Metabolism,PTH Sensitivity and PTH Secretory Rhythm in Postmenopausal Women With Established Osteoporosis

Introduction : Growth hormone (GH) replacement improves target organ sensitivity to PTH, PTH circadian rhythm, calcium and phosphate metabolism, bone turnover, and BMD in adult GH‐deficient (AGHD) patients. In postmenopausal women with established osteoporosis, GH and insulin like growth factor‐1 (IGF‐1) concentrations are low, and administration of GH has been shown to increase bone turnover and BMD, but the mechanisms remain unclear. We studied the effects of GH administration on PTH sensitivity, PTH circadian rhythm, and bone mineral metabolism in postmenopausal women with established osteoporosis. Materials and Methods : Fourteen postmenopausal women with osteoporosis were compared with 14 healthy premenopausal controls at baseline that then received GH for a period of 12 mo. Patients were hospitalized for 24 h before and 1, 3, 6, and 12 mo after GH administration and half‐hourly blood and 3‐h urine samples were collected. PTH, calcium (Ca), phosphate (PO₄), nephrogenous cyclic AMP (NcAMP), β C‐telopeptide of type 1 collagen (βCTX), procollagen type I amino‐terminal propeptide (PINP), and 1,25‐dihydroxyvitamin D [1,25(OH)₂D] were measured. Circadian rhythm analysis was performed using Chronolab 3.0 and Student's t‐test and general linear model ANOVAs for repeated measures were used where appropriate. Results : IGF‐1 concentration was significantly lower in the women with established osteoporosis compared with controls (101.5 ± 8.9 versus 140.9 ± 10.8 μg/liter; p < 0.05) and increased significantly after 1, 3, 6, and 12 mo of GH administration (p < 0.001). Twenty‐four‐hour mean PTH concentration was higher in the osteoporotic women (5.4 ± 0.1 pM) than in healthy controls (4.4 ± 0.1 pM, p < 0.001) and decreased after 1 (5.2 ± 0.1 pM, p < 0.001), 3 (5.0 ± 0.1 pM, p < 0.001), 6 (4.7 ± 0.1 pM, p < 0.001), and 12 mo (4.9 ± 0.1 pM, p < 0.05) of GH administration compared with baseline. NcAMP was significantly lower in osteoporotic women (17.2 ± 1.2 nM glomerular filtration rate [GFR]) compared with controls (21.4 ± 1.4 nM GFR, p < 0.05) and increased after 1 (24.2 ± 2.5 nM GFR, p < 0.05), 3 (27.3 ± 1.5 nM GFR, p < 0.001), and 6 mo (32.4 ± 2.5 nM GFR, p < 0.001) compared with baseline. PTH secretion was characterized by two peaks in premenopausal women and was altered in postmenopausal women with a sustained increase in PTH concentration. GH administration also restored a normal PTH secretory pattern in the osteoporotic women. The 24‐h mean adjusted serum calcium (ACa) concentration increased at 1 and 3 mo (p < 0.001) and PO₄ at 1, 3, 6, and 12 mo (p < 0.001). 1,25(OH)₂D concentration increased after 3, 6, and 12 mo of GH (p < 0.05). An increase in urine Ca excretion was observed at 3 and 6 mo (p < 0.05), and the renal threshold for maximum tubular phosphate reabsorption rate (TmPO4/GFR) increased after 1, 3, 6, and 12 mo (p < 0.05). βCTX concentration increased progressively from 0.74 ± 0.07 μg/liter at baseline to 0.83 ± 0.07 μg/liter (p < 0.05) at 1 mo and 1.07 ± 0.09 μg/liter (p < 0.01) at 3 mo, with no further increase at 6 or 12 mo. PINP concentration increased progressively from baseline (60 ± 5 μg/liter) to 6 mo (126 ± 11 μg/liter, p < 0.001), with no further increase at 12 mo. The percentage increase in PINP concentration was significantly higher than βCTX (p < 0.05). Conclusions : Our study shows that GH has a regulatory role in bone mineral metabolism. GH administration to postmenopausal osteoporotic women improves target organ sensitivity to PTH and bone mineral metabolism and alters PTH secretory pattern with greater increases in bone formation than resorption. These changes, resulting in a net positive bone balance, may partly explain the mechanism causing the increase in BMD after long‐term administration of GH in postmenopausal women with osteoporosis shown in previous studies and proposes a further component in the development of age‐related postmenopausal osteoporosis.     

Effect of Basic Prehospital Trauma Life Support Program on Cognitive and Trauma Management Skills

p < 0.05) compared to 9.1 ± 2.3 for group II. Pre-PHTLS Adherence to Priority scores on a scale of 1 to 7 were similar (1.1 ± 0.9 for group I and 1.2 ± 1.0 for group II). Post-PHTLS group I Priority scores increased to 5.9 ± 1.1. Group II (1.1 ± 1.0) did not improve their post-PHTLS scores. The pre-PHTLS Organized Approach scores in the simulated trauma patients on a scale of 1 to 5 were 2.1 ± 1.0 for group I and 1.9 ± 1.2 for group II (NS) compared to 4.2 ± 0.9 ( p < 0.05) in group I and 2.0 ± 0.8 in group II after PHTLS. This study demonstrates improved cognitive and trauma management skills performance among prehospital paramedical personnel who complete the basic PHTLS program.     

Heart Rate Variability,Left Ventricular Functions,and Cardiac Autonomic Neuropathy in Patients Undergoing Chronic Hemodialysis

Objective.?Autonomic neuropathy and impairment of left ventricular functions (LVF) have been frequently encountered in chronic renal failure (CRF). The aim of the present study was to evaluate the relationship of cardiac autonomic modulation impairments, as assessed by means of heart rate variability (HRV), with clinical characteristics, and left ventricular function in the patients with CRF undergoing hemodialysis (HD). Methods.?Twenty control subjects (Group I) and 22 comparable by age and gender patients with CRF undergoing hemodialysis (Group II) were enrolled in the study. After routine clinical and biochemical evaluations, electrocardiography, and 2 Dimensional, M Mode echocardiography were performed in all participants. Frequency domain HRV analysis was studied by using Kardiosis System. The powers (P₁ and P₂) and the central frequencies (F₁ and F₂) of low and of high frequency spectral bands were recorded. Results.?End systolic (ESV) and end diastolic volumes (EDV) were significantly higher in Group II (59.3 ± 21.1 mL vs. 34.0 ± 14.3 mL and 131.5 ± 37.3 mL vs. 96.9 ± 18.9 mL, p<0.01, p<0.05, respectively) when compared to those of Group I. Ejection fraction (EF) and fractional shortening (FS) were significantly lower in Group II than in control subjects (52.3 ± 2.4% vs. 63.7 ± 10.1% and 0.29 ± 0.01 vs. 0.34 ± 0.07, p<0.001, p<0.05, respectively). P1 and P2 were decreased in Group II than in Group I (136.2 ± 173.9 m s² vs. 911.0 ± 685.5 and 96.5 ± 149.6 vs. 499.7 ± 679.5, p<0.001, p<0.01, respectively). Significant correlations were found between high frequency spectral power and dialysis duration (DD), ESV, EDV, EF, FS (r = 0.52 p<0.01, r = 0.68 p<0.001, r = 0.65 p<0.002, r = 0.66 p<0.02, and r = 0.69 p<0.01). Conclusion.?As a result, the dependence of cardiac autonomic neuropathy on the disease duration and degree of left ventricular function impairment was shown in the patients undergoing chronic hemodialysis.     

Liposome‐Encapsulated Hemoglobin Accelerates Bronchial Healing After Pneumonectomy in the Rat With or Without Preoperative Radiotherapy

Liposome‐encapsulated hemoglobin (LEH) has been reported to accelerate wound healing in the stomach and skin in an experimental setting. LEH was tested in bronchial anastomotic healing after radiation and pneumonectomy in the rat. Sprague‐Dawley rats (n = 61) received preoperative radiation (20 Gy) to the chest and underwent left pneumonectomy with bronchial stump closure using the Sweet method 4 days later, when they were randomized to receive intravenous infusion of LEH with high O₂ affinity (P₅₀O₂ = 17 mm Hg, 10 mL/kg, n = 32) or saline (n = 29). Additional rats (n = 18) were treated in the same way without preoperative radiation. Bronchial anastomotic healing was evaluated 2 days after surgery by determining the bursting pressure and infiltration of neutrophils, monocytes, and macrophages. Bronchial bursting pressure was elevated in the rats receiving LEH both in the unirradiated group (LEH 212 ± 78 vs. saline 135 ± 63 mm Hg, P < 0.05) and in rats with preoperative radiation (LEH 162 ± 48 vs. saline 116 ± 56 mm Hg, P < 0.01). Moreover, the percentage of rats with bursting pressure <100 mm Hg tended to be smaller in the unirradiated group (LEH 1/9 [11.1%] vs. saline 4/9 [44.4%], NS) and was significantly reduced in irradiated animals (LEH 3/32 [9.4%] vs. saline 11/29 [38%], P < 0.05). There were no morphological differences except for macrophage infiltration to the anastomotic area, which was significantly prominent in the LEH‐treated rats (P < 0.05) regardless of the presence or absence of preoperative irradiation (IR). The results suggest that LEH with high O₂ affinity may improve mechanical strength and morphological findings in bronchial anastomosis in rats regardless of the presence or absence of preoperative IR. The irradiated rats later treated with LEH had equivalent or better bronchial healing than that of saline‐treated naïve animals undergoing pneumonectomy alone.     

Procaine in Cardioplegia: The Effect on EDHF‐Mediated Function in Porcine Coronary Arteries

Abstract Objectives: Hyperkalemia in cardioplegia impairs the endothelium‐derived hyperpolarizing factor (EDHF)‐mediated function. This study examined the effect of procaine in cardioplegia on the EDHF‐mediated response in porcine coronary arteries. Methods: An isometric force study was performed in a myograph. Two rings taken from the same artery (diameter 200–450 μm) were incubated with Krebs solution (group I) or 20 mM K⁺ (group II) with/without procaine (1 mM) at 37°C for 1 hour. The EDHF‐mediated relaxation was induced by bradykinin (BK,‐10 ?‐6.5 log M) after U₄₆₆₁₉ (‐8 log M, in group I) or K⁺‐precontraction (in group II) in the presence of indomethacin (7 μM), N^G‐nitro‐L‐arginine (300 μM), and hemoglobin (20 μM). The membrane potential of a single smooth muscle cell was measured by a microelectrode after superfusion with Krebs solution with/without procaine for 1 hour. Results: The EDHF‐mediated relaxation was increased by the treatment with procaine with the EC₅₀ shifted leftward (97.3 ± 0.6% vs. 83.0 ± 5.1% at‐7 log M and 99.4 ± 0.6% vs. 96.7 ± 1.6% at‐6.5 log M, p < 0.05; EC₅₀.‐8.57 ± 0.24 vs.‐7.92 ± 0.23 log M, p < 0.05). Procaine decreased the BK‐induced hyperpolarization from‐72.3 ± 0.7 mV to‐68.8 ± 0.8 mV (‐6.5 log M, p < 0.01). The EDHF‐mediated relaxation in arteries exposed to 20 mM K⁺ was not altered by procaine (49.9 ± 7.4% vs. 55.8 ± 7.6%, p > 0.05). Conclusions: In the coronary arteries, procaine has a depolarizing effect but it enhances EDHF‐mediated relaxation. Addition of procaine in cardioplegia did not change the EDHF‐mediated endothelial function.     

Effect of Ulcerative Colitis in the Bursting Strength of Colonic Anastomoses in Rats

Inflammatory bowel disease may have a deleterious effect on bowel healing, but its difficult to demonstrate in clinical practice because of the association of multiple factors. An experiment was conducted in rats. They were divided in two groups: group I, a model of acetic acid induced-colitis, and group II, the control group. Both groups underwent a rectal resection and primary anastomosis. On postoperative day 7, the bursting strength of the anastomosis was evaluated. There were 44 rats in group I and 38 in group II. In 91% of group I rats there were histopathological changes compatible with inflammatory bowel disease (IBD). Mean bursting was significantly reduced in rats with acetic acid-induced IBD (142.18 ± 18.22 mm Hg in group I, and 208.85 ± 14.8 mm Hg in group II; p < .05). These results suggest a deleterious effect of IBD on bowel healing.     

Basic fibroblast growth factor accelerates and improves second‐degree burn wound healing

Second‐degree burns are sometimes a concern for shortening patient suffering time as well as the therapeutic choice. Thus, adult second‐degree burn patients (average 57.8 ± 13.9 years old), mainly with deep dermal burns, were included. Patients receiving topical basic fibroblast growth factor (bFGF) or no bFGF were compared for clinical scar extent, passive scar hardness and elasticity using a Cutometer, direct scar hardness using a durometer, and moisture analysis of the stratum corneum at 1 year after complete wound healing. There was significantly faster wound healing with bFGF, as early as 2.2 ± 0.9 days from the burn injury, compared with non‐bFGF use (12.0 ± 2.2 vs. 15.0 ± 2.7 days, p<0.01). Clinical evaluation of Vancouver scale scores showed significant differences between bFGF‐treated and non‐bFGF–treated scars (p<0.01). Both maximal scar extension and the ratio of scar retraction to maximal scar extension, elasticity, by Cutometer were significantly greater in bFGF‐treated scars than non‐bFGF–treated scars (0.23 ± 0.10 vs. 0.14 ± 0.06 mm, 0.59 ± 0.20 vs. 0.49 ± 0.15 mm: scar extension, scar elasticity, bFGF vs. non‐bFGF, p<0.01). The durometer reading was significantly lower in bFGF‐treated scars than in non‐bFGF–treated scars (16.2 ± 3.8 vs. 29.3 ± 5.1, p<0.01). Transepidermal water loss, water content, and corneal thickness were significantly less in bFGF‐treated than in non‐bFGF–treated scars (p<0.01).     

The value and limitations of L-arginine infusion on glomerular and tubular function in the ischemic/reperfused kidney

Purpose: The nitric oxide precursor, L-arginine, has been shown to have a salutary effect on ischemia and reperfusion injury in skeletal muscle, skin, and intestines. Because L-arginine also increases renal blood flow, glomerular filtration, and urine flow in experimental animals with normal renal function, we postulated that L-arginine may also improve renal function after renal ischemic injury.Methods: Eighteen adult New Zealand white rabbits weighing 3 to 3.5 kg were subjected to bilateral normothermic renal ischemia by clamping both renal pedicles for 1 hour followed by 2 hours of reperfusion. The animals were randomized into three groups: group I (control, n = 6) received no additional treatment; group II (pretreatment, n = 6) received systemic intravenous L-arginine at 150 mg/kg over 20 minutes before induction of ischemia; group III (posttreatment, n = 6) received systemic intravenous L-arginine at 150 mg/kg over 20 minutes from the onset of reperfusion. Urine flow, creatinine clearance (C_CR), fractional excretion of sodium (FENa), and renal failure index (RFI) were calculated before ischemia and 2 hours after reperfusion, by use of standard formulas. The changes of the various renal parameters were compared among the three groups.Results: Bilateral normothermic renal ischemia for 1 hour produced a significant deterioration of glomerular filtration as evidenced by a C_CR decrease from 11.1 ± 1.8 to 2.49 ± 0.9 ml/min ( p < 0.01), FENa increase from 2.9% ± 1.0% to 20.8% ± 1.5% ( p < 0.01) and RFI increase from 4.0 ± 1.3 to 28.8 ± 2.6 ( p < 0.01). Pretreatment with L-arginine (group II) minimized the deleterious effects caused by ischemia on glomerular filtration (C_CR of 2.49 ± 0.9 ml/min in group I vs 4.95 ± 2.5 ml/min in group II, p < 0.05) and tubular function (FENa of 20.8% ± 1.5% in group I vs 13.0% ± 5.6% in group II and RFI of 28.8 ± 2.6 in group I vs 18.6 ± 8.0 in group II, p < 0.05). Infusion of L-arginine at the onset of reperfusion (group III) produced a significant diuretic effect (urine flow from 32.6 ± 13.4 ml/hr in group I to 63.3 ± 18.8 ml/hr in group III, p < 0.05) and also minimized glomerular damage (C_CR from 2.49 ± 0.9 ml/min in group I to 4.80 ± 1.2 ml/min in group III, p < 0.05); however, no beneficial effect was observed on tubular function.Conclusion: Induction of nitric oxide production by systemic L-arginine infusion can best preserve glomerular and tubular function in the ischemic/reperfused kidney when given before the ischemic insult. (J VASC SURG 1995;21:453-9.)     

Does prostate configuration affect the efficacy and safety of GreenLight HPS™ laser photoselective vaporization prostatectomy (PVP)?

We evaluate the efficacy and safety of GreenLight HPS? laser photoselective vaporization prostatectomy (PVP) for the treatment of benign prostatic hyperplasia (BPH) with different prostate configuration. Patients were stratified into two groups: bilobe (group I) and trilobe (group II) BPH. Transurethral PVP was performed using a 120 W GreenLight HPS? side-firing laser system. American Urological Association Symptom Score (AUASS), Quality of Life (QoL) score, maximum flow rate (Q _max), and postvoid residual (PVR) were measured preoperatively and at 1 and 4 weeks and 3, 6, 12, 18, 24 and 36 months postoperatively. A number of 160 consecutive patients were identified (I: 86, II: 74). Among the preoperative parameters, there were significant differences (p?<?0.05) in prostate volume (I: 46.0?±?19.8; II: 87.5?±?39.6 ml), Q _max (I: 9.9?±?3.9; II: 8.7?±?3.5 ml/sec), PVR (I: 59.2?±?124.6; II: 97.7?±?119.1 ml) and PSA (I: 1.4?±?1.4; II: 3.6?±?2.6 ng/ml), while AUASS and QoL were similar (p?>?0.05). Significant differences (p?<?0.05) in laser utilization (I: 9.5?±?6.6; II: 19.5?±?11.6 min) and energy usage (I: 63.1?±?43.9; II: 132.5?±?81.1 kJ) were noted. Clinical outcomes (AUASS, QoL, Q _max, and PVR) showed immediate and stable improvement from baseline (p?<?0.05) within each group, but no significant differences between the two groups were observed during the follow-up period (p?>?0.05). The incidences of adverse events were low and similar in both groups. Our experience suggests that BPH configuration has little effect on the efficacy and safety of GreenLight HPS? laser PVP.     

Endotoxin‐induced inflammation in a rodent model up‐regulates IL‐1a expression and CD45+ leukocyte recruitment and increases the rate of reepithelialization and wound closure

Wound healing is traditionally divided into inflammation, proliferation, and remodeling phases. Several inflammatory mediators and cells regulate the inflammation phase. The specific roles for different mediators have not been clearly defined. The effects of inflammation phase modulation on wound healing were evaluated in this study. Rat full‐thickness wounds were divided into different experimental groups: (1) sterile hyper‐inflammatory wounds/endotoxin (topical endotoxin), (2) sterile hypo‐inflammatory/inhibitor group (cocktail of topical COX‐1 plus COX‐2 plus lipoxygenase inhibitors), and (3) control groups: topical saline or DMSO. After full‐thickness wound creation, custom‐made titanium chambers enclosed the wound, creating an isolated well‐controlled environment. Wound healing was followed over time; tissue biopsies and wound fluid samples were collected on days 1, 4, and 8 postoperatively. The validity of the inflammation model was confirmed by increased IL‐1a expression, increased CD45+ leukocytes recruitment in the hyper‐inflamed group as compared to the inhibitor and control groups. The reepithelialization percentage was significantly increased in the endotoxin group as compared to the inhibitor group on day 4 (60.75 vs. 22.05, p‐value <0.05) and both the inhibitor and the control group on day 8 (control group: 63.2%, inhibitor group: 28.9%, endotoxin group: 84.2%, p‐value <0.05). Also, the macroscopic wound closure was increased in the endotoxin group as compared to the inhibitor group and control group both on day 4 (control group: 69.9%, inhibitor group: 62.9%, endotoxin group: 81.9%, p‐value <0.05) and on day 8 (control group: 68.5%, inhibitor group: 69.1%, endotoxin group: 83.7%, p‐value <0.05). Endotoxin‐induced sterile inflammation up‐regulates IL‐1a expression and CD45+ leukocyte recruitment and results in faster rate of wound reepithelialization and wound closure in full‐thickness rodent wounds. Conversely, the wound reepithelialization and wound closure can be significantly delayed on treatment with a combination of cyclooxygenase and lipoxygenase inhibitors.     

L-Carnitine inhibits eryptosis induced by uremic serum and the related mechanisms

Abstract

Objective: To investigate whether L-carnitine (LC) inhibits eryptosis induced by uremic serum and the related mechanism. Methods: One percent erythrocyte suspension was cultured by three kinds of mediums in vitro, which was included in the control group (Group C, phosphate buffered saline [PBS]), the uremic serum group (Group U, 30% uremic serum?+?70% PBS) and the LC group (Group L, 30% uremic serum?+?70% PBS?+?200?umol/L LC), respectively. Erythrocytes were collected at 24 and 48?h, respectively. Phosphatidylserine (PS) was estimated from Annexin-V-binding and reactive oxygen species (ROS) by flow cytometry, glutathione (GSH) was estimated from Enzyme linked immunosorbent assays (ELISA) by Microplate reader. Results: Eryptosis in Group C increased as the incubating time extended (3.43?±?0.37 at 24?h, 4.21?±?0.44 at 48?h). Eryptosis increased in Group U compared with Group C (6.5 1?±?0.71 at 24?h, p?<?0.01; 8.55?±?0.76 at 48?h, p?<?0.01), while decreased in Group L compared with Group U (5.80?±?0.69 at 24?h, p?<?0.05; 7.87?±?0.76 at 48?h, p?<?0.05). Meanwhile, ROS of erythrocytes increased in Group U compared with Group C (33.12?±?1.61 versus 14.83?±?2.22 at 24?h, p?<?0.01; 42.06?±?1.81 versus 20.94?±?1.78 at 48?h, p?<?0.01), and GSH decreased in Group U compared with Group C (25.66?±?0.32 versus 31.27?±?0.38 at 24?h, p?<?0.01; 8.53?±?0.59 versus 17.29?±?0.54 at 48?h, p?<?0.01). ROS of erythrocytes decreased in Group L compared with Group C (26.29?±?1.69 at 24?h, p?<?0.01; 36.21?±?2.00 at 48?h, p?<?0.01). GSH increased in Group L compared with Group U (27.54?±?0.60 at 24?h, p?<?0.01; 15.18?±?0.42 at 48?h, p?<?0.01). Conclusions: LC inhibits eryptosis induced by uremic serum, which possibly relates to oxidative stress in part.     

Surgery for Asymptomatic Carotid Stenosis: A Study of Three Patient Subgroups

p < 0.01). Seven patients died within the first 30 postoperative days, including three who underwent combined single-stage procedures. Nine patients presented nonfatal stroke, including three who progressively recovered. The cumulative death-stroke rate (CDSR) was 5.12% overall, 3.54% in group I, 12.24% in group II, and 4.09% in group III. The difference between groups I and II was statistically significant (p < 0.05). Taking into account only deaths related to carotid surgery and stroke with permanent disability, the CDSR was 2.83% in group I and 3.25% in group III. Follow-up ranged from 24 to 132 months (mean: 66.2) with a total of 11 patients being lost from follow-up. Actuarial 5-year survival was 81.99 ± 7.13% in group I, 70.65 ± 13.72% in group II, and 68.51 ± 8.93% in group III. Differences between group I and both groups II (p < 0.01) and III (p < 0.05) were statistically significant. Overall 5-year patency was 95.59 ± 2.28%. Stroke occurred during follow-up in 13 patients. The probability of stroke-free survival was 95.29 ± 3.76% in group I, 91.03 ± 8.52% in group II, and 89.09 ± 6.39% in group III. The difference between groups I and III was statistically significant (p < 0.05). Patients with asymptomatic carotid lesions can be divided into different prognostic groups. Life expectancy is shorter for patients with multiple artery disease. Long-term stroke risk is higher in patients with nonhemispheric neurological manifestations.     

Effects of hPTH(1‐34) Infusion on Circulating Serum Phosphate, 1,25‐Dihydroxyvitamin D,and FGF23 Levels in Healthy Men

Fibroblast growth factor 23 (FGF23) promotes phosphaturia and suppresses 1,25‐dihydroxyvitamin D [1,25(OH)₂D] production. PTH also promotes phosphaturia, but, in contrast, stimulates 1,25(OH)₂D production. The relationship between FGF23 and PTH is unclear, and the acute effect of pharmacologically dosed PTH on FGF23 secretion is unknown. Twenty healthy men were infused with human PTH(1‐34) [hPTH(1‐34)] at 44 ng/kg/h for 24 h. Compared with baseline, FGF23, 1,25(OH)₂D, ionized calcium (iCa), and serum N‐telopeptide (NTX) increased significantly over the 18‐h hPTH(1‐34) infusion (p < 0.0001), whereas serum phosphate (PO₄) transiently increased and then returned to baseline. FGF23 increased from 35 ± 10 pg/ml at baseline to 53 ± 20 pg/ml at 18 h (p = 0.0002); 1,25(OH)₂D increased from 36 ± 16 pg/ml at baseline to 80 ± 33 pg/ml at 18 h (p < 0.0001); iCa increased from 1.23 ± 0.03 mM at baseline to 1.46 ± 0.05 mM at hour 18 (p < 0.0001); and NTX increased from 17 ± 4 nM BCE at baseline to 28 ± 8 nM BCE at peak (p < 0.0001). PO₄ was 3.3 ± 0.6 mg/dl at baseline, transiently rose to 3.7 ± 0.4 mg/dl at hour 6 (p = 0.016), and then returned to 3.4 ± 0.5 mg/dl at hour 12 (p = 0.651). hPTH(1‐34) infusion increases endogenous 1,25(OH)₂D and FGF23 within 18 h in healthy men. Whereas it is possible that the rise in PO₄ contributed to the observed increase in FGF23, the increase in 1,25(OH)₂D was more substantial and longer sustained than the change in serum phosphate. Given prior data that suggest that neither PTH nor calcium stimulate FGF23 secretion, these data support the assertion that 1,25(OH)₂D is a potent physiologic stimulator of FGF23 secretion.     

Influence of the ratio of particulate autogenous bone graft/platelet‐rich plasma on bone healing in critical‐size defects: A histologic and histometric study in rat calvaria

The purpose of this study was to analyze histomorphometrically the influence of the ratio of particulate autogenous bone (AB) graft/platelet‐rich plasma (PRP) on bone healing in surgically created critical‐size defects (CSD) in rat calvaria. Fifty rats were divided into five groups: Group C (control), Group AB, Group AB/PRP‐50, Group AB/PRP‐100, and Group AB/PRP‐150. A 5‐mm diameter critical‐size defect was created in the calvarium of each animal. In Group C, the defect was filled by blood clot only. In Group AB, the defect was filled with 0.01 mL of AB graft. In Groups AB/PRP‐50, AB/PRP‐100, and AB/PRP‐150, the defects were filled with 0.01 mL of AB graft combined with 50, 100, and 150 µL of PRP, respectively. All animals were euthanized at 30 days postoperative. Histomorphometry, using image analysis software, and histology analyses were performed. New Bone Area (NBA) and the remaining bone graft particles area (RPA) were calculated as a percentage of the total area of the original defect. Percentage data were transformed into arccosine for analysis. No defect completely regenerated with bone. Group AB/PRP‐50 (41.78 ± 13.48%) had a significantly greater NBA than Groups C (19.29 ± 5.11%), AB (27.43 ± 10.90%) or AB/PRP‐150 (19.17 ± 8.45%) (p < 0.05). No significant differences were observed between groups AB/PRP‐50 and AB/PRP‐100 or among groups AB, AB/PRP‐100, and AB/PRP‐150 with regard to NBA (p > 0.05). Group AB/PRP‐150 (31.59 ± 3.22%) had a significantly greater RPA than Groups AB (19.09 ± 5.21%), AB/PRP‐50 (17.33 ± 4.43%), and AB/PRP‐100 (19.72 ± 3.62%) (p < 0.001). No significant differences were observed among groups AB, AB/PRP‐50, and AB/PRP‐100 with regard to RPA (p > 0.05). The ratio AB graft/PRP influences bone healing in surgically created CSD in rat calvaria. © 2009 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 28:468–473, 2010     

Thymosin β4 administration enhances fracture healing in mice

Thymosin β₄ (Tβ₄) is a regenerative peptide that we hypothesized would promote healing of fractured bone. Mice received a bilateral fibular osteotomy and were given i.p. injections of either Tβ₄ (6 mg/kg) or saline. Calluses from saline‐ and Tβ₄‐treated mice were analyzed for: (1) biomechanical properties and (2) composition using micro‐computed tomography (µCT) and histomorphometry. Biomechanical analysis showed that Tβ₄‐treated calluses had a 41% increase in peak force to failure (p < 0.01) and were approximately 25% stiffer (p < 0.05) than saline‐treated controls. µCT analysis at 21 days post‐fracture showed that the fractional volume of new mineralized tissue and new highly mineralized tissue were respectively 18% and 26% greater in calluses from Tβ₄‐treated mice compared to controls (p < 0.01; p < 0.05, respectively). Histomorphometry complemented the µCT data; at 21 days post‐fracture, Tβ₄‐treated calluses were almost 23% smaller (p < 0.05), had nearly 47% less old cortical bone (p < 0.05) and had a 31% increase in new trabecular bone area/total callus area fraction compared with controls (p < 0.05). Our finding of enhanced biomechanical properties of fractures in mice treated with Tβ₄ provides novel evidence of the therapeutic potential of this peptide for treating bone fractures. © 2014 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 32:1277–1282, 2014.     

Topical application of the lectin Artin M accelerates wound healing in rat oral mucosa by enhancing TGF‐β and VEGF production

The lectin Artin M has been shown to accelerate the wound‐healing process. The aims of this study were to evaluate the effects of Artin M on wound healing in the palatal mucosa of rats and to investigate the effects of Artin M on transforming growth factor beta (TGF‐β) and vascular endothelial growth factor (VEGF) secretion by rat gingival fibroblasts. A surgical wound was created on the palatal mucosa of 72 rats divided into three groups according to treatment: C—Control (nontreated), A—Artin M gel, and V—Vehicle. Eight animals per group were sacrificed at 3, 5, and 7 days postsurgery for histology, immunohistochemistry and determination of the levels of cytokines, and growth factors. Gingival fibroblasts were incubated with 2.5 μg/mL of Artin M for 24, 48, and 72 hours. The expression of VEGF and TGF‐β was determined by enzyme‐linked immunosorbent assay. Histologically, at day 7, the Artin M group showed earlier reepithelialization, milder inflammatory infiltration, and increased collagen fiber formation, resulting in faster maturation of granular tissue than in the other groups (p < 0.05). Artin M–induced cell proliferation in vivo and promoted a greater expression of TGF‐β and VEGF in both experiments (p < 0.05). Artin M was effective in healing oral mucosa wounds in rats and was associated with increased TGF‐β and VEGF release, cell proliferation, reepithelialization, and collagen deposition and arrangement of fibers.     

The effects of local vanadium treatment on angiogenesis and chondrogenesis during fracture healing

This study quantified the effects of local intramedullary delivery of an organic vanadium salt, which may act as an insulin‐mimetic on fracture healing. Using a BB Wistar rat femoral fracture model, local vanadyl acetylacetonate (VAC) was delivered to the fracture site and histomorphometry, mechanical testing, and immunohistochemistry were performed. Callus percent cartilage was 200% higher at day 7 (p < 0.05) and 88% higher at day 10 (p < 0.05) in the animals treated with 1.5 mg/kg of VAC. Callus percent mineralized tissue was 37% higher at day 14 (p < 0.05) and 31% higher at day 21 (p < 0.05) in the animals treated with 1.5 mg/kg of VAC. Maximum torque to failure was 104% and 154% higher at 4 weeks post‐fracture (p < 0.05) for the healing femurs from the VAC‐treated (1.5 and 3.0 mg/kg) animals. Animals treated with other VAC doses demonstrated increased mechanical parameters at 4 weeks (p < 0.05). Immunohistochemistry detected 62% more proliferating cells at days 7 (p < 0.05) and 94% more at day 10 (p < 0.05) in the animals treated with 1.5 mg/kg VAC. Results showed 100% more vascular endothelial growth factor‐C (VEGF‐C) positive cells and 80% more blood vessels at day 7 (p < 0.05) within the callus subperiosteal region of VAC‐treated animals (1.5 mg/kg) compared to controls. The results suggest that local VAC treatment affects chondrogenesis and angiogenesis within the first 7–10 days post‐fracture, which leads to enhanced mineralized tissue formation and accelerated fracture repair as early as 3–4 weeks post‐fracture. © 2012 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 30:1971–1978, 2012     

Selective adenosine-A2A activation reduces lung reperfusion injury following transplantation

Background: The adenosine-A_2A receptor on the neutrophil is responsible for several anti-inflammatory actions. We hypothesized that DWH-146e, a selective adenosine-A_2A agonist, would reduce lung reperfusion injury following transplantation.MethodsWe used an isolated, whole blood–perfused, ventilated rabbit lung model. Donor rabbits underwent lung harvest after pulmonary arterial PGE₁ injection and Euro-Collins preservation solution flush, and lungs were preserved for 18 hours at 4°C. Group I lungs (n = 9) served as control subjects. Group II lungs (n = 9) were reperfused with whole blood that was first passed through a leukocyte-depleting filter. In group III (n = 9), DWH-146e was added to the blood reperfusate (25 μg/kg) immediately before reperfusion and was administered throughout the reperfusion period (1 μg/kg/min). All lungs were reperfused for 30 minutes.ResultsArterial oxygenation in group II and group III was significantly higher than that of group I after 30 minutes of reperfusion (514.27 ± 35.80 and 461.12 ± 43.77 vs 91.41 ± 20.58 mm Hg, p < .001). Pulmonary vascular resistance was significantly reduced in group III (22,783 ± 357 dynes · s · cm⁻⁵) compared to both group II and group I (31,057 ± 1743 and 36,911 ± 2173 dynes · s · cm⁻⁵, p < .001). Airway compliance was improved in groups II and III when compared to group I (1.68 ± 0.08 and 1.68 ± 0.05 vs 1.36 ± 0.13, p = .03). Microvascular permeability in group III was reduced to 106.82 ± 17.09 compared with 165.70 ± 21.83 ng Evans blue dye per gram of tissue in group I (p = .05). Group III myeloperoxidase activity was 39.88 ± 4.87 compared with 88.70 ± 18.69 ΔOD/g/min in group I (p = .03); group II myeloperoxidase activity was 56.06 ± 7.46.ConclusionsDWH-146e reduced lung neutrophil sequestration and dramatically improved pulmonary graft function. Neutrophils are important components of the inflammatory cascade of reperfusion injury and their source may include both the circulating blood and the lung graft itself. Selective adensosine-A_2A activation interrupts the neutrophil-mediated inflammatory response and reduces lung reperfusion injury following transplantation.     

Ischemia Increases the Twitch Latent Period in the Soleus and Extensor Carpi Radialis Longus Muscles from Adult Rats

Complete ischemia and reperfusion effects on twitch force (∫(F·t)), twitch latent period (TLP), maximal rate of rise of twitch tension (δF/δt)_max, and twitch maximum relaxation rate (TMRR) were assessed. We divided 36 adult rats into four groups; two control groups (n = 9), a group undergoing 1 hour of ischemia followed by 1 hour of reperfusion (n = 9), and one group exposed to 2 hours of ischemia followed by 1 hour of reperfusion (n = 9). We have induced twitch contractions every 10 minutes in the soleus and the extensor carpi radialis longus (ECRL). Twitch contractions were recorded and then analyzed for ∫(F·t), TLP, (δF/δt)_max, and TMRR. During 1 hour and 40 minutes of ischemia, TLP increased to 179 ± 24% (p < 0.05) in the soleus and to 184 ± 16% (p < 0.05) in the ECRL, an effect that was partially recovered during 1 hour of reperfusion. This increase started after 20 minutes of ischemia in the soleus and after 40 minutes of ischemia in the ECRL. The increase was faster in the ECRL and peaked at the same time for both muscular groups. ∫(F·t) and (δF/δt)_max decreased during 1 hour of ischemia to 46 ± 7% (p < 0.05) in the soleus and to 40 ± 7% (p < 0.05) in the ECRL. TMRR decreased during 1 hour of ischemia to 39 ± 5% (p < 0.05) in the soleus and to 54 ± 8% (p < 0.05) in the ECRL. During 1 hour of reperfusion all of them recovered close to control values.