Alexandre A. Doueik

Expression and role of the angiotensin II AT2 receptor in human prostate tissue: In search of a new therapeutic option for prostate cancer

Evidence shows that angiotensin II type 1 receptor (AT1R) blockers may be associated with improved outcome in prostate cancer patients. It has been proposed that part of this effect could be due to angiotensin II type 2 receptor (AT2R) activation, the only active angiotensin II receptor in this situation. This study aimed to characterize the localization and expression of AT2R in prostate tissues and to assess its role on cell morphology and number in prostatic epithelial cells in primary culture.

Effects of postnatal smoke exposure on laryngeal chemoreflexes in newborn lambs.

Laryngeal chemoreflexes (LCR), which are elicited by the contact of liquids such as gastric refluxate with laryngeal mucosa, may trigger some cases of sudden infant death syndrome. Indeed, while LCR in mature mammals consist of protective responses, previous animal data have shown that LCR in immature newborns can include laryngospasm, apnea, bradycardia, and desaturation. The present study was aimed at testing the hypothesis that postnatal exposure to cigarette smoke is responsible for enhancing cardiorespiratory inhibition observed with LCR. Eight lambs were exposed to cigarette smoke (20 cigarettes/day) over 16 days and compared with seven control lambs. Urinary cotinine/creatinine ratio was measured at a level relevant to previously published levels in infants. On days 15 and 16, 0.5 ml of HCl (pH 2), milk, distilled water, or saline was injected onto the larynx via a chronic supraglottal catheter during sleep. Results showed that exposure to cigarette smoke enhanced respiratory inhibition (P < 0.05) and tended to enhance cardiac inhibition and decrease swallowing and arousal during LCR (P < 0.1). Overall, these results were observed independently of the state of alertness and the experimental solution tested. In conclusion, 16-day postnatal exposure to cigarette smoke increases cardiorespiratory inhibition and decreases protective mechanisms during LCR in nonsedated full-term lambs.

Effects of simulated reflux laryngitis on laryngeal chemoreflexes in newborn lambs

It has been suggested that reflux laryngitis (RL) is involved in apneas-bradycardias of the newborn. The aim of the present study was to develop a unique RL model in newborn lambs to test the hypothesis that RL enhances the cardiorespiratory components of the laryngeal chemoreflexes (LCR) in the neonatal period. Gastric juice surrogate (2 ml of normal saline solution with HCl pH 2 + pepsin 300 U/ml) (RL group, n = 6) or normal saline (control group, n = 6) was repeatedly injected onto the posterior aspect of the larynx, 3 times a day for 6 consecutive days, via a retrograde catheter introduced into the cervical esophagus. Lambs instilled with gastric juice surrogate presented clinical signs of RL, as well as moderate laryngitis on histological observation. Laryngeal chemoreflexes were thereafter induced during sleep by injection of 0.5 ml of HCl (pH 2), ewes milk, distilled water or saline into the laryngeal vestibule via a chronic, transcutaneous supraglottal catheter. Overall, RL led to a significantly greater respiratory inhibition compared with the control group during LCR, including longer apnea duration (P = 0.01), lower minimal respiratory rate (P = 0.002), and a more prominent decrease in arterial hemoglobin saturation (SpO(2)) (P = 0.03). No effects were observed on cardiac variables. In conclusion, 1) our unique neonatal ovine model presents clinical and histological characteristics of RL; and 2) the presence of RL in newborn lambs increases the respiratory inhibition observed with LCR, at times leading to severe apneas and desaturations.

Inhibition of DHCR24/Seladin-1 impairs cellular homeostasis in prostate cancer†‡§

Seladin‐1 belongs to a subgroup of androgen‐dependent genes associated with anti‐proliferative, pro‐differentiation, and pro‐apoptotic functions and plays a protective role against oncogenic stress. The present study aims to investigate the localization and expression of Seladin‐1 protein in normal and tumoral human prostatic tissues as well as to explore its role in proliferation and steroid secretion in androgen‐dependent (LnCaP) and androgen‐independent (DU145) cell lines and in human prostate primary cell culture.

Effects of postnatal environmental tobacco smoke on non-nutritive swallowing-breathing coordination in newborn lambs.

While prenatal environmental tobacco smoke (ETS) exposure is a well-known risk factor for sudden infant death syndrome, the effect of postnatal ETS exposure is less clear. The objective of this study was to investigate the effect of postnatal ETS exposure on non-nutritive swallowing (NNS) and NNS-breathing coordination, which are crucial to prevent aspiration related-cardiorespiratory events. Eighteen newborn lambs (6 per group) were randomly exposed to either 10 cigarettes/day, 20 cigarettes/day or room air for 15 days. Lambs were instrumented for recording states of alertness, swallowing, electrocardiogram and breathing; recordings were performed in non-sedated lambs at the end of ETS exposure. Urinary cotinine/creatinine ratio confirmed relevant real-life exposure. Postnatal ETS exposure had no effect on NNS frequency but tended to decrease inspiratory NNS (p=0.07) during quiet sleep. No effect on respiratory or heart rate (p>0.6), apnea index (p=0.2) or sleep states (p=0.3) was observed. In conclusion, postnatal ETS exposure in lambs had only mild effects on NNS-breathing coordination.

Presence of task-1 channel in the laryngeal mucosa in the newborn lamb.

ABSTRACT Nearly 40 potassium channels have been described in respiratory epithelial cells. Of these are found several members of the 4-transmembrane domain, 2-pore K+ channel family (K2P family), namely Twik-1 and -2, Trek-1 and -2, Task-2, -3, and -4, Thik-1, and KCNK7. The aim of this study was to verify whether the Twik-related acid-sensitive K+ channel, subtype 1 (Task-1) (also known as KCNK3), is present in the laryngeal mucosa in the newborn lamb. Through the use of immunohistochemistry and nested polymerase chain reaction (PCR) amplification, results indicate that Task-1 protein and mRNA are present in the laryngeal mucosa, in both the ciliated, pseudostratified columnar (respiratory) epithelium and the nonkeratinized, stratified squamous epithelium. The complete ovine Task-1 protein sequence showed high homology levels with previously reported mouse, bovine, and human Task-1 sequences. This includes a complete homology for the C-terminal amino acid sequence, which is mandatory for protein trafficking to the cell membrane. These results represent the first demonstration that Task-1, a pH-sensitive channel responsible for setting membrane potential, is present in the laryngeal mucosa of a newborn mammal.

Effects of reflux laryngitis on non-nutritive swallowing in newborn lambs

Reflux laryngitis in infants may be involved not only in laryngeal disorders, but also in disorders of cardiorespiratory control through its impact on laryngeal function. Our objective was to study the effect of reflux laryngitis on non-nutritive swallowing (NNS) and NNS-breathing coordination. Two groups of six newborn lambs, randomized into laryngitis and control groups, were surgically instrumented for recording states of alertness, swallowing and cardiorespiratory variables without sedation. A mild to moderate reflux laryngitis was induced in lambs from the experimental group. A significant decrease in the number of NNS bursts and apneas was observed in the laryngitis group in active sleep (p=0.03). In addition, lower heart and respiratory rates, as well as prolonged apnea duration (p<0.0001) were observed. No physiologically significant alterations in NNS-breathing coordination were observed in the laryngitis group. We conclude that a mild to moderate reflux laryngitis alters NNS burst frequency and autonomous control of cardiac activity and respiration in lambs.

Malignant peripheral nerve sheath tumour of the renal parenchyma presenting as a fast growing atypical renal cyst

Malignant peripheral nerve sheath tumours (MPNST) of the kidney are very rare, with only 3 cases reported in the English and French literature. However, we report the first case of fast growing atypical renal cyst where a magnetic resonance imaging was an interesting adjunct to the computed tomography scan in imaging this rare tumour.