Diversity of Vibrio spp. isolated at ambient environmental temperature in the Eastern English Channel as determined by pyrH sequencing.

AIMS: To describe the diversity of the culturable mesophilic and potentially pathogenic vibrios isolated at 22 and 37°C on TCBS medium, in September 2009 from seawater and surface sediments. METHODS AND RESULTS: q-PCR assays previously selected for the identification of bacterial strains isolated at 37°C were used in combination with the partial sequencing of two housekeeping genes, pyrH and toxR, to identify 315 strains isolated at 22°C. The great majority of the 37°C strains was identified by q-PCR assays, (five of the six species) with the predominance of Vibrio alginolyticus (85·9%) and V. harveyi (10·7%). The human pathogens V. parahaemolyticus and V. cholerae were rarely detected (two strains each). The 22°C strains were successfully identified by the phylogeny analysis of pyrH and toxR genes, revealing 20 Vibrio species, with the predominance of the clam pathogen V. celticus (36·8%). The Splendidus and the Harveyi groups represented the main Vibrio group at 22°C (80%) and 37°C (99·5%), respectively. CONCLUSIONS: The combination of q-PCR assays and the sequencing of pyrH and toxR genes highlighted two different Vibrio communities at 22 and 37°C both dominated by pathogenic species for marine organisms. SIGNIFICANCE AND IMPACT OF THE STUDY: The sequencing of the pyrH gene revealed to be a valuable tool to identify environmental Vibrio spp. strains isolated at 22°C, as 92·3% of them were identified in this study.

[Contribution of the 6-minutes walking test and the plasma NT-proBNP at admission and discharge to the prognostic evaluation of patients with NYHA class II-III Heart Failure.] / Contribution du test de marche de six minutes et des taux de NT-proBNP à l'admission et la sortie dans l'évaluation pronostique de l'insuffisance cardiaque classe II-III de la NYHA.

OBJECTIVE: To study the 6MWT and NT-proBNP contribution to the prognosis evaluation of patients with NYHA class II-III heart failure in the Yalgado Ouédraogo Teaching Hospital. METHODS: We carried out a nine months prospective observational cohort from the 1st February to the 31st October 2020. Patients with NYHA class II-III HF who consented to participate were included in the study. We identified two variables of interest: death and readmission. RESULTS: We included 50 patients with congestive heart failure representing 37.3% of heart failure. The average follow up time of patients was 154.58 ± 74.8 days. Twelve patients (24%) were readmited and 11 passed away with five during hospitalisation. On admission, The average distance on the 6MWT (194.6 ± 85.5 m) on admission and average NT-proBNP (5812.1±4729.4 ng/L) measured on admission and before discharge wasn't significantly correlated to the risk of death and re-hospitalisation. The average distance on the 6MWT before discharge (306.2±84.6) was significantly correlated to an increase risk of death and re-hospitalisation. Patients with an increase in NT-proBNP superior to 30% from measurement on admission to the one before discharge had a high risk of re-hospitalisation and death compare to those with a decrease of more than 30% with a moderate to good correlation coefficient of 0.6 between the two. CONCLUSION: 6MWT and NT-proBNP variations from admission to discharge have been necessary to evaluate the prognosis of patients with CHF.

Real-time PCR optimization to identify environmental Vibrio spp. strains.

AIMS: To identify Vibrio vulnificus, Vibrio cholerae and Vibrio alginolyticus using standardized DNA extraction method and real-time PCR assays, among a large number of bacterial strains isolated from marine environment. METHODS AND RESULTS: Methods for DNA extraction and real-time PCR were standardized to identify a large number of Vibrio spp. strains isolated through regular collection campaigns of environmental samples. Three real-time PCR assays were developed from a multiplex PCR, targeting V. vulnificus, V. cholerae and V. alginolyticus on the dnaJ gene. After testing their specificity, these systems were applied for the identification of 961 strains isolated at 22°C (446 strains) and 37°C (515 strains) in September 2009. The predominance of V. alginolyticus (82·6%) among the Vibrio spp. strains isolated at 37°C was shown. At 22°C, only 1·6% of the strains were identified by PCR and they were V. alginolyticus. CONCLUSIONS: Reproducible and specific real-time PCR assays combined to a DNA extraction method on microplates were used to constitute a large environmental Vibrio strains collection and to identify and detect potential human pathogenic Vibrio isolated at 37°C. For environmental strains isolated at 22°C, because of the higher species diversity, other approaches, like sequencing, should be chosen for identification. SIGNIFICANCE AND IMPACT OF THE STUDY: The protocol developed in this study provides an appropriate and rapid screening tool to identify a large number of bacterial strains routinely isolated from the environment in long-term studies.

Acute renal failure in the postpartum due to calcified myoma: a case report.

BACKGROUND: It has been reported that delivery can be a cause of urine retention. This complication occurs especially in case which are associated with a pelvic mass like calcified uterine myoma. But this unusual aspect of myoma can make ultrasonographic traps. OBJECTIVE: To report an unusual case of calcified uterine myoma which was unnoticed during pregnancy and made so obstructive renal failure few days after the delivery. CASE REPORT: Seven days after delivery a Twenty-nine-year-old Senegalese woman was admitted at a private hospital for a slight alteration of consciousness(Glasgow Coma Scale at 12). Emergency check-up showed an acute obstructive renal failure. Biological investigations showed ascendancy of granulocytes, deterioration of renal function with creatinin in 78 mg / l and urea in 1.82 g/l. Ultrasonographic examination revealed bilateral dilatation of renal calyces and an interstitial calcified uterine myoma compressing the bladder. Management consisted on a urethral catheterization of bladder, correction of hydro-electrolytic troubles and antibiotherapy (ciprofloxacin).Global evolution leads to fast fully consciousness, with disappearance of biological and ultrasonographic disorders. CONCLUSION: Calcified myoma can look like cephalic pole during pregnancy. This unusual aspect can be sometimes source of acute obstructive renal failure requiring urinary drainage in emergency. Improvement of women's management during postpartum can prevent such complications.

Apolipoprotein B secretion and atherosclerosis are decreased in mice with phospholipid-transfer protein deficiency.

Increased secretion and levels of ApoB-containing lipoproteins (BLp) commonly occur in familial hyperlipidemia, obesity and diabetes. The plasma phospholipid-transfer protein (PLTP) is known to mediate transfer of phospholipids between BLp and HDL during their intravascular metabolism. To address a possible role of PLTP in dyslipidemia and atherogenesis, we bred mice deficient in the gene encoding PLTP (PLTP-deficient mice) using different hyperlipidemic mouse strains. In ApoB-transgenic and ApoE-deficient backgrounds, PLTP deficiency resulted in reduced production and levels of BLp and markedly decreased atherosclerosis. BLp secretion was diminished in hepatocytes from ApoB-transgenic PLTP-deficient mice, a defect that was corrected when PLTP was reintroduced in adenovirus. The studies reveal a major, unexpected role of PLTP in regulating the secretion of BLp and identify PLTP as a therapeutic target.

[Contribution of the musculocutaneous flap of pectoralis major in head and neck oncology: 26 observations in Senegal]. / Apport du lambeau musculo-cutané du pectoralis major en carcinologie cervico-faciale: 26 observations au Sénégal.

INTRODUCTION: The pectoralis major musculocutaneous flap constitutes a significant advance in cervicofacial carcinology. At our institution, it has allowed most surgical problems to be resolved in a single-stage procedure. The objective of this study was to report our experience with this flap. PATIENTS AND METHODS: This retrospective study includes 26 cases observed over a 10-year period (January 1994-December 2003). The parameters studied were clinical and paraclinical. All patients included in this study received a pectoralis major musculocutaneous flap. Patients treated using another type of flap were not included. RESULTS: Mean patient age was 51 years (range, 20 to 74). The sex ratio was 12 (24 men and 2 women). At the time of admission, 73% of patients showed marked impairment of general condition. In 21 patients (81%), the effect of the pectoralis major musculocutaneous flap was observed immediately after surgery unlike pharyngostome (19%) in which the flap is used in a second stage procedure. With a mean follow-up of 7 years, failure has been observed in 4 cases (15%). CONCLUSION: The pectoralis major musculocutaneous flap is an excellent tool for cervicofacial reconstruction after carcinological exeresis. It reduces the duration of hospitalization. Acquiring proper flap harvesting technique is an important factor in improving outcome.

[Peritoneal dialysis in a tropical area, a reality]. / Dialyse péritonéale en milieu tropical, une réalité.

INTRODUCTION: Chronic kidney disease is now regarded as amajor public health concern. This is especially true in developing countries where it accounts for significant morbidity, mortality and decreased life expectancy. The main problem for developing countries is the cost of dialysis. Indeed, the availability of peritoneal dialysis for renal replacement therapy is low in sub-Saharan Africa. Since March 2004 peritoneal dialysis has been available to some patients with end-stage renal disease in Senegal. The purpose of this study was to assess epidemiologic, clinical, technical patterns and outcomes in patients who underwent peritoneal dialysis in the first three years of the program. MATERIALS AND METHODS: This three-year retropective study identified 26 patients who underwent peritoneal dialysis for end-stage renal disease for a period of at least 15 days. Patients not meeting these criteria were not included. All patients had a Baxter type transfer set. Lactate-bicarbonate solution was used for countinuous ambulatory peritoneal dialysis. In 3 cases, Icodextrin- and amino-acid based-solutions were employed. In automated peritoneal dialysis, the Home Choice machine was used for all patients. Epidemiological, clinical/paraclinical data and outcomes were noted for each patient. RESULTS: Twenty-six patients were included in the study. Median age was 48 +/- 6 years with a M/F sex ratio of 1.17. Most patients (84%) were literate. Diabetic nephropathy and nephroangiosclerosis were the main causes of end-stage renal disease. The mean Charlson score was 3 (range, 2 to 5). Mean residual diuresis was 435 mL/day. The peritonitis rate was 1 per 20 patient months. Staphylococcus aureus and Pseudomonas aeruginosa were the most common germs. Six patients presented catheter infection: exit-site in 4 and tunnel in 2. Catheter obstruction occurred in three cases. At the end of the study, 6 patients were still in automated peritoneal dialysis and 8 in countinuous ambulatory peritoneal dialysis. Six 6 patients died and 6 were switched to hemodialysis. CONCLUSION: Peritoneal dialysis is available as a renal replacement therapy in Senegal. It has allowed end-stage renal disease patients greater autonomy in their working place.

[Systemic vasculitis: study of 27 cases in Senegal]. / Vascularites systémiques: 27 observations au Sénégal.

Studies on vasculitis in black Africa are rare. The purpose of this report is to describe a retrospective study of systemic vasculitis managed in the internal medicine, ORL and cardiolology departments of the Aristide le Dantec University Hospital in Dakar, Senegal from 1995 to 2007. A series of 27 cases involving 7 men and 20 women with a mean age of 49 years was compiled. Primary vasculitis included Horton disease in 3 cases, Wegener disease in 2, Takayasu disease in 1, and Buerger disease in 1. Secondary vasculitis included mixed cryoglobulinemia with Gougerot Sjögren syndrome in 7 cases, primary Goujeröt syndrome in 4, rheumatoid arthritis in 3, nodosa periarteritis with hepatitis B in 2, SHARP syndrome in 1, and polymyositis in 1. The remaining two cases involved abdominal periaortitis including one associated with retrosperitoneal fibrosis and tuberculosis and the other with spondylarthropathy. Corticotherapy in combination with anticoagulants, immunosuppressive therapy, and surgery, when necessary, allowed effective management in 24 cases. The findings of this study show that systemic vasculitis can have numerous etiologies and indicate that secondary forms are the most common. Appropriate care modalities are needed to prevent severe outcome in Senegalese hospitals.

Complications of sinusitis: An 80-case series from the ENT and neurosurgery departments of the Fann university hospital center of Dakar, Senegal.

INTRODUCTION: Locoregional complications of sinusitis are dominated by oculo-orbital and/or cranioencephalic manifestations that may be life-threatening or jeopardize functional prognosis. The aim of this study was to report epidemiological, diagnostic and therapeutic aspects. MATERIALS AND METHODS: A retrospective study included inpatients managed for sinusitis complications in the ENT and neurosurgery departments of the Fann university hospital center in Dakar, Senegal between January 1, 2005 and December 31, 2016. RESULTS: In all, 80 files were collected. Mean age was 18.5 years, with male predominance. Mean time to treatment was 18.2 days. Cranio-encephalic complications were the most frequent (54 cases; 67.5%): mainly subdural empyema (30 cases) and brain abscess (10 cases). Seventeen patients (21.25%) had oculo-orbital complications: mainly orbital cellulitis (52.9%) and preseptal cellulitis (29.4%). Nine patients (11.25%) had both cranioencephalic and oculo-orbital complications. Acute sinusitis (82.5%) was the main cause of complications. 52.5% of patients showed pansinus involvement. Medical treatment consisted in broad-spectrum antibiotic therapy combining third-generation cephalosporins, metronidazole and gentamycin in cranio-encephalic complications and clavulanic acid and metronidazole in oculo-orbital complications. Thirty-four patients (42.5%) underwent surgical sinus drainage. Neurosurgical drainage was performed in 35 cases (43.75%). Post-treatment course was marked by 6.25% mortality (5 cases) and 16.25% sequelae. CONCLUSION: With 6.25% mortality and a high rate of functional sequelae, complications of sinusitis are a serious concern in our region. Improving prognosis requires earlier management and better coordination between health professionals.

[Cardio-Renal Syndrome In Patients Hospitalized In The Cardiology Department Of The University Hospital Center Yalgado OUEDRAOGO (CHUYO): Epidemiology, Clinic, Paraclinic And Course's Aspects]. / Le Syndrome Cardio-Renal Dans Le Service De Cardiologie Du Centre Hospitalier Universitaire Yalgado OUEDRAOGO (CHU-YO) : Aspects Epidemiologiques, Cliniques, Para-Cliniques Et Evolutifs.

OBJECTIVE: The objective of this work was to study cardio-renal syndrome in patients hospitalized in the cardiology department of the University Hospital Center Yalgado OUEDRAOGO (CHUYO). PATIENTS AND METHODS: This was a retrospective, descriptive study for a period of three years, from 1st January 2010 to 31st December 2012. The study incorporated patients with associated signs of Heart Failure (HF) and Renal Insufficiency (RI). Sociodemographic, clinical and paraclinical parameters were considered in the study. We evaluated the value of creatinine clearance at admission and its progress during the hospitalization until patients were discharged. RESULTS: Sample group of 119 patients over the period; the prevalence of the syndrome cardio-renal (CRF) was 10.93%. The mean age of our patients was 52.6 ± 16.6 years. (extremes: 15-85 years). The sex ratio was 1.33. Our patients' medical histories were dominated by high blood pressure (58.8%) and hypertensive heart disease (33.6%). Dyspnea was the major functional sign in our study (84.9%). Left heart failure syndrome (LHFS) was the most frequently encountered clinical picture (91.3%). The mean value of the creatinine clearance at baseline was 41.5 ± 24.3 mL/min/1.73m2. The signs ECGs and Doppler echocardiograms were those of underlying heart disease: the hypertensive heart disease. An abdominal-pelvic ultrasound found a bilateral kidney failure in 65.7% cases. The average length of hospitalization was 17.7 ± 17.5 days. Death occurred in 19.5% cases. CONCLUSION: The prevalence of CRS was high in the CHU-YO. The prognosis was largely influenced by whether it was an acute or chronic kidney failure. Emphasis should be placed on primary prevention of CRS, early diagnosis and etiology of renal failure.

OBJECTIF: L'objectif de ce travail était d'étudier du syndrome cardio-rénal chez des malades hospitalisés dans le service de cardiologie du CHUYO. PATIENTS ET MÉTHODES: Il s'est agi d'une étude rétrospective à visée descriptive sur une période de trois ans allant du 1er janvier 2010 au 31 décembre 2012. Ont été inclus les dossiers de malades ayant des signes d'Insuffisance Cardiaque (IC) associés une Insuffisance Rénale (IR). Les paramètres sociodémographiques, cliniques et para-cliniques ont été étudiés. Nous avons évalué la valeur de la clairance de la créatinine à l'entrée et son évolution au cours de l'hospitalisation jusqu'à la sortie des patients. RÉSULTATS: Ainsi, nous avons retenu 119 sur la période; la prévalence du syndrome cardio-rénal (SCR) était de 10,93%. L'âge moyen de nos patients était de 52,6 ± 16,6 ans (extrêmes : 15-85 ans). Le sex-ratio était de 1,33. Les antécédents de nos patients étaient dominés par l'hypertension artérielle (58,8%) et les cardiopathies hypertensives (33,6%). La dyspnée constituait le signe fonctionnel majeur dans notre étude (84,9%). Le syndrome d'insuffisance cardiaque gauche (ICG) constituait le tableau clinique le plus fréquemment rencontré (91,3%). La valeur moyenne de la clairance de la créatininémie à l'entrée était de 41,5 ± 24,3 ml/min/1,73m2. Les signes ECG et échocardiographies Doppler étaient ceux de la cardiopathie sous jacente : la cardiopathie hypertensive. Une échographie abdomino-pelvienne retrouvait une souffrance rénale bilatérale dans 65,7% des cas. La durée d'hospitalisation moyenne était de 17,7 ± 17,5 jours. Le décès est survenu dans 19,5% des cas. CONCLUSION: La prévalence du SCR était élevée dans le service de cardiologie du CHU-YO. Son pronostic était largement influencé par le caractère aigu ou chronique de l'insuffisance rénale. L'accent doit être mis sur la prévention primaire du SCR, le diagnostic précoce et étiologique de l'insuffisance rénale.

A mouse model with features of familial combined hyperlipidemia.

Familial combined hyperlipidemia (FCHL) is a common inherited lipid disorder, affecting 1 to 2 percent of the population in Westernized societies. Individuals with FCHL have large quantities of very low density lipoprotein (VLDL) and low density lipoprotein (LDL) and develop premature coronary heart disease. A mouse model displaying some of the features of FCHL was created by crossing mice carrying the human apolipoprotein C-III (APOC3) transgene with mice deficient in the LDL receptor. A synergistic interaction between the apolipoprotein C-III and the LDL receptor defects produced large quantities of VLDL and LDL and enhanced the development of atherosclerosis. This mouse model may provide clues to the origin of human FCHL.

[Two cases of Crimean-Congo haemorrhagic fever (CCHF) in two tourists in Senegal in 2004]. / Deux cas de fièvre hémorragique de Crimée-Congo (FHCC) contractée au Sénégal, en 2004, par des résidentes temporaires.

Two cases of Crimean-Congo haemorrhagic fever (CCHF) occurred in two French tourists during their visit in Senegal in November 2004. Febrile and hemorrhagic syndrome with ulorrhagia, petechiae, haematemesis, haematomas associated with biological signs of disseminated intramuscular coagulation were observed. For the first case who had a medical evacuation to France before diagnosis, Crimean-Congo virus infection was revealed by laboratory tests performed by the National Reference Center for Hemorrhagic Fevers (NRCHF, Institut Pasteur, Lyon) and secondly by the Centre de Référence OMS sur la Recherche des Arbovirus et des virus des Fièvres Hémorragiques (CRORA) in the Dakar Pasteur Institute (DPI). The second case diagnosed by the CRORA died after clinical deterioration with liver failure and severe haemorrhages. Healthcare workers and family members who had contact with tissue or blood from patients were followed up after the putative exposure either in France or in Senegal.

[Solitary neurofibroma of the maxillary sinus]. / Neurofibrome isolé du sinus maxillaire.

OBJECTIVE: To illustrate the rarity and difficulty diagnosing maxillary sinus neurofibroma through a case report. PATIENTS AND METHODS: A 35-year-old female consulted our department for left cheek swelling evolving over 6 months, upper gum swelling, and a dental occlusion disorder. RESULTS: A computed tomography scan showed a tumor of the left maxillary sinus with bone destruction. Histological examination of a biopsy fragment found an in situ carcinoma. A maxillary resection was performed to excise the tumor. Histological examination of the specimen showed a neurofibroma. No sign of recurrence was noted after 8 months of follow-up. CONCLUSION: The difficulty diagnosing maxillary sinus neurofibroma is related to its nonspecific clinical and radiological signs. Consequently, the otorhinolaryngologist must keep this rare histological variety in mind within the range of tumors of the paranasal sinuses.

Hypertensive crises in sub-Saharan Africa: Clinical profile and short-term outcome in the medical emergencies department of a national referral hospital in Burkina Faso.

BACKGROUND: Data on hypertensive crises (HC) are limited in sub-Saharan Africa (SSA). We aimed to characterize the pattern and short-term mortality of hypertensive emergencies (HE) and urgencies (HU). METHODS: This was a prospective cohort study. Consecutive patients with acute and severely elevated blood pressure (systolic>180mmHg and/or diastolic >120mmHg) with or without acute target-organs damage attending the emergency department (ED) of the Teaching Hospital of Yalgado Ouedraogo, Ouagadougou, Burkina Faso were included with a one-month follow-up. RESULTS: One hundred and sixty-six of 1254 patients presenting to the ED (January to march 2016) had HC (13.2%) and 113 of them (68.1%) had HE. The mean age was 50.9±15.9 years and males were 63.3% (n=105). Younger age (<45 years) accounted for 55% of the cases. History of known HTN was reported in 101 patients (60.8%). Among patients with HE, 62.8% had brain-related events, 30.1% had cardiac involvement and 31% had acute renal impairment. The overall survival rate was 89% within the first 72hours and 81% at fourteen days follow-up. At one-month follow-up, 36 patients died with a survival rate of 77.8%. Factors independently associated with death were history of known hypertension, acute brain-related damage and renal dysfunction and not being transferred to a specialized department. CONCLUSION: HC are not rare in SSA and are associated with higher morbidity and mortality in HE. Further studies are needed to determine factors that promote HC in African patients in order to better address the prevention and management strategies of such hypertensive entity.

Cholesterol efflux pathways and other potential mechanisms involved in the athero-protective effect of high density lipoproteins.

Plasma high density lipoprotein (HDL) levels bear a strong independent inverse relationship with atherosclerotic cardiovascular disease. Although HDL has anti-oxidant, anti-inflammatory, vasodilating and anti-thrombotic properties, the central anti-atherogenic activity of HDL is likely to be its ability to remove cholesterol and oxysterols from macrophage foam cells, smooth muscle cells and endothelial cells in the arterial wall. To some extent, the pleotropic athero-protective properties of HDL may be related to its ability to promote sterol and oxysterol efflux from arterial wall cells, as well as to detoxify oxidized phospholipids. In cholesterol-loaded macrophages, activation of liver X receptors (LXRs) leads to increased expression of adenosine triphosphate (ATP) binding cassetter transporter (ABCA1), ATP binding cassetter transporter gene (ABCG1) and apoE and promotes cholesterol efflux. ABCA1 stimulates cholesterol efflux to lipid-poor apolipoproteins, whilst ABCG1 promotes efflux of cholesterol and oxysterols to HDL. Despite some recent setbacks in the clinical arena, there is still intense interest in therapeutically targeting HDL and macrophage cholesterol efflux pathways, via treatments with niacin, cholesterol ester transfer protein inhibitors, LXR activators and infusions of apoA-1, phospholipids and peptides.

[The otolaryngological manifestations of gastroesophageal reflux disease]. / Manifestations oto-rhino-laryngologiques du reflux gastro-oesophagien (RGO).

The otolaryngological symptoms during gastro-oesophageal reflux disease may be very frequent. When the global estimation in the literature go round 20%, the prevalence in the African studies is variable, between 4 and 43 %. The most common disease encountered are laryngitis and pharyngitis's manifestations. When it is not possible to perform the oesophageal pH-metry, the most sensitive examination in gastro-oesophageal reflux, endoscopic examination and therapeutic test with IPP can be proposed to any patient with ENT symptoms and manifestations of gastro-oesophageal reflux.

Mechanisms of enhanced cholesteryl ester transfer from high density lipoproteins to apolipoprotein B-containing lipoproteins during alimentary lipemia.

In vitro lipoprotein lipase enhances the cholesteryl ester transfer protein (CETP)-mediated transfer of cholesteryl esters from high density lipoproteins (HDL) to very low density lipoproteins as a result of lipolysis-induced alterations in lipoprotein lipids that lead to increased binding of CETP. To determine if there are similar changes during alimentary lipemia, we measured the transfer of cholesteryl esters from HDL to apo B-containing lipoproteins in incubated fasting and postprandial plasma. In seven normolipidemic subjects there was 2-3-fold stimulation of cholesteryl ester transfer in alimentary lipemic plasma. Cholesteryl ester transfer was stimulated when either the d less than 1.063-or d greater than 1.063-g/ml fraction of lipemic plasma was recombined with its complementary fraction of fasting plasma. To determine the distribution of CETP, plasma was fractionated by agarose chromatography and CETP activity was measured in column fractions in a standardized assay. In fasting plasma, most of the CETP was in smaller HDL, and a variable fraction was nonlipoprotein bound. During lipemia there was increased binding of CETP to larger phospholipid-enriched HDL and in two subjects an increase in CETP in apo B-containing lipoproteins. The total CETP activity of fractions of lipemic plasma was increased 1.1-1.7-fold compared with fasting plasma. Lipemic CETP activity was also increased when measured in lipoprotein-free fractions after dissociation of CETP from the lipoproteins. When purified CETP was incubated with phospholipid-enriched HDL isolated from alimentary lipemic or phospholipid vesicle-treated plasma, there was increased binding of CETP to the phospholipid-enriched HDL compared with fasting HDL, with a parallel stimulation in CETP activity. Thus, the pronounced stimulation of cholesteryl ester transfer during alimentary lipemia is due to (a) an increased mass of triglyceride-rich acceptor lipoproteins, (b) a redistribution of CETP, especially increased binding to larger phospholipid-enriched HDL, and (c) an increase in total activity of CETP, perhaps due to an increased CETP mass.

Sterol upregulation of human CETP expression in vitro and in transgenic mice by an LXR element.

The cholesterol ester transfer protein (CETP) facilitates the transfer of HDL cholesterol esters from plasma to the liver. Transgenic mice expressing human CETP, controlled by its natural flanking region, increase expression of this gene in response to hypercholesterolemia. We established a CETP promoter-luciferase reporter assay in differentiated 3T3-L1 adipocytes to map the sterol upregulatory element. Promoter mutagenesis suggested that a direct repeat of a nuclear receptor binding sequence separated by 4 nucleotides (DR4 element, -384 to -399) was responsible for this activity. Using mice carrying normal or mutated promoter sequences, we confirmed the importance of this element for gene induction by dietary sterol. A gel retardation complex containing LXR/RXR was identified using the CETP DR4 element and adipocyte nuclear extracts. Both LXRalpha/RXRalpha and LXRbeta/RXRalpha transactivated the CETP promoter via its DR4 element in a sterol-responsive fashion. Thus, the positive sterol response of the CETP gene is mediated by a nuclear receptor binding site that is activated by LXRs. That Cyp7a, the rate-limiting enzyme for conversion of cholesterol into bile acids in the liver, is also regulated by LXRalpha suggests that this class of nuclear receptor coordinates the regulation of HDL cholesterol ester catabolism and bile acid synthesis in the liver.

Plasma lipid transfer protein as a determinant of the atherogenicity of monkey plasma lipoproteins.

This study was undertaken to determine potential tissue sources of plasma cholesteryl ester transfer protein (CETP), and to assess the influence of CETP on lipoprotein concentrations and atherosclerosis. In a group of 28 cynomolgus monkeys fed high fat, high cholesterol diets, plasma CETP concentration was strongly correlated with the abundance of CETP mRNA in liver and in adipose tissue, and with the output of CETP in liver perfusates. Plasma CETP concentration showed a strong inverse correlation with HDL cholesterol concentrations (r = -0.62, P less than 0.001) and a positive correlation with LDL cholesterol concentration (r = 0.54, P less than 0.005) and molecular weight (r = 0.57, P less than 0.001). The extent of coronary artery atherosclerosis was positively correlated with LDL cholesterol concentration and molecular weight, and with plasma CETP concentration. Thus, in monkeys fed an atherogenic diet, individual variation in CETP mRNA abundance in liver and adipose tissue probably plays a major role in the determination of plasma CETP levels. In plasma, CETP influences the distribution of cholesteryl esters between LDL and HDL, and CETP concentration appears to be a key determinant of the relative atherogenicity of the plasma lipoproteins.

Foam cell-forming J774 macrophages have markedly elevated acyl coenzyme A:cholesterol acyl transferase activity compared with mouse peritoneal macrophages in the presence of low density lipoprotein (LDL) despite similar LDL receptor activity.

Cholesteryl ester (CE) accumulation in arterial wall macrophages (foam cells) is a prominent feature of atherosclerotic lesions. We have previously shown that murine J774 macrophages, unlike mouse peritoneal macrophages, accumulate large amounts of CE from unmodified low density lipoprotein (LDL). We now report a direct comparison of acyl coenzyme A:cholesterol acyl transferase (ACAT) activity in J774 and mouse peritoneal macrophages. Despite similar chloroquine-inhibitable 125I-LDL degradation in the two macrophages, ACAT activity in LDL-treated J774 macrophages was 10-30-fold higher than that in LDL-treated mouse peritoneal macrophages. In contrast, acetyl-LDL (matched for degradation with LDL) caused marked stimulation of ACAT activity in mouse peritoneal macrophages. From these data we conclude that in the presence of LDL, J774 macrophages have a highly active ACAT cholesterol esterification pathway compared with mouse peritoneal macrophages; and in mouse peritoneal macrophages, there is a marked difference in the ability of acetyl-LDL vs. LDL to stimulate ACAT even when the lipoproteins are matched for degradation.