Does the Hepatic Branch of Vagus Mediate the Secretion of Glucagon-Like Peptide-1 During the Roux-en-Y Gastric Bypass Surgery?

Objectives

The purpose of this study is to investigate the impact of the hepatic branch of the vagus and Roux-en-Y gastric bypass (RYGB) on the level of fasting and postprandial serum glucagon-like peptide-1 (GLP-1) in type 2 diabetic mellitus rats.

Methods

Randomized block design, factorial experiment. Forty-five type 2 diabetic rats were divided into four groups: sham operation (S, n?=?10) and sham operation with the hepatic branch of the vagotomy (SV, n?=?11), Roux-en-Y gastric bypass (RYGB, n?=?12) and RYGB without preservation of the vagus (RYGBV, n?=?12). Levels of fasting and postprandial serum GLP-1 30 min after 50 % glucose solution (2 g/kg) by gavage were determined before surgery and postoperatively at 1, 4, and 8 weeks. Interactions between RYGB and the common hepatic branch were also assessed.

Results

Roux-en-Y gastric bypass surgery significantly increased the concentration of postprandial serum GLP-1 and maintained it at a higher level (P?GLP-1 at the initial stage (P?P?>?0.05). Both RYGB and vagotomy of the hepatic branch had no influence on fasting serum GLP-1 (P?>?0.05).

Conclusions

During RYGB surgery for the long-term treatment of T2DM, preservation of the hepatic branch of the vagus might have no impact on serum GLP-1 level.     

Effects of weight reduction surgery on the abdominal wall fascial wound healing process

Background

Bariatric surgery patients enter into a catabolic state postoperatively, which can lead to an aberrant wound healing process. To improve the future treatment of morbidly obese patients, the aim of our study was to understand the link between bariatric surgery and alterations in the wound healing processes.

Methods

A total of 18 morbidly obese Zucker rats were separated into three groups and underwent one of three surgical procedures: Roux-en-Y gastric bypass (RYGB; n = 6); sleeve gastrectomy (GS; n = 6); or midline laparotomy only (n = 6). The rats were weighed on postoperative day 0, 3, 7, and 14. On day 14, the abdominal wall was harvested and underwent histologic and biomechanical evaluation.

Results

A significant difference was found in the weight gain between the laparotomy control group (LC) and bariatric surgical groups at 7 and 14 d. By postoperative day 7, the GS and RYGB rats weighed significantly less than the LC group, losing, on average, 7% and 6% of their initial body weight, respectively, and the LC gained 4% of their weight (P < 0.05). By postoperative day 14, the LC had gained 20% of their original weight, and the two bariatric groups both weighed significantly less (P < 0.05). The breaking strength in the RYGB group (0.42 ± 0.18 N/mm) was significantly lower statistically than LC (0.69 ± 0/19 N/mm). The LC and GS groups (0.62 ± 0.27 N/mm) did not show a significant difference. The results of the histologic analysis showed that the collagen deposition in the wound was significantly lower statistically in the RYGB group compared with the LC group. No histologic difference was noted between the RYGB and GS groups.

Conclusions

Malabsorptive bariatric surgery negatively affects wound healing both histologically and biomechanically compared with nonbariatric models. Although obesity remains a significant factor in the wound healing process, understanding the link between bariatric surgery and alterations in wound healing is imperative before advocating simultaneous repair of ventral hernias during concomitant bariatric surgery.     

Fenofibrate does not affect burn-induced hepatic endoplasmic reticulum stress

Background

Burn injury causes major metabolic derangements such as hypermetabolism, hyperlipidemia, and insulin resistance and is associated with liver damage, hepatomegaly, and hepatic endoplasmic reticulum (ER) stress. Although the physiological consequences of such derangements have been delineated, the underlying molecular mechanisms remain unknown. Previously, it was shown that fenofibrate improves patient outcome by attenuating postburn stress responses.

Methods

Fenofibrate, a peroxisome proliferator–activated receptor alpha agonist, regulates liver lipid metabolism and has been used to treat hypertriglyceridemia and hypercholesterolemia for many years. The aim of the present study is to determine the effects of fenofibrate on burn-induced hepatic morphologic and metabolic changes. We randomized rats to sham, burn injury, and burn injury plus fenofibrate. Animals were sacrificed and livers were assessed at 24 or 48 h post burn.

Results

Burn injury decreased albumin and increased alanine transaminase (P = 0.1 versus sham), indicating liver injury. Fenofibrate administration did not restore albumin or decrease alanine transaminase. In addition, ER stress was significantly increased after burn injury both with and without fenofibrate (P < 0.05 versus sham). Burn injury increased fatty acid metabolism gene expression (P < 0.05 versus sham), downstream of peroxisome proliferator–activated receptor alpha. Fenofibrate treatment increased fatty acid metabolism further, which reduced postburn hepatic steatosis (burn versus sham P < 0.05, burn + fenofibrate versus sham not significant).

Conclusions

Fenofibrate did not alleviate thermal injury–induced hepatic ER stress and dysfunction, but it reduced hepatic steatosis by modulating hepatic genes related to fat metabolism.     

Late Biliary Obstruction in Wistar Rats After Intermittent Hepatic Pedicle Clamping

Introduction

The temporary vascular occlusion of hepatic flow is one of the essential procedures in hepatic surgery.

Aim

Evaluate the late liver alterations after intermittent pedicle hepatic clamping (IHPC) in Wistar rats.

Methods

Male Wistar rats (n = 14) with average weight of 281.1 g, were anesthetized with intraperitoneal ketamine 5%. The IHPC group (n = 7) was submitted to U-shaped abdominal incision; the hepatic pedicle was isolated and submitted to IHPC ischemia 4 times, 5 minutes each, followed by reperfusion 4 times, 5 minutes each. The simulated operation group (n = 7) was subjected to anesthesia, laparotomy, and manipulation of the hepatic pedicle. On day 35, after fasting for 12 hours, liver biopsies were collected and blood was tested for liver aminotransferases (aspartate aminotransferase/alanine aminotransferase).

Results

All the IHPC group animals had a dilated common bile duct and increased liver enzymes (P < .05 by Mann-Whitney test). Ductular proliferation (100% of cases), porta-porta septa (42.8%), formation of lumps (42.8%), foci of necrosis (14.2%), and bile plugs (14, 2%) were observed only in the IHPC group.

Conclusion

In rats, IHPC caused morphologic features leading to biliary obstruction.     

Diabetes remission and glycemic response to pre-bariatric surgery diet

Background

Before bariatric surgery, some patients with type 2 diabetes mellitus (T2DM) experience improvement in blood glucose control and reduced insulin requirements while on a preoperative low-calorie diet (LCD). We hypothesized that patients who exhibit a significant glycemic response to this diet are more likely to experience remission of their diabetes in the postoperative period.

Materials and methods

Insulin-dependent T2DM patients undergoing bariatric surgery between August 2006 and February 2011 were eligible for inclusion. Insulin requirements at day 0 and 10 of the LCD were compared. Patients with a ≥50% reduction in total insulin dosage to maintain appropriate blood glucose control were considered rapid responders to the preoperative LCD. All others were non–rapid responders. We analyzed T2DM remission rates up to 1 y postoperatively.

Results

A total of 51 patients met inclusion criteria and 29 were categorized as rapid responders (57%). The remaining 22 were considered non–rapid responders (43%). The two groups did not differ demographically. Rapid responders had greater T2DM remission rates at 6 (44% versus 13.6%; P = 0.02) and 12 mo (72.7% versus 5.9%; P < 0.01). In patients undergoing laparoscopic gastric bypass, rapid responders showed greater excess weight loss at 3 mo (40.1% versus 28.2%; P < 0.01), 6 mo (55.2% versus 40.2%; P < 0.01), and 12 mo (67.7% versus 47.3%; P < 0.01).

Conclusions

Insulin-dependent T2DM bariatric surgery patients who display a rapid glycemic response to the preoperative LCD are more likely to experience early remission of T2DM postoperatively and greater weight loss.     

Selective double disconnection for cirrhotic portal hypertension

Background

To evaluate the effect of selective double portazygous disconnection with preserving vagus (SDPDPV) for patients with portal hypertension (PHT) in the authors' hospital.

Methods

Patients (453) with cirrhotic PHT who underwent either SDPDPV or pericardial devascularization with splenectomy (PDS) for variceal bleeding from February 2007 to January 2013 were retrospectively reviewed. The operation-relevant information, change of lavatory examination data, postoperative complications, and clinical outcomes were analyzed.

Results

There were no significant difference between the SDPDPV group and the PDS group of mean operative time and intraoperative blood loss (P >0.05). The free portal pressure in the SDPDPV group was much lower than PDS group significantly after operation (P <0.05). The test of biochemical profile of hepatocyte functions and Child-Pugh score at the end of the first postoperative year were significantly more altered in the SDPDPV group than in the PDS group (P <0.05). Except encephalopathy, occurrences or development of postoperative complications including rebleeding, ascites, and gastric stasis showed great difference between the two groups (P <0.05). The operative mortality rate and the 3-y survival rates were great difference between the two groups too (P <0.05).

Conclusions

The SDPDPV not only controls recurrent bleeding from varices with PHT effectively but also maintains normal dynamics of stomach and physiological function of intestine and hepatobiliary.     

Comparison Between Resection and Transplantation in Combined Hepatocellular and Cholangiocarcinoma

Objective

The treatment of choice for combined hepatocellular and cholangiocarcinoma (cHCC-CC) is surgical resection. However, the efficacy of liver transplantation is not clear. We compared the surgical outcome of hepatic resection and liver transplantation for cHCC-CC.

Patients and methods

From 1995 to 2012, 89 patients were diagnosed with cHCC-CC after hepatic resection and 8 patients diagnosed with cHCC-CC after liver transplantation. We excluded 21 patients who were American Joint Committee on Cancer Staging Stage III or IV and lost to follow-up. The outcomes were reviewed retrospectively.

Results

The poor prognostic factors in cHCC-CC patients who underwent hepatectomy were large tumor size (>5 cm), small safety margin (<2 cm), and low preoperative albumin level. The disease-free survival (DFS) and overall survival (OS) between the hepatectomy group (n = 68) and the liver transplant group (n = 8) was not statistically different (5-year DFS: 26.2% vs 37.5%, P = .333; 5-year OS: 42.1% vs 50%, P = .591). In the small tumor subgroup (tumor size <5 cm), the DFS and OS between the 2 surgical procedures was not different, and in the adequate resection margin subgroup (safety margin >2 cm), survival was comparable.

Conclusions

In well-selected cases with small tumor size and with preserved liver function, liver resection should be considered when complete resection is possible.     

Comparable early changes in gastrointestinal hormones after sleeve gastrectomy and Roux-En-Y gastric bypass surgery for morbidly obese type 2 diabetic subjects

Background

Sleeve gastrectomy (SG) and Roux-en-Y gastric bypass (RYGBP) are associated with similar type 2 diabetes mellitus (T2DM) resolution rates for morbidly obese subjects. However, the mechanisms underlying the resolution of T2DM after SG have not been clarified to date. This study aimed to compare the early changes in gastrointestinal hormones involved in insulin and glucagon secretion in morbidly obese T2DM subjects undergoing SG or RYGBP.

Methods

This prospective study investigated 12 subjects with T2DM who had undergone SG (n?=?6) or RYGBP (n?=?6). Five body mass index (BMI)-matched obese non-diabetic subjects and five BMI-matched obese diabetic subjects served as control subjects. Glucose, insulin, glucagon, glucagon-like peptide 1 (GLP-1), glucose-dependent insulinotropic polypeptide (GIP), and GLP-2 were determined after a standardized mixed liquid meal before surgery and 6?weeks afterward.

Results

After 6?weeks, five of the six subjects in each surgical group presented with T2DM remission, although the area under the curve (AUC)_0–120 of glucose was greater than that of the non-diabetic control subjects (P?0–120 of GLP-1 (P?P?P?Conclusions The data show that in a cohort of morbidly obese T2DM subjects, SG and RYGBP are associated with an early improvement in glucose tolerance, similar changes in insulin and glucagon secretion, and a similar GLP-1, GIP, and GLP-2 response to a standardized mixed liquid meal.     

Gastric Bypass-Related Effects on Glucose Control, β Cell Function and Morphology in the Obese Zucker Rat

Background

Roux-en-Y gastric bypass (RYGB) may improve beta cell function by mechanisms other than caloric restriction and body weight loss. We aimed to assess the impact of anatomical and hormonal alterations specific to RYGB on glucose homeostasis, β cell function and morphology.

Methods

Male Zucker^fa/fa rats underwent either RYGB (n?=?11) or sham surgeries (n?=?10). Five of the shams were then food restricted and body weight matched (BWM) to the RYGB rats. Six male Zucker^fa/+ rats underwent sham surgery and served as additional lean controls. Twenty-seven days after surgery, an oral glucose tolerance test (OGTT) was performed and plasma levels of glucose, insulin and glucagon-like peptide-1 (GLP-1) were measured. Immunohistological analysis of pancreatic islets was performed, and GLP-1 receptor and PDX-1 mRNA content were quantified.

Results

Shams consumed more food and gained more weight compared to both RYGB and BWM (p?<?0.001). Hyperglycaemia was evident in ad libitum-fed shams, whilst postprandial glucose levels were lower in RYGB compared to the BWM sham group (p?<?0.05). During the OGTT, RYGB rats responded with >2.5-fold increase of GLP-1. Histology revealed signs of islet degeneration in ad libitum-fed shams, but not in RYGB and sham BWM controls (p?<?0.001). GLP-1 receptor and PDX-1 mRNA content was similar between the RYGB and BWM shams but higher compared to ad libitum shams (p?<?0.05).

Conclusions

Combined molecular, cellular and histological analyses of pancreatic function suggest that weight loss alone, and not the enhancement of GLP-1 responses, is predominant for the short-term β cell protective effects of RYGB.

     

GLP-1 Response to a Mixed Meal: What Happens 10 Years after Roux-en-Y Gastric Bypass (RYGB)?

Background

Oral meal consumption increases glucagon-like peptide 1 (GLP-1) release which maintains euglycemia by increasing insulin secretion. This effect is exaggerated during short-term follow-up of Roux-en-y gastric bypass (RYGB). We examined the durability of this effect in patient with type 2 diabetes (T2DM) >10?years after RYGB.

Methods

GLP-1 response to a mixed meal in the 10-year post-RYGB group (n?=?5) was compared to lean (n?=?9), obese (n?=?6), and type 2 diabetic (n?=?10) controls using a cross-sectional study design. Analysis of variance (ANOVA) was used to evaluate GLP-1 response to mixed meal consumption from 0 to 300?min, 0?C20?min, 20?C60?min, and 60?C300?min, respectively. Weight, insulin resistance, and T2DM were also assessed.

Results

GLP-1 response 0?C300?min in the 10-year post-RYGB showed a statistically significant overall difference (p?=?0.01) compared to controls. Furthermore, GLP-1 response 0?C20?min in the 10-year post-RYGB group showed a very rapid statistically significant rise (p?=?0.035) to a peak of 40?pM. GLP-1 response between 20 and 60?min showed a rapid statistically significant (p?=?0.041) decline in GLP-1 response from ~40?pM to 10?pM. GLP-1 response in the 10-year post-RYGB group from 60 to 300?min showed no statistically significant difference from controls. BMI, HOMA, and fasting serum glucose before and >10?years after RYGB changed from 59.9????40.4, 8.7????0.88, and 155.2????87.6?mg/dl, respectively, and were statistically significant (p?Conclusions An exaggerated GLP-1 response was noted 10?years after RYGB, strongly suggesting a durability of this effect. This phenomenon may play a key role in maintaining type 2 diabetes remission and weight loss after RYGB.     

Vagal Innervation of Intestine Contributes to Weight Loss After Roux-en-Y Gastric Bypass Surgery in Rats

Background

It is conceivable that overstimulation of chemo- and mechano-sensors in the Roux and common limbs by uncontrolled influx of undigested nutrients after Roux-en-Y gastric bypass surgery (RYGB) could lead to exaggerated satiety signaling via vagal afferents and contribute to body weight loss. Because previous clinical and preclinical studies using vagotomy came to different conclusions, the aim was to examine the effects of selective and histologically verified celiac branch vagotomy on reduced food intake and body weight loss induced by RYGB.

Methods

Male Sprague–Dawley rats underwent either RYGB + celiac branch vagotomy (RYGB/VgX, n?=?15), RYGB + sham celiac branch vagotomy (RYGB/Sham VgX; n?=?6), Sham RYGB + celiac branch vagotomy (Sham/VgX; n?=?6), or sham RYGB + sham celiac branch vagotomy (Sham/Sham; n?=?6), and body weight, body composition, and food choice were monitored for 3 months after intervention.

Results

In rats with RYGB, histologically confirmed celiac branch vagotomy significantly moderated weight loss during the first 40 days after surgery, compared to either sham or failed vagotomy (P?P?Conclusions The results suggest that signals carried by vagal afferents from the mid and lower intestines contribute to the early RYGB-induced body weight loss and reduction of food intake.     

Increased platelet storage time is associated with mitochondrial dysfunction and impaired platelet function

Background

Hemorrhagic shock is a leading cause of death following severe trauma, and platelet transfusions are frequently necessary to achieve hemostasis. Platelets, however, require special storage conditions, and storage time has been associated with loss of platelet quality. We hypothesized that standard storage conditions have a deleterious effect on platelet mitochondrial function and platelet activation.

Materials and methods

Platelet donations were collected from healthy donors (n = 5) and stored in gas-permeable collection bags according to American Association of Blood Bank recommendations. Platelet units were sampled from day of collection (day 0) until day 7. High-resolution respirometry was used to assess baseline mitochondrial respiration, maximal oxygen utilization, and individual mitochondrial complex-dependent respiration. Fluorescence-activated cell sorting was performed to analyze mitochondrial content, mitochondrial reactive oxygen species, the expression of P-selectin (both before and after challenge with thrombin receptor–activating peptide), and apoptosis. Data were analyzed using analysis of variance and Pearson correlation (P < 0.05 significant).

Results

Mitochondrial respiration decreased significantly in platelets stored longer than 2 d (P < 0.05). Platelets also demonstrated a persistent decrease in response to stimulation with thrombin receptor–activating peptide by the third day of storage (P < 0.05) as well as an increase in mitochondrial reactive oxygen species and apoptosis (P < 0.05). Mitochondrial respiration significantly correlated with platelet capacity to activate (r = 0.8, P < 0.05).

Conclusions

Platelet mitochondrial respiratory function and activation response decrease significantly in platelets stored for 3 d or more. Because platelet transfusions almost universally occur between the third and fifth day of storage, our findings may have significant clinical importance and warrant further in vivo analysis.     

Remain recipient partial liver during liver transplant after Hassab

Background

The Hassab procedure is the primary method for treating and preventing recurrent esophagogastric variceal bleeding in portal hypertension patients. These patients have worsening liver function and eventually require liver transplantation. Abnormal anatomical structures and severe tissue adhesion caused by the Hassab procedure increase the risks of transplantation. We investigated the safety and efficacy of retaining part of the left lateral hepatic lobe during transplantation.

Materials and methods

This retrospective study evaluated outcomes in 22 patients who underwent the Hassab procedure followed by liver transplantation. The patients were separated into two groups: group A (complete liver resection, n = 14) and group B (incomplete liver resection with left lateral remnant, n = 8). We statistically analyzed pre-, intra-, and post-operative variables in both groups.

Results

Preoperative demographic data showed no significant differences between the groups. Operation time was significantly greater in group A (10.85 ± 0.79 h) than in group B (7.25 ± 0.59 h), and median blood loss (2807 ± 472 mL) was significantly greater in group A than in group B (1023 ± 141 mL, P < 0.05 for both). Overall complication rates were not significantly different; the 1- and 3-y survival rates were 85.7% and 71.4% for group A and 87.5% and 75.0% for group B, respectively (P > 0.05).

Conclusions

Retention of some left hepatic lobe tissue during liver transplantation after the Hassab procedure is safe and feasible because it increases the success rate by reducing surgical difficulty and time.     

Exendin-4 ameliorates renal ischemia-reperfusion injury in the rat

Background

Glucagon-like peptide-1 receptor (GLP-1R) activation exerts protective effects against reactive oxygen species by inducing the oxidative defense gene heme oxygenase-1 (HO-1), and provides protection in mice against transient focal cerebral ischemia and ischemia-reperfusion injury in the rat heart. GLP-1R is also expressed in the kidney, but it is unknown whether GLP-1R activation is able to protect against ischemia-reperfusion injury in the rat kidney.

Materials and methods

We used a rat model of renal ischemia-reperfusion injury. The rats were pretreated with the GLP-1R agonist, exendin-4 before reperfusion. We used real-time polymerase chain reaction to evaluate expression of the oxidative defense gene HO-1 and Western blot analysis for HO-1 and GLP-1R. Renal function was assessed at baseline and 24 and 72 h after reperfusion. The kidneys were processed for histologic and morphometric analysis, caspase-3, and ED1 immunohistochemistry at 72 h. The degree of apoptosis of the renal tubular cells was determined using terminal deoxynucleotidyl transferase deoxyuridine triphosphate-biotin nick end labeling assays.

Results

Exendin-4 pretreatment resulted in GLP-1R activation and upregulation of HO-1. Preconditional activation of GLP-1R significantly improved the serum creatinine levels compared with vehicle (P < 0.05). Furthermore, tissue injury, caspase-3 and ED1 expression, and apoptosis were less severe, as quantified by application of a standardized histologic scoring system in a blinded manner.

Conclusions

These results have demonstrated that preconditional activation of the GLP-1R with exendin-4 in the kidney significantly protected against ischemia-reperfusion injury in rats by increasing HO-1 expression.     

Effects of Sleeve Gastrectomy and Gastric Bypass on Postprandial Lipid Profile in Obese Type 2 Diabetic Patients: a 2-Year Follow-up

Background

Bariatric surgery (BS) is known to favorably impact fasting lipid profile. Fasting and postprandial lipids were evaluated before and 2 years after BS in obese type 2 diabetic (T2DM) patients.

Methods

A prospective study was conducted in 19 obese T2DM patients: ten undergoing sleeve gastrectomy (SG) and nine undergoing Roux-en-Y gastric bypass (RYGB). Before and 2 years after BS, clinical parameters and the response of lipid and incretin hormones to a mixed meal (MM) were assessed.

Results

The two groups had similar characteristics at baseline. After BS, weight loss was similar in the two groups (p?≤?0.01). Fasting glucose, insulin, and triglycerides decreased while HDL cholesterol increased in a similar way (p?<?0.05); in contrast, fasting LDL cholesterol decreased only after RYGB (p?<?0.05). Post-meal glucose concentrations decreased while early insulin response significantly improved after both procedures (p?<?0.001 for both). Postprandial triglycerides decreased after both procedures (p?<?0.05) while postprandial LDL cholesterol decreased only after RYGB (p?<?0.05). Meal-GLP-1 increased postoperatively in both groups although to a greater extent after RYGB (p?<?0.001 vs. SG). GIP decreased after both procedures, especially after RYGB (p?=?0.003). At multivariate analysis, GLP-1 peak was the best predictor of LDL reduction (β?=??0.552, p?=?0.039) while the improvement of HOMA-IR (β?=?0.574, p?=?0.014) and weight loss (β?=?0.418, p?=?0.036) predicted triglycerides reduction.

Conclusions

Both surgical procedures markedly reduce fasting and postprandial triglycerides and increase HDL cholesterol levels. LDL cholesterol decreases only after RYGB through a mechanism likely mediated by the restoration of GLP-1.

     

Pre- and post-intervention study to assess the impact of a sedation protocol in critically ill surgical patients

Introduction

Sedation and pain management for mechanically ventilated critically ill surgical patients pose many challenges for the intensivist. Even though daily interruption of sedatives and opioids is appropriate in medical intensive care unit (ICU) patients, it may not be feasible in the surgical patients with pain from surgical incision or trauma. Therefore we developed an analgesia/sedation based protocol for the surgical ICU population.

Methods

We performed a two-phase prospective observational control study. We evaluated a prescriber driven analgesia/sedation protocol (ASP) in a 12-bed surgical ICU. The pre-ASP group was sedated as usual (n = 100) and the post-ASP group was managed with the new ASP (n = 100). Each phase of the study lasted for 5 mo. Comparisons between the two groups were performed by χ² or Fisher’s exact test for categorical variables and the Mann-Whitney test for nonparametric variables. A P value <0.05 was statistically significant.

Results

We found a significant reduction in the use of fentanyl (P < 0.001) and midazolam (P = 0.001). We achieved sedation goals of 86.8% in the post-ASP group compared to 74.4% in the pre-ASP (P < 0.001). Mean mechanical ventilations days in pre- and post-ASP group were 5.9 versus 3.8 (P = 0.033).

Conclusion

In our cohort of critically ill surgery patients implementation of an ASP resulted in reduced use of continuously infused benzodiazepines and opioids, a decline in cumulative benzodiazepine and analgesic dosages, and a greater percentage of Richmond Agitation Sedation Scale scores at goal. We also showed reduced mechanical ventilation days.     

Endothelial differentiation of diabetic adipose-derived stem cells

Background

Diabetic (DM) patients frequently lack autologous vascular tissue required for revascularization procedures and dialysis access creation. We have developed a tissue-engineered graft that uses adipose-derived stem cells (ASC) as endothelial cell substitutes. Here, we compare DM versus nondiabetic (NDM) ASC in terms of isolation efficiency, proliferation, commitment toward endothelial lineage, and seeding onto the luminal surface of a graft.

Methods

ASC were isolated from liposuction specimens of vascular surgery patients. Proliferation was assessed by constructing growth curves over 14 d. ASC were differentiated in endothelial growth medium (EGM2). Endothelial commitment was assessed by measuring endothelial cell-specific gene expression (CD31, von Willebrand factor) and by cord formation on Matrigel. Finally, ASC were seeded onto a vascular scaffold, flow conditioned, and imaged with confocal microscopy.

Results

Diabetes did not alter ASC isolation efficiency (224,028 ± 20,231 cells/g adipose for DM (n = 53) versus 259,345 ± 15,441 cells/g adipose for NDM (n = 145; P = 0.21). Growth curves for DM (n = 6) and NDM (n = 6) also appeared similar. After culture in EGM2, upregulation of CD31 and von Willebrand factor message was observed in NDM; these markers were found within the primary cultures of DM but no upregulation was observed after culture in EGM2. Both groups exhibited similar cord formation on Matrigel and retention to vascular scaffolds.

Conclusions

Isolation and proliferation studies suggest that adipose is a promising source of stem cells for tissue engineering in the DM population. The angiogenic potential of DM ASC appears intact; however, differences in acquisition of endothelial cell markers suggest that differentiation may be inhibited or delayed by diabetes.     

Evaluation of Oxidative Stress in the Late Postoperative Stage of Liver Transplantation

Introduction

Liver transplant recipients are at an increased oxidative stress risk due to pre-existing hepatic impairment, ischemia-reperfusion injury, immunosuppression, and functional graft rejection. This study compared the oxidative status of healthy control subjects, patients with liver cirrhosis on the list for transplantation, and subjects already transplanted for at least 12 months.

Patients and Methods

Sixty adult male patients, aged between 27 and 67 years, were subdivided into 3 groups: a control group (15 healthy volunteers), a cirrhosis group (15 volunteers), and a transplant group (30 volunteers). Oxidative stress was evaluated by activity of reduced glutathione, malondialdehyde, and vitamin E.

Results

There was a significant difference (P < .01) in the plasma concentration of reduced glutathione in the 3 groups, with the lowest values observed in the transplanted group. The malondialdehyde values differed significantly (P < .01) among the 3 groups, with the transplanted group again having the lowest concentrations. The lowest concentrations of vitamin E were observed in patients with cirrhosis compared with control subjects, and there was a significant correlation (P < .05) among the 3 groups. No correlations were found between reduced glutathione and vitamin E or between vitamin E and malondialdehyde. However, there were strong correlations between plasma malondialdehyde and reduced glutathione in the 3 groups: control group, r = 0.9972 and P < .0001; cirrhotic group, r = 0.9765 and P < .0001; and transplanted group, r = 0.8981 and P < .0001.

Conclusions

In the late postoperative stage of liver transplantation, oxidative stress persists but in attenuated form.     

Sport Activity and Health-Related Quality of Life After Kidney Transplantation

Objective

Considering the importance of sport activity for enhancing quality of life, the aim of this study was to investigate the effects of regular sport activity on quality of life of kidney transplant recipients.

Methods

Health-related quality of life (HRQoL) was assessed with the use of the SF-36 questionnaire on a group of 118 active kidney transplant patients (AKTPs) practicing different sports at low to moderate intensity (5 ± 4 h/wk). Scores were compared with those of 79 sedentary kidney transplant patients (SKTPs) and with 120 active healthy control subjects (AHCs).

Results

AKTPs reported higher scores than SKTPs in the SF-36 scales of Physical Functioning (P < .05), Role Limitations due to Physical Problems (P < .05), General Health (P < .01), Vitality (P < .05), Social Functioning (P < .05), Role Limitations due to Emotional Problems (P < .05), and Mental Health (P < .01). AKTPs obtained higher scores than AHCs on the Mental Health (P < .01) and Social Functioning scales (P < .01) and similar scores (P > .05) on all the other scales. The effect of quantity of sport activity was significant on the General Health (P < .01; η² = 0.05), and Role Physical scales (P = .04; η² = 0.03), with higher sport activity associated with higher HRQoL. The effect of sex was significant for Bodily Pain (P = .05; η² = 0.02), Vitality (P = .08; η² = 0.06), Social Functioning (P = .08; η² = 0.05), and Mental Health (P = .05; η² = 0.02), with male participants scoring higher than female participants.

Conclusions

This study indicates that regular sport activity significantly improves different dimensions of HRQoL among kidney transplant recipients. The benefits of sport activity go beyond its impact on physical health to involve psychologic and social components of quality of life. Spontaneous and low to moderate sport activity may play an important role after kidney transplantation that has been largely underestimated in the literature.     

Effects of adrenomedullin and vascular endothelial growth factor on ischemia/reperfusion injury in skeletal muscle in rats

Background

In this study we investigated the effects of adrenomedullin (AM) and vascular endothelial growth factor (VEGF) on skeletal muscle ischemia/reperfusion (I/R) injury in a rat model.

Materials and methods

Thirty-six Wistar rats were randomized into six groups (n = 6). Laparotomy was performed in all groups under general anesthesia. Nothing else was done in Group S (Sham). The Group I/R underwent I/R performed by clamping and declamping of the infrarenal abdominal aorta for 120 min, respectively. Group VEGF and Group AM received intravenous infusion of VEGF (0.8 μg/kg) or AM (12 μg/kg) respectively, without I/R. Group I/R + VEGF and Group I/R + AM received intravenous infusion of VEGF (0.8 μg/kg) or AM (12 μg/kg) immediately after 2 h period of ischemia, respectively. At the end of reperfusion period, skeletal muscle samples of lower extremity were taken from all groups for biochemical and histopathologic examinations.

Results

Tissue levels of malondialdehyde (MDA), superoxide dismutase (SOD), nitric oxide (NO), and hypoxia inducible factor 1 alpha (HIF 1α) were found to be significantly higher in Group I/R than the levels in Group S (P < 0.05). Tissue levels of MDA, SOD, NO, and HIF 1α were significantly lower in Group I/R + AM compared with the levels in Group I/R (P < 0.05). In Group I/R + VEGF, tissue levels of MDA and NO were significantly lower than the levels in Group I/R (P < 0.05). No statistically significant difference was found in the tissue levels of catalase among the groups. Histologic examination revealed a larger central muscular necrosis than the peripheral necrosis, red blood cells in the lumens of capillary vessels, and a stronger atrophy and elliptical or round shape in muscle fibers in Group I/R. Terminal deoxynucleotidyl transferase mediated dUPT nick end labeling (TUNEL)-positive cell count was significantly lower in groups I/R + AM and I/R + VEGF than Group I/R (P < 0.0001, P < 0.0001, respectively).

Conclusions

These results indicate that AM and VEGF have protective effects on I/R injury in skeletal muscle in a rat model.