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Biomedical subjects

C Amiel

Publications and source records attributed to C Amiel.

At least 19 recordsLinked to original sources

Spontaneous association of hydrophobized dextran and poly-beta-cyclodextrin into nanoassemblies. Formation and interaction with a hydrophobic drug.

New nanoassemblies were instantaneously prepared by mixing two aqueous solutions, one containing a beta-cyclodextrin polymer (pbetaCD), and the other a hydrophobically modified by alkyl chains dextran (MD). The formation mechanism and the inner structure of these nanoassemblies were analysed using surface tension measurements and (1)H NMR spectroscopy. The effect of a hydrophobic guest molecule, such as benzophenone (BZ), on the formation and stability of the nanoassemblies was also evaluated. MD exhibited the typical behaviour of a soluble amphiphilic molecule and adsorbed at the air/water interface. Whereas the injection of native beta-CDs in the solution beneath the adsorbed MD monolayer did not produce any change in the surface tension, that of the pbetaCD resulted in an increase in the surface tension, indicating the desorption of the polymer from the interface. This result accounts for a cooperative effect of beta-CDs linked together in the pbetaCD polymer on dextran desorption. The presence of benzophenone in the system hindered the sequestration of dextran alkyl moieties by beta-CD in the polymer without impeding the formation of associative nanoassemblies of 100-200 nm. (1)H NMR investigations demonstrated that, in the BZ-loaded nanoassemblies, the hydrophobic molecule was mainly located into the cyclodextrin cavities.

Benzophenones↗

DNA compaction into new DNA vectors based on cyclodextrin polymer: surface enhanced Raman spectroscopy characterization.

The ability of DNA to bind polycation yielding polyplexes is widely used in nonviral gene delivery. The aim of the present study was to evaluate the DNA compaction with a new DNA vector using Raman spectroscopy. The polyplexes result from an association of a beta-cyclodextrin polymer (polybeta-CD), an amphiphilic cationic connector (DC-Chol or adamantane derivative Ada2), and DNA. The charge of the polymeric vector is effectively controlled by simple addition of cationic connector in the medium. We used surface enhanced Raman spectroscopy (SERS) to characterize this ternary complex, monitoring the accessibility of adenyl residues to silver colloids. The first experiments were performed using model systems based on polyA (polyadenosine monophosphate) well characterized by SERS. This model was then extended to plasmid DNA to study polybeta-CD/Ada2/DNA and polybeta-CD/DC-Chol/DNA polyplexes. The SERS spectra show a decrease of signal intensity when the vector/DNA charge ratio (Z+/-) increases. At the highest ratio (Z+/- = 10) the signal is 6-fold and 3-fold less intense than the DNA reference signal for Ada2 and DC-Chol polyplexes, respectively. Thus adenyl residues have a reduced accessibility as DNA is bound to the vector. Moreover, the SERS intensity variations are in agreement with gel electrophoresis and zeta potential experiments on the same systems. The overall study clearly demonstrates that the cationic charges neutralizing the negative charges of DNA result in the formation of stable polyplexes. In vitro transfection efficiency of those DNA vectors are also presented and compared to the classical DC-Chol lipoplexes (DC-Chol/DNA). The results show an increase of the transfection efficiency 2-fold higher with our vector based on polybeta-CD.

Animals↗

[Adherence to antiretroviral therapy during HIV infection, a multidisciplinary approach].

Since HIV infection has become a chronic disease, antiretroviral therapy is now used on a long-term basis. Response to treatment is conditioned by numerous inter-dependent factors, including non-compliance, which can result in failure of the therapeutic regimen. Although compliance is crucial for long-term efficacy of the treatment, it is a dynamic factor, and therefore difficult to evaluate. This literature review proposes a multidisciplinary approach to treatment adherence during HIV infection, and deals with the following questions: how should adherence and non-adherence be defined? How are they correlated to the treatment response? How is adherence measured in trials and cohorts, as well as in clinical practice? By what factors is it influenced? What tools can be implemented to improve adherence? The interaction between adherence and response to antiretroviral therapy requires communication between clinicians, healthcare providers, patients, virologists, pharmacologists, and the companies responsible for developing drugs. The pharmaceutical industry must sustain its efforts to ensure a balance between demands for efficacy and adherence when developing new drugs. And the methods implemented by numerous healthcare teams plead in favour of a dynamic approach to adherence, with the active participation of all.

Anti-HIV Agents↗

Surface plasmon resonance study of the interaction of a beta-cyclodextrin polymer and hydrophobically modified poly(N-isopropylacrylamide).

Surface plasmon resonance (SPR) technique is used to follow, both in real time and in situ, the association between a physically adsorbed polymer of beta-cyclodextrin (pbetaCD) and different hydrophobically modified poly(N-isopropylacrylamide) (PNIPAM) copolymers containing either adamantyl or dodecyl groups. This association is due to the complex formation between the hydrophobic groups and the betaCD cavities. Therefore, the adsorbed amount of PNIPAM onto the pbetaCD layer depends on the substituent and on its substitution level. The association and dissociation rate constants are evaluated from the kinetics of PNIPAM adsorption. An estimation of the association constants leads to values higher than 10(4) M(-1), reflecting the strong interaction between these polymers.

Acrylic Resins↗

[Human granulocytic ehrlichiosis in Europe].

Human granulocytic ehrlichiosis is an emerging infectious disease, which is transmitted by the tick Ixodes ricinus in Europe, like other diseases: Lyme disease, tick-borne encephalitis, babesiosis... This tick lives in the forest and its hematophagic activity ranges from April to October. Flu and febrile symptoms ten days after tick bite should suggest diagnosing the disease. Disease evolution is generally favorable, even if serious complications may occur. Leukopenia, thrombocytopenia, and elevated serum transaminases are common laboratory findings. Complementary assays useful for the diagnosis are: blood smear, indirect immunofluorescence, and polymerase chain reaction. Biological diagnostic criteria are more and more accurate, with the evolution of knowledge and technique. Tetracycline treatment generally leads to clinical and biological recovery. Informing physicians and occupationally exposed people should reinforce current prevention measures against tick bites.

Animals↗

BMD is reduced in HIV-infected men irrespective of treatment.

UNLABELLED: Osteoporosis has be reported to be a complication of active antiretroviral therapy of HIV infection. We studied 148 HIV-infected men stratified according to their treatment. Our data show that these patients have an average 9% decreased BMD, irrespective of their treatment. Low body mass index and high resorption markers were associated with low bone density. INTRODUCTION: Osteoporosis has been reported in HIV-infected (HIV+) patients, and it has been suggested that it may be linked to protease-inhibitor treatments (PI). MATERIALS AND METHODS: To assess this risk and to investigate its putative link with treatments, we compared the bone density of HIV+ men, who were either receiving treatment (including PI [PI+], n = 49; without PI [PI-], n = 51) or untreated (UT, n = 48). We included 81 age-matched control HIV-negative (HIV-) males (age, 40 +/- 8 years). RESULTS: BMD adjusted for age (Z-score) was lower in the HIV+ patients at the lumbar spine (HIV+: -1.08 +/- 1.21, HIV-: -0.06 +/- 1.26, p < 0.001) and the femoral neck (HIV+: -0.39 +/- 1.05, HIV-: 0.25 +/- 0.87, p < 0.001). The prevalence of osteoporosis was 16% in HIV+ and 4% in HIV- subjects (p < 0.01). In the HIV+ subjects, the Z-score was correlated only to body mass index (r = 0.27 at lumbar spine and 0.35 at femoral neck). Untreated HIV+ patients had a negative Z-score (-0.82 +/- 1.15 for the lumbar spine), which was not different from the one of treated HIV+ patients. In the PI+ and PI- groups, the Z-score did not depend on the presence of lipodystrophy or the proportion of fat in the abdomen and legs measured by DXA. Markers of bone remodeling were measured in the 132 HIV+ and 35 HIV- subjects. Compared with controls, HIV+ patients had lower bone alkaline phosphatase and higher urinary cross-laps/Cr, which was negatively correlated with the Z-score at both the femoral neck (r = -0.22) and lumbar spine (r = -0.21). TNFalpha was increased in untreated compared with treated HIV+ subjects and was not correlated to the Z-score. CONCLUSION: Our cross-sectional study does not show any deleterious effect of the treatment but does indicate a decrease in bone density in HIV+ patients irrespective of the treatment. This low bone density is in part related to the low body weight and is associated with increased bone resorption.

Adult↗

Effects of acute and chronic hypertension on the labyrinthine barriers in rat.

Hearing loss, vertigo, and tinnitus have been related to arterial hypertension. The aim of the present work was to study the permeability of the blood-perilymph and of the labyrinthine barrier, between endolymph and perilymph, to small molecules during chronic and acute hypertension. Experiments were performed in normotensive Wistar-Kyoto (WKY) and spontaneously hypertensive rats (SHR). Acute hypertension was induced by phenylephrine. Perilymph was sampled from the first turn of the scala vestibuli and the Na, K, urea, and radioactive concentrations ((14)C-urea and (3)H-mannitol) were measured. In another experimental set, the endocochlear potential was recorded from the basal turn of scala media, before and after phenylephrine injection. The composition of the perilymph and the kinetic constants for (14)C-urea and (3)H-mannitol were similar in WKY and SHR, and not modified after acute hypertension. In endolymph, the endocochlear potential in SHR (+80+/-2.7 mV, n=24) was lower (P<0.001) than in WKY (+98+/-1.5 mV, n=29). The endocochlear potential was decreased by 40 mV during acute hypertensive peak in seven out of 19 WKY but not in SHR rats (n=13). In conclusion, chronic or acute hypertension did not severely alter the permeability to small molecules of the blood-perilymph barrier. The relationship between the low endocochlear potential and hypertension in SHR remains to be evaluated. After acute hypertensive peak, the presence of vascular protective mechanisms in the cochlea could account for the stable endocochlear potential recorded in SHR and 60% of normotensive rats.

Acute Disease↗

Selective regulation of human immunodeficiency virus-infected CD4(+) lymphocytes by a synthetic immunomodulator leads to potent virus suppression in vitro and in hu-PBL-SCID mice.

We have previously observed that the synthetic immunomodulator Murabutide inhibits human immunodeficiency virus type 1 (HIV-1) replication at multiple levels in macrophages and dendritic cells. The present study was designed to profile the activity of Murabutide on CD8-depleted phytohemagglutinin-activated lymphocytes from HIV-1-infected subjects and on the outcome of HIV-1 infection in severe combined immunodeficiency mice reconstituted with human peripheral blood leukocytes (hu-PBL-SCID mice). Maintaining cultures of CD8-depleted blasts from 36 patients in the presence of Murabutide produced dramatically reduced levels of viral p24 protein in the supernatants. This activity correlated with reduced viral transcripts and proviral DNA, was evident in cultures harboring R5, X4-R5, or X4 HIV-1 isolates, was not linked to inhibition of cellular DNA synthesis, and did not correlate with beta-chemokine release. Moreover, c-myc mRNA expression was down-regulated in Murabutide-treated cells, suggesting potential interference of the immunomodulator with the nuclear transport of viral preintegration complexes. On the other hand, daily treatment of HIV-1-infected hu-PBL-SCID mice with Murabutide significantly reduced the viral loads in plasma and the proviral DNA content in human peritoneal cells. These results are the first to demonstrate that a clinically acceptable synthetic immunomodulator with an ability to enhance the host's nonspecific immune defense mechanisms against infections can directly regulate cellular factors in infected lymphocytes, leading to controlled HIV-1 replication.

Acetylmuramyl-Alanyl-Isoglutamine↗

Symptomatic hyperlactataemia: an emerging complication of antiretroviral therapy.

BACKGROUND: Fatal lactic acidosis is a serious complication of therapy with nucleoside analogues. OBJECTIVE: To examine symptomatic hyperlactataemia in HIV-infected adults treated with antiretroviral drugs. METHODS: In this prospective study, arterial blood lactate levels were measured in patients presenting with unexplained clinical symptoms. When these levels were high, functional respiratory tests (FRT) were carried out. Liver or muscle biopsies were further proposed. Incidences were calculated by comparison with the entire cohort of patients treated in the department. RESULTS: Fourteen HIV-infected adults treated with antiretroviral drugs were identified with symptomatic hyperlactataemia during a 2-year period follow-up study. The incidence of hyperlactataemia was 0.8% per year but reached 1.2% if only patients treated with a regimen including stavudine were considered. Clinical symptoms included abnormal fatigue, tachycardia, abdominal pain, weight loss, peripheral neuropathy, and more specifically exercise-induced dyspnoea occurring despite effective antiretroviral treatment. FRT showed a metabolic deviation towards anaerobiosis with a high lactate/pyruvate ratio. Ultrastructural mitochondrial abnormalities were seen in all four patients for whom this was examined. There was a marked decrease in complex IV activity in muscle biopsies from four of five patients, consistent with a mitochondrial dysfunction. Evolution was favourable in 13 patients, probably because of an early diagnosis. CONCLUSIONS: Potentially fatal adverse events occurring during antiretroviral treatment may be avoided by close monitoring of clinical signs and blood lactate levels. If other studies confirm that the cumulative long-term toxicity of antiretroviral drugs results from mitochondrial dysfunction, the incidence of hyperlactataemia and its clinical consequences may become more important.

Acidosis, Lactic↗

[Piercing and its infectious complications. A public health issue in France].

CHARACTERISTIC FEATURES: Piercing, an act that modifies the body, has progressed considerably in France over the last few years. The population involved has grown and become more diversified. Performed with a solid needle or a catheter, a wide variety of anatomic localizations are concerned, particularly the nose, ears, and navel. The shape of the "rings", generally made of surgical steel, niobium or titanium, varies greatly. Wound healing by epithelialisation can take up to several months. INFECTIOUS RISK: Between 10% and 20% of all piercings lead to a local infection. The most commonly found causal agests are Staphylococcus aureus, group A Streptococcus and Pseudomonas sp. These germs can cause severe life-threatening complications even in common localizations (earlobe). Viral transmission is another risk (hepatitis B, hepatitis C, hepatitis delta, HIV). A few cases of fatal fulminant hepatitis have been described immediately after piercing. SAFETY MEASURES: Generally performed under less than desirable sanitary conditions, safety measures are needed for piercing. Among professional "piercers", a certain number have emphasized the need for providing their clients with safer services. The prevention of infection risk should be a priority for all. Work along this line has been done in the United States and Canada. In light of the impact on public health, it is important to rapidly develop guidelines and regulations for piercing in France. Both professional piercers and health care workers should participate in developing these safety measures in order to assure their implementation.

Cosmetic Techniques↗

Cytokine analysis at the single cell level and lymphoproliferative responses to mycobacterial antigens in HIV-1 patients with successful virologic response to potent antiretrovirals.

Immunologic parameters, known to be grossly abnormal in HIV-1-infected subjects, were analyzed in 22 patients with sustained viral load suppression (<200 copies/ml) following long-term highly active antiretroviral therapy (HAART). Responses were compared with those from 18 HIV-seronegative healthy controls. Persistent phenotypic alterations in patients' blood mononuclear cells were minimal, though the percentages of lymphocytes that could be activated to produce interleukin-2 (IL-2) remained severely depressed. Using lymphoproliferative assays, a striking deficit in the capacity of patients to respond to the common mycobacterial antigens and particularly to recombinant heat-shock proteins paralleled the absence of responses to virus p24 antigen. In view of the important immunoregulatory role of stress proteins, these findings reveal profound functional deficiencies and persistent immune dysregulation in HIV-1 patients, despite successful HAART and a considerable recovery of CD4+ lymphocyte numbers. Rational immunotherapeutic approaches should be aimed to correct the characterized immune abnormalities.

Antigens, Bacterial↗

A study of strontium binding to albumins, by a chromatographic method involving atomic emission spectrometric detection.

A chromatographic method involving ICP-AES (inductively coupled plasma atomic emission spectrometry) detection has been successfully applied for the study of strontium-protein complexes. The chromatographic step involves the use of gel filtration-a large-zone Hummel and Dreyer method-which allows to dissociate the bound metallic ions and the free ones. This step is followed by an ICP-AES analysis of fractions collected throughout the chromatographic experiment: the concentration of ionic metallic species in solution can therefore be calculated. Two proteins have been tested: bovine serum albumin, which showed only weak interactions with Sr2+ ions, and bovine alpha-lactalbumin: this protein, well-known for its calcium binding capacity, proved to interact strongly with strontium. The influence of various parameters on the formation of strontium-lactalbumin complexes were determined, namely temperature, pH. Competition experiments between Sr2+ ions and, respectively Na+ and Ca2+ ions were also performed, by varying ionic strength of the medium, and by using both apo and native forms of bovine alpha-lactalbumin.

Albumins↗

Interleukin-16 (IL-16) inhibits human immunodeficiency virus replication in cells from infected subjects, and serum IL-16 levels drop with disease progression.

The role of recombinant interleukin-16 (rIL-16) in regulating human immunodeficiency virus type 1 (HIV-1) replication in endogenously infected cells has been investigated. Cultures of CD8 cell-depleted mitogen-activated lymphocytes from 22 of 26 HIV-1-infected subjects presented variable levels of secreted p24 antigen. The presence of rIL-16 throughout the 14-day culture period dramatically inhibited p24 release into the culture supernatants. This effect was found to be mediated through inhibition of viral transcription but to be independent of the induced levels of other cytokines or chemokines known to regulate viral replication. Analysis of serum samples from HIV-1-infected subjects over a period of 8 years showed maintained or even increased IL-16 levels during the whole asymptomatic phase and a significant drop on progression to disease. These results strongly support a potential therapeutic value of rIL-16 in HIV-1 infection and the use of serum IL-16 levels to monitor disease progression.

Acquired Immunodeficiency Syndrome↗

Enterocytozoon bieneusi multiorgan microsporidiosis in a HIV-infected patient.

Multiorgan microsporidiosis due to Enterocytozoon bieneusi was diagnosed in an HIV-infected patient. The parasite was found and identified as E. bieneusi by transmission electron microscopy in stools, duodenal biopsy, nasal discharge and sputum. No clinical improvement or parasite eradication was obtained after albendazole therapy, but the patient remained alive 9 months after diagnosis.

AIDS-Related Opportunistic Infections↗

Effect of locally applied drugs on the endolymphatic sac potential.

In Ménière's disease, an inner ear disorder related to an endolymphatic hydrops, an alteration of the functioning of the endolymphatic sac has been proposed. The endolymphatic sac is assumed to be involved in the secretion/resorption of endolymph. The epithelial transport systems have been indirectly studied by the recording of the endolymphatic sac transepithelial potential (ESP) in control conditions and after the local injection of drugs such as diuretics that have been proposed in the treatment of Ménière's disease. The ESP was recorded, in vivo, in guinea pigs up to 150 minutes after the perisaccular injection of 5 microL of a 150 mmol/L (mM) NaCl solution containing various drugs known to inhibit ionic transport systems. The initial ESP was +8.4+/-0.3 mV (mean +/- SEM, n = 78). The basolateral injection of 5 microL of 150 mM NaCl induced an ESP decrease of 64%+/-6.0% (n = 12), 5 minutes after the end of the injection. Then ESP increased, returning to its initial value at 60 minutes and surpassing it at 120 minutes. Diuretics such as acetazolamide (10[-3] mol/L [M]), an inhibitor of carbonic anhydrase, and amiloride (10[-4] M), an inhibitor of Na channel or Na/H exchanger, decreased the ESP recovery. At variance, bumetanide (10[-6] M, 10[-4] M), the Na-K-Cl cotransport inhibitor, and chlorothiazide (10[-4] M), a Na-Cl cotransporter inhibitor, failed to alter the ESP as compared with the control group. Ouabain (10[-3] M), the Na+,K+-adenosine triphosphatase (ATPase) inhibitor, prevented the ESP recovery otherwise observed 60 minutes after the NaCl injection. Bafilomycin A1, the inhibitor of the vacuolar-type H+-ATPase, prevented the recovery of the ESP with a log-dose/effect (10[-5] M, 10[-6] M, 10[-8] M). Disulfonic acid stilbene (DIDS) (10[-4] M), an inhibitor of transporters involving HCO3-, also prevented the ESP recovery. These results suggest that the genesis of the ESP was highly dependent on acid-base transport systems including carbonic anhydrase, a vacuolar-type H+-ATPase, and an anionic transport system blocked by DIDS. Further studies are needed to confirm the alteration of the acid-base balance in this epithelium and its possible involvement in the pathogenesis of Ménière's disease.

4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid↗

Genital mycoplasmas in patients with acquired immunodeficiency syndrome.

To determine whether Mycoplasma fermentans. Mycoplasma genitalium and Mycoplasma penetrans were present in the genitourinary tract of HIV infected patients in Nancy, France, we have used culture and polymerase chain reactions on urine from 54 HIV-infected patients. Both techniques failed to reveal these bacteria. This renders their presence very unlikely in our population.

Acquired Immunodeficiency Syndrome↗

Chromatographic method involving inductively coupled plasma atomic emission spectrometric detection for the study of metal-protein complexes.

A chromatographic method has been used to study metal ion-protein complexes. It involves successively a gel filtration technique to separate and distinguish the complexed from the free metallic ions, and a spectrometric technique, inductively coupled plasma atomic emission spectrometry (ICP-AES), which allows us to calculate accurately the concentration of ionic metallic species in solution. In the chromatographic step, we applied a large-zone Hummel and Dreyer method. Thus, fractions can be collected throughout the chromatographic experiment and their metal concentration measured by ICP-AES, at constant and known protein concentration. This method has been tested on the copper complex of bovine serum albumin. Results of our study are in good agreement with previous studies on this complex.

Chromatography, Gel↗