Brucella central carbon metabolism: an update.

The brucellae are facultative intracellular pathogens causing brucellosis, an important zoonosis. Here, we review the nutritional, genetic, proteomic and transcriptomic studies on Brucella carbon uptake and central metabolism, information that is needed for a better understanding of Brucella virulence. There is no uniform picture across species but the studies suggest primary and/or secondary transporters for unknown carbohydrates, lactate, glycerol phosphate, erythritol, xylose, ribose, glucose and glucose/galactose, and routes for their incorporation to central metabolism, including an erythritol pathway feeding the pentose phosphate cycle. Significantly, all brucellae lack phosphoenolpyruvate synthase and phosphofructokinase genes, which confirms previous evidence on glycolysis absence, but carry all Entner-Doudoroff (ED) pathway and Krebs cycle (and glyoxylate pathway) genes. However, glucose catabolism proceeds through the pentose phosphate cycle in the classical species, and the ED pathway operates in some rodent-associated brucellae, suggesting an ancestral character for this pathway in this group. Gluconeogenesis is functional but does not rely exclusively on classical fructose bisphosphatases. Evidence obtained using infection models is fragmentary but suggests the combined or sequential use of hexoses/pentoses, amino acids and gluconeogenic substrates. We also discuss the role of the phosphotransferase system, stringent reponse, quorum sensing, BvrR/S and sRNAs in metabolism control, an essential aspect of the life style of facultative intracellular parasites.

[Varenicline: an aid to smoking cessation therapy]. / Le sevrage tabagique: une nouvelle molécule orale, la varenicline (Champix).

Varenicline orally administered nicotine acetylcholine receptor partial agonist is approved by the US FDA and the MEA for use as an aid to smoking cessation therapy. Varenicline is more effective than bupropion but does not reduce weight gain after cessation. The superiority of de varenicline on the nicotine is not demonstrated. Nausea is a frequent adverse effect. The long term safety of varenicline is unknown. The major weapons for smoking cessation are represented by the motivation of the patient and a long term psychotherapy. As to the subject of drugs, varenicline is situated in second position, after the failure of a nicotine substitute.

[Omalizumab, an anti-IgE monoclonal antibody to treat severe asthma]. / L'omalizumab (Xolair), un anticorps monoclonal anti-IgE pour traiter l'asthme sévère.

Omalizumab (Xolair) is the first representative of a new therapeutical class for severe allergic asthma. By neutralizing Ac IgE, omalizumab fulfils an anti-inflammatory action of which the effect has been shown beneficial in the treatment of severe allergic asthma and particularly in severe asthma for which the therapeutical arsenal is for the time being disappointing and associated to frequent side effects there where omalizumab is well tolerated.

[Insulin analogues: place of detemir (Levemir)]. / Les analogues de l'insuline: la place de la détémir (Levemir).

Insulin detemir (Levemir) is a soluble long-acting human insulin analogue acylated with a 14-carbon fatty acid. Insulin detemir is 98-99% albumin bound in plasma. It has a more predictable glucose-lowering effect than NPH insulin or insulin glargin. There is a dose-response relationship, but at the dose of 0.4 units/kg (an average normal dose), the duration of action reaches nearly 24 h. Therefore, detemir, most often injected once per day at bedtime, seems to be the ideal basal insulin in the basal-prandial therapy for type 1 diabetic patients. The boli of insulin, in order to cover shown to reduce the risk of (severe) hypoglycaemias, particularly nocturnal (up to 50 %). Fasting hyperglycaemia is often lower, but it is not necessarily true for glycated haemoglobin. In addition, detemir has been associated with less weight gain than NPH insulin. Detemir is well tolerated and no specific safety concerns have been raised.

[Insulin analogues: place of detemir (levemir)]. / Les analogues de l'insuline: la place de la détémir (levemir).

Insulin detemir (Levemir) is a soluble long-acting human insulin analogue acylated with a 14-carbon fatty acid. Insulin detemir is 98-99% albumin bound in plasma. It has a more predictable glucose-lowering effect than NPH insulin or insulin glargin. There is a dose-response relationship, but at the dose of 0.4 units/ kg (an average normal dose), the duration of action reaches nearly 24 h. Therefore, detemir, most often injected once per day at bedtime, seems to be the ideal basal insulin in the basal-prandial therapy for type 1 diabetic patients. The boli of insulin, in order to cover the meals, may be done with a rapid acting human insulin and/or a fast acting analogue. In comparison with NPH insulin, detemir has been shown to reduce the risk of (severe) hypoglycaemias, particularly nocturnal (up to 50%). Fasting hyperglycaemia is often lower, but it is not necessarily true for glycated haemoglobin. In addition, detemir has been associated with less weight gain than NPH insulin. Detemir is well tolerated and no specific safety concerns have been raised.

[Omalizumab, an anti-IgE monoclonal antibody to treat severe asthma]. / L'omalizumab (Xolair), un anticorps monoclonal anti-IgE pour traiter l'asthme sévère.

Omalizumab (Xolair) is the first representative of a new therapeutical class, which will be soon available in severe allergic asthma. By neutralizing Ac IgE, omalizumab fulfils an anti-inflammatory action of which the effect has been shown beneficial in the treatment of severe allergic asthma and particularly in severe asthma for which the therapeutical arsenal is for the time being disappointing and associated to frequent side effects there where omalizumab is well tolerated.

[Omega-3 fatty acids and cardiovascular diseases]. / Les acides gras oméga-3 et les pathologies cardio-vasculaires.

Most--but not all--epidemiological studies have demonstrated that omega-3 intake, either from nutrition or supplementation, reduces cardiovascular risk. A few intervention studies have shown a reduction of studden death in patients followed after a myocardial infarction. However EBM studies from the Cochrane Library do not confirm the real advantage of omega-3 in any group of subjects. Probably, the most interesting prescription of omega-3 supplementations would benefit to the patients after myocardial infarction, in addition to drugs that have proved their efficacy (aspirine, beta-blocker statin and ACE inhibitor).

[Pregabalin (Lyrica) and neuropathic pain syndromes]. / La prégabaline (Lyrica) et les douleurs neuropathiques périphériques.

Pregabalin is a novel central nervous system (CNS) drug with no interaction at benzodiazepine or GABA receptor. Its mechanism of action is correlated with its high affinity for the alpha/delta submit of the voltage-dependant CNS calcium channel. Pregabalin is rapidly absorbed with at least 90% bioavailable irrespective of dose, does not bind to plasma proteins and is excreted virtually unchanged by the kidneys. Pharmacokinetics are linear and predictable across the therapeutic dose range (150-600 mg/ day). Pregabalin is indicated, like gabapentin, in the treatment of neuropathic pain syndromes like post-herpetic neuralgia (PHN) and diabetic polyneuropathy (DPN). Efficacy in other neuropathic pain syndromes need further investigations. This paper emphasizes advantages and disadvantages on a clinical point of view.

[Inhaled human insulin (Exubera): a revolution?]. / L'insulinothérapie par voie inhalée (Exubera), une révolution?

Type 2 diabetes is a step by step process which, at the end, leads to insulin injections. This last step is accomplished in many cases with great delay which increases the risk of micro- and macro-vascular complications. Patients are often reluctant to accept insulin injections and clinicians frequently postpone insulin prescription for many reasons. Any method which could favour more insulin initiation is welcome and this is the case with inhaled insulin. Efficacy has been demonstrated in type 2 and type 1 patients as well as safety if indications are strictly followed by patients and physicians. Long-term results (about 4 years) have been published, indicating efficacy and safety. At the present time, no cost/benefit study has been published and the extra cost of such a treatment will probably retard its clinical application.

[Rimonabant (Acomplia), specific inhibitor of the endocannabinoid system]. / Le rimonabant (Acomplia), inhibiteur spécifique du système endocannabinoïde.

The endocannabinoid system plays a major role in the regulation of body energy by stimulation of the appetite in the hypothalamus and increase of fat accumulation in adipocytes. The blockade of the cannabinoid system (CB1) by the specific inhibitor (rimonabant) decreases food intake and adiposity in animals and in humans. Moreover rimonabant lowers tobacco addiction. Clinical studies (RIO-LIPIDS and RIO-EUROPE) have recently confirmed that rimonabant combined with a hypocaloric diet over 1 year, promoted significant decrease of body weight, waist circumference and improvement of dyslipidemia. Rimonabant was well tolerated with mild and transient side effects. The future place of rimonabant in the strategy of obesity is still to be clarified.

[Rimonabant (Acomplia), specific inhibitor of the endocannabinoid system]. / Le rimonabant (Acomplia), inhibiteur spécifique du système endocannabinoïde.

The endocannabinoid system plays a major role in the regulation of body energy by stimulation of the appetite in the hypothalamus and increase of fat accumulation in adipocytes. The blockade of the cannabinoid system (CB1) by the specific inhibitor (rimonabant) decreases food intake and adiposity in animals and in humans. Moreover rimonabant lowers tobacco addiction. Clinical studies (RIO-LIPIDS and RIO-EUROPE) have recently confirmed that rimonabant combined with a hypocaloric diet over 1 year, promoted significant decrease of body weight, waist circumference and improvement of dyslipidemia. Rimonabant was well tolerated with mild and transient side effects. The future place of rimonabant in the strategy of obesity is still to be clarified.

[Dutasteride (Avodart): a novel 5-alpha reductase inhibitor for treatment of benign prostate hypertrophy]. / Dutasteride (Avodart): un nouvel inhibiteur de la 5-alpha réductase pour traiter l'hypertrophie bénigne de la prostate.

Dutasteride (Avodart), a novel dual 5-alpha reductase inhibitor is effective for the treatment of benign prostate hypertrophy, of more than 30 cc because the reduction of the level of dihydrotestosterone. By reducing prostatic volume, dutasteride improves moderate to severe symptoms and flow rate. It allows a reduction of disease progression by reducing the rate of acute urinary retention and need for surgery.

[Treatment of Paget's disease of bone with zoledronic acid]. / Le traitement de la maladie osseuse de Paget par l'acide zolédronique.

Bone pain and bone deformities are the most common manifestations of Paget's disease of bone, even if the diagnosis is nowadays most often made by chance following a routine measurement of serum alkaline phosphatase. Woven bone is formed following a marked increase in bone resorption due to a stimulation of osteoclast activity. Biphosphonates constitute the modern treatment of Paget's disease of bone. Tiludronate (Skelid), or better risedronate (Actonel), are administered orally every day during at least 2 months. Zoledronic acid (Aclasta), as a single 15-min 5 mg infusion, has been recently compared to risedronate, 30 mg/d orally for 2 months, in two randomized studies including 357 patients. Zoledronic acid had a superior therapeutic efficacy, as judged by its rapidity of action, the duration of the biochemical response and the percentage of responders. Thus, at 6 months, alkaline phosphatase levels were normalized in 89% of the patients in the zoledronic acid group as compared to 58% in the risedronate group. The most frequent side effect was a flu-like syndrome, observed in 10% of the patients. An adequate intake of calcium and vitamin D is recommended to avoid posttreatment hypocalcemia. The introduction of Aclasta should simplify and improve the therapeutic management of Paget's disease of bone.

[Obesity in adult patients: check up and treatment]. / L'obésité chez l'adulte: mise au point et prise en charge.

Obesity is now one of the major health problems in industrial countries as well as in developing world. Excess caloric intake and reduction of the physical activity are the main causes of obesity. This epidemic precedes a tremendous increase of type 2 diabetes, which is generally linked to weight excess. Obesity and type 2 diabetes are associated with morbidity and mortality and are very expensive for the social security. The important point is to define the risks linked to obesity taking into account the Body Mass Index and the importance of visceral obesity evaluated by waist measurement. After medical check up, a strategy will be discussed with the patient, including moderate caloric restriction and increased physical activity. Our patients and also some doctors suggest "popular diets" whose efficacy has not been demonstrated as superior. On a short time basis, low carbohydrate and high protein diets have some advantages, which can help our obese subjects but on long term, only hypocaloric and equilibrated diets are advisable. Drugs that proved their efficacy and tolerance may be prescribed in case of failure. Three drugs are presented, orlistat, sibutramine and metformine: their efficacy, secondary effects, interactions and finally their positioning. Bariatric surgery will be proposed to highly selected patients presenting morbid obesity.

Spironolactone and altizide in systemic hypertension: ambulatory multicenter study.

A multicenter study was performed in 919 hypertensive patients, 780 of whom could be evaluated. Patients in group I (n = 482) were treated with Aldactazine alone (altizide + spironolactone, 2 tablets per day). The other 298 patients (group II) were treated with 1 or 2 tablets per day of Aldactazine plus a conventional antihypertensive agent, e.g., a beta blocker, alpha-methyldopa or clonidine. After 45 days of treatment with Aldactazine alone, mean systolic and diastolic blood pressure (BP) decreased by 15 and 14%, respectively, vs baseline values. The addition of the other antihypertensive agent decreased BP further; however, the best results were obtained with the combination of Aldactazine and clonidine. With this combination, systolic and diastolic BP decreased by 16.6 and 18%, respectively, vs baseline. In terms of adverse effects, a few cases of gastrointestinal disturbances and orthostatic hypotension were reported.

Effect of antihypertensive treatment on office and self-measured blood pressure: the Autodil study.

OBJECTIVE: To examine prospectively the effects of antihypertensive therapy on office blood pressure (BP) and home BP, in a large-scale hypertensive population followed by their general practitioners. PATIENTS: A total of 760 hypertensive patients either never treated or after a 2-week washout period, aged 18-75 years, with a diastolic office BP between 95 and 110 mm Hg and a systolic office BP below 180 mm Hg. METHODS: Patients measured their BP at home using an automated printer-equipped oscillometric device (OMRON-HEM 705 CP) twice daily for 8 days before the visit to their general practitioner who recorded three office BP. These measurements were performed before and after 8 weeks of antihypertensive therapy with sustained-release diltiazem 300 mg once daily. RESULTS: Diltiazem reduced systolic and diastolic office BP and home BP and heart rate (P < 0.01). Systolic and diastolic office BP were higher than home BP before (P < 0.01) but not during treatment. Correlation coefficients between the two methods before and during therapy were 0.6 and 0.7 for systolic BP and 0.4 and 0.6 for diastolic BP (P < 0. 01). Both methods did not agree equally throughout the range of BP: home BP was higher than office BP for high values and lower for low values. CONCLUSION: The results show that BP measured at home by patients can be higher than office BP in the highest range of BP. Journal of Human Hypertension (2000) 14, 525-529

Open randomized study comparing doxycycline and co-amoxiclav in the treatment of acute suppurative tracheobronchitis in adults. The Collaborative Group of the Centre Universitaire de Medécine Générale de L'Université Libre de Bruxelles (CUMG-ULB) Investigators.

Doxycycline and co-amoxiclav were compared in a randomized clinical trial involving adult patients with acute suppurative tracheobronchitis. Patients were treated for 5 to 10 days with either antibiotic following three schemes: co-amoxiclav 500 mg three times daily, or doxycycline 200 mg on day 1 followed by 100 mg daily, or 200 mg daily. Assessment after 5-9 days was based only on clinical parameters. Patients with inadequate response to the initial treatment were crossed over to the alternative antibiotic. Of the 210 patients enrolled, 206 were available for evaluation of efficacy. Both antibiotic regimens proved equally efficacious, with rates of clinical response (cure or improvement) of 89% and 91% for doxycycline and coamoxiclav, respectively. Patients who were crossed over to the alternative antibiotic had a significantly lower cure rate after their second course of antibiotics (22% compared with 70%). Adverse effects, most often of gastro-intestinal origin, were more common in the co-amoxiclav group than in the doxycycline-treated group, but rarely caused cessation of treatment.

Azithromycin compared with clarithromycin in the treatment of adult patients with acute purulent tracheobronchitis: a cost of illness study.

Adult, professionally active patients with acute purulent tracheobronchitis were treated with azithromycin (3 or 5 days; n = 62) or clarithromycin (7 to 10 days; n = 69) in an open, randomized study. Bronchitis-related costs and treatment efficacy were assessed at day 5-6 and day 14-21. Both antibiotics were of equal clinical efficacy, although the median time to improvement of symptoms was significantly shorter for azithromycin patients than for clarithromycin patients. Some 77% of azithromycin patients and 78% of clarithromycin patients were unable to work for at least 1 day. The total time when patients were unable to work was shorter for azithromycin patients than for clarithromycin patients, but this difference did not remain significant when weekends and holidays were taken into account. Further studies are needed to assess the impact of azithromycin on time to clinical improvement, on lost working days, and on the associated costs.

[A case of mesenteric venous thrombosis. Review of the literature]. / A propos d'un cas de thrombose veineuse mésentérique (TVM). Revue de la littérature.

A case is presented in which a venous mesenteric thrombosis necessitated an extended small bowel resection. The postoperative follow-up with its complications is presented. Review of the literature.

[Multiple bacterial resistance in daily practice]. / La multirésistance bactérienne et ses implications au quotidien.

Present and future solutions to the problem of bacterial multiple resistance involve physicians, patients and veterinarians. Their behaviour should evolve to take into account the medical and economical issues of antibiotic prescription. The clinical diagnosis requires a more rigorous assessment, based on bacteriological and rapid antigenic tests. Vaccination in both young people and the elderly, is an essential prophylactic tool, which is too often neglected. When a bacterial infection is suspected or proven, priority should be given to a targeted antimicrobial therapy with a bactericidal activity, in order to quickly eradicate pathogens. Therapies should be shorter and questionable antibioprophylaxis should also be avoided. A watch laboratory network should provide physicians with an adequate information on local bacterial resistance patterns on a regular basis, in order to allow them adjusting their prescription.