bluuebunny/crossref_metadata_2025 huggingface dataset:
Palmoplantar keratoderma – Mal de Meleda syndrome
Authors: Rajashekhar Nadiga , Moideen Rafeeq
Published: August 2010

One sister and one brother (of four), aged 18 and 12 years, respectively, born of a consanguineous marriage between first cousins, presented with thickening of the palms and soles after 1 year of life, which was slowly increasing, and the simultaneous appearance of thickened skin: colored plaques on the dorsal aspect of the hands, feet, knees, and ankles. There was hyperhidrosis of the palms and soles, but no history of similar complaints in the maternal/paternal family. The pedigree was as shown in Fig. 1.

On examination, the sister showed diffuse palmoplantar keratoderma extending to the dorsal surface with sharp margins. The fingers were short and mutilated, and the nails showed subungual hyperkeratosis, onycholysis, and Beau's lines (Figs 2 and 3). Circular hyperkeratotic knuckle‐pad‐like thickenings were present on all proximal interphalangeal joints and some knuckles. Irregular‐shaped hyperkeratotic plaques and linear keratosis were present on the flexor aspect of the wrists and on the dorsal aspect of the feet, ankles, and knees.

The brother (12 years old) showed the same type of clinical features.

The histopathology revealed hyperkeratosis, hypergranulosis, acanthosis, and chronic inflammatory dermal infiltrate.

General and systemic examination of all the sisters and brothers was normal. Ophthalmologic examination was normal. Oto‐rhino‐laryngologic examination showed a high arched palate. Intelligence testing of all sisters and brothers was normal.

The patients were given oral vitamin A with vitamin E and topical keratolytes. They are under follow‐up at present.
Pyoderma gangrenosum associated with anticardiolipin antibodies in a pregnant patient
Authors: Freedman Alan M. , Phelps Robert G. , Lebwohl Mark
Published: August 2010

A 40‐year‐old pregnant woman at 17 weeks of gestation presented with a 10‐day history of pain and erythema in the right leg. She had experienced a similar episode in the postpartum period (1 week) 14 months earlier, lasting 2 months. This was diagnosed as cellulitis and resolved following antimicrobial therapy. The patient had no fever or chills. Pertinent past medical history involved a possible history of ampicillin allergy.

The initial differential diagnosis included cellulitis and thrombophlebitis. Antibiotic therapy with intravenous (IV) cefazolin was started at the same time as anticoagulation with heparin. Over the next few days the ulceration enlarged. No microbial growth was detected on wound cultures and Doppler studies carried out prior to admission revealed normal venous flow. The patient did not respond to therapy.

A dermatology consult was requested. When the patient was first examined by us, the ulceration had been progressively increasing in size. There was an oozing ulcerated patch 7 cm in diameter on the right distal medial thigh (Fig. 1). The ulcer contained crater‐like holes and fistulous tracts from which pus could be expressed upon application of pressure. The surrounding border was undermined and violaceous. A clinical diagnosis of pyoderma gangrenosum (PG) was made.

Antinuclear antibodies and antibodies to Smith antigen were negative; anticardiolipin antibody was positive. A 3‐mm punch biopsy showed an intense neutrophilic response with fibrinoid change in some vessels (Fig. 2), which was felt to be consistent with PG with a concomitant small vessel vasculitis. No fibrin thrombi were noted. The heparin was replaced with aspirin and the IV antibiotics were changed to oral cephalexin. Intralesional triamcinolone (40 mg/cc) was started and a 3‐day course (80 mg/40 mg/20 mg) of oral prednisone was initiated. Within 2 days of starting steroid therapy, the inflammation and discharge were greatly reduced.

Approximately 2 weeks after admission the therapy was noted to halt the progression. The lesion became more well demarcated with healthy granulation tissue and decreased tenderness and warmth.

The patient was discharged on Burow's solution, saline soaks, and bacitracin and was seen by us on two occasions after discharge for intralesional steroid administration. One flare‐up since discharge was controlled by increasing her prednisone from 10 mg to 20 mg daily. The patient had premature rupture of membranes at 37 weeks, had a spontaneous vaginal delivery, and delivered a healthy baby boy weighing 5 Ib 14 oz. Since then, the ulcer had re‐epithelialized with tapering doses of prednisone.
Large B‐cell lymphoma of the leg
Authors: Vasquez‐del‐Mercado Elsa , Toussaint Sonia , De La Barreda Fernando , Ortiz‐Hidalgo Carlos
Published: August 2010

A 74‐year‐old Mexican man presented with an 18‐month history of multiple, violaceous, coalescing, firm, tender nodules with an ulcer in the anterior aspect of the right leg (Fig. 1) and slightly infiltrated, ill‐defined erythematous plaques affecting the left leg and both forearms. He had not received any treatment for his condition. Past medical history was relevant for noninsulin‐dependent diabetes mellitus and hypertension without formal treatment and a history of heavy alcohol intake in his youth. A biopsy specimen of both plaque‐type lesions of the forearm and tumorous lesions of the leg showed a diffuse, nonepidermotropic mononuclear infiltrate throughout the dermis and extending to the subcutis. The infiltrate was composed of pleomorphic, atypical, large mononuclear cells (Fig. 2). Immunostaining with CD20 was positive for the atypical cells while CD3 was positive for normal appearing lymphocytes, characterized as reactive T cells. Additional laboratory and image studies ruled out extracutaneous involvement. The diagnosis of primary cutaneous large B cell lymphoma of the leg (LBCLL) was made. The patient was initiated on radiotherapy localized to the right leg with a very good initial response, nevertheless resolution was not achieved and the plaques in the rest of the limbs remained unchanged. Thus, the patient started chemotherapy with CHOP (Cyclophosphamide, Vincristine, Doxorubicin, Prednisone). He has currently finished his fourth cycle with this chemotherapy regimen. The tumorous lesions involuted leaving only residual hyperpigmentation (Fig. 3) and the plaques in the rest of the limbs disappeared, the area of the ulcer diminished considerably. There is still no evidence of extracutaneous involvement.

Nodules and ulcer in the anterior aspect of the right leg

image

Atypical lymphocytes, with large, pleomorphic nuclei and multiple nucleoles. Positivity for CD20 antigen was demonstrated by immunohistochemical analysis (hematoxylin and eosin; X 600)

image

Residual hyperpigmentation and granulation tissue after chemotherapy

image
Caspase‐9 expression is increased in endothelial cells of active Behçet's disease patients
Authors: Öztaş Pınar , Lortlar Neşe , Polat Muhterem , Allı Nuran , Ömeroğlu Suna , Basman Adil
Published: August 2010

Background  Behçet's disease is a multisystem disease of unknown etiology. Caspase‐9 is responsible for initiating the caspase activation cascade during apoptosis. The aim of this study was to examine caspase‐9 expression in both endothelial and perivascular infiltrates of patients with active Behçet's disease.

Methods  Fifteen patients with active Behçet's disease, attending the First Dermatology Department, Ankara Numune Hospital, Ankara, Turkey between June 2003 and December 2005, were included in the study. Oral biopsy specimens from nine healthy volunteers were taken as the healthy control group, and skin biopsies from 18 psoriasis patients were used as the inflammatory control group. The specimens were examined with caspase‐9 primary antibody. Statistical analyses were performed using SPSS 11.5.

Results  The mean caspase‐9‐positive endothelial cell counts were 7.17 ± 2.45 in active Behçet's disease, 4.81 ± 0.76 in healthy controls, and 4.35 ± 1.34 in inflammatory controls. The difference between Behçet's disease and healthy controls was statistically significant, with increased endothelial staining in active Behçet's disease (P = 0.049). The difference between Behçet's disease and inflammatory controls was also statistically significant; the rate of staining was higher in Behçet's disease (P = 0.006). The mean caspase‐9‐positive dermal perivascular cell counts were 5.15 ± 2.32 in Behçet's disease, 3.32 ± 0.82 in healthy controls, and 5.54 ± 4.95 in inflammatory controls. These values did not show any statistically significant difference (P = 0.407).

Conclusion  Endothelial cells are one of the key cells in Behçet's disease, and our findings support the role of endothelial cells in the etiopathogenesis of Behçet's disease.
A case of linear IgA disease in a child with IgA and IgG circulating antibodies directed to BPAg2
Authors: Viglizzo Gianmaria , Cozzani Emanuele , Nozza Paolo , Occella Corrado , Parodi Aurora
Published: August 2010

A 7‐year‐old Caucasian girl had multiple bullae on the trunk, upper and lower limbs (Fig. 1a,b) for 10 days. The lesions were large, tense, and asymptomatic, and mucosae were not involved. Laboratory findings were all normal. Histopathology revealed a subepidermal blister containing numerous neutrophils, eosinophils, and fibrin. Direct immunofluorescence of perilesional skin disclosed linear deposition of IgA and slight linear deposits of IgM at the basement membrane zone (Fig. 2). Indirect immunofluorescence on monkey esophagus and on human salt‐split skin was negative. Immunoblot assay (IB), performed with an epidermal extract, revealed IgA and IgG antibodies directed to BPAg2 antigen (Fig. 3), while it was negative when performed on dermal extract. Enzyme‐linked immunosorbent serologic assay using a commercial kit (MBL, Naka‐Ku Nagoya, Japan) with the noncollagenous domain (NC16A) of the BPAg2 antigen was negative for both IgA and IgG. A diagnosis of linear IgA disease (LAD) was made and a treatment with dapsone (50 mg/day) and prednisolone (30 mg/day) was initiated. One month later, lesions had cleared.

Multiple tense bullae on the limbs

image

Direct immunofluorescence shows a continuous linear IgA deposit at the basement membrane zone (BMZ) (magnification ×300)

image

Immunoblot assay (IB) of the patient's serum on an epidermal extract using an anti‐IgG antiserum (lane 2) and an anti‐IgA antiserum (lane 3) reveals a 180‐kDa medium wave band, identical to that revealed by a BPAg2 IgG positive control serum (lane1)

image
Polish dermatology in the 19th and the first half of the 20th centuries
Authors: Grzybowski Andrzej
Published: August 2010

The beginnings of Polish dermatology date back to the first half of the 19th century in Kraków. The first textbook of dermatology was written by Ludwik Bierkowski. Later the progress in the development of this field of medicine was due to Franciszek Krzyształowicz, Marian Grzybowski, Franciszek Walter, and Jan Alkiewicz. Krzyształowicz's most remarkable achievements were related to his studies of the Treponema pallidum of syphilis. Grzybowski's main contribution to international dermatology was the first description in the medical literature of a specific variant of keratoacanthoma, which has since then been called Grzybowski's eruptive keratoacanthoma or generalized eruptive keratoacanthoma – Grzybowski's variant. Alkiewicz described trachyonychia, or twenty‐nail dystrophy, a disease that became well established in the dermatological literature; he also described the so‐called transverse net in onychomycosis. Walter identified the syphilitic skin and bone lesions in some figures carved in the Veit Stoss's altar in Kraków, thus presenting the famous thesis of the non‐American origin of syphilis in Europe. Considering all these achievements, it is the goal of this paper to review Polish contributions to international dermatology.
Buschke–Ollendorff syndrome
Authors: Schena Donatella , Germi Lerica , Zamperetti Maria Rosa , Colato Chiara , Girolomoni Giampiero
Published: August 2010

Background  Buschke–Ollendorff syndrome is a rare autosomal dominant disease featuring osteopoikilosis and skin lesions. It is caused by genetic mutations in a protein deeply involved in bone and connective tissue morphogenesis.

Methods  We describe a 39‐year‐old woman with Buschke–Ollendorff syndrome.

Results  After a minor trauma, radiologic examination of the left ankle of a 39‐year‐old woman revealed features of osteopoikilosis. Physical examination of the patient showed multiple asymptomatic nodules on both thighs, present since the age of 20 years, which had increased in size and number. Recently, a linear, string‐like lesion had appeared on the right thigh.

Conclusion  The correct diagnosis of Buschke–Ollendorff syndrome may require a high index of suspicion.
The frequency and seasonal variations in juvenile outpatients treated in a dermatology polyclinic
Authors: Cicek Demet , Kandi Basak , Oguz Sevilay , Ucak Haydar , Saral Yunus , Kurt Abdullah
Published: August 2010

Objective  This study was carried out to evaluate the frequency and seasonal characteristics of dermatological problems of juvenile outpatients in the dermatology polyclinic.

Material and method  Children under the age of 17 treated in an outpatient setting in our polyclinic within a 10‐year period were retrospectively evaluated.

Results  The study registered a total of 3244 patients, of whom 1651 (50.90%) were females, and 1593 (49.10%) were males. The largest group was infectious diseases, with 1031 patients (31.78%). This was followed by the dermatitis group with 635 patients (19.57%). The months when the number of presentations at the hospital was the highest were August and November, and the months with the lowest number of presentations were January and July.

Conclusion  In the present study we found that the most frequent cause of hospital visits of juvenile outpatients at our polyclinic was infectious diseases and dermatitis, and that there was significant correlation between diseases and seasons.
Mycobacterium tuberculosis chaperonin 10 and N‐truncated fragments Their synthesis and purification by the isoelectric focusing technique carried out in solution
Authors: LUCIETTO PIERLUIGI , FOSSATI GIANLUCA , BALL HAYDN L. , GIULIANI PAOLA , MASCAGNI PAOLO
Published: August 2010

The Mycobacterium tuberculosis chaperonin 10 protein and fragments corresponding to sequences 59‐99, 51‐99 and 26‐99 were synthesised by the solid‐phase methodology using a double coupling protocol and without the aid of capping agents. After the final acid cleavage using the low TFMSA‐high HF protocol the polypeptides were purified by either the ion exchange chromatography/RP‐HPLC combination or the isoelectric separation carried out in solution and followed by semi‐preparative RP‐HPLC. Comparison of the results obtained through the two approaches indicated that in general the isoeletricfocusing/HPLC combination was superior both in terms of recovery of final material and its purity. The advantages found were as follows: (i) Unlike ion exchange chromatography, no tailoring of the separation conditions is required. (ii) Several consecutive focusings can be carried out in progressively narrower pH gradients. This increases the separation resolution without the need of changing other separation parameters, (iii) Very little manipulation is needed, and each focusing requires 3‐5 h. (iv) Full compatibility with non‐ionic denaturants such as 8 M urea. This increases solubility so that using the ROTOFOR instrument described here 50‐100 mg crude polypeptide can be processed daily.

Thus the isoelectric focusing technique carried out in solution is a valid and inexpensive alternative to ion exchange chromatography. © Munksgaard 1997.
Aza‐peptides II. X‐Ray structures of aza‐alanine and aza‐asparagine‐containing peptides
Authors: ANDRÉ FRÉDÉRIC , BOUSSARD GUY , BAYEUL DANIEL , DIDIERJEAN CLAUDE , AUBRY ANDRÉ , MARRAUD MICHEL
Published: August 2010

In order to determine the structural consequences of the Nx/CxH exchange in aza‐peptides, we have solved the crystal molecular structures of some derivatives containing the aza‐analogue of asparagine [Z‐AzAsn(Me)‐NMe2 (1), Z‐AzAsn(Me)‐Pro‐NHiPr (2) and Piv‐Pro‐AzAsn(Me)‐NHiPr (5), aspartic acid [Z‐AzAsp(OEt)‐Pro‐NHiPr (3) and alanine (Boc‐AzAla‐Pro‐NHiPr (4), by using X‐ray diffraction. They reveal that the α‐nitrogen accommodates a pyramidal (1–4) or planar (5) structure depending on the sequence. When pyramidal, the α‐nitrogen assumes the R (D‐like) chiralily. All of the derivatives but 1 adopt either a β1‐folded (2–4) or βII‐folded (5) structure in which the (AzAsn)NδH bond is intramolecularly hydrogen‐bonded to the α‐nitrogen. © Munksgaard 1997.
Technetium‐99m labeled epidermal growth factor‐tumor imaging in mice
Authors: RUSCKOWSKI M. , CHANG T. QU, F. , HNATOWICH D. J.
Published: August 2010

We have shown previously that the epidermal growth factor peptide (EGF) may be radiolabeled with 99mTc at room temperature and neutral pH by using the N‐hydroxysuccinimide ester of S‐acetyl mercaptoacetyltriglycine (MAG3) as a bifunctional chelator. By a competition binding assay, we found that MAG3‐conjugated EGF retained biological activity. Furthermore, the labeled peptide exhibited saturation binding to EGF receptor‐positive tumor cell lines which could be inhibited by presaturation of the cells with unlabeled, native EGF. Biodistribution in normal mice at 3 h postadministration showed rapid clearance with minimal retention of the label in sampled organs. We have now investigated the tumor localization properties in mice of this labeled peptide. Nude mice implanted with the EGF receptor‐positive tumors A431 and LS‐174T were administered labeled EGF and a labeled control peptide (BPTI, aprotinin). Tumor uptake at 12 h postadministration was 0.44% injected dose/g for EGF/g vs. 0.09 for the control. Pretreatment of tumored mice with unlabeled EGF blocked about half the tumor uptake. Animals were also administered an anti‐EGF receptor antibody labeled with 99mTc via MAG3. Relative to the antibody, tumor‐to‐muscle ratios were improved from 6 to 15 and tumor‐to‐blood ratios from 0.4 to 7 with EGF. These favorable results along with documented evidence of overexpression of the EGF receptor in many human tumors suggest that 99mTc‐EGF should be considered further for tumor detection. © Munksgaard 1997.
Preparations of Boc‐Cys(S‐Pyr)‐OH and Z‐Cys(S‐Pyr)‐OH and their applications in orthogonal coupling of unprotected peptide segments
Authors: HUANG HAIHONG , CAREY ROBERT I.
Published: August 2010

Boc‐Cys(S‐Pyr)‐OH and Z‐Cys(S‐Pyr)‐OH were prepared by addition of their cysteine derivatives to 3 equiv of 2,2′‐dipyridyldisulfide in one portion. 2‐Mercaptopyridine was removed by addition of 0.1 M CU(NO3)2 to the solution. Both derivatives are white solids and can be used to facilitate the formations of heterodisulfide bonds. Two methods of synthesizing peptides with N‐terminal Cys(S‐Pyr) were also provided. Two peptide thiocarboxylic acids H‐Tyr‐Ser‐Ala‐Glu‐Leu‐Val‐SH and H‐Tyr‐Ser‐Ala‐Glu‐Leu‐Gly‐SH were prepared on the thioester benzhydryl resin with the cleavage condition of 1.0 m TFMS A/TFA instead of HF. From the orthogonal couplings of these peptides with H‐Cys(S‐Pyr)‐Tyr‐Ser‐Glu‐Leu‐Ala‐NH2, both intramolecular acyl transfers finished at pH 7 at about 15 to 20 min. The intermediate acyl disulfide peptide was collected by high‐performance liquid chromatography and identified by liquid chromatography‐mass spectrometry.
Self‐assembling bis‐dendritic peptides: design, synthesis and characterization of oxalyl‐linked bis‐glutamyl peptides [Glun(CO2Me)n+1‐CO‐]2; n = 1,3,7
Authors: RANGANATHAN DARSHAN , KURUR SUNITA , MADHUSUDANAN K. P. , ROY RAJA , KARLE ISABELLA L.
Published: August 2010

Three generations of glutamic acid dendrons [Glun(CO2Me)n+1; n = 1,3,7] have been joined together head‐to‐head by an oxalyl unit to form highly sterically congested bis‐Glu‐dendritic peptides with gelling properties. The single crystal X‐ray structure of the first generation bis‐dendritic peptide showed an extended hydrogen‐bonded chiral tape with modest nonlinear optical activity.
Structural studies on endothelin receptor subtype B specific agonist IRL 1620 (suc‐[Glu9,Ala11,15]ET‐1(8‐21)) and its analogs with dipalmitoyl phosphatidylcholine vesicles by NMR spectroscopy
Authors: KATAHIRA RITSUKO , UMEMURA ICHIRO , TAKAI MICHIHIRO , ODA KYOKO , OKADA TOSHIKAZU , NOSAKA ATSUKO Y.
Published: August 2010

IRL 1620 {suc‐[Glu9,Ala11,15]ET‐1(8‐21)} is a potent and specific agonist for the ETB receptor. Five analogs of IRL 1620 were synthesized in this study. These were all C‐terminal linear peptides of endothelin 1 (ET‐1) comprising 14 amino acid residues and exhibiting highly potent ETB receptor binding affinities. The peptides consisted of three pairs and each component of the pairs differed from its partner in only the 18th residue, i.e. Asp was replaced by Gly. The replacements resulted in more than a 10‐fold increase in affinity to the ETA receptor. The structures of these peptides were investigated in the presence of phospholipid vesicles (dipalmitoyl phosphatidylcholine) by NMR spectroscopy. By the replacement of Asp by a less bulky Gly, the C‐terminal tripeptide region folded back toward the helical region, making it shorter than the Asp‐substituted peptide helical region. Such a folded conformational feature may explain the increased binding affinity to ETA receptor.
Characterization of the thiol/disulfide chemistry of peptides corresponding to the 603‐609 disulfide loop of the human immunodeficiency virus (HIV) envelope glycoprotein gp41
Authors: RABENSTEIN DALLAS L. , RUSSELL JAMES , GU JUAN
Published: August 2010

The redox chemistry of two synthetic model peptides for the 603‐609 disulfide loop found in envelope glycoprotein gp41 of the human immunodeficiency virus type 1 (HIV‐1) are reported. The two peptides:

image

and

image

were synthesized by the solid phase method. Peptide I corresponds to amino acids 601–611 of gp41 of the North American/European strain of HIV‐1. Peptide II incorporates amino acid replacements frequent in African HIV‐1 isolates. The redox chemistry of the disulfide bonds in the two peptides was characterized in aqueous and aqueous/urea solution by studying their thiol‐disulfide exchange reactions with the tripeptide glutathione (GSH). GSH reacts with the disulfide bonds to form mixed disulfides, which in turn react with another molecule of GSH to give the dithiol form of the peptide and GSSG. Equilibrium constants were determined for each step and for the overall reduction reactions. Redox potentials of −0.246V and −0.241V were calculated from the equilibrium constants for the disulfide bonds in peptides I and II in aqueous solution at 25°C and pH 7.0. The overall equilibrium constants are less in 8 M urea solution, which indicates a stabilization of the reduced, dithiol form of both peptides by secondary structure which can be denatured by urea. This conclusion is supported by nuclear Overhauser enhancement data obtained from 2D‐ROESY NMR spectra which provide evidence of elements of secondary structure for the reduced forms of both peptides. The results are discussed in terms of a protein disulfide isomerase catalyzed reduction of the disulfide bond in gp41.
Effect of oxidation of β‐amyloid precursor protein on its β‐secretase cleavage. A model study with synthetic peptides and candidate β‐secretases
Authors: Rpaea‐Kozik M. , Kozik A. , Travis J.
Published: August 2010

As the amyloidogenic processing of β‐amyloid precursor protein (βAPP) proceeds under conditions of oxidative stress, the methionine‐596 residue at the β‐secretase cleavage point is likely in an oxidized state. In the present work, possible consequences of the oxidation of Met‐596 for the generation of the N‐terminus of amyloid p protein were modeled using synthetic peptide substrates, matching 587‐606 sequence fragment of βAPP and containing either intact methionine or methionine sulfoxide. Patterns and rates for the cleavage of these substrates by purified mast cell chymase, cathepsin G, cathepsin D, matrix metallopro‐teinase‐3 and neutrophil elastase, were compared. Only the three first proteases, all previously suggested as candidate β‐secretases, preferentially cleaved the “intact” substrate after Met‐596. For chymase and cathepsin G, the specificity of this cleavage increased upon a shift from optimal alkaline pH to acidic pH, which is also more compatible with the plausible intracellular localization of amyloidogenic βAPP processing. The substitution of methionine sulfoxide for methionine in the substrate slowed down the cleavage rate for all the enzymes tested, by a factor of 6‐15. This was associated with shifts of cleavage preferences to points of minor importance for the “intact” peptide, suggesting a specific resistance of the peptide bond after MetSO‐596 against proteolysis.
Sequence‐assisted peptide synthesis (SAPS)
Authors: Larsen B. Due , Holm A.
Published: August 2010

In solid‐phase peptide synthesis (SPPS) the growing peptide chain may undergo chain aggregation which can cause serious synthetic problems. A number of investigations concerning this problem have been reported in the chemical literature. During a study of such “difficult sequences” using the Fmoc‐protection strategy, we have observed that peptide‐chain aggregation may be significantly reduced when certain amino acid sequences are incorporated C‐terminally (1). Thus, synthesis of the difficult poly‐alanine, (Ala)n, sequence (n ≦ 20) has been investigated with (Lys(Boc))m (m lE; 6) and (Glu(tBu))m (m ≧ 6) as pre‐sequences. With m ≧ 3, peptides are obtained as single, homogeneous products while a complex mixture of deletion peptides and corresponding Fmoc‐protected peptides is formed (n ≧ 6) without the pre‐sequence. A mixed pre‐sequence, (Lys(Boc)Glu(tBu))3, has a similar favorable effect on the synthetic results, but the positive effect seems confined to a rather narrow framework of amino acids and side‐chain protecting groups in the pre‐sequence as discussed in the article.

Among other reputedly difficult sequences the synthesis of H‐(Thr‐Val)5‐OH, H‐Val‐Asn‐Val‐Asn‐Val‐Gln‐Val‐Gln‐Val‐Asp‐OH, the Acyl Carrier Protein (65–74) and the human insulin B‐chain has been investigated. In all cases introduction of a pre‐sequence gives rise to satisfactory synthetic results. In the latter case, the lysine pre‐sequence may be cleaved enzymatically to give the desB30 insulin B‐chain.

NIR‐FT Raman studies of the synthesis of the poly‐alanine, (Ala)n, sequences have shown that the pre‐sequence (Lys(Boc))6 shifts the conformation of the growing peptide chain from a β‐structure (n ≧ 6) to a random coil conformation (1c). This result is in agreement with the general observation that SPPS proceeds optimally under random coil conditions.
Solid‐phase synthesis, conformational analysis, and biological activity of AVRp elicitor peptides of the fungal tomato pathogen Cladosporium falvum
Authors: Mahé E. , Vossen P. , Van den Hooven H. W. , Le‐Nguyen D. , Vervoort J. , De Wit P. J. G. M.
Published: August 2010

The race‐specific peptide elicitor AVR9 of the fungal pathogen Cladosporium fulvum specifically induces a hypersensitive response in tomato genotypes carrying the complementary resistance gene Cf‐9. The total chemical syntheses of this 28‐residue AVR9 peptide containing three disulfide bonds, and of three mutant peptides [R8K]AVR9, [F10A]AVR9 and [F21A]AVR9, have been accomplished. The syntheses were carried out using a stepwise solid‐phase approach based on tBoc chemistry. The disulfide bridges were formed by air oxidation. The correctness of the chemical structure of all folded synthetic peptides was confirmed by combined NMR and MS analyses. The biological activity and a number of physicochemical properties of folded synthetic AVR9 are identical to those of native fungal 28‐residue AVR9. The overall conformations of the folded synthetic mutant peptides were comparable to that of synthetic wild‐type AVR9 as demonstrated by NMR spectroscopy. Mutant [R8K]AVR9 showed a threefold higher, and mutant [F10A]AVR9 a threefold lower necrosis‐inducing activity when compared to synthetic wild‐type AVR9. However, mutant [F21A]AVR9 showed hardly any necrosis‐inducing activity. Affinity for polyclonal antibodies raised against native fungal AVR9 is positively correlated with the necrosis‐inducing activity of the synthetic AVR9 peptides ([R8K]AVR9 > wild‐type AVR9 > [F10A]AVR9 > [F21A]AVR9).
Design of peptides with αβ‐dehydro residues: Synthesis, crystal structure and molecular conformation of N‐Boc‐L‐Ile‐ΔPhe‐L‐Trp‐OCH3
Authors: Vijayaraghavan R. , Kumar P. , Dey S. , Singh T.P.
Published: August 2010

The dehydro‐peptide Boc‐L‐Ile‐ΔPhe‐L‐Trp‐OCH3 was synthesized by the azlactone method in the solution phase. The peptide was crystallized from methanol in an orthorhombic space group P212121 with a = 10.777(2), b= 11.224(2), c= 26.627(10) Å. The structure was determined by direct methods and refined to an R value of 0.069 for 3093 observed reflections [l≥ 2σ(l)].The peptide failed to adopt a folded conformation with backbone torsion angles: φ1, = 90.8(8)°, ψ1= ‐151.6(6)°, φ2= 89.0(8)°, ψ2= 15.9(9)°, φ3= 165.7(7)°, ψT3= ‐166.0(7)°. A general rule derived from earlier studies indicates that a three‐peptide unit sequence with a ΔPhe at the (i+ 2) position adopts a β‐turn II conformation. Because the branched β‐carbon residues such as valine and isoleucine have strong conformational preferences, they combine with the ΔPhe residue differently to generate a unique set of conformations in such peptides. The presence of β‐branched residues simultaneously at both (i+ 1) and (i+ 3) positions induces unfolded conformations in tetrapeptides, but a β‐branched residue substituted only at (i+ 3) positron can not prevent the formation of a folded β‐turn II conformation. On the other hand, the present structure shows that a β‐branched residue substituted at the (i+ 1) position prevents the formation of a β‐turn II conformation. These observations indicate that a β‐branched residue at the (i+ 1) position prevents a folded conformation whereas it cannot generate the same degree of effect from the (i+ 3) position. This may be because of the trans disposition of the planar ΔPhe side‐chain with respect to the C=O group in the residue. The molecules are packed in an anti‐parallel manner to generate N2‐H2…O2 (‐x,y‐1/2, ‐z+ 3/2) and Nε13‐Hε13…O1(‐x,y ‐1/2, ‐z+ 3/2) hydrogen bonds.
Structure‐function analysis of the Saccharomyces cerevisiae tridecapeptide pheromone using alanine‐scanned analogs
Authors: Abel M.G. , Zhang Y.L. , Lu H.‐F. , Naider F. , Becker J.M.
Published: August 2010

Twenty‐six peptide analogs of the Saccharomyces cerevisiaeα‐factor, a tridecapeptide mating pheromone (W1H2W3L4Q5L6K7P8G9Q10p11M12Y13) with either l‐ or D‐alanine replacement of each amino acid residue (Ala‐scanned) and with the isosteric replacement of methionine at position 12 by norleucine, were synthesized, purified to homogeneity and assayed for biological activity and receptor binding. Two new and effective antagonists. [D‐Ala3,Nle12]α‐factor and [D‐Ala4,Nle12]α‐factor, were found among the series, and the [D‐Ala10,Nle12]α‐factor demonstrated a marked ability to increase the biological activity of [Nle12]α‐factor without having any effect by itself. One analog, the [L‐Ala1α‐factor, showed a 3‐fold increase in bioactivity over the [Nle12]α‐factor, although its binding to the α‐factor receptor was about 70‐fold less than [Nle12]α‐factor. Residues near the carboxyl terminus contributed more strongly to receptor binding than other residues, whereas those near the amine terminus of the α‐factor played an important role in signal transduction. The effect of insertion of D‐Ala residues at positions 7, 8, 9 and 10 on bioactivity and receptor binding of the peptide suggested a specific positioning role of the central loop in establishing optimal contacts between the receptor and the ends of the pheromone. We conclude that the α‐factor may be divided into segments with dominant roles in forming the biologically active pheromone conformation, in receptor binding and in initiating signal transduction. The discovery of such relationships was made possible by the systematic variation of each residue in the peptide and by the testing of each analog in highly defined biological and binding assays.
Influence of orientations of guidewire tip on the placement of subclavian venous catheters
Authors: Park H‐P. , Jeon Y. , Hwang J‐w. , Han S‐H. , Bahk J‐H. , Oh Y‐S.
Published: August 2010

Background:  The role of a J‐type guidewire tip has been known to prevent vascular or cardiac wall damage. We hypothesized that the course of the guidewire may be influenced by the initial orientations of the J‐type guidewire tip during the subclavian approach. The purpose of this study was to investigate the influence of the direction of the needle bevel and J‐wire tip on successful placement of subclavian catheters.

Methods:  A total of 140 adult patients of either sex were studied. Patients were randomly divided by the direction of the needle bevel (neutral vs. downward) and the direction of the J‐wire tip (upward vs. downward). Under general anesthesia, right infraclavicular subclavian catheterization was attempted using the Seldinger technique.

Results:  There was no statistically significant difference among the successful and unsuccessful placements in relation to factors including sex, body mass index, and needle bevel direction. The success rate was high when the J‐wire tip was directed downward (P = 0.001).

Conclusion:  These data suggest that the orientation of the J‐wire tip downward can increase successful placement rates of right subclavian venous catheterization.
Risk factors for acute renal failure requiring dialysis after surgery for congenital heart disease in children
Authors: Pedersen K. R. , Povlsen J. V. , Christensen S. , Pedersen J. , Hjortholm K. , Larsen S. H. , Hjortdal V. E.
Published: August 2010

Background:  Limited data exist on the risk factors for acute renal failure (ARF) following cardiac surgery in children with congenital heart disease. This cohort study was conducted to examine this subject, as well as changes in the incidence of ARF from 1993 to 2002, the in‐hospital mortality and the time spent in the intensive care unit (ICU).

Methods:  One thousand, one hundred and twenty‐eight children, operated on for congenital heart disease between 1993 and 2002, were identified from our prospectively collected ICU database to obtain data on potential risk factors.

Results:  A total of 130 children (11.5%) developed ARF after surgery. A young age [≥1.0 vs. <0.1 year; odds ratio (OR), 0.23; 95% confidence interval (CI), 0.12–0.46], high Risk Adjusted Classification of Congenital Heart Surgery (RACHS‐1) score (OR, 2.72; 95% CI, 1.66–4.45) and cardiopulmonary bypass (CPB) (<90 min vs. none; OR, 2.68; 95% CI, 1.03–6.96; ≥90 min vs. none; OR, 12.94; 95% CI, 5.46–30.67) were independent risk factors for ARF. The risk of ARF decreased during the study period. Children with ARF spent a significantly longer time in the ICU (2–7 days vs. <2 days, P = 0.002; ≥7 days vs. <2 days, P < 0.001) compared with non‐ARF patients, and showed increased in‐hospital mortality (20% vs. 5%, P < 0.001).

Conclusion:  A young age, high RACHS‐1 score and CPB were independent risk factors for ARF after surgical procedures for congenital heart disease in children. The risk of ARF decreased during the study period. Children with severe ARF spent a longer time in the ICU, and the mortality in ARF patients was higher than that in non‐ARF patients.
Remifentanil and the brain
Authors: FODALE V. , SCHIFILLITI D. , PRATICÒ C. , SANTAMARIA L. B.
Published: August 2010

Background and aim: Remifentanil is an ultra‐short‐acting opioid, increasingly used today in neuroanesthesia and neurointensive care. Its characteristics make remifentanil a potentially ideal agent, but previous data have cast a shadow on this opioid, supporting potentially toxic effects on the ischemic brain. The aim of the present concise review is to survey available up‐to‐date information on the effects of remifentanil on the central nervous system.

Method: A MEDLINE search within the past seven years for available up‐to‐date information on remifentanil and brain was performed.

Results: Concise up‐to‐date information on the effects of remifentanil on the central nervous system was reported, with a particular emphasis on the following topics: cerebral metabolism, electroencephalogram, electrocorticography, motor‐evoked potentials, regional cerebral blood flow, cerebral blood flow velocity, arterial hypotension and hypertension, intracranial pressure, cerebral perfusion pressure, cerebral autoregulation, cerebrovascular CO2 reactivity, cerebrospinal fluid, painful stimulation, analgesia and hyperalgesia, neuroprotection, neurotoxicity and hypothermia.

Conclusion: The knowledge of the influence of remifentanil on brain functions is crucial before routine use in neuroanesthesia to improve anesthesia performance and patient safety as well as outcome.
Decreases in myocardial glucose and increases in pyruvate but not ischaemia are observed during porcine endotoxaemia
Authors: CHEW M. S. , JOHANSSON A. , ANDERSON C. , ERSSON A. , TØNNESEN E.
Published: August 2010

Background: Myocardial dysfunction occurs commonly in septic shock. It is not known whether this is due to local ischaemia and metabolic disturbances. Our hypothesis was that endotoxaemic myocardial dysfunction may be associated with interstitial ischaemic and metabolic changes, measured using interstitial microdialysis (MD).

Methods: Eighteen pigs were randomized to control (n=6) or endotoxin infusion (n=12). MD catheters were inserted into the myocardium for measurement of interstitial glucose, pyruvate and lactate concentrations. Plasma glucose and lactate concentrations and systemic haemodynamic parameters were measured simultaneously.

Results: Compared with the control group, the endotoxaemic animals had significantly decreased left ventricular stroke work and venous oxygen saturation (SvO2), and increased mean pulmonary artery pressure and plasma lactate. In the endotoxaemic group, decreases in interstitial glucose were observed, occurring simultaneously with increases in interstitial pruvate. Interstitial lactate : pyruvate ratios decreased with time in all animals.

Conclusions: Despite severe systemic and pulmonary haemodynamic changes, interstitial MD measurements revealed no evidence of anaerobic metabolism in the myocardium of endotoxaemic pigs. There were, however, changes in glucose and pyruvate concentrations, suggesting local energy metabolic disturbances.
Intraoperative dreams reported after general anaesthesia are not early interpretations of delayed awareness
Authors: SAMUELSSON P. , BRUDIN L. , SANDIN R. H.
Published: August 2010

Background: Dreams are more frequently reported than awareness after surgery. We define awareness as explicit recall of real intraoperative events during anaesthesia. The importance of intraoperative dreaming is poorly understood. This study was performed to evaluate whether intraoperative dreams can be associated with, or precede, awareness. We also studied whether dreams can be related to case‐specific parameters.

Methods: A cohort of 6991 prospectively included patients given inhalational anaesthesia were interviewed for dreams and awareness at three occasions; before they left the post‐anaesthesia care unit, days 1–3 and days 7–14 after the operation. Uni‐ and multivariate statistical relations between dreams, awareness and case‐specific parameters were assessed.

Results: Two hundred and thirty‐two of 6991 patients (3.3%) reported a dream. Four of those also reported awareness and remembered real events that were distinguishable from their dream. Awareness was 19 times more common among patients who after surgery reported a dream [1.7% vs. 0.09%; odds ratio (OR) 18.7; P=0.000007], but memories of dreams did not precede memories of awareness in any of the 232 patients reporting a dream. Unpleasant dreams were significantly more common when thiopentone was used compared with propofol (OR 2.22; P=0.005). Neutral or pleasant dreams were related to lower body mass index, female gender and shorter duration of anaesthesia.

Conclusions: We found a statistically significant association between dreams reported after general anaesthesia and awareness, although intraoperative dreams were not an early interpretation of delayed awareness in any case. A typical dreamer in this study is a lean female having a short procedure.
Ketamine blocks enhancement of spinal long‐term potentiation in chronic opioid treated rats
Authors: HAUGAN F. , RYGH L. J. , TJØLSEN A.
Published: August 2010

Background: Long‐term opioid treatment is associated with the development of hyperalgesia. In a rat model we wanted to study if chronic opioid treatment changed the induction and maintenance of spinal long‐term potentiation (LTP), a form of hyperexcitability in the spinal cord. We also wanted to investigate if the clinically available NMDA receptor antagonist ketamine inhibited the effect of chronic opioid treatment on LTP.

Methods: The animals were randomized into four groups (saline, morphine 20 mg/kg/day, ketamine 20 mg/kg/day, morphine 20 mg/kg/day and ketamine 20 mg/kg/day). Drugs were given as continuous subcutaneous infusions by means of osmotic minipumps. After 7 days of treatment and during ongoing treatment single unit extracellular recordings were made from the lumbar deep dorsal horn under urethane anesthesia. Single electrical stimuli were applied to the sciatic nerve, and the C‐fiber evoked responses of WDR neurons were recorded before and during 3 h following low frequency (3 Hz) electrical conditioning stimulation.

Results: The potentiation of C‐fiber evoked responses by conditioning stimulation was significantly increased in the morphine‐treated group compared to the saline group, while there was no significant difference between the saline, the ketamine and the morphine/ketamine groups. The potentiated responses in the morphine/ketamine group were significantly reduced compared to the morphine group (P=0.01).

Conclusion: Our results indicate that animals treated with long‐term opioid show amplification of stimulus‐induced central sensitisation compared to opioid naïve animals. Ketamine inhibited the morphine‐induced enhancement of LTP, supporting the role of ketamine in prevention of opioid induced hyperalgesia.
Caudal midazolam does not affect sevoflurane requirements and recovery in pediatric day‐case hernioplasty
Authors: HONG J.‐Y. , LEE I. H. , SHIN S. K. , PARK E. Y. , BAN S. Y. , CHO J. E. , KIL H. K.
Published: August 2010

Background: This prospective, randomized, double‐blind study aimed to determine whether caudal midazolam combined with ropivacaine affects anesthetic requirements, recovery profiles, and post‐operative analgesia compared with ropivacaine alone in pediatric day‐case hernioplasty.

Methods: Sixty boys (2–5 years old) received caudal injections of 0.2% ropivacaine 1 ml/kg and epinephrine 1 : 200,000 with (RM group) or without (R group) 50 μg/kg of midazolam under sevoflurane anesthesia. The sevoflurane requirement was determined by adjusting to a bispectral index score=50.

Results: Concentrations of end‐tidal sevoflurane (ETsevo%) after induction were similar in both groups. After caudal block, ETsevo% before and after surgical stimuli did not show significant intra‐ or intergroup differences. Recovery characteristics, including post‐operative sedations, were similar in both groups. Post‐operative pain scores were significantly lower in the RM group than the R group.

Conclusions: Caudal midazolam (50 μg/kg) added to 2% ropivacaine did not influence sevoflurane requirement or recovery but improved post‐operative analgesia compared with ropivacaine alone in pediatric day‐case hernioplasty.
Influence of pre‐operative fluid infusion on volume status during oesophageal resection – a prospective trial
Authors: RAUE W. , HAASE O. , LANGELOTZ C. , NEUß H. , MÜLLER J. M. , SCHWENK W.
Published: August 2010

Background: Perioperative fluid therapy is controversially debated in surgery. In malnourished and hypovolaemic patients, a restrictive fluid regimen may lead to hypoperfusion and increased incidence of complications. The present prospective cohort study was performed to assess whether pre‐operative i.v. fluid administration improves intraoperative cardiac preload in patients undergoing oesophageal resection.

Methods: Intraoperatively, the intrathoracic blood volume index (ITBVI) was monitored in 44 consecutive patients undergoing elective oesophagectomies with the transthoracic thermodilution technique. Twenty‐two of these patients received a pre‐operative i.v. fluid loading with a balanced crystalloid solution (1 ml/kg/h over 48 h).

Results: After induction of anaesthesia ITBVI was low but not different between the groups [767 (512–1314) vs. 775 (531–1200) ml/m2, P=0.81]. In the intervention group, the extravascular lung water increased above normal levels during the operation. The groups did not differ in cardiac output, blood pressure, heart rate and central venous pressure. Post‐operative morbidity was not different between the cohorts.

Conclusion: Pre‐operative i.v. fluid loading with crystalloid solutions could not be shown to improve the intraoperative volume status and cardiac function in this study. Randomised trials with other volume replacement techniques are recommended.
Untersuchungen über Zusammensetzung und Verdaulichkeit der Leinsaatkapselspreu
Authors: Fißmer E.
Published: August 2010

Für Leinsaatspreu, die aus der Flachsröste in Ahrensböck (Holstein) stammte, wurden folgende Verdauungswerte gefunden:
Der Einfluß künstlicher Trocknung auf den Futterwert von eingesäuerten Rübenblättern
Authors: Kirsch W. , Jantzon H.
Published: August 2010

Gärfutter aus Futterrübenblättern wurden unter vergleichbaren Bedingungen im frischen (eingesäuerten) und getrockneten Zustande auf seine Zusammensetzung und seine Verdaulichkeit geprüft. Die Trocknung erfolgte schonend auf einer Darre.

Die Zusammensetzung wurde durch die Trocknung kaum beeinflußt, nur machte sich eine starke Verminderung des Essigsäuregehaltes (freie flüchtige Essigsäure) bemerkbar, was nur günstig bewertet werden kann.

Die Verdaulichkeit wurde durch die Trocknung vermindert, und zwar bei der organischen Substanz um ‐6,5%, beim Rohprotein um ‐10,7%. Die Veränderung der Rohproteinverdaulichkeit glauben wir auf einen spezifischen Einfluß der künstlichen Trocknung zurückführen zu können.