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J Domenech

Publications and source records attributed to J Domenech.

At least 55 records · Page 3Linked to original sources

Structure-absorption relationships of a series of 6-fluoroquinolones.

The physicochemical constants and some structural parameters (topological, steric, and electronic) of eight third-generation monofluorate quinolones (six uncommercialized and two used clinically [ciprofloxacin and enrofloxacin]) were determined: pKa, intrinsic solubility (S0), chromatographic capacity factor, partition coefficient (P), valency molecular connectivity, molecular volume, molecular surface area, dipolar moment, and charges associated with each atom of the molecule. The apparent intestinal absorption rate constants (K(abs)) in rat (in vivo perfusion) and the MICs at which 90% of the isolates are inhibited (MIC90s) against 100 Escherichia coli strains were also determined. We sought to establish simple nonlinear and multiple linear correlations between K(abs), on the one hand, and lipophilic parameters and other physicochemical and structural parameters estimated. Of the nonlinear functions examined, the hyperbolic had the best correlation between K(abs) and P, which was in accordance with the Wagner-Sedman (J. G. Wagner and A. J. Sedman, J. Pharmacokinet. Biopharm. 1:23-50, 1973) equation, whereas, after application of the stepwise multiple linear regression method, a multiple linear correlation with some predictive value could be established only between K(abs) as a dependent variable and log P and log S0 as independent variables. In conclusion, the K(abs) and MIC90 of the quinolone CNV 8902 suggest that it is a sufficiently interesting compound to warrant the investigation of its potential therapeutic use orally.

Animals↗

The mechanisms involved in the impairment of hematopoiesis after autologous bone marrow transplantation.

Hematopoiesis after autologous bone marrow transplantation (BMT) is characterized by a prolonged and severe deficiency of marrow progenitors for several years, especially of erythroid and megakaryocyte progenitors, while the peripheral blood cells and marrow cellularity have reached relatively normal values within a few weeks. These anomalies are comparable to those reported for allogeneic BMT, despite the absence of any allo-immune reaction or post-graft immunosuppressive therapy. Post-graft hematopoietic impairment is the consequence of quantitative and qualitative changes involving both stem cell and stromal compartments which are expressed by an impaired capacity of stem cell self-renewal and commitment towards erythroid and megakaryocytic lineages. Besides the toxicity of conditioning regimens, hematopoietic reconstitution using autologous grafts is particularly dependent on a combination of factors related to the patient, such as underlying disease and pre-graft chemotherapy regimens, and to the graft processing itself, such as in vitro purging with chemotherapeutic agents.

Antineoplastic Agents↗

Influence of formulation on the in vitro transdermal penetration of flutrimazole.

Flutrimazole (1-[(2-fluorophenyl)(4-fluorophenyl)phenylmethyl]-1 H-imidazole, CAS 119006-77-8, UR-4056) is a new wide spectrum local imidazolic antifungal agent that has already been formulated as a dermal cream (FDC). A comparative study was carried out of the release of flutrimazole from two emulsions in which the drug has been incorporated differently: one dissolved in the oily phase (E24) and the other dispersed in the aqueous formulation phase (E25). Based on the E25 formulation, two more dermal creams were prepared, E27 with benzyl alcohol and E28 with diazolidinyl urea as preservative agents. A comparative study of transdermal penetration including E27, E28, FDC (reference 1% flutrimazole dermal cream) and 1% flutrimazole hydroalcoholic solution was also performed. An amount of the sample dosage form containing 10 mg of flutrimazole was applied to a Franz type cell. The penetration membrane used was cellulose acetate in the release studies and human skin provided by a plastic surgery clinic in the transdermal penetration study. The amount released after 7 h was 36.3 +/- 4.9 micrograms when flutrimazole was dissolved (E24) and 35.9 +/- 5.3 micrograms when flutrimazole was dispersed (E25). Although the differences were not significant, the cream with dispersed flutrimazole was selected for further penetration studies due to its better stability observed in previous studies. The amounts of drug penetrated after 44 h were 31.3, 41.5, 38.3 and 186.5 micrograms for E27, E28, FDC dermal creams and topical hydroalcoholic solution, respectively. The solution showed a statistically significant difference (p < 0.05) from the other formulations, however, no differences were observed between the dermal cream formulations. No differences were neither obtained between the different dermal creams when the amount of drug retained in the skin was compared. This allows to assert that the excipients used do not have different influences on transdermal penetration. In all cases, the mean quantity penetrated in relation to the dose applied was at most 0.5%. These results allow to infer that flutrimazole shows scarce transdermal penetration. Further, the amount of flutrimazole retained per gram of skin is more than 100 times the MIC per gram obtained in previous in vitro studies. It may be assumed that the topical application of the new formulations assayed would allow to obtain a good therapeutic response.

Administration, Cutaneous↗

An antigenic water-soluble glucogalactomannan extracted from cell walls of Paecilomyces fumosoroseus and Paecilomyces farinosus.

The water-soluble fraction (F1S) obtained after solubilizing in alkali the cell walls of four strains of Paecilomyces fumosoroseus and two of Paecilomyces farinosus amounted to 8.3-14.5% of the dry cell wall material. Two polysaccharides, F1S-A (13-20%) and F1S-B (57-68%) were separated from F1S by gel permeation through Sepharose CL-6B. 1H and 13C NMR spectra of F1S-B were recorded and showed analogous structural features in the six isolates of the two species. The fractions isolated from P. fumosoroseus strain CBS 375.70 were subjected to structural analysis and shown to be a (1-->4)-alpha-glucan (F1S-A) and a branched (1-->6)-mannan with terminal residues of beta-galactopyranose (F1S-B). Polyclonal antibodies against the latter polysaccharide were obtained (titre 1/8000). These antibodies reacted specifically with the F1S-B polysaccharides obtained from the four strains of P. fumosoroseus and the two strains of P. farinosus, but they did not react with similar fractions from other species of the same or related genera. The antibodies specifically stained P. fumosoroseus hyphae in indirect immunofluorescence tests.

Antigens, Fungal↗

Manifestation and epidemiology of contagious bovine pleuropneumonia in Africa.

Contagious bovine pleuropneumonia (CBPP) is one of the major threats to cattle health and production in Africa. This article reviews the clinical manifestations, lesions and epidemiology of the disease. The clinical manifestations and lesions are typical and are no different in Africa from those seen in other countries. CBPP is a respiratory disease characterised by pneumonia and serofibrinous pleurisy. The usual form of this disease is acute but chronic forms are frequent, particularly in endemic regions. Hyperacute forms, with a high mortality rate, can be seen at the beginning of outbreaks in newly infected regions. The epidemiology of the disease in Africa is dominated by four factors, namely: cattle are the only species affected, there is no reservoir in wild animals, clinical cases or chronic carriers are the usual sources of infection, through direct contact, and cattle movements play a very important role in the maintenance and extension of the disease. CBPP is widespread in Africa and, according to the Office International des Epizooties and to various reports in 1995, the disease is present in 24 countries of tropical Africa. In western Africa, CBPP is mainly enzootic or sporadic but in some countries the incidence is increasing. The situation in Central Africa is not very alarming. However, in eastern and south-eastern Africa, CBPP has become a major issue, placing southern Africa under direct threat. An evaluation of economic losses due to the disease and the cost-benefit ratio of control programmes is indispensable, since such economic assessments are needed before policy-makers decide on programmes of control or eradication. This is an area which needs to be addressed immediately, as the launching of new campaigns, particularly in eastern and southern Africa, is urgently needed.

Africa↗

Granulocyte-macrophage colony-stimulating factor accelerates hematopoietic recovery after autologous bone marrow or peripheral blood progenitor cell transplantation and high-dose chemotherapy for lymphoma.

The use of recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF) as an adjunct to autologous bone marrow transplantation (ABMT) or peripheral blood progenitor cell (PBPC) transplantation was evaluated in 59 lymphoma patients. Patients were divided into three groups. In group I (n = 21) patients received rhGM-CSF (5 micrograms/kg daily) at the time of PBPC collection and during the recovery phase post-infusion. In group II (n = 12) patients received rhGM-CSF as an adjunct to ABMT. In group III (n = 26) they were grafted with bone marrow without rhGM-CSF. Administration of rhGM-CSF (groups I and II) significantly reduced the time to myeloid engraftment, the number of febrile days and the median duration of antibiotics administration and of hospital stay when compared with the group in which patients did not receive rhGM-CSF. The only difference between ABMT and PBPC, given with rhGM-CSF support, was observed in the duration of hospitalization (group I > group II, P < 0.05). These data show that rhGM-CSF is highly effective in reducing the duration of aplasia following BMT and PBPC transfusion, and there appears to be little difference in efficacy between these techniques, provided that patients also receive rhGM-CSF.

Adolescent↗

Prolonged impairment of hematopoiesis after high-dose therapy followed by autologous bone marrow transplantation.

Hematopoietic reconstitution has been studied in 180 patients after autologous bone marrow transplantation based on peripheral blood cell (PBC) recovery time and marrow progenitor counts sequentially tested for up to 4 years. Several factors that could influence hematopoietic reconstitution have been analyzed including sex, age, diagnosis, disease status, conditioning regimen, graft progenitor content, graft in vitro purging, and postgrafting administration of growth factors. Before transplantation, marrow progenitor values were normal only for colony-forming unit granulocyte macrophage (CFU-GM) in contrast to colony-forming unit-erythroid (CFU-E), burst-forming unit-erythroid (BFU-E), and colony-forming unit-megakaryocyte (CFU-Meg). After transplantation, as described with allogenic grafts, these values remained low for several years, although PBC counts were nearly normalized within a few weeks. Pregraft values were reached after 2 years for CFU-GM and BFU-E, and after 4 years for CFU-E, while CFU-Meg failed to reach pregraft values after this time. Normal levels were reached after 4 years only by CFU-GM. On univariate and multivariate analysis, the following factors appeared to delay both PBC and marrow progenitor reconstitution: underlying disease (particularly acute myeloid leukemias), graft characteristics such as low stem cell content and in vitro purging, conditioning regimens with total body irradiation or busulfan, and lack of postgraft administration of growth factors. In conclusion, high-dose therapy followed by bone marrow transplantation induces a deep and prolonged impairment of hematopoiesis irrespective of any alloimmune reaction or postgraft immunosuppressive therapy.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Protection of goats against rinderpest by vaccination with attenuated peste des petits ruminants virus.

The ability of the attenuated peste des petits ruminants vaccine virus to protect small ruminants against virulent rinderpest virus was investigated. Out of four susceptible goats that were infected with the highly virulent Saudi strain of rinderpest virus by intranasal ioculation, three developed mild clinical signs of disease and infected susceptible in-contact goats and cattle with rinderpest virus. However, four goats which had been vaccinated with the attenuated peste des petits ruminants virus resisted challenge with virulent rinderpest virus and did not infect susceptible in-contact animals.

Animals↗

Electrocardiographic diagnosis of the responsible coronary artery in acute inferior myocardial infarction through right chest leads V3R-V8R. A prospective study.

In order to identify the electrocardiographic changes that occur in right-chest leads V3R-V8R for the most significant diagnosis of the responsible coronary artery of acute myocardial infarction, the authors performed a prospective study on 66 patients in whom coronary arteriography was done between the first and twelfth weeks after suffering the infarction. Electrocardiograms were done within the first six hours after the onset of symptoms. Lesions of the right coronary artery were found in 46 patients--27 at a proximal level and 19 at a distal one--and in 20 patients the circumflex coronary artery was injured. The electrocardiographic findings were studied in 2 groups of leads: V3R-V4R and V5R-V8R. An ST elevation equal to or higher than 0.5 mm and the presence of Q waves in V3R-V4R are specific markers of lesions of the right coronary artery (P < 0.001). Lowering of the ST segment in V3R-V4R is a specific marker of a circumflex artery lesion (P < 0.001). An ST elevation equal to or higher than 1 mm in V3R-V4R is specific for a proximal lesion of the right coronary artery (P < 0.001). No specific marker for a lesion of the distal right coronary artery was identified, its more significant characteristic being an "isoelectrical" ST segment (between 0 and 0.4 mm), an rS morphology and positive T waves in V3R-V4R.

Aged↗

Overview and epidemiology of contagious bovine pleuropneumonia in Africa.

Contagious bovine pleuropneumonia (CBPP) is widespread in Africa and in other regions of the world. This disease is particularly important in the semi-arid, sub-humid and arid zones of tropical Africa, but CBPP incidence seems to be increasing in some parts of East Africa. The epidemiology of CBPP is characterised by the occurrence of sub-acute and symptomless infections, and the persistence of chronic carriers. Spread of the disease is associated with cattle movement. The major obstacles to eradication of CBPP are the difficulties in controlling cattle movement and applying quarantine and slaughter policies. Other difficulties arise due to the absence of a field test for diagnosis, the relatively short duration of post-vaccinal immunity and the lack of data on the economic impact of the disease. The Pan-African Rinderpest Campaign strategy for CBPP control and eradication conforms with national control programmes, which include cost/benefit analysis. It is planned to perform blanket vaccination against the disease for three to five years, depending on the economic situation of each country. Stringent control of cattle movement will complement vaccination campaigns. The eradication phase, including slaughter measures, will be instituted following reduction of CBPP incidence. Regional and international coordination will be instituted to control international cattle movement and harmonise control strategies.

Africa↗

Cytokine production in long-term marrow cultures after autologous bone marrow transplantation.

We compared the release of granulocyte-macrophage colony-stimulating factor (GM-CSF), granulocyte colony-stimulating factor (G-CSF) and tumor necrosis factor alpha (TNF alpha) in the supernatant of long-term bone marrow cultures (LTBMC) derived from 10 control patients and from 14 patients before and 3 months after autologous bone marrow transplantation (BMT). The three cytokines were spontaneously present in the supernatant of cultures established from patients before and after autologous BMT, while GM-CSF remained undetectable in the supernatants of control patients. The maximal levels of cytokines were produced after the first week and were not statistically different between control, patients before and after grafts although the granulocyte-macrophage colony-forming unit (CFU-GM) production in long-term culture (LTC) was lower in patients after graft compared with control patients (median values at LTC initiation: 32 and 158, respectively, P < 0.001 and median values of the total production: 510 and 12406, respectively, P < 0.002). However, GM-CSF was more frequently detected in patients after graft than in control patients. This study demonstrated that the production of GM-CSF, G-CSF and TNF alpha is not impaired in patients after graft (medians 0, 870.5, 173.5 pg/ml and ranges 0-31.2, 0-10 000 and 0-1426, respectively) compared with control patients (medians 0, 69, 66 pg/ml and ranges 0, 0-13 280 and 0-1318, respectively), although patients after graft were shown to have lower marrow CFU-GM counts. These results suggest that the ability of the accessory cells to produce these cytokines was not reduced after autologous BMT.

Adolescent↗

Long-term cultures to evaluate engraftment potential of CD34+ cells from peripheral blood after mobilization by chemotherapy with and without GM-CSF.

In this study we used a long-term culture system to evaluate engraftment potential of human peripheral blood (PB) cells mobilized by chemotherapy (CT) associated or not with granulocyte-macrophage colony-stimulating factor (GM-CSF). In six patients who underwent blood cell transplantation, PB CD34+ cells were cultured after mobilization and were compared to CD34+ cells in steady state from PB and bone marrow (BM). Qualitative differences were shown between PBC samples obtained after CT with and without GM-CSF. Despite similar CFU-GM counts at culture initiation, GM-CSF-mobilized CD34+ cells might contain a lower proportion of primitive stem cells, as suggested by the significant decrease in CFU-GM numbers produced beyond week 5 compared to CT-mobilized CD34+ cells (p = 0.033). Likewise, the percentage of CFU-GM produced beyond week 5 in relation to initial input was significantly lower than steady-state PB (p = 0.039) and than CT-mobilized CD34+ cells (p = 0.033). However, this CFU-GM production with GM-CSF-mobilized PB CD34+ cells was not different from cultures with BMC CD34+ cells. These results suggest that GM-CSF can mobilize CFU-GM in the blood mainly by differentiation at the expense of the primitive stem cell compartment. It appears valuable to define clearly for each mobilizing procedure a particular threshold of CFU-GM which reflects sufficient numbers of primitive stem cells to ensure long-term engraftment.

Adolescent↗

A comparative in vitro study of transdermal absorption of antiemetics.

Transdermal absorption of a series of antiemetics (alizapride, bromopride, clebopride, domperidone, metoclopramide, metopimazine, and scopolamine) was studied in vitro with the skin of hairless rats as the membrane. The aim of the study was to determine the permeation parameters [transdermal permeability rate constant (Kp), lag time, and flux] as a measure of the intrinsic permeability of these drugs across the skin, with a view to predicting their potential therapeutic formulation in Transdermal Therapeutic Systems. A linear correlation was established between the log Kp values corresponding to the antiemetics studied and their melting point (r = 0.8120, p < 0.05). The logarithm of Kp for the antiemetics studied can be predicted from the logarithm of the intrinsic partition coefficient (n-octanol-water) by a parabolic function (r = 0.9284, p < 0.01). Bromopride showed the shortest lag time (19.73 h), whereas clebopride was the most suitable drug as a candidate for formulation in transdermal delivery systems.

Administration, Cutaneous↗

Haemopoiesis of transplanted patients with autologous marrows assessed by long-term marrow culture.

We assessed the effect of antitumoural therapy at intensive doses on the haemopoietic system using long-term marrow cultures (LTMC) established from 33 patients (25 with haematological diseases and eight with solid tumours) after autologous bone marrow transplantation (ABMT). When compared to 42 pre-graft patients, a decreased CFU-GM production and a defect in stromal layer (SL) confluence were found after ABMT on day 90 but also on day 365. However, these abnormalities were observed only in patients with haematological diseases and no differences between pre-graft and post-graft results were found in patients with solid tumours. Among the patients with haematological diseases, on day 90 those with acute lymphoid leukaemias showed lower CFU-GM production whereas patients with non-Hodgkin's lymphomas developed more frequently subconfluent or confluent SL. Other factors studied such as sex, patient age, disease status, marrow purging and post-graft administration of growth factors did not appear to influence post-graft LTMC results. Multivariate analysis including all the patients has shown (a) that solid tumours were associated with higher CFU-GM production, and (b) that conditioning regimens with total body irradiation (TBI) or busulfan led more frequently to non-confluent SL. In conclusion, high-dose therapy followed by ABMT can induce a persistent impairment of the stem cell and stromal cell compartments, particularly in patients with haematological diseases conditioned with TBI, despite the absence of any alloimmune reaction and post-graft immunosuppressive therapy.

Adolescent↗

[Epidemiologic study of bluetongue in sheep, cattle and different species of wild animals in the Ivory Coast].

Between 1992 and 1993, a serological survey was conducted in Côte d'Ivoire on 623 sera from sheep, 215 sera from cattle and 211 sera from wild herbivores. These sera were tested for bluetongue virus (BTV) antibodies using an agar gel immunodiffusion test. The purpose of this survey was twofold: to establish the incidence of bluetongue in the country, and to analyse the putative role of BTV in the reproductive pathology of sheep. Seroprevalence was 52 +/- 4% in sheep, 95 +/- 3% in cattle, and 56 +/- 7% in wild herbivores. The authors found antibodies against BTV in kob (Kobus kob Erxleben, 1777), common waterbuck (Kobus ellipsiprymnus Ogilby, 1833), roan antelope (Hippotragus equinus Desmarest, 1804), buffalo (Syncerus caffer Sparrman, 1779), hartebeest (Alcelaphus buselaphus Pallas, 1766) and elephant (Loxodonta africana Blumenbach, 1797). A significant difference was found in seroprevalence in sheep between the three areas covered by the survey. Antibody prevalence increased significantly with age in sheep and wild herbivores, and seroprevalence was higher in dams with a history of abortion. It can therefore be concluded that bluetongue is enzootic in Côte d'Ivoire.

Age Factors↗

[Nervous syndrome in sheep on the Ivory Coast. I. Epidemiological and clinical study, methods of diagnosis and treatment].

The ovine nervous syndrome in Côte-d'Ivoire is similar to the cerebrocortical necrosis (CCN) due to vitamin B1 deficiency. All classical symptoms of CCN were observed (locomotor ataxia with subsequent paralysis) and histological evidence for polioencephalomalacia was given. However, the circumstances for occurrence of the disease are very different in the two cases, i.e. CCN is a disease encountered in young fattening ruminants in developed countries while the ovine nervous syndrome is mainly observed in Côte-d'Ivoire during the dry season when pastures become sparse and dry and when the feed supply is insufficient. Thus, the main cause, which is rather univocal, is a sudden decrease in the nutritive value of the diet, but the accurate etiopathogenesis of the disease has not yet been determined. In a flock where 10-30% of the animals are ill, the mortality may reach 80-90%. No classical biochemical assays were specific enough to establish a precise diagnosis of the nervous syndrome. However, it should be pointed out that the CK (creatinine kinase) values very regularly rose and that the ASAT (aspartate aminotransferase) values were high in 75% of the cases. In the present African field conditions, the precise diagnosis is based on the efficiency of the vitamin B1 treatment and, for the dead animals, on the histological analysis of the brain.

Animals↗