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Biomedical subjects

M Maillard

Publications and source records attributed to M Maillard.

At least 19 recordsLinked to original sources
PubMed1999

Adducin polymorphism affects renal proximal tubule reabsorption in hypertension.

Abnormalities in renal sodium reabsorption may be involved in the development and maintenance of experimental and clinical hypertension. Adducin polymorphism is thought to regulate ion transport in the renal tubule. It has recently been shown that there is a significant linkage of alpha-adducin locus to essential hypertension and that the 460Trp allele is associated with hypertension. Patients with this allele display larger blood pressure changes with body sodium variation. The aim of this study was to test whether alpha-adducin polymorphism is involved in abnormalities of renal function. Because proximal tubular reabsorption has been shown to be tightly coupled to renal perfusion pressure, this segmental tubular function was investigated in 54 (29 Gly/Gly and 25 Gly/Trp) untreated hypertensive patients in basal conditions with the use of endogenous lithium concentration and uric acid. Fractional excretions of lithium and uric acid were significantly decreased in the Gly/Trp hypertensive patients compared with the Gly/Gly hypertensives. The contribution of alpha-adducin to fractional excretion of lithium was investigated by multiple regression analysis. Adducin genotype was significantly (R2=0.11, F=6.5; P<0.01) and directly related to fraction excretion of lithium; gender, age, urinary Na+, urinary uric acid, mean blood pressure, and plasma renin activity were not related. In conclusion, the adducin gene can be considered to be a 'renal hypertensive gene' that modulates the capacity of tubular epithelial cells to transport Na+ and hence contributes to the level of blood pressure.

Adult↗
PubMed1999

Angiotensin II receptor blockade in normotensive subjects: A direct comparison of three AT1 receptor antagonists.

Use of angiotensin (Ang) II AT1 receptor antagonists for treatment of hypertension is rapidly increasing, yet direct comparisons of the relative efficacy of antagonists to block the renin-angiotensin system in humans are lacking. In this study, the Ang II receptor blockade induced by the recommended starting dose of 3 antagonists was evaluated in normotensive subjects in a double-blind, placebo-controlled, randomized, 4-way crossover study. At 1-week intervals, 12 subjects received a single dose of losartan (50 mg), valsartan (80 mg), irbesartan (150 mg), or placebo. Blockade of the renin-angiotensin system was assessed before and 4, 24, and 30 hours after drug intake by 3 independent methods: inhibition of the blood pressure response to exogenous Ang II, in vitro Ang II receptor assay, and reactive changes in plasma Ang II levels. At 4 hours, losartan blocked 43% of the Ang II-induced systolic blood pressure increase; valsartan, 51%; and irbesartan, 88% (P<0.01 between drugs). The effect of each drug declined with time. At 24 hours, a residual effect was found with all 3 drugs, but at 30 hours, only irbesartan induced a marked, significant blockade versus placebo. Similar results were obtained when Ang II receptor blockade was assessed with an in vitro receptor assay and by the reactive rise in plasma Ang II levels. This study thus demonstrates that the first administration of the recommended starting dose of irbesartan induces a greater and longer lasting Ang II receptor blockade than that of valsartan and losartan in normotensive subjects.

Adult↗
PubMed1998

Evaluation of the detection of human papillomavirus genotypes in cervical specimens by hybrid capture as screening for precancerous lesions in HIV-positive women.

Given the frequency and persistence of human papillomavirus (HPV) infection and associated cytological alterations in HIV-1-positive women, the incidence of uterine cervix neoplasm is likely to increase along with patient survival. More appropriate screening programs, which, in addition to Pap smears (PS), also include tests to detect and type HPV, are needed for the early identification of precancerous cervical lesions. This prospective study involved 168 HIV-positive (group A) and 100 HIV-negative women (group B). Cervicovaginal samples were collected for a PS and HPV DNA search. The detected virus was typed as high-intermediate oncogenic risk HPV (HR-HPV) and low-risk HPV (LR-HPV) using hybrid capture (HC) (Murex-Digene) and in-house PCR tests. The HC-detected prevalence of HPV was 111/168 (66%:HR 75.6%) in group A and 15/100 (15%:HR 42.9%) in group B (P < 0.0001). Polymerase chain reaction (PCR) was positive in 91% and 48%, respectively. No significant difference was observed between drug addicts and heterosexual HIV-1-positive women (P = 0.09). HPV was detected in 94% of the 57 HIV-positive women with cytological alterations. HR-HPV was found in 41/49 women with low-grade and 7/8 with high-grade squamous intraepithelial lesions (LSIL and HSIL, respectively). In women with a negative PS, HPV was detected in 57/111 cases (HR 63%) of group A and in 13/98 of group B (6 cases of HR). Of the 54 group A women who underwent biopsy, histology revealed that 41 had LSIL (18 with negative PS, 19 with LSIL, and 4 with HSIL; HR-HPV in 73% and LR-HPV in 17%), nine had HSIL (5 LSIL and 4 HSIL on cytology; HR-HPV in 89% and LR-HPV in 11%), and four were negative (all cytology negative; 3 HR-HPV and 1 LR-HPV). HR-HPV was more frequent as immunodepression worsened. These results show that cytological evaluation alone underestimated histological alterations in 23/50 women (42.6%), whereas the combination of Pap smear and HPV detection reduced this underestimate to 5%.

Adult↗
PubMed1998

Cytotoxic coumarins from the aerial parts of Tordylium apulum and their effects on a non-small-cell bronchial carcinoma line.

Seven coumarins were isolated from the aerial parts of Tordylium apulum; their structures were established by spectroscopic means. All compounds were tested in vitro for their cytotoxicity against two cell line systems. The antiproliferative effects for three of them were studied at the level of the cell cycle in asynchronous cells of the NSCLC-N6 line with a flow cytometry apparatus.

Antineoplastic Agents, Phytogenic↗
PubMed1997

Preparation and anti-HIV activity of N-3-substituted thymidine nucleoside analogs.

A series of 22 derivatives of AZT substituted at the N-3 position of the thymine base were prepared and evaluated for anti-HIV activity in cell culture (Lai strain of HIV-1 in CEM-c113 cells). The AZT analogs bearing a N-3 amino group (7), a hydroxyalkyl chain (12f), and a phosphonomethyl (12k) substituent displayed activities in the 0.045-0.082 microM range. The analogs 12d, 12e, 12q, 15, and 19 were active at <0.5 microM concentration. Compound 18 in which two molecules of AZT are connected at N-3 via a two-carbon link and "dimer" 11 also displayed significant activity. To obtain information concerning the mechanism of RT inhibition by these AZT analogs, compounds 7, 12d, 12e, and 12q were incubated with recombinant HIV-1 RT in the presence of poly(A)-oligo[dT(12-18)] and poly(C)-oligo[dG(12-18)] template-primers. In contrast to AZT-TP (control), none of these nucleosides displayed any significant inhibition of RT in the recombinant enzyme assay, indicating that phosphorylation is a necessary prerequisite for activity.

Anti-HIV Agents↗
PubMed1997

Monitoring antiretroviral activity using ICDp24 and CD4 counts in HIV infection.

The fluctuations of HIV-1 p24 antigen concentration have been monitored in the follow-up of 118 subjects in different clinical stages and compared to their CD4 cell count; 104 patients received antiretroviral therapy. Persistent (65%) or sporadic (28%) antigenaemia has been detected in most patients in different clinical stages. The variations of the p24 Ag level are significantly correlated with the CD4 cell count and therapy administration (P = 0.0001). In patients with relatively conserved immune function (CDC II and III), antiretroviral therapy shows the best efficacy and can be efficiently monitored by p24 and CD4 surrogate markers. The data here suggest that although the informative value of p24 Ag is not representative of an AIDS-defining event, it can be used as a short-term and relatively inexpensive virological marker of antiviral activity in vivo, to support the routine management of patients.

Anti-HIV Agents↗
PubMed1997

Application of neural networks to the follow-up of AIDS patients.

The present work aims to obtain groups of patients with similar profiles of p24 antigen concentration and of CD4+ cell counts. These two markers were chosen because their evaluation represents a significant step in the clinical follow up of HIV-1 infected subjects. The classifications were obtained by a Kohonen neural net trained in three ways: with p24 antigen profiles only, with CD4+ cell count profiles only and with both sets of profiles. The results show that the clustering fashion of the two parameters closely resembles the clustering fashion of CD4+ only rather than the one of p24Ag, both with reference to cluster formation and with reference to distance among clusters.

Acquired Immunodeficiency Syndrome↗
PubMed1996

Risks and benefits of aerosolized pentamidine and cotrimoxazole in primary prophylaxis of Pneumocystis carinii pneumonia in HIV-1-infected patients: a two-year Italian multicentric randomized controlled trial. The Italian PCP Study Group.

We randomized 220 HIV-1-infected subjects to receive aerosolized pentamidine (300 mg/4 weeks) or orally trimethoprim-sulfamethoxazole (320-1600 mg/day) for primary prophylaxis of Pneumocystis carinii pneumonia (PCP), and evaluated PCP and toxoplasmic encephalitis (TE) occurrence and survival. Patients developing toxicity switched to the other regimen. Analysis was on intention-to-treat. At 1 year of study, we observed in the pentamidine group a non-significant excess of PCP (4 vs. 1) and TE (7 vs. 3), and a significant increased death rate (15 vs. 2). After 2 years, no significant differences were observed: adjusted RR estimates for pentamidine vs. cotrimoxazole were 1.20 (95% CI, 0.33-4.37) for PCP (6 cases vs. 5), 1.23 (95% CI, 0.46-3.29) for TE (10 vs. 8) and 1.52 (95% CI, 0.83-2.79) for death (30 vs. 18). Crossovers were more frequent in the cotrimoxazole group (41 vs. 4, P < 0.001). Aerosolized pentamidine and cotrimoxazole were equally effective in preventing PCP, and no major differences were observed in TE occurrence and survival after 2 years follow-up.

AIDS-Related Opportunistic Infections↗
PubMed1995

Better efficacy of twice-monthly than monthly aerosolised pentamidine for secondary prophylaxis of Pneumocystis carinii pneumonia in patients with AIDS. An Italian multicentric randomised controlled trial. The Italian PCP Study Group.

The aim of this multicentric randomised controlled trial was to evaluate long-term efficacy and safety of once-monthly versus twice-monthly 300 mg aerosolized pentamidine (AP) as secondary prophylaxis of Pneumocystis carinii pneumonia (PCP). We randomised 205 patients with a previous confirmed episode of PCP (107 treated with 300 mg once-monthly AP, and 98 with 300 mg twice monthly AP); the median review period was 232 days. Kaplan-Meier method and Cox's hazard regression model were used for analysis. The main outcome assessments were PCP recurrence, survival and incidence of drug toxicity. The two groups were balanced for prognostic predictors. In the once-monthly AP group, 14 relapses of confirmed PCP were observed, while five occurred in the twice-monthly AP group; the crude relative risk (RR) was 2.69 (95% CI 1.002-7.236, P=0.0496) and the adjusted RR accounting for prognostic predictors was 2.62 (95% CI 0.92-7.5, P=0.071). Death occurred in 36 of 26 patients respectively (adjusted RR 1.32, 95% CI 0.8-2.18, P=0.28). Two patients interrupted the study because of intolerance to AP (one in each group), and severe coughing occurred in two patients (one in each group). At the end of the study, pulmonary function tests were not changed compared with baseline and were the same between the two groups. Our study suggests that 300 mg twice-monthly AP is more effective than 300 mg once-monthly AP as secondary prophylaxis of PCP.

Acquired Immunodeficiency Syndrome↗
PubMed1994

Comparative studies on the affinities of ATP derivatives for P2x-purinoceptors in rat urinary bladder.

1. Radioligand binding assays have been used to determine the affinities of a series of ATP derivatives with modifications of the polyphosphate chain, adenine and ribose moieties of the ATP molecule for [H]-alpha,beta-methylene ATP ([3H]-alpha,beta-MeATP) binding sites in rat urinary bladder. 2. The replacement of the bridging oxygen in the triphosphate chain of ATP (pIC50 = 5.58) with a methylene or imido group markedly increased the affinity (691 fold in IC50 values for beta,gamma-imidoATP, 15 fold for beta,gamma-methylene ATP), and the replacement of an ionized oxygen on the gamma-phosphate with a sulphur (ATP gamma S) also led to increased affinity (5623 fold in IC50 values). 3. Modifications at N6, N1, and C-8 positions on the purine base usually reduced the affinity of ATP (a decrease of 2.8 fold in IC50 values for N6-methylATP and 8.9 fold for 8-bromo ATP), while the attachment of an alkylthio group to the C-2 position greatly increased the affinity for P2x-purinoceptors (from 3.5 to 98 fold increase in IC50 values). 4. Replacement of the 3'-hydroxyl group on the ribose with substituted amino or acylamino groups produced more potent P2x-purinoceptor agonists (an increase of 447 fold in IC50 values for 3'-deoxy-3'-benzylamino ATP and 28 fold for 3'-deoxy-3'-(4-hydroxyphenylpropionyl)amino ATP. 5. Diadenosine polyphosphates (Ap[n]A) were also shown to displace the [3H]-alpha,beta-MeATP binding. The rank order of potency was Ap6A > Ap5A > Ap4A >> Ap3A >> Ap2A. 6. Suramin, PPADS, and reactive blue 2 could competitively displace the binding of [3H]-alpha,beta-MeATP toP2X-purinoceptors, with pIC50 values of 6.26, 5.35, and 6.22, respectively.

Adenosine Triphosphate↗
PubMed1993

8-(3-Chlorostyryl)caffeine (CSC) is a selective A2-adenosine antagonist in vitro and in vivo.

An adenosine antagonist, 8-(3-chlorostyryl)caffeine (CSC), was shown previously to be 520-fold selective for A2a-adenosine receptors in radioligand binding assays in the rat brain. In reversing agonist effects on adenylate cyclase, CSC was 22-fold selective for A2a receptors in rat phenochromocytoma cells (Kb 60 nM) vs. A1 receptors in rat adipocytes (Kb 1.3 microM). Administered i.p. in NIH mice at a dose of 1 mg/kg, CSC shifted the curve for locomotor depression elicited by the A2a-selective agonist APEC to the right (ED50 value for APEC shifted from 20 micrograms/kg i.p. to 190 micrograms/kg). CSC had no effect on locomotor depression elicited by an ED50 dose of the A1-selective agonist CHA. CSC alone at a dose of 5 mg/kg stimulated locomotor activity by 22% over control values. Coadministration of CSC and the A1-selective antagonist CPX, both at non-stimulatory doses, increased activity by 37% (P < 0.001) over CSC alone, suggesting a behavioral synergism of A1- and A2-antagonist effects in the CNS.

Adenosine↗
PubMed1993

Structure-activity relationships of 8-styrylxanthines as A2-selective adenosine antagonists.

A series of substituted 8-styryl derivatives of 1,3,7-alkylxanthines was synthesized as potential A2-selective adenosine receptor antagonists, and the potency at rat brain A1- and A2-receptors was studied in radioligand binding experiments. At the xanthine 7-position, only small hydrophobic substituents were tolerated in receptor binding. 7-Methyl analogues were roughly 1 order of magnitude more selective for A2 versus A1 receptors than the corresponding 7-H analogues. 1,3-Dimethylxanthine derivatives tended to be more selective for A2-receptors than the corresponding 1,3-diallyl, diethyl, or dipropyl derivatives. Substitutions of the phenyl ring at the 3-(monosubstituted) and 3,5-(disubstituted) positions were favored. 1,3, 7-Trimethyl-8-(3-chlorostyryl)xanthine was a moderately potent (Ki vs [3H]CGS 21680 was 54 nM) and highly A2-selective (520-fold) adenosine antagonist. 1,3,7-Trimethyl-8-[(3-carboxy-1-oxopropyl)amino] styryl]xanthine was highly A2-selective (250-fold) and of enhanced water solubility (max 19 mM). 1,3-Dipropyl-7-methyl-8-(3,5-dimethoxystyryl) xanthine was a potent (Ki = 24 nM) and very A2-selective (110-fold) adenosine antagonist.

Adenosine↗
PubMed1993

Search for antifungal, molluscicidal and larvicidal compounds from African medicinal plants.

African medicinal plants provide a rich source of biologically-active natural products. By the use of simple bioassays in conjunction with an approach involving bioactivity guided fractionation, it is possible to isolate novel compounds with interesting properties. Several hundred plant extracts have been submitted to different screens, including bioautography on TLC plates with the fungi Cladosporium cucumerinum and Candida albicans. Among the other test systems are a bioassay for molluscicidal activity with the schistosomiasis-transmitting snail Biomphalaria glabrata and a benchtop assay for larvicidal activity with larvae of the mosquito Aedes aegypti, the vector of yellow fever. Using a variety of modern separation techniques, a number of compounds with activity in these bioassays have been isolated. These include prenylated xanthones, tetracyclic phenols and saponins. The role of saponins and saponin-containing plants in the control of schistosomiasis is outlined.

Animals↗
PubMed1991

Ion channels involved in the presynaptic hyperexcitability induced by herpes virus suis in rat superior cervical ganglion.

Rat superior cervical ganglia infected with herpes virus suis (pseudorabies virus) display a spontaneous bursting activity of still unknown origin. Previous intracellular recordings from the ganglionic neurons combined with pharmacological studies showed that the postganglionic action potentials are induced by acetylcholine release spontaneously from the preganglionic nerve. In this study we investigated whether the acetylcholine release is caused by mechanisms which are dependent on action potentials spontaneously generated on the preganglionic nerve or by mechanisms which occur without any changes in the excitability of presynaptic fibers. Simultaneous intra- and extracellular recordings from the ganglion cells and from the preganglionic nerve, respectively, were performed 32-38 h after the inoculation of herpes virus suis (strain Aujeszky) into the anterior chamber of one eye of the rat. Tetrodotoxin, well known to prevent the generation of action potentials by blocking the fast sodium channels, completely and reversibly abolished, whereas the potassium channel blockers 4-aminopyridine and apamin, enhanced the spontaneous, bursting activity at pre- and postsynaptic levels. The nicotinic receptor antagonist hexamethonium abolished the postsynaptic discharges and reduced the preganglionic activity by 50%. Pre- and postsynaptic electrical activities were suppressed in low calcium Krebs' solution, demonstrating that extracellular calcium is required not only for acetylcholine release but also for triggering the presynaptic action potentials. It is concluded that in the infected ganglia the spontaneous acetylcholine release is due to the generation of action potentials in the preganglionic nerve. Voltage-gated sodium and calcium channels contribute to the presynaptic electrogenesis, while the latter appears to be damped by the activation of voltage- and calcium-dependent potassium channels. Possible factors as well as mechanisms inducing such an increase in excitability are discussed.

4-Aminopyridine↗
PubMed1991

[Indications of lithium plasma levels in professional practice. Average of a 7-year follow-up].

With a mean follow-up duration of 7 years, the retrospective analysis of 57 charts of lithiotherapy shows that: Better results are observed when the lithium blood level reactus 0.87 mmoles/l. In that case, the best lithiotherapy indication is the major recurrent long cycles depression. We also propose as lithiotherapy indication in order of efficacy: 1--The maniac-depressive psychosis (P.M.D.) in its mixed form. 2--The schizo-affective troubles. The curative and preventive lithium efficacy is on favour of the diagnosis of recurrent endogenous psychiatric disease.

Adult↗
PubMed1989

Partially N-desulfated heparin as a non-anticoagulant heparin: some physico-chemical and biological properties.

A partially N-desulfated preparation of heparin (UFH) obtained by thermally inactivating heparinic acid for 24 hours at 50 degrees C (TIHA) was examined for its physico-chemical and biological properties in vitro and in vivo. TIHA has a molecular weight of 14,700 and 27% remaining N-sulfate groups (UFH = 17,500; 100% N-sulfate groups). TIHA has no anticoagulant activity measurable by conventional amidolytic or clotting tests. However, in a rabbit stasis-induced thrombosis model and using two different thrombogenic stimuli (Feiba and PCC(Konyne)/RVV), TIHA afforded a dose-dependent (1.0-2.5 mg/kg) protection sufficient to impair thrombosis (UFH: fully effective at 0.13 mg/kg). TIHA did not produce any bleeding at supramaximal antithrombotic dosage in a rat tail bleeding and a rabbit ear blood loss model and it did not augment ADP-induced aggregation of platelets. In contrast, a completely N-desulfated derivative of UFH (Inoue and Nagasawa, Carbohydr. Res. 46, 87-95, 1976) also lacking measurable in vitro activity was completely inactive in vivo. The results in this study suggest that TIHA may be considered as a non-anticoagulant heparin still retaining antithrombotic activity and also with lower haemorrhagic effect than UFH.

Adenosine Diphosphate↗