Structure-function relationship between a natural cosmetic active ingredient and the olfactory receptor OR2AT4.

OBJECTIVE: Although the olfactory receptor OR2AT4 was described as involved in epidermal renewal, there is no data about a cosmetic active ingredient activating this receptor. The aim of this research work was thus to identify a natural molecule binding to this receptor in order to stimulate keratinocyte migration. METHODS: For this purpose, natural molecules were extracted from Cocos nucifera flour. Then, efficacy of this natural extract was evaluated on keratinocyte migration in vitro. Molecules of the Cocos nucifera flour extract were then identified by UPLC-MS/MS. Molecular docking was finally conducted to investigate the potential interaction between identified molecules and the olfactory receptor OR2AT4. RESULTS: The Cocos nucifera flour extract significantly increased keratinocyte migration and results demonstrated that this effect was mediated by the olfactory receptor OR2AT4. Metabolomic analysis revealed two molecules, nonioside D and butyl 4-O-alpha-D-glucopyranosyl-beta-D-glucopyranoside, as significantly present in the Cocos nucifera flour extract compared to both Cocos nucifera oil and water. Finally, molecular docking revealed that butyl 4-O-alpha-D-glucopyranosyl-beta-D-glucopyranoside could interact with the extracellular domain 2 of the OR2AT4. CONCLUSION: This study highlighted for the first time a natural molecule, extracted from Cocos nucifera flour, able to interact with the olfactory receptor OR2AT4 and promote the keratinocyte migration and thus the epithelialization.

OBJECTIF: Bien que le récepteur olfactif OR2AT4 a été décrit comme étant impliqué dans le renouvellement de l'épiderme, il n'y a à ce jour aucune donnée concernant un ingrédient actif cosmétique activant ce récepteur. Le but de cette étude est donc d'identifier une molécule naturelle capable de se fixer au récepteur OR2AT4 afin de stimuler la migration des kératinocytes. METHODE: L'efficacité de cet extrait naturel sur la migration des kératinocytes in vitro a ensuite été évaluée. Les molécules présentes dans l'extrait de farine de Cocos nucifera ont ensuite été identifées par UPLC-MS/MS. Enfin, des expérimentations de docking moléculaire ont été réalisées afin d'identifier une potentielle interaction entre les molécules précédemment identifiées et le récepteur olfactif OR2AT4. RESULTATS: L'extrait de farine de Cocos nucifera augmente significativement la migration des kératinocytes via l'activation du récepteur olfactif OR2AT4. Les analyses métabolomiques ont révélées deux molécules, le nonioside D et le butyl 4-O-alpha-D-glucopyranosyl-beta-D-glucopyranoside, comme étant significativement présentes dans l'extrait de farine de Cocos nucifera en comparaison avec l'huile et l'eau de coco. Enfin, le docking moléculaire révèle que le butyl 4-O-alpha-D-glucopyranosyl-beta-D-glucopyranoside, présent dans l'extrait de farine de Cocos nucifera peut interagir avec le domaine extracellulaire 2 du récepteur olfactif OR2AT4. CONCLUSION: Cette étude a identifié pour la première fois une molécule naturelle, extraite de la farine de Cocos nucifera, capable d'interagir avec le récepteur olfactif OR2AT4, afin de stimuler la migration kératinocytaire et ainsi favoriser le processus de ré-épithélialisation.

Prostate cancer screening: contrasting trends.

PURPOSE: Our previously published data showed rapidly increasing rates of prostate cancer screening in men aged 50-74, which rose from 36% in 2005 to 48% in 2008. Based on men's reported intentions at that time, this was expected to rise to 70% in 2011. Here we report the actual rate of prostate cancer screening. METHOD: Three nationwide observational telephone surveys (EDIFICE opinion polls) were conducted in 2005, 2008, and 2011. The overall target was a representative sample of > 1,500 individuals living in France and aged 40-75 years, including 481 men aged 50-74 years. RESULTS: Within this male population, the rate of screening reported remained stable between 2008 and 2011 (48 and 49%, respectively). However, comparison of privileged versus disadvantaged populations showed significant differences, with a relative decrease in screening among those of higher socioprofessional status (p = 0.03) and from higher-income groups (p = 0.02). For households with a monthly income above 2,500€, the screening rate decreased from 61% in 2008 to 51% in 2011 (p = 0.05), while for those with an income below 2,500€, it increased from 36% in 2008 to 44 % in 2011 (p = 0.18). CONCLUSION: A plateau or even a reduction in prostate cancer screening is currently being observed; this is possibly due to progressive recognition among the population at large of the controversy surrounding prostate cancer screening, whereas this speculation was formerly limited to health-care professionals. After previously being more likely to undergo prostate cancer screening, it is the younger, wealthier populations that are currently showing the most noteworthy step backwards.

Melanoma risk-takers: fathers and sons.

OBJECTIVES: The incidence of skin cancers, melanoma in particular, is increasing rapidly. Consequently, specific recommendations for sun-protection measures now exist. This survey set out to assess the compliance of the general population with these guidelines. METHODS: The French nationwide observational survey, EDIFICE Melanoma, was conducted (28 September to 20 October 2011) through phone interviews of a representative sample of 1502 subjects aged ≥ 18 years, using the quota method. Sun-protection was defined as frequent or systematic use of clothes or sunscreen. The group of individuals who declared exposure to the sun (N = 1172) was subdivided: risk-takers (N = 442), and those who used sun protection (N = 730). RESULTS: Risk-takers were significantly more often male (62% vs. 44%, P < 0.01), had a lower level of education (40% vs. 26%, P < 0.01), lower incomes (2587 euros vs. 2948 euros/month) and were more often smokers (42% vs. 31%, P < 0.01). In contrast, age, marital status and use of sunbeds were not significantly different between the two groups. Interestingly, risk-takers had less risk factors for melanoma. However, they were less well-informed about high-risk exposure and optimal use of sunscreen. Sun-protection measures for their children were less stringent than those of the group who used sun protection: systematic/frequent use of sunglasses (42% vs. 59%, P < 0.01), systematic use of sunscreen (77% vs. 86%, P < 0.01), and frequent renewal (69% vs. 82%, P < 0.01), high sun protection factors (SPF) (46% vs. 56%, P < 0.01), use of clothing (84% vs. 92%, P < 0.01) and hats (88% vs. 94%, P < 0.01). CONCLUSIONS: Risk-takers are characterized by a lesser understanding of sun-protection measures and behaviours. Their children benefit less from protective measures than those of people who use sun protection themselves. Improved understanding may well improve behaviours; one can therefore legitimately predict a considerable impact on parents' attitude to their own protection and that of their children.

Accuracy of dry vaginal self-sampling for detecting high-risk human papillomavirus infection in cervical cancer screening: a cross-sectional study.

OBJECTIVE: Cervical cancer screening coverage remains insufficient in most countries. Testing self-collected samples for high-risk human papillomavirus (HR-HPV) could be an alternative to the Pap smear, but costs, sampling methods and transport issues hamper its wide use. Our objective was to compare diagnostic accuracy of 2 vaginal self-collection methods, a dry swab (vsc-DRY) or swab in liquid medium (vsc-LIQ), for detecting HR-HPV cervical infection assessed by a cervical clinician-collected sample in liquid medium (ccc-LIQ). METHODS: Women 20 to 65 years attending a Pap smear were recruited between September, 2009 and March, 2011. Each sample (3 per woman) underwent HPV DNA testing. Samples were classified as HR-HPV+ with detection of at least one HR-HPV or probable HR-HPV type. RESULTS: Of 734 women included, 722 had complete HPV data. HR-HPV was detected in 20.9% of ccc-LIQ samples. Estimated sensitivity and specificity to detect HR-HPV in vsc-DRY samples were 88.7% and 92.5%, respectively, and in vsc-LIQ samples, 87.4% and 90.9%. Cytology findings were abnormal for 79 women (10.9%): among 27 samples of low-grade squamous intraepithelial lesions, 25 were HR-HPV+ in vsc-DRY, vsc-LIQ and ccc-LIQ samples. Among 6 samples of high-grade squamous intraepithelial lesions, all were HR-HPV+ in vsc-DRY samples, 1 was HR-HPV- in vsc-LIQ samples and 1 was HR-HPV- in ccc-LIQ samples. CONCLUSIONS: Vaginal self-sampling with a dry swab is accurate to detect HR-HPV infection as compared with cervical clinician-collection and accurate as compared with cytology results. This cheap and easy-to-ship sampling method could be widely used in a cervical cancer screening program.

[Breast cancer screening program in France: for optimization of the information]. / Dépistage organisé du cancer du sein en France : pour une optimisation de l'information.

BACKGROUND: Based on international and national recommendations, organized breast cancer screening in France raises questions of medical ethics built around the key concepts of individual autonomy and public health policy. Because of the evolving knowledge, professionals and institutions involved in the program must review the ethical values associated with this medical practice. METHODS: The ethical aspects of organized breast cancer screening were studied. In response to newly acquired knowledge highlighted by a review of texts governing this practice in France, proposals for changes resulting from reflections of a working group coordinated by the National Cancer Institute are presented. RESULTS: Ethical issues raised by screening must find expression in the general principles of the program's organization: acceptability of screening, efficiency, adverse effects, equity of access, free care…, but also at different stages of the procedure: information delivery, first and second invitations, refusal of further diagnostic investigation… CONCLUSION: A better match between breast cancer screening and recently developed knowledge requires optimal information delivery to women targeted by the program as well as a stronger role for the referring healthcare professional.

[Colorectal cancer: from diagnosis to screening]. / Cancer colorectal: du diagnostic au dépistage.

Colorectal cancer fulfils the conditions required for mass screening. Data from controlled studies indicate that it is possible to reduce colorectal cancer mortality at a population level using faecal occult blood testing. Screenings rely on biennial testing in between 50 and 74average risk subjects. Compliance must be over 50%. Colorectal cancer mortality decrease in this case between 15 and 18% in the general population, 33 and 39% among participants to screening. The European Commission, on the basis of available data recommended to organise colorectal cancer screening in the European Union. Generalisation of screening has become a reality in France. Epidemiological studies allow us to define subjects at very high risk (genetic origin) and high risk for colorectal cancer. Colonoscopy screening is recommended in first degree relatives of patients with colorectal cancer or large adenoma diagnosed before 60years or with two affected first-degree relatives, in subjects with an extended inflammatory bowel disease, or with a personal history of large bowel cancer or large adenoma. Promising research strategies are arising: immunochemical tests in the short term, stool-based DNA tests in stools and proteome-based approach in the long term.

Frequent alteration of DNA damage signalling and repair pathways in human colorectal cancers with microsatellite instability.

Accumulation of frameshift mutations at genes containing coding mononucleotide repeats is thought to be the major molecular mechanism by which mismatch repair-deficient cells accumulate functional alterations. These mutations resulting from microsatellite instability (MSI) can affect genes involved in pathways with a putative oncogenic role, but may also arise in genes without any expected role in MSI carcinogenesis because of the high mutation background of these tumours. We here screened 39 MSI colorectal tumours for the presence of mutations in 25 genes involved in DNA damage signalling and repair pathways. Using a maximum likelihood statistical method, these genes were divided into two different groups that differed significantly in their mutation frequencies, and likely represent mutations that do or do not provide selective pressure during MSI tumour progression. Interestingly, the so-called real-target mutational events were found to be distributed among genes involved in different functional pathways of the DNA metabolism, for example, DNA damage signalling (DNA-PKcs, ATR), double-strand break (DSB) repair (DNA-PKcs, RAD50), mismatch repair (MSH3, MSH6, MBD4) and replication (POLD3). In particular, mutations in MRE11 and/or RAD50 were observed in the vast majority of the tumours and resulted in the concomitant loss of immunohistochemical expression of both proteins. These data might explain why MSI colorectal cancers (CRC) behave differently in response to a wide variety of chemotherapeutic agents, notably those targeting DNA. More generally, they give further insights into how MSI leads to functional changes with synergistic effects in oncogenic pathways.

A new adjuvant treatment with polyadenylic-polyuridylic acid in operable breast cancer.

Adjuvant treatment with polyadenylic-polyuridylic acid poly A-poly U was tested in 300 patients with operable breast cancer who had all received the same locoregional treatment. They were randomized into two groups; 155 patients receiving 30 mg poly A-poly U i.v. once a week for 6 weeks and 145 controls. Overall survival was significantly improved in the poly A-Poly U group (P less than 0.05). The most striking difference (less than 0.03) was observed in the group of positive node patients, who had a 5-year relapse-free actuarial survival rate of 71% versus 47% in the controls.

[Gastric stromal tumor with osteoclast-like multinucleated giant cells during Lynch II syndrome]. / Tumeur stromale gastrique à cellules géantes multinucléées de type ostéoclastique au cours d'un syndrome de Lynch II.

We report an unusual case of gastric tumor: a stromal tumor with osteoclast-like giant cells. This type of cells has been described in epithelial tumors, especially in adenocarcinoma of the pancreas, lung, thyroid and breast. It has also been reported in smooth cell tumors such as uterine leiomyosarcoma and malignant fibrous histiocytoma. In our patient, this gastric stromal tumor with osteoclast-like giant cells was diagnosed in a man with adenocarcinoma of the colon in the context of a familial cancer syndrome. This is the first report of stromal tumor with osteoclast-like giant cells associated with Lynch syndrome.

[Hepatic artery ligation for liver metastasis of a acinar cell carcinoma of the pancreas revealed by a nodular panniculitis]. / Ligature de l'artère hépatique pour métastases hépatiques d'un carcinome à cellules acineuses du pancréas révélé par une panniculite nodulaire.

We report the case of a 67-year-old-man presenting with pancreatic acinar cell carcinoma revealed by dermatological manifestations of cytosteatonecrosis and treated by hepatic artery ligation. The pancreatic etiology of these lesions was suspected due to hyperlipasemia, and was confirmed by abdominal computerized tomography showing a pancreatic tumor and multiple liver nodules, and by histological examination of one of these lesions. Because of symptomatic treatment failure, rapid impairment of patient's general condition, and by analogy with the treatment of hepatic metastases of neuroendocrine tumors, hepatic artery ligation was performed. Lipasemia decreased markedly and symptoms disappeared for 45 days. Hepatic artery obstruction may be used for emergency treatment of secreting liver metastases.

[Myotomy for esophageal muscular hypertrophy with eosinophil infiltration of the esophagus associated with toxocariasis revealed by esophageal motor disorder]. / Myotomie pour hypertrophie musculaire avec infiltration à éosinophiles de l'oesophage associée à une toxocarose et révélée par un trouble moteur oesophagien.

We report the case of a 61-year-old-man with an eosinophilic esophagitis with esophageal motor disorder associated with toxocariasis. He complained of non cardiac chest pain and had eosinophilia leading to the detection of Toxocara canis infection. Pain persisted despite treatment of toxocariasis. Basal manometry was normal but ambulatory 24-hour manometry-pHmetry showed diffuse esophageal spasm. Ultrasonography showed a thickening of the esophageal musculature in the two inferior thirds of the esophagus. After failure of treatment with sodium cromoglycate steroids and esophageal dilatation, calcium antagonists were partially effective. A long esophageal myotomy was performed permiting the disappearance of symptoms. The histological examination of a side myotomy biopsy showed an eosinophilic infiltration of the esophageal muscle layer. This observation leads to discuss the possible relation between toxocariasis, the esophageal motor disorder and the eosinophilic infiltration of the esophageal muscle layer.

[Benign symmetrical lipomatosis of the tongue]. / Lipomatose bénigne symétrique de la langue.

INTRODUCTION: Lipomatosis of the tongue is rarely observed. CASE REPORT: An 85-year-old man with chronic alcoholism presented several symmetrical lipomas of the tongue with no other clinical manifestations. There was no capsule at the histology examination. DISCUSSION: The multiple and symmetrical nature of the lesion without a capsule led to the diagnosis of benign symmetrical lipomatosis of the tongue, the fourth case reported in the literature.

[Percutaneous resection of benign renal cysts]. / Resección percutánea de los quistes renales benignos.

Six patients carrying bulky renal cysts located in the kidney lower pole were treated by percutaneous resection of the cystic wall. No complications were observed during the peri and postoperational period. In all cases disappearance of symptoms was observed, and the total success rate (absence of residual cavity) recorded was 4/6, two cases presenting persistence of a small residual cavity which originated one case of relapse. The paper presents the technique used, and the indications and possible therapeutic actions for the treatment of simple kidney cysts are discussed.

[Endoscopic treatment of vesico-ureteral reflux after reimplantation of the ureter (transplants excluded)]. / Traitement endoscopique du reflux vésico-urétéral après réimplantation de l'uretère (greffes exclues).

O'Donnell's technique was used to treat 9 refluxing ureteric units after surgical reimplantation of the ureter in 8 patients (mean age: 45 years) between May 1986 and January 1991. The reimplantation was performed according to Cohen's technique in 5 cases (including ureteric remodelling in one case), Leadbetter's technique in 2 cases (including ureteric remodelling in one case), the Campos Freire technique in 1 case and a direct reimplantation in 1 case (with Boari). The reflux was grade II for 1 ureter, grade III for 54 ureters, grade IV for 2 ureters and grade V for 1 ureter. A single injection was performed in 5 patients and multiple injections were required in 3 patients. An associated bladder neck incision was performed in 2 male patients. No complications were observed. Correction of reflux was obtained for 8 ureteric units, i.e. 87% success with a mean follow-up of 28 months. The failure corresponded to the case of grade V reflux in a megaureter reimplanted with remodelling. The authors recommend that endoscopic treatment of reflux be performed as first-line treatment for reflux of reimplanted ureters because of the simplicity and efficacy of this technique.

[100 percutaneous endopyelotomies. Technique, indications, results]. / 100 endopyélotomies per-cutanées. Technique, indication, résultats.

100 percutaneous endopyelotomies were performed in 95 patients from October 1985 to February 1991 to treat 46 cases of acquired stenosis and 54 cases of congenital hydronephrosis. The acquired stenoses were treated by scalpel incision, while the congenital hydronephrosis were generally treated by electrocautery. The evaluable results for 81 ureteric units with a mean follow-up of 37 months showed an overall success rate of 84%. No significant difference in the results was observed in relation to the patient's age, the technique used or the stage of the hydronephrosis (81% success rate): the results in the treatment of congenital hydronephrosis (86%) are slightly inferior to the results of surgical pyeloplasty.

[What is the role of endoscopy in the diagnosis and treatment of tumors of the upper urinary tract?]. / Quelle doit être la place de l'endoscopie dans le diagnostic et le traitement des tumeurs de la voie excrétrice du haut appareil?

17 patients with upper urinary tract tumours were investigated by endoscopy. 3 patients (Group I) with fibrous or fibroepithelial polyps were treated via a retrograde approach and did not develop any recurrences. 2 patients (Group II) developed unexplained haematuria: the diagnosis of high-grade carcinoma was confirmed by endoscopy and they were treated by nephroureterectomy. 12 patients (Group III) with low grade non-invasive urothelial carcinoma, in whom radical surgical was not indicated, were treated conservatively via the percutaneous (13 tumours) or retrograde (1 tumour) endoscopic approach. The local recurrence rate was 33% (4 out of 12 tumours) for a mean follow-up of 22 months. The recurrences were treated by repeated endoscopy in 3 patients, and by nephroureterectomy in 1 patient. Endoscopic treatment of upper urinary tract tumours should be reserved for benign tumours and selected cases of low-grade, non-invasive urothelial carcinoma.

[Percutaneous treatment of simple kidney cysts]. / Traitement per-cutané des kystes simples du rein.

Percutaneous treatment of renal cysts is an effective and minimally invasive alternative to surgery for the treatment of simple, symptomatic renal cysts or cysts complicated by renal stones or hydronephrosis. Moderately large cysts and parapelvic cysts should be treated by sclerotherapy, while very large and peripheral cysts should be resected percutaneously. A series of 29 cysts was treated: 6 percutaneous resections, 22 scleroses, 1 simple puncture-aspiration. Pain relief was obtained in 96% of cases. Resolution of hydronephrosis and renal stones was obtained in 100% of cases. The morbidity (infection, haematoma) was low (10%), but 9 patients (32%) presented with a small residual cavity which, in 1 case, evolved towards a true recurrence of the cyst. The long-term outcome of these asymptomatic residual cavities is unknown.

[A quiet revolution: the Wallstent urethral prosthesis (Urolume AMS)]. / Une révolution tranquille: l'endoprothèse uréthrale de Wallstent (Urolume AMS).

14 patients (mean age: 57 years) with posterior urethral stricture were treated by internal urethrotomy and implantation of one or several Wallsten prostheses. The stent had to be removed in 2 patients (15%), while 12 patients (85%) obtained satisfactory urethral patency (mean follow-up: 17.5 months). Complications were observed in 50% of cases. They were able to be treated endoscopically with a satisfactory result in 5 out of 6 cases (intraprosthetic calculi or stenosis of the ends of the stent; 2 patients who became incontinent after insertion of the stent regained normal continence after insertion of an artificial sphincter above the stent. The Wallsten endoprosthesis therefore appears to be a very satisfactory treatment for recurrent complex strictures of the posterior urethra.

[Does magnetic resonance imaging allow the assessment of the loco-regional extension of cancer of the prostate? Report of 27 anatomo-radiologic comparisons]. / L'imagerie par Résonance Magnétique permet-elle d'apprécier l'extension loco-régionale du cancer de la prostate? A propos de 27 confrontations anatomo-radiologiques.

27 patients with histologically proven prostatic carcinoma were investigated by magnetic resonance imaging (MRI) (0.5 Tesla) in order to determine the local spread of the cancer. These patients then underwent ilio-obturator lymph node dissection with frozen section examination, followed by radical prostatectomy. Histological examination of the resection specimens was performed on slides prepared from large transverse sections every 5 mn. The MRI examination was especially designed to confirm the diagnosis of capsular effraction based on the signals of the periprostatic fat (PF), periprostatic venous plexuses (PVP) and seminal vesicles (SV). An abnormality of at least one of these structures was considered to indicate the diagnosis of capsular effraction. The MRI data were compared to the histological findings. The results demonstrated a sensitivity of 62% for the PF signal, 52% for the PVP signal and 40% for the SV signal. The overall MRI-Histology correlation was found to be exact in 23 out of 27 cases (Accuracy = 85%). All of our four errors represented understaging (Sensitivity = 81%). When a rigorous methodology is respected, the high accuracy and sensitivity of MRI makes this modality an investigation of choice for the study of the prostatic capsule, as part of the routine staging of prostatic cancer. It should allow a better selection of patients with intracapsular cancer (T1-2), who constitute candidates for radical treatment.

[The contribution of endoscopy in the diagnosis of unilateral hematuria of renal origin and pseudotumors of the upper urinary tract]. / Apport de l'endoscopie au diagnostic des hématuries unilatérales d'origine rénale et des fausses tumeurs de la voie excrétrice supérieure.

From 1985 to 1992, 9 patients (6 males, 3 females) with a mean age of 47 years, presenting with a clinical picture suggestive of a tumour of the upper urinary tract (haematuria and/or pelvic or caliceal radiolucent filling defect), underwent retrograde (6 cases) and/or percutaneous (9 cases) endoscopic exploration of the upper urinary tract. The percutaneous examination allowed a precise diagnosis and appropriate treatment adapted to the lesion detected (papillary necrosis: 2 cases; ectopic papilla: 2 cases; hypertrophy of Brunn's nests: 1 case; papillary angioma: 1 case; haemorrhagic papillitis: 3 cases) in every case. Endoscopic exploration of radiolucent lesions of the upper tract and unexplained renal haematuria is therefore justified whenever the diagnosis of upper tract tumour is uncertain on the basis of the radiological and cytological assessment.