Hypothermic preservation of rat hearts using antifreeze glycoprotein.

Antifreeze proteins are an effective additive for low-temperature preservation of solid organs. Here, we compared static hypothermic preservation with and without antifreeze glycoprotein (AFGP), followed by nonfreezing cryopreservation of rat hearts. The heart was surgically extracted and immersed in one of the cardioplegia solutions after cardiac arrest. Control rat hearts (n=6) were immersed in University of Wisconsin (UW) solution whereas AFGP-treated hearts (AFGP group) (n=6) were immersed in UW solution containing 500 ?g/ml AFGP. After static hypothermic preservation, a Langendorff apparatus was used to reperfuse the coronary arteries with oxygenated Krebs-Henseleit solution. After 30, 60, 90, and 120 min, the heart rate (HR), coronary flow (CF), cardiac contractile force (max dP/dt), and cardiac diastolic force (min dP/dt) were measured. Tissue water content (TWC) and tissue adenosine triphosphate (ATP) levels in the reperfused preserved hearts were also assessed. All the parameters were compared between the control and AFGP groups. Compared with the control group, the AFGP group had significantly (p<0.05) higher values of the following parameters: HR at 60, 90, and 120 min; CF at all four time points; max dP/dt at 90 min; min dP/dt at 90 and 120 min; and tissue ATP levels at 120 min. TWC did not differ significantly between the groups. The higher HR, CF, max dP/dt, min dP/dt, and tissue ATP levels in the AFGP compared with those in control hearts suggested that AFGP conferred superior hemodynamic and metabolic functions. Thus, AFGP might be a useful additive for the static/nonfreezing hypothermic preservation of hearts.

Hypercholesterolemia accelerates bone loss in postmenopausal women.

OBJECTIVES: To clarify the effect of lipid profiles on postmenopausal bone loss using a longitudinal method and to determine whether cytokines are involved in bone loss. METHODS: The subjects were Japanese residents participating in the Iwaki Health Promotion Projects. Women with one or more of the following factors were excluded: a history of surgical menopause, current or past users of bisphosphonates or current user of other drugs known to influence bone and lipid metabolism, and current medication for diabetes or hypertension. Consequently, 99 postmenopausal women (61.2 ± 7.7 years old) and 85 premenopausal women (41.2 ± 8.6 years old) were selected for this study. The osteo-sono-assessment index (OSI) of the left calcaneal bone was obtained twice at 1-year intervals and the annual percentage change in OSI was calculated. Serum total cholesterol, high and low density lipoprotein cholesterol, triglycerides, homocysteine and cytokines such as adipocytokines, interleukins and tumor necrosis factor-α were measured. Postmenopausal women were grouped into three groups according to their basal cholesterol level, and the relationship between basal cholesterol level and annual change in OSI was studied. RESULTS: The annual percentage change in OSI in postmenopausal women with a serum total cholesterol level ≥240 mg/dl was significantly higher compared to those with a normal total cholesterol level, suggesting that hypercholesterolemia accelerates postmenopausal bone loss. No significant differences were seen in any of the cytokines that presumably cause bone resorption. CONCLUSION: These results showed that hypercholesterolemia has an inverse effect on bone loss independent of cytokines presumed to mediate bone loss.

Serum high-molecular weight adiponectin is related to early postprandial glycemic increases and gastric emptying in patients with type 2 diabetes mellitus.

BACKGROUND: Postprandial hyperglycemia and hyperlipidemia are frequently associated with type 2 diabetes mellitus. The aim of the present study is to investigate the clinical determinants of postprandial glycemia and lipemia, especially serum high-molecular weight adiponectin. METHODS: Twenty-seven diabetic patients treated with diet alone and 13 healthy volunteers took liquid test meal containing 53 g carbohydrate and 47 g lipid, dosed with nonradioactive isotope (13)C-acetate. Venous blood and breath samples were obtained for 180 min after the meal. Gastric emptying was evaluated by peak excretion time of (13)CO(2) in the breath samples. Delayed gastric emptying was defined as peak excretion time > 2.5 h (mean + 2 SD in the healthy volunteers). RESULTS: Diabetic patients showed delayed insulin secretion, postprandial hyperglycemia and hyperlipidemia compared with control. Postprandial glycemic increases significantly correlated with enhanced gastric emptying. Serum high-molecular weight adiponectin correlated with postprandial glycemic increases at 30 and 60 min after meal (r = 0.42, p < 0.05; r = 0.37, p < 0.05, respectively). Serum high-molecular weight adiponectin also correlated with gastric emptying (versus peak excretion time r = - 0.58, p < 0.05). In addition, diabetic patients with delayed gastric emptying showed the suppressed postprandial glycemia with lower serum high-molecular weight adiponectin than those with normal gastric emptying. On the other hand, postprandial increases in serum triglyceride were not related to serum high-molecular weight adiponectin or gastric emptying, but significantly related to liver function test (serum transaminases) and body mass index. CONCLUSIONS: Early postprandial glycemic increases were related to elevated serum high-molecular weight adiponectin, which might be associated with enhanced gastric emptying.

Altered postural regulation of foot skin oxygenation and blood flow in patients with type 2 diabetes mellitus.

AIMS: Although skin oxygenation is an important factor in the development and healing of foot ulcers, its regulation was not fully understood. We studied changes in foot skin oxygenation and blood flow during postural changes in patients with type 2 diabetes mellitus. METHODS: Skin oxygenation was measured using transcutaneous oxygen pressure (TcPO(2)) and skin blood flow by laser Doppler flowmetry in 40 patients with type 2 diabetes mellitus without evidence of peripheral arterial disease and 13 healthy control subjects. RESULTS: TcPO(2) in the supine position was significantly lower in patients with type 2 diabetes mellitus compared with control, although skin blood flow was not different. In the sitting position, TcPO(2) significantly increased in control and diabetic patients. The postural change-related increase in TcPO(2) was significantly enhanced in diabetic patients. On the other hand, skin blood blow significantly decreased in the sitting position from the supine position in control subjects but remained stable in diabetic patients. Orthostatic drop in systolic blood pressure correlated negatively with TcPO(2) in the supine position while correlated positively with %change in TcPO(2) and blood flow by postural changes. CONCLUSIONS: The present study demonstrated the dissociated regulation of skin oxygenation and blood flow in response to leg dependency. Impaired postural vasoconstriction was associated with altered regulation of skin oxygenation probably due to sympathetic vascular dysfunction in diabetic patients.

Combination treatment of vitamin C and desferrioxamine suppresses glomerular superoxide and prostaglandin E production in diabetic rats.

AIMS: Increased oxidative stress may contribute to the development of diabetic nephropathy. Conversely, it has been proposed that enhanced glomerular production of prostaglandin E(2) (PGE(2)) may be the cause of glomerular hyperfiltration in streptozotocin (STZ)-induced diabetic rats. As the role of superoxide anion (O(2-)) production in early diabetic nephropathy is not fully understood, we investigated the effect of vitamin C and desferrioxamine treatment on glomerular O(2-) and PGE(2) production in diabetic rats. METHODS: STZ-induced diabetic rats were given drinking water containing 1 g/l of vitamin C and desferrioxamine for 10 days, and glomerular O(2-) production, glomerular PGE(2) synthesis and creatinine clearance were examined. RESULTS: Glomerular O(2-) production increased in untreated diabetic rats compared to non-diabetic controls (142.2 +/- 12.4 vs. 65.4 +/- 3.6 counts/mg protein/min). Treatment with vitamin C and desferrioxamine significantly decreased glomerular O(2-) production (93.7 +/- 6.7 counts/mg protein/min). Glomerular PGE(2) synthesis and creatinine clearance were significantly increased in untreated diabetic rats compared to controls and PGE(2) synthesis was reduced and creatinine clearance tended to decrease by the treatment. CONCLUSIONS: Our results demonstrated that vitamin C and desferrioxamine suppressed the enhanced glomerular O(2-) production with subsequent decrease in PGE(2) production. Antioxidant therapy may be beneficial in preventing the development of diabetic nephropathy.

Smoking cessation and glycaemic control in type 2 diabetic patients.

AIM: To elucidate the relationship between glycaemic control, blood pressure and body-weight change after smoking cessation in type 2 diabetic patients. METHODS: We examined HbA(1c), blood pressure and body weight in 15 type 2 diabetic patients before, 6 and 12 months after quitting smoking. Sixteen type 2 diabetic patients who did not quit smoking served as control. RESULTS: Body weight slightly increased after quitting smoking. Although HbA(1c) levels showed no change in the control group, those in patients who quit smoking significantly increased (6.8 +/- 0.3% before quitting smoking; 7.4 +/- 0.3% 6 months after quitting smoking, p < 0.05; 7.8 +/- 0.4% 12 months after quitting smoking, p < 0.001). Fasting blood glucose also increased in patients who quit smoking. The increase in body weight after quitting smoking did not correlate with the deterioration of glycaemic control. Diastolic blood pressure showed no change in control, whereas that in patients who quit smoking increased at month 12 (69 +/- 3 vs. 76 +/- 3 mmHg, p < 0.01). The increase in HbA(1c) at month 12 after quitting smoking correlated with body mass index before quitting smoking (r = 0.72, p < 0.005) and serum triglyceride before quitting smoking (r = 0.68, p < 0.01). CONCLUSIONS: Glycaemic control and diastolic blood pressure deteriorated in type 2 diabetic patients after quitting smoking. Type 2 diabetic patients who want to stop smoking need a caution to prevent deterioration of glycaemic control and blood pressure after quitting smoking.

[Successful emergent replacement of ruptured aortic arch aneurysm in an inpatient waiting for surgery: report of a case].

A 71-year-old male was admitted to our hospital for examination of mediastinal abnormal shadow, which was diagnosed aortic arch aneurysm. Once he was discharged and stayed at home for 2 weeks, and then re-admitted for surgery. On the 3rd day of 2nd admission, he suddenly fainted away in the ward and was in shock by hemorrhagic cardiac tamponade. He was transferred to operation room within an hour from onset of rupture. Emergent aortic arch replacement was performed under circulatory arrest with deep hypothermia and retrograde cerebral perfusion. His postoperative course was uneventful without any neurological deficits. Prompt diagnosis and surgery may contribute to improvement of surgical result in patients with ruptured aortic arch aneurysms.

[Treatment for bilateral multiple lung cancers].

During a 27-year period 1,839 patients with lung cancer were treated at Kanazawa University Hospital. Of these 1,839 patients, 25 (1.3%) were classified as bilateral multiple lung cancers by Martini's criteria. They consisted of 14 synchronous carcinomas and 11 metachronous carcinomas. For the patients with synchronous carcinomas, 5 underwent bilateral operation, and 5 underwent ipsilateral operation and contralateral combination therapy (Nd:YAG, irradiation or chemotherapy). Four did not undergo operation. While for the patients with metachronous carcinomas, 9 underwent operation for bilateral lesions, 2 were treated by radiotherapy for the second primary lung cancer. When a pulmonary resection for bilateral multiple lung cancers is required, radicality and the need to preserve residual respiratory function and cardiac function (FEV1.0 more than 500 ml/DSA, performance status) must be considered in making the decision to operation. The 5-year survival rate was 67%, 41%, and 33% in cases treated by operation for bilateral lesions, ipsilateral operation and contralateral combination therapy, and non-surgical therapy. Multidisciplinary treatment based on surgical resection contributed to good prognosis of bilateral multiple lung cancers. A long-term detailed follow-up is necessary to detect second lung carcinoma after the first operation as soon as possible.

[Early and late survival of total aortic arch replacement in patients with dissecting or atherosclerotic aneurysm].

Forty-seven patients (pts) were underwent total aortic arch replacement (TAAR) were studied to compare the early and late results between atherosclerotic (AA) and dissecting aneurysm (DA). There were 23 pts with AA and 24 pts with 24 pts. Preoperative risk were observed with shock in 12 pts (26%), major organ ischemia in 2 pts (4%), rupture in 8 pts (17%), stroke in 8 pts (17%) and coronary artery disease in 4 pts (9%). Operative procedure was TAAR in 22 pts, TAAR with ascending aorta replacement in 14 pts, and TAA with descending aorta replacement in 11 pts. Hospital mortality was 21 pts (45%) and late mortality was a surgical death after thoracoabdominal aneurysm in 1 pts. There was no difference in early and late survival rate, however early mortality was higher in pts with ruptured AA and with DA suffered from preoperative shock. There were 19 of early death in recent pts without rupture in AA and preoperative shock in DA.

Urocortin in the synovial tissue of patients with rheumatoid arthritis.

Urocortin is a newly identified member of the corticotropin-releasing factor (CRF) neuropeptide family, and is known to be involved in the modulation of the inflammatory process. We examined the expression of urocortin, CRF and their receptors (CRF receptor; CRF-R) in the synovial tissue of patients with rheumatoid arthritis (RA) in order to study the possible biological roles of urocortin. Synovial tissues/fluids were obtained from 38 patients with RA, nine patients with osteoarthritis and four with trauma. We studied the concentration of urocortin in the synovial fluid using RIA, and the expression of urocortin in synovial tissue using immunohistochemistry, mRNA in situ hybridization and reverse transcriptase-PCR (RT-PCR). In addition, we examined the immunolocalization of CRF and the expression of CRF-R1, -R2-alpha and -R2-beta mRNAs utilizing RT-PCR in these synovial tissues. Urocortin concentrations in synovial fluid were higher in RA patients (79.8+/-154 pg/ml) than in control patients (12.3+/-4.8 pg/ml; P< or =0.05). Urocortin immunoreactivity and mRNA signals were both detected in synovial cells, lymphocytes, fibroblasts and macrophages. The number of urocortin-positive cells in the synovium was significantly higher in RA (73.1+/-32.1 cells per high-power field) than in control (18.4+/-10.4 cells per high-power field) patients. In addition, both urocortin immunoreactivity and mRNA signals in the synovium reached maximum levels in the active stage of RA inflammation. Moreover, the number of immunoreactive urocortin-positive cells was significantly correlated with the urocortin concentration in synovial fluid (r=0.705; P<0.001) and with histologically defined local inflammatory activity (r=0.641; P<0.001). The distribution and number of immunoreactive CRF-positive cells in synovial tissue were similar to those of urocortin-positive cells (r=0.701; P<0.001). Urocortin, CRF-R1 and CRF-R2-alpha mRNAs detected by RT-PCR were expressed in in the synovium of 10/10, 10/10 and 2/10 RA patients respectively, but CRF-R2-beta was not expressed. Urocortin was actively synthesized in the synovium of RA patients. The present study suggests that urocortin may play an important role as an autocrine and/or paracrine regulator of synovial inflammation in RA.

Effect of nicardipine versus enalapril on plasma endothelin-1 in hypertensive patients with type 2 diabetes mellitus.

We compared the effects of dihydropyridine type Ca channel blocker slow-release nicardipine and angiotensin converting enzyme inhibitor enalapril on plasma endothelin-1 (ET-1) levels in hypertensive type 2 diabetic patients (n=20). Nicardipine or enalapril was administered for 6 months by a crossover design. Nicardipine and enalapril comparably lowered blood pressure. Enalapril significantly reduced urinary albumin excretion in microalbuminuric patients, whereas nicardipine did not. Urinary beta2-microglobulin excretion was significantly increased during nicardipine treatment. However, both drugs significantly reduced plasma ET-1 as compared with pretreatment levels, close to that in healthy control (2.9 +/- 0.3 pg/ml in control, 4.8 +/- 0.3 pg/ml before treatment, 3.2 +/- 0.3 pg/ml during nicardipine vs before treatment p<0.05, 2.9 +/- 0.4 pg/ml during enalapril vs before treatment p<0.01). The decrease in plasma ET-1 was significantly correlated with the increase in natriuresis in normoalbuminuric patients treated with enalapril ( r= -0.82, p<0.01) but not in those treated with nicardipine. Although nicardipine and enalapril had different renal effects, both drugs equally suppressed plasma ET-1 levels in hypertensive patients with type 2 diabetes.

A case of insulin dependent diabetes mellitus following systemic treatment for Vogt-Koyanagi-Harada syndrome.

A 29-year-old man developed acute visual impairment, cough, and headache. Both eyes showed serous retinal detachment in the posterior fundus. Fluorescein angiography showed subretinal pooling of fluorescein in the late phase. A diagnosis of Vogt-Koyanagi-Harada (VKH) syndrome was made based on clinical features. Treatment with systemic corticosteroids resulted in improvement of uveitis and both eyes showed "sunset glow" fundus 11 months later. Insulin-dependent diabetes mellitus (IDDM) developed 13 months later (3 months after systemic corticosteroid therapy). Despite treatment with insulin, glycemic control was poor. Human leukocyte antigen (HLA) typing showed HLADR9 and DQB 1*0303 related to IDDM. We postulated that treatment with corticosteroids precipitated IDDM, a yet unknown common autoimmune mechanism might have caused IDDM and VKH, or both conditions occurred coincidentally.

Effects of monosodium glutamate-induced obesity in spontaneously hypertensive rats vs. Wistar Kyoto rats: serum leptin and blood flow to brown adipose tissue.

We compared the effects of hypothalamic obesity induced by neonatal monosodium glutamate (MSG) treatment between spontaneously hypertensive rats (SHR) and normotensive Wistar Kyoto rats (WKY). Newborn WKY and SHR were injected intraperitoneally with 4 mg/kg body weight of MSG daily for 5 days. At 6 months of age, the obesity of SHR was more advanced than that of WKY, but at 14 months of age the severity of obesity was similar between the two strains. Hypertriglyceridemia was enhanced in MSG-treated SHR as compared with MSG-treated WKY. Systolic blood pressure measured by the tail-cuff method was consistently lower in MSG-treated SHR than in control SHR, whereas blood pressure was not affected by neonatal MSG treatment in WKY. Food restriction reduced body weight more in control SHR than in control WKY, with the former also showing enhanced ketogenesis. Neonatal MSG treatment abolished the accelerated reduction of body weight in SHR. Serum leptin concentration was markedly increased in MSG-treated obese rats, though no differences were seen between WKY and SHR in the control or MSG-treated groups. Serum leptin was closely correlated with both Lee obese index and mesenteric fat weight over the strain. Blood flow in interscapular brown adipose tissue (BAT) measured by Laser Doppler flowmetry was significantly increased in response to beta3-adrenoceptor agonist BRL26830A in both the control and MSG-treated rats. However, the response of blood flow was not affected by MSG treatment or strain difference. The present study demonstrated some strain differences in response to neonatal MSG treatment between WKY and SHR. These differences could not be explained by the difference in serum leptin level or beta3-adrenergic reactivity in BAT.

Auditory agnosia restricted to environmental sounds following cortical deafness and generalized auditory agnosia.

We encountered a case of auditory agnosia restricted to environmental sounds, which was associated with the development of bilateral subcortical lesions after suffering a bilateral putaminal hemorrhage. The patient had a history of a putaminal hemorrhage on her left side without any major disability. Three years later, she suffered a putaminal hemorrhage on the other side. The clinical picture started with cortical deafness, then changed to generalized auditory agnosia for verbal and environmental sounds, and finally developed into auditory agnosia confined to the perception of environmental sounds. Her errors in a test of sound recognition were discriminative rather than associative in nature. Neuro-radiological examinations revealed bilateral subcortical lesions involving the fibers from the medial geniculate body to the temporal lobes after bilateral putaminal hemorrhage. This case suggested that the subcortical lesion involving bilateral acoustic radiation could cause either cortical deafness, auditory agnosia of all sounds, or auditory agnosia restricted to environmental sounds.

A case of adrenocortical carcinoma associated with recurrence after laparoscopic surgery.

Laparoscopic adrenalectomy has become increasingly popular because of its minimally invasive nature, but guidelines for selection of cases suitable for this surgical procedure have not been established. We report a 52-year-old woman with adrenocortical carcinoma, manifesting as Cushing's syndrome, treated with laparoscopic adrenalectomy. The tumour was removed in toto and had been histologically diagnosed as adrenocortical adenoma. However, the patient developed intra-abdominal peritoneal dissemination of carcinoma 15 months after surgery. Review of the histopathological findings of the resected adrenocortical tumour revealed that the neoplasm met five out of nine histological criteria for adrenocortical malignancy, and was diagnosed as adrenocortical carcinoma. Histopathological examination of the tumour was also consistent with adrenocortical carcinoma. The patient responded extremely well to chemotherapy, including carboplatin, etoposide and o,p'-DDD (1,1-dichlorodiphenyldichloroethane), and a subsequent CT (computed tomography) scan 12 months after the start of chemotherapy demonstrated no evidence of disease. However, the patient developed neurological impairment, including dysarthria, as a side-effect of o, p'-DDD. The patient died of aspiration pneumonia due to a decreased pharyngeal reflex. Postmortem examination revealed no foci of residual carcinoma. This case report emphasizes the importance of excluing possible adrenocortical malignancy in patients considered for laparoscopic adrenalectomy, histopathological diagnosis of adrenocortical malignancy and careful monitoring for neurotoxicity during o,p'-DDD treatment.

Peroxisome proliferator-activated receptor gamma1 (PPARgamma1) expresses in rat mesangial cells and PPARgamma agonists modulate its differentiation.

Thiazolidinediones, synthetic ligands of peroxisome proliferator-activated receptor gamma (PPARgamma), are reported to have direct beneficial effects on diabetic nephropathy without lowering blood glucose levels in human and rat. We hypothesized these effects of thiazolidinediones might be derived from PPARgamma activation of kidney cells, and we examined the expression of PPARgamma and the effect of PPARgamma agonists, troglitazone and 15-deoxy-delta-prostaglandin J2 (15d-PGJ2), on the proliferation and differentiation in rat mesangial cells. A single band of mRNA of PPARgamma with a predicted size was detected in reverse transcription-polymerase chain reaction products (RT-PCR) using established PCR probes of PPARgamma. PPARgamma protein in rat mesangial cells was identified as PPARgamma1 by a Western blot. In a gel mobility shift assay to determine a binding activity of PPARgamma, the nuclear protein from rat mesangial cells bound to a (32)P-labeled oligonucleotide probe, including PPAR response elements. A synthetic and a natural ligand of PPARgamma, troglitazone and 15d-PGJ2, decreased thymidine incorporation in a dose dependent manner. After 7 days incubation with troglitazone and 15d-PGJ2, alpha-smooth muscle actin expression, a marker of mesangial cell de-differentiation, was decreased significantly compared to that of control. These results indicate that PPARgamma1 is expressing in rat mesangial cells, and PPARgamma1 activation with its agonists modulates the proliferation and differentiation of cultured rat mesangial cells.

Normal pressure hydrocephalus in diabetic patients with recurrent episodes of hypoglycemic coma.

The pathophysiology of brain damage induced by severe hypoglycemia is still unknown. We experienced a case with type 1 diabetes and recurrent severe hypoglycemic coma who showed a central brain atrophy and an abnormal cerebrospinal fluid flow, suggesting normal pressure hydrocephalus. Following this case, the CSF flow was studied using 111In-DTPA cisternography in six consecutive diabetic patients admitted for repeated episodes of hypoglycemic coma. All the patients showed the central brain atrophy on computed tomography and four of them (67%) had the ventricular reflux, with delayed clearance of 111In-DTPA. Two patients with abnormal CSF flow showed cognitive dysfunction by WAIS or WAIS-R. In contrast, none of five randomly selected diabetic patients, without hypoglycemic coma showed abnormal CSF flow. Our results suggest the presence of normal pressure hydrocephalus in diabetic patients with recurrent hypoglycemic coma. It may associate with the cognitive dysfunction.

Urocortin and corticotropin-releasing factor receptor expression in the human colonic mucosa.

Urocortin is a newly identified member of the CRF neuropeptide family. Urocortin has been found to bind with high affinity to CRF receptors. The present study investigated urocortin and CRF receptor expression in human colonic mucosa. Non-pathologic sections of adult colorectal tissues were obtained from patients with colorectal cancer at surgery. Urocortin expression was examined using immunohistochemistry and messenger (m) RNA in situ hybridization. Isolated lamina propria mononuclear cells (LPMC) and epithelial cells were also analyzed by flow cytometry for the characterization of urocortin-positive cells, and by RT-PCR for detection of urocortin, CRF, and CRF receptor mRNA. Urocortin peptide distribution at various stages of human development (n = 35, from 11 weeks of gestation to 6 years of age) was examined by immunohistochemistry using surgical and autopsy specimens. Immunoreactive urocortin and urocortin mRNA were predominantly detected in lamina propria macrophages. Urocortin peptide expression was detected from as early as three months of age, but not before birth or in neonates. Urocortin, CRF receptor type 1 and type 2 alpha mRNA were detected in LPMC. CRF receptor type 2 beta mRNA, a minor isoform in human tissues, was also detected in LPMC, but at lower levels. Urocortin is locally synthesized in lamina propria macrophages and may act on lamina propria inflammatory cells as an autocrine/paracrine regulator of the mucosal immune system. The appearance of urocortin after birth indicates that the exposure to dietary intake and/or luminal bacteria after birth may contribute to the initiation of urocortin expression in human gastrointestinal tract mucosa.