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P Gayral

Publications and source records attributed to P Gayral.

At least 37 records · Page 2Linked to original sources
PubMed1994

Macrofilaricidal activity of albendazole-ivermectin combination: histopathological evaluation of adult Molinema dessetae.

The macrofilaricidal effect of albendazole in association with ivermectin was assessed in the rodent Proechimys oris, infected with Molinema dessetae. The drug combination was given to five rodents 190 days after infection. A similar group was used as control. The doses administered were 10 mg per kg for albendazole and 0.04 mg per kg for ivermectin over five days. The histological examination of intra-peritoneal nodules done six weeks after therapy revealed a clear-cut macrofilaricidal effect. The number of dead worms was significantly higher in the treated group. The histological examination revealed a lesion pattern that was related to the drug exposure. This consisted of nodules, each containing a necrotic worm that had its morphology preserved and was surrounded by a foreign body granuloma. This lesion was only seen in the treated group. A pattern related with the spontaneous death of worms was also observed. The results obtained here show the importance that albendazole-ivermectin combination could have in human filariasis therapy. Further studies in man should be done to confirm the macrofilaricidal effect of this drug combination in human filariasis.

Albendazole↗
PubMed1994

Synthesis and nematocidal activity of arylmercaptovinyltetrahydropyrimidines.

A set of mercaptovinyl tetrahydropyrimidines was synthesized in good yields by lithiation of 1,2-dimethyltetrahydropyrimidine with n-butyl lithium in tetrahydrofurane, followed by condensation with aromatic thioesters. Against three nematode genera, anthelminthic screening shows little activity; 2b and 2d were the most potent against Molinema dessetae.

Animals↗
PubMed1993

Microtopography of Nippostrongylus brasiliensis (Nematoda: Heligmosomatidae): free-living larval stages.

Microtopographic features of the various growth stages of the three free-living larval stages of the rat hookworm Nippostrongylus brasiliensis (Nematoda) were surveyed by scanning electron microscopy. These worms have a rounded anterior end and an elongated tail. Cuticular annulations were observed along the body, which also bore two ribbon-like lateral alae. Two rings of six lip-like lappets were observed around the triradiate oral opening in all larval stages. The cephalic space contained two lateral amphidial pits. The excretory pore in the third anterior part was observed in a ventral view of the larvae. No deirids were observed. The anus with a crescent-shape opening was located posteriorly. Phasmidial apertures, only observed in the third-stage larvae, opened on the lateral alae in the tail region.

Animals↗
PubMed1993

Microtopography of Nippostrongylus brasiliensis (Nematoda: Heligmosomatidae): parasitic larval stages and adults.

Specimens of the rat hookworm, Nippostrongylus brasiliensis (Nematoda) were recovered from lungs (third- and fourth-stage larvae) and intestine (fourth-stage larvae and adults). The following features were studied in the different stages by scanning electron microscopy: cephalic structures, especially sense organs, synlophe, cervical region, and caudal part. The main differences between the third and fourth stages concerned the lip-like structures around the oral aperture, the appearance of the cephalic space with the presence of a cephalic cap in fourth-stage larvae, the pattern of longitudinal ridges, and sexual differentiation. Pore-like papillae, not seen in third-stage larvae, developed in later stages. Deirids were observed only in adults, and phasmids were poorly discerned. Some of these morphological features, such as the cephalic sense organ apertures and cuticle pores and micropores, can be observed only by scanning electron microscopy. The possible functions of these different structures and their relationship with the behavior of the worms during their life cycle are discussed.

Animals↗
PubMed1993

Comparative effects of anthelmintics on c-MDH from Molinema dessetae (Nematoda: Filarioidea) and from a mammal.

Malate dehydrogenase (MDH) (E.C.1.1.1.37) activity was detected in the filaria Molinema dessetae at a level similar to those found in other filariae. In M. dessetae, the cytoplasmic form (c-MDH) predominated and the study was performed on partially purified fractions. The pH optimum for oxaloacetate reduction was 6.1, with maximal activity at 7811 nmol min-1 mg protein-1, but high concentrations of oxaloacetate inhibited MDH activity. The Km value for oxaloacetate was determined as 22 microM for M. dessetae c-MDH and 33 microM for mammalian c-MDH. Anthelmintic drugs were compared as potential inhibitors of filarial and mammalian c-MDH. Among the compounds evaluated, amocarzine showed a specific inhibitory effect on filarial c-MDH through only at high concentrations. Suramin alone showed an inhibitory effect at low concentrations (Ki = 1.15 microM) but without selective action towards filarial c-MDH. The suramin type of inhibition was found to be competitive. Suramin probably acts on both enzymes in the same manner. Nevertheless, M. dessetae c-MDH is proposed as a suitable enzyme assay model to screen MDH inhibitors as potential filaricides.

Animals↗
PubMed1993

Levels of ecdysteroid-like material in adults of Nippostrongylus brasiliensis during the intestinal phase.

Total ecdysteroid-like immunoreactive material was assayed and quantified in adults of the parasitic nematode N. brasiliensis during the intestinal phase in the rat in order to detect possible physiological fluctuations in titre. Worms of the same sex isolated from one rat were pooled in order to quantify ecdysteroids using enzyme immunoassay (EIA). The concentration of ecdysteroids fluctuated during adult life according to the sex and the age of the parasite. Important differences of levels of ecdysteroid-like compounds between the two sexes of parasites were noted particularly at 128 and 168 h post-infection. The peak at 128 h, present in female, but not in male worms, corresponds to the time of egg-laying. Following HPLC-EIA analysis, the presence of ecdysone, 20-hydroxyecdysone and apolar ecdysteroid-like material was ascertained during this peak. The physiological role and the possible origin of ecdysteroids in this nematode are discussed.

Animals↗
PubMed1993

Purification and properties of phosphoenolpyruvate carboxylase from Molinema dessetae (Nematoda: Filarioidea).

The presence of phosphoenolpyruvate (PEP) carboxylase (EC 4.1.1.31), an enzyme at the branchpoint of glycolysis and the Krebs cycle was detected in the Filaria Molinema dessetae. This enzyme has not previously been identified in Helminths, which have so far been found to only possess a phosphoenolpyruvate carboxykinase (EC 4.1.1.32). This enzyme had a level of activity comparable to that of pyruvate kinase, and was relatively less active than enzymes such as malate dehydrogenase or lactate dehydrogenase. We propose here a method of purification of M. dessetae PEP-carboxylase. When purified to electrophoretic homogeneity, the enzyme had a molecular weight of 64 kDa. Kinetic studies indicated that the carboxylation reaction had an optimal pH of 5.8. The enzyme was inhibited by cations such as Fe2+, Zn2+, Cd2+, Cu2+ but required the presence of Mg2+ or Mn2+. The enzyme was thermostable. The apparent Km value of 2.38 mmol for phosphoenolpyruvate for the carboxylation reaction was higher than previously reported values. The Km value for KHCO3 was found to be 1.6 mmol. PEP-carboxylase did not catalyse the reverse reaction.

Animals↗
PubMed1993

Design, synthesis and biological study of new antiparasitic spiroarsoranes.

Thirty-eight new spiroarsoranes were synthesized after structure-activity relationship studies from the first series. These compounds were predicted to cross more easily the membrane of protozoae or the cuticle of Nematodes and to reach their biological target with efficiency. The spiroarsoranes were evaluated for their antiparasitic properties, on helminths and protozoa models in regard of their parent arsonic acids. The following parasite models were used: Entamoeba histolytica and Trichomonas vaginalis in vitro; Molinema dessetae infective larvae in vitro, adults and microfilariae in vivo; Nippostrongylus brasiliensis infective larvae in vitro. The results obtained on these models indicated that the "spiranization" of arsonic acids produced new compounds with a biological activity 10-fold superior to those of arsonic acids. Nevertheless, each parasite had its own sensitivity to spiroarsoranes. Moreover, in vivo results showed that the lipophilicity of the molecules should be optimal to avoid high toxicity in host such as arsenical encephalopathy.

Animals↗
PubMed1993

Spiroarsoranes of second generation: evaluation of trypanocidal properties against Trypanosoma brucei brucei.

The spiroarsoranes are a series of pentavalent arsenicals having interesting trypanocidal properties. They are less toxic than trivalent arsenicals but their activity appear at higher doses and concentrations. The structure-activity relationships study from the first series led to a new generation of spiroarsoranes which has been synthesized and evaluated in vitro and in vivo against Trypanosoma brucei brucei bloodstream forms. Among 40 compounds, 5 were active in vitro at concentrations less than 10 mumol/l and 7 were active in vivo. The most interesting compound of this series (compound I e 2) showed an in vitro activity at 125 mumol/l after 24 hours incubation time and in vivo all the mice were cured after a subcutaneous treatment at 600 mumol/kg in one single dose. The spiranization and the substitution of para-arsanilic acid allowed to obtain a better mean survival time at 300 mumol/kg comparatively to para-arsanilic acid itself used as reference compound. Nevertheless, this second generation of compounds was less active than the selected compound of the first series which was efficient at 150 mumol/kg in subcutaneously one single dose.

Animals↗
PubMed1992

Effects of ecdysteroids on reproductive physiology of Nippostrongylus brasiliensis (Nematoda) in vivo.

1. The influence of ecdysteroids (ecdysone and ecdysterone) was investigated on the control of reproduction in the parasitic nematode Nippostrongylus brasiliensis in vivo. 2. Infestive larvae (L3) were immersed in solutions of ecdysteroids (2.2 microM) at 37 degrees C for 4 hr before injection into the host. The effect on egg-laying was observed two stages later. 3. The treatment increased egg-laying, but had no influence on the timing of the reproductive period. The greatest effect was observed with ecdysone, ecdysterone only inducing a small and non-significant stimulation under our experimental conditions. 4. The physiological role of ecdysteroids in meiosis and gonadal development in nematodes is discussed.

Animals↗
PubMed1992

Molluscicidal constituents of Calophyllum from Madagascar: activity of some natural and synthetic neoflavonoids and khellactones.

Crude extracts of seeds, leaves and barks of four Madagascan Calophyllum species: C. inophyllum, C. recedens, C. chapelieri, and C. verticullatum, have been tested for molluscicidal activity against Biomphalaria glabrata. All seed extracts showed significant activity. The major constituents of the most active Calophyllum species were examined. Some related coumarinic derivatives were synthesized in order to improve the biological activity. Among the compounds prepared, 5,7-dihydroxy-6-(2-methylbutyryl)-4-phenyl-coumarin presented an interesting molluscicidal activity.

Animals↗
PubMed1992

Synthesis of the orally macrofilaricidal and stable glycerolipidic prodrug of melphalan, 1,3-dipalmitoyl-2-(4'(bis(2''-chloroethyl)amino)phenylalaninoyl)gl ycerol.

A new strategy is presented to develop macrofilaricidal compounds orally administered and able to concentrate in the lymphatic system. A diglyceride derivative of melphalan, 1,3-dipalmitoyl-2-(4'(bis(2''-chloroethyl)amino)phenylalaninoyl)gl y cerol, was synthesized. The esterification of melphalan by 1,3-dipalmitin allowed chemical stabilization of the alkylating agent in aqueous dispersion. No degradation of this prodrug was observed after a 3-month storage of an aqueous dispersion at 4 degrees C. The filaricidal activity of the prodrug was compared with those of melphalan in vitro against adults, infective larvae and microfilariae of Molinema dessetae, and evaluated in vivo on Molinema dessetae infected Proechimy oris. In vitro, melphalan and the glycerolipidic prodrug were inactive against microfilariae but active at 1 mmol/l against infective larvae and adults. In vivo studies were performed with rodents subcutaneously inoculated with infective larvae from Aedes aegypti. The number of macrofilariae was significantly reduced following treatment with a single oral dose of the alkylating agent prodrug (0.082 mmol/kg).

Aedes↗
PubMed1992

In vitro and in vivo evaluation of macrofilaricidal activity of GABA and 1,3-dipalmitoyl-2-(4-aminobutyryl)glycerol HCl: a diglyceride prodrug.

A new therapeutic target has been identified from the filaria Molinema dessetae: the gabaergic system. gamma-aminobutyric acid (GABA) itself showed antifilarial effect in vitro and a macrofilaricidal action in vivo at high dose by intraperitoneal route (10(-2) M). Nevertheless, no action was observed by oral route. The study we report here consists to obtain an antifilarial effect by oral route using a diglyceride prodrug. Such a strategy is based on the triglycerides metabolism. A diglyceride prodrug of gamma-aminobutyric acid has been synthesized and its filaricidal activity compared with that of GABA, in vitro on adults of Molinema dessetae and in vivo on Molinema dessetae infected Proechimys oris. In vitro, GABA at 2.5 x 10(-3) M induced a temporary paralysis and the ester drug at the same concentration was fully active on adults. In vivo, no significant activity was observed by oral administration of a daily dose of GABA (10(-2) M). A five day course of GABA at 10(-2) M via the intraperitoneal route induced a significant reduction of male and female worms. We did not find any activity of the prodrug in vivo, either by the oral route (10(-2) M) or after an intraperitoneal administration (10(-3) M). The interest of GABA and GABA derivatives as potential filaricidal drugs was discussed.

Animals↗
PubMed1992

Pharmacomodulations on new organometallic complexes of Ir, Pt, Rh, Pd, Os: in vitro and in vivo trypanocidal study against Trypanosoma brucei brucei.

New organometallic complexes have been synthesized by association of an active organic molecule with a metallic element such as Pt, Rh, Ir, Pd, Os. Their trypanocidal activity was studied in vitro and in vivo against T. b. brucei. The more active compounds were pentamidine derivatives. The Ir- COD-pentamidine complex, and Iridium (I) cationic and organometallic complex showed and in vitro activity at 60 micrograms/l. Moreover, all infected mice were cured by this compound subcutaneously administered in a single dose at 0.5 mg/kg (0.317 mumol/kg). In the same conditions, pentamidine cured all the mice at 5 mumol/kg. Ir-COD-pentamidine (or P1995) was 16 fold more efficient than pentamidine. Since the chemotherapeutic index of this molecule was 7.5 fold higher than those of pentamidine, P1995 can be considered as a potential trypanocidal drug of the future.

Animals↗
PubMed1991

Biogenic amines and GABA in the larval and adult forms of the nematode Nippostrongylus brasiliensis.

1. Simultaneous detection (HPLC and electrochemical detection) of biological extracts of larval and adult stages of Nippostrongylus brasiliensis was performed in order to assay biogenic amines. 2. Gamma-amino-butyric acid was assayed in the same samples. 3. Tryptophan, 5-hydroxyindoleacetic acid were at the same level in adults and larvae. 4. 5-Hydroxytryptophan, serotonin, dihydroxyphenylalanine and dopamine were significantly higher in larvae in which gamma-amino-butyric acid was not detected.

Aging↗
PubMed1991

Biogenic amine levels in the cockroach Blaberus craniifer Burm. nervous system.

1. Apart from octopamine, the same indolamines and catecholamines were detected in the whole nervous system of the cockroach Blaberus craniifer Burm., at the same time. 2. However, levels were found to depend on sex, age, and the anatomic region within the nervous system. 3. Although not established, it is thought that these substances act synchronously from the ganglia. 4. The differences in levels between males and females and between anatomical regions during imaginal life suggest, in this species of cockroach, the physiological importance of the metameric organization in metabolic pathways or functional aspects of biogenic amines.

Acetylation↗