The Oldest Bryophyte Herbarium Specimens from Central Europe, Collected by M. E. Boretius in 1717: Taxonomy, Nomenclature, Datation and Ethnopharmacology.

The WA Herbarium at the University of Warsaw houses a collection of plants created in 1717 by Matthew Ernest Boretius. They were gathered in former East Prussia, near Angerburg, now Wegorzewo (Poland). It is the oldest plant collection from this part of Europe. Boretius compiled the herbarium as a collection of all the surrounding plants, but their folk names (Polish and German) recorded in the herbarium confirm the ethnobiological or ethnopharmaceutical importance of some species. We identified bryophyte species and checked the accuracy of their original identifications recorded in the herbarium. We provided their Latin (scientific, pre-Linnaean) nomenclature together with German and Polish vernacular names. We contextualised this information within the history of the medicinal use of bryophytes around 1717, when the plant collection was created. We also investigated whether the specimens could have come from Northeastern Poland. Mosses and liverworts from the herbarium were identified nomenclaturally (by means of their original scientific polynomial names written on herbarium sheets) and taxonomically. The herbarium holds two species and one subspecies of liverwort and 27 species and one variety of moss. The accuracy of the original identifications was assessed, with a particular focus on the species considered medicinal at the time. We found that bryophytes were poorly known in the time of Boretius, which was the last period in bryology before the introduction of magnifying devices into this science (this crucial step was made by Dillenius in 1741). The vernacular names used in the herbarium were recorded for Marchantia polymorpha and Polytrichum commune-the only two species with confirmed medicinal use by the year 1717.

Kisspeptin-10 increases collagen content in the myocardium by focal adhesion kinase activity.

The aim of the study was to evaluate the role of kisspeptin-10 (KiSS-10) in the regulation of collagen content in cardiac fibroblasts. An attempt was also made to describe the mechanism of the effect of KiSS-10 on collagen metabolism. The studies indicate that kisspeptin-10 significantly increases the content of intracellular collagen in the myocardium. KiSS-10 also elevates the level of phosphorylated focal adhesion kinase (FAK) in human cardiac fibroblasts. The inhibition of FAK negates the stimulatory effect of KiSS-10 on collagen deposition in vitro. These changes correlate with an increase in the level of propeptides of procollagen type I (PICP) and III (PIIICP) in fibroblast culture medium and mouse PIIICP in serum. Moreover, this hormone inhibits the release of metalloproteinases (MMP-1,-2,-9) and elevates the secretion of their tissue inhibitors (TIMP-1,-2,-4). KiSS-10 also enhances the expression of α1 chains of procollagen type I and III in vitro. Thus, KiSS-10 is involved in the regulation of collagen metabolism and cardiac fibrosis. Augmentation of collagen deposition by KiSS-10 is dependent on the protein synthesis elevation, inhibition of MMPs activity (increase of TIMPs release) or decrease of MMPs concentration. The profibrotic activity of KiSS-10 is mediated by FAK and is not dependent on TGF-ß1.

Melatonin increases collagen content accumulation and Fibroblast Growth Factor-2 secretion in cultured human cardiac fibroblasts.

BACKGROUND: The extracellular matrix serves as a scaffold for cardiomyocytes, allowing them to work in accord. In rats, collagen metabolism within a myocardial infarction scar is regulated by melatonin. The present study determines whether melatonin influences matrix metabolism within human cardiac fibroblast cultures and examines the underlying mechanism. METHODS: The experiments were performed on cultures of cardiac fibroblasts. The Woessner method, 1,9-dimethylmethylene blue assay, enzyme-linked immunosorbent assay and quantitative PCR were used in the study. RESULTS: Melatonin treatment lowered the total cell count within the culture, elevated necrotic and apoptotic cell count as well as augmented cardiac fibroblast proliferation, and increased total, intracellular, and extracellular collagen within the fibroblast culture; it also elevated type III procollagen α1 chain expression, without increasing procollagen type I mRNA production. The pineal hormone did not influence matrix metalloproteinase-2 (MMP-2) release or glycosaminoglycan accumulation by cardiac fibroblasts. Melatonin increased the release of Fibroblast Growth Factor-2 (FGF-2) by human cardiac fibroblasts, but cardiotrophin release was not influenced. CONCLUSION: Within human cardiac fibroblast culture, collagen metabolism is regulated by melatonin. The profibrotic effect of melatonin depends on the elevation of procollagen type III gene expression, and this could be modified by FGF-2. Two parallel processes, viz., cell elimination and proliferation, induced by melatonin, lead to excessive replacement of cardiac fibroblasts.

Dysphania schraderiana (Schult.) Mosyakin & Clemants - An overlooked medicinal and ritual plant used in Poland.

ETHNOPHARMACOLOGICAL RELEVANCE: The paper discusses the traditional ritual, medicinal and insect repellent use of Dysphania schraderiana in Poland, a plant with little ethnobotanical and phytochemical data. Our research suggests that its properties should be further studied comparing it with the related D. botrys and D. ambrosioides. AIM OF THE WORK: D. schraderiana is an aromatic and medicinal annual herb related to D. ambrosioides and D. botrys and practically absent from historical accounts of plant uses in Europe. The aim of this work is to characterise the current use of D. schraderiana in south east Poland on the background of historical Dysphania species use in Europe. MATERIALS AND METHODS: The data on D. schraderiana was collected in 2020, based on interviews with 42 people in rural areas of south-eastern Poland where the species is used today. A range of textual sources were searched including old medicinal herbals, pharmaceutical handbooks, ethnobotanical publications and culinary databases regarding all the uses of Dysphania species in Europe. RESULTS: In the study area D. schraderiana occurs in the whole spectrum of cultivation stages - from being intentionally cultivated to completely wild. The plant is used mainly as an apotropaic and insect repellent, blessed during Catholic church holidays (mainly Assumption Day), and sometimes used as incense in churches (and blessed on Epiphany Day). D. schraderiana rarely occurs in European historical sources, except sometimes classed as a false, inferior form of D. botrys, which has been known for centuries as a moth repellent and treatment for respiratory illness. We hypothesise that the plant was not easily distinguished from D. botrys and their uses strongly overlapped. For some unknown reason the use of D. botrys died out, whereas a relatively large semi-feral population of D. schraderiana exists in south-eastern Poland where it has remained a culturally important plant. CONCLUSIONS: D. schraderiana is a rare case of a non-native plant traditionally used within an area of Europe but previously nearly overlooked in European ethnobotanical literature. Historical uses of Dysphania spp. in other areas of Poland and former Poland (now western Ukraine) suggest that the genus was used more widely in regions beyond the one studied. However, a very compact distribution of use suggests that D. schraderiana may have been brought to SE Poland from a single source outside the study area. Its common name, and use as a holy incense plant, is associated it with the well-known biblical tree resin obtained from Commiphora myrrha (Nees) Engl.

The Stiffness of Cardiac Fibroblast Substrates Exerts a Regulatory Influence on Collagen Metabolism via α2ß1 Integrin, FAK and Src Kinases.

Information about mechanical strain in the extracellular space is conducted along collagen fibers connected with integrins and then transmitted within cells. An aim of the study is to verify the hypothesis that the stiffness of cardiac human fibroblast substrates exerts a regulatory effect on collagen metabolism via integrin α2ß1 and downstream signaling. The experiments were performed on human cardiac fibroblasts cultured on stiff or soft polyacrylamide gels. Extracellular and intracellular collagen content, metalloproteinase-1 (MMP-1), metalloproteinase-9 (MMP-9) and expression of the α1 chain of the procollagen type I gene (Col1A1) were elevated in cultures settled on soft substrate. The substrate stiffness did not modify tissue inhibitors of matrix metalloproteinase capacity (TIMPs 1-4). Integrin α2ß1 inhibition (TC-I 15) or α2 subunit silencing resulted in augmentation of collagen content within the culture. Expression of Col1A1 and Col3A1 genes was increased in TC-I 15-treated fibroblasts. Total and phosphorylated levels of both FAK and Src kinases were elevated in fibroblasts cultured on stiff substrate. Inhibition of FAK (FAK kinase inhibitor 14) or Src kinase (AZM 47527) increased collagen content within the culture. The substrate stiffness exerted a regulatory influence on collagen metabolism via integrin α2ß1 and its downstream signaling (FAK and Src kinases) in cardiac fibroblasts.

Histamine is involved in the regulation of collagen content in cultured heart myofibroblasts via H2, H3 and H4 histamine receptors.

Histamine is involved in the regulation of collagen metabolism during healing following a myocardial infarction; however, its effects on the intact heart tissue is unknown. The aim of the present study was to determine whether histamine may influence collagen content in cells isolated from intact heart, and to identify the histamine receptor involved in the regulation of collagen deposition. Cells were isolated from intact rat hearts and subjected to identification by flow cytometry. The effects of histamine and its receptor agonists and antagonists were investigated. The heart cells were found to be actin, desmin and vimentin positive. Histamine (used at a concentrations of 1x10-10-1x10-5 M) increased collagen content within the culture and increased the expression of α1 chain of the procollagen type III gene. The H2, H3 and H4 receptor inhibitors ranitidine, ciproxifan and JNJ 7777120 blocked the effect of histamine on collagen content. All tested histamine receptor agonists, viz. 2-pyridylethylamine dihydrochloride (H1 receptor agonist), amthamine dihydrobromide (H2 receptor agonist), imetit (H3 receptor agonist) and 4-methylhistamine hydrochloride (H4 receptor agonist), elevated collagen content within the heart myofibroblast cultures. The cells isolated from the intact heart were identified as myofibroblasts. Thus, the results of the present study showed that histamine augmented collagen content in the heart myofibroblast culture by activation of three histamine receptors (H2, H3 and H4). The effect of the amine was also dependent on the activation of collagen type III gene expression.

Four Centuries of Medicinal Mosses and Liverworts in European Ethnopharmacy and Scientific Pharmacy: A Review.

(1) Medicinal use of bryophytes dates to ancient times, but it has always been marginal due to their small size, difficult identification, lack of conspicuous organs which would attract attention (flowers, fruits) and insipid taste of the herb. The earliest testimonies of their medical use come from the 1500s. The interest in medicinal bryophytes diminished considerably in the 1880s, except for Sphagnum spp., which became a source of dressing material. The second half of the 20th century saw the revival of the study of bryophyte chemistry. (2) Historical printed sources from 1616 to 1889 were queried. Bryophyte species found were taxonomically identified and presented against the background of their confirmed properties and ecology. The study was supplemented with historical vs. modern ethnomedicinal data. (3) In 26 publications, 28 species were identified. Modern usage was known for 10 of them. Medicinal properties of 16 species were confirmed. (4) Species of wide geographical distribution range were (or are still being) used in local folk medicines. Historical ethnobiological and ethnopharmaceutical uses of them are sometimes convergent with their confirmed properties, mostly external (as antimicrobial or cytotoxic remedies).

Histamine augments collagen content via H1 receptor stimulation in cultures of myofibroblasts taken from wound granulation tissue.

The inflammatory reaction influences the deposition of collagen within wound granulation tissue. The aim of the present study is to determine whether histamine acting directly on myofibroblasts derived from wound granulation tissue may influence collagen deposition. It also identifies the histamine receptor involved in this process. The experiments were carried out on cells isolated from the granulation tissue of a wound model (a polypropylene net inserted subcutaneously to rats) or intact rat skin. Collagen content was measured following the addition of different concentrations of histamine and treatment with histamine receptor antagonists (ketotifen - H1 inhibitor, ranitidine - H2 inhibitor) and a histamine receptor H1 agonist (2-pyridylethylamine dihydrochloride).The cells were identified as myofibroblasts: alpha-smooth muscle actin, vimentin, and desmin positive in all experimental conditions. Histamine increased the collagen level within both cell cultures, i.e., those isolated from granulation tissue or intact skin. It did not, however, influence the expression of either the collagen type I or III genes within the cultured myofibroblasts. Histamine activity was reduced by ketotifen (the H1 receptor inhibitor) and increased by the H1 receptor agonist, as demonstrated by changes in the levels of collagen in the myofibroblast culture. Histamine increased collagen content within the cultures, acting directly on myofibroblasts via H1 receptor stimulation.

The stiffness-controlled release of interleukin-6 by cardiac fibroblasts is dependent on integrin α2ß1.

Cardiac fibroblasts are able to sense the rigidity of their environment. The present study examines whether the stiffness of the substrate in cardiac fibroblast culture can influence the release of interleukin-6 (IL-6), interleukin-11 (IL-11) and soluble receptor of IL-6 (sIL-6R). It also examines the roles of integrin α2ß1 activation and intracellular signalling in these processes. Cardiac fibroblasts were cultured on polyacrylamide gels and grafted to collagen, with an elasticity of E = 2.23 ± 0.8 kPa (soft gel) and E = 8.28 ± 1.06 kPa (stiff gel, measured by Atomic Force Microscope). Flow cytometry and ELISA demonstrated that the fibroblasts cultured on the soft gel demonstrated higher expression of the α2 integrin subunit and increased α2ß1 integrin count and released higher levels of IL-6 and sIL-6R than those on the stiff gel. Substrate elasticity did not modify fibroblast IL-11 content. The silencing of the α2 integrin subunit decreased the release of IL-6. Similar effects were induced by TC-I 15 (an α2ß1 integrin inhibitor). The IL-6 levels in the serum and heart were markedly lower in α2 integrin-deficient mice B6.Cg-Itga2tm1.1Tkun/tm1.1Tkun than wild type. Inhibition of Src kinase by AZM 475271 modifies the IL-6 level. sIL-6R secretion is not dependent on α2ß1 integrin. Conclusion: The elastic properties of the substrate influence the release of IL-6 by cardiac fibroblasts, and this effect is dependent on α2ß1 integrin and kinase Src activation.

Central European ethnomedical and officinal uses of peat, with special emphasis on the Tolpa peat preparation (TPP): An historical review.

ETHNOPHARMACOLOGICAL RELEVANCE: Medical or hygienic uses of peat mosses dates back to the 18th century. Peat was used externally (as poultices) in the early 19th century. The peat preparation invented by Stanislaw Tolpa (Tolpa peat preparation, TPP) was patented in Poland in 1991; its concept had emerged in the 1980s. It raised high therapeutic expectations still being researched in the early 1990s. Profound expectations for peat, a natural product well known in Central European (and Polish) spas (for medicated baths and poultices), earned Tolpa's preparation great renown before any actual benefits (internal actions) were scientifically confirmed. AIM OF THE REVIEW: We study the origins of medical interest in peat in Polish science against the background of the historical ethnopharmacy of peat and Sphagnum moss in Central Europe. It is aimed at shedding a new light on the history of TPP, its connections with local ethnopharmacological traditions and inspirations for local medical studies on peat products and peat-derived drugs of the 1980s and early 1900s. MATERIALS AND METHODS: The literature on peat baths was found and reviewed including the information and data about the studies of TPP from published though unknown sources as well as from Polish patents, unpublished typescripts, press interviews and reports. RESULTS: Tolpa's research team missed the historical data about external and topical actions of Sphagnum peat or its preparations which were published in the 19th- and early 20th-century. This is strange because folk medicine based on peat emanated eastwards from ethnic Austria along the Vistula river and the Carpathians. Tolpa ignored balneotherapeutic (external) applications as well as the action of sphagnan from Sphagnum herb, and rejected this kind of peat as scientifically not promising, based on a single biological test on plants. The concept of an active principle in peat or its preparations evolved, and speculation concerning its nature was not followed by adequate basic research. The active principle was not found. Results concerning plant meristem growth were too readily applied in animal production and finally human medicine. The natural ingredient in TPP production was never defined botanically. Anti-cancer properties ascribed to the TPP on the basis of bio-stimulation tests stirred powerful social emotions. CONCLUSIONS: Topical peat cure originated in Austria in about 1820. It evolved as a whole branch of Central European balneotherapy which had been completely scientifically described by the 1950s. At that time an undefined peat extract was once successfully used in ear infections in paediatrics. Stanislaw Tolpa's research project to find any internal application of peat ignored the achievements of ethnobiology, balneotherapy, surgery and otorhinolaryngology known at that time. His strenuous and insistent efforts, carried out in isolation, crucially failed pre-clinical and clinical tests in any branch of his therapy. Three commercial drugs were allowed for 3 years before substantial clinical proofs of peat efficacy were achieved. Social impact was high and resulted in the birth of the Polish legend of Tolpa's marvellous drug.

Intra-cerebral implantation of a variety of collagenous scaffolds with nervous embryonic cells.

Collagenous scaffolds provide good conditions for embryonic nerve cell growth. The aim of the current study was to assess the brains reaction to the implantation of 3D sponge-shaped scaffolds. These scaffolds consisted of collagen (Col) and Col with chondroitin sulphate, which is modified by carbodiimide, or Col crosslinked with dialdehyde cellulose. The current study also evaluated the expression of integrins α2 and ß1 in embryonic nerve cells. Embryonic nerve cells were isolated from the brains of rat embryos. Acellular scaffolds, or scaffolds populated with embryonic nerve cells, were implanted into the rats brain. The fibers of all the implanted scaffolds remained intact and served as a template for cell infiltration. The implants induced minimal to moderate inflammatory responses and minimal glial scar formations. Immunohistochemical studies did not indicate any microtubule-associated protein 2 or glial fibrillary acidic protein-positive cells inside the scaffolds. Acellular and cell-populated scaffolds yielded similar responses in the brain. The expression of integrin α2 and ß1 was observed in embryonic nervous cells. TC-I15, the integrin α2ß1 inhibitor, was not demonstrated to modify cell entrapment within the collagenous scaffolds. All applied scaffolds were well tolerated by the tissue and were indicated to support blood vessel formation. Therefore, all tested biomaterials are recommended for further studies. Additional chemical modifications of the material are suggested to protect the seeded cells from apoptosis after implantation into the brain.

Collagenous scaffolds supplemented with hyaluronic acid and chondroitin sulfate used for wound fibroblast and embryonic nerve cell culture.

BACKGROUND: Tissue engineering is a strategy aimed at improving the regeneration of injured tissues. OBJECTIVES: The aim of the present study was to determine whether a tri-copolymer composed of crosslinked collagen, chondroitin sulfate and hyaluronic acid (Col + CS + HA) provides a better environment for fibroblast and embryonic nerve cell culture than a collagenous scaffold (Col). MATERIAL AND METHODS: The porosity of each of the matrices was characterized with a scanning electron microscope. Fibroblasts were isolated from rat wound granulation tissue (polypropylene net implanted subcutaneously). Embryonic nerve cells were obtained from the brains of rat embryos. The cells were applied to scaffolds and then stained with bisbenzimide to calculate cell entrapment within the material. The metabolic activity of the cells cultured within the scaffolds was tested using the 3-(4,5-dimethythiazol2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay. RESULTS: The Col scaffolds had a homogenously porous structure with a pore diameter of 50 µm for 70% of pores. The pore diameter in the tri-copolymer (Col + HA + CS) ranged from 24 to 160 µm (95% of total pore volume). Four times more cells (fibroblasts and embryonic nerve cells) were trapped within the superficial part of the collagenous scaffold than that of the tri-copolymer. On the third day of culture the metabolic activity of the fibroblasts within the 2 tested scaffolds was significantly higher than in the control conditions (cell culture on a laminin-coated surface). Also, the embryonic nerve cells demonstrated increased metabolic activity in Col + CS + HA scaffolds than the Col scaffolds. CONCLUSIONS: Both fibroblasts and embryonic nerve cells could be seeded within the 2 tested scaffolds. Both the scaffolds provide good conditions for fibroblast culture. However, the Col + CS + HA tri-copolymer is preferable for embryonic nerve cell engineering.

Tangled history of the European uses of Sphagnum moss and sphagnol.

ETHNOPHARMACOLOGICAL RELEVANCE: Sphagnum mosses and peat could have been utilized as wound dressings for centuries, however reliable data on this subject are ambiguous; sometimes even no distinction between peat moss (Sphagnum spp.) and peat is made or these terms become confused. The first scientific account on surgical use of peat comes from 1882: a peat digger who successfully, by himself and in the way unknown to the then medicine, cured an open fracture of his forearm with peat. The peat, and very soon the peat moss itself (which is the major constituent of peat) drew attention of the 19th-century surgeons. AIMS OF THE WORK: We search for reliable information on: (1) inspirations for Sphagnum usage for medical purposes and its beginnings in the 19th century, (2) substances or products named sphagnol and their connections with (1); (3) on the origin of this name, (4) and on the occurrence of this name in medical sources. MATERIALS AND METHODS: We have identified and studied published sources on the uses of peat-based and Sphagnum-based preparations and products of any processing level (including herbal stock, distillate, isolated pure or impure active principle, or a mixture of such) in surgery, pharmacy or cosmetics. A special attention was paid to the name sphagnol, which appeared many a time, in more than one context since 1899. Source publications were critically analysed from the taxonomical, pharmacognostical and ethnopharmacological points of view. Gathered data were cross-checked with the modern knowledge of the biologically active principles of Sphagnum and the prospects of their medical use. RESULTS: The application of peat in surgery started 1882. The use of peat moss as dressings was developed in the 1880's. It returned to surgical practice during WW1. The name sphagnol has two meanings: (1) A chemical substance isolated from the cell walls of Sphagnum mosses in 1899. A post-1950 research showed it to be a mixture of phenols dominated by sphagnum acid. (2) A product of dry distillation of peat contains solid and liquid fractions and was applied in skin diseases due to antiseptic properties. It was added to ointments and medicated soaps manufactured up to the late 1960's. Today none of these two sphagnols is in use. CONCLUSIONS: Surgical application of peat had an ethnopharmacological origin: a case of wound treatment with peat as a remedy rather than a dressing (1880, published 1882) shortly shifted the surgeons' attention to peat moss as an absorptive dressing. The 1880's tests of antiseptic properties of peat and peat moss failed, the sterilization methods overrode the physiological effects of Sphagnum dressings. Sphagnan, a polysaccharide from Sphagnum cell walls, discovered 1983, inhibits microbial growth, tans the collagen and removes ammonia from microbial environments. Portions of raw peat could be sterile. The isolation of sphagnol (1899) from Sphagnum cell walls was not inspired by old surgery. Main component of sphagnol, the sphagnic acid, was used clinically during WW2, but was proved a weak antimicrobial agent. A homonymous name sphagnol appeared independently for a product of dry distillation of peat, introduced commercially probably about 1899, too, which gave rise to confusions: a) the commercial, "distilled" sphagnol was not the crystalline principle of Sphagnum cell walls. 2) the "distilled" sphagnol was hardly defined technologically or pharmacologically, never standardized in terms of the substrate (a variety of peat rather than Sphagnum herb) and the production process. This sphagnol, resembling pitch or tar, was an additive to medicated soaps and ointments for skin treatment and care. It must have been a low-scale product although advertised worldwide. Neither sphagnum acid nor sphagnan are used medicinally today.

Effects of electrospun scaffolds of di-O-butyrylchitin and poly-(ε-caprolactone) on wound healing.

BACKGROUND: We sought to determine the usefulness of electrospun dibutyrylchitin (DBC) or poly-(ε-caprolactone [PCL]), in wound treatment. We investigated the mechanisms of action of these polymers on wound healing. METHODS: We synthesized DBC, a newly identified ester derivative of chitin, using a patented method comprising the substitution of butyryl groups at positions C-3 and C-6 in chitin molecules. We confirmed the double substitution by the butyric groups using infrared spectrometry. The fibrous scaffolds were obtained using the electrospinning method. A polypropylene net was implanted subcutaneously in the rat and served as a wound model. RESULTS: Both DBC and PCL increased granulation tissue weight in the wound. In contrast to PCL, DBC did not abolish glycosaminoglycan changes in wounds. The tested samples did not impair total collagen synthesis or induce excessive fibrosis. In both PCL- and DBC-treated wounds, we observed a lower level of soluble collagen (compared with controls). The results show better hydration of the wounds in both the DBC and PCL groups. No induction of large edema formation by the tested materials was observed. These polymers induced almost identical macrophage-mediated reactions to foreign-body implantation. The implants increased the blood vessel number in a wound. CONCLUSION: Both PCL and DBC could be used as scaffolds or dressings for wound treatment. The materials were safe and well tolerated by animals. As DBC did not disturb glycosaminoglycan accumulation in wounds and absorbed twice as much liquid as PCL, it can be considered superior.

CONTEXTE: Nous avons cherché à déterminer l'utilité du dibutyryl-chitine (DBC) ou du poly-(ε-caprolactone [PCL]) électrofilés dans le traitement des plaies. Nous avons étudié les mécanismes d'action de ces polymères sur la cicatrisation des plaies. MÉTHODES: Nous avons synthétisé le DBC, un dérivé ester récemment identifié de la chitine, à l'aide d'une méthode brevetée incluant la substitution des groupes butyryl aux positions C-3 et C-6 des molécules de chitine. Nous avons confirmé la substitution double par les groupes butyriques à l'aide de la spectrométrie infrarouge. Les échafaudages fibreux ont été obtenus grâce à la méthode de filage électrostatique. Un filet en polypropylène a été implanté par voie sous-cutanée dans le rat et a servi de modèle de plaie. RÉSULTATS: Le DBC et le PCL ont tous deux augmenté le poids du tissu de granulation dans la plaie. Contrairement au PCL, le DBC n'a pas supprimé les changements des glycosaminoglycanes des plaies. Les échantillons examinés n'ont pas perturbé la synthèse totale de collagène ni entraîné une fibrose excessive. Nous avons observé un niveau inférieur de collagène soluble (par rapport aux témoins) tant dans les plaies traitées par PCL que par DBC. Les résultats montrent une amélioration de l'hydratation des plaies tant pour les groupes DBC que PCL. Les matériaux à l'étude n'induisaient pas d'œdème étendu. Ces polymères ont induit des réactions macrophagiques presque identiques à l'implantation d'un corps étranger. Les implants ont accru le nombre de vaisseaux sanguins de la plaie. CONCLUSION: Tant le PCL que le DBC pourraient être utilisés comme échafaudages ou pansements pour le traitement des plaies. Les matériaux étaient sécuritaires et ont été bien tolérés par les animaux. Comme le DBC n'a pas perturbé l'accumulation des glycosaminoglycanes des plaies et a absorbé 2 fois plus de liquide que le PCL, il peut être considéré comme étant supérieur.

The role of histamine in the regulation of the viability, proliferation and transforming growth factor ß1 secretion of rat wound fibroblasts.

BACKGROUND: Inflammation mediators play a regulatory role in repair processes. The study will examine the influence of histamine on wound fibroblast metabolic activity, viability, proliferation, and TGFß1 secretion. The study also will identify the histamine receptor involved in regulation of the tested repair processes. METHODS: Fibroblasts were obtained from the granulation tissue of wounds or intact dermis of rats. The MTT and BrdU assays were used to examine the effect of histamine (10-8M-10-4M) on the viability and metabolic activity of fibroblasts, and on their proliferative capacity. The influence of histamine receptor antagonists (i.e., ketotifen, ranitidine, ciproxifan and JNJ7777120) and agonists (2-pyridylethlamine dihydrochloride, amthamine dihydrobromide) was also investigated. The TGFß1 and histamine receptors H1 were evaluated by enzyme-linked immunosorbent assay. RESULTS: Histamine significantly increased granulation tissue fibroblast viability and metabolic activity at 10-8 and 10-6M but did not change their proliferative activity. Only the blockade of the H1 receptor removed this effect of histamine. H1 receptor agonist (2-pyridylethlamine dihydrochloride) increased cell viability, thereby mimicking histamine action. Both Histamine (10-4M) and 2-pyridylethlamine dihydrochloride increased TGFß1 concentration in cell culture medium. However, ketotifen blocked histamine-induced augmentation of TGFß1. H1 receptor expression on wound fibroblasts was confirmed. CONCLUSION: The regulatory influence of histamine on wound fibroblast function (viability/metabolic activity or secretion of TGFß1) is dependent on H1 receptor stimulation. Contrary to wound fibroblasts, these cells express a very low level of H1 receptors when isolated from intact dermis and histamine is unable to modify their metabolic activity.

Comparison of various types of collagenous scaffolds applied for embryonic nerve cell culture.

The purpose of the study was to confirm whether collagen-based scaffolds using different cross-linking methods are suitable elaborate environments for embryonic nerve cell culture. Three 3D sponge-shaped porous scaffolds were composed using collagen alone, collagen with chondroitin sulphate modified by 1-ethyl-3-(3-dimethyl aminopropyl) carbodiimide hydrochloride, and collagen cross-linked by 2,3-dialdehyde cellulose (DAC). Embryonic nerve cells from rats were applied to the scaffolds and stained with bisbenzimide to study cell entrapment within the scaffolds. The metabolic activity of the cells cultured in the scaffolds was determined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. The majority of cells were differentiated into neurocytes or oligodendrocytes. Collagen and collagen-chondroitin sulphate scaffolds entrapped a low number of cells. The highest cell density was found in the collagen-DAC scaffold. Moreover, in collagen-DAC scaffolds, the metabolic activity was markedly higher than in the other samples. Although all used scaffolds are suitable for the culture of embryonic nerve cells, the collagen-DAC scaffold properties are the most favorable. This scaffold entraps the highest number of cells and constitutes a favorable environment for their culture. Hence, the Col-DAC scaffold is recommended as an effective carrier for embryonic nerve cells.

Timeline and bibliography of early isolations of plant metabolites (1770-1820) and their impact to pharmacy: A critical study.

Plant metabolites became objects of chemical research for pharmaceutical and medicinal reasons. The period of pure plant substances in chemistry started 1770 with isolation of tartaric acid from wine (wine in pharmacy is a plant-derived preparation). Carl Scheele isolated 7 plant acids: tartaric, benzoic, citric, oxalic, malic, glucuronic and gallic. The era of alkaloids started 1803 when narcotine was discovered and published. Since that time, pharmacists and toxicologists began to recognize alkaloids (or substances regarded as such) as highly active principles responsible for their powerful, thus easily-observed actions to humans and test animals. By 1820 when solanine was isolated, pharmaceutical chemistry has dealt with increasing number of natural plant-derived substances as organic medicines or reagents. The following historical facts have been unknown: Scheele's tartaric acid was introduced officially as a medicinal substance as early as in 1775, benzoic, citric and oxalic acids became official by the end of the 18th century. Morphine was effectively published in 1806 (not 1804), hence the first alkaloid known in isolated state is narcotine (published 1803, official since 1827). Morphine became official in French pharmacy in 1818. And, 1814 is the year when 2 first toxicological accounts on plant-derived acids (oxalic and tartaric) appeared. Practical use in therapy, sometimes soon after discovery, inspired practical pharmacy and stimulated the progress of toxicology. We studied the earliest 50years of plant metabolites isolations era. A revised bibliography and a timeline chart for 24 plant substances from this period is provided. Plants from original publications are taxonomically identified.

Chinese vegetative materia medica in a venereological treatise by Jean Astruc from 1740.

ETHNOPHARMACOLOGICAL RELEVANCE: Historical medical sources can be still queried for forgotten cures and remedies. Traditional Chinese medicine has dealt with lues venerea (syphilis) since the Five Dynasties period (10th century). Chinese indigenous materia medica and remedies recorded, studied or imported by the Europeans can reveal known or quite unknown medicinal plants. The studied Jean Astruc's work is a published ethnopharmacological survey carried out in Beijing in the 1730s and it deserves a modern interpretation. AIM OF THE STUDY: This is the first proposal to identify historical Chinese medicinal plants listed in a scarcely known medical treatise De Morbis venereis… ('On venereal diseases…') by Jean Astruc from 1740. I searched for the current uses and position of the taxonomically identified herbal stock in both traditional Chinese and official medical knowledge, with special attention to syphilis. MATERIAL AND METHODS: Chinese names of drugs and their botanical identities (originally expressed by means of pre-Linnaean polynomials, and now interpreted as accepted binomials) were independently cross-checked with younger till most recent taxonomical and ethnopharmacological sources. Plants and drugs identified this way were queried for their modern applications in traditional Chinese and official medicine with special attention to sexually transmitted diseases (STD) and other uses which are similar to the 18th-century understanding of venereology. RESULTS: For 24 items of medicinal stock, 34 medicinal plants have been identified or suspected: Acacia catechu, Achyranthes bidentata, Akebia quinata, Angelica dahurica, A. sinensis, Aquilaria sinensis, Aralia cordata, Aristolochia fangchi, Chaenomeles sinensis, Ch. speciosa, Clematis vitalba, Coix lacryma-jobi, Commiphora myrrha, Cydonia oblonga, Daemonorops draco, D. jenkinsiana, Dictamnus dasycarpus, Dryobalanops sumatrensis, Forsythia suspensa, Glycyrrhiza uralensis, Lonicera confusa, L. hypoglauca, L. japonica, Ligusticum striatum (=L. chuanxiong), Piper kadsura, Pterocarpus officinalis, Saposhnikovia divaricata, Sassafras tzumu, Smilax china, S. glabra, Stephania tetrandra, Styphnolobium japonicum, Trichosanthes japonica, T. kirilowii; China wax is also mentioned. Out of them, only Lonicera japonica is being used in China in late syphilis, Achyranthes bidentata in gonorrhoea, and Dictamnus dasycarpus in gynaecological problems. In the Astruc's study, 3 medicinal plant species and 5 further plant genera are correctly determined; other plant parts were misidentified. CONCLUSIONS: Antisyphilitic actions ascribed to the Chinese medical formulas and their constituents studied by Astruc, seem to have come from Hg or As compounds rather than from vegetative materia medica. The formulas contained only one species still known in TCM as a remedy for syphilis.

Central European medicinal bryophytes in the 16th-century work by Caspar Schwenckfeld, and their ethnopharmacological origin.

ETHNOPHARMACOLOGICAL RELEVANCE: Ubiquitous bryophyte species are reported from European, American and Asian ethnopharmacies. Some of their traditional medicinal uses are similar in distant and isolated cultures, and moreover, medicinal properties of some bryophytes are currently confirmed as justified by their chemical constituents. Aims of the work: we identify bryophytes listed in a medicinal and botanical work from 1600, and compare their medicinal applications (known in Europe between 1530-1600) with other ethnopharmacological data about these species and with modern pharmacological knowledge. This way we attempt to display origins of medicinal usage of bryophytes in Central Europe. MATERIALS AND METHODS: Bryophyte species in bibliographical sources printed in Central Europe (starting from O. Brunfels' Herbarum vivae Eicones... Argentorati, 1530) were identified according to old and recent taxonomical references. Caspar Schwenckfeld's scientific output from 1600 was treated here as a summary of 16th-century knowledge about medicinal bryophytes. RESULTS: Central European pharmacy about the year 1600 was familiar with the following bryophytes: Marchantia polymorpha L., Polytrichum commune Hedw., P. formosum Hedw. and Funaria hygrometrica Hedw. CONCLUSIONS: Between 1530-1600 in Central Europe the number of medicinal bryophytes increased from 2 (Lichen sive Hepatica and Polytrichon) to 4. Pharmaceutical usage of them was similar as in other, distant ethnopharmacies. Further 2-4 mosses (Rhytidiadelphus loreus and Rh. squarrosus; Thuidium tamariscinum and Th. delicatulum) were recognised as non-medicinal.