Lack of association between body mass index and plasma adiponectin levels in healthy adults.

OBJECTIVES: To test the hypothesis that obesity (increase in fat mass) independently affects the level of adipokines: adiponectin, tumor necrosis factor-α (TNFα) and interleukin (IL)-6. METHODS: Publications in the past decade reporting adult plasma adiponectin, leptin, TNFα and/or IL-6 levels were compiled. Mean gender-specific values were extracted from studies that included medical screening to confirm physical health (43 groups, total 4852 subjects). Correlation analysis was conducted between adipokine levels and body mass index (BMI), a widely used estimate of adiposity. RESULTS: For healthy lean to obese adults of both genders, no significant correlation between plasma adiponectin and BMI was detected. There was also no gender difference in plasma adiponectin level. In contrast, leptin levels showed a positive correlation with BMI in both genders, and women had significantly higher levels of plasma leptin consistent with a higher percentage of body fat. The proinflammatory cytokine TNFα failed to show correlation with BMI. Although IL-6 showed a positive correlation with BMI in women, the obesity-related increase was very limited. CONCLUSIONS: Data analysis based on studies performed on healthy adults did not support the hypothesis that obesity independently affects the plasma level of adiponectin and TNFα. Reported obesity-related changes in plasma adipokine levels may be a consequence of obesity-related metabolic disorders. Future studies are especially needed to understand the homeostasis of adiponectin.

Ileocolorectal intussusception due to caecal hamartoma.

Although 75% of intussusceptions occur within the first two years of life, they can also develop in teenage years. This is a case report of a 13-year old boy with an ileocolorectal intussusception from a large caecal hamartoma (10 x 6 x 2 cm3) adjacent to the ileocaecal valve. Partial resection of the ascending colon and terminal ileum was performed, and the pathology of the resected mass revealed a hamartoma. Ileocolorectal intussusception secondary to hamartoma represents a particularly rare event in the paediatric population. With early surgical intervention, this patient's outcome was uneventful.

Pulmonary carcinosarcoma in a 25-year-old male patient--a case report.

Pulmonary carcinosarcoma is a rare malignancy composed of epithelial and mesenchymal elements. In general, these neoplasms occur in older individuals at the age of 60 on average and are more commonly found in males who are heavy smokers. We report a 25-year-old male with a tumour shadow of the right middle lobe that was revealed by chest X-ray during a health checkup and was confirmed by subsequent computed tomography. The patient underwent thoracotomy with right middle lobe lobectomy. Histological examination of the resected specimen showed adenocarcinoma and undifferentiated sarcoma components. The clinical and histopathologic features of this rare tumour are discussed with a review of the literature.

Unusual right upper quadrant Stump Appendicitis.

Stump appendicitis is often not considered in patients with a surgical history of appendectomy. We report an unusual case of right upper quadrant stump appendicitis after previous operation for intussusception with incidental appendectomy. Abdominal computed tomographic scan is more efficient to make an early diagnosis of stump appendicitis to prevent further complications and prolonged hospitalization.

Ejaculatory duct obstruction after transurethral resection of the prostate.

Transurethral resection of the prostate is currently the most commonly employed surgical procedure for benign prostatic hyperplasia. Although several complications after the procedure have been well documented, ejaculatory duct obstruction is a rare complication. We describe this unusual complication in a 77-year-old male who presented with severe pain and a feeling of fullness in the lower abdomen and with dry ejaculate on three occasions after undergoing post-transurethral resection of the prostate. The patient's post-ejaculatory urinalysis demonstrated no sperm. Transrectal ultrasonography also showed no dilatation of the bilateral seminal vesicles or ejaculatory ducts. However, ejaculatory duct obstruction was finally diagnosed on vasovesiculography. The patient was successfully treated with transurethral resection of the ejaculatory duct and remained asymptomatic 6 months postoperatively. Although transrectal ultrasonography is currently widely used to evaluate ejaculatory duct obstruction, we suggest that vasovesiculography is still a feasible and useful tool that provides detailed anatomic information for the advanced confirmation of ejaculatory duct obstruction in patients with a high suspicion of ejaculatory duct obstruction who have normal transrectal ultrasonography findings.

Rising incidence of thyroid cancer in Singapore not solely due to micropapillary subtype.

Introduction The annual incidence of thyroid cancer is known to vary with geographic area, age and gender. The increasing incidence of thyroid cancer has been attributed to increase in detection of micropapillary subtype, among other factors. The aim of the study was to investigate time trends in the incidence of thyroid cancer in Singapore, an iodine-sufficient area. Materials and methods Data retrieved from the Singapore National Cancer Registry on all thyroid cancers that were diagnosed from 1974 to 2013 were reviewed. We studied the time trends of thyroid cancer based on gender, race, pathology and treatment modalities where available. Results The age-standardised incidence rate of thyroid cancer increased to 5.6/100,000 in 2013 from 2.5/100,000 in 1974. Thyroid cancer appeared to be more common in women, with a higher incidence in Chinese and Malays compared with Indians. Papillary carcinoma is the most common subtype. The percentage of papillary microcarcinoma has remained relatively stable at around 38% of all papillary cancers between 2007 and 2013. Although the incidence of thyroid cancer has increased since 1974, the mortality rate has remained stable. Conclusion This trend of increase in incidence of thyroid cancer in Singapore compares with other published series; however, the rise seen was not solely due to micropapillary type. Thyroid cancer was also more common in Chinese and Malays compared with Indians for reasons that needs to be studied further.

Metallothionein localization and cisplatin resistance in human hormone-independent prostatic tumor cell lines.

Metallothioneins (MT) are major cysteine-rich proteins with poorly characterized functions. We have examined the MT amount, isotype expression, and subcellular distribution in 4 human hormone-independent prostatic carcinoma cell lines. Both PC-3 and DU-145 cells were thiol-rich cells with similar MT and glutathione levels, while HPC36M and PC-3 MA2 were thiol-poor cells with lower MT and glutathione levels. All 4 prostatic cell lines expressed the MTIIA isoform at a basal level; DU-145 cells also constitutively expressed MTIE mRNA. Using antibodies for both total MT and MTIIA, we defined MT to cytoplasmic and nuclear domains in PC-3 cells, to perinuclear and nuclear domains in HPC36M cells, and to prominent nonnucleolar nuclear domains in DU-145 and PC-3 MA2 cells. These results indicate that the subcellular distribution is cell type specific and not reflective of the total MT content or MT isoform. Resistance to cadmium in all 4 cell lines was correlated with total MT levels, while resistance to the anticancer agent cisplatin correlated best with nuclear MT content. We suggest that the subcellular localization of MT is functionally important in cellular protection against the anticancer agent cisplatin in human prostatic cancer cells.

Transport of celiprolol across human intestinal epithelial (Caco-2) cells: mediation of secretion by multiple transporters including P-glycoprotein.

1. The transepithelial transport of the beta-adrenoceptor blocking drug, celiprolol, was investigated in monolayers of the well differentiated human intestinal epithelial cell line, Caco-2. 2. The basal-to-apical transport (secretion) of [14C]-celiprolol (50 microM) was 5 times higher than apical-to-basal transport (absorption). In the presence of an excess (5 mM) of unlabelled celiprolol the basal-to-apical transport was reduced by more than 80%, whereas the apical-to-basal transport remained unchanged. 3. Net celiprolol secretion obtained in the concentration range 0.01 to 5 mM displayed saturable kinetics with an apparent Km of 1.00 +/- 0.23 mM and Vmax of 113 +/- 11 pmol/10(6) cells min-1. These results are consistent with saturable active secretion and provide an explanation for the dose-dependent bioavailability of celiprolol. 4. The secretion of celiprolol was sensitive to pH, and decreased in the absence of sodium and in the presence of ouabain, suggesting that transport was coupled to proton and sodium gradients. 5. The secretion of celiprolol was inhibited by substrates for P-glycoprotein (vinblastine, verapamil and nifedipine) and either inhibited or stimulated by typical substrates for the renal organic cation-H+ exchanger (cimetidine, N1-methylnicotinamide, tetraethylammonium and choline), suggesting that there are at least two distinct transport systems. 6. The secretion of celiprolol was also inhibited by other beta-adrenoceptor blocking drugs (acebutolol, atenolol, metoprolol, pafenolol and propranolol) and by the diuretics, acetazolamide, chlorthalidone and hydrochlorothiazide, suggesting that the clinically observed effect of chlorthalidone on the bioavailability of celiprolol occurs at the level of the intestinal epithelium.

Antiproliferative potency of structurally distinct dietary flavonoids on human colon cancer cells.

Dietary flavonoids are known to be antiproliferative and may play an important role in cancer chemoprevention, especially cancers of the gastrointestinal tract, because of a direct contact with food. This study was designed to compare the antiproliferative potency of several structurally distinct dietary flavonoids in colon cancer cells, Caco-2 and HT-29, and in rat non-transformed intestinal crypt cells, IEC-6. Flavonoids varied significantly in their antiproliferative potency depending on the structural features but the observations were consistent among the three cell lines studied. Of the two most potent flavonoids, quercetin and genistein, the effect was found to be dose-dependent and chromatin condensation, an indication of apoptosis, was noticed. Quercetin was found to distribute throughout the cell with higher amounts in the perinuclear and nucleoli areas. The lack of specific cell membrane enrichment by quercetin was consistent with its lack of effect on the transepithelial resistance. While several flavonoids including quercetin were found to be unstable, the chemical instability did not correlate with the antiproliferative potency, although it may contribute to the antiproliferative effect.

Effect of antiproliferative flavonoids on ascorbic acid accumulation in human colon adenocarcinoma cells.

Dietary flavonoids were found to be antiproliferative for human colon cancer cells, Caco-2 and HT-29, and rat nontransformed intestinal crypt cells, IEC-6. The antiproliferative potency was found to be structure-dependent. We report here a correlation between the antiproliferative potency of these flavonoids and their ability to inhibit cellular accumulation of ascorbic acid (vitamin C). Caco-2, HT-29 and IEC-6 cells were found to accumulate ascorbic acid in a sodium-dependent fashion although some ascorbic acid may also enter the cells through sodium-independent mechanisms. Flavonoids that have been found to be antiproliferative, quercetin and genistein, inhibited the accumulation of ascorbic acid. The inhibition was dose-dependent and could be observed after as short as 10-min of incubation. The degree of inhibition of accumulation was more during rapid cell division as compared to post-confluency Caco-2 cells. Flavonoids that were found to show little antiproliferative effect, naringenin and catechin, also had little effect on ascorbic acid accumulation. The antiproliferative property of flavonoids could be linked to their ascorbic acid deprivation property.

Expression of antioxidant proteins in human intestinal Caco-2 cells treated with dietary flavonoids.

Dietary flavonoids are known to scavenge free radicals but little information is available on their roles in antioxidant protein gene expression. The goal of this paper is to investigate the effect of flavonoid treatment on the antioxidant protein expression in human intestinal Caco-2 cells. The antioxidant proteins of interest were metallothionein (MT), catalase (CAT), and superoxide dismutase (SOD). Treatment of Caco-2 cells with 100 microM genistein, biochanin A, daidzein or kaempferol significantly increased MT mRNA up to 15 fold. On the contrary, CAT mRNA level was not affected by various flavonoids. We also developed gel activity assays to determine the specific activities of CAT and Cu/Zn SOD in flavonoid-treated Caco-2 cells. Compared to the conventional spectrophotometric assays, the gel assays allow a separation of antioxidant activities of the enzymes from that of the flavonoids. CAT and Cu/Zn SOD were found not to be affected by 48-h treatment of 100 microM dietary flavonoids (genistein, biochanin A, daidzein, flavone, quercetin, or kaempferol). In conclusion, the effects of flavonoids on antioxidant protein expression are structure- and gene-specific. When evaluating antioxidant capacity of flavonoids, their ability to modulate antioxidant protein expression should also be taken into consideration.

Effect of PVA-AA on dentine bonding of HEMA.

PVA-AA, an esterification product of poly(vinyl alcohol) and acryloyl chloride, was synthesized and tested for its dentine bonding ability as an additive to 2-hydroxyethyl methacrylate (HEMA). The dentine bonding strength increased significantly by increasing the concentration of PVA-AA in HEMA. The dentine tensile bonding strength attained by the mixture of 10 wt% PVA-AA in HEMA is about 38% higher than that of HEMA or Gluma bonding agent. The dentine shear bonding strength also increased by increasing the acrylate content of the PVA-AA up to about 30%. Test results of cell culturing indicate that no toxic substance is released from PVA-AA to inhibit the cell growth.

Heterogeneity of anion exchangers mediating chloride transport in the proximal tubule.

Three distinct anion exchangers are described that directly or indirectly mediate Cl- transport across the luminal membrane of the proximal tubule cell. Studies on the intact proximal tubule indicate that the Cl(-)-formate exchanger is a major mechanism for Cl- transport under physiologic conditions. As just discussed, the physiologic importance of the Cl(-)-oxalate and SO4 = (oxalate)-CO3 = exchangers mediating Cl- transport across the luminal membrane of the proximal tubule cell is currently unknown. These three anion exchangers are part of a larger group of at least eight distinct anion transporters in the proximal tubule that share with erythrocyte Band 3 the properties of stilbene sensitivity and/or the ability to mediate anion exchange. It is tempting to speculate that these proximal tubule anion transporters are members of a family of proteins structurally related to the prototypic anion exchanger, erythrocyte Band 3. If this is true, comparing the structures of these anion transporters with each other and with Band 3 should provide important insight into the molecular basis for differences in substrate and inhibitor specificity within this family of transport proteins.

17beta-estradiol inhibition of ascorbic acid accumulation in human intestinal Caco-2 cells.

We investigated the effect of estrogen on the accumulation of ascorbic acid by human intestinal Caco-2 cells. 17beta-estradiol, synthetic estrogen diethylstilbestrol, and partial agonist tamoxifen were found to inhibit ascorbic acid accumulation in a dose-dependent fashion. The inhibitory effect of estrogens can be observed at as short as 5 min of incubation. An additive effect was observed when they were used in combination. Similar to dietary flavonoids, inhibition was also observed in two other intestinal cell lines, HT-29 and IEC-6. These chemicals affected both Na+ -dependent and Na+ -independent(K+ substituting Na+) accumulation of ascorbic acid and did not affect the efflux of accumulated ascorbic acid. Kinetic analysis of diethylstilbestrol showed a non-competitive inhibition with an apparent Ki of 23 microM. The hormone-ascorbic acid interaction in the intestinal cell could help to explain the known reduction in blood ascorbic acid level among oral contraceptive users and female guinea pigs given contraceptive hormones.

Transepithelial transport and accumulation of flavone in human intestinal Caco-2 cells.

Flavonoids are found in many food items of plant origin. Intake of flavonoids has been linked to the prevention of human diseases including cancer. However, little is known about the intestinal absorption of flavonoids in the cellular level. This study was designed to study the absorption of dietary flavonoids using cultured human intestinal epithelial cell monolayer as a model system and 14C-flavone as a model compound. 14C-flavone at 10 microM was found to move across the cell monolayer rapidly both from the luminal to basolateral direction and from the basolateral to luminal direction. The rate of transport from the luminal to basolateral direction was 5 times of the rate for phenylalanine, an aromatic amino acid. Flavone also accumulated substantially in the cells. Replacing sodium in the transport buffer with potassium did not affect the transport but reducing the incubation temperature significantly decreased the initial rate of transport. The presence of protein in the transport buffer reduced the initial rate of transport to half. Other flavonoids and hydrophobic chemicals at 100 microM had no effects on the transport. Together with the evidence from microscopic observation (Cancer Letts. 110: 41-48, 1996), this study supports that rapid diffusional transport may be the main route for flavonoid absorption. The ability of intestinal cells to accumulate flavone is consistent with the role of flavonoids in colon cancer prevention.

Changes in maternal taurine levels in response to pregnancy and lactation.

Taurine levels in various tissues and fluids of female rats were measured throughout pregnancy and lactation. The taurine concentration of liver markedly increased at days 19 and 21 of pregnancy to 188% of levels for nonpregnant, nonlactating control rats and then fell rapidly after delivery to reach only 30% of the control level by 3 days postpartum. Muscle and heart taurine concentrations were significantly negatively correlated with liver taurine levels. Brain taurine levels were low at days 14, 19 and 21 of pregnancy and day 14 of lactation. Urinary excretion of taurine decreased to 32% of control levels at day 21 of pregnancy and was negatively correlated with the hepatic taurine concentration over the course of pregnancy and lactation. The ratio of glycine- to taurine-conjugated bile acids was strongly negatively correlated with the hepatic taurine concentration. The milk taurine level was positively correlated with hepatic taurine concentration during lactation. The hepatic taurine pool appears to increase just before parturition and to rapidly decrease during the first few days of lactation when high levels of taurine are secreted in the milk. Our data suggests that the accumulation of taurine in the liver may be related to both a decreased renal clearance of taurine and a shifting of tauring from other tissues to the liver and that this enlarged pool of hepatic taurine may serve as a source of taurine for secretion in the early milk.

Dihydropyridine calcium channel blockers inhibit ascorbic acid accumulation in human intestinal Caco-2 cells.

We investigated the effect of commonly used medications on the accumulation of ascorbic acid in human intestinal Caco-2 cells. Although ascorbic acid is negatively charged at physiological pH, anionic compounds including drugs and metabolites had little effect on its accumulation. On the other hand, hydrophobic 1,4-dihydropyridine compounds (nifedipine and nicardipine), but not other structurally unrelated calcium channel blockers, were found to be potent inhibitors. They inhibited both Na+-dependent and Na+-independent (K+ substituting Na+) accumulation of ascorbic acid. The inhibition was non-competitive with a Ki of 108 microM and 9 microM for nifedipine and nicardipine, respectively. The efflux of ascorbic acid from cells was not affected. Previously, we reported a similar inhibition of ascorbic acid accumulation by estrogens. When nifedipine and estrogens were included in the buffer together, the combined inhibitory effect was less than additive implying that they may act through the same mechanism. The potential clinical significance of dihydropyridine usage on ascorbic acid status in human needs to be considered.