Effect of Baohuoside-1 aglycone and tacrolimus monotherapy and combination therapy on prevention of acute heart allograft rejection in the rat

Baohuoside-1 (B-1), a recently introduced novel immunosuppressant that was proved to be potent in inhibition of T and B cell proliferation and B-1, also prevents cardiac allograft rejection in rodents. The present study further proved that monotherapy of B-1's analogue B-1 aglycone effectively prolongs cardiac allograft survival and combination therapy of B-1 aglycone with tacrolimus (FK506) produces synergistic effect in prevention acute cardiac allograft rejection in the rat. .     

Low-Volume Walking Program Improves Cardiovascular-Related Health in Older Adults

Although numerous sources of evidence show that regular physical activity is beneficial to health, most individuals do not engage in a sufficient amount of physical activity to meet the guidelines set out by expert panels. In addition, the minimum amount of physical activity associated with reduced cardiovascular disease risk markers is not clear in older adults. The purpose of this study was to determine the effects of a 12-week walking program involving an exercise volume below the current minimum physical activity recommendation on cardiovascular disease risk markers in older adults. The participants were recruited from the following two groups separately: a walking group (n = 14) and a control group (n = 14). In the walking group, participants walked 30 to 60 minutes per session on 2 days per week for 12 weeks (average walking time, 49.4 ± 8.8 min/session). Plasma oxidised low-density lipoprotein concentrations tended to be lower than baseline values in the walking group after 12 weeks (paired t-test, p = 0.127). The ratio of oxidised low-density lipoprotein to high-density lipoprotein cholesterol was significantly lower than the baseline ratio in the walking group after 12 weeks (paired t-test, p = 0.035). Resting systolic blood pressure and diastolic blood pressure were significantly lower than baseline values in the walking group after 12 weeks (paired t-tests, p = 0.002, p < 0.0005, respectively). Our findings demonstrate that a 12-week walking program comprising a low volume of physical activity confers a benefit to cardiovascular-related health in older adults.

Key Points

• It is important to consider baseline physical activity levels when evaluating physical activity program.
• Being physically active is important to reduce the potential risk marker of cardiovascular disease in older adults.
• These data imply that a small volume of 12-week walking program confers a benefit to cardiovascular-related health in older adults.

Key words: blood pressure, exercise, lipid metabolism, older adults, oxidised low-density lipoprotein     

Use of argatroban as a substitute for heparin in a patient with suspected HIT type II undergoing carotid endarterectomy

Heparin-induced thrombocytopenia (HIT) type II is characterized by a decrease in platelet count and thrombosis following heparin administration. We anesthetized a 67-year-old woman with suspected HIT type II undergoing carotid endarterectomy (CEA). Preoperatively, the patient had received anticoagulation therapy with heparin for cerebral infarction due to thrombosis and she developed thrombocytopenia with deterioration of cerebral infarction. Platelet level recovered by discontinuation of heparin and platelet infusion. During the surgical procedure, a substitution for heparin as an anticoagulant was necessary and we used argatroban, a direct thrombin inhibitor, with monitoring activated coagulation time (ACT). The ACT values were maintained above 200 sec during endoarterectomy and the operation was successfully carried out. We believe that argatroban is one of the choices for anticoagulants in a patient with HIT type II.     

Effect of pulsatile left ventricular assist system implantation on Doppler measurements of renal hemodynamics in patients with advanced heart failure

The effects of left ventricular assist system (LVAS) implantation on renal hemodynamics remains to be fully elucidated. We evaluated renal function and intrarenal blood flow in five advanced heart failure patients who had been supported with a Toyobo LVAS for bridge to heart transplantation. Renal function expressed as estimated glomerular filtration rate (eGFR) was calculated using the modified formula of Modification of Diet in Renal Disease. Mean blood velocities in the bilateral segmental arteries during systolic and diastolic perfusion were measured using duplex Doppler sonography, and renal vascular resistance (resistive index [RI]) of the segmental arteries was defined as (peak systolic velocity [PSV]-end-diastolic velocity [EDV])/PSV. All studies were performed before and after implantation (mean duration of support, 15.6±10.9 months). LVAS implantation significantly improved eGFR (42.7±7.9 to 64.1±16.3mL/min, P<0.05). Beat-by-beat measurements of heart rate did not change significantly. Mean PSV decreased significantly (38.2±8.9 to 28.3±2.2cm/s, P<0.05), and mean EDV increased significantly (8.3±3.2 to 11.3±1.3cm/s, P<0.05), and thus, mean RI was significantly improved (0.79±0.06 to 0.60±0.04, P<0.01). In conclusion, in advanced heart failure patients, pulsatile LVAS implantation is associated with improved renal function, and this improvement may be mediated in part through an improvement of intrarenal hemodynamics.     

Glycosaminoglycan and proteoglycan inhibit the depolymerization of beta2-microglobulin amyloid fibrils in vitro

BACKGROUND: Although several kinds of evidence suggest that glycosaminoglycans (GAGs) and proteoglycans (PGs) may contribute to the development of beta2-microglobulin-related (Abeta2m) amyloidosis, the precise roles of these molecules for the development of Abeta2m amyloidosis are poorly understood. METHODS: We investigated the effects of GAGs and PGs on the depolymerization of Abeta2m amyloid fibrils at a neutral pH, as well as on the formation of the fibrils at an acidic pH in vitro, using fluorescence spectroscopy with thioflavin T and electron microscopy. RESULTS: Depolymerization of Abeta2m amyloid fibrils at pH 7.5 at 37 degrees C was inhibited dose-dependently by the presence of some GAGs (heparin, dermatan sulfate, or heparan sulfate) or PGs (biglycan, decorin, or keratan sulfate proteoglycan). Electron microscopy revealed that a significant amount of Abeta2m amyloid fibrils remained in the reaction mixture with some lateral aggregation. Second, when monomeric beta2m was incubated with aggrecan, biglycan, decorin, or heparin at pH 2.5 at 37 degrees C for up to 21 days, the thioflavin T fluorescence increased depending on dose and time. Electron microscopy revealed the formation of rigid and straight fibrils similar to Abeta2m amyloid fibrils in beta2m incubated with biglycan for 21 days. CONCLUSION: These results suggest that some GAGs and PGs could enhance the deposition of Abeta2m amyloid fibrils in vivo, possibly by binding directly to the surface of the fibrils and stabilizing the conformation of beta2m in the fibrils, as well as by acting as a scaffold for the polymerization of beta2m into the fibrils.     

Platelet-derived endothelial cell growth factor gene therapy for limb ischemia

OBJECTIVES: Platelet-derived endothelial cell growth factor (PD-ECGF) is identical to thymidine phosphorylase (TP), and it can induce angiogenesis, including arteriogenesis, in chronically ischemic canine myocardium. Because its effect on peripheral arterial disease has not been elucidated, we investigated whether overexpression of PD-ECGF/TP could ameliorate chronic limb ischemia in rabbits. METHODS: Left femoral arteries were resected from 24 male rabbits. After 10 days, a plasmid vector containing human PD-ECGF/TP complimentary DNA was injected into 10 sites in the adductor muscles. Control groups received either the LacZ plasmid vector or saline vehicle only (n = 8 per group). Blood pressure was measured in the calf before surgery, at the onset of ischemia, 10 days later, and 20 and 30 days after gene transfer. Collateral vessel development and limb perfusion were assessed by angiography, and resected tissues underwent molecular and histologic examination. RESULTS: In the PD-ECGF/TP group, human PD-ECGF/TP messenger RNA and protein were still detected at 30 days after treatment. Calf blood pressure decreased significantly after femoral artery resection in all three groups. It subsequently showed a greater increase in the PD-ECGF/TP group than in either control group, and the difference was significant at 20 days after treatment (PD-ECGF/TP, 97.4 +/- 7.4; LacZ, 58.6 +/- 6.9; saline, 41.3 +/- 3.6). Immunohistochemical staining demonstrated an increased ratio of capillaries and arterioles to muscle fibers in the PD-ECGF/TP group (2.14 +/- 0.13 and 1.51 +/- 0.06), but not in the LacZ group (1.39 +/- 0.04 and 0.71 +/- 0.05) or the saline group (1.34 +/- 0.05 and 0.71 +/- 0.04, P < .01). The angiographic score was higher in the PD-ECGF/TP group (0.96 +/- 0.08) than in the LacZ group (0.50 +/- 0.02) or saline group (0.51 +/- 0.03) at 30 days after gene transfer (P < .01). CONCLUSIONS: This study demonstrated that PD-ECGF/TP gene transfer induced angiogenesis and decreased ischemia in a rabbit hindlimb model by promoting arteriogenesis, suggesting that targeting this gene may be a promising therapeutic strategy for peripheral vascular disease.     

Delayed laparoscopic subtotal cholecystectomy in acute cholecystitis with severe fibrotic adhesions

Background  Conversion rate to open surgery is higher for patients with acute cholecystitis than in those without acute cholecystitis. We attempted to develop a laparoscopic subtotal cholecystectomy to decrease this conversion rate. Methods  From 2000 to 2005, laparoscopic cholecystectomy for acute cholecystitis was performed in 60 patients (22 women, 38 men). Patients were divided into two groups: group A (2000 to 2002, n = 22) and group B (2003 to 2005, n = 38). When significant difficulty was encountered dissecting the gallbladder from its bed, we incised the gallbladder wall leaving the posterior wall and cauterizing the remnant mucosa (subtotal cholecystectomy, SC-1). When dissection of the gall bladder neck and triangle of Calot was difficult, the neck of the gallbladder was sutured despite clipping (SC-2). Results  Mean duration from onset of symptoms to operation was 55.3 ± 52.0 days. SC-1 was performed in 8 patients in group A and 18 patients in group B. SC-2 was performed in three patients in Group B. Conversion rate was 18.1% (4/22) in group A and 0% (0/38) in group B, compared to 0.4% (1/221) for patients without acute cholecystitis. No complications were associated with ablated gallbladder mucosa. Conclusion  Laparoscopic subtotal cholecystectomy offers safe and effective treatment for acute cholecystitis. The conversion rate in group B is decreased by avoiding hazardous dissection of the cystic duct.     

Triangle target principle for the placement of trocars during video-assisted thoracic surgery.

OBJECTIVE: The baseball-diamond principle is generally used for trocar placement during video-assisted thoracic surgery; however, we are unable to treat all peripheral lung lesions using this principle. Therefore, we have developed another method for determining trocar placement based on a modification of the conventional principle. We have termed this method the triangle target principle. This report describes the instrument positioning that we now use for many video-assisted thoracic surgical procedures. METHODS: We position 3 trocars in an equilateral triangle, with the target lesion at the apex. One vertex of the base becomes the site of the first trocar placement for introduction of the thoracoscopic camera. Another vertex of the base becomes the site for the second trocar for forceps or the endoscopic stapler. The third trocar is for forceps and is inserted to create the vicinity of target lesion. Four types of the triangle target principle were developed according to sites of the target lesion. RESULTS: Between January 2000 and December 2002, we used this principle for 161 patients who underwent video-assisted thoracic surgery and all intrathoracic lesions were accessible except in 3 patients requiring intraoperative modifications. CONCLUSIONS: We conclude that video-assisted thoracic surgery by this principle is more effective and easier than the conventional principle to treat intrathoracic disease.     

Results of orbital preservation for advanced malignant maxillary sinus tumors

OBJECTIVE: The purpose of the study was to examine the oncological and functional outcomes of multimodality therapy for patients with advanced malignant maxillary sinus tumors that invaded the orbit. STUDY DESIGN: Retrospective study. METHODS: The medical records of 26 patients with orbital invasion were retrospectively analyzed. The patient group consisted of 16 men and 10 women, with a median age of 58 years. The mean follow-up period was 73 months. The most common disease was squamous cell carcinoma. Seven patients had nodal disease. All patients underwent simultaneous combined therapy consisting of conservative surgery through a sublabial incision, radiotherapy, and regional chemotherapy. Patients with nodal disease were treated with either irradiation or selective neck dissection. RESULTS: The 5- and 10-year overall survival rates were 68% and 51%, respectively. The 5- and 10-year local control rates were 66% and 51%, respectively. Overall survival rates and local control rates were significantly worse in patients with disease other than squamous cell carcinoma. Local control rates were significantly worse in patients with orbital apex disease than in patients without orbital apex disease. All 26 patients, despite orbital involvement, retained their orbital contents. Nineteen of these patients demonstrated adequate ocular function. CONCLUSIONS: Combined therapy with conservative surgery, radiotherapy, and regional chemotherapy is an effective method for local control and preservation of ocular function. However, performing orbital conservation procedure in patients with disease other than squamous cell carcinoma and with orbital apex disease must be considered carefully.     

Association of CD26 with CD45RA outside lipid rafts attenuates cord blood T-cell activation

CD26 is a T-cell activation antigen that contains dipeptidyl peptidase IV activity and binds adenosine deaminase. Recent work showed that specialized membrane microdomains, also known as lipid rafts, play a key role in T-cell signaling. In this study, we investigate the role of CD26 in cord blood T-cell activation and signal transduction. We demonstrated that different expression levels of CD26 were observed between cord blood T cells (CBTCs) and peripheral blood T cells (PBTCs) and that CD26(+)CD45RA(+) CBTCs were different compared with CD26(+)CD45RA(+) PBTCs. Moreover, the comitogenic effect of CD26 was not as pronounced in CBTCs as in PBTCs. We also showed that CD26 cross-linking induced less phosphorylation of T-cell receptor-signaling molecules, lymphoid T-cell protein tyrosine kinase (Lck), zeta-associated protein 70 (ZAP-70), T-cell receptor zeta (TCRzeta), and linker for activator of T cells (LAT) in CBTCs than in PBTCs. Furthermore, CD26 molecules associated with CD45RA molecules outside lipid rafts in CBTCs. Our results suggest that strong physical linkage of CD26 with CD45RA outside lipid rafts may be responsible for the attenuation of T-cell activation signaling through CD26, which may be responsible for immature immune response and the low incidence of severe graft-versus-host disease in cord blood transplantation.