Green Tea Induced Cellular Proliferation and the Expression of Transforming Growth Factor-ß1 in the Jejunal Mucosa of Fasting Rats.

OBJECTIVE: The aim of this study was to understand whether or not the protective effect of green tea after fasting-induced damage in the jejunal mucosa of rat is dependent on cell proliferation and the stimulation of specific growth factors. MATERIALS AND METHODS: Sixty adult male Wistar rats were used in this study. The animals were divided randomly into 5 groups, with 12 in each group (G1-5). The animals in G1 (control group) were fed a rat chow diet and water ad libitum. The animals in G2 (fasting group) were fasted for 3 days. The animals in the G3, G4, and G5 groups were fasted for 3 days as G2, but were given water (G3), green tea (G4), or a vitamin E (G5) solution, respectively, for another 7 days. The animals were euthanized, and the jejunum was removed and processed for histological and immunohistochemical analysis. RESULTS: Compared to the G3 group, the jejunal mucosa of G4 rats showed a 70.6% higher level (p < 0.001) of expression of proliferating cell nuclear antigen and 98% higher level (p = 0.0001) of the expression of transforming growth factor-ß1 (TGF-ß1), whereas the level of fibroblast growth factor-1 (FGF-1) and insulin-like growth factor-1 (IGF-1) expression was 22 and 11% lower, respectively, in G4 animals as compared to G3 rats. These differences in the expression of FGF-1 and IGF-1 in G4 animals were not statistically significant. CONCLUSION: In this study, green tea repaired the fasting-induced damage in the jejunal mucosa of rats, mainly by inducing a significant expression of TGF-ß1 in the jejunal mucosa.

Effect of green tea on kidney tubules of diabetic rats.

It has been documented that green tea (GT) and its catechin components improve renal failure and inhibit the growth of mesangial cells. In the present study we examined the long-term effect of GT extract on streptozotocin (STZ)-induced diabetic nephropathy and on the glycogen accumulation in the kidney tubules. Male Sprague-Dawley rats were randomly assigned to normal control groups (2, 6, 8 and 12 weeks) and five diabetic groups (n 10) of comparable age. A GT diabetic group received 16 % concentration of GT for 12 weeks post-diabetes induction as their sole source of drinking water. GT treatment significantly (P < 0.01) reduced the serum glucose, glycosylated protein, serum creatinine and blood urea N levels by 29.6 (sem 3.7), 22.7 (sem 5.2), 38.9 (sem 10) and 41.7 (sem 1.9) %, respectively, compared with the diabetic group of comparable age. In addition, the GT-treated group showed a significant 44 (sem 10.8) % higher creatinine clearance (Ccr) compared with the untreated diabetic group. Likewise, GT reduced the urea N, creatinine, glucose and protein excretion rates by 30 (sem 7.6), 35.4 (sem 5.3), 34.0 (sem 5.3) and 46.0 (sem 13.0) % compared with the 12 weeks diabetic group. Administration of GT to 12 weeks diabetic rats significantly (P < 0.001) prevented (99.98 (sem 0.27) % less) the accumulation of glycogen in the kidney tubules. These results indicate that in STZ diabetes, kidney function appears to be improved with GT consumption which also prevents glycogen accumulation in the renal tubules, probably by lowering blood levels of glucose. Therefore, GT could be beneficial additional therapy in the management of diabetic nephropathy.

Pathobiological features of breast tumours in the State of Kuwait: a comprehensive analysis.

BACKGROUND: Breast cancer accounts for 30.3% of all cancer types in Kuwaiti women. Death occurs in approximately 43% of these patients. Our goal was to conduct a comprehensive analysis of the pathobiological characteristics of the tumours in an attempt to determine any particular trend that could be present. METHODS: One hundred and sixty-six cases were included in this study. All the pathology reports and paraffin blocks pertaining to these cases were collected. Four micrometer sections were taken from each block, and immunostaining against Her-2, ER, and PgR was performed. Both the proportion and intensity of immunostaining were scored according to the Allred's method, and typing of the tumour was done according the WHO criteria regarding tumour classification. Grading of invasive carcinomas was done according to the modified Bloom-Richardson-Elston's method, and tumour stage was determined according to the criteria set by the American Joint Committee on Cancer. RESULTS: The mean age of the patients below 55 years was 40, as compared to 68 for those above 55 (p < 0.0001). More than half of the cases were in the right breast, and were surgically treated by total mastectomy with axillary clearance. The majority of the tumours had irregular (stellate) margins, was invasive, and had a surrounding breast tissue of adenosis or fibrocystic type. Their mitotic index was 10-20 or >20 with a marked to moderate nuclear pleomorphism. They were mostly grade II or III, sized 2-5 or > 5 cm, had absent or scanty tumour lymphocytes, and were stage II or III. The in situ tumours were mainly ductal carcinoma (DCIS) of which comedo and cribriform were the major histological subtypes. The major histological subtypes of the invasive tumours were ductal-not otherwise specified, lobular, and tubular/cribriform. In this study, we also found a significant (p < 0.05) association between over expression of Her-2, lack of expression of ER and some of the characteristics mentioned above. CONCLUSION: Breast cancer in Kuwait seems to be more aggressive than what is currently seen in Europe, North America, Australia, and parts of Asia. Further investigations regarding the features observed in this study need to be performed.

Fine-needle aspiration cytologic features of four special types of breast cancers: mucinous, medullary, apocrine, and papillary.

Recognition of special types of breast cancers by fine-needle aspiration (FNA) cytology may have prognostic implications but some difficulties still exist in the ability of cytopathologists to determine the tumor subtypes. Detailed cytomorphological features were studied in the four special and unusual types of breast cancer cases (8 cases of mucinous, 9 medullary, 9 apocrime, and 11 papillary) and compared between themselves and with those of 32 duct cell carcinomas, not otherwise specified (NOS). Papillary carcinomas were also compared with 10 benign papillary lesions. The significance of the differences was determined using Fishers' Exact Test of Probability. In mucinous carcinoma, the frequency of signet ring cells (62.5%), and background pools of mucin (87.5%) were significantly higher than those of duct cell carcinoma (NOS), medullary carcinoma, apocrine carcinoma, and papillary carcinoma (P = 0.0408 to < 0.0001). In medullary carcinomas, lymphomononuclear cell infiltration (100.0%) was observed in significantly higher number of cases than in papillary, mucinous, and apocrine types (P < 0.0001). Further, moderate to marked nuclear pleomorphism (100.0%) and nuclear irregularity (77.8%) was significantly higher than those of mucinous carcinoma and papillary carcinoma (P = 0.0294 to <0.0003). Abnormal apocrine cells and papillary formation, characterizing all the apocrine carcinomas and papillary carcinomas, respectively, were present in significantly lower number in other variants and in duct cell carcinoma (NOS) (P = 0.0002 to <0.0001). Glycogen vacuoles (63.6%) were observed in a significantly higher number of papillary carcinoma as compared to duct cell carcinoma (NOS), apocrine, and medullary carcinomas (P = 0.0047 to 0.0022). The significant parameters differentiating papillary carcinoma and benign papillary lesions were loose cohesive clusters (P = 0.001) and acinar formation by neoplastic cells (P = 0.0237). Histopathology reports available in 36 cases, confirmed the cytodiagnosis of carcinoma in all 35 cases and the benign lesion in one case. Cytological subtyping was confirmed in 13 of 16 special types of carcinomas and all the 15 duct cell carcinoma (NOS). Thus, special and unusual variants of duct cell carcinomas like mucinous, medullary, apocrine, and papillary have specific cytomorphological features, which differentiate them from one another and from duct cell carcinoma (NOS). However, differentiating features between papillary carcinoma and benign papillary lesions were very few in this study.

Gastric Calcifying Fibrous Tumor Resembling Gastrointestinal Stromal Tumor: A Case Report.

Calcifying fibrous tumor (CFT) is a rare mesenchymal tumor, affecting children and young adults with a predilection for the soft tissue and the abdominal cavity. CFT of the tubular gastrointestinal tract is very rare with less than 20 cases of gastric CFTs reported in English literature. This benign hypocellular fibrosclerotic calcifying lesion can resemble other spindle cell tumors particularly sclerosing gastrointestinal stromal tumor of the stomach. Differentiating between these lesions is particularly important for prognostic and therapeutic purposes. Herein a case of gastric calcifying fibrous tumor incidentally detected during bariatric surgery in a 27-year-old woman is described, with a discussion on its clinicopathological features and differential diagnoses.

Cysticercosis: imported and autochthonous infections in Kuwait.

Intracerebral and non-central nervous system (non-CNS) cysticercosis caused by the larval pork tapeworm Taenia solium was diagnosed in patients in an Islamic state. The mode of transmission and challenges in diagnosis are highlighted. Sixteen patients with neurocysticercosis and six with non-CNS lesions were diagnosed by imaging studies (computerized tomography [CT]/magnetic resonance imaging [MRI]) and serology (ELISA and/or enzyme-linked immunoelectrotransfer blot assay [EITB]). Four of 55 family members, including servants, tested for antibodies were positive by the EITB and ELISA. Only one of these sera tested for antibodies to adult T. solium was positive: that of the cook, the probable source of the infection. We postulate a similar mode of transmission in the other Kuwaitis. Evaluation of several commercially available ELISA kits showed they were of poor specificity. Even in countries where pork consumption is proscribed by religious laws, physicians should include cysticercosis in their differential diagnosis in patients with neurological symptoms or non-CNS lesions, especially in non-endemic countries with a large expatriate population such as Kuwait. In children particularly, and in this region, suspected tuberculous lesions on CT must be investigated to rule out cysticerci by a more diligent use of the sensitive and specific EITB assay. Failure to understand the local epidemiology leads to empirical, inappropriate and prolonged therapy for chronic disease.

Effect of green tea in the prevention and reversal of fasting-induced intestinal mucosal damage.

OBJECTIVE: Epidemiologic studies have suggested that high consumption of green tea protects against the development of chronic active gastritis and decreases the risk of stomach cancer. The effect of green tea on the intestinal mucosa was not studied previously, so we examined the effects of green tea on the intestinal mucosa of fasting rats in a controlled experimental setting. METHODS: Two sets of experiments were performed. In the recovery set, rats were fasted for 3 d, after which they were allowed free access to water, black tea, green tea, or vitamin E for 7 d. On day 8, the animals were killed, and small bowels were removed for histologic examination. In the pretreatment set, rats were allowed a normal diet, but the water supply was replaced with green tea, black tea, or vitamin E for 14 d. They were subsequently fasted for 3 d. On day 4, the rats were killed, and small bowels were removed for histologic examination. RESULTS: In the recovery set, fasting for 3 d caused shortening of villi, atrophy, and fragmentation of mucosal villous architecture, with a significant (P < 0.0001) reduction in the length and surface area of the villi. Ingestion of green tea and, to a lesser extent, vitamin E for 7 d helped in the recovery of villi to normal. In the pretreatment set, drinking green tea, black tea, or vitamin E for 14 d before fasting protected intestinal mucosa from damage. CONCLUSION: The mucosal and villous atrophy induced by fasting was reverted to normal by the ingestion of green tea and, to a lesser extent, vitamin E. Black tea ingestion had no effect. In addition, ingestion of black tea, green tea, and vitamin E before fasting protected the intestinal mucosa against atrophy.

Serum anti-modified citrullinated vimentin antibody concentration is associated with liver fibrosis in patients with chronic hepatitis.

BACKGROUND AND AIMS: The hepatic stellate cell, which plays a pivotal role in hepatic fibrosis, contains the filament vimentin which is known to undergo protein citrullination and become immunogenic. The aims of this study were to find out if anti-modified citrullinated vimentin (anti-MCV) antibodies are produced in patients with chronic hepatitis and if such production is associated with liver fibrosis. METHODS: Sera and liver biopsy specimens were collected from 100 patients with chronic hepatitis. Sera were also collected from 100 healthy controls. The liver biopsies were graded according to the Metavir fibrosis scores. The serum concentrations of anti-MCV antibody were measured in both patients and controls by ELISA using commercially available kits. RESULTS: The mean serum concentration of anti-MCV antibody in patients with chronic hepatitis (54.90 ± 6.09 U/mL) was significantly higher (P = 0.001) than that of controls (17.38 ± 0.56 U/mL). Furthermore, serum anti-MCV antibody titer was able to separate patients with no fibrosis from those with moderate or severe fibrosis or cirrhosis. Using receiver operating characteristic curves, a serum concentration of anti-MCV antibody of 8.82 U/mL was able to diagnose cirrhosis with 60% specificity and 60% sensitivity. CONCLUSION: We concluded that serum anti-MCV antibody concentration may be a sensitive noninvasive marker for liver cirrhosis that needs to be investigated further.

Tubulolobular carcinoma of the breast with grooved and cerebriform nuclei: failure to identify this specific subtype in a case during routine fine needle aspiration cytology and histopathological diagnosis.

Tubulolobular carcinoma (TLC) is a rare tumor of the breast in which histologic features of both tubular and lobular carcinoma are combined. We report a case of TLC, in which the specific subtype was missed at routine cytologic and histopathological examination. A 69-year-old woman presented with a right breast lump. Imaging studies indicated a malignant lesion in right upper quadrant. Routine fine needle aspiration (FNA) cytology diagnosis was a duct cell carcinoma (small cell type). In a setting of cystic thyroid lesions, presence of excessive nuclear grooves, and rare intranuclear cytoplasmic inclusion, metastatic papillary thyroid carcinoma was also considered. However, both these possibilities were not supported by immunocytochemical findings (estrogen receptor+, thyroglobulin-, and chromogranin-). The histopathology diagnosis was invasive duct cell carcinoma. Review of FNA smears and paraffin sections led to the diagnosis of TLC, which was supported by positive immunohistochemical stainings for markers like e-cadherin and ß-catein.

Peptidyl arginine deiminase: A novel immunohistochemical marker for liver fibrosis in patients with chronic hepatitis.

Peptidylarginine deiminase (PAD) is an enzyme known to be involved in the pathogenesis of rheumatoid arthritis (RA). Since many of the molecular events present in the joints in RA also take place in the injured liver, we postulated in this study that PAD may be involved in liver fibrosis. The objectives of this study therefore were to find out if PAD could be demonstrated immunohistochemically in liver biopsies of patients with chronic hepatitis and if it is associated with METAVIR activity and fibrosis scores. Liver biopsies were obtained from 100 patients with chronic liver diseases between September 2006 and 2007. The biopsies were scored by two histopathologists according to the METAVIR activity and fibrosis scores after histological preparation. Immunohistochemistry for PAD was performed on the biopsies using a monoclonal antibody against PAD. PAD could not be demonstrated in normal liver biopsies but was found in the hepatocytes of patients with chronic hepatitis. PAD labeling could distinguish patients with no fibrosis from either F1 or F2 or F3 or F4 fibrosis. Similarly, PAD labeling could separate patients with no inflammatory activity from those with mild or moderate or severe activity. We concluded that PAD could be demonstrated immunohistochemically in liver biopsies of patients with chronic hepatitis and that its immunodetection was significantly associated with Metavir activity and fibrosis scores.

The predictive value of CD38 positive hepatic stellate cell count for assessing disease activity and fibrosis in patients with chronic hepatitis.

The activation of hepatic stellate cells (HSCs) is a critical event in hepatic fibrosis. The objectives of this study were to find out if cluster of differentiation 38 (CD38) can be demonstrated immunohistochemically on HSCs in liver biopsies from patients with chronic liver disease and if CD38 immunopositive HSC count is correlated with METAVIR inflammatory and fibrosis scores. Immunohistochemical labelling for CD38 was performed on 100 liver biopsies from patients with chronic liver disease. The CD38 immunopositive HSCs were identified and counted. The CD38 immunopositive HSC count was found to be associated with both the METAVIR score and the fibrosis scores. The CD38 immunopositive HSC count was able to discriminate between no fibrosis and stages 2, 3 or 4 fibrosis, but could not discriminate between no fibrosis and stage 1 fibrosis. Using receiver operating characteristic (ROC) curves, a cut-off point of 10 HSCs per 10 high power field (hpf), or 25 per 100 hepatocytes, is 80% sensitive and 70% specific for predicting fibrosis. The specificity rose to 100% in patients with hepatitis C viral (HCV) infection. We conclude that CD38 positive HSCs can be demonstrated immunohistochemically and that the count is highly predictive of moderate to severe hepatic fibrosis.

Severe emphysematous pyelonephritis in diabetic patients: diagnosis and aspects of surgical management.

PURPOSE: Emphysematous pyelonephritis (EPN) is a rare, severe gas-forming infection of renal parenchyma and surrounding tissues seen mostly in diabetic patients. Diagnosis and adequate therapeutic regimen are controversial. We reviewed the clinical presentation, diagnosis and aspects of surgical management of patients presenting with severe EPN. PATIENTS AND METHODS: Patients with EPN managed in our unit between 1996 and 2004 were reviewed. Diagnosis was confirmed by CT scan appearance of gas in the renal or perirenal area in a very ill patient. We compared the outcome of immediate nephrectomy with drainage of perinephric abscesses in patients presenting with severe EPN. RESULTS: Seven patients were managed in our unit during the 8-year period. All patients were diabetic and women outnumbered men (6:1). Renogram in all 7 patients showed renal function of affected kidney to be less than 15% in 6 patients. Escherichia coli was isolated in all patients from either urine, blood or perinephric pus. Management consisted of intensive resuscitation, control of blood glucose and use of intravenous antibiotics. Emergency nephrectomy was performed in 3 patients, delayed nephrectomy after an initial period of percutaneous drainage in 2 patients, incision and drainage in one patient and immediate percutaneous drainage was performed in one patient. One patient died 5 days post-nephrectomy of myocardial infarction. Patients who had immediate nephrectomy recovered quicker (18-21 days) and had no postoperative complications. Patients who had incision and drainage, or percutaneous drainage presented with recurrent discharging sinuses or perinephric abscesses requiring further surgical interventions and spent longer time in hospital (28-37 days). CONCLUSION: Patients with severe EPN often present in extremis and require intensive medical treatment. The diagnosis must be entertained in diabetic women presenting with flank pain and septicemia. The function of the affected kidney is often very poor and early nephrectomy offers the best outcome. Percutaneous drainage or incision and drainage of the abscess may be performed in patients too ill for immediate formal nephrectomy.

Transjugular liver biopsy in patients with end-stage renal disease.

PURPOSE: To assess the efficacy and safety of transjugular liver biopsy (TJLB) in patients with end-stage renal disease (ESRD) who are undergoing hemodialysis treatment. MATERIALS AND METHODS: Forty-six consecutive patients with liver disease who were undergoing hemodialysis were included in this study. An 18-gauge Tru-cut transjugular needle with a 20-mm throw was used to obtain liver tissue. All procedures were performed under fluoroscopic guidance. A single pathologist reviewed the biopsy specimens and assessed the size of fragments, number of portal tracts, and adequacy of the specimens for histologic diagnosis. All complications were recorded. The results were compared with the outcomes of percutaneous liver biopsy carried out at our institution in 32 patients with ESRD. RESULTS: TJLB and percutaneous biopsy techniques yielded adequate specimens for histologic diagnosis in all patients. The mean length of the largest fragments of tissue obtained via the transjugular and percutaneous routes were 16 mm +/- 4 and 14 mm +/- 3, respectively (P = NS). There were no major complications among patients who underwent TJLB. Percutaneous liver biopsy was complicated by hemorrhage in four of 32 patients (12%), three of whom required blood transfusion. CONCLUSION: TJLB is an effective and safe technique to obtain liver tissue in patients with ESRD and is associated with a lower complication rate than percutaneous liver biopsy.