Structure-function relationship of new anthralin derivatives assayed for growth inhibition and cytotoxicity in human keratinocyte cultures.

HaCaT keratinocyte cultures were exposed to twelve hydrophilic anthralin derivatives 1 to 12 with substituents at C-1 and C-8 of the anthrone skeleton, of one H at C-10 and of both H's at C-10 by lacton rings. After 3 microM treatment growth was determined by cellular protein content, 3H-thymidine- and 14C-amino-acid-uptake and cytotoxicity by the release of cytoplasmic LDH into the culture medium. In comparison to acetone control (100%) anthralin suppressed mean protein content, as well as DNA- and protein-synthesis to 33, 28, and 21%, respectively, and the drug revealed an enzyme release of 660%. In relation to the parent drug we found similar cell growth inhibitory effects of compounds 4, 6, 8, 9, 10, and 12. Deriv. 4, 8, and 10 were, however, to some extent less cytotoxic than anthralin, whereas deriv. 6, 9, and 12 were in the same range. An extreme suppression of growth parameters which differed from the anthralin effect by a factor 0.5-0.8 was caused by deriv. 11, showing the same cytotoxicity. Deriv. 1, 2, 3, 5, and 7 did not demonstrate any cytotoxicity. Concerning growth parameters, deriv. 2 induced a slight stimulation, deriv. 3 and 7 were completely ineffective, deriv. 1 and 5 induced slightly to moderately inhibited proliferation but both being much less effective than anthralin. These data indicate that the "minimum structure" concept by Krebs and Schaltegger--claiming 1-hydroxy-9-anthrone as a precondition for clinical antipsoriatic potency--is not valid at least in cell-biological tests and point toward possible usefulness of some experimental model compounds as alternative antipsoriatics.     

A new heparin fragment decreases liver ischemia-reperfusion injury

<正>To the Editor:Ischemia-reperfusion injury following surgery and transplantation can lead to irreversible multiorgan failure.Intracellular calcium overload is associated to cellular death during ischemiareperfusion.A recently discovered heparin fragment (HF),trisulfated disaccharide (TD),that acts on sodium-calcium exchanger(NCX) decreasing intracellular Ca²⁺,showed effectiveness on protecting hepatocytes from ischemia-reperfusion injury [1],     

Mechanical evaluation of fracture fixation augmented with tricalcium phosphate bone cement in a porous osteoporotic cancellous bone model

OBJECTIVE: The purpose of this study was to examine the effects of resorbable bone cement on screw and plate-screw fracture fixation in a porous osteoporotic bone model. METHODS: Experiment 1: Screw pullout strength was assessed for 4 sets of 4.5-mm cortical screws inserted into a synthetic osteoporotic cancellous bone model, including screws inserted without cement augmentation (control), screws augmented with tricalcium phosphate (TCP) bone cement (Norian SRS; Synthes USA, Paoli, PA), and screws augmented with polymethylmethacrylate. Experiment 2: The effects of cement augmentation on plate-screw fixation strength were examined by performing cantilever bending tests on 4 sets of 8 plate-screw constructions, including nonaugmented and TCP-augmented standard and locked screw-plate constructions in a similar bone model. RESULTS: Experiment 1: Cement augmentation with both TCP and polymethylmethacrylate increased screw pullout strength from a porous osteoporotic cancellous bone model by about 4-fold (P < 0.05), and there was no significant difference between the 2 cements (P > 0.1). Experiment 2: Fixation strength was 1.5 times higher for locked plates compared with standard plates when neither was augmented with cement (P = 0.07). Cement augmentation with TCP improved fixation strength by 3.6 times for a standard plate-screw construction (P < 0.05) and 3.3 times for a locked plate-screw construction (P < 0.05). The most stable construction was the TCP-augmented locked plate, in which a 5-fold increase was observed compared with that of standard plates without TCP (P < 0.05). CONCLUSIONS: This study indicates augmenting screws with TCP cement during osteosynthesis improves fixation strength in an osteoporotic cancellous bone model. CLINICAL RELEVANCE:: In fracture situations in which osteoporotic bone makes screw and screw-plate fixation tenuous, screw augmentation with TCP cement should be considered as adjunct treatment.     

Dislocation of the proximal tibiofibular joint in association with a tibial shaft fracture: two case reports and a literature review.

Dislocation of the proximal tibiofibular joint (PTFJ) in association with a displaced tibial shaft fracture and an intact fibula is an exceedingly rare injury. We present 2 cases of tibia fractures associated with an intact fibula and a PTFJ dislocation. The first case involves a man who sustained a closed spiral fracture of the distal tibial shaft, with an intact fibula, an anterolaterally dislocated PTFJ, and a partial tear of the lateral collateral ligament. The tibia was percutaneously plated, and the PTFJ was reduced and then stabilized with temporary screw fixation. The second case involves a woman who sustained a closed fracture of the tibia in association with a PTFJ dislocation. The tibia was fixed with an intramedullary nail, and the PTFJ was similarly reduced and fixed with a temporary screw. We also provide a brief literature review focusing on classification of PTFJ dislocations, mechanism of injury, associated injuries, and treatment options.     

Radical Resection of Giant Congenital Melanocytic Nevus and Reconstruction With Meek-Graft Covered Integra Dermal Template

BACKGROUND: Giant congenital melanocytic nevi represent a surgical challenge, particularly in cases in which the size of the nevus exceeds certain extend and malignant transformations have to be considered. OBJECTIVE: To discuss through case report considerable surgical options when extensive giant congenital melanocytic nevi with malignant transformation are encountered. METHODS: We present an unusual case of a giant congenital melanocytic nevi of the entire back of a 44-year-old patient. To achieve radical resection with direct appropriate wound closure and acceptable outcome, the integument of the entire back was excised and covered with Integra, followed by split-thickness skin grafting after stable integration of the matrix. RESULTS: The approach resulted in a complete excision of the tumor and acceptable cosmetic and excellent biomechanical outcome. CONCLUSION: The introduced practice demonstrates a useful alternative to established methods, particularly if tumor excision in large areas and subsequent wound closure might be achieved in one procedure.     

一些保肝药物对原代培养大鼠肝细胞糖原合成功能的影响

本文参照PO Seglen的方法并加以修改,建立了原代培养大鼠肝细胞糖原合成功能的测定体系。观察到联苯双酯既能使正常肝细胞合成糖原增加88%,又能保护肝细胞完全拮抗四氯化碳对其功能的损伤;银耳多糖能使四氯化碳对肝细胞糖原合成功能的损伤减轻57%;去甲斑蝥素10μg/ml能增加肝细胞糖原合成,浓度增加到100μg/ml时,此作用减弱,1000μg/ml则明显抑制糖原的合成,而且在10～100μg/ml浓度时,即能加强四氯化碳的损伤作用;100μg/ml CL₁₅₀₀和熊果酸二钠单独应用可增加肝细胞糖原合成,但与四氯化碳同时应用,反而加重对糖原合成的抑制作用。     

Allergic contact dermatitis from phenylephrine in eyedrops.

Phenylephrine is widely used as an ophthalmic drug. However, there are only very few reports on allergic contact dermatitis induced by phenylephrine. In addition, little is known on cross reactivity patterns between the sympathomimetics phenylephrine, epinephrine and ephedrine which share a similar chemical structure. We report on a man who developed allergic contact dermatitis to Neosynerphin POS eyedrops containing phenylephrine hydrochloride. Cross reactivity between phenylephrine, epinephrine and ephedrine was studied by patch testing. Patch tests were performed with the European standard, an ophthalmics and preservatives series, Neosynerphin POS eyedrops, phenylephrine hydrochloride 10% aq., epinephrine and ephedrine (both 1.0 % aq.). Test sites were read after 48, 72 and 168 hours according to the recommendations of the ICDRG. Neosynerphin POS and phenylephrine hydrochloride 10 % aq. gave positive reactions, whereas epinephrine and ephedrine tested negative. Although phenylephrine is an epinephrine analog delayed type hypersensitivity to phenylephrine did not result in cross reactivity with chemically related epinephrine and ephedrine.     

Expanding the spectrum of PTH1R mutations in patients with primary failure of tooth eruption

Objectives

Primary failure of tooth eruption (PFE) is a rare autosomal-dominant disease characterized by severe lateral open bite as a consequence of incomplete eruption of posterior teeth. Heterozygous mutations in the parathyroid hormone 1 receptor (PTH1R) gene have been shown to cause PFE likely due to protein haploinsufficiency. To further expand on the mutational spectrum of PFE-associated mutations, we report here on the sequencing results of the PTH1R gene in 70 index PFE cases.

Materials and methods

Sanger sequencing of the PTH1R coding exons and their immediate flanking intronic sequences was performed with DNA samples from 70 index PFE cases.

Results

We identified a total of 30 unique variants, of which 12 were classified as pathogenic based on their deleterious consequences on PTH1R protein while 16 changes were characterized as unclassified variants with as yet unknown effects on disease pathology. The remaining two variants represent common polymorphisms.

Conclusions

Our data significantly increase the number of presently known unique PFE-causing PTH1R mutations and provide a series of variants with unclear pathogenicity which will require further in vitro assaying to determine their effects on protein structure and function.

Clinical relevance

Management of PTH1R-associated PFE is problematic, in particular when teeth are exposed to orthodontic force. Therefore, upon clinical suspicion of PFE, molecular DNA testing is indicated to support decision making for further treatment options.     

EAACI/GA2LEN/EDF guideline: definition, classification and diagnosis of urticaria

This guideline is the result of a consensus reached during a panel discussion at the 2nd International Consensus Meeting on Urticaria, Urticaria 2004, a joint initiative of the European Academy of Allergology and Clinical Immunology Dermatology Section and the European Union (EU)-funded network of excellence, GA2LEN. It covers the definition and classification of urticaria, taking into account the recent progress in identifying causes, eliciting factors and pathomechanisms of this disease. We have outlined useful diagnostic approaches for different subtypes of urticaria. This guideline was, in addition, accepted by the European Dermatology Forum (EDF) and was formally approved by the European Union of Medical Specialists (UEMS).