N-acetylcysteine expresses powerful anti-inflammatory and antioxidant activities resulting in complete improvement of acetic acid-induced colitis in rats.

High free radical production, low antioxidant capacity and excessive inflammation are well known features in the pathogenesis of inflammatory bowel disease. N-acetylcysteine (NAC) is a powerful antioxidant and a scavenger of hydroxyl radicals. Recently, NAC has also been shown to have anti-inflammatory activities in tissues. Our study objective was to investigate the effects of NAC on tissue inflammatory activities using an ulcerative colitis model induced by acetic acid (AA) in rats. Wistar rats (n = 32) were divided into four groups. AA-induced colitis was performed in two of the groups while the other two groups were injected with saline intrarectally. One of the AA-induced colitis groups and one of the control groups were administered NAC (500 mg/kg/day) intrarectally, and the other control groups were given saline. After 4 days, colonic changes were evaluated biochemically by measuring proinflammatory cytokines [tumor necrosis factor (TNF)-α, interleukin (IL)-1ß and IL-6], myeloperoxidase (MPO), malondialdehyde (MDA), glutathione (GSH) and superoxide dismutase (SOD) levels in tissue homogenates and by histopathological examination. AA caused colonic mucosal injury, whereas NAC administration suppressed these changes in the AA-induced colitis group (p < 0.001). AA-administration resulted in increased TNF-α, IL-1ß, IL-6, MPO and MDA levels, and decreased GSH and SOD levels, whereas NAC reversed these effects (all p < 0.001). In conclusion, the present study proposes that intrarectal NAC therapy has a dual action as an effective anti-inflammatory and an antioxidant, and may be a promising therapeutic option for ulcerative colitis.

Time course of collagen peak in bile duct-ligated rats.

BACKGROUND: One of the most useful experimental fibrogenesis models is the "bile duct-ligated rats". Our aim was to investigate the quantitative hepatic collagen content by two different methods during the different stages of hepatic fibrosis in bile duct-ligated rats on a weekly basis. We questioned whether the 1-wk or 4-wk bile duct-ligated model is suitable in animal fibrogenesis trials. METHODS: Of the 53 male Wistar rats, 8 (Group 0) were used as a healthy control group. Bile duct ligation (BDL) had been performed in the rest. Bile duct-ligated rates were sacrificed 7 days later in group 1 (10 rats), 14 days later in group 2 (9 rats), 21 days later in group 3(9 rats) and 28 days later in group 4 (9 rats). Eight rats underwent sham-operation (Sham). Hepatic collagen measurements as well as serum levels of liver enzymes and function tests were all analysed. RESULTS: The peak level of collagen was observed biochemically and histomorphometricly at the end of third week (P < 0.001 and P < 0.05). Suprisingly, collagen levels had decreased with the course of time such as at the end of fourth week (P < 0.01 and P < 0.05). CONCLUSION: We have shown that fibrosis in bile duct-ligated rats is transient, i.e. reverses spontaneously after 3 weeks. This contrasts any situation in patients where hepatic fibrosis is progressive and irreversible as countless studies performed by many investigators in the same animal model.

Melatonin expresses powerful anti-inflammatory and antioxidant activities resulting in complete improvement of acetic-acid-induced colitis in rats.

INTRODUCTION: Increased free-radical production, decreased antioxidant capacity, and excessive inflammation are well-known features in the pathogenesis of inflammatory bowel disease. Melatonin is a powerful antioxidant and a scavenger of hydroxyl radicals. Melatonin has also been shown to have anti-inflammatory activities in tissues. Our study objective is to investigate the effects of melatonin on tissue inflammatory activities using an ulcerative colitis (UC) model induced by acetic acid (AA) in rats. METHODS: Wistar rats (n = 32) were divided into four groups. AA-induced colitis was performed in two of the groups, while the other two groups were injected with saline intrarectally. One of the AA-induced colitis groups and one of the control groups were administered 100 mg/kg/day melatonin intraperitoneally, and the pair groups were given saline. After 4 days, colonic changes were evaluated biochemically by measuring proinflammatory cytokines [tumor necrosis factor (TNF)-α, interleukin (IL)-1ß, and IL-6], myeloperoxidase (MPO), malondialdehyde (MDA), glutathione (GSH), and superoxide dismutase (SOD) levels in tissue homogenates and by histopathological examination. RESULTS: AA caused colonic mucosal injury, whereas melatonin suppressed these changes in the AA-induced colitis group (P < 0.001). AA administration resulted in increased TNF-α, IL-1ß, IL-6, MPO, and MDA levels, and decreased GSH and SOD levels, whereas melatonin administration reversed these effects (all P < 0.001). CONCLUSIONS: The present study proposes that melatonin has a dual action as an effective anti-inflammatory and an antioxidant, and may be a hopeful therapeutic agent for UC.

Vitamin E has a dual effect of anti-inflammatory and antioxidant activities in acetic acid-induced ulcerative colitis in rats.

BACKGROUND: Increased free radical production, decreased antioxidant capacity and excessive inflammation are well-known features in the pathogenesis of inflammatory bowel disease. Vitamin E is a powerful antioxidant and a scavenger of hydroxyl radicals, and it has been shown to have anti-inflammatory activities in tissues. We investigated the effects of vitamin E on inflammatory activities using an acetic acid (AA)-induced ulcerative colitis model in rats. METHODS: Wistar rats were divided into 4 groups. Acetic acid was given to 2 groups of animals to induce colitis while the other 2 groups received saline intrarectally. One AA-induced colitis group and 1 control group received vitamin E (30 U/kg/d) intraperitoneally and the pair groups received saline. After 4 days, we evaluated colonic changes biochemically by measuring proinflammatory cytokine levels in tissue homogenates and by histopathologic examination. RESULTS: Acetic acid caused colonic mucosal injury, whereas vitamin E administration suppressed these changes in the AA-induced colitis group (p < 0.001). Administration of AA resulted in increased levels of tumour necrosis factor-α, interleukin-1ß, interleukin-6, myeloperoxidase and malondialdehyde, and decreased levels of glutathione and superoxide dismutase; vitamin E reversed these effects (all p < 0.001). CONCLUSION: Our study proposes that vitamin E is an effective anti-inflammatory and antioxidant and may be a promising therapeutic option for ulcerative colitis.

Melatonin ameliorates liver fibrosis induced by bile-duct ligation in rats.

BACKGROUND: Hepatic stellate cells, the main mediators in the pathogenesis of fibrosis, are triggered by free radicals and produce collagen. Melatonin is a powerful physiologic scavenger of hydroxyl radicals. It is also involved in the inhibitory regulation of the collagen content in tissue. There is no effective treatment available for liver fibrosis. Our objective was to evaluate the effects of melatonin on liver fibrosis induced by bile-duct ligation (BDL) in rats. METHODS: We divided male Wistar rats (n = 32) into 4 groups. Two groups received BDL and 2 groups received sham operations. One of the BDL groups and one of the sham groups were administered melatonin (100 mg/kg/day via intraperitoneal injection), and the controls were given vehicle only. After 1 month, we biochemically evaluated the changes in hepatic fibrosis by measuring tissue collagen levels and histopathologic examination. We evaluated the levels of malondialdehyde (MDA), glutathione (GSH), luminal and lucigenin in tissue homogenates, and we studied proinflammatory cytokines in serum using commercially available kits. RESULTS: Bile-duct ligation caused hepatic fibrotic changes, whereas melatonin suppressed these changes in 5 of 8 rats (p < 0.001). Bile-duct ligation resulted in increased collagen, MDA, luminal and lucigenin levels and decreased GSH levels, whereas melatonin reversed these effects. CONCLUSION: We found that melatonin functions as an effective fibrosuppressant and antioxidant, and the results suggest that it can be used as a therapeutic option.

Melatonin ameliorates methionine- and choline-deficient diet-induced nonalcoholic steatohepatitis in rats.

Nonalcoholic steatohepatitis (NASH) may progress to advanced fibrosis and cirrhosis. Mainly, oxidative stress and excessive hepatocyte apoptosis are implicated in the pathogenesis of progressive NASH. Melatonin is not only a powerful antioxidant but also an anti-inflammatory and anti-apoptotic agent. We aimed to evaluate the effects of melatonin on methionine- and choline-deficient diet (MCDD)-induced NASH in rats. Thirty-two male Wistar rats were divided into four groups. Two groups were fed with MCDD while the other two groups were fed a control diet, pair-fed. One of the MCDD groups and one of the control diet groups were administered melatonin 50 mg/kg/day intraperitoneally, and the controls were given a vehicle. After 1 month the liver tissue oxidative stress markers, proinflammatory cytokines and hepatocyte apoptosis were studied by commercially available kits. For grading and staging histological lesions, Brunt et al.'s system was used. Melatonin decreased oxidative stress, proinflammatory cytokines and hepatocyte apoptosis. The drug ameliorated the grade of NASH. The present study suggests that melatonin functions as a potent antioxidant, anti-inflammatory and antiapoptotic agent in NASH and may be a therapeutic option.

The effects of pegylated interferon alpha 2b on bile-duct ligation induced liver fibrosis in rats.

OBJECTIVE: To test the effects of peginterferon in an unrecoverable model of bile-duct ligation (BDL) induced liver fibrosis. MATERIAL AND METHODS: Thirty-seven Wistar rats were divided into five groups: group 1, BDL + peginterferon (n = 8); group 2, BDL (n = 8); group 3, sham + peginterferon (n = 7); group 4, sham (n = 7); and group 5, control group (n = 7). Peginterferon-alpha 2b (50 microgr/kg) or saline (1 mL/kg) was administered intraperitonealy every week for four weeks. Serum biochemical markers, liver tissue oxidative stress, collagen and transforming growth factor-beta (TGF-beta) levels were examined after four weeks. Liver slides were stained by hematoxylin and eosin and Masson trichrome\Gomory reticulum staining. RESULTS: The levels of tissue collagen, TGF-beta, biochemical markers (AST, ALT, bilirubins, alkaline phosphates, gamma-glutamyl transpeptidase) and oxidative stress markers (Malondialdehyde, luminal, lucigenin) of the BDL group were higher than the sham operated and control groups (all-p < 0.001). Peginterferon improved malondialdehyde, luminal and glutathione levels in the BDL + peginterferon group (p < 0.05). Histopathological examination of the BDL groups showed stage-3 fibrosis, while all the control groups were normal. Peginterferon showed no improvement in fibrosis either histologically, or biochemically. CONCLUSIONS: Peginterferon improved levels of malondialdehyde, glutathione and luminal in the rat model of BDL induced liver fibrosis. Peginterferon however,showed no anti-fibrotic effects in this model and therefore may not be a useful treatment for liver fibrosis.

Efficacy of tigecycline and vancomycin in experimental catheter-related Staphylococcus epidermidis infection: microbiological and electron microscopic analysis of biofilm.

Central venous catheters are frequently used. The commonest cause of catheter-related bloodstream infections (CRBSI) is coagulase-negative staphylococci (CoNS) associated with adherent biofilm. Tigecycline, a derivative of tetracycline, acts against strains producing biofilm. In this study, we aimed to determine the effect of tigecycline in a CRBSI model. A single dose of 10(8) colony-forming units (CFU)/mL of slime-producing Staphylococcus epidermidis was given through polyethylene catheters inserted into 24 rabbits. After 72 h, groups of eight rabbits were treated with heparin, vancomycin/heparin or tigecycline/heparin. Blood obtained from peripheral veins and the catheter lumen as well as catheter tips were cultured, and three catheters from each group were studied using electron microscopy. Surfaces were randomly subdivided and areas with ≥50 bacteria were compared. Blood cultures were positive from all heparin-treated rabbits but were negative from those receiving either antibiotic (P<0.001). Catheter tip cultures revealed growth from six, two and one rabbit(s) given heparin, vancomycin and tigecycline, respectively. Electron microscopy showed that catheters from heparin-treated rabbits were most heavily colonised (more areas with ≥50 CFU) compared with catheters from animals treated with vancomycin or tigecycline (P<0.003 and P<0.001, respectively). In conclusion, this study shows that tigecycline and vancomycin are both effective for treating CRBSI due to CoNS. Electron microscopy of catheters themselves suggests that tigecycline is superior to vancomycin (P<0.001). Tigecycline may be useful for the treatment of CRBSI.

Recurrent granulomatous mastitis mimicking inflammatory breast cancer.

Granulomatous mastitis (GM) is an uncommon benign breast lesion. Diagnosis is a matter of exclusion from other inflammatory, infectious and granulomatous aetiologies. Here, we presented an atypical GM case, which had clinical and radiologic features overlapping with inflammatory breast cancer (IBC). The disease had multiple recurrences. The patient is a 40-year-old Caucasian woman with a sudden onset of left breast swelling accompanied by diffuse skin redness, especially of the subareolar region and malodorous yellow nipple discharge from the left nipple. The disease progressed on antibiotic treatment and recurred after local resection. A similar lesion developed even after bilateral mastectomy. GM may show clinical/radiologic features suggestive of IBC. Multiple recurrences can be occasionally encountered. GM after recurrence could be much more alarming clinically. Pathology confirmation is the key for accurate diagnosis and a multidisciplinary approach is important to rule out IBC.

Association between bactericidal/permeability increasing protein (BPI) gene polymorphism (Lys216Glu) and inflammatory bowel disease.

BACKGROUND: Increasing evidence suggests that innate immune system may have a key role in the pathogenesis of the inflammatory bowel disease (IBD). Bactericidal/permeability increasing protein (BPI) has an important role in the recognition and neutralization of gram-negative bacteria by host innate immune system. The polymorphism on BPI gene called Lys216Glu is on the suspected list of IBD pathogenesis. METHODS: We studied the Lys216Glu polymorphism on BPI gene, in a Turkish IBD patient population. A total of 238 IBD patients; 116 Crohn's disease (CD) and 122 ulcerative colitis (UC), besides 197 healthy controls were included in this study. RESULTS: The Glu/Glu genotype and allele frequencies were found to be statistically higher compared to healthy control group not only in CD patients [P: 0.03, OR: 1.87 (CI 95% 1.02-3.42) and P: 0.00001 (OR: 2.07 CI 95% 1.47-2.91) respectively] but also in UC patients [P: 0.0002, OR: 2.71 (CI 95% 1.53-4.80) and P: 0.00002 (OR: 2.71 CI 95% 1.53-4.80) respectively]. CONCLUSIONS: BPI polymorphism (Lys216Glu) is associated both to CD and UC. Our findings differ from the two Western European studies; one without any association and the other indicating an association only with CD. Our study is the first one reporting a novel association between BPI gene mutation (Lys216Glu) and UC.

The role of occupational upper extremity use in breast cancer related upper extremity lymphedema.

BACKGROUND: Upper extremity (UE) use has been related to breast cancer-related lymph edema (BCRL). Our aim was to evaluate severity of BCRL in different occupation groups, according to upper extremity use. METHODS: Fifty-five women with BCRL were recruited. Group-1 (n = 21), with a mean age of 59, included patients who worked continuously <30 min at a time and 1 h and >8 h per day. RESULTS: The age, operation type, infection occurrence, radiotherapy status, and the operation on the side of the dominant hand were not statistically different between the groups. The stage and grade of the BCRL in group-3 were higher than the other groups (both p < 0.001). The restriction of shoulder movements on the operation side (p = 0.04) and shoulder physiotherapy need (p < 0.001) were the highest in group-3. Arm pain (p = 0.004) and pain medicine needs (p = 0.028) in group-1 were lower than the other groups. CONCLUSION: Group-3 had the worst BCRL clinical stage and grade status and other breast cancer treatment related morbities. Occupations that require greater use of the upper extremities. At present there is a need for closer monitoring of patients with more severe BCRL. Potential exacerbating and maintaining factors of functional limitations and pain need to considered so that clinical management addresses these in relation to daily use of the affected UE.

Effects of a long-acting somatostatin analogue, lanreotide, on bile duct ligation-induced liver fibrosis in rats.

BACKGROUND/AIMS: Somatostatin receptors have been shown on hepatic stellate cells, and somatostatin infusion has been shown to inhibit hepatic stellate cells activation. We aimed to test the effects of a long-acting somatostatin analogue, lanreotide, on bile duct ligation-induced liver fibrosis in rats. METHODS: Thirty-seven Wistar rats were divided into 5 groups as follows: Group 1, bile duct ligation+lanreotide; Group 2, bile duct ligation; Group 3, sham+lanreotide; Group 4, sham; and Group 5, control group. Lanreotide-autogel (20 mg/kg/month) or saline in intraperitoneal doses was administered. Serum biochemical parameters, liver collagen level, and oxidative stress and histological parameters were determined after 28 days. RESULTS: The tissue collagen level, biochemical parameters (AST, ALT, bilirubins, alkaline phosphatase, γ-glutamyl transpeptidase) and oxidative stress parameters (malondialdehyde, luminal, lucigenin) in the bile duct ligation groups were higher than in the sham-operated and control groups (p<0.001 for all). Lanreotide improved malondialdehyde and glutathione levels in the bile duct ligation+lanreotide group. In histopathological examination, bile duct ligation groups showed stage-3 liver fibrosis, while all the controls were normal. Lanreotide did not improve the liver fibrosis histologically or biochemically. CONCLUSIONS: A monthly active somatostatin analogue, lanreotide, improved malondialdehyde and glutathione; however, it was not able to improve bile duct ligation-induced liver fibrosis in rats. Although lanreotide is a long-acting medication, it did not show anti-fibrotic effects in the model.

Radioguided occult lesion localization (ROLL) for non-palpable breast cancer: a comparison between day-before and same-day protocols.

BACKGROUND: Although radioguided occult lesion localization (ROLL) has become a widely accepted technique, the optimal time interval between the radioisotope injection and surgery has not yet been determined. AIM: To delineate the effects of time from the injection of the radionuclide until surgery on the ROLL success rate in a patient population diagnosed as having non-palpable breast cancer. METHODS: Between December 2004 and May 2009, 75 patients underwent ROLL procedure. The day-before protocol and same-day protocols included 50 and 25 breast cancer patients respectively. RESULTS: The two study groups were comparable in terms of age, localization technique, radiological findings and the type of surgical procedures (P > 0.05). No statistically significant difference was noticed in the pathological diagnosis, cancer size and the surgical margin clearance between the two groups (P > 0.05). CONCLUSIONS: Same-day injection of the radiotracer was not superior to the day-before injection in ROLL. The day-before protocol can be scheduled for the convenience of both patients and hospital staff.

R72P polymorphism of TP53 in ulcerative colitis patients is associated with the incidence of colectomy, use of steroids and the presence of a positive family history.

P53 tumor suppressor protein is one of the pivotal regulators for genome integrity, cell cycle and apoptosis. The most commonly and extensively studied single nucleotide polymorphism (SNP) of p53 is Arg>Pro substitution on codon 72 (R72P). Although we know that the SNP has unique functional effects on the protein, its clinical significance is not clearly identified yet. Aim of the study was to access the relationship between R72P genotype distribution and clinical variables in patients with ulcerative colitis (UC) and colorectal cancer (CRC). Genomic DNA samples were extracted from 95 UC, 50 CRC, and 219 healthy controls. R72P genotype analysis was carried out with polymerase chain reaction following by restriction enzyme digestion. We observed that Pro allele carriage is a strong risk factor for CRC (OR = 3.03; 95%CI = 1.91-2.40; p = 0.003), but only modest association with UC (OR = 1.61; 95%CI = 0.98-2.65; p = 0.059) (Pro/Pro and Pro/Arg genotypes vs. Arg/Arg genotype). We did not find any correlation between genotype distribution of the polymorphism and clinical parameters of CRC, but in UC, Pro/Pro genotype was significantly related to an inflammatory bowel disease family history (OR = 8.0; 95%CI = 1.68-38.08, p = 0.015), and Arg/Pro genotype was significantly associated with the history of disease-related colectomy (OR = 17.77; 95%CI = 0.98-323.34, p = 0.012) and steroid use (OR = 10.14; 95%CI = 2.63-39.12, p = 0.0002). Our data suggest that R72P variant seems to be associated with high risk for development of CRC but carries low risk for development of UC. R72P genotypes might be a useful predictive marker for surgical and medical treatment of UC.

Axillary Web Syndrome after Sentinel Node Biopsy.

BACKGROUND: Axillary web syndrome (AWS) is a self-limiting cause of morbidity in the early postoperative period after axillary surgery, but it is encountered also after sentinel lymph node biopsy. The syndrome is characterized by cords of subcutaneous tissue extending from the axilla into the medial arm. CASE REPORT: Here, we report a patient presenting with AWS several weeks after sentinel lymph node biopsy. CONCLUSION: AWS has been reported to be resolved spontaneously in all patients 8-16 weeks after axillary surgery, and shoulder movements improve in this period. There is no definitive treatment modality for AWS. Patients should be reassured and informed that this condition will improve even without treatment.

Doxycycline-induced ulceration mimicking esophageal cancer.

INTRODUCTION: Doxycycline-induced esophageal ulcer patients are mostly young persons with no history of esophageal dysfunction. Heartburn, midsternal pain and dysphagia are the most common symptoms. It has generally a benign course. The present case is the first report of doxycycline-induced extensive ulcerations, mimicking esophageal cancer in two esophageal segments alongside, in the literature. CASE PRESENTATION: This report describes a 16-year-old Caucasian girl who, while taking doxycycline capsules100 mg twice a day for acne vulgaris for 3 months, developed these symptoms. An upper endoscopy revealed multiple circumferential deep ulcerations surrounding fragile, irregular, hyperemic and hypertrophic mucosa at the level of the mid-esophagus and concomitantly in the lower esophageal sphincter. The lesions were biopsied to exclude esophageal carcinoma because of the suspicious appearance in the endoscopic examination. The histopathological examination, haematoxylin and eosin stained sections showed ulceration with a mixed inflammatory infiltrate. Doxycycline was discontinued and she was given sucralfate 1 g qid and omeprazole 20 mg bid orally. All symptoms of the patient were resolved on the third day of the treatment. After 4 weeks of the therapy, an upper endoscopic control examination demonstrated normal findings. CONCLUSION: The present case has been an uncommon presentation of doxycycline-induced extensive ulcerations, mimicking esophageal cancer in two esophageal segments, concomitantly. Even the lesions were biopsied to exclude esophageal carcinoma. A modification on the behavior of taking drugs can prevent these unpleasant complications.

Mucinous tumor of uncertain malignant potential in a perforated appendectomy specimen. A case report.

Mucinous tumors of uncertain malignant potential are rare; there are only occasional reports. We report the first case where the tumor was identified incidentally following resection of a perforated appendicitis. There was no previous history to suggest for a mucinous tumor. No other abnormalities were found at surgery. Treatment included right hemicolectomy, considering the risk of residual or metastatic disease of about 10%. The patient is alive and well twelve months after resection of the tumor.

The effects of N-acetylcysteine on bile duct ligation-induced liver fibrosis in rats.

Stellate cells are activated by free radicals, and synthesize collagen. N-acetylcysteine (NAC) is a precursor of reduced glutathione and a potent scavenger of hydroxyl radicals and has potential antifibrotic effects. We aimed to test the effects of NAC on bile duct ligation (BDL) induced liver damage in rats. Forty-seven Wistar rats were divided into 5 groups: group 1, BDL+NAC (n=10); group 2, BDL (n=10); group 3, sham+NAC (n=10); group 4, sham (n=10); and group 5, control group (n=10). NAC (50 micromol/kg per day) or saline of single doses were administered intraperitoneally for 28 days. Serum biochemical and liver oxidative stress parameters were studied. Liver collagen level was determined by the method of Lopez de Leon and Rojkind. Liver slides were stained by hematoxylin and eosin and Masson trichrome\Gomory reticulum staining. Aspartate aminotransferase (AST) and alkaline phosphatase levels in the BDL+NAC group were lower than the BDL group and were higher than the control groups (all P< .001). Malondialdehyde, luminal, and glutathione levels in group 1 were lower than the BDL group (P= .01, P= .002, and P< .001) and higher than the control groups (all P< .001). NAC had no effect on alanine aminotransferase (ALT), gammaglutamyl transferase, bilirubin, albumin, or lucigenin levels. Liver collagen levels were higher in the BDL groups (P< .001); however, NAC had no effect on the collagen levels. The BDL groups showed stage 3 fibrosis; all the control groups were normal. NAC improved some biochemical parameters (AST, alkaline phosphatase) and oxidative stress parameters (malondialdehyde, luminol, glutathione) in the BDL model. NAC was found to be effective on cholestasis-induced hepatotoxicity. However, NAC was inefficient as an antifibrotic agent within a 1-month period of administration in the BDL model.