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.

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.

Preparation of nano-sized particles from collagen II by a high-voltage electrostatic field system.

The pilot study describes a novel method for preparing nano-sized particles from collagen II using a high-voltage electrostatic field system. Observations from transmission electron microscopy showed that, in one of the cases, the nano-sized collagen II particles exhibited good sphericity, and the particles were in the range of 23.3+/-1.7 nm in diameter at the experimental setting of 3 kV cm(-1), for a 3 h treatment period and at 25 degrees C (with a collagen concentration of 0.2 mg ml(-1)). When the treatment temperature increased to 30 degrees C, the collagen II began to lose the tendency to form individually separated spherically shaped nano-particles. Moreover, a fibrous structure of collagen II was formed instead of a nano-particle shape at the temperature of 37 degrees C. This result is probably contributed to by an entropy-driven process that is termed fibrillogenesis, a larger force causing the collagen molecules to self-assemble and then form collagen fibrils. It is interesting to note that this is practically the first attempt to produce nano-particles directly from collagen II solution under the treatment of a high-voltage electrostatic field, together with a set of working parameters for the collagen concentration and low-temperature setting.

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.

Quercetin cumulatively enhances copper induction of metallothionein in intestinal cells.

Wilson's disease, a genetic copper-overload condition, is currently treated with zinc because of the ability of zinc to induce metallothionein. We are interested in nonmetal chemicals that may alter intestinal copper metabolism and thus help to alleviate copper toxicity. Previously, we have shown that quercetin, a dietary flavonoid, can chelate copper. This study further examined the interaction of quercetin and copper in intestinal epithelial cells. We found that quercetin enhanced metallothoinein induction by copper and the effect was dose dependent. Quercetin also exerted a cumulative effect after repeated exposure. Repeated low-dose treatment (3-10 microM) of cells with quercetin can lead to the same effect on metallothoinein as one higher concentration treatment (100 microM). This property of quercetin is distinct from its chemical interaction with copper, but both can contribute to a reduction of copper toxicity. Among other flavonoids tested, two other copper chelators, catechin and rutin, did not increase copper induction of metallothionein, whereas genistein, an isoflavone that does not interact with copper chemically, increased copper induction of metallothionein. The effect of quercetin on copper metabolism is unique. Quercetin decreased zinc-stimulated metallothionein expression and had no effect on the cadmium induction of metallothionein. The clinical application of our observation needs to be explored.

Determination of 14 elements in Taiwanese bones.

The objective of this study was to measure the concentration of 14 elements in human bone and investigate the affecting factors. This study aims to establish a database of elements in Taiwanese bone. Seventy-seven bone samples were taken from 70 subjects who were undertaking various bone surgeries from a medical center in central Taiwan. Bone samples were pretreated using microwave digestion and then, after determining the optimal conditions for analysis, fourteen elements were analyzed using Inductively Coupled Plasma-Atomic Emission Spectroscopy (ICP-AES). Results showed that Ca had the highest concentration, followed by Mg and Zn. The lowest concentrations were of Mn, followed by Cd and Co. There was a positive correlation between the frequency of seafood intake and presence of all the 14 elements in human bone. There were several elements that had positive inter-correlation: As with Co; Al, Ag and Ca; Ni with Co, Mn and Al; Co with Al, Ag and Ca; Mn with Cr and Cu; Cr with Cu; Mg with Ca; Al with Ag and Ca; Ag with Ca; and also Zn with Mg. There were no significant differences found between concentrations of elements and etiology of bone disease and age. The authors suggest that further studies be conducted to establish a normal value of elements in human bone in Taiwan. This will greatly benefit the understanding of the relationship between disease pattern and elements in human bone.

Genistein increases metallothionein expression in human intestinal cells, Caco-2.

Flavonoids found in common vegetables, fruits, and legumes have been shown to possess antioxidant property. This study is the first to demonstrate that one member of the flavonoid family, genistein, can induce the expression of metallothionein (a metal-binding protein with antioxidant property). We found the effect of genistein to be time- and dose-dependent (10-100 microM). The effect can be observed at both protein and mRNA levels and was synergistic to that of 30 microM zinc. Genistein was shown previously to interact with the estrogen receptor and induce gene expression similar to estrogens at a lower affinity. We thus tested the hypothesis that the effect of genistein on metallothionein expression was mediated through the steroid hormone pathway. We found that various glucocorticoids do not affect metallothionein expression in Caco-2 cells. 17Beta-estradiol at 10-100 microM (concentrations much higher than needed to activate the estrogen response element) induced metallothionein expression in Caco-2 cells. However, a synthetic estrogen, diethylstilbestrol, did not increase metallothionein level at 10 microM. 17Beta-estradiol also did not act synergistically with zinc. Thus, genistein may enhance metallothionein expression through an uncharacterized mechanism. Further studies are needed to delineate the molecular mechanism and to determine whether the expression of other genes is also affected by genistein.

Amination of polycarbonate surface and its application for cell attachment.

The polycarbonate sheet was modified with ammonia gaseous plasma and characterized by the contact angle measurement and ESCA analysis. The contact angles decreased significantly from 77 degrees to about 20 degrees-40 degrees, indicate that the polycarbonate sheet become more hydrophilic after plasma treatment. The ESCA analysis results showed that the hydrophilicity was mainly derived from the amino groups on the modified surface. In this study, a flow-chamber system was also constructed to evaluate the 3T3 fibroblast cells attachment phenomena on these modified sheets. Before the experimental run, the parameters of inoculated cell number and cell passage were examined previously. The results revealed that these two parameters are independent in shear experiment. And besides, 3-hours plating time has the better adhering fraction. The experimental results showed that the 3T3 fibroblast cells adhesion strength increased significantly on the plasma modified sheet.

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.

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.

Dietary flavonoids interact with trace metals and affect metallothionein level in human intestinal cells.

Flavonoids are natural compounds found in food items of plant origin. The study examined systematically the interaction of structurally diverse dietary flavonoids with trace metal ions and the potential impact of dietary flavonoids on the function of intestinal cells. Spectrum analysis was first performed to determine flavonoid-metal interaction in the buffer. Among the flavonoids tested, genistein, biochanin-A, naringin, and naringenin did not interact with any metal ions tested. Members of the flavonol family, quercetin, rutin, kaempferol, flavanol, and catechin, were found to interact with Cu(II) and Fe(III). On prolonged exposure, quercetin also interacted with Mn(II). Quercetin at 1:1 ratio to Cu(II) completely blocked the Cu-dependent color formation from hematoxylin. When quercetin was added to the growth medium of cultured human intestinal cells, Caco-2, the level of metal binding antioxidant protein, metallothionein, decreased. The effect of quercetin on metallothionein was dose- and time-dependent. Genistein and biochanin A, on the contrary, increased the level of metallothionein. The interaction between dietary flavonoids and trace minerals and the effect of flavonoids on metallothionein level imply that flavonoids may affect metal homeostasis and cellular oxidative status in a structure-specific fashion.

The protein thiol metallothionein as an antioxidant and protectant against antineoplastic drugs.

Metallothioneins (MTs) are major zinc-binding protein thiols that are readily inducible and whose functions remain unclear. Recent evidence supports a role for MT as an antioxidant. Mechanisms underlying this function may include direct interception of free radicals, complexation of redox sensitive transition metals, altered zinc homeostasis or interaction with glutathione (GSH). MT overexpression after direct gene transfer in cultured cells, decreases cytotoxicity, to partially reduce reactive oxygen and nitrogen species and markedly attenuates intracellular oxidation of reporter molecules including dichlorofluorescein and cis-parinaric acid. Conversely, enhanced intracellular oxidation is seen in cells derived from mice lacking both functional MTI and MTII genes. GSH levels are unaffected in MT null cells relative to wildtype, suggesting the antioxidant function of MT is independent of GSH. In tumor cells there is at least a 400-fold range in MT levels and a 10-fold difference in the ratio of nuclear to cytoplasmic distribution. No correlation exists between MT levels and GSH levels demonstrating the autonomous regulation of intracellular thiol pools. This may be important for cancer chemotherapies since MT overexpression is seen in human tumor cells with acquired drug resistance. The authors found no evidence for altered MT isoform profiles in drug resistant cells that overexpress MT. Recent evidence suggests MT subcellular location may dictate functionality and MT may help determine the threshold for apoptosis. Thus, MT is a stress-inducible protein with antioxidant attributes that may participate independently or in conjunction with GSH to protect cells against injurious agents.