Inhibition by gossypol of cyclic AMP production in mouse leydig cells

Gossypol has been shown to inhibit steroidogenesis in leydig cells. This study examined the mechanism of this action by investigating the effect of gossypol on leydig cell hCG receptor binding, adenylate cyclase activity and cyclic AMP production in leydig cells. Gossypol had no effect on hCG binding to cell membranes but inhibited LH-stimulated cyclic AMP production in whole purified leydig cells. It also reduced the stimulation caused by LH, Gpp(NH)p, forskolin and fluoride in membranes from leydig cells and also from liver. It is therefore possible that gossypol affects cyclic AMP production at the level of ATP conversion to cyclic AMP, although effects on the G-protein and catalytic subunit cannot be ruled out.     

Abrogation of head and neck squamous cell carcinoma growth by epidermal growth factor receptor ligand fused to pseudomonas exotoxin transforming growth factor alpha-PE38.

PURPOSE: This study was undertaken to determine whether low intratumoral doses of the epidermal growth factor receptor ligand-transforming growth factor alpha (TGF-alpha) fused to Pseudomonas exotoxin (TGF-alpha-PE38)-abrogated head and neck squamous cell carcinoma (HNSCC) tumor growth in vitro and in vivo. EXPERIMENTAL DESIGN: In vitro cytotoxicity assays were carried out to determine the sensitivity of HNSCC cells to TGF-alpha-PE38. TGF-alpha-PE38-treated HNSCC cells were examined by immunoblotting for cleaved poly(ADP-ribose) polymerase to evaluate apoptosis. Nude mice bearing established HNSCC xenografts were treated with several doses of TGF-alpha-PE38 to evaluate the antitumor efficacy in vivo. Tumor sections were stained with terminal deoxynucleotidyl transferase-mediated nick end labeling for apoptosis. To determine the effect of oral administration of TGF-alpha-PE38, gavage injections of TGF-alpha-PE38 were administered, and the esophagus and surrounding soft tissue were then stained for apoptotic cells. RESULTS: HNSCC cell lines examined were sensitive to low doses of TGF-alpha-PE38 (EC(50) in the range of 1.6 to 10 ng/mL). HNSCC cells treated with TGF-alpha-PE38 undergo apoptosis. Antitumor effects were observed using 0.1 and 0.03 microg of TGF-alpha-PE38 administered intratumorally. At these doses, the treatment was well tolerated. Tumors treated with the toxin had a higher number of apoptotic cells compared with the control tumors. No apoptotic cells were observed in the pharyngoesophageal tissues of the mice after gavage administration of the toxin suggesting that the toxin could be orally administered without toxicity. CONCLUSIONS: These results indicate that topical or intratumoral administration of low doses of TGF-alpha-PE38 may demonstrate antitumor effects in HNSCC without associated systemic toxicity.     

ADHD presenting as recurrent epistaxis: a case report

Epistaxis is an important otorhinolaryngological emergency, which usually has an apparent etiology, frequently local trauma in children. Here we present a case report wherein the epistaxis was recalcitrant, and proved to have a psychiatric disorder as an underlying basis. The child was diagnosed with Attention Deficit/Hyperactivity Disorder, hyperactive type, which led to trauma to nasal mucosa due to frequent and uncontrolled nose picking. Treatment with atomoxetine controlled the patient's symptoms and led to a remission of epistaxis.     

Age of puberty in Iranian girls living in Tehran

The aim of this study was to determine the age of appearance of secondary sexual characteristics in Iranian girls living in Tehran. A cross-sectional study was conducted between 2003 and 2004 on 1420 6–17-year-old females in different parts of Tehran. Data were collected on the basis of a multistage probability sampling. Secondary sexual characteristics were evaluated by inspection and palpation, and were recorded according to Tanner staging. The subjects were asked about the occurrence of menarche and the age of its onset. Generalized additive logistic modelling was used for the analysis of data. The median age (percentile 10–percentile 90) of Tanner 2 of breast development (B2) and Tanner 2 of pubic hair growth (P2) among 1136 girls was 9.74 years (8.23–11.94) and 10.49 years (8.86–12.17), respectively. The ages of the 2.5 percentile for B2 and P2 were 7.42 and 7.03 years, respectively, so the onset of puberty at <7 years and 5 months is considered precocious in this population. The median age of menarche in 399 girls was 12.68 years (11.27–15.96).     

Expression of EGFR, VEGF, and NOTCH1 Suggest Differences in Tumor Angiogenesis in HPV-Positive and HPV-Negative Head and Neck Squamous Cell Carcinoma

There is current interest in anti-angiogenesis therapies for head and neck squamous cell carcinomas (HNSCC), although the utility of these therapies in human papillomavirus (HPV) positive and HPV-negative HNSCC is unclear. Therefore, we explored heterogeneity in expression of a distal factor in angiogenesis (EGFR, the epidermal growth factor receptor), a proximal factor in angiogenesis (VEGF, the vascular endothelial growth factor) and a putative factor in angiogenesis (NOTCH1) in a HNSCC case series using immunohistochemistry in N = 67 cases (27 HPV-positive, 40 HPV-negative, by in situ hybridization). Box plots and the Wilcoxon rank sum or Kruskal–Wallis tests were used to compare staining scores (intensity × percent of cells staining) by HPV status and lifestyle factors. Associations between EGFR, VEGF, and NOTCH1 were assessed using box plots and Spearman correlation (ρ) in all cases, and stratified by HPV status. HPV-negative HNSCC over-expressed EGFR [median (range): 30 (0–300)] relative to HPV-positive HNSCC [7.5 (0–200)] (P = 0.006). VEGF and NOTCH1 were unrelated to HPV status (P > 0.05). EGFR was associated with VEGF in HPV-negative (ρ = 0.40, P = 0.01) but not HPV-positive HNSCC (ρ = 0.25, P = 0.20). NOTCH1 and VEGF were associated in HPV-negative (ρ = 0.40, P = 0.01) but not HPV-positive tumors (ρ = −0.12, P = 0.57). NOTCH1 was not associated with EGFR (P > 0.05). Our results are suggestive of heterogeneity in HNSCC angiogenesis. Future studies should explore angiogenesis mechanisms in HPV-positive and HPV-negative HNSCC.

Electronic supplementary material

The online version of this article (doi:10.1007/s12105-013-0447-y) contains supplementary material, which is available to authorized users.