A patient tailored approach to the surgical treatment of hemorrhoids leads to equal satisfaction following hemorrhoidectomy, stapled hemorrhoidopexy or a combination of both.

Purpose: Up to 20% of patients suffering from symptomatic hemorrhoids will require surgery. Excisional hemorrhoidectomy (EH) and stapled hemorrhoidopexy (SH) are both standard and safe procedures. While SH has a short-term advantage of faster recovery and lower postoperative pain, its long-term efficacy is debatable.

Structure-activity relationships for contact allergenic potential of gamma,gamma-dimethyl-gamma-butyrolactone derivatives. 2. Quantitative structure-skin sensitization relationships for alpha-substituted-alpha-methyl-gamma,gamma-dimethyl-gamma-butyrolactone s.

A skin sensitization cross-challenge dataset for a series of alpha-(X-substituted-methyl)-gamma,gamma-dimethyl-gamma-butyrolactones is analyzed in terms of the relative alkylation index (RAI) model. The data analyzed consist of guinea pig sensitization response data for tests in which one lactone derivative is used for the induction stage and then the animals are challenged with another lactone derivative to elicit the response. RAI values are based on calculated log P (octanol/water) values together with measured relative rate constants for reactions of the lactones with n-butylamine to form alpha-methylene-gamma,gamma-dimethyl-gamma-butyrolactone.

Structure-activity relationships for contact allergenic potential of gamma,gamma-dimethyl-gamma-butyrolactone derivatives. 1. Synthesis and electrophilic reactivity studies of alpha-(omega-substituted-alkyl)-gamma,gamma-dimethyl-gamma-butyrolacton es and correlation of skin sensitization potential and cross-sensitization patterns with structure.

A series of alpha-(X-substituted-methyl)-gamma,gamma-dimethyl-gamma-butyrolactones (series 1), a series of alpha-(2-X-substituted-ethyl)-gamma,gamma-dimethyl-gamma-butyrolactones (series 2), where X is a leaving group, and the compound alpha-(3-bromopropyl)-gamma,gamma-butyrolactone (3) were synthesized. Their reactions as electrophiles toward n-butylamine, used as a model for nucleophilic groups on skin proteins whose in vivo chemical modification leads to skin sensitization, were investigated. The compounds of series 1 were shown to react via a two-stage elimination--Michael addition sequence whereby the elements of HX are eliminated to form alpha-methylene-gamma,gamma-dimethyl-gamma-butyrolactone, which reacts more slowly with n-butylamine to give alpha-[(N-butylamino)methyl]-gamma,gamma-dimethyl-gamma-butyrolactone.

Optimization of the mouse ear swelling test for in vivo and in vitro studies of weak contact sensitizers.

Murine models for the assessment of the contact sensitizing properties of chemicals rely on mouse ear swelling tests (Mest), which are not sensitive enough to detect weak sensitizers. The aim of the present study was to develop in mice an adjuvant-free Mest appropriate for in vivo detection of any type of sensitizer (weak to strong), and useful for in vitro assessment of contact sensitivity (CS). 3 haptens were tested: dinitrochlorobenzene (DNCB), para-phenylenediamine (pPD) and isoeugenol.

Synthesis and interaction studies of 13C labeled lactone derivatives with a model protein using 13C NMR.

Two molecules 9 and 14, representatives of two series of electrophilic lactone derivatives, have been synthesized, and labeled with carbon 13 at their reactive sites. The mechanism and the products of the reaction of these two molecules with human serum albumin (HSA) under various reaction conditions have been studied by 13C NMR using DEPT 135 sequences. Results using the protein dissolved in aqueous medium or butylamine (a model nucleophile) dissolved in organic solvent were very similar.

Quantitative structure-activity relationships for skin sensitization potential of urushiol analogues.

The relative alkylation index (RAI), a theoretically derived parameter intended to quantify the relative extent of carrier haptenation resulting from a given dose of a given sensitizer, has previously been successfully applied to the analysis of relative sensitization potential and dose-response data for a variety of contact allergens which are directly electrophilic. Here the RAI concept is applied to analysis of data on compounds related to urushiol (i.e.

Bihaptens with 5- and 6-methyl-substituted alkylcatechols and methylene lactone functional groups: tools for hapten (allergen or tolerogen)-protein interaction studies.

In order to investigate hapten-protein interactions in vivo, potential skin sensitizers 1-3, with two different haptenic ends, (a) a catechol, a 5-methylcatechol, and a 6-methylcatechol respectively, and (b) an alpha-methylene-gamma-butyrolactone moiety, separated by a straight 10-carbon chain, have been prepared and used to sensitize guinea pigs. Related "monohapten lactones" 19-21, containing an electrophilic alpha-methylene-gamma-butyrolactone moiety connected to the protected catechol structures, and "monohapten catechols" 25-27, containing a reduced alpha-methyl-gamma-butyrolactone linked to the catechol, also have been prepared. Bihaptens 1 and 2 which were found to have very close biological activities appear to react with proteins through the catechol ring, indicating a low importance of the C-6 position in the binding of catechols with amino acids.

A murine in vitro model of allergic contact dermatitis to sesquiterpene alpha-methylene-gamma-butyrolactones.

The use of a lymphocyte transformation test (LTT) to provide evidence of allergic contact dermatitis was investigated. The haptens studied were alantolactone and isoalantolactone, two moderate allergens from Inula helenium L., a decorative and medicinal plant.

A successful murine model for contact sensitization to a sesquiterpene-alpha-methylene-gamma-butyrolactone: sensitization to alantolactone in four strains of mice.

Induction of allergic contact hypersensitivity to a sesquiterpene lactone, alantolactone, was studied in four strains of mice: C3H/He, DBA/2, Balb/b, and Balb/c. The last three were successfully sensitized. A significant dose/response was demonstrated in these species, as well as an experimental "overload effect" in Balb/c and Balb/b strains.

Allergic contact dermatitis caused by naturally occurring quinones.

Quinones play a major role in allergic contact dermatitis caused by plants. The principal allergens are benzoquinones or naphthoquinones but also compounds, such as catechols and other phenolic or flavonoid compounds, which are bioconverted into ortho-quinones or para-quinones. The high electrophilic reactivity of these compounds toward nucleophilic residues of proteins associated with lipophilic properties may explain that they are strong sensitizers.

Perfluorinated analogues of poison ivy allergens. Synthesis and skin tolerogenic activity in mice.

3-(Tridecafluoroundecyl)catechol (8) and 3-(nonafluoropentadecyl)catechol (9), perfluorinated analogues of pentadecylcatechol (PDC), a constituent of poison ivy, have been synthesized. These compounds were nonsensitizers in mice. Compounds 8 and 9, however, were elicitors of allergic contact dermatitis in PDC-sensitized animals.

Refinement of the relative alkylation index (RAI) model for skin sensitization and application to mouse and guinea-pig test data for alkyl alkanesulphonates.

A derivation, more rigorous than hitherto, of the Relative Alkylation Index (RAI) as a quantifier of carrier protein haptenation in skin sensitization tests is presented. It is shown that the RAI, which is a composite parameter made up of dose, reactivity and lipophilicity terms, is likely to require a higher weighting for the reactivity term in the case of non-adjuvant tests than in the case of Freund's adjuvant-based tests. Methyl alkane-sulphonates, RSO3Me with R ranging from n-C6H13 to n-C16H33, were found to be skin sensitizers in a mouse ear swelling test, in agreement with published findings in a guinea-pig adjuvant model.

Patch testing with the "sesquiterpene lactone mix": a marker for contact allergy to Compositae and other sesquiterpene-lactone-containing plants. A multicentre study of the EECDRG.

6278 patients were patch tested with a sesquiterpene lactone mix (SL-mix) in 10 European clinics. 4011 patients were tested only with 0.1% SL-mix, 63 (approximately 1.

Cross-reaction in allergic contact dermatitis from alpha-methylene-gamma-butyrolactones: importance of the cis or trans ring junction.

Cross-reaction in allergic contact dermatitis (ACD) is a highly stereoselective process. The importance of the cis or trans ring junction in alpha-methylene-gamma-butyrolactones in cross-reactivity was investigated by reacting Helenin (mostly a mixture of natural allergenic sesquiterpene lactones alantolactone 1 and isoalantolactone 2, which present a cis ring junction) in guinea pigs sensitized to model allergenic alpha-methylene-gamma-butyrolactones: cis-bicyclic lactone 3 and trans-bicyclic lactone 4.

Molecular recognition in allergic contact dermatitis. The concept of double-headed haptens.

The sensitizing capacity of double-headed haptens containing the pyrocatechol and alpha-methylene-gamma-butyrolactone groups reveals that only the pyrocatechol end is recognized as a sensitizer. Prior sensitization to the double-headed hapten provides protection against (induces immune tolerance to) further sensitization to the lactone hapten.

Sensitizing capacity of three methyl alkanesulphonates: a murine in vivo and in vitro model of allergic contact dermatitis.

A murine model for in vivo and in vitro studies of contact sensitization to methyl alkanesulphonate derivatives has been developed. Contact sensitivity was quantified in vivo by measuring the ear thickness increase, and the influence of the alkyl chain length (hexyl, dodecyl, hexadecyl) was investigated. Long chain methyl alkanesulphonates (dodecyl and hexadecyl) are strong sensitizers, while the shorter alkyl chain, methyl hexanesulphonate, is a weak sensitizer.

ATPase and morphologic changes in Langerhans cells induced by epicutaneous application of a sensitizing dose of DNFB.

We have previously described an ATPase Langerhans cell (LC) staining technique allowing progression from light to electron microscope observation. Using this technique we have studied, following epicutaneous application of a sensitizing dose of a hapten, 2,4-dinitro-1-fluorobenzene (DNFB), the fate of the epidermal LC located in the sensitization zone. We wanted to know, under the light microscope, if the density and/or morphology of the LC are modified by such a treatment and, under the electron microscope, what are the ultrastructural changes accompanying the possible light microscope modifications.

Allergic contact dermatitis to Ginkgo biloba L.: relationship with urushiol.

A Ginkgo biloba L. fruit extract was prepared and purified. Three groups of guinea pigs were sensitized to the crude extract, anacardic acids 1, and cardanols 2 respectively, using the FCAT method, and the fourth group to urushiol using the epicutaneous route.

Allergic contact dermatitis to tulips: an example of enantiospecificity.

Allergic contact dermatitis (ACD), an immunological reaction of the skin resulting from contact with reactive compounds occurring in plants was shown to the enantiospecific (animals sensitized to a compound do not react to its nonsuperimposable mirror image). Thus, when guinea pigs were experimentally sensitized to (+)-tulipalin B (a compound present in tulip bulbs) they did not react to its enantiomer, (-)-tulipalin B. This was also true for (+)- and (-)-beta-hydroxy-gamma-methyl-alpha-methylene-gamma-butyrolactones.

Stereospecificity in allergic contact dermatitis to simple substituted methylene lactone derivatives.

The enantiomers of beta,gamma-dimethyl- and beta-methyl-alpha-methylene-gamma-butyrolactones have been synthesized stereospecifically from glutamic acid and beta-hydroxy isobutyric acid, respectively. Guinea pigs have been sensitized (Freund complete adjuvant technique) and tested to them. Both enantiomers of beta-methyl lactone as well as (+)-beta,gamma-dimethyl lactone induced enantiospecific allergic contact dermatitis (ACD); in turn, (-)-beta,gamma-dimethyl lactone showed no specificity.

Human epidermal Langerhans cells internalize by receptor-mediated endocytosis T6 (CD1 "NA1/34") surface antigen. Birbeck granules are involved in the intracellular traffic of the T6 antigen.

Using immunogold staining of a suspension of living human epidermal cells to identify the Langerhans cell membrane-associated antigen T6 (revealed by the monoclonal antibody BL6), we have observed internalization of T6 antigen in Langerhans cells. This phenomenon is at least partly due to receptor-mediated endocytosis involving coated pits, coated vesicles, endosomes, the smooth endoplasmic reticulum, and lysosomes. These ultrastructural results suggest that T6 antigen may be part of a receptor site.

Contact dermatitis. A review.

In recent years, there has been a dramatic rise in our understanding of contact dermatitis. This paper is a review of our knowledge of the mechanisms involved in contact dermatitis and related phenomena, the investigation of these events and the emergence of significant new allergens during the last 5 years.

Double-headed haptens with pyrocatechol (poison ivy like) and methylene lactone functional groups: a search for skin-tolerance inducers.

In order to develop new theories for desensitization, a potential skin sensitizer, 1, with two different haptenic ends, a pyrocatechol group and an alpha-methylene-gamma-butyrolactone moiety, separated by a straight nine-carbon-atom chain has been prepared and used to sensitize guinea pigs. A "monohapten" 8 containing an electrophylic alpha-methylene-gamma-butyrolactone, connected to a dimethoxybenzene group, has also been prepared. Both the "bihapten" 1 and the "monohapten" 8 were shown to be sensitizers.