Distribution and metabolism of topically applied progesterone in a rat model

This study investigated the transdermal uptake and subsequent tissue distribution of [³H]progesterone applied in a commercially available progesterone cream in a rat model. Concentrations of lipid- and water-soluble metabolites of [³H]progesterone were also measured in plasma, urine and selected tissues (uterus, liver, kidney, salivary gland) 3 h after its topical application. Female rats were ovariectomized and adrenalectomized to remove all endogenous progesterone, and 4 weeks later were anaesthetized and 150 mg Pro-Feme® cream (containing progesterone 3.2% w/w and 200 μCi [³H]progesterone) was applied to the abdominal skin. Six arterial blood samples were then obtained from a carotid cannula over the following 3 h, and urine and selected tissue samples were collected after the final blood sample. Plasma progesterone increased progressively until 90 min, then remained relatively stable. Plasma levels of [³H]progesterone were high by the 15-min sample and increased only slightly thereafter. Water-soluble metabolites were detectable in plasma at 15 min, whereas lipid-soluble metabolites became apparent only by 60 min then increased progressively to 180 min. The tissue:plasma concentration ratio for [³H]progesterone exceeded 1 in all tissues, most notably in uterus (8.4) and lung (9.6), whereas urinary [³H]progesterone levels were only half those in plasma. Concentrations of lipid- and water-soluble progesterone metabolites were most prevalent in liver and kidney, and both reached very high concentrations in urine. These results demonstrate that topically applied progesterone is rapidly absorbed transdermally and that its patterns of distribution and metabolism are comparable to those previously reported for intravascularly administered progesterone.     

Substance P-immunoreactive nerve fibres in the anterior segment of the rabbit eye

Summary Substance P-immunoreactive nerve terminals were found in several locations in the anterior segment of the rabbit eye. In the iris they occurred in the sphincter muscle and were randomly distributed in the iris stroma with some fibres running close to the dilator muscle. In the ciliary body these immunoreactive elements were few and occurred within bundles of nerve fibres, while in the ciliary processes they were more numerous with a predominantly subepithelial location. Blood vessels in the anterior uvea were often surrounded by substance P-immunoreactive fibres. No substance P-fibres were found in the cornea, while the sclera contained very few such elements.Using conventional in vitro techniques it was found that the sphincter pupillae muscle of the iris responded to electrical stimulation with a contraction that was resistant to cholinergic and adrenergic blockade, but was inhibited by the neuronal blocker tetrodotoxin. This indicates the existence of a non-cholinergic, non-adrenergic neuronal mediator of the contractile response. Exogenously applied substance P produced a long-lasting contraction of the spincter muscle, an observation compatible with the view that substance P is the noncholinergic, non-adrenergic neurotransmitter involved.     

Four compartment mammillary model applied to the pharmacokinetics of a spiroarsorane administered orally to rabbits

Rekik et al.¹ dealt with the pharmacokinetics of two spiroarsoranes molecules^1,2 administered intravenously or orally to rabbits. For the intravenous study they used an open two-compartment model. For the oral study they admitted that they were unable to fit the data to a model. In this paper the plasma concentration profile of molecule 2 after oral administration using a four mammillary open compartment model is described. This type of model (which requires a fourth degree equation) has been previously described². Here it is applied to a concrete situation.     

In vivo metabolism of topically applied retinol and all-trans retinoic acid by the rabbit cornea

Corneas of normal and vitamin A-deficient rabbits were treated topically with [11, 12-3H] retinol or [11, 12-3H] all-trans retinoic acid. Methanol extracts of these corneas were analyzed by high pressure liquid chromatography. Radiolabeled compounds were extracted from the corneas which co-migrated chromatographically with known retinoid standards. In agreement with studies on other tissues and organs, retinol was metabolized to retinoic acid and more polar compounds by corneas of normal and vitamin A-deficient rabbits. All-trans retinoic acid was isomerized to 13-cis retinoic acid in normal rabbit corneas; however, this trans-cis isomerization did not occur in vitamin A-deficient, xerophthalmic corneas.     

Quantitative determination of concentration profiles of skin components and topically applied oils by tailored multivariate curve resolution-alternating least squares using in vivo confocal Raman micro-spectroscopy

The main components of the stratum corneum (SC), water, lipids, and proteins, are non-homogeneously distributed throughout the depth. The quantitative determination of their concentration profiles and penetration depth of topically applied substances are urgent topics of dermatological and cosmetic research. Confocal Raman micro-spectroscopy has distinct advantages when determining semi-quantitative concentrations of SC components and topically applied substances non-invasively and in vivo. In this work, we applied a tailored multivariate curve resolution-alternating least squares (tMCR-ALS) method to analyze Raman spectra of the SC in the 2000–4000 cm⁻¹ region for quantitatively determining the concentrations of water, lipids, proteins, and topically applied oils using substance-related spectral loadings which were allowed to change depth-dependently from the SC's surface toward its bottom. tMCR-ALS makes matching of depth-dependent signal attenuation, that is, the normalization on keratin, unnecessary and requires only a few additional experiments for calibration – Raman spectra of the pure materials and their densities.     

Effect of reaction media concentration on the solubility and the chemical structure of lignin model compounds

In plant cell walls, lignin polymerization occurs in concentrated polysaccharide gel. The effect of high polysaccharide concentrations on the structure of lignin-like polymers (DHPs=dehydrogenation polymers), were investigated by running lignification-like polymerization under three reaction conditions in which the concentrations of all reactants (xylan/coniferyl alcohol (CA)/oxidising system) were gradually increased. Control experiments were also run in similar conditions but without polysaccharides. DHPs showed increased solubility with increased concentrations of reactants in the presence of xylans but were mostly insoluble in buffer control experiments. The structures of DHPs were characterized by thioacidolysis and size exclusion chromatography (SEC). Results indicated that the frequency of beta-alkyl aryl ether bonds and DHP molecular weight increased with increasing concentration of the reaction mixture in the presence of xylans whereas those of control DHPs decreased slightly under the same conditions. This emphasizes the role of the pre-existing polysaccharide gel and high concentrations existing in the cell wall during construction of the lignin polymer.     

Nonlinear parameter estimation applied to a model of smooth pursuit eye movements

We present a procedure that optimally adjusts specified parameters of a mathematical model to describe a set of measured data. The technique integrates a dynamic systems-simulation language with a robust algorithm for nonlinear parameter estimation, and it can be implemented on a microcomputer. Sensitivity functions are generated that indicate how the operation of the model is affected by each updated parameter. This procedure offers a greater resolution of optimal parameter values than other, less rigorous methods. To illustrate this technique we have applied it to the model of human smooth pursuit eye movements proposed by D.A. Robinson and colleagues (1986).     

The distribution of topically applied heavy metals in the soil

Summary Long-term pot experiments were conducted to determine the leaching potential of topically applied lead, cadmium, and nickel through the soil. Four rates of each metal (0, 10, 100 and 200 mg/kg soil), in the nitrate form were used. Metals were extracted with acidic ammonium acetate after 30 weeks of intermittent leaching. The concentration of extractable element varied with the depth in the soil and the type of extractable metal. Lead was confined to the upper few centimeters of soil whereas cadmium moved down to a considerable depth. Nickel was more uniformly distributed over the total soil depth than the other two metals. The concentration gradients observed are discussed with respect to their effect on germination and yield of plants.     

Adipose compartments of the upper eyelid: anatomy applied to blepharoplasty

Many authors have indicated the presence of ectopic or accessory upper eyelid fat pads, but the effective rate of eyelid fat variations and the corresponding clinical features are still unclear. The purpose of this study was to evaluate the variability of upper lid fat and to define the anatomical landmarks of the adipose pockets of the upper lid. From January of 1998 to January of 2002, the authors investigated the upper eyelid fat compartments of 47 patients who underwent upper blepharoplasty. To support surgical findings, 11 fresh cadavers were also investigated; the anatomy of the intraorbital fat and of the upper eyelid fat compartments was reviewed. Ten patients (21.3 percent) showed an accessory fat pad in the upper lid, which was found on both sides in nine cases. In all patients, the third fat pad was situated lateral to the two classic compartments described by Castanares, behind the orbital septum. Surgical dissections demonstrated that this fat pad derived from the preaponeurotic fat. Anatomical dissections in three cadavers demonstrated an accessory fat compartment protruding under the inferior border of the lacrimal gland. This protruding fat derived from the preaponeurotic fat in all cases and might justify the clinical appearance of a bulge or fullness in the lateral third of the upper eyelid. In the authors' experience, the presence of an accessory upper eyelid fat pad was a frequent finding during blepharoplasty; it could be found and actually resected in about 21 percent of all cases. Surgical and experimental findings put this element as a lateral physiological extension of the preaponeurotic fat that can anteriorly protrude under the inferior border of the lacrimal gland toward the orbital septum. The clinical appearance may be a bulge or fullness in the upper eyelid, and its resection can better define the lateral one third of the supratarsal fold.     

Effect of changes in blood glucose concentration on the standing potential of the rabbit eye

The paper deals with the study of the influence of changes of glucose blood concentration in rabbits on the standing potential of the eye, which reflects the functioning of the retinal pigment epithelium and photoreceptors. Recordings of the electrooculogram (EOG), determination of glucose blood level and ophthalmoscopic and histological examinations of the eye were performed in 48 rabbits. Short-term increase of glucose concentration was accompanied by the increase in the standing potential and Arden EOG ratio, with hypoglycemia evoking the opposite effect. A long-term (4 month) hyperglycemia was accompanied by the reversible decrease of both parameters studied. No ophthalmoscopic and histological changes were observed.     

Intraocular fate of dexamethasone disodium phosphate topically applied to the eyes of rabbits

After instillation of ³H-dexamethasone into the eyes of a rabbit, ³H-9α-fluoro-11β-hydroxy-16α-methyl-1,4-androstadiene-3,17-dione was found in the aqueous humor. The same metabolite was also formed by incubating ³H-dexamethasone with the anterior ocular tissues of rabbit. Identification of ³H-9α-fluoro-11β-hydroxy-16α-methyl-1, 4-androstadiene-3, 17-dione was performed by its mobility on a thin layer plate and by proving its radiochemical homogeneity after recrystailization with the unlabeled sample which had been synthesized from dexamethasone by oxidation with sodium bismuthate.When dexamethasone disodium phosphate was instilled into rabbit's eyes, it was hydrolyzed to free dexamethasone and then metabolized to 9α-fluro-11β-hydroxy-16α-methyl-1, 4-androstadiene-3,17-dione.