Effects of Antibiotics and <Emphasis Type="Italic">Saccharomyces boulardii</Emphasis> on Bacterial Translocation in Burn Injury

Purpose To investigate the effects of antibiotics and the probiotic, Saccharomyces boulardii, on indigenous microflora and bacterial translocation (BT) in burned rats.Methods Twenty-three male albino rats were divided into a sham burn group (group 1, n = 7) exposed to 21°C water, a burn + antibiotic group (group 2, n = 8), and a burn + antibiotic + S. boulardii group (group 3, n = 8) exposed to 95°C water for 10s, producing a full-thickness burn to 30% of the total body surface area. Ampicillin-sulbactam (1000mg/kg per day) was given as two doses via an orogastric feeding tube to groups 2 and 3. Saccharomyces boulardii (1mg/g body weight per day) was given as two doses via the same route to group 3. All rats were killed on the fifth day postburn and cultures of the mesenteric lymph nodes, liver, spleen, blood, and cecal contents were done.Results The incidences of BT were 0% (0/7) in group 1, 87.5% (7/8) in group 2, and 37.5% (3/8) in group 3. A significant increase in the BT incidence was found in group 2 (P 0.01), while a significant decrease was found in group 3 when compared with group 1. The total bacteria count of cecal flora was significantly lower in group 3 than in group 1 (P 0.01). The decrease in Gram-negative bacteria in the cecal flora was significant in group 3.Conclusion These results suggest that the incidence of BT in burn injury is enhanced by using an antibiotic, and that S. boulardii decreases the incidence of antibiotic-induced BT. Thus, we conclude that S. boulardii can effectively protect the intestinal ecologic equilibrium and prevent BT in burn injury victims.     

Organ Transplantation: From Myth to Reality

Short bowel syndrome comprises the sequel of nutrient, fluid, and weight loss that occurs subsequent to greatly reduced functional surface area of the small intestine. The aim of this study is to investigate the trophic and functional effects of bombesin on remaining gut in rats with experimentally induced short bowel syndrome. Thirty-two rats were allocated randomly and experimental short bowel syndrome was induced by 80% bowel resection in all rats. A regular enteral diet and isocaloric elemental enteral nutrition for 12 days were given in the control group and the elemental nutrition group, respectively. In the bombesin group 10 μg/kg subcutaneous bombesin (tid) for 10 days with regular enteral diet for 12 days was given. In the elemental nutrition and bombesin group the diet consisted of 10 μg/kg subcutaneous bombesin (tid) for 10 days with isocaloric elemental enteral nutrition for 12 days was given. All rats underwent physical, histological, and biochemical evaluation. Reduction in weight loss, bowel diameter, fecal fat content, and glycemia, increase in cellularity, and d-xylose absorption were observed in all treatment groups. These changes were more evident in the bombesin treatment groups. Increases in serum protein and albumin levels were seen with bombesin treatment with or without elemental diet, whereas reductions in villous height and crypt depth were observed only with bombesin treatment without elemental diet. Serum calcium, iron, and vitamin B₁₂levels were not affected with any treatment. It is concluded that bombesin may be a useful trophic agent contributing to increased absorptive capacity and improved biochemical values even in the absence of elemental nutrition.     

Influence of oral intake of Saccharomyces boulardii on Escherichia coli in enteric flora

Enteric flora constitutes 95% of the cells in the human body. It has been shown that the bacterial content of this flora is affected by diet and changes in nutrition. Considering that urinary tract infections (UTI) are mostly due to ascending infections from the gut flora, the importance of the elements of this flora and their characteristics becomes more evident. The aim of this study was to evaluate the influence of oral Saccharomyces boulardii (S. boulardii) intake on the number of Escherichia coli (E. coli) colonies in the colon. This study was carried out with 14 boys and 10 girls (total of 24 children) aged between 36 and 192 months (mean: 104.3±45.1 months). A commercial capsule or powder containing 5 billion colony-forming units (cfu) of S. boulardii was administered once a day for 5 days. The number of E. coli and yeast colonies was measured in the stool samples of the study group before and after the use of this drug. Before treatment, the mean number of E. coli colonies in g/ml stool was 384,625±445,744. This number decreased significantly to 6,283±20,283 after treatment (p=0.00). S. boulardii was not detected in stool before treatment and the number of colonies increased to 11,047±26,754 in g/ml stool. S. boulardii may be effective in reducing the number of E. coli colonies in stool. The influence of this finding on clinical practice such as prevention of UTI needs to be clarified by further studies.     

Effects of <Emphasis Type="Italic">N</Emphasis>-acetylcysteine on regeneration following partial hepatectomy in rats with nonalcoholic fatty liver disease

Purpose  To investigate the effect of N-acetylcysteine on regeneration following partial hepatectomy in rats with nonalcoholic fatty liver disease (NAFLD). Methods   N-Acetylcysteine was given to seven rats with NAFLD (group 1); physiological saline was given to seven rats with NAFLD (group 2); and physiological saline was given to seven rats with a normal liver (group 3). We performed two-thirds hepatectomy in all rats and removed the remnant liver tissue 48 h later to measure the mitotic index (MI), proliferating cell nuclear antigen, glutathione (GSH), and malondialdehyde (MDA) levels. Results  Mitotic index values were significantly higher in group 1 than in groups 2 and 3, and higher in group 3 than in group 2. Proliferating cell nuclear antigen values were significantly higher in group 1 than in group 2, but no significant difference was found in comparison with group 3. Glutathione values in group 1 were significantly higher than in group 2 and MDA values in group 1 were lower than in group 2. There was no significant difference between groups 1 and 3 in GSH and MDA values, in both the two-thirds hepatectomy and 48-h tissues. Conclusions   N-Acetylcysteine enhanced regeneration after partial hepatectomy in rats with NAFLD. We believe that it exerted this effect through its influence on oxidative stress.     

Bone metabolic disorders caused by small bowel resection,and the influence of 1α-hydroxyvitamin D3 on the rats

Metabolic bone disorders caused by resection of the distal three quarters of the small bowel and the effects of 1α-hydroxyvitamin D₃ (1α(OH)D₃) on the rats were investigated biochemically and histomorphologically. 1α(OH)D₃ was administered orally to the rats for 13 weeks. A group of “ sham operation” animals and the 75%-distal-small-bowel-resected control animals received only the vehicle. Bone changes developed 13 weeks after the partial bowel resection. The disorder was characterized by reductions in ash content of the femur and by the disappearance of the trabecular bone in tibial metaphysis. Decreased Ca absorption from the intestines was demonstrated by a radiotracer technique, and biochemical studies showed significant decreases in serum Ca and 1,25(OH)₂D concentrations in the bowel-resected rats. These findings suggest that 75% distal small bowel resection impairs intestinal absorption of calcium and results in a negative calcium balance, which may contribute to the development of bone metabolic disorder in rats. This disorder was demonstrated as high bone turnover via urinalysis and by a radiotracer technique. Administration of 1α(OH)D₃ increased dose-dependent Ca absorption from the intestine and the serum Ca, normalized the bone turnover rate and prevented the development of bone metabolic disorder.     

Bombesin in short bowel syndrome.

Short bowel syndrome comprises the sequel of nutrient, fluid, and weight loss that occurs subsequent to greatly reduced functional surface area of the small intestine. The aim of this study is to investigate the trophic and functional effects of bombesin on remaining gut in rats with experimentally induced short bowel syndrome. Thirty-two rats were allocated randomly and experimental short bowel syndrome was induced by 80% bowel resection in all rats. A regular enteral diet and isocaloric elemental enteral nutrition for 12 days were given in the control group and the elemental nutrition group, respectively. In the bombesin group 10 microg/kg subcutaneous bombesin (t.i.d.) for 10 days with regular enteral diet for 12 days was given. In the elemental nutrition and bombesin group the diet consisted of 10 microg/kg subcutaneous bombesin (t.i.d.) for 10 days with isocaloric elemental enteral nutrition for 12 days was given. All rats underwent physical, histological, and biochemical evaluation. Reduction in weight loss, bowel diameter, fecal fat content, and glycemia, increase in cellularity, and d-xylose absorption were observed in all treatment groups. These changes were more evident in the bombesin treatment groups. Increases in serum protein and albumin levels were seen with bombesin treatment with or without elemental diet, whereas reductions in villous height and crypt depth were observed only with bombesin treatment without elemental diet. Serum calcium, iron, and vitamin B(12) levels were not affected with any treatment. It is concluded that bombesin may be a useful trophic agent contributing to increased absorptive capacity and improved biochemical values even in the absence of elemental nutrition.     

Novel xylan-controlled delivery of therapeutic proteins to inflamed colon by the human anaerobic commensal bacterium

Introduction

Growth factors such as keratinocyte growth factor-2 (KGF-2) and transforming growth factor-beta (TGF-β) are important immunoregulatory and epithelial growth factors. They are also potential therapeutic proteins for inflammatory bowel disease. However, owing to protein instability in the upper gastrointestinal tract, it is difficult to achieve therapeutic levels of these proteins in the injured colon when given orally. Furthermore, the short half-life necessitates repeated dosage with large amounts of the growth factor, which may have dangerous side effects, hence the importance of temporal and spatial control of growth factor delivery.

Methods

The human commensal gut bacterium, Bacteroides ovatus, was genetically engineered to produce human KGF-2 or TGF-β ₁ (BO-KGF or BO-TGF) in a regulated manner in response to the dietary polysaccharide, xylan. The successful application of BO-KGF or BO-TGF in the prevention of dextran sodium sulphate induced murine colitis is presented here.

Results

This novel drug delivery system had a significant prophylactic effect, limiting the development of intestinal inflammation both clinically and histopathologically. The ability to regulate heterologous protein production by B ovatus using xylan is both unique and an important safety feature of this drug delivery system.

Conclusions

The use of genetically engineered B ovatus for the controlled and localised delivery of epithelial growth promoting and immunomodulatory proteins has potential clinical applications for the treatment of various diseases targeting the colon.     

Early effects of laparotomy and laparoscopy on bacterial behavior and proinflammatory cytokines on bacterial peritonitis in rats I: Escherichia coli

Purpose

The aim of this study was to investigate in rats with peritonitis the effect of CO₂ insufflation on behavior of bacteria, including antibiotic resistance, and the systemic and regional host response.

Methods

Inbred weaned Wistar albino rats were used. Escherichia coli ATCC 25922 was used to induce peritonitis. Rats with peritonitis were allocated to 4 groups: group 1, control; group 2, laparotomy; group 3, laparoscopy; group 4, laparoscopy + laparotomy and were killed at the end of the second hour of peritonitis. Serum, peritoneal fluid, and intraabdominal organs were taken for microbiological (biochemical markers—urease, citrate, indole; virulence factors—biofilm, protease, gelatinase, adherence), systemic immunologic (interleukin 1 [IL-1]α, IL-1β, tumor necrosis factor α, IL-6), and regional histopathologic evaluations. Isolated strains were tested against minimum inhibitory concentrations (MICs) and sub-MICs of amikacin and amoxicillin.

Results

Regional inflammatory response was the highest in group 2 but the lowest in group 4. Systemic IL-1α level was significantly higher in group 2, and TNF-α level was higher in group 3. After the peritonitis process, Escherichia coli began to use citrate and urea in control groups (without antibiotic treatment). In groups 2 and 4, amoxicillin resistance developed.

Conclusions

In peritonitis, in all experimental groups, Escherichia coli used different metabolic pathways other than in normal atmospheric conditions. Amoxicillin resistance developed in open surgery groups. Further kinetic microbiological and immune response studies are needed concerning the early and late effects of CO₂ insufflation on various strains of bacteria and mixed infections.     

IL-12 inhibits TNF-α induced osteoclastogenesis via a T cell-independent mechanism in vivo

It has been reported that TNF-α plays an important role in bone resorption in pathological conditions. IL-12, which is a T cell mediator, is also an important inflammatory cytokine. We previously reported that IL-12 induces apoptosis in bone marrow cells treated with TNF-α in vitro via an interaction between TNF-α-induced Fas and IL-12-induced Fas ligand (FasL), and that, as a result, osteoclastogenesis is inhibited. The purpose of this study was to investigate the effects of IL-12 on TNF-α-mediated osteoclastogenesis in vivo. We administered TNF-α with and without IL-12 into the supracalvaria in mice. The numbers of osteoclasts in the sutures in the calvaria were higher in mice administered TNF-α than in control mice not administered TNF-α. The numbers of osteoclasts in mice administered both TNF-α and IL-12 were lower than those in mice administered only TNF-α. Next, we determined the levels of mRNAs for cathepsin K and tartrate-resistant acid phosphatase (TRAP). mRNA levels were increased in mice administered TNF-α compared with control mice, but not in mice administered both TNF-α and IL-12. We also evaluated the amounts of tartrate-resistant acid phosphatase 5b (TRACP 5b) in mouse sera. The levels of TRACP 5b in mice administered TNF-α were higher than those in control mice. On the other hand, in mice administered both TNF-α and IL-12, the levels were lower than those in mice administered TNF-α alone. Fas and FasL expression levels were analyzed by real-time RT-PCR. The levels of Fas mRNA were increased in the calvaria of mice administered TNF-α compared with control mice, while those of FasL mRNAs were increased in the calvaria of mice administered IL-12. In TdT-mediated dUTP-biotin nick end-labeling (TUNEL) assays, many apoptotic cells were found in the sutures in the calvaria of mice administered both TNF-α and IL-12. IL-12 also inhibited TNF-α-induced osteoclastogenesis in mice whose T cells were blocked by anti-CD4 and anti-CD8 antibodies. These results suggest that IL-12 inhibits TNF-α-mediated osteoclastogenesis and induces apoptotic changes through an interaction between TNF-α-induced Fas and IL-12-induced FasL, in vivo, via a T cell-independent mechanism.     

Probiotics prophylaxis in children with persistent primary vesicoureteral reflux

Probiotics, beneficial living microorganisms, have been proven to be effective in preventing gastrointestinal infections, but their effect in preventing urinary tract infection (UTI) is inconclusive. A prospective randomized controlled study was done to compare the preventive effect of probiotics with conventional antibiotics in children with persistent primary vesicoureteral reflux (VUR). One hundred twenty children who had had persistent primary VUR after antibiotic prophylaxis for 1 year were randomly allocated into a probiotics (Lactobacillus acidophilus 10⁸ CFU/g 1 g b.i.d., n = 60) or an antibiotics (trimethoprim/sulfamethoxazole 2/10 mg/kg h.s., n = 60) prophylaxis group during the second year of follow-up. The incidence of recurrent UTI was 18.3% (11/60) in the probiotics group, which was not different from 21.6%(13/60) in the antibiotic group (P = 0.926). The causative organisms of recurrent UTI were not significantly different between the two groups (P = 0.938). Even after stratification by VUR grade, age, gender, phimosis, voiding dysfunction and renal scar, the incidence of recurrent UTI did not differ significantly between the two groups (P > 0.05). The development of new renal scar was not significantly different between the two groups (P > 0.05). In conclusion, probiotics prophylaxis was as effective as antibiotic prophylaxis in children with persistent primary VUR.     

Elevated plasma thymosin-α1 levels in lung cancer patients

Objective: Prothymosin-α, the precursor of thymosin-α1, may play a role in cell proliferation, and the plasma level of thymosin-α1 may reflect the degree of proliferation of the tumor cells. Methods: Recently, a new sandwich immunoradiometric assay for thymosin-α1 was developed using monoclonal and polyclonal antibodies. In this investigation, we used this assay to measure plasma and tissue level of thymosin-α1 in 131 lung cancer patients. Results: We found that the mean plasma thymosin-α1 levels in lung cancer patients were higher than in normal individuals (P<0.001). However, half of the patients showed normal levels. Thymosin-α1 levels correlated neither with the stage nor pathological subtype of the lung cancer, and did not decrease significantly in the 4 weeks after the resection of the tumor. Thymosin-α1 levels of lung cancer patients with another cancer were higher than those without evidence of other cancers (P=0.03). Survival of patients with normal levels of plasma thymosin-α1 was significantly better than that with higher levels (P=0.04). Conclusions: The plasma level of thymosin-α1 may be used as a marker for the prognosis of lung cancer patients. Further investigations are warranted to determine its role in the lung cancer.     

Effects of prostaglandin E2 and F2α on the skeleton of osteopenic ovariectomized rats

This article contains the histomorphometric evaluation of the effects of prostaglandin F_2α (PGF_2α on cancellous bone from the lumbar vertebra and cortical bone from the tibial shaft of ovariectomized, osteopenic rats. These effects were then compared with those of prostaglandin E₂ (PGE₂). Three-month-old rats were either ovariectomized (ovx) or shamovx. Then, either PGF_2α or PGE₂ in doses of 1 and 3 mg/kg/day was given subcutaneously for 21 days at 150 days post ovx. Histomorphometric analysis was performed separately on both the primary and secondary spongiosae of the fourth lumbar vertebral bodies (LVB) and on tibial shafts. The ovx rats exhibited osteopenia in both primary (−23% to −37%) and secondary (−20%) spongiosae of the LVB, but not in the tibial shafts at 150 and 171 days post ovx. In the LVB, PGE₂ in doses of 1 or 3 mg/kg/day for 21 days restored trabecular bone volume to the levels of sham-ovx controls in the primary spongiosa. However, in the secondary spongiosa, the treatments only thickened the trabeculae. The effects of the PGF_2α treatment were similar to those of the PGE₂ in both the primary and the secondary spongiosae. While both PGF_2α and PGE₂ treatments stimulated bone formation in the LVB as indicated by the increases in labeled perimeter, tissue and bone area-based bone formation rates, PGE₂ is about 10 times more potent than PGF_2α in these effects. The PGE₂ treatment also elevated activation frequency in the LVB, while the PGF_2α treatment did not. The treatments differed in that PGE₂ at these dose levels did not alter the eroded surface in the LVB while PGF_2α decreased it significantly. Thus, the increase of the ratio of labeled to eroded perimeter in the LVB in PGF_2α treated animals was much more than that in PGE₂-treated animals. In the tibial shafts, PGE₂ in doses of I and 3 mg/kg/day produced new marrow trabeculae in 2 of 6 and 3 of 6 of the ovx rats. However, no new trabecula was found in PGF_2α treated tibial shafts. Higher doses of PGE₂ also increased periosteal labeled perimeter, MAR, and BFR/BS, while PGF_2α did not produce any significant change in these parameters. Both PGE₂ and PGF_2α in doses of 1 and 3 mg/kg/day increased the labeled perimeter, MAR and BFR/BS and decreased the eroded perimeter in the endocortical surface. We concluded that both PGF_2α and PGEE₂ in doses of 1 and 3 mg/kg/day for 21 days exhibited anabolic bone effects. The effects were mostly confined to an increase in trabecular volume in the primary spongiosa of the LVB and in the endocortical surface of tibial shafts. The tissue level mechanism behind this appears to be that PGEE₂ and PGF_2α can both stimulate osteoblast recruitment and activity. Overall, we found PGE₂ to be more potent than PGF_2α at the same dose level at the endocortical surface. Furthermore, new marrow trabecular bone formed only after PGE₂ treatment. PGF_2α differed from PGE₂ by significantly reducing the trabecular eroded surface in ovx rats.     

Effect of endogenous hypergastrinemia on carcinogenesis in the rat esophagus

We surgically prepared a hypergastrinemia model in rats and studied the effects of hypergastrinemia on chemically induced carcinogenesis in the esophagus. Operations were performed on 5-week-old male Donryu rats as follows: (1) truncal vagotomy plus pyloroplasty (group V), (2) segmental gastrectomy plus pyloroplasty (group G), (3) antrectomy (group A), and (4) no operation (group C) as a control. From the age of 6 weeks, the animals were given 0.003% N-methyl-N-amylnitrosamine (MAN) solution as drinking water for 8 weeks. After 20 weeks of MAN administration, the animals were bled and killed. The average serum gastrin levels in groups V and G were significantly higher than those groups C or A. There were significant differences between C and V in the incidence of carcinoma, and between V and A in the incidence of carcinoma including severe dysplasia. The incidence of histologically identified lesions per animal was determined, and significant differences were observed between C and both V and G in the incidence of carcinoma including severe dysplasia. Furthermore, we also detected gastrin receptors in the esophageal lesions produced by the oral administration of MAN to rats. The results of the present study suggest that endogenous hypergastrinemia has a positive influence on chemically induced carcinogenesis in the rat esophagus.     

The immunosuppressive effects of a leukotriene B4 receptor antagonist on liver allotransplantation in rats

The immunosuppressive effects of a leukotriene B₄ (LTB₄) receptor antagonist, ONO4057, on liver allotransplantation in rats were evaluated, and the levels of prostaglandin E₂ (PGE₂) in the liver tissue during rejection of the allografts examined. The rats were divided into four groups: group 1: Lewis rats (LEW) given a sham operation with dimethyl sulfoxide (DMSO); group 2: LEW given syngenic orthotopic liver transplantation (OLT) from LEW, with DMSO; group 3: LEW given allogenic OLT from ACI rats (ACI), with DMSO; and group 4: LEW given allogenic OLT from ACI, with ONO4057 as 10, 30, or 100 mg/kg per day dissolved in DMSO to subgroups 4a, 4b, and 4c, respectively. Histological examinations were performed, survival times monitored, and liver tissue PGE₂ levels 3, 5, 7, and 14 days after transplantation measured. The mean graft survival times in groups 4a, b, and c, at 37.5±10.4, 52.2±24.4, and 34.0±4.9 days (mean±SEM), respectively, were significantly longer than that in group 3 (at 13.0±3.2 days). Moreover, the levels of tissue PGE₂ in the liver allografts in group 4a were significantly higher than those in group 3 on days 5 and 7. These results suggest that ONO4057 has an immunosuppressive effect on liver allotransplantation since it reduces the activities of LTB₄ which augments immune responses, and also because it indirectly increases the PGE₂ level.     

Influence of Rifampin on Capsule Formation Around Silicone Implants in a Rat Model

This study investigated the effect of rifampin on the thickness of capsules around silicone implants by bactericidal activity against Stapylococcus epidermidis. Silicone blocks (1 × 1 cm) were placed into pockets created for each of the 40 rats included in the study. In group 1, the operation was performed under aseptic conditions. In group 2, standard S. epidermidis was inoculated into the pocket, whereas rifampin and S. epidermidis were applied in group 3. In group 4, only rifampin was applied topically on implants. After 12 weeks, the peri-implant capsules were removed and examined under a photomicroscope and a scanning electron microscope. The mean thickness of the capsules was 63.307 μm in group 1, 111.538 μm in group 2, 43.076 μm in group 3, and 30.384 μm in group 4. The differences between groups 2 and 3 and groups 2 and 4 were found to be statistically significant (p < 0.001). Rifampin appears to be an agent for preventing peri-implant capsule formation.     

Penile rehabilitation with a vacuum erectile device in an animal model is related to an antihypoxic mechanism: blood gas evidence

Our previous study showed that vacuum erectile device (VED) therapy has improved erectile function in rats with bilateral cavernous nerve crush (BCNC) injuries. This study was designed to explore the mechanism of VED in penile rehabilitation by analyzing cavernous oxygen saturation (SO₂) and to examine the effect of VED therapy on preventing penile shrinkage after BCNC. Thirty adult Sprague–Dawley rats were randomly assigned into three groups: group 1, sham surgery; group 2, BCNC; and group 3, BCNC+VED. Penile length and diameter were measured on a weekly basis. After 4 weeks of therapy, the penile blood was extracted by three methods for blood gas analysis (BGA): method 1, cavernous blood was aspirated at the flaccid state; method 2, cavernous blood was aspirated at the traction state; and method 3, cavernous blood was aspirated immediately after applying VED. SO₂ values were tested by the blood gas analyzer. The results showed that VED therapy is effective in preventing penile shrinkage induced by BCNC (Penile shortening: BCNC group 1.9±1.1 mm; VED group 0.3±1.0 mm; P<0.01. Penile diameter reduction: BCNC group 0.28±0.14 mm; VED group 0.04±0.14 mm; P<0.01). The mean SO₂±s.d. values were increased by VED application (88.25%±4.94%) compared to the flaccid (76.53%±4.16%) or traction groups (78.93%±2.56%) (P<0.05). The calculated blood constructs in the corpus cavernosum right after VED application were 62% arterial and 38% venous blood. These findings suggest that VED therapy can effectively preserve penile size in rats with BCNC injury. The beneficial effect of VED therapy is related to antihypoxia by increasing cavernous blood SO₂.     

A comparative histopathologic evaluation of the effects of three different solutions used for whole bowel irrigation: an experimental study

PURPOSE: Although whole bowel irrigation (WBI) is a widely used method of bowel preparation in daily surgical practice, almost nothing is known about the histopathologic alterations caused by WBI and whether these differences have any detrimental effect on the outcome of gastrointestinal surgical procedures. Therefore, an experimental study has been conducted to evaluate and compare the effects of WBI with various solutions on the histology of gastrointestinal tract. METHODS: During the experimental procedures animals were divided into 4 groups consisting of 8 animals each as follows: group A, WBI performed by using isotonic saline solution; group B, WBI performed by using an isoosmolar solution containing polyethylene glycol (PEG); group C, WBI performed by using Lactated Ringer's solution; group D, Animals that were not irrigated but sham operations that were performed served as controls. Four hours after WBI the animals underwent laparotomy and a segment of transverse colon with intact vascular peduncle was prepared. After waiting for 30 minutes, specimens from duodenum, small intestine, large bowel, colonic segment, and liver were obtained from each animal. Histopathologically, all of the specimens were evaluated and graded by 3 parameters including congestion, edema, and inflammation. RESULTS: Although varying degrees of congestion, edema, and inflammation were encountered from all of the specimens of group A, B, and C, only slight congestion was noted in all specimens of group D. The difference between group D and other groups was statistically very significant (P < .001). When the sections from duodenums of groups were evaluated, the degree of congestion, edema, and inflammation were found to be moderate in group B, mild-moderate in group A, and mild in group C. Histopathologic examinations of specimens of the small, large bowel, and isolated colonic segment showed severe congestion, edema, and inflammation in group A, moderate-mild in group B, and mild in group C. The difference between A and B, A and C, and A and D was statistically significant (P < .01). Although severe congestion was encountered in liver specimens of group A, only mild congestion was encountered in groups B and C (P= .0001). The matched durations of irrigations and total volume of irrigation solutions were found to be not related with the difference in histopathologic findings. CONCLUSIONS: WBI has induced varying degrees of histopathologic alterations from mild to severe in the rat gastrointestinal tract. Lactated Ringer's solution and PEG solution have induced the least alterations. Therefore, WBI with Lactated Ringer's solution and PEG solution seem to be safe alternatives of mechanical bowel preparation before elective large bowel surgery. Because saline solution has caused detrimental alterations in distal gastrointestinal tract histology, WBI with saline solution seems to be unadvisable.     

<Emphasis Type="Italic">Candida albicans</Emphasis>-Infected Pancreatic Pseudocyst: Report of a Case

We report the case of a 48-year-old man with a pseudocyst infected by Candida albicans, and review the relevant literature. The patient was successfully treated by a Roux-en-Y cystojejunostomy of the pseudocyst and adjunctive therapy with amphotericin B. Candida species isolated from a pancreatic pseudocyst or abscess should be considered pathogenic, and treated aggressively.     

The nephrotoxicity of <Emphasis Type="Italic">Aristolochia manshuriensis</Emphasis> in rats is attributable to its aristolochic acids

Background. Although Aristolochia manshuriensis (AM), which was incriminated in the Japanese variety of Chinese herbs nephropathy, has been recently shown to be nephrotoxic in rats, less is known about whether this toxicity is attributable to its aristolochic acids (AA). We compared the renal effect of AM with that of Akebia quinata (AQ), which has similar components to AM but is free of AA; we also compared this effect of AM with that of pure AA, and studied its possible mechanism. Methods. In study 1, rats were divided into four groups. Each group was orally given either 0.4g of AM, 4g of AM, or 4g of AQ per day, or vehicle, for 5 days. In study 2, rats were given 4g of AM (which contained 4mg of AA), or 4mg of pure AA per day, or vehicle, for 5 days. Renal function, and renal histology were evaluated on day 5 in study 1 and on days 1, 3, 5, and 14 in study 2. In study 2, terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end-labeling (TUNEL) and proliferating cell nuclear antigen (PCNA) staining were also performed. In study 3, rats were treated in the same way as in study 2, but were all killed on day 5. Concentrations of AA (I + II) were measured in serum and urine in study 2, and in the kidney, lung, heart, liver, and spleen in study 3. Results. In study 1, only the rats that received 4g/day of AM developed tubular necrosis, azotemia, proteinuria, and glucosuria. In study 2, both AM- and AA-treated rats showed progressive tubular damage, decreased renal function, and increased urinary protein excretion. The degree of these alterations was comparable in the AM and AA groups. Moreover, the concentrations of AA (I + II), in serum, urine, and kidney were also comparable in the AM- and AA-treated rats. High levels of AA were detected in the lung and kidney. Apoptotic tubular cells increased on day 5 and had decreased by day 14 after the withdrawal of AM or AA. Meanwhile, proliferating tubular cells progressively increased from day 3 to day 14. Conclusions. Our study indicates that the renal toxicity of AM can be attributed to its AA component. Tubular cell apoptosis might be one of the mechanisms involved in this renal injury.Part of this study was presented at the 43rd Annual Meeting of the Japanese Society of Nephrology (May 2000, Nagoya, Japan) and at the ASN/ISN World Congress of Nephrology (October 2001, San Francisco, USA).     

Successful management of Brucella mellitensis endocarditis with combined medical and surgical approach

Objectives: Brucella endocarditis is an underdiagnosed complication of human brucellosis, associated with high morbidity and mortality. We report the successful management of a number of cases of Brucella mellitensis endocarditis. Patients and methods: Seven consecutive cases of Brucella mellitensis endocarditis were treated over the last 20 years, based on high suspicion of the disease at first place. The early suspicion of Brucella endocarditis relied on medical history and a standard tube agglutination titer ≥1:320. Blood and/or cardiac tissue cultures were positive in all patients, but available late following surgery. All patients were successfully treated with a combination of aggressive medical and early surgical therapy. All affected valves were replaced within 1 week from admission (five aortic and three mitrals). Medical treatment included co-trimoxazole, tetracyclines and streptomycin, before surgery, followed by co-trimoxazole and tetracyclines for a median of 12 months (range: 3–15 months) after surgery until the titers returned to a level ≤1:160. Results: There were neither operative deaths nor recurrence of infection. One patient died two years after the operation due to massive cerebrovascular accident. Ten-year survival was 85.7±13.2%. Conclusion: Although Brucella mellitensis endocarditis is a rare entity, its optimum management should be a combination of aggressive medical treatment and early surgical intervention, based on high degree of suspicion in areas with high incidence of the disease.