miR 204-5p inhibits apoptosis in dacarbazine-treated melanoma cells

Melanoma is one of the most aggressive types of malignant tumors, commonly affecting young individuals. The treatment of metastatic tumors remains obscure due to the resistance of tumor cells to drugs mediated by various mechanisms. The acquisition of a resistant phenotype is associated with both genetic and epigenetic alterations in cancer cells. Therefore, the current study aimed to investigate whether microRNA (miR)-204-5p could promote alterations in the cell cycle and apoptosis of dacarbazine (DTIC)-treated melanoma cells. Quantitative real time PCR showed that transfection of DTIC-treated SK-MEL-2 melanoma cells with miR-204-5p mimics significantly upregulated miR-204-5p. However, flow cytometric analysis revealed that the proportion of cells in different phases of the cell cycle remained unchanged. Additionally, the proportion of early apoptotic cells was notably enhanced following cell treatment with DTIC, accompanied by a profound increase in Ki-67 negative cells, as verified by an immunofluorescence assay. Furthermore, miR-204-5p overexpression reduced the percentage of early apoptotic DTIC-treated melanoma cells. The proportion of Ki-67 negative cells was only increased by 3%. Overall, the results of the current study indicated that miR-204-5p overexpression could mostly attenuate cell apoptosis in DTIC-treated cells rather than promote their transition from the G0 phase of the cell cycle in response to chemotherapeutic agent-induced stress.     

Relationship between serum leptin and thyroid hormones in children

BACKGROUND: Because leptin decreases food intake and increases energy expenditure, the possible influence of thyroid status on the leptin system has been investigated mainly in adults and animals. However, the data available at present are very confusing. The aim of the present study was to assess the possible interaction of thyroid hormones with the leptin system. METHODS: Serum free thyroxine (FT4), a biologically active thyroid hormone, and thyroid stimulating hormone (TSH), a sensitive and reliable index of thyroid status, were examined in 51 children (19 males, 32 females) with mass screening-detected congenital hypothyroidism on continuous L-thyroxine (L-T4) substitution therapy. The subjects were divided into younger (n = 35, aged 1 month-5 years) and older (n = 16, 6 years-11 years) children groups. Serum levels of leptin and thyroid hormones were measured in the subjects. Body mass index (BMI) was estimated by the formula bodyweight (kg)/height x height (m2), which is known as the Kaup index in younger children and BMI in older children and adults. RESULTS: In the younger children group, serum leptin levels showed no correlation with serum TSH, FT4 or T4. In the older children group, serum leptin concentrations significantly correlated with T4 (r = 0.510, P < 0.05) and BMI (n = 16, r = 0.647, P < 0.01), but not with TSH or FT4. CONCLUSION: The role of thyroid hormones in modulating leptin synthesis and secretion seems to have little, if any, clinical or biological relevance.     

Serum lipoproteins and apolipoprotein E in infants with congenital hypothyroidism

BACKGROUND: Hypothyroid adults have a high risk of atherosclerosis, secondary to increased levels of various cholesterol fractions, particularly low-density lipoprotein cholesterol (LDL-C). We investigated the existence of a correlation between thyroid hormone deficiency and serum lipoproteins and a possible effect of different apolipoprotein E (apoE) phenotypes on lipoprotein levels in 75 infants with hypothyroidism. METHODS: Seventy-three of the 75 infants had congenital hypothyroidism. At the age of one month, prior to the initiation of thyroid hormone substitution therapy, thyroid-stimulating hormone (TSH), thyroid hormones and lipid profile parameters were determined. Subsequently, apoE phenotyping in all patients was performed by isoelectric focusing followed by immunoblotting. RESULTS: Significant negative correlations were identified between triiodothyronine (T3) and LDL-C and total cholesterol (TC) levels and between thyroxine (T4) and TC levels. There were no correlations between TSH and free (F)T4 and lipid profile parameters. Although infants carrying at least one E4 allele had higher LDL-C (as well as TC and triglyceride) levels than those carrying at least one E2 allele, these differences were not statistically significant. No significant differences in thyroid hormones were noted in E4 allele carriers in comparison with other patients. CONCLUSIONS: The observed lack of a significant correlation between thyroid hormones (except T3), apoE phenotypes and lipoprotein levels suggests that, early in infancy, other factors may play a more important role in determining lipoprotein levels.     

Atrial Pressure and Experimental Atrial Fibrillation

SIDERIS, D.A., et al .: Atrial Pressure and Experimental Atrial Fibrillation . A possible profibrillatory effect on the atria of an elevated atrial pressure and the site of atrial stimulation was examined. In 15 anesthetized dogs, right or left atrial or biatrial pacing was applied at a high rate (300–600/min) for 5 seconds at double threshold intensity under a wide range of atrial pressures achieved by venous or arterial transfusion or bleeding. Induction of atrial fibrillation in 236 of 1,971 pacing runs was associated with a significantly higher (P < 0.001) atrial pressure (21.6 ± 12.2 mmHg, mean ± SD) than maintenance of sinus rhythm (16.8 ± 11.1 mmHg in 1,735 of 1,971 pacing runs). Stimulation of the right atrium resulted in atrial fibrillation more frequently than left atrial or biatrial stimulation, with biatrial stimulation less frequent than right or left atrial stimulation. The induction of atrial fibrillation was related to the atrial pressure and to the site of stimulation but not to the pacing rate or the prepacing heart rate. The prepacing heart rate, associated with failure to induce sustained atrial fibrillation, was higher than that associated with atrial fibrillation in 12 of 15 experiments (significantly in 6) and not significantly lower in 3 of 15. Atrial fibrillation lasting 1 minute or more was more frequently associated with simultaneous stimulation of both atria than of either atrium alone. Thus, an elevated atrial pressure may facilitate the induction of atrial fibrillation. The site of stimulation also plays an important role for both the induction and maintenance of atrial fibrillation in this model.     

Antitumor effect of ascorbic acid, lysine, proline, arginine, and green tea extract on bladder cancer cell line T-24

AIMS: Bladder cancer, the fourth highest incident cancer in men and tenth in women, is associated with a high rate of recurrence, even when treated in situ, and prognosis is poor once the cancer metastasizes to distant sites. Based on anticancer properties, we investigated the effect of a mixture of lysine, proline, arginine, ascorbic acid, and green tea extract on human bladder cancer cells T-24 by measuring: proliferation, matrix metalloproteinase (MMP) expression, and cancer cell invasive potential. METHODS: Human bladder cancer cells T-24 (ATCC) were grown in McCoy medium supplemented with 10% fetal bovine serum, penicillin (100 U/mL) and streptomycin (100 mg/mL) in 24-well tissue culture plates. At near confluence, the cells were treated with the nutrient mixture dissolved in media and tested at 0, 10, 50, 100, 500, and 1000 microg/mL in triplicate at each dose. Cells were also treated with PMA 200 ng/mL to study enhanced MMP-9 activity. Cell proliferation was evaluated by MTT assay, MMP activity by gelatinase zymography, and invasion through Matrigel. RESULTS: Nutrient mixture inhibited the T-24 cell secretion of MMP-2 and -9, with virtual total inhibition of MMP-2 at 500 microg/mL and MMP-9 at 100 microg/mL. The nutrient mixture significantly reduced the invasion of human bladder cancer cells T-24 through Matrigel in a dose-dependent fashion, with 95% inhibition at 500 microg/mL and 100% at 1000 microg/mL nutrient mixture (P < 0.001). CONCLUSION: Our results suggest that our nutrient mixture is an excellent candidate for therapeutic use in the treatment of bladder cancer, by inhibiting critical steps in cancer development and spread, such as MMP secretion and invasion.     

Removal of Porcelain Veneers Aided by a Fluorescing Luting Cement

Purpose: Porcelain veneers are a safe and effective treatment modality for selected teeth that have poor esthetics. However, removal of porcelain veneers that have failed may be time‐consuming and involve considerable removal of sound tooth structure adjacent to the veneer. The aim of this study was to evaluate a novel method of porcelain laminate veneer removal by incorporating a fluorescent dye into the luting cement that allows the practitioner to visualize the cement on the tooth and remove the veneer without causing residual damage to the adjacent tooth substance. Materials and Methods: Porcelain veneers were luted on extracted teeth with a luting cement modified with a fluorescing agent. Faculty teaching staff and final year dental undergraduates were asked to remove the veneers with the aid of a curing light to render the luting cement visible by fluorescing. They were then asked to compare the removal of comparable veneers without this visual aid and to complete a standard questionnaire. The depth of cure of the conventional and modified cements was measured using a penetrometer. Results: Results of the questionnaire indicated that the operators found removing the veneer cemented with the modified (fluorescing) cement considerably easier than removing the veneer cemented with the conventional cement. Microscopy indicated that more damage was caused to the underlying tooth during removal of conventionally cemented veneers. The incorporation of the dye into the cement reduced the depth of cure from 4.238 mm (SD = 0.025) to 3.761 mm (SD = 0.096). CLINICAL SIGNIFICANCE The fluorescent cement was considered to be superior to conventional cements in its ease of visibility, and as a consequence, veneers cemented with the fluorescing cement are easier to remove. The fluorescing dye significantly reduced the depth of cure, but this may not be clinically significant, because of the small thickness of cement employed when luting adhesive restorations. The use of such fluorescing materials may not be restricted to a luting cement for veneers but may also be incorporated into bases and lining materials so they can be visualized on removal of tooth‐colored restorations, to prevent further tooth destruction.     

The structure of bronchial plugs in mucoid impaction, bronchocentric granulomatosis and asthma

The structure of bronchial plugs was examined in 12 lobectomy specimens from patients with bronchocentric granulomatosis and mucoid impaction, two bronchial biopsies from patients with mucoid impaction, sections from one postmortem showing evidence of mucoid impaction and bronchocentric granulomatosis as well as aspergilloma with tissue invasion and from post-mortems on eight patients who had died during a persisting exacerbation of their asthma. In both mucoid impaction and asthma eosinophils were arranged in layers within the mucus, but the pattern of lamination was different in the two groups. In asthma the layers of eosinophils appeared as whorls and eddies. In mucoid impaction the lamination was parallet to the circumference of the plug and the eosinophils were tightly compacted and appeared degenerate; fungal elements were found in all cases and were more readily seen among the eosinophils than in the mucus. The histological appearance of even small fragments of such plugs is diagnostic of allergic bronchopulmonary fungal disease with mucoid impaction. In all our cases bronchocentric granulomatosis appears to have been a complication of allergic bronchopulmonary aspergillosis with mucoid impaction. The clusters of inspissated eosinophils so typical of the peripheral lesion of bronchocentric granulomatosis appear to be fragments of the mucus plugs formed in the larger bronchi.     

Thyroxine inversely regulates serum intermediate density lipoprotein levels in children with congenital hypothyroidism

BACKGROUND: Although there have been numerous studies on the effects of thyroid hormones on serum lipid profiles, the effects of thyroxine on intermediate how density lipoprotein (IDL) remain uncertain. In an attempt to clarify, this issue, under conditions with very little influence exerted by sex hormones on serum lipid profiles, we studied the relationship between serum thyroid hormone levels and the proportion of serum IDL fractions in children. METHODS: Nineteen children with congenital hypothyroidism and 13 children with non-thyroid diseases were enrolled in this study. Blood samples were taken to measure serum thyroid stimulating hormone, triiodothyronine, free thyroxine (FT4), total cholesterol, high density lipoprotein (HDL) cholesterol, triglyceride and apolipoprotein levels. Lipoprotein fractions, including very low density lipoprotein (VLDL), IDL, low density lipoprotein (LDL) and HDL, were determined by their electrophoretic mobility in a non-denaturing polyacrylamide gel. RESULTS: The proportion of IDL fractions showed a significant inverse correlation with serum FT4 levels and a significant correlation with serum total cholesterol and apolipoprotein B and C-II levels. Serum VLDL, LDL and HDL fractions did not correlate with serum thyroid hormone levels. CONCLUSION: From these results and other studies, we suggest that thyroxine promotes the conversion of IDL into LDL, possibly by its stimulatory effects on hepatic lipase activity.     

Six‐ and Twelve‐Month Clinical Outcomes after Implantation of Prokinetic BMS in Patients with Acute Coronary Syndrome

Aims: To evaluate the Prokinetic bare metal stent implanted in patients presenting with acute coronary syndrome (ACS). Methods: We retrospectively studied ACS patients who underwent percutaneous coronary intervention (PCI) with a Prokinetic stent implantation. Excluded were patients presenting with cardiogenic shock, undergoing PCI to left main coronary artery (LM), or having implantation of additional stents other than Prokinetic. Six and 12 months clinical follow‐up was obtained by phone. Results: A total of 140 Prokinetic stents were implanted in 117 patients (age 64±13.0 years, 78% men). Thirty two percent of the patients had unstable angina, 36% had non ST‐elevation myocardial infarction (NSTEMI) and 33% had ST‐elevation myocardial infarction (STEMI). Forty two percent of lesions were categorized as B2 and 21% as C type. Procedural success was achieved in 99.1% of lesions. Clinical success was achieved in 97.4% of patients. Major adverse cardiac events (MACE) rate was 8.5% and 11.1% at 6 and 12 months follow‐up, respectively. The incidence of cardiac death, MI and TLR was 2.6%, 3.4% and 2.6%, respectively at 6 months, and 4.3%, 4.3%, 2.6% respectively at 12 months. Conclusions: Clinical outcomes at 6 and 12 months after Prokinetic stent implantation are excellent and may be attributable to its unique combination of composition, design and coating. (J Interven Cardiol 2010;23:377–381)