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Biomedical subjects

M Roland

Publications and source records attributed to M Roland.

At least 19 recordsLinked to original sources

Factors affecting iontophoretic mobility of metoprolol.

The effect of different factors on the iontophoretic transport of metoprolol was analyzed. In vitro experiments were first performed in a diffusion cell with a cellophane membrane. Comparison of different pH, buffers, and ionic strengths in the donor compartment showed that higher iontophoretic transport was obtained with phthalate buffer (0.01 M) at pH 3. When the current density increased, the flux of metoprolol also increased. A decrease in drug concentration or an increase in viscosity slowed down the iontophoretic transport of metoprolol. The fluxes of metoprolol through hairless rat skin were strongly enhanced compared with passive diffusion. Direct current seemed to be more efficient than pulse current. When the on:off ratio of the pulse current was reduced, the flux also decreased.

Algorithms

Macrophage activation by polymeric nanoparticles of polyalkylcyanoacrylates: activity against intracellular Leishmania donovani associated with hydrogen peroxide production.

Nanoparticles of polyalkylcyanoacrylates (PACA) can be useful carrier for the targeting of antileishmanial drugs into macrophages and also possess significant antileishmanial activity by themselves. No significant difference in antileishmanial activity could be detected between nanoparticles of five PACAs with differing alkyl side chains, suggesting that the main degradation products of PACA are not involved in their antileishmanial action. The effect of polyisohexylcyanoacrylate (PIHCA) on the induction of the respiratory burst in a macrophage-like cell line (J774G8) was assessed in non-infected macrophages and in macrophages infected with amastigotes of Leishmania donovani infantum, by measuring nitroblue tetrazolium (NBT) reduction and hydrogen peroxide production. Phagocytosis of PIHCA nanoparticles led to a respiratory burst, which was more pronounced in infected than in uninfected macrophages. The production of reactive oxygen intermediates associated with the respiratory burst was inhibited by addition of superoxide dismutase and catalase to the cell suspensions. The addition of catalase to the culture medium together with PIHCA nanoparticles significantly reduced the antileishmanial activity of PIHCA. Moreover PIHCA nanoparticles did not induce interleukin-1 release by macrophages. It is suggested that the antileishmanial action of PIHCA and other PACA nanoparticles results from the activation of respiratory burst in macrophages.

Animals

Drug targeting with polyalkylcyanoacrylate nanoparticles: in vitro activity of primaquine-loaded nanoparticles against intracellular Leishmania donovani.

The efficacy of primaquine-loaded polyisohexylcyanoacrylate (PIHCA) nanoparticles was evaluated using J774G8 macrophage-like cells infected with Leishmania donovani: as an in vitro model of visceral leishmaniasis. The in vitro antileishmanial activity of primaquine-loaded nanoparticles showed a 21-fold increase in ED50 compared with free primaquine. Although unloaded PIHCA nanoparticles also exhibited a significant anti-leishmanial effect, the loaded nanoparticles showed a synergistic effect compared with a mixture of unloaded nanoparticles and free primaquine at equivalent concentrations. Primaquine release and isohexanol production were evaluated in a lysosomal fraction; the correlation of both with protein concentration and the rapid drug release indicate the processes are associated with an enzymatic degradation. The results indicate that PIHCA and other polyalkylcyanoacrylates may be useful for targeting drugs at intracellular Leishmania, and that the unloaded carrier itself could be of interest in experimental chemotherapy of leishmaniasis.

Animals

Comparison of nephrotoxicities of different polyoxyethyleneglycol formulations of amphotericin B in rats.

The aim of the present study was to assess whether amphotericin B (AmB)-Myrj 59, AmB-polyoxyethyleneglycol 24 cholesterol (PC), and AmB-Synperonic A50 (SA50) were less nephrotoxic than AmB-deoxycholate (DC). Rats were treated with the different AmB formulations (10 mg/kg of body weight) intraperitoneally or with the surfactants alone. A group of control rats receiving the vehicle was also examined. After 6 days of daily intraperitoneal injections of AmB-DC, decreased body weight and glomerular filtration rate as well as increased degree of diuresis, uremia, microalbuminuria, and N-acetyl-beta-D-glucosaminidase excretion in urine were noted. Urinary excretion of potassium and sodium was also decreased in AmB-DC-treated rats. Most of these effects were more pronounced with AmB-PC and AmB-SA50. In contrast, AmB-Myrj 59 was less nephrotoxic than AmB-DC. Indeed, after 6 days of treatment with AmB-Myrj 59, the natriuria, kaliuria, albuminuria, and glomerular filtration rates were unchanged compared with those of controls. Moreover, the body weight loss and uremia increase of the rats treated by AmB-Myrj 59 were less than those of the rats treated with the commercial preparation. Among the surfactants, only PC was toxic for the rats. The intrinsic toxicity of PC and the higher systemic exposure to AmB could contribute to increased toxicities of AmB-PC and AmB-SA50, respectively. AmB-Myrj 59 was less nephrotoxic than AmB-DC at equivalent areas under the plasma concentration-time curves. These preliminary results suggest that this formulation could be a good alternative to the commercial product.

Amphotericin B

Boneline: evaluation of an initiative to improve communication between specialists and general practitioners.

In response to a previous study of GPs' and consultants' satisfaction with orthopaedic outpatient referrals, orthopaedic surgeons at Doncaster Royal Infirmary made themselves available for telephone consultations with general practitioners (GPs) at advertised times. This service, called 'Boneline', was used infrequently, though the GPs who did use it found it valuable, and reported that a number of referrals had been avoided by speaking to the consultant. There was, however, no significant change in the rate at which requests for out-patient appointments were received during the six months of Boneline's operation. Opportunities for improving telephone communication between GPs and consultants are discussed.

Communication

The influence of Myrj 59 on the solubility, toxicity and activity of amphotericin B.

The effect of Myrj 59 (a polyoxyethyleneglycol derivative of stearic acid) on amphotericin B (Am B) solubility, toxicity and activity has been investigated. We showed that Myrj 59 could solubilize the antibiotic. Moreover, it also decreased and abolished the haemolytic activity of the drug by increasing the resistance of the red blood cells and impairing the interaction of Am B with the cellular membrane cholesterol, but it did not modify the in-vitro antifungal activity of the drug. On the other hand, Myrj 59 did not decrease the acute in-vivo toxicity of the drug (LD50 and nephrotoxicity). In a previous study we have shown that a polyoxyethleneglycol derivative of cholesterol could solubilize Am B and was able to decrease the in-vitro and in-vivo toxicity of the antibiotic without altering its in-vitro antifungal activity. The results of the present study suggest that the cholesterol moiety of the surfactant is not necessary to decrease the in-vitro lytic activity of the drug but could play a role in the reduction of the in-vivo toxicity.

Amphotericin B

A seven-year follow-up of proximal gastric vagotomy. Clinical results.

During a 7-year period proximal gastric vagotomy (PGV) was performed in 565 patients. Of these, 210 patients with duodenal ulcer and 14 with dyspepsia without demonstrable ulcer at the time of operation were followed for 5--7 years. Sixty-six percent are symptom-free (Visick I), 23% have no complaints when they take certain dietary measures (Visick II), 3% are improved but still have periods of dyspepsia (Visick III), and 8% are failures because of recurrent ulcer (Visick IV). There were 4 duodenal, 3 pyloric, 5 prepyloric, and 7 lesser-curve gastric recurrences. There were one operative death (0.2%) and one major complication (0.2%). The side effects after PGV are mild, infrequent, and seldom of any significance to the patients. Diarrhoea and dumping are virtually eliminated. Body weight was stable during the whole period of study, and blood chemistry did not disclose any deficiency in haemoglobin, serum iron, or vitamin B12 which might be attributed to PGV. It is concluded that 5--7 years after proximal gastric vagotomy for duodenal ulcer there is a 10% recurrence rate, but the low risk of death and of severe complications and the lack of significant side effects more than outweight the high recurrence rate.

Body Weight

Advances in tuboplasty.

Reconstructive oviductal surgery was performed on 205 private patients with primary and secondary infertility, who were selected from 1075 endoscopic examinations. Each patient underwent an infertility survey which included gamete formation, reception and deposition of gametes, nidation, post-coital, and semen analysis. Only those with tubal abnormalities, not responding to conservative therapy after a minimum period of six months following laparoscopic examination, were selected for tuboplasty. Spiral stents for fimbrioplasty and straight teflon tubing for mid-portion and cornua obstruction were employed. These stents were removed eight weeks post-surgery, under local anesthesia at the office. Of the 205 tuboplasties, 193 patients had sustained patency; 75 conceived; 7 aborted; and 1 had an ectopic pregnancy. Pregnancy occurred between 1 and 26 months after removal of the stents. Complications were very few. The use of Roland spiral teflon stents has resulted in a greater percentage in patency and pregnancy rates, as compared to those without use of stents.

Fallopian Tubes

Light and electron microscopical studies of parietal cells before and one year after proximal gastric vagotomy in duodenal ulcer patients.

In 4 duodenal ulcer patients the morphology of parietal cells has been studied before and one year after proximal gastric vagotomy (PGV). The average basal gastric acid secretion of the 4 patients was reduced from 9.2 m.mol/h before to 0.9 m.mol/h one year after PGV (90% reduction). The reduction in acid secretion was not accompanied by changes in the morphology of the parietal cells. Light microscopical studies indicated that the average cell size was about the same before and one year after PGV. Electron micro scopical studies showed only negligible changes in the parietal cell ultrastructure.

Duodenal Ulcer