Biomedical subjects

S Janicki

Publications and source records attributed to S Janicki.

At least 19 recordsLinked to original sources

PubMed2004

Development, evaluation, and application of sediment quality targets for assessing and managing contaminated sediments in Tampa Bay, Florida.

Tampa Bay is a large, urban estuary that is located in west central Florida. Although water quality conditions represent an important concern in this estuary, information from numerous sources indicates that sediment contamination also has the potential to adversely affect aquatic organisms, aquatic-dependent wildlife, and human health. As such, protecting relatively uncontaminated areas of the bay from contamination and reducing the amount of toxic chemicals in contaminated sediments have been identified as high-priority sediment management objectives for Tampa Bay. To address concerns related to sediment contamination in the bay, an ecosystem-based framework for assessing and managing sediment quality conditions was developed that included identification of sediment quality issues and concerns, development of ecosystem goals and objectives, selection of ecosystem health indicators, establishment of metrics and targets for key indicators, and incorporation of key indicators, metrics, and targets into watershed management plans and decision-making processes. This paper describes the process that was used to select and evaluate numerical sediment quality targets (SQTs) for assessing and managing contaminated sediments. These SQTs included measures of sediment chemistry, whole-sediment and pore-water toxicity, and benthic invertebrate community structure. In addition, the paper describes how the SQTs were used to develop site-specific concentration-response models that describe how the frequency of adverse biological effects changes with increasing concentrations of chemicals of potential concern. Finally, a key application of the SQTs for defining sediment management areas is discussed.

Ecosystem↗

PubMed2004

Dissolution test for ivermectin in oral veterinary paste.

A dissolution test for oral veterinary pastes with ivermectin using the Ph. Eur. paddle apparatus was developed. Sink conditions were achieved with sodium lauryl sulphate in a concentration of 0.5% as dissolution medium. By means of HPLC fast degradation of ivermectin was observed in HCl 0.1 M solution. Rotation speed of the paddle at 75 rpm was appropriate as demonstrated in a study comparing two different products.

Anthelmintics↗

PubMed2002

Acute protection against exercise-induced bronchoconstriction by formoterol, salmeterol and terbutaline.

The onset of bronchoprotection as obtained by various beta2-agonists has not been examined in a comparitive study. In this study, the onset of bronchodilation and protection against exercise-induced bronchoconstriction in asthmatics after inhalation of the long-acting beta2-agonists formoterol and salmeterol and the short-acting beta2-agonist terbutaline were measured. Twenty-five subjects with asthma and a history of exercise-induced bronchoconstriction (mean baseline forced expiratory volume in one second (FEV1): 90% predicted; mean fall in FEV1 after exercise: 31% from baseline) were enrolled in this double-blind, double-dummy, placebo-controlled, randomized, four-period crossover study. Exercise challenges were performed on 12 days at either 5, 30, or 60 min after inhalation of a single dose of formoterol (12 microg Turbuhaler), salmeterol (50 microg Diskus), terbutaline (500 microg Turbuhaler) or placebo. Exercise-induced bronchoconstriction (maximum fall in FEV1 or area under the curve) did not differ significantly between terbutaline, formorerol and salmeterol either 5, 30, or 60 min after inhalation of the study medication. In contrast, the onset of bronchodilation was slower after salmeterol compared to terbutaline and formoterol (p<0.05, each), which both showed a similar time course. At all time points between 5 and 60 min, formoterol provided significantly greater bronchodilation than salmeterol (p<0.05). These data indicate that equipotent doses of the bronchodilators salmeterol, formoterol and terbutaline were similarly effective with respect to their short-term protective potency against exercise-induced bronchoconstriction, despite the fact that the time course of bronchodilation was significantly different between the three beta2-agonists.

Administration, Inhalation↗

PubMed2002

Dose reduction of inhaled corticosteroids under concomitant medication with montelukast in patients with asthma.

The present study aimed at comparing the effects of a dose reduction of inhaled corticosteroids on lung function, indirect measures of airway inflammation and clinical scores during treatment with a leucotriene receptor antagonist. In 50 patients (mean forced expiratory volume in one second (FEV1) 94% predicted), steroid doses (800 microg beclomethasone dipropionate) were first reduced to 50% and then to 25%, for 6 weeks each. One group received a placebo and the other group received montelukast (10 mg). The first reduction did not cause significant effects. During the second, FEV1 and peak expiratory flow decreased in both groups (p<0.001). Daytime symptoms were not altered with placebo but were reduced by montelukast (p<0.05). Night-time symptoms were slightly elevated with placebo (p<0.05) but not montelukast, as well as the use of supplemental salbutamol. Changes in provocative concentration of methacholine causing a 20% fall in FEV1 (PC20), sputum eosinophils and exhaled nitric oxide were mostly nonsignificant for both placebo and montelukast. These data demonstrate that a 75% reduction in the dose of steroid given to patients with asthma led to a deterioration in lung function not prevented by montelukast, whereas changes in clinical state seemed to favour montelukast treatment. It therefore appears that potential effects of montelukast, in the presence of low-dose steroids, could not be attributed to single indices of lung function or airway inflammation.

Acetates↗

PubMed2001

Studies on the effect of pH on the lipoidal route of penetration across stratum corneum.

The effect of pH on the excised skin permeability towards two model lipophilic compounds was studied in the range of pH 1.0-10.0 and 1.0-12.0, for hydrocortisone and testosterone, respectively. Suspensions of the model compounds in appropriate buffers (0.1-0.2 M) were applied to the intact skin, delipidized skin, skin pretreated with Azone or sodium lauryl sulfate solution and the percutaneous penetration was observed for 28 h. Within the studied pH range, up to pH 11.0 no change in the penetration through the skin and skin accumulation was observed for both compounds. Significant, 3-4-fold, increase of penetration of testosterone was noted only at pH 12.0, however the change was neither fast not progressing with time. None of the pretreatment procedure influenced the observed relationship between pH and skin permeability. It is concluded that the lipoidal route of penetration is not affected by solutions at pH within the range 1.0-11.0.

Anti-Inflammatory Agents↗

PubMed2001

In vitro studies on penetration of terpenes from matrix-type transdermal systems through human skin.

Polyurethane matrices containing up to 39% of the terpenes eucalyptol, L-limonene, D-limonene, dipentene or terpinolene were produced. Release of the terpenes directly to the acceptor fluid, as well as through isolated human epidermis and dermis, was studied. In the presence of dermis the penetration profiles were very similar to the release profiles, indicating that dermis does not present a barrier for penetration of terpenes. For all terpenes the penetration was slower in the presence of epidermis (K(p) was in the range 0.21-1.8x10(-3) cm/h). Release and penetration through the epidermis and dermis were fastest for dipenetene (mixture of D-limonene and L-limonene), being at least 3-4 times faster than for D-limonene and L-limonene. Large amounts of terpenes found in epidermis (approximately 1.5 mg/cm(2)) indicate that affinity of these compounds to the stratum corneum is very high.

Administration, Cutaneous↗

PubMed2001

Submicron emulsions as drug carriers. Studies on destabilization potential of various drugs.

Few drugs have been successfully formulated as submicron emulsions. The physicochemical stability of submicron emulsions on admixture of drugs is the main factor limiting a wider use of this type of vehicle for parenteral or other routes of administration. In a short-term stability studies we have investigated 35 drugs with regard to their compatibility with 20 or 5% parenteral fat emulsions. The study has shown that interaction of drugs with submicron emulsions is complex in nature. Taking into consideration the physicochemical properties of a drug e.g. lipophilicity or ionization, it is difficult to predict changes in the physical stability of the system. If destabilization occurs it is maximal at saturated concentrations and the presence of even significant amounts of the solid phase formed by undissolved drug does not influence the short-term stability of the system. Due to the increased ratio of emulgator to oil, emulsions containing 5% of oily phase are less susceptible to destabilization than 20% emulsions.

Chemical Phenomena↗

PubMed2001

Bioavailability of diazepam from aqueous-organic solution, submicron emulsion and solid lipid nanoparticles after rectal administration in rabbits.

The bioavailability of diazepam in rabbits after rectal administration of three formulations: organic-aqueous Relsed rectal solution (containing ethanol, benzyl alcohol and propylene glycol), submicron emulsion and solid lipid nanoparticles (SLN), was studied. Submicron emulsion contained MCT oil (20% w/w), egg lecithin and poloxamer; SLN were prepared with cetyl palmitate 10% w/v and non-ionic emulsifying agent, Plantacare. All formulations contained 4 mg/ml of diazepam and the dose administrated to rabbits was 2 mg/kg. In both submicron preparations nearly the same mean size of the dispersed particles (201-206 nm) and the fraction of the free drug in aqueous phase (0.9-1.5%) was determined. Besides very moderate prolongation of drug release, the submicron emulsion as a vehicle did not alter pharmacokinetics of diazepam when compared with the solution: the mean C(max) was 48.9+/-24.0 and 49.5+/-17.0 ng/ml, and area under the curve was 134.0+/-42.3 and 186.8+/-59.8 ng h/ml, for solution and emulsion, respectively. The low relative bioavailability, 47% compared to the solution, was observed after administration of SLN. Transmission electron microscopy pictures revealed that some of diazepam is present on the surface of the SLN and this fraction was immediately absorbed, while the diffusion of the drug in the solid core was not efficient enough to allow a complete release. It may be concluded that submicron emulsion may be a good choice of an ethanol-free drug formulation, but lipid matrix, which is solid at body temperature, is not advantageous system for diazepam rectal delivery, even if delivered as a submicron dispersion.

Administration, Rectal↗

PubMed2001

Evaluation of paracetamol suppositories by a pharmacopoeial dissolution test--comments on methodology.

Ph.Eur. and BP have introduced a dissolution apparatus for suppositories. Suitability of the apparatus for quality control of paracetamol suppositories was evaluated and the effect of experimental conditions on dissolution profiles was studied. Paracetamol suppositories containing 80-500 mg of the drug, on fatty base, were obtained from four manufacturers (A, B, C, D). The diffusion cell was modified by incorporation of an in-built thermoprobe and large difference (up to 1.7 degrees C) between temperature in the water-bath and in the dissolution chamber was observed. This effect was avoided by increasing the length of tubing immersed in the thermostat at the inlet of the cell. The most reproducible results were observed for A and C suppositories, however from suppository C the total dose of paracetamol was released after 3.5-4.5 h while the release from suppository A was slow with only 40-87% of the total dose liberated during 6 h. Suppositories B did not melt at 37 degrees C and less than 5% of the drug was released. Fast release was observed after melting when the temperature was elevated to 39.5 degrees C. The results demonstrate clearly that essentially complete melting of a suppository in the dissolution chamber is required for an appropriate dissolution of paracetamol in vitro. Disintegration time, softening time, drop point and particle size of the suspended drug were measured and the relevance of these parameters for dissolution behaviour of the preparations was discussed.

Acetaminophen↗

PubMed2001

Diazepam submicron emulsions containing soya-bean oil and intended for oral or rectal delivery.

Physically stable diazepam submicron emulsions were prepared using soya-bean oil. Diazepam concentration 4 mg/ml, suitable for rectal or oral delivery, was achieved in 20% emulsions. Mixture of egg lecithin (1.2%) and poloxamer (2.0%) has been chosen as the most suitable emulsifying agent. Composition of the emulsion may be supplemented with alpha-tocopherol and parabens. However, the system was not stable when either phenylethanol or chlorhexidine gluconate was added. Taste masking agents commonly used as food additives decreased stability of the preparation and were not efficient in elimination of a bitter taste of the drug-loaded emulsions.

Administration, Oral↗

PubMed2000

Increased partitioning of pilocarpine to the oily phase of submicron emulsion does not result in improved ocular bioavailability.

Submicron emulsions containing pilocarpine as ion-pair with mono-dodecylphosphoric acid were prepared. Physical stability of these preparations was confirmed during 4 months of storage at 4 degrees C. Approximately 50% of the drug was found in the aqueous phase of emulsion separated using an ultrafiltration technique, while the rest was present in the oily phase and interphase. The miotic effect observed in rabbits after application of the ion-pair in aqueous solution or in submicron emulsion was the same; indicating that the drug distribution into the oily phase of the colloidal vehicle does not improve ocular bioavailability.

Animals↗

PubMed2000

Effect of penetration enhancers on isosorbide dinitrate penetration through rat skin from a transdermal therapeutic system.

Percutaneous absorption of isosorbide dinitrate (ISDN) from a transdermal therapeutic system (TTS) with or without penetration enhancers was studied. The concentration of ISDN and its metabolites, isosorbide-5-mononitrate (IS-5-MN) and isosorbide-2-mononitrate (IS-2-MN), was determined in rat plasma during a 48 h application of TTS. The increased skin-penetration enhancing effect of oleic acid and propylene glycol in comparison to polyethylene glycol 400 and isopropyl myristate on percutaneous permeation of ISDN was shown. It was expressed by higher values of C(max) and AUC. After the application of TTS, a lower ISDN and molar ratio of its metabolites was observed than after oral administration.

Administration, Cutaneous↗

PubMed2000

[Percutaneous absorption of heparin: a critical review of experimental results].

Percutaneous penetration of heparin is limited by its large molecular weight, negative charge and hydrophilicity. Although some authors did not find any significant anticoagulant effect of transdermally delivered heparin but several other papers indicate that heparin penetrates the skin barrier. The actual article provides a critical review of the in vitro and in vivo studies on percutaneous absorption of heparin and heparinoids. It is concluded that there is no sufficient evidence that heparin is able to penetrate intact skin. However under clinical conditions the integrity of the skin barrier may be changed what results in promotion of heparin penetration and justifies usage of topical drug formulations like ointments and gels.

Administration, Cutaneous↗

PubMed1999

Miotic effect and irritation potential of pilocarpine prodrug incorporated into a submicron emulsion vehicle.

Pilocarpine prodrug, O,O'-dipivaloyl(1,2-ethylene) bispilocarpic acid diester, was introduced to a submicron emulsion vehicle in a dose equivalent to 0.5% pilocarpine base, and the formulation was studied in albino rabbits using miotic assay. Compared with pilocarpine HCl 0.5% solution delayed and prolonged miosis was observed after application of the prodrug emulsion. AUC(0-6 h) values for the prodrug emulsion and pilocarpine solution were 9252+/-1345 and 6845+/-1967%xmin, respectively. The prodrug was also administered twice daily for 5 days in the form of aqueous solution or submicron emulsion in order to study ocular irritation. Irritation potential of the prodrug was significantly reduced when submicron emulsion was used as a vehicle.

Animals↗

PubMed1999

Studies on the effect of pilocarpine incorporation into a submicron emulsion on the stability of the drug and the vehicle.

In order to obtain a novel ocular formulation with a potential for prolonging pilocarpine activity, the drug (2.0%) was incorporated into a submicron emulsion containing soya-bean oil and lecithin as emulgator. The effect of drug incorporation into the emulsion on its physical stability and on the other hand, the potential of the vehicle to reduce drug degradation at pH higher than 5.0 was studied. The pH was adjusted to 6.5 or 5.0 and the physicochemical stability of the formulations was observed. The mean diameter of oily particles in the resulting emulsions measured by a laser diffractometer was 0.6-0.7 micron and this was larger than in a drug-free emulsion where a 0.33 micron value was measured. The formulations were physically stable for 6 months at 4 degrees C, but progressing chemical degradation of pilocarpine was noted at pH 6.5. At that pH nearly 8% of pilocarpine was degraded to isopilocarpine and pilocarpic acid, both in the emulsion and in the solution. Thus, it may be concluded that pilocarpine in submicron emulsion is not protected against degradation. The presence of pilocarpine changes the physical stability of the vehicle since the formulation was easily destabilized during autoclaving or at room temperature. In the presence of higher concentration of lecithin (2.4%) or co-emulgators (poloxamer 2.0% or Tween 80 0.5%) the mean droplet size in the emulsions was the same as in a drug-free system. However the emulsions containing poloxamer were not stable during storage. Viscosity of pilocarpine emulsions can be increased by addition of methylcellulose or sodium carmellose (1.0%), but an intensive creaming occurs in these systems. Pilocarpine base is less suitable for emulsion preparation than hydrochloride salt, and emulsions prepared at pH 5.0 show the most satisfying stability.

Chemistry, Pharmaceutical↗

PubMed1998

Intracellular or intercellular localization of the polar pathway of penetration across stratum corneum.

A pharmacokinetic hypothesis of stratum corneum with two parallel pathways, lipophilic and porous hydrophilic, is not well documented yet. Still questionable is the localization of the pores, and the present experiments were designed to elucidate the contribution of extracellular lipids and intracellular keratin to the structure of this pathway. Percutaneous penetration of baclofen, a model zwitterion, was studied in vitro using human cadaver skin. Aqueous or ethanolic saturated solutions of the drug (Cs = 4.6 and 0.4 mg/mL, respectively) were applied on the skin that was pretreated with: methanol/chloroform (Me/Ch) or acetone-chloroform (Ac/Ch) (1:1) mixtures, or with these solvents followed by 0.2% solution of sodium lauryl sulfate (SLS). As controls, baclofen penetration through the intact full-thickness skin was determined, and the fluxes were 0.18 +/- 0.08 and 0.14 +/- 0.07 microg/cm2/h for aqueous and ethanolic solutions, respectively. When Me/Ch was used for 1 h, an expected increase of the penetration was observed, but the lag time, Tlag, was still nearly 20 h. When the less polar mixture, Ac/Ch, was used, no flux enhancement was observed, and with ethanol as the vehicle, decreased penetration was even noted. No effect on baclofen penetration was observed when SLS was used for 1 h after delipidization of the skin was done with either the Me/Ch or Ac/Ch mixture. The results suggest that the polar pathway may be located intercellularly and comprises aqueous regions surrounded by polar lipids, which create the walls of such microchannels.

Baclofen↗

PubMed1997

Increased apoptosis arising from increased expression of the Alzheimer's disease-associated presenilin-2 mutation (N141I).

Mutations in the genes for presenilin 1 and 2 (PS-1 and PS-2) have been linked to development of early-onset Alzheimer's disease (AD). As neither the normal function of either presenilin is known nor why mutations cause disease, we examined the properties of wild-type, truncated, and mutant PS-2 upon expression in HeLa cells. Although HeLa cells are strongly predisposed to continued mitosis, expression of PS-2 induced programmed cell death (apoptosis). Direct evidence for apoptosis was obtained by double staining for terminal deoxynucleotide transferase nick end labeling (TUNEL) and PS-2 expression and by following green fluorescent protein-tagged PS-2 over time. Deletion analysis indicates that as little as 166 NH2-terminal residues of PS-2 are sufficient for endoplasmic reticulum (ER) localization and apoptosis. Moreover, the AD- associated PS-2 missense mutation (N141I) more efficiently induced cell death compared to wild-type PS-2 despite lower mutant protein accumulation. Expression of the presenilins in several other cell lines and transgenic mice has been accompanied by rapid protein cleavage without the induction of cell death. In contrast, PS-2 expressed in HeLa cells was not cleaved, and cell death occurred. We hypothesize that full-length but not cleaved PS-2 may be important in the regulation or induction of apoptosis.

Alzheimer Disease↗

PubMed1995

The first intron of the mouse neurofilament light gene (NF-L) increases gene expression.

Neurofilament expression is developmentally and post-transcriptionally controlled. Using transient transfection assays in mouse L cells, we demonstrate that the expression of the mouse neurofilament light subunit (NF-L) is influenced by intron sequences. NF-L expression was decreased twenty fold upon deletion of the three intron sequences. Elements contained principally within a 350 bp region of intron 1 were responsible for enhanced NF-L expression. Enhancement of expression did not occur when intron I was placed 3' to a heterologous chloramphenicol acetyl transferase (CAT) gene whose expression was driven by NF-L 5' sequences. The intron enhancement of NF-L expression was not promoter-specific and also occurred with the mouse sarcoma virus (MSV) LTR promoter. These data suggest intron sequences may be important in regulating NF gene expression.

Animals↗