MATERIALS AND METHODS: In the present study, the anticancer effects and the mechanisms of action of 17βH-neriifolin (cardiac glycoside) were evaluated by terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL) assay and a proteomic approach in treated and non-treated SKOV-3 ovarian cancer cells.
RESULTS: 17βH-neriifolin was found to be active with IC50 values of 0.01 ± 0.001 in SKOV-3 ovarian cancer cell line, as evaluated by the sulforhodamine B (SRB) assay. RESULTS from TUNEL assay indicated that 17βH-neriifolin caused apoptosis in SKOV-3 cells in a dose-dependent manner. Based on differential analysis of treated and non-treated SKOV-3 two-dimensional electrophoresis (2-DE) profiles, four proteins, namely vimentin (VIM), pyruvate kinase, muscle (PKM), heterogeneous nuclear ribonucleoprotein A1 (HNRNPA1) and transgelin (TAGLN1) were identified to be involved in apoptosis. Other proteins including piggybac transposable element derived 5 (PGBD5), DENN/MADD domain containing 2D (DENND2D) and formin-like 1(FMNL) have also been identified to be associated in SKOV-3 cell death induced by 17βH-neriifolin.
CONCLUSION: These findings may provide new insights on the potential of 17βH-neriifolin's mechanism of action in killing ovarian cancer cells.
METHODS: This study encompassed children born in the Auckland region (New Zealand) with a newborn screen TSH level of 8 to 14 mIU/L blood, age 6.9 to 12.6 years at assessment, and their siblings. Thyroid function tests (serum TSH and free thyroxine) and neurocognitive assessments were performed, including IQ via the Wechsler Intelligence Scale for Children, fourth edition.
RESULTS: Ninety-six mTSHe individuals were studied, including 67 children recruited with 75 sibling controls. Mean mTSHe newborn TSH level was 10.1 mIU/L blood and 2.4 mIU/L at assessment (range, 0.8-7.0 mIU/L, serum). Although higher newborn TSH levels in the mTSHe group correlated with lower full-scale IQ scores (r = 0.25; P = .040), they were not associated with the magnitude of the IQ difference within sibling pairs (P = .56). Cognitive scores were similar for mTSHe and controls (full-scale IQ 107 vs 109; P = .36), with a minor isolated difference in motor coordination scores.
CONCLUSIONS: Our data do not suggest long-term negative effects of neonatal mild TSH elevation. TSH elevation below the screen threshold appears largely transient, and midchildhood neurocognitive performance of these children was similar to their siblings. We propose that associations between neonatal mild TSH elevation and IQ are due to familial confounders. We caution against the practice of reducing screening CH cutoffs to levels at which the diagnosis may not offer long-term benefit for those detected.
METHODS: This is a prospective, cross-sectional study of consecutive thyrotoxicosis patients seen at the endocrine clinic of a tertiary medical center. Thyroid status was determined biochemically before prolonged exercise test. Compound muscle action potential (CMAP) amplitudes postexercise were compared against pre-exercise amplitudes and recorded as percentage of mean baseline CMAP amplitude. Comparisons of time-dependent postexercise CMAP amplitudes and mean CMAP amplitude decrement were made between hyperthyroid and nonhyperthyroid groups.
RESULTS: Seventy-four patients were recruited, 23 (31%) men, 30 (41%) Chinese, and the mean age was 48.5 ± 16.8 years. Of 74 patients, 32 (43%) were hyperthyroid and 42 (57%) were nonhyperthyroid viz. euthyroid and hypothyroid. Time-dependent CMAP amplitudes from 10 to 45 minutes after exercise were significantly lower in hyperthyroid patients compared with nonhyperthyroid patients (P < 0.01). Mean CMAP amplitude decrement postexercise was significantly greater in hyperthyroid than nonhyperthyroid patients (23.4% ± 11.4% vs. 17.3% ± 10.5%; P = 0.02).
CONCLUSIONS: Compound muscle action potential amplitude declines on prolonged exercise test were significantly greater in hyperthyroid patients compared with nonhyperthyroid patients. Muscle membrane excitability is highly influenced by thyroid hormone level. Thyrotoxic periodic paralysis occurs from increased levels of thyroid hormone activity in susceptible patients.
Methodology: This is a cross-sectional study looking at data over a period of 16 years (2000-2016). Confirmed cases had thyroid scan at the age of 3-years-old and repeated TFT (after 6 weeks off medications). Relevant data was collected retrospectively.
Results: Forty (60% female) children with CHT were included in the study. Thirty (75%) children presented with high cord TSH. Nine (23%) presented after 2 weeks of life. Majority were diagnosed with TDH (42.5%) with TD and TH of 40% and 17.5% respectively. Median cord TSH of children with TD was significantly higher compared to TDH and TH (p=0.028 and p=0.001 respectively). L-thyroxine doses were not significantly different between TD, TDH and TH at diagnosis or at 3 years.
Conclusions: TDH is highly prevalent in our population. TD may present after 2 weeks of life. One in five children treated for CHT had TH. Differentiating TD, TDH and TH before initiating treatment remains a challenge in Malaysia. This study provides clinicians practical information needed to understand the possible aetiologies from a patient's clinical presentation, biochemical markers and treatment regime. Reassessing TH cases may be warranted to prevent unnecessary treatment.
METHODS: Female rats, once rendered hypothyroid via oral administration of methimazole (0.03% in drinking water) for twenty-one days were mated with fertile euthyroid male rats at 1:1 ratio. Pregnancy was confirmed by the presence of vaginal plug and this was designated as day-1. Thyroxine (20, 40 and 80 μg/kg/day) was then subcutaneously administered to pregnant, hypothyroid female rats for three days. A day after last injection (day four pregnancy), female rats were sacrificed and expression of thyroid hormone receptors (TR-α and β), retinoid X receptor (RXR) and extracellular signal-regulated kinase (ERK1/2) in uterus were quantified by Western blotting while their distribution in endometrium was visualized by immunofluorescence.
RESULTS: Expression of TRα-1, TRβ-1 and ERK1/2 proteins in uterus increased with increasing doses of thyroxine however no changes in RXR expression was observed. These proteins were found in the stroma with their distribution levels were relatively higher following thyroxine treatment.
CONCLUSIONS: Increased expression of TRα-1, TRβ-1 and ERK1/2 at day 4 pregnancy in thyroxine-treated hypothyroid pregnant rats indicate the importance of thyroxine in up-regulating expression of these proteins that could help mediate the uterine changes prior to embryo implantation.