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Biomedical subjects

P Lapalus

Publications and source records attributed to P Lapalus.

At least 73 records · Page 4Linked to original sources

Changes in lymphocyte beta-adrenoceptor density after dilevalol oral treatment.

Dilevalol (R,R'-isomer of labetalol) is an antihypertensive agent combining non-specific beta blockade with peripheral vasodilatation due to beta 2-receptor agonism. The aim of this study was to determine the effects of chronic dilevalol administration on lymphocyte beta 2-adrenoceptor density. The investigation was conducted as a double-blind, placebo-controlled comparison. Ten days of chronic dilevalol (400 mg) or placebo treatment was administered to 12 healthy normotensive volunteers. Clinical and biochemical parameters: heart rate (HR) systolic and diastolic blood pressure (SBP, DBP), electrocardiogram, norepinephrine (NE), epinephrine (E), MHPG (3-methoxy-4-hydroxyphenylethylene glycol; one of the major brain metabolites of NE) were analysed on the first day (D1) before (H0) and 3 h after oral treatment (H3) and on the tenth day (D10). Clinical results showed no significant changes in HR, DBP, SBP in the two groups (placebo, n = 6; dilevalol, n = 6). NE increased 3 h after the first oral dilevalol intake (p less than 0.05). This increase is greater than that due to the circadian variation observed in the placebo group. Acute dilevalol treatment seems to increase the plasma circulating NE level, which returns to normal values after 10 days of chronic treatment. Binding assays were performed before and after 10 days of treatment. In the placebo group, no change in beta-adrenoceptor density was observed (36.6 +/- 8.3 versus 38.3 +/- 9.4 femtomol/mg of protein). Lymphocyte beta-adrenoceptor density (Bmax) significantly decreased after 10 days of dilevalol treatment without any changes in affinity (KD). Results were 40.3 +/- 11.6 (D1) and 30 +/- 7.6 (D10) (p less than 0.05). It was concluded that dilevalol down-regulated lymphocyte beta 2-adrenoceptor density, suggesting that beta 2 agonism of dilevalol is predominant.

Adult↗

Influence of hemodialysis on zidovudine (AZT) and its glucuronide (GAZT) pharmacokinetics: two case reports.

Zidovudine (AZT) is a new anti retroviral agent widely used in the treatment of AIDS and related diseases. It has a short elimination half-life (1 h) in patients with normal hepatic and renal functions, and it is extensively metabolized to a glucuronide derivative (GAZT). In patients with end stage renal disease, the AZT elimination half-life is slightly increased (1.9 h) while for GAZT the very important increase of this parameter results in a major risk of accumulation. A 4-h hemodialysis is more efficient in removing GAZT than AZT. In these patients not only AZT but also GAZT plasma levels should be closely monitored.

Acquired Immunodeficiency Syndrome↗

Steady-state serum pharmacokinetics and bioequivalence of 500 mg oral versus 200 mg intravenous ciprofloxacin.

The pharmacokinetics of ciprofloxacin were examined after five days of treatment with 500 mg orally and 200 mg intravenously twice a day, in six healthy volunteers in an open, randomized crossover study. The ciprofloxacin concentrations were determined in serum by high performance liquid chromatography. The mean serum peak concentrations were obtained in 1 to 1.5 h by the oral route and the values reached were similar after the oral and intravenous dose (2.56 +/- 0.62 micrograms/ml and 2.6 +/- 0.67 micrograms/ml respectively). The terminal elimination half-life was about 4.5 h for oral form and 5 h for intravenous form. The absolute bioavailability of the oral ciprofloxacin was about 83%.

Administration, Oral↗

[Effects of antibiotics on the production of prostaglandins by macrophages in vitro].

Many reports have pointed out a relationship between antibiotics and immunity. It has been shown that antibiotics are able to modify polynuclear chemotactism, bacteria phagocytosis by macrophages, lymphocyte proliferation and the production of various cytokines (interleukins I, II...). On the other hand, the immunoregulatory activity of metabolites of arachidonic acid is proposed to explain, in part, these properties. For example it is well established that PGE2 has a negative retro control on Interleukin production by monocytes. Moreover eicosanoids are probably involved in the inflammatory and vasoactive reactions during the septic shock syndrome observed frequently during phagocytosis and bacterial lysis of Gram negative bacteria. Thus it seems interesting to evaluate the antibiotics activity on eicosanoid monocyte production. We have studied the influence of ciprofloxacin, ofloxacin, pefloxacin, imipenem, doxycycline, clindamycin and cefadroxil at various concentrations on eicosanoid production by A 13187 calcium ionophore activated mouse peritoneal macrophages (P 388 D1). The analyzed prostaglandins are: 6 keto (PGI2), PGE1, PGE2, F2 alpha, A2, B2, TxB2 et PG D2. All the antibiotics tested show either an inhibiting or a stimulating action on eicosanoid production. These immunomodulatory and pro-inflammatory effects must be considered, together with anti-infectious activity before the prescription of an antibiotic.

Animals↗

Immunohistopathologic findings in proliferative diabetic retinopathy.

We performed immunopathologic studies on pars plana specimens obtained by biopsy in patients with diabetes mellitus type I or II and by autopsy in diabetic patients and normal subjects. Frozen sections were treated with several antisera, including anti-IgG, complement components, and major histocompatibility complex antigens, as well as anti-factor VIII to detect vascular structures. The results showed IgG in a linear pattern at the basal pole of pigment epithelial cells and complement deposits of C3c, C3d, and C4 at the same location and in the stroma. HLA-DR expression was found at the level of the pigmented cells. These data suggest that some autoimmune processes may be involved in proliferative diabetic retinopathy at the level of the pigment epithelium, but it is unknown whether they are an epiphenomenon of neovascularization or if they play a role in its initiation.

Adult↗

Neurotransmitters and intraocular pressure.

The role of the ocular autonomic nervous system in IOP regulation has been well established. Pharmacological and autohistoradiographic studies confirmed the high density of beta 2 and alpha 2 receptors on ciliary processes and iris epithelium. Their respective pharmacological activation or blockade is discussed. The role of other ocular neurotransmitters is also complex, as shown by the paradoxical similar action of dopamine agonists and antagonists on IOP. Concerning the cholinergic system, ocular muscarinic receptors are pharmacologically not well documented. Numerous other neurotransmitters may modulate IOP without necessarily leading to the development of new drugs. Drugs of the future will probably concentrate on dopaminergic agonists, cAMP-stimulators such as forskolin, prostaglandins, and cannabinoids.

Animals↗

HLA DR and DQ distribution in normal human ocular structures.

HLA DR and DQ distribution was investigated in normal human ocular tissues, together with class I antigens and immunocompetent cell subsets, by immunofluorescence and immunoperoxidase procedures. In the anterior segment, our findings, consistent with those of previous reports, showed the wide distribution of class I antigens, specially in the corneal epithelium, while class II antigens were restricted to very rare cells scattered in the conjunctiva, the peripheral cornea and the stroma of the ciliary processes. Some non pigmented epithelial cells of the ciliary processes were HLA DR and DQ positive. In the posterior segment, class I antigens were abundantly represented in the choroid and the retinal layers. Few HLA DR and DQ positive cells were seen in the choroid, similar to those found in the anterior segment. Normal RPE did not react with any monoclonal antibody, but numerous cells located in the retina were strongly HLA DR and DQ positive, all around the blood vessels, and not at the sites of endothelial cells. The characterization of those cells, which could be hypothetized as pericytes needs further studies but suggests close relationships between neuroretina and the immune system. This study may provide insight in the implication of the immune system in many poorly understood ocular diseases.

Adult↗

[Kinetics of pefloxacin diffusion in human bone tissue following a single infusion of 800 mg. Evaluation of an extraction technic using chloroform].

A better understanding of the pharmacokinetics of pefloxacin in human bone is warranted by the efficacy of this drug in the treatment of bone and joint infections. Surgical bone samples were taken at 30 mn, 1h, 6h, 12h and 24 h after the administration of a single 800 mg intravenous dose of pefloxacin over 1 hour for 26 patients who underwent surgery in an orthopedic surgery ward. Drug concentration was measured by a microbiological method (extraction of the antibiotic in buffer or with chloroform). Up until the 24th hour, in 25/26 cases, the bone levels were superior to 2 mg/l (the critical concentration of pefloxacin) in cortical as well as in spongy bone. Our study reveals a good diffusion of pefloxacin in bone, results which support the idea that this antibiotic may be prophylactically effective in orthopedic surgery.

Bone and Bones↗

Effects of aFGF and bFGF on wound healing in rabbit corneas.

After the debridement of the entire corneal epithelium of the rabbit eye, epithelial cells of conjunctival origin cover the denuded corneal surface. Under such experimental conditions, the rate of wound healing is considerably delayed and total regeneration is completed within 15 to 20 days, allowing evaluation of various drugs, such as the Fibroblast Growth Factor. Both acidic and basic FGF were administered topically on totally de-epithelialized rabbit eye, at three different concentrations of 1.5 and 10 Stimulation Units/50 microliters, 3 times per day. A dose-response effect was observed and in each case, acidic FGF was found to be much more potent than bFGF in increasing the rate of wound healing of the cornea. These results are correlated with a new purification procedure, avoiding acid treatment of the tissue extract. The systemic diffusion of FGF allows the contralateral eye cells to be also stimulated for mitosis and migration and to heal faster than the control eyes.

Animals↗

Autoradiographic localization of beta-adrenergic receptors in rabbit eye.

Using an in vitro autoradiography, beta-adrenergic receptors were localized in the rabbit eye. Autoradiograms were generated by apposition of isotope-sensitive film to slide-mounted eye sections, labelled with [125I](-)Iodocyanopindolol. A high density of silver grains was obtained in conjunctival, corneal and ciliary process epithelium. Binding sites were also present in corneal endothelium, iris epithelium, lens epithelium, choroid and extraocular muscles. In some areas, retina was also labelled. Studies with beta-adrenergic compounds showed that the majority of beta-adrenergic receptors, detectable by autoradiography, were of the beta2 type in the rabbit eye.

Animals↗

[Effects of rifampicin on the pharmacokinetics of doxycycline].

Because of the potential of doxycycline-rifampicin for oral therapy of infectious diseases with intracellular bacteria, specially brucellosis and the well known cytochrome P450 enzyme system inductive activity of rifampicin, we may speculate that this antibiotic can altered the serum concentration-time profile of doxycycline when given in combination. So, the main pharmacokinetic parameters of doxycycline (200 mg/day orally) in seven patients before and after rifampicin association (10 mg/kg/day). According to the results two groups may be individualized: the first (n = 3) showed no variation in the doxycycline++ pharmacokinetic; the second (n = 4) had significant differences (p less than 0.05) for all pharmacokinetic parameters (AUC, T1/2, Cl, Cmax) after association with rifampicin (AUC were half reduced). Moreover, as regard doxycycline half-life, a difference was observed between these two groups before rifampicin treatment: in one case T1/2 was of 17.9 + 6.6 hours, while in the other it was of 9.2 + 2.3 hours. The group with obvious enzyme induction had the longer half life. This suggests that the inductive rifampicin effect would be essentially observed in patients considered as "poor metabolizers". The pharmacokinetic modifications observed are likely of clinical significance on account of the doxycycline serum concentrations decrease under the MIC of most agents of intracellular infections.

Adult↗

Expression of the antigens recognized by monoclonal antibodies to human amnion (GB4, GB9, GB11) on the rabbit eye during embryonic development.

Three monoclonal antibodies to human amnion (GB4, GB9 and GB11) which recognized well-defined structures of the adult rabbit eye were used to study the embryonic eye development. The reactivity of GB4 could be identified on the migrating neural crest cells under the corneal epithelium at 2 weeks of gestation. At 3 weeks of gestation, the conjunctival epithelium, corneal epithelium and corneal endothelium reacted with GB4. In the newborn rabbit, the corneal epithelium was reactive with GB9 instead of GB4; corneal endothelium was positive with GB4 at this stage, but gradually became negative in the adult rabbit; the subcapsular epithelium of the lens was recognized by GB4 when it changed from pseudostratified to simple cuboidal epithelium. During early embryonic life, GB11 was positive on the external retinal layer of the optic cup and lens vesicle. In the adult, GB11 reacted only with the pigmented epithelium of the ciliary processes. The results of this study demonstrated that the expression of antigens recognized by GB4, GB9 and GB11 could be mapped according to the epithelial differentiation of the rabbit eye during embryogenesis.

Amnion↗

Effects of a new anti-allergic agent: the magnesium salt of N-acetyl-aspartyl-glutamic acid on experimental allergic inflammation of the rabbit eye.

We evaluated the efficacy of N-Acetyl-Aspartyl-Glutamic acid (magnesium salt) (NAAGA) eye-drops in preventing the conjunctival and uveal allergic inflammation induced by reverse passive Arthus reaction in the rabbit. The permeability of the blood-conjunctival and blood-aqueous barriers was investigated by the leakage of 125I-labelled rabbit serum albumin injected intravenously prior to the challenge with the antigen. Permeability of both barriers was markedly increased 2 hours after the triggering of the allergic reaction; marked edema of the conjunctiva was also observed. Pretreatment with 1, 3, 6% (w/w) NAAGA eye-drops prevented the conjunctival inflammatory changes in a dose related manner and to a lesser degree, the breakdown of the blood-aqueous barrier. The distribution of topically applied 14C-NAAGA in the rabbit eyes was also investigated.

Animals↗

Monoclonal antibodies to human amnion recognize different components of the rabbit eye.

The epithelium of the eye originates from embryonic ectoderm, whereas the amnion is an extra-embryonic membrane that bears close relationship with many ectodermal tissues. Shared antigens have been identified between human amnion and cornea using rabbit antisera to human amnion. Three monoclonal antibodies to human amnion, GB4, GB9, and GB11 were studied by immunofluorescence on the anterior segment of the rabbit eye. GB4 recognized the epithelium of the conjunctiva and the subcapsular epithelium of the lens. GB9 reacted only with the central four fifths of the corneal epithelium; the peripheral epithelium near the limbus was not reactive. GB11 detected the pigmented epithelial cells in ciliary processes.

Amnion↗