Induced adiposity and adipocyte hypertrophy in mice lacking the AMP-activated protein kinase-alpha2 subunit

AMP-activated protein kinase (AMPK) is considered as a cellular energy sensor that regulates glucose and lipid metabolism by phosphorylating key regulatory enzymes. Despite the major role of adipose tissue in regulating energy partitioning in the organism, the role of AMPK in this tissue has not been addressed. In the present study, we subjected AMPKalpha2 knockout (KO) mice to a high-fat diet to examine the effect of AMPK on adipose tissue formation. Compared with the wild type, AMPKalpha2 KO mice exhibited increased body weight and fat mass. The increase in adipose tissue mass was due to the enlargement of the preexisting adipocytes with increased lipid accumulation. However, we did not observe any changes in adipocyte marker expression, such as peroxisome proliferator-activated receptor-gamma, CCAAT/enhancer-binding protein alpha (C/EBPalpha) and adipocyte fatty acid-binding protein (aFABP/aP2), or total cell number. Unlike impaired glucose homeostasis observed on normal diet feeding, when fed a high-fat diet AMPKalpha2 KO mice did not show differences in glucose tolerance and insulin sensitivity compared with wild-type mice. Our results suggest that the increase in lipid storage in adipose tissue in AMPKalpha2 KO mice may have protected these mice from further impairment of glucose homeostasis that normally accompanies high-fat feeding. Our study also demonstrates that lack of AMPKalpha2 subunit may be a factor contributing to the development of obesity.     

Replacement of the aortic root for acute prosthetic valve endocarditis: prosthetic composite versus aortic allograft root replacement

OBJECTIVE: Aortic root replacement for prosthetic aortic valve endocarditis with accompanying destruction of the aortic root is a well-established surgical intervention. However, there is still no consensus whether prosthetic material or allogeneic material should be used. Here we report on our experience with prosthetic composite and aortic allograft root replacement in such patients during a 10-year interval. METHODS: From 1991 through 2001, 29 patients with prosthetic aortic valve endocarditis combined with aortic root destruction underwent reoperation at our institution. Sixteen patients received aortic root replacement with a cryopreserved aortic root allograft (group A) and 13 with a prosthetic composite graft (group B). The interval between the initial operation and reoperation was 29 months (range, 5-168 months) in group A and 55 months (range, 7-248 months) in group B. RESULTS: Hospital mortality was 18.5% (n = 5 patients, 3 in group A and 2 in group B). Median follow-up was 21 months (range, 1-48 months) for group A and 34 months (range, 1-152 months) for group B (P >.2). Survival at 1 and 5 years was 81% +/- 10% and 81% +/- 10% in group A and 85% +/- 10% and 85% +/- 10% in group B, respectively. No patient underwent reoperation for recurrent prosthetic aortic valve endocarditis. CONCLUSIONS: Our results indicate that excellent long-term results can be achieved regardless of the material used for aortic root replacement in patients with prosthetic aortic valve endocarditis.     

The Vista system: a new bipolar resection device for endourological procedures: comparison with conventional resectoscope

OBJECTIVE: Conventional transurethral resection of the prostate (TURP) uses a monopolar electrocautery system in which the current passes from the active electrode through the patient's body towards the return plate and may cause distant negative effects. In this study a new developed resection device, the Vista system, using a bipolar electrocautery system and 0.9% sodium chloride solution for irrigation, was evaluated in an ex-vivo model. METHODS: The modified model of the isolated blood perfused kidney was used to determine cutting qualities, ablation rate, blood loss and coagulation depth of the bipolar resectoscope. After ablating the renal tissue of a perfused kidney in a surface area, blood loss was semiquantitatively determined. Afterwards samples were taken and processed for histological evaluation of the coagulation depth. We compared the new bipolar resection device against a conventional monopolar resectoscope. RESULTS: We found good cutting qualities of the bipolar resectoscope although it is more difficult to start a cut. The ablation rate is determined by the width of the electrode and is similar to the standard device (30 cm(2)/min). The bleeding is reduced with increasing output powers (26.13 +/- 6.15 g/min (level 5); 20.49 +/- 5,47 g/min (level 6); 13.16 +/- 5,47 g/min (level 7); 10.43 +/- 4.76 g/min (level 8) and lower compared to a conventional monopolar resectoscope (17.08 +/- 4.47 g/min). The coagulation depth increases with higher output powers but is reduced compared to the standard device (118 +/- 22 microm (level 5); 121 +/- 23 microm (level 6); 141 +/- 62 microm (level 7); 163 +/- 30 microm (level 8) versus 287 +/- 57 (monopolar resectoscope)). CONCLUSION: Our results with the bipolar resection device for TURP suggest that it may offer an alternative to conventional TURP. As active and the return electrode are placed on the resectoscope, high current densities are achieved locally and complications caused by distant negative effects of the current are theoretically reduced in vivo. Furthermore the risk of TUR syndrome is theoretically eliminated by using physiological sodium chloride solution for irrigation. To prove the clinical significance of our ex-vivo findings, clinical studies including large numbers of patients have to be performed.     

The neuroprotective effect of lactate is not due to improved glutamate uptake after controlled cortical impact in rats

Abstract For many years lactate was considered to be a waste product of glycolysis. Data are accumulating that suggest that lactate is an important energy substrate for neurons during activation. In severe traumatic brain injury (TBI) glutamate release and ischemic cerebral blood flow (CBF) are major factors for a mismatch between energy demand and supply and for neuronal cell death. Although ATP and behavior could be improved by lactate treatment after TBI, no histological correlate nor any linkage to better astrocytic glutamate uptake or CBF as possible mechanisms have been described. We subjected male rats to a controlled cortical impact (CCI; 5?m/sec, 2.5?mm). To study the effects of lactate treatment on lesion volume, glutamate release, and CBF, animals were infused with either NaCl or 100?mM lactate for up to 3?h. The role of endogenous lactate was investigated by inhibiting transport with α-cyano-4-hydroxy-cinnamic acid (4-CIN; 90?mg/kg). Lactate treatment 15?min post-CCI reduced lesion volume from 21.1±2.8?mm(3) to 12.1±1.9?mm(3) at day 2 after CCI. Contusion produced a significant three- to fourfold increase of glutamate in microdialysates, but there was no significant difference between treatments that began 30?min before CCI. In this experiment lesion volume was significantly reduced by lactate at day 7 post-CCI (23.7±4 to 9.3±1-2?mm(3)). CBF increased immediately after CCI and dropped thereafter below baseline in all animals. Lactate infusion 15?min post-CCI elevated CBF for 20?min in 7 of 10 animals, whereas 7 of 8 NaCl-treated animals showed a further CBF decline. Neuroprotection was achieved by lactate treatment following contusion injury, whereas blocking of endogenous lactate transport exerted no adverse effects. Neuroprotection was not achieved by improved glutamate uptake into astrocytes, but was supported by augmented CBF following CCI. Due to its neuroprotective property, lactate might be a beneficial pharmacological treatment for TBI patients.     

Hybrid neurofibroma/schwannoma is overrepresented among schwannomatosis and neurofibromatosis patients

We analyzed the histologic features of peripheral nerve sheath tumors occurring in 14 patients with schwannomatosis. Among a total of 31 tumors, 19 tumors (61%) showed schwannoma-like nodules within a neurofibroma-like tumor, corresponding to hybrid neurofibroma/schwannoma. At least 1 hybrid tumor occurred in 10 of 14 (71%) schwannomatosis patients. We then retrieved cases of hybrid tumors without documented relation to schwannomatosis from our database and identified 41 tumors arising in 23 patients. More than half of these patients (14/23) were reported to suffer from multiple peripheral nerve sheath tumors, favoring a tumor syndrome. Indeed, analysis of clinical records revealed the diagnosis of neurofibromatosis type 2 (NF2) in 26% (6/23), neurofibromatosis type 1 (NF1) in 9% (2/23), definite schwannomatosis in 4% (1/23), and possible schwannomatosis in 13% (3/23) of patients with multiple nerve sheath tumors. Our findings suggest that hybrid neurofibroma/schwannoma represents a common tumor type in schwannomatosis and shows a striking association with neurofibromatoses.     

Clinical outcomes in patients with renal artery stenosis treated with stent placement with embolic protection compared with those treated with stent alone

Purpose: To compare the clinical outcomes in patients with chronic renal insufficiency (CRI) and renal artery stenosis (RAS) following renal artery (RA) stent placement with and without embolic protection device (EPD) usage. Materials and Methods: Eighteen patients who had RA stent placement with EPD were matched to control patients (RA stent only). Blood pressure, number of hypertensive medications, and estimated glomerular filtration rate (eGFR) at 3 months before the procedure and after 12 months were determined. An increase of ≥ 20% in eGFR at 12 months from baseline was defined as "improvement," decrease of ≥20% as "deterioration," and an eGFR change between those values as "stabilization" at 12 months. Results: At 12 months, stage 4 patients treated with EPD had significantly higher eGFR than controls (P = .01). There was no statistical difference in blood pressure outcomes between the 2 groups. Conclusions: Patients with stage 4 CRI did significantly better with EPD than those treated without it.     

Positron-emission tomography imaging of early events after transplantation of islets of Langerhans

The aim of our study was to assess cell trafficking and early events after intraportal islet transplantation. Sprague-Dawley rat islets were incubated for various times, with various concentrations of 2-[F]fluoro-2deoxy-D-glucose (FDG), and in presence of various glucose concentrations. FDG-labeled syngeneic islets or FDG alone were injected in rats. Radioactivity was measured in the liver and in various organs by positron-emission tomography for 6 hours. FDG uptake increased with incubation time or FDG concentration and decreased in presence of glucose. In vivo, all islets implanted in the liver, with an uptake 4.4 times higher than controls (44.2% vs. 10.1%, P=0.02). Radioactivity in the liver decreased at the same rate after injection of labeled-islets and FDG alone. Ex vivo labeling of islets and imaging of posttransplant early events were feasible. Islets engrafted exclusively in the liver. No islet loss could be demonstrated 6 hours after transplantation.     

Ex Vivo Repair and Renal Autotransplantation for Complex Renal Artery Aneurysms in a Solitary Kidney

Renal artery aneurysm (RAA) is a rare clinical entity with an incidence of 0.015-1%. Indications for interventional or surgical repair of RAAs are expanding aneurysms, diameter >2.5 cm, intractable renovascular hypertension, dissecting RAA, hematuria, and renal infarction after distal embolization. Interventional insertion of a stent graft as well as aortorenal bypass implantation are both low-risk procedures in simple aneurysms of the proximal renal artery. However, complex distal renal aneurysms involving several renal artery branches require not only an excellent result of vascular reconstruction, but also a surgical technique offering maximal protection for the kidney during the ischemic period. Here, we present a case of a solitary kidney with two consecutive RAAs of segmental renal artery branches (type 2 RAA). A surgical strategy including renal explantation, ex vivo renal preservation, ex vivo reconstruction of the renal artery, and renal heterotopic autotransplantation was successfully applied. The technique of ex vivo repair is a safe and effective surgical procedure in this clinical setting.     

Biodegradable implants for Pipkin fractures

The current study was designed to clarify whether biodegradable poly-L/DL lactide pins provide an operative alternative for fixation of Pipkin fractures. Nine patients with Pipkin fractures (one with Pipkin Type I, one with Pipkin Type II, and seven with Pipkin Type IV fractures) were treated surgically between 1996 and 2002. In all patients, the femoral head fractures were fixed with biodegradable, 2.7-mm and 2.0-mm polylactide pins. Eight patients were followed up for an average of 54.2 months. One patient died before the final followup. Eight fractures healed uneventfully. In one patient, a persisting femoral head defect led to posttraumatic arthritis requiring insertion of a femoral endoprosthesis at 1 year. The average range of motion of the affected hips of all patients at followup was 109 degrees -0 degrees -0 degrees in flexion and extension. External and internal rotation averaged 37 degrees -0 degrees -29 degrees . One patient had Brooker Grade I heterotopic ossification develop, and another had a Grade II heterotopic develop. Merle d'Aubigne and Postel ratings showed two excellent and five satisfactory results (average score, 13.1). Adverse effects from the polylactide implants were not observed. Pipkin fractures can be fixed successfully with biodegradable polylactide pins.