Nocturnal continuous measurement of blood pressure in sleep apnea syndromes. Comparison between normotensive and hypertensive patients

Sleep apnea syndrome and systemic hypertension are frequently associated but their causal relationship is unclear. We compared the oscillations of systemic blood pressure and heart rate during polysomnography in 8 normotensive subjects (2 females) and 5 hypertensive (supine awake blood pressure: 165 +/- 7/96 +/- 5 mmHg) without treatment. Their ages (normotensive: 52.1 +/- 11.0 yrs, hypertensive: 51.2 +/- 6.4 yrs) and body mass indices (32.6 +/- 9.6 kg/m2 vs 33.2 +/- 5.2 kg/m2 respectively) were not statistically different. Systemic blood pressure was continuously monitored by a non invasive digital plethysmography (Finapres). Both groups had similar respiratory events indices (normotensive: 45.2 +/- 18.1/hr, hypertensive: 48.4 +/- 20.5/hr) and minimal oxygen saturations (79.4 +/- 9.1% vs 82.4 +/- 7.0% respectively). During apneas in slow-wave sleep were observed the minimal values for systolic and diastolic pressures which were significantly higher in hypertensive than in normotensive (138.2 +/- 9.6/83.2 +/- 16.1 mmHg vs 105.9 +/- 11.1/60.5 +/- 10.9 mmHg respectively). During resumption of ventilation maximal blood values were recorded which were also higher in hypertensive than in normotensive (185.0 +/- 13.8/113.2 +/- 21.5 mmHg vs 155.9 +/- 19.8/88.7 +/- 17.1 mmHg respectively) (p less than 0.05). Although absolute variations of blood pressure were similar, relative changes in systolic pressure were significantly higher in normotensive (p less than 0.05). Maximal heart rate was 76.8 +/- 6.2 bpm in normotensive and 76.6 +/- 3.9 bpm in hypertensive during resumption of ventilation.(ABSTRACT TRUNCATED AT 250 WORDS)     

Stable micro-dystrophin gene transfer using an integrating adeno-retroviral hybrid vector ameliorates the dystrophic pathology in mdx mouse muscle

The ability to transfer the dystrophin gene stably to the skeletal muscle of DMD patients is a major confounding issue in establishing an effective gene therapy for this disease. To overcome this problem, we have examined the ability of muscle fibres from mdx mice to act as in situ factories of retroviral vector production. Tibialis anterior (TA) muscles from 4-week-old mdx mice were injected with an adenoviral vector expressing LacZ within a retroviral expression cassette (AdLZIN). Retroviral vector production was induced by the inclusion of two additional adenoviral vectors expressing retroviral gag-pol (AdGagPol) and 10A1 env genes (Ad10A1). Upon introduction of infected muscles into cell culture, colonies of beta-galactosidase-expressing myotubes formed only in cultures where the muscle was injected with AdLZIN, AdGagPol and Ad10A1, but not from muscle injected with AdLZIN only. Muscles from mdx/nude mice producing retroviral vector displayed a 4.6-fold increase in beta-galactosidase-positive myofibres after 1 month, compared with contralateral muscle in the same animal injected with AdLZIN and AdGagPol only. By constructing a hybrid adeno-retroviral vector expressing a truncated micro-dystrophin construct (AdmicroDyIN), we were able to partially correct the mdx dystrophic phenotype. AdmicroDyIN-mediated expression of micro-dystrophin in mdx TA muscle restored the formation of the dystrophin-associated glycoprotein complex and significantly reduced the level of muscle degeneration over uninjected controls. By stimulating in situ production of retroviral vector expressing micro-dystrophin, we achieved 92%+/-6% transduction of myofibres in the TA muscle by 4 weeks. Strikingly, by 3 months post injection, micro-dystrophin was still expressed to high levels in nearly all the myofibres of the TA muscle. By comparison, there was a pronounced drop in the levels of micro-dystrophin expressed by muscles injected with AdmicroDyIN only. Finally, using a novel PCR approach, we detected reverse-transcribed, integrated proviral sequences in TA muscle genomic DNA by 4 weeks post injection, the levels of which were found to increase after 3 months.     

Methods of leaks detection under therapy with continuous positive airway pressure

To assess the performance of continuous positive airway pressure devices in treatment of sleep breathing disorders during polysomnographic studies, analysis are based essentially on the patient airflow signal measured by a pneumotachograph and the mask pressure. These signals used either by the softwares or the physicians provide powerful information on respiratory events occurring during the night. However, sometimes signals are artifacted by airflow leaks at the mask or the mouth. These artifacts are causes of information loss and then of possible wrong interpretations. We studied the relationship between airflow and mask pressure at the occurrence of leaks. We used analogy with electrical models and Kirchoff laws to estimate mask leaks and to detect mouth breathing. A Starling model connected to a flow generator simulated respiratory movements. A positive pressure was maintained in the model and artificial leaks comparable to mask leaks were provoked. Then, we replaced the Starling model and the flow generator by two healthy volunteers. We computed mask leaks in both conditions and found no contradiction between the simulated model and the subjects. Equations of the analog circuit were helpful to assess mask leaks and to detect mouth breathing. Such equations could be included in polysomnographs or in pressure generator algorithms either for detecting leaks or adjusting airway pressure.     

Th1 cell development induced by cysteine proteinases A and B in localized cutaneous leishmaniasis due to Leishmania guyanensis

The cysteine proteinases CPA and CPB from Leishmania major induced Th1 responses in patients with leishmaniasis due to Leishmania guyanensis. Furthermore, cysteine proteinases induced neither interleukin 4 (IL-4) nor IL-13 and low levels of IL-10 in controls and patients. The results suggest that CPs would be quite good candidates for a vaccine against different Leishmania species.     

Loss of RhoB expression in human lung cancer progression.

PURPOSE: RhoB is a low molecular weight GTPase belonging to the Ras protein superfamily. Whereas most Rho proteins have been shown to have a positive role in proliferation and malignant transformation, the specific role of RhoB appears more divergent. We reported previously that RhoB inhibits cell proliferation in various human cancer cells. Here, we studied the specific role played by RhoB in human lung cancer. EXPERIMENTAL DESIGN: We analyzed the expression of RhoB protein by immunostaining in human lung tissues ranging from normal to invasive carcinoma from different histological types in two large independent studies of, respectively, 94 and 45 samples. We then studied the cellular effect of RhoB overexpression in a model of lung cancer (A549, adenocarcinoma) and tumorigenicity in nude mice. RESULTS: We showed in both studies that RhoB protein was expressed in normal lung and decreased dramatically through lung cancer progression (P < 0.01). Interestingly, RhoB expression was lost in 96% of invasive tumors and reduced by 86% in poorly differentiated tumors compared with the nonneoplastic epithelium. Moreover, the loss of expression of RhoB correlated significantly with tumor stage and proliferative index, whereas no correlation was found between RhoB and p53 or Bcl-2 expression. We then showed that ectopic expression of RhoB in lung cancer cell line A549 suppressed cell proliferation, anchorage-independent growth, and xenograft tumor growth in nude mice. CONCLUSIONS: RhoB loss of expression occurs very frequently in lung carcinogenesis, reinforcing its putative tumor suppressive activity, and raising the value of its potential use in cancer therapy.     

Nicotine-associated cues maintain nicotine-seeking behavior in rats several weeks after nicotine withdrawal: reversal by the cannabinoid (CB1) receptor antagonist, rimonabant (SR141716).

Conditioned stimuli are important for nicotine dependence and may trigger craving and relapse after prolonged nicotine abstinence. However, little is known about the pharmacology of this process. Among the systems that have been shown to play a role in drug-seeking behavior is the endocannabinoid transmission. Therefore, the present study examined the resistance to extinction of drug-seeking behavior elicited by nicotine-associated environmental stimuli and the effects of the selective CB1 cannabinoid antagonist rimonabant (SR141716) on the reinforcing effects of nicotine-related stimuli. Rats were trained to self-administer nicotine (0.03 mg/kg/injection, i.v.) under conditions in which responding was reinforced jointly by response-contingent nicotine injections and stimuli (light and tone). After self-administration acquisition, nicotine was withdrawn and lever pressing was only reinforced by contingent presentation of the audiovisual stimuli. Under such a condition, responding persisted for 3 months, following which nonpresentation of the cues produced a progressive extinction of responding. As expected, rats trained to lever-press for saline injections paired with the audiovisual stimuli did not acquire the self-administration. These findings indicate that the cues required learned association with nicotine to acquire reinforcing properties and to function as conditioned reinforcers. When administered 1 month following nicotine withdrawal, rimonabant (1 mg/kg, i.p.) decreased conditioned behavior. These results showing the persistence of a nicotine-conditioned behavior are congruent with the role of nicotine-related environmental stimuli in nicotine craving in abstinent smokers. Rimonabant, which has been shown previously to reduce nicotine self-administration, may be effective not only as an aid for smoking cessation but also in the maintenance of abstinence.     

An integrative view of Luria’s perspective on arithmetic problem solving: The two sides of environmental dependency

Introduction: A. R. Luria was the first author to hypothesize that executive dysfunction can lead to specific deficits in arithmetic problem solving, showing that patients’ performance depends on the structure of the tasks. Cummings (1995. Anatomic and behavioral aspects of frontal-subcortical circuits. Annals of the New York Academy of Sciences, 15, 1–13) proposed the term “environmental dependency” to define such behavioral disorders triggered by the characteristics of the test and pointed out also the role of executive impairments. Few studies compare executive functioning and problem solving in brain-damaged patients, and none have examined the question from this point of view. Thus, the main aim of the present paper was to study the relationship between environmental dependency and executive functions. Method: Fifty neurological patients with frontal, subcortical, and posterior brain lesions were compared to 45 matched healthy controls and were divided into two groups (dysexecutive/nondysexecutive) according to their performances on executive tasks. Then, we confronted the results of the two groups on an experimental protocol designed in accordance with Luria’s proposals. We made also comparisons between groups on the basis of lesion location. Results: Our findings indicate a high association between executive functions and environmental dependency, showing that dysexecutive patients’ performances were dependent on task demands. In addition, a specific frontal behavior not associated with executive functions and characterized by the solving of insoluble problems was highlighted. Conclusion: The discussion focused on the interest to take into account the methodological and clinical contributions of environmental dependency. Based on our findings and theoretical arguments, we highlight the need to fractionate this concept.