Fish-oil emulsion (omega-3 polyunsaturated fatty acids) attenuates acute lung injury induced by intestinal ischemia–reperfusion through Adenosine 5′-monophosphate-activated protein kinase–sirtuin1 pathway

Background

Activated macrophage infiltration into the lungs is paramount in the pathogenesis of acute lung injury (ALI) induced by intestinal ischemia–reperfusion (I/R). Omega-3 polyunsaturated fatty acid (ω-3 PUFA) is a potent activator of the Adenosine 5′-monophosphate-activated protein kinase–sirtuin1 (AMPK/SIRT1) pathway against macrophage inflammation. We aimed to evaluate whether ω-3 PUFAs may protect against ALI induced by intestinal I/R via the AMPK/SIRT1 pathway.

Methods

Ischemia in male Wistar rats was induced by superior mesenteric artery occlusion for 60 min and reperfusion for 240 min. One milliliter per day of fish-oil emulsion (FO emulsion, containing major ingredients as ω-3 PUFAs) or normal saline (control) was administered by intraperitoneal injection for three consecutive days to each animal. All animals were sacrificed at the end of reperfusion. Blood and tissue samples were collected for analysis.

Results

Intestinal I/R caused intestinal and lung injury, evidenced by severe lung tissue edema and macrophage infiltration. Pretreatment with FO emulsion improved the integrity of microscopic structures in the intestine and lungs. Intestinal I/R induced the expression of macrophage-derived mediators (macrophage migration inhibitory factor and macrophage chemoattractant protein-1), inflammatory factors (nuclear factor κB, tumor necrosis factor α, interleukin 6, and interleukin 1β), and proapoptosis factor p66shc. There was a decrease in the expression of AMPK, SIRT1, and claudin 5. FO emulsion significantly inhibited macrophage infiltration into the lungs, inflammatory factor expression, and p66shc phosphorylation. Importantly, FO emulsion restored AMPK, SIRT1, and claudin 5 in the lungs.

Conclusions

Pretreatment with ω-3 PUFAs effectively protects intestinal and lung injury induced by intestinal I/R, reduces macrophage infiltration, suppresses inflammation, inhibits lung apoptosis, and improves the lung endothelial barrier after intestinal I/R in a manner dependent on AMPK/SIRT1. Thus, there is a potential for developing AMPK/SIRT1 as a novel target for patients with intestinal I/R–induced ALI.     

Tetrahydrobiopterin restores endothelial function in hypercholesterolemia.

In hypercholesterolemia, impaired nitric oxide activity has been associated with increased nitric oxide degradation by oxygen radicals. Deficiency of tetrahydrobiopterin, an essential cofactor of nitric oxide synthase, causes both impaired nitric oxide activity and increased oxygen radical formation. In this study we tested whether tetrahydrobiopterin deficiency contributes to the decreased nitric oxide activity observed in hypercholesterolemic patients. Therefore, L-mono-methyl-arginine to inhibit basal nitric oxide activity, serotonin to stimulate nitric oxide activity, and nitroprusside as endothelium-independent vasodilator were infused in the brachial artery of 13 patients with familial hypercholesterolemia and 13 matched controls. The infusions were repeated during coinfusion of L-arginine (200 microg/kg/min), tetrahydrobiopterin (500 microg/min), or the combination of both compounds. Forearm vasomotion was assessed using forearm venous occlusion plethysmography and expressed as ratio of blood flow between measurement and control arm (M/C ratio). Tetrahydrobiopterin infusion alone did not alter M/C ratio. Both the attenuated L-mono-methyl-arginine-induced vasoconstriction as well as the impaired serotonin-induced vasodilation were restored in patients during tetrahydrobiopterin infusion. Tetrahydrobiopterin had no effect in controls. In conclusion, this study demonstrates restoration of endothelial dysfunction by tetrahydrobiopterin suppletion in hypercholesterolemic patients.     

Gonocyte transformation to spermatogonial stem cells occurs earlier in patients with undervirilisation syndromes

Aim

Fertility post-orchidopexy is dependent on transformation of neonatal gonocytes (G) into adult dark spermatogonia at about 3 months, the same time as gonadotrophins stimulate androgen secretion. We examined how androgen blockade affects transformation of gonocytes to spermatogonial stem cells (SSC) during this period in patients with undervirilisation syndromes.

Methods

Patients with undervirilisation syndromes (n = 30, 1.5 weeks–16 years) underwent review of medical records, pathology reports, and H&E slides of testes (ethics HREC32164). Fluorescent immunohistochemistry against anti-Mullerian hormone (AMH, Sertoli cells), mouse VASA homologue (MVH, germ cells) and DAPI (nuclei) allowed the number of MVH-positive gonocytes/spermatogonial stem cells per seminiferous tubular cross-section (G/T or SSC/T) to be counted.

Results

Gonocytes (MVH-positive cells in the tubular lumen) were present in 15/16 patients under 2 years old. SSC (MVH-positive cells on the tubule basement membrane) were present in 25/30 patients. With increasing age, the mean number of SSC/T decreased from ~ 4 to 0, and G/T decreased from ~ 1.5 to 0. SSC were present in CAIS and PAIS patients at 1.5 and 3.5 weeks old, respectively.

Conclusions

Gonocytes transform into SSC earlier than expected in patients with undervirilisation syndromes. Lack of androgens may stimulate non-androgenic regulators to trigger transformation. Understanding how gonocytes transform may enable optimization of spermatogonial development to preserve fertility post-orchidopexy.     

Review of stoma site and midline incisional hernias after stoma reversal

Background

The incidence of incisional hernias after stoma reversal is not well reported. The aim of this study was to systematically review the literature reporting data on incisional hernias after stoma reversal. We evaluated both the incidence of stoma site and midline incisional hernias.

Methods

A systematic review identified studies published between January 1, 1980, and December 31, 2012, reporting the incidence of incisional hernia after stoma reversal at either the stoma site or at the midline incision (in cases requiring laparotomy). Pediatric studies were excluded. Assessment of risk of bias, detection method, and essential study-specific characteristics (follow-up duration, stoma type, age, body mass index, and so forth) was done.

Results

Sixteen studies were included in the analysis; 1613 patients had 1613 stomas formed. Fifteen studies assessed stoma site hernias and five studies assessed midline incisional hernias. The median (range) incidence of stoma site incisional hernias was 8.3% (range 0%–33.9%) and for midline incisional hernias was 44.1% (range 8.7%–58.1%). When evaluating only studies with a low risk of bias, the incidence for stoma site incisional hernias is closer to one in three and for midline incisional hernias is closer to one in two.

Conclusion

Stoma site and midline incisional hernias are significant clinical complications of stoma reversals. The quality of studies available is poor and heterogeneous. Future prospective randomized controlled trials or observational studies with standardized follow-up and outcome definitions/measurements are needed.     

Selective inhibition of histone deacetylase 6 alters the composition of circulating blood cells in a lethal septic model

Background

Phagocytes, especially monocytes, macrophages, and dendritic cells, play a pivotal role in the innate and adaptive immune responses during sepsis. We have shown that inhibition of histone deacetylase 6 improves survival and increases bacterial clearance in a mouse model of cecal ligation and puncture (CLP). The aim of this study was to determine whether this effect was associated with changes in the number and composition of different blood cell types in the circulation.

Methods

C57BL/6J mice were subjected to CLP, and 1 h later given an intraperitoneal injection of either Tubastatin A dissolved in dimethyl sulfoxide, or dimethyl sulfoxide only. Sham-operated animals were treated in an identical fashion but not subjected to CLP. Forty-eight hours later, peripheral blood was obtained via cardiac puncture and analyzed using a HemaTrue veterinary hematology analyzer.

Results

Tubastatin A administration increased the number of circulating monocytes in the sham-operated and the CLP animals. In comparison with the sham, CLP animals displayed an increase in the granulocyte percentage in white blood cells and decrease in the lymphocyte number and percentage, with a resultant increase in the granulocyte-to-lymphocyte ratio. Treatment of CLP animals with Tubastatin A decreased the granulocyte percentage and restored the lymphocyte number and percentage, which decreased the granulocyte-to-lymphocyte ratio. In the sham animals, Tubastatin A increased red blood cell number, hematocrit, and hemoglobin. This effect was not seen in CLP animals.

Conclusions

Tubastatin A treatment has significant impact on the composition of circulating blood cells. It increases the number of circulating monocytes and the red blood cell mass in sham-operated animals. In the CLP animals, it increases the monocyte count, decreases the percentage of granulocytes, restores the lymphocyte population, and decreases the granulocyte-to-lymphocyte ratio. These results may explain why Tubastatin A treatment improves survival in the septic models.     

Reduction of alkaline reflux gastritis and marginal ulcer by modified Braun enteroenterostomy in gastroenterologic reconstruction after pancreaticoduodenectomy

Background

The incidence of alkaline reflux gastritis (ARG) after pancreaticoduodenectomy (PD) is high. Although Braun enteroenterostomy (BEE) may reduce ARG, BEE may result in marginal ulcers (MUs) due to the additional anastomotic stoma. We conducted this study to compare clinical outcomes of using a modified BEE (MBEE) with traditional gastrojejunostomy (TGJ), by inducting a purse-string suture instead of an additional anastomotic stoma.

Materials and methods

All 62 patients underwent standard PD at the Department of Hepatobiliopancreatic Surgery of West China Hospital between January 1, 2008 and January 31, 2012. Demographics, perioperative and postoperative factors, and follow-up morbidity were compared in those patients who underwent MBEE (n = 32, three patients were lost to follow-up) to those who underwent TGJ (n = 30, nine patients were lost to follow-up).

Results

Patients who underwent the MBEE experienced a decrease in total morbidity including ARG and MUs, relative to those who underwent TGJ (24.1% versus 58.3%, P = 0.011). With regard to the MBEE group, the total ARG rate was statistically significantly lower compared with the TGJ group (13.8% versus 37.5%, P = 0.046). In addition, the incidence of MUs was reduced.

Conclusions

In patients undergoing PD, the MBEE was safely performed with significantly more patients having reduced incidence of ARG and related sequela compared with those who underwent TGJ. These results support further study of patients undergoing gastroenterostomy after resection of the distal stomach in larger, randomized studies.