Ming-Shian Tsai

Aminoguanidine prevents arterial stiffening in a new rat model of type 2 diabetes

Background  Formation of advanced glycation end‐products (AGEs) on collagen within the arterial wall may be responsible for the development of diabetic vascular injury. This study focused on investigating the role of aminoguanidine (AG), an inhibitor of AGE formation, in the prevention of noninsulin‐dependent diabetes mellitus (NIDDM)‐derived arterial stiffening and cardiac hypertrophy in rats.

Autonomic neuropathy precedes cardiovascular dysfunction in rats with diabetes

Background  Our team previously demonstrated arterial stiffening and cardiac hypertrophy in type 2 diabetic rats at 8 but not 4 weeks after being administered streptozotocin (STZ) and nicotinamide (NA). The present study focused on investigating the effects of type 2 diabetes on cardiac autonomic nerve function in the STZ‐ and NA‐treated animals, using modern spectral estimation technique.

Enhanced expression of cardiac nerve growth factor and nerve sprouting markers in rats following gastric perforation: the association with cardiac sympathovagal balance.

Endotoxemia and/or systemic inflammation may lead to disturbances in the cardiac autonomic nervous system and consequent arrhythmia. The underlying mechanism remains unclear. Therefore, we investigated the expression of nerve growth factor (NGF) and its association with cardiac sympathovagal balance in a rodent model of self-limited peritonitis. Male Wistar rats were randomized into the following groups: normal control, sham, gastric perforation (GP), and GP treated with methylprednisolone. Cardiac expression of NGF, growth-associated protein 43 (GAP43), along with other nerve markers were evaluated at several time points (6 h to 2 weeks) after GP. An autoregressive process was performed on each detrended electrocardiogram to calculate the heart rate power spectrum. Compared with the normal control and sham groups, expression of NGF was significantly elevated for 1 week after GP. We also found the up-regulated GAP43 and tyrosine hydroxylase protein levels in the GP group, which persisted after recovery from peritonitis. Gastric perforation caused a biphasic change in the ratio of low-frequency to high-frequency power (an index of sympathovagal balance), with an initial decrease followed by recovery at 24 h. Increased NGF and cardiac sympathetic marker expression were temporally associated with the restoration of the cardiac sympathovagal balance. Methylprednisolone abrogated the NGF up-regulation induced by GP and delayed the resumption of sympathovagal balance. We conclude that GP resulted in up-regulation of cardiac NGF, GAP43, and tyrosine hydroxylase expression that coincided with recovery of cardiac sympathovagal balance. Moreover, methylprednisolone can effectively block GP-induced NGF up-regulation.

Effects of acetyl‐L‐carnitine and oxfenicine on aorta stiffness in diabetic rats

Eur J Clin Invest 2010; 40 (11): 1002–1010

Pyridoxamine protects against mechanical defects in cardiac ageing in rats: studies on load dependence of myocardial relaxation

What is the central question of this study? This study aimed to investigate the hypothesis that pyridoxamine, one of the three natural forms of vitamin B6, can protect against myocardial relaxation of senescent animals by targeting arterial stiffening and contractile dysfunction of the left ventricle. What is the main finding and its importance? We found that treating the senescent rats with pyridoxamine for 5 months might improve myocardial relaxation rate, at least partly through its ability to enhance myocardial contractile performance, increase wave transit time and decrease wave reflection factor.

Methylprednisolone stiffens aortas in lipopolysaccharide-induced chronic inflammation in rats.

Introduction Glucocorticoids are commonly used as therapeutic agents in many acute and chronic inflammatory and auto-immune diseases. The current study investigated the effects of methylprednisolone (a synthetic glucocorticoid) on aortic distensibility and vascular resistance in lipopolysaccharide-induced chronic inflammation in male Wistar rats. Methods Chronic inflammation was induced by implanting a subcutaneous slow-release ALZET osmotic pump (1 mg kg−1 day−1 lipopolysaccharide) for either 2 or 4 weeks. Arterial wave transit time (τ) was derived to describe the elastic properties of aortas using the impulse response function of the filtered aortic input impedance spectra. Results Long-term lipopolysaccharide challenge enhanced the expression of advanced glycation end products (AGEs) in the aortas. Lipopolysaccharide also upregulated the inducible form of nitric oxide synthase to produce high levels of nitric oxide (NO), which resulted in vasodilation, as evidenced by the fall in total peripheral resistance (Rp). However, lipopolysaccharide challenge did not influence the elastic properties of aortas, as shown by the unaltered τ. The NO-mediated vascular relaxation may counterbalance the AGEs-induced arterial stiffening so that the aortic distensibility remained unaltered. Treating lipopolysaccharide-challenged rats with methylprednisolone prevented peripheral vasodilation because of its ability to increase Rp. However, methylprednisolone produced an increase in aorta stiffness, as manifested by the significant decline in τ. The diminished aortic distensibility by methylprednisolone paralleled a significant reduction in NO plasma levels, in the absence of any significant changes in AGEs content. Conclusion Methylprednisolone stiffens aortas and elastic arteries in lipopolysaccharide-induced chronic inflammation in rats, for NO activity may be dominant as a counteraction of AGEs.

Surgery is justified in patients with bowel obstruction due to radiation therapy

The management of the patient with radiation-induced bowel obstruction remains controversial. To reassess the surgical therapy for radiation-induced bowel obstruction, we analyzed 22 patients operated upon at the National Taiwan University Hospital. In 10 patients, peritoneal carcinomatosis was found during operation. We classified them as “recurrence group” and the remaining 12 patients as the “study group.” Three patients in the study group had metastases, which did not cause bowel obstruction. The clinical presentation and image findings of both groups were not significantly different. The patients of the study group tended to have a low body mass index (mean ± SD, 18.7 ± 1.92 kg/m2) and decreased serum albumin level (mean ± SD, 3.12 ± 0.32 g/dl). Total parenteral nutrition was given for 27.1 ± 16.0 days (mean ± SD). The strategies of operation included resection and anastomosis (nine patients), bypass (two patients), or ileostomy (one patient). Operation resolved bowel obstruction and enteral nutrition was resumed in all the patients postoperatively. No early postoperative mortality occurred. Four patients had morbidity, including one reoperation because of anastomotic failure, one enterovesical fistula, and two cases of wound infection. The estimated median survival time of the study group (21 months) was significantly longer than that of the recurrence group (5 months). Specifically in the patients without previous neoplasm recurrence or metastasis, overall survival was 100%, 80%, and 53%, at 1, 2, and 5 Years after surgery, respectively. We conclude surgery plays a role in both diagnostic and therapeutic aspects of radiation bowel injury. For selected patients, resection and primary anastomosis is an appropriate choice.

Enhanced Aortic Nerve Growth Factor Expression and Nerve Sprouting in Rats Following Gastric Perforation

BACKGROUND Nerve growth factor (NGF) up-regulation during inflammation has been demonstrated to occur in several different tissues. Herein, the expression of aortic nerve growth factor and its association with nerve sprouting in a rodent model of self-limited peritonitis were investigated. MATERIALS AND METHODS Male Wistar rats were randomized into one of three groups: gastric perforation (GP), sham group, and GP group treated with methylprednisolone (GP-M). Aortic expression of NGF and growth associated protein 43 (GAP43) were evaluated at several different time points (range, 6 h to 2 wk) after GP or sham. RESULTS Compared with the sham group, expression of NGF was significantly elevated during the inflammatory period (the first week post-GP) in GP rats. The GP group also had enhanced nerve sprouting, which persisted after the peritonitis recovered. Methylprednisolone abrogated NGF up-regulation and nerve sprouting induced by GP. CONCLUSIONS GP resulted in up-regulation of aortic NGF that coincided with aortic nerve sprouting. Methylprednisolone effectively blocked GP-induced NGF up-regulation. Further studies are necessary to decipher the causality of these observed changes.

Chylous ascites after excision of a choledochal cyst in a child

We report a case of chylous ascites developing 2 weeks after excision of a choledochal cyst with a Roux-en-Y hepaticojejunostomy. Despite the failure of the initial attempts to resolve the chylous ascites by fasting, subsequently, we successfully treated the patients chylous ascites with intravenous somatostatin. No obvious adverse side effects occurred during the use of somatostatin. To the best of our knowledge, this is the first report of chylous ascites after choledochal cyst excision in children, which was successfully treated with somatostatin. Somatostatin may be considered as a therapeutic option of managing pediatric postoperative chylous ascites.

Modified Paul-Mikulicz Ileostomy in a Swine Model of Isolated Small Bowel Transplantation

BACKGROUND Intestinal transplantation (ITx) is a life-saving procedure for patients with intestinal failure. The poorer outcome of ITx than of other organ transplantation, however, warrants more clinical and basic research on ITx. Herein, we developed a modified Paul-Mikulicz ileostomy procedure in a swine model of ITx, and investigated its feasibility for obtaining intestinal samples of both the graft and the recipient. MATERIALS AND METHODS We performed ITx in 10 pairs of piglets, each weighing 15-20 kg. Procurement included an isolated segment of the small bowel, constituting a model of a living, related donor surgery. The recipient procedures included end-to-end anastomosis of vascular stumps, a proximal jejuno-jejunal anastomosis, and a distal modified Paul-Mikulicz ileostomy. The procedure differed from the classic Paul-Mikulicz ileostomy in that a common channel was created in a side-to-side fashion. RESULTS Vascular thrombosis occurred in three pigs, resulting in immediate loss of the graft. All other pigs underwent ITx successfully and survived for at least 1 wk (7-180 d). No pig experienced anastomotic leaks, ileus, or stoma-related complications. Moreover, this technique enabled us to obtain tissue samples of both the graft and the native ileum without disturbing the natural bowel conduit. CONCLUSIONS The modified Paul-Mikulicz ileostomy was feasible in a swine model of ITx. It facilitated the collection of intestinal samples of both the graft and the recipient.