Prevalence and risk indicators of buccal gingival recessions in a Moroccan periodontitis patients: A retrospective study.

Background: This study investigates the prevalence, distribution and risk indicators of buccal gingival recessions (GRs) in periodontitis patients. Methods: A retrospective examination of 400 periodontitis patients files was performed using an operating sheet. Univariate logistic regression analysis was performed to identify risk indicators of GRs. Multivariate regression analysis was conducted for selected variables with p < 0.05. Results: 354/400 (88.5 %) patients have at least one GR ≥ 1 mm. The prevalence of recession type (RT) at the patient level was 0.5 %, 2.25 % and 85.75 % for RT1, RT2 and RT3 respectively. Lower incisors are the most affected teeth (79.8 %). Upper canines present the lowest frequency (41.8 %). The univariate logistic regression showed that age (SE = 0.021; 95 % CI 1.01-1.10; p = 0.006), plaque index (SE = 0.50; 95 % CI 1.49-10.50; p = 0.006), level of plaque control (SE = 0.529; 95 % CI 0.90-0.72; p = 0.010) and periodontitis stage (SE = 0.41; 95 % CI 1.41-7.07; p = 0.005) were significantly associated with the presence of GR. In the multivariate regression model, significant results were confirmed only for age (SE = 0.021; 95 % CI 1.02-1.17; p = 0.006) and periodontitis stage (SE = 0.41; 95 % CI 1.35-6.75; p = 0.007). Conclusion: The cross-sectional study showed a high prevalence of GRs. Lower incisors were the most affected teeth. Most patients have GRs with advanced interproximal attachment loss (RT3 GRs). Age, plaque index, level of plaque control and periodontitis stage resulted as risk indicators of GRs.

NLRP7 Promotes Choriocarcinoma Growth and Progression through the Establishment of an Immunosuppressive Microenvironment.

The inflammatory gene NLRP7 is the major gene responsible for recurrent complete hydatidiform moles (CHM), an abnormal pregnancy that can develop into gestational choriocarcinoma (CC). However, the role of NLRP7 in the development and immune tolerance of CC has not been investigated. Three approaches were employed to define the role of NLRP7 in CC development: (i) a clinical study that analyzed human placenta and sera collected from women with normal pregnancies, CHM or CC; (ii) an in vitro study that investigated the impact of NLRP7 knockdown on tumor growth and organization; and (iii) an in vivo study that used two CC mouse models, including an orthotopic model. NLRP7 and circulating inflammatory cytokines were upregulated in tumor cells and in CHM and CC. In tumor cells, NLRP7 functions in an inflammasome-independent manner and promoted their proliferation and 3D organization. Gravid mice placentas injected with CC cells invalidated for NLRP7, exhibited higher maternal immune response, developed smaller tumors, and displayed less metastases. Our data characterized the critical role of NLRP7 in CC and provided evidence of its contribution to the development of an immunosuppressive maternal microenvironment that not only downregulates the maternal immune response but also fosters the growth and progression of CC.

Vascular endothelial growth factor (VEGF) and Endocrine gland-VEGF (EG-VEGF) are down regulated in head and neck cancer.

OBJECTIVE: To characterise the role of VEGF, EG-VEGF and its receptors in the development and progression of HNC. DESIGN: Human serum and tissues samples were collected from healthy, epulis and HNC patients and used for ELISA assays and immunohistochemistry studies, respectively. SETTING: Ibn Rochd Hospital of Casablanca (Morocco), INSERM and University of Grenoble Alpes (France). PARTICIPANTS: We used serum from 64 patients with head and neck cancers and from 71 controls without general pathology. Tissues samples were collected from seven patients with OSCC and from seven patients with Epulis. MAIN OUTCOME MEASURES: We compared circulating VEGF and EG-VEGF in normal and HNC patients and determined the expression, localisation and quantification of VEGF, EG-VEGF and its receptors; PROKR1 and PROKR2 as well as Ki67, CD31 and CD34 in OSCC and Epulis patients. RESULTS: Both EG-VEGF and VEGF circulating levels were significantly decreased in the HNC (P < .01). OSCC patients expressed less EG-VEGF and VEGF proteins, higher PROKR1 and PROKR2 with no change in CD31 and CD34 levels. A significant increase in Ki67 was observed in OSCC. CONCLUSIONS: We demonstrated that circulating VEGF and EG-VEGF are downregulated in HNC patients and in OSCC tissue. EG-VEGF receptors were increased in OSCC, along with a stabilisation of two key markers of angiogenesis. These findings strongly suggest that downregulation of angiogenesis in HNC might explain its moderate metastatic feature.

Risk factors and poor prognostic factors of preeclampsia in Ibn Rochd University Hospital of Casablanca: about 401 preeclamptic cases.

Preeclampsia is a gestational pathology that complicates 2 to 8% of pregnancies and is one of the major causes of maternal and fetal morbidity and mortality worldwide. The aim of this work was to study the epidemiological profile of preeclampsia in Casablanca and to identify risk factors as well as factors of poor maternal and fetal prognosis. 401 preeclamptic cases were collected in the gynecology-obstetrics "C" Service of Lalla Meryem Maternity of Ibn Rochd University Hospital of Casablanca (2010-2011) were included in this study and a statistical analysis with the SPSS software version (16.0) was performed. We used the Chi-2 test to analyze qualitative variables and Student's test and ANOVA (analysis of variance) for quantitative variables. The incidence of preeclampsia was (7.1%). The epidemiological profile was that of a primipara (57.6%), average age 30 years and (66.8%) of pregnancies were not followed. Multiparity was a factor of poor maternal prognosis (p = 0.007). The low gestational age and no prenatal care were factors of maternal as well as fetal prognosis. Risk factors frequently found in our patients were obesity (15.21%) and chronic hypertension (5.73%) as vascular-renal history; abortion (16.46%) and perinatal death (5.24%) as obstetric history. Preeclampsia is a common obstetric pathology in our context. Better prenatal care and early diagnosis could reduce its incidence.

Endocrine gland-derived vascular endothelial growth factor (EG-VEGF) and its receptor PROKR2 are associated to human colorectal cancer progression and peritoneal carcinomatosis.

BACKGROUND: The highest risk factor for mortality among malignant tumors is metastasis. Endocrine gland-derived vascular endothelial growth factor (EG-VEGF) is an angiogenic factor which biological activity is mediated via two G protein-coupled receptors, prokineticin receptor1 (PROKR1) and PROKR2. Recent studies suggested that EG-VEGF expression is deregulated in multiple cancers including colorectal cancer (CRC). METHODS: Using distinctive CRC and peritoneal carcinomatosis (PC) cohorts and a corresponding control cohort, we determined the circulating levels of EG-VEGF and its in situ expression, and that of its related receptors. RESULTS: Circulating EG-VEGF levels were significantly increased in patients with metastatic PC compared to CRC and control patients (p< 0.05). Furthermore, according to clinicopathologic examinations, local EG-VEGF expression correlated with higher tumor and nodal stages (p< 0.001) of CRC. EG-VEGF and PROKR2 were highly expressed in colorectal primary lesions compared to positive controls. PROKR1 expression was lower and did not change in tumor specimens. Also, EG-VEGF and its receptor PROKR2 were differentially expressed in the colorectal primary lesions and in the control groups. CONCLUSION: Altogether these findings suggest that EG-VEGF/receptors system might be an important actor in the CRC progression into PC and might be involved in the ability of tumor cells to invade other organs. Circulating EG-VEGF could be proposed as a prognostic marker in human CRC and its progression into PC.

[Descriptive epidemiology of peritoneal carcinosis of gastrointestinal origin at the Ibn Rochd University Hospital, Casablanca (2008-2010)]. / Épidémiologie descriptive de la carcinose péritonéale d'origine digestive à l'Hôpital Universitaire Ibn Rochd de Casablanca (2008-2010).

INTRODUCTION: Peritoneal carcinosis is characterized by ineluctably terminal diffuse spread of abdominal cancer. It is the sign of an advanced disease or a re-emerging disease most often associated with a dark prognosis. Approximately two thirds of all peritoneal carcinomas are of gastrointestinal origin and one third are of non-digestive origin. METHODS: We conducted a retrospective descriptive study between January 2008 and December 2010 in order to establish epidemiological features and risk factors of peritoneal carcinosis of gastrointestinal origin at the Ibn Rochd University hospital, Casablanca. RESULTS: Forty-seven cases of peritoneal carcinosis of gastrointestinal origin were recorded (22 women, 25 men), corresponding to a prevalence of 6.19% and to a mean number of 15.6 cases per year. Age was the major risk factor in our case series (with an average age of 55.55 ± 12.32 years). Even family history was a risk factor to consider. CONCLUSION: This study concluded that the major risk factors for peritoneal carcinosis of digestive origin are age and family history at the Ibn Rochd University hospital, Casablanca (2008-2010).

Antagonism of EG-VEGF Receptors as Targeted Therapy for Choriocarcinoma Progression In Vitro and In Vivo.

Purpose: Choriocarcinoma (CC) is the most malignant gestational trophoblastic disease that often develops from complete hydatidiform moles (CHM). Neither the mechanism of CC development nor its progression is yet characterized. We recently identified endocrine gland-derived vascular endothelial growth factor (EG-VEGF) as a novel key placental growth factor that controls trophoblast proliferation and invasion. EG-VEGF acts via two receptors, PROKR1 and PROKR2. Here, we demonstrate that EG-VEGF receptors can be targeted for CC therapy.Experimental Design: Three approaches were used: (i) a clinical investigation comparing circulating EG-VEGF in control (n = 20) and in distinctive CHM (n = 38) and CC (n = 9) cohorts, (ii) an in vitro study investigating EG-VEGF effects on the CC cell line JEG3, and (iii) an in vivo study including the development of a novel CC mouse model, through a direct injection of JEG3-luciferase into the placenta of gravid SCID-mice.Results: Both placental and circulating EG-VEGF levels were increased in CHM and CC (×5) patients. EG-VEGF increased JEG3 proliferation, migration, and invasion in two-dimensional (2D) and three-dimensional (3D) culture systems. JEG3 injection in the placenta caused CC development with large metastases compared with their injection into the uterine horn. Treatment of the animal model with EG-VEGF receptor's antagonists significantly reduced tumor development and progression and preserved pregnancy. Antibody-array and immunohistological analyses further deciphered the mechanism of the antagonist's actions.Conclusions: Our work describes a novel preclinical animal model of CC and presents evidence that EG-VEGF receptors can be targeted for CC therapy. This may provide safe and less toxic therapeutic options compared with the currently used multi-agent chemotherapies. Clin Cancer Res; 23(22); 7130-40. ©2017 AACR.

Prokineticins in central and peripheral control of human reproduction.

Prokineticin 1 (PROK1) and (PROK2), are two closely related proteins that were identified as the mammalian homologs of their two amphibian homologs, mamba intestinal toxin (MIT-1) and Bv8. PROKs activate two G-protein linked receptors (prokineticin receptor 1 and 2, PROKR1 and PROKR2). Both PROK1 and PROK2 have been found to regulate a stunning array of biological functions. In particular, PROKs stimulate gastrointestinal motility, thus accounting for their family name "prokineticins". PROK1 acts as a potent angiogenic mitogen, thus earning its other name, endocrine gland-derived vascular endothelial factor. In contrast, PROK2 signaling pathway has been shown to be a critical regulator of olfactory bulb morphogenesis and sexual maturation. During the last decade, strong evidences established the key roles of prokineticins in the control of human central and peripheral reproductive processes. PROKs act as main regulators of the physiological functions of the ovary, uterus, placenta, and testis, with marked dysfunctions in various pathological conditions such as recurrent pregnancy loss, and preeclampsia. PROKs have also been associated to the tumor development of some of these organs. In the central system, prokineticins control the migration of GnRH neurons, a key process that controls reproductive functions. Importantly, mutations in PROK2 and PROKR2 are associated to the development of Kallmann syndrome, with direct consequences on the reproductive system. This review describes the finely tuned actions of prokineticins in the control of the central and peripheral reproductive processes. Also, it discusses future research directions for the use of these cytokines as diagnostic markers for several reproductive diseases.

The multiple roles of EG-VEGF/PROK1 in normal and pathological placental angiogenesis.

Placentation is associated with several steps of vascular adaptations throughout pregnancy. These vascular changes occur both on the maternal and fetal sides, consisting of maternal uterine spiral arteries remodeling and placental vasculogenesis and angiogenesis, respectively. Placental angiogenesis is a pivotal process for efficient fetomaternal exchanges and placental development. This process is finely controlled throughout pregnancy, and it involves ubiquitous and pregnancy-specific angiogenic factors. In the last decade, endocrine gland derived vascular endothelial growth factor (EG-VEGF), also called prokineticin 1 (PROK1), has emerged as specific placental angiogenic factor that controls many aspects of normal and pathological placental angiogenesis such as recurrent pregnancy loss (RPL), gestational trophoblastic diseases (GTD), fetal growth restriction (FGR), and preeclampsia (PE). This review recapitulates EG-VEGF mediated-angiogenesis within the placenta and at the fetomaternal interface and proposes that its deregulation might contribute to the pathogenesis of several placental diseases including FGR and PE. More importantly this paper argues for EG-VEGF clinical relevance as a potential biomarker of the onset of pregnancy pathologies and discusses its potential usefulness for future therapeutic directions.

[Effect of inorganic nitrates on the morphofunctional condition of the kidney in the rat]. / Impact des nitrates inorganiques sur l'aspect morphofonctionnel du rein chez le rat.

AIM: The aim of our experimental study was to determine the effect of exogenic nitrates on certain biological parameters in relation to renal insufficiency. RESULTS: Chronic treatment of rats for 5 months with varying nitrate concentrations (50, 100, 150 and 500 mg/L) induced a dose-dependent reduction in plasma concentrations of total proteins and a dose-dependent increase in plasma urea concentrations and creatinine. DISCUSSION: This histological study of the kidney shows that nitrates at doses of 150 and 500 mg/L cause a deterioration in the epithelia of the renal tubules. CONCLUSION: In conclusion, a high nitrate intake induces morphofunctional disturbances of the kidney and could thus be regarded as a causative factor in renal insufficiency.

[Effects of inorganic nitrates on thyroid gland activity and morphology in female rats]. / Effets des nitrates inorganiques sur l'aspect morphofonctionnel de la glande thyroïde chez le rat femelle.

The present study was undertaken to determine the effects of intake of inorganic nitrates in drinking water on thyroid gland activity and morphology in female rats. During 5 months of treatment, nitrates 50, 150 and 500 mg/L induced a significant dose-dependent decrease in bodyweight gain, compared with the control rats. At the end of the experiment, nitrates 150 and 500 mg/L induced hypertrophy of the thyroid gland, accompanied by an increase in the size of the thyroid follicles and hyposecretion of thyroid hormones T3 (triiodothyronine) and T4 (tetraiodothyronine). We concluded that a high nitrate intake in water influenced thyroid gland activity and morphology and might be considered to be a goitrogenic factor.