Do teas rich in antioxidants reduce the physicochemical and peroxidative risk factors for calcium oxalate nephrolithiasis in humans? Pilot studies with Rooibos herbal tea and Japanese green tea.

Several experimental and animal studies have demonstrated that substances rich in antioxidants can reduce the physicochemical and peroxidative risk factors for calcium oxalate (CaOx) renal stone formation in urine and blood. However, there are very few such investigations in humans. In the present pilot study, two varieties of tea, a green one from Japan (JGT) and a herbal one from South Africa (Rooibos) (RT), both rich in antioxidants, were administered to a group of CaOx stone formers (SF) (n = 8) for 30 days. Both teas were analysed for polyphenols by high-performance liquid chromatography and for minerals by plasma atomic and optical emission spectroscopy. 24 h urines (baseline and day 30) were analysed for lithogenic factors. CaOx metastable limits and crystal nucleation and growth kinetics were also determined in each urine sample. Deposited crystals were inspected by scanning electron microscopy. Blood samples were collected (baseline and day 30). Biomarkers of oxidative stress including plasma and urinary thiobarbituric acid reactive substances (TBARS) and urinary N-acetyl-ß-D-glucosaminidase (NAG) were also determined. Urinary physicochemical risk factors were also investigated after ingestion of RT for 30 days in two control groups (CG1 and CG2), the latter one of which consisted of habitual JGT drinkers. Statistical analyses were performed using Wilcoxon signed rank tests and Mann-Whitney tests for paired and independent measurements, respectively. Several flavonoids and catechins were quantified in RT and JGT, respectively, confirming that both teas are rich sources of antioxidants. Mineral content was found to be far below dietary reference intakes. There were no significant changes in any of the urinary physicochemical or peroxidative risk factors in the control groups or in SF, except for the supersaturation (SS) of brushite (Bru) which decreased in the latter group after ingestion of JGT. Crystal morphology showed a tendency to change from mixed CaOx mono- and di-hydrate to monohydrate after ingestion of each tea. Since the latter form has a stronger binding affinity for epithelial cells, this effect is not protective. Analysis of the physicochemical and peroxidative risk factors in CG1 and CG2 did not reveal any evidence of a synergistic effect between the two teas. Paradoxically, baseline risk factors in the habitual JGT control group were significantly raised relative to those in CG1. Our preliminary results suggest that ingestion of RT and JGT does not reduce the risk factors for CaOx stone formation in humans, but these findings need to be tested in further studies involving much larger sample sizes.

Preoperative oral supplementation support in patients with esophageal cancer.

OBJECTIVE: Surgeries for cancer of the esophagus are still associated with a high rate of postoperative morbidity. There are few reports of perioperative nutritional support for patients undergoing esophageal cancer surgery, and there is insufficient evidence to recommend routine use of immunonutrition in these patients. The aim of this study was to determine whether preoperative immunonutrition positively influences key clinical outcomes such as postoperative infectious complications, mortality, length of hospital stay, and short-term survival in this population. DESIGN AND SETTING: We undertook a retrospective investigation of the effects of preoperative nutritional support on the postoperative course of esophageal cancer surgery at the Department of Gastroenterological Surgery, International University of Health and Welfare Mita Hospital, Tokyo, Japan. PARTICIPANTS: Fifty-five patients who underwent esophagectomy for esophageal cancer were included in this study. Of the 55 patients, 26 patients consumed a liquid dietary supplement (IMPACT group) before surgery and 29 patients did not (STANDARD group). INTERVENTION: Before surgery, the IMPACT group consumed 750 ml (3 packs)/day of Impact for 5 consecutive days. MEASUREMENTS: The analysis was based on postoperative complications, hospital mortality, length of hospital stay, and short-term survival. RESULTS: Significantly fewer patients developed postoperative infections in the IMPACT group compared with the STANDARD group (p=.007): 4 of 21 patients in the IMPACT group and 10 of 29 patients in the STANDARD group. Either an infectious complication or another complication developed in 8 patients in the IMPACT group and 13 patients in the STANDARD group, with the result that 6 patients in the STANDARD group died of postoperative complications (p=.001). The duration of hospitalization was 34 days in the IMPACT group and 48 days in the STANDARD group; hence, hospitalization was significantly shorter in patients treated with Impact (p=.008). The mean 6-month survival rates for the IMPACT group and the STANDARD group were 92% (24/26) and 72% (21/29), respectively (p=.028). CONCLUSION: Simple preoperative supplementation significantly improved outcome. Administration of the supplemental diet before esophageal surgery appeared to be an effective strategy in reducing infectious complications, mortality, and hospitalization, and improving short-term survival.

Endorectal pull-through with posterior sagittal approach to the repair of postoperative rectourethral and rectovaginal fistula.

BACKGROUND/PURPOSE: Rectourethral (RUF) or rectovaginal fistula (RVF) is a troublesome complication after anorectal surgery because of dense adhesions around the fistula. The authors applied a new technique for the redo surgery. METHODS: Case 1 is Hirschsprung's disease in a 1-year-old boy who underwent modified Duhamel's procedure and had RUF. Case 2 is rectovestibular fistula in an 11-year-old girl who had anterior sagittal anorectoplasty complicated by RVF. Case 3 is multiple urogenital anomalies including rectovesical fistula in a 4-year-old boy in whom transvesical repair was unsuccessful. The colon was mobilized as far as possible at laparotomy. The rectum was opened via a posterior sagittal approach leaving 1 cm of the anal canal. Extended endorectal mucosectomy was performed to the dentate line, and the fistula was closed from inside of the rectum. The remaining mucosal cuff was everted out of the anus and the intact colon was pulled through the rectum and anastomosed to the cuff extraanally. RESULTS: The postoperative contrast enema showed no recurrent fistula, and defecation was not impaired. CONCLUSIONS: Endorectal pull-through of the intact colon can spare troublesome mobilization of the fistula and can prevent the recurrence of fistula. Rectal incision via a posterior sagittal approach provides a direct view of the fistula.

[A case of postoperative multiple hepatic metastasis from esophageal cancer successfully treated by surgical resection and hepatic arterial infusion chemotherapy].

A 66-year-old male who underwent radical resection for esophageal cancer (stage IV) was diagnosed with multiple hepatic metastasis 1 year and 3 months after the surgery. He underwent hepatic resection and received systemic chemotherapy (FAP: 5-FU, ADR, CDDP), as the post-operative adjuvant therapy. One year and 3 months later, there was a huge recurrence in the residual liver and hepatic arterial infusion chemotherapy (FAP) was performed. The recurrent lesion disappeared completely after 3 sessions of arterial infusion chemotherapy. The arterial infusion chemotherapy was continued in the outpatient clinic and the recurrent lesion is well controlled. At present, this patient has returned to social life, 2 years and 3 months after the hepatic resection. The utility of hepatic arterial infusion chemotherapy and hepatectomy for postoperative multiple hepatic metastasis from esophageal cancer was shown in the present case.

[Bacterial contamination of salvaged blood in open heart surgery: is that an airborne contamination or a normal skin flora contamination?].

We investigated sources of bacterial contamination of intraoperative salvaged blood producted by autologous transfusions device (CS; CELL SAVER 5, Heamonetics Corp., Braintree, MA). Eleven patients undergone open heart surgeries including 2 emergency operations with a median sternotomy enrolled in this study. Blood samples were drawn from salvaged blood bags. Airborne contaminants (AB) were collected by a blood agar plate put besides the operation bed for 30 minutes. The median wounds samples were collected by a swab. Bacterial growth was detected in 81.8% of salvaged blood samples. Twenty-nine bacterium were isolated from CS, 72.4% of those were Staphylococci. 9.1% of sample was positive in wound swabs. Forty bacterium were isolated from plate cultures. 65% of them were Staphylococci. Staphylococcus epidermidis and coagulase negative Staphylococcus isolated both CS and AB in the 2 cases had the same identify codes, and incubated from several AB cultures. Corynebacterium sp. is also isolated from both CS and AB cultures in other 2 same cases. In 7 out of 8 cases (87.5%), from which Staphylococci isolated in CS, the Staphylococci were cultured from AB in not the same but the other cases. In conclusion, highly incidence of the identification in identical code of Staphylococci indicated that the main source of CS contamination was highly suspected to AB.

[A case of choroidal hemangioma with bullous exudative retinal detachment treated successfully by transpupillary thermotherapy].

BACKGROUND: Choroidal hemangioma associated with bullous retinal detachment may be difficult to treat, due to varying results with conventional laser photocoagulation, radiotherapy, or surgical drainage. Here we report on a case of extensive bullous retinal detachment secondary to circumscribed choroidal hemangioma that was resolved after combined treatment with vitrectomy, silicone oil tamponade, and transpupillary thermotherapy. CASE: A 29-year-old woman presented with a large choroidal hemangioma in her right eye associated with serous retinal detachment. The tumor measured 8 disc diameters in size and was located in the inferotemporal macula, abutting the fovea. RESULTS: Laser photocoagulation of the tumor was unsuccessful in inducing absorption of subretinal fluid. Because of progressive bullous retinal detachment, surgery was performed consisting of external drainage of subretinal fluid, vitrectomy, endolaser photocoagulation of the tumor, and silicone oil tamponade. The silicone oil was removed four weeks postoperatively at which time almost complete resolution of the retinal detachment was observed. However, retinal detachment recurred eight weeks later, and transpupillary thermotherapy was then applied to the tumor. By four weeks after transpupillary thermotherapy, total reabsorption of subretinal fluid, visual acuity improvement, and decreased height of the choroidal hemangioma were noted. CONCLUSION: Transpupillary thermotherapy is an effective treatment for serous retinal detachment associated with choroidal hemangioma.

Nitric oxide synthase inhibitor attenuates inflammatory lesions in the skin of zinc-deficient rats.

Skin lesions are common manifestations of zinc deficiency in humans and animals, but the pathogenic mechanisms have not been fully clarified. In the present study, a nitric oxide synthase inhibitor, NG-nitro-L-arginine methyl ester (L-NAME), was given to zinc-deficient (ZD) rats to see whether it prevents or delays the occurrence of skin lesions. Weanling male rats were given free access to a ZD diet (2 mg zinc/kg) for 4 wk to induce zinc deficiency. Control rats, including pair-fed (PF) and ad libitum (AL) groups, were given a diet supplemented with zinc (50.8 mg zinc/kg. L-NAME (0.3 g/L in drinking water) was given to some ZD rats for 3 wk, starting at the second week of their ZD dieting. Dermatitis of the extremities, balanitis, stomatitis, and alopecia appeared in ZD but not in AL and PF rats. Administration of L-NAME significantly reduced the frequency of cutaneous and mucocutaneous inflammatory lesions but did not prevent alopecia in the ZD rats. Reverse transcription polymerase chain reaction showed that inducible nitric oxide synthase mRNA was expressed in the paw skin of ZD but not of AL and PF rats. Evaluation of skin microvascular permeability by the Evans blue leakage technique indicated that L-NAME administration significantly attenuated extravasation of Evans blue in the paw skin of ZD rats. Furthermore, stains positive for terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling were condensed and diffusely distributed over the epidermis, dermis, and subcutaneous tissue of paws in ZD rats. ZD rats had intense cell infiltration and parakeratosis in the paw skin. L-NAME administration effectively prevented these morphologic changes. These results demonstrate that nitric oxide synthase inhibitor ameliorates inflammatory lesions of the skin in ZD rats.

The importance of the plasma amino acid molar ratio in patients with biliary atresia.

BACKGROUND: Plasma amino acid patterns and the therapeutic benefits of amino acid supplements are not examined well in postoperative patients with biliary atresia (BA). This study aimed to investigate profiles of the amino acid molar ratio, the Fischer molar ratio (FR, valine + leucine + isoleucine/phenylalanine + tyrosine), and relationships with other nutritional parameters and to assess the efficacy of enteral nutrient preparations for hepatic failure in patients with BA. METHODS: In study 1 profiles of FR were analyzed in 24 patients with BA (aged 3 to 12 years) in the postoperative period and compared with liver function tests and anthropometric measures. In study 2 10 patients with BA with a FR < 2.0 were begun on a dietary regimen consisting of an ordinary diet supplemented with a branched-chain amino acid-enriched elemental diet. RESULTS: Study 1: In jaundiced patients with total bilirubin levels > 2.0 mg/dL the FR remained below 2.0 throughout the period of observation, in contrast with nonjaundiced patients. The FR was closely related to the levels of serum albumin and plasma rapid turnover proteins and anthropometric measures as well as biochemical data reflecting intrinsic liver function. Study 2: A significant increase in rapid turnover proteins and improvement of general status were noted concurrently with an increase of the FR. CONCLUSIONS: The FR indicates a combination of nutritional status and intrinsic liver function in post-operative BA patients. The FR is a useful parameter in conducting nutritive therapy with a branched-chain amino acid-enriched elemental diet in those patients.

Nitric oxide synthase inhibitor attenuates intestinal damage induced by zinc deficiency in rats.

A nitric oxide synthase (NOS) inhibitor, NG-nitro-L -arginine methyl ester (L-NAME), was given to zinc-deficient (ZD) rats to determine whether it prevents the intestinal damage usually observed under these conditions. Weanling male rats were given free access to a ZD diet (2 mg zinc/kg), whereas control rats including pair-fed (PF) and ad libitum consumption (AL) groups were given a zinc-supplemented (50.8 mg zinc/kg) diet for 4 wk. Half of the ZD rats received L-NAME (0.3 g/L in drinking water) for 3 wk starting at the wk 2 of the deficient period. Plasma zinc concentration in ZD rats was significantly lower (P < 0.05) than that of AL and PF rats. Administration of L-NAME did not alter this concentration. Intestinal zinc concentration did not differ among groups. However, metallothionein-1 (MT-1) mRNA level was significantly lower in the intestine of ZD rats than in AL or PF rats. Treatment of ZD rats with L-NAME did not affect this level. Intestinal microvascular permeability evaluated by Evans blue showed significantly higher extravasation in ZD rats than in AL rats, whereas L-NAME administration inhibited the extravasation. Expression of inducible NOS mRNA was observed in intestine of ZD but not of AL or PF rats, and there was no significant difference between ZD rats, regardless of L-NAME treatment. The activity ratio of inducible NOS to total NOS in ZD rats not receiving L-NAME was significantly higher than that in AL rats or ZD rats treated with L-NAME (P < 0.05). The number of apoptotic-positive and goblet cells in intestinal villi was significantly higher in ZD rats compared with AL or PF rats. L-NAME administration in ZD rats reversed this effect. These results indicate that inhibition of NOS ameliorates zinc deficiency-induced intestinal damage in rats.

Is barium enema reduction safe and effective in patients with a long duration of intussusception?

The aim of this study was to determine whether barium enema reduction (BER) is safe and effective in patients with a long duration of intussusception. Over the last 17 years, 104 patients were admitted to our hospital with a diagnosis of intussusception. All except 1 with peritonitis underwent BER primarily. Of the 103 intussusceptions treated primarily by BER, 84 (82%) were reduced by the enema alone, whereas 19 (18%) underwent surgical reduction. There were no differences in mean duration of disease between the patients with successful and failed enema reduction (successful: 15 +/- 14 h; failures: 14 +/- 11 h, P = 0.6). The success rate of BER was 85% within 12 h of symptoms, 76% for 12-24 h, and 71% for more than 24 h. Of 8 cases with a second trial, 4 (50%) were reduced by repeated barium enema. There were no deaths and no intestinal perforations. The success rate of more than 70% even in patients with a long duration of intussusception suggests that BER is safe and effective regardless of the duration of the disease.

The importance of total parenteral nutrition-associated tissue zinc distribution in wound healing.

It is well known that zinc (Zn), an essential trace element, plays a role in wound healing. Although the importance of Zn supplementation in total parenteral nutrition (TPN) has been recognized, the difference in tissue Zn distribution induced by TPN and whether this difference influences local wound healing remains uncertain. Thus, we conducted a study using 30 Sprague-Dawley rats to investigate the influence of TPN-induced changes in tissue Zn distribution on wound healing at sites of intestinal anastomosis, muscle, and skin sutures. In the ordinary diet group, no significant differences were observed between subgroups with and without supplemental Zn in tissue Zn distribution or in the healing of intestinal, muscular, and cutaneous wounds. In the subgroup given a low-protein diet without supplemental Zn, a gross change in tissue Zn distribution was noted to occur with a concomitant marked decrease in Zn concentration and the tensile strength of wounded skin. These results indicate an association between wound healing and Zn concentration in the respective tissues in TPN-induced Zn deficiency with alternations in tissue Zn distribution. They also provide evidence of the local action of Zn in wound healing.

Alanyl-glutamine-supplemented parenteral nutrition increases luminal mucus gel and decreases permeability in the rat small intestine.

BACKGROUND: Effect of supplemental alanyl-glutamine in standard TPN (S-TPN) on luminal mucus gel and small intestinal permeability was investigated. METHODS: Thirty Sprague-Dawley rats were divided into group I (n = 10), receiving standard rat diet; group II (n = 10), receiving S-TPN; and group III (n = 10), receiving alanyl-glutamine-supplemented TPN for 1 week. After 1 week, fluorescein isothiocyanate (FITC)-dextran was injected into the small intestine of the rats, and they were killed. A small intestinal sample and portal blood were obtained for morphologic and functional analysis of mucus gel and intestinal permeability. RESULTS: In group II, thickness and optical density of mucus gel per millimeter serosal length of intestine were significantly lower than group I (p<.001) and were significantly higher in group III than in group II (p<.001). The number of goblet cells in the villi and in the crypt of the small intestine was significantly lower in group II than in group I (p<.001) and was significantly higher in group III than in group II (p<.001), with the exception of the villi of jejunum. Villous and crypt surface area per millimeter serosal length of intestine was significantly lower in group II than in group I (p<.001) and was significantly higher in group III than in group II (p<.001). Small intestinal permeability to FITC-dextran was significantly higher in group II than in group I (p<.001) and was significantly lower in group III than in group II (p<.001). Glucosamine synthetase level was significantly higher in group III than in group I and ileum of group II (p<.001). CONCLUSIONS: Alanyl-glutamine-supplemented TPN prevents a decrease in mucus gel and an increase in small intestinal permeability associated with S-TPN.

Functional ileus in neonates: Hirschsprung's disease-allied disorders versus meconium-related ileus.

Sixty-eight neonates with functional ileus were reviewed. Twelve required laparotomy; in seven, histological studies revealed decreased ganglia and ganglion cells of the myenteric plexus (MP) (Group A), and in five, MP was normal (Group B). In the remaining 56 cases, obstructive symptoms were relieved following conservative therapy (Group C). All Group A cases except one had normal birth weight, while Group B and C cases showed significantly lower birth weights. A marked caliber change of the small intestine and/or small-caliber distal intestine with meconium stagnation in the proximal intestine was commonly demonstrated at operation in Group A and B, or on contrast enema in Group C. Four Group A cases died of enteritis, and three survivors suffered from prolonged obstructive symptoms. The grade of histological abnormality of MP correlated with the clinical outcome. In Group B, three died of sepsis shortly after surgery, but two survivors have been free from symptoms. Group A can be categorized as Hirschsprung's disease-allied disorders (HAD). Group B and C can be categorized as meconium-related ileus (MRI). The similarity of the macroscopic findings of HAD and MRI, and the occurrence of MRI exclusively in low birth weight neonates, strongly suggest that functional immaturity of MP plays a role in the etiology of MRI.

Transcatheter arterial chemoembolization in the treatment of hepatoblastoma.

BACKGROUND: The prognosis of hepatoblastoma is poor unless the tumor is completely resected. Various types of chemotherapy have been developed to increase its resectability. Recently, transcatheter arterial chemoembolization (TACE) has been developed for the treatment of unresectable adult hepatoma with favorable results. The authors applied this procedure to hepatoblastoma in infants and children. METHODS: TACE was performed in eight hepatoblastoma cases. After an intraarterial catheter was inserted into the main feeding artery of the tumor, injection of adriamycin or THP-adriamycin (20 to 30 mg/m2) dispersed in lipiodol and cisplatin (40 to 60 mg/m2) followed by embolization using Gelfoam pieces was performed. Effects of TACE were evaluated according to shrinkage of tumor mass on imaging examinations, alpha-fetoprotein (AFP) levels, and pathological findings of the surgical specimens 4 weeks after TACE. RESULTS: A marked reduction in tumor size associated with a decrease in AFP level occurred 1 month after the treatment. Tumor shrinkage ranged from 0.9% to 45.0% with a mean value of 25.8%. AFP levels decreased by 0.2% to 11.9% with a mean level of 4.6% from initial levels. In addition, there was no marked chemotherapeutic agent-induced toxicity noted during the observation period. Resection of the tumors was performed safely after TACE in all cases. Pathological examination showed massive necrosis in the surgical specimens, and the mean percentage of necrotic area within the tumor was 71.1%. Two patients died of extensive lung metastasis 2 months and 3 years after the operation, respectively. The remaining six were doing well and free of disease at a mean follow-up period of 50 months. CONCLUSION: TACE is an effective, safe, and useful method for the initial treatment of hepatoblastoma.

Intraocular cytokine quantification of experimental autoimmune uveoretinitis in rats.

Elevations of inflammatory cytokines have been implicated in the pathogenesis of experimental autoimmune uveoretinitis (EAU) in rats, although such analysis has relied on indirect methods of assessment such as measurement of mRNA content. In this study, we examined the feasibility of directly measuring cytokine concentrations in intraocular extracts prepared by ultrasonic disruption. Cytokines were measured by ELISA in eyes from EAU-induced Lewis rats immunized with interphotoreceptor retinoid-binding protein (IRBP), and compared to eyes from rats immunized with adjuvant only and from normal rats. Interferon-gamma (IFN-gamma), tumor necrosis factor-alpha (TNF-alpha), interleukin-2 (IL-2), interleukin-4 (IL-4), and interleukin-10 (IL-10) were detectable in EAU eyes at near peak inflammation, with IFN-gamma achieving the highest mean concentration (331 pg/ml). In eyes from rats immunized with adjuvant only and in normal eyes, IFN-gamma, TNF-alpha, and IL-10 were nondetectable. IL-2 and IL-4 were detected at significantly lower mean concentrations (32.3 pg/ml and 69.4 pg/ml, respectively) compared to EAU eyes (217 pg/ml and 230 pg/ml, respectively); IL-4 was also detected in eyes from rats immunized with adjuvant alone (141 pg/ml). Thus, a direct method of measuring intraocular cytokine concentrations was successfully applied to reveal an elevation of IFN-gamma, TNF-alpha, IL-2, IL-4, and IL-10 in EAU eyes from rats immunized with IRBP, compared to rats immunized with adjuvant alone and to normal rats. These cytokine elevations reflect the local intraocular environment near peak inflammation, and suggest an important role for these cytokines in the mechanisms of onset and resolution of EAU in rats.

Zinc deficiency enhances interleukin-1alpha-induced metallothionein-1 expression in rats.

This study investigated whether interleukin-1alpha-induced metallothionein gene expression is affected by zinc deficiency. Weaning male rats were fed a zinc-deficient (ZD) diet (2 mg zinc/kg) or a zinc-supplemented diet [50.8 mg zinc/kg; controls for the diet included pair-fed (PF) and ad libitum consumption groups (AL)] for 4 wk. All rats except those that served as controls for interleukin-1alpha administration, (injected with vehicle and killed at 0 h) were then injected subcutaneously with interleukin-1alpha (2 x 10(7) units/kg body wt) and killed at 3, 6, 12, 24 and 72 h after the injection. Compared with AL and/or PF rats, zinc depletion significantly reduced zinc concentrations in plasma and liver but not in kidney or intestine, and significantly reduced hepatic, renal, and intestinal metallothionein-1 mRNA levels analyzed by competitive reverse transcription-polymerase chain reaction (RT-PCR). Interleukin-1alpha injection reduced plasma zinc concentration and enhanced liver zinc concentration, but did not affect zinc levels in kidney or intestine. Metallothionein-1 mRNA was significantly elevated by interleukin-1alpha in liver, kidney and intestine of all groups; the levels in liver and kidney of ZD rats 6 h after the injection were significantly higher than those of AL or PF rats. Liver metallothionein protein levels were enhanced after interleukin-1alpha injection in both AL and ZD rats. Semiquantitative RT-PCR revealed significantly higher hepatic levels of interleukin-1 receptor type-I mRNA in ZD rats than in AL and PF rats but no differences in renal or intestinal tissues among groups before interleukin-1alpha challenge. In conclusion, zinc deficiency induces upregulation of metallothionein-1 gene expression in response to interleukin-1alpha challenge in rats.

Induction of nitric oxide synthase in rat intestine by interleukin-1alpha may explain diarrhea associated with zinc deficiency.

Synthesis of inducible nitric oxide synthase (iNOS) in the intestine may result in local tissue damage. We investigated whether a challenge with interleukin-1alpha could give rise to intestinal iNOS expression and diarrhea in rats of differing zinc status. Weaning male rats were fed a zinc-deficient (ZD) diet (2 mg zinc/kg) for 4 wk to induce zinc deficiency or a zinc-supplemented diet [50.8 mg zinc/kg; controls, including pair-fed (PF ) and ad libitum (AL) consumption groups], and then subcutaneously injected with interleukin-1alpha (2 x 10(7) units/kg body wt). Without the interleukin-1alpha challenge, ZD rats had significantly lower plasma zinc concentration than the other groups. Intestinal metallothionein-1 mRNA abundance was lower in ZD rats than in AL rats. iNOS was expressed in the intestine of ZD rats but not in the others. None of the rats experienced diarrhea during the feeding period. Interleukin-1alpha led to a reduction in plasma zinc concentration, enhancement in intestinal metallothionein-1 mRNA levels, and expression of the intestinal iNOS gene in all groups. However, the abundance of iNOS mRNA was significantly higher in ZD rats than in the other groups. The presence of iNOS protein was demonstrated by immunohistochemical staining in the intestine of ZD rats that had been treated with interleukin-1alpha 12 h earlier. In addition, diarrhea occurred in most of the ZD rats and some of the PF rats but not in AL rats after interleukin-1alpha treatment. We conclude that ZD rats respond to interleukin-1alpha challenge more severely than controls, reflected by a more marked and prolonged iNOS expression and a greater incidence of diarrhea.

Beneficial effects of growth hormone combined with parenteral nutrition in the management of inflammatory bowel disease: an experimental study.

BACKGROUND: Growth hormone (GH) improves net protein anabolism and stimulates wound healing. Although GH is also known to exert the trophic effect on the intestinal tract, its role in the healing of intestinal ulceration is not known. The aim of this study was to evaluate the effects of exogenous GH coinfused with parenteral nutrition (PN) in an experimental model of inflammatory bowel disease in rats. METHODS: All rats underwent central venous cannulation and were randomized to two groups after induction of small intestinal ulceration with indomethacin. Both groups received the same PN formula. In addition, the GH group (n = 10) received subcutaneous injections of human GH at a dose of 1.0 IU/kg daily for 4 days, whereas the control group (n = 10) received injections of normal saline solution. Nitrogen balance, macroscopic inflammation score, intestinal myeloperoxidase activity, DNA content, and mucosal permeability were determined for each rat. Insulin-like growth factor-I (IGF-I) mRNA was detected by reverse transcription and polymerase chain reaction. RESULTS: Administration of GH significantly improved the cumulative nitrogen balance, ameliorated the gross inflammation score, and decreased intestinal myeloperoxidase activity. Similarly, intestinal permeability was significantly decreased in the GH group as compared with the control group. GH treatment resulted in increased plasma concentration of IGF-I and IGF-I mRNA expressions in both the liver and the small intestine compared with those in the control group. CONCLUSIONS: Exogenous GH plays an important role in accelerating intestinal healing in an experimental model of small bowel ulceration in rats. The mechanisms may include the stimulated IGF-I production, which thereafter augments intestinal epithelial cell growth.

Adhesive mucous gel layer and mucus release as intestinal barrier in rats.

BACKGROUND: Although it has been reported that total parenteral nutrition induces an increased intestinal permeability and a decreased mucous gel layer covering the intestinal epithelium, the role of mucous gel on intestinal permeability has not been well understood. We examined the in vivo effects of N-acetyl cysteine (NAC) as mucolytic agent and colchicine as suppressant of the mucus production on the intestinal transmission of fluorescein isothiocyanate dextran 70,000 (FITC-dextran). METHODS: Rats were divided into four groups. In each group, FITC-dextran (750 mg/kg) with or without NAC (3000 mg/kg) was injected into the small intestinal lumen 3 hours after intraperitoneal injection of saline or colchicine (Col, 10 mg/kg). Thirty minutes after injection of FITC-dextran, blood samples were taken from portal vein to analyze plasma fluorescein concentration by fluorescence spectrometry. Samples of small intestine were sectioned in a cryostat for fluorescence microscopy, and the identical sections were stained by periodic acid-Schiff reaction. RESULTS: Plasma FITC-dextran level in NAC group was higher than that in control group (p < .01), that in Col + NAC group was higher than that in Col group (p < .01) and that in Col + NAC group was higher than that in NAC group (p < .05). The spaces between villi were filled with mucous gel in the control and Col groups, whereas those were not entirely filled with mucous gel in NAC and Col + NAC groups. FITC-dextran and mucous gel showed complementary distribution in all rats. The villous interstitial edema was recognized in NAC group and the villi were disrupted in Col + NAC group. CONCLUSIONS: These results suggest that intestinal permeability is possibly affected not only by the mucous gel covering the intestinal epithelium but also by mucus release from goblet cells of the small intestine.

Alanyl-glutamine dipeptide-supplemented parenteral nutrition improves intestinal metabolism and prevents increased permeability in rats.

OBJECTIVE: The authors determined the effects of alanyl-glutamine-supplemented total parenteral nutrition (TPN) on mucosal metabolism, integrity, and permeability of the small intestine in rats. METHODS: Male Sprague-Dawley rats were randomized to receive TPN supplemented with a conventional amino acids mixture (STD group) or the same solution supplemented with alanyl-glutamine; both solutions were isocaloric and isonitrogenous. On the seventh day of TPN, D-xylose and fluorescein isothiocyanate (FITC)-dextran were administered orally. One hour later, superior mesenteric vein (SMV) D-xylose and plasma FITC-dextran concentration were measured. Intestinal blood flow and calculated intestinal substrates flux were measured with ultrasonic transit time flowmetery. RESULTS: Plasma FITC-dextran increased significantly in the STD group. Intestinal blood flow and SMV D-xylose concentration did not differ between the groups. Mucosa weight, villus height, mucosal wall thickness, mucosal protein, and DNA and RNA content in jejunal mucosa were significantly increased in the alanyl-glutamine group. Jejunal mucosal glutaminase activity and net intestinal uptake of glutamine (glutamine flux) were significantly higher in the alanyl-glutamine group as compared with the STD group. CONCLUSION: Addition of alanyl-glutamine dipeptide to the TPN solution improves intestinal glutamine metabolism and prevents mucosal atrophy and deterioration of permeability.