bluuebunny/crossref_metadata_2025 huggingface dataset:
Changes in brain gene expression after long‐term sleep deprivation
Authors: Cirelli Chiara , Faraguna Ugo , Tononi Giulio
Published: August 2006

Long‐term sleep deprivation in rats produces dramatic physiological changes including increase in energy expenditure, decrease in body weight, and death after 2–3 weeks. Despite several studies, the sleep deprivation syndrome remains largely unexplained. Here, to elucidate how prolonged sleep loss affects brain cells we used microarrays and screened the expression of > 26 000 transcripts in the cerebral cortex. Rats were sleep deprived using the disk‐over‐water method for 1 week. Seventy‐five transcripts showed increased expression in these animals relative to controls that had been spontaneously awake or sleep deprived for a few hours. Most of them were induced as a result of chronic sleep loss and not non‐specific effects of the disk stimulation. They include transcripts coding for several immunoglobulins, stress response proteins (macrophage inhibitor factor‐related protein 14, heat‐shock protein 27, α‐B‐crystallin), minoxidil sulfotransferase, globins and cortistatin. Twenty‐eight transcripts decreased their expression in long‐term sleep‐deprived rats. Sixteen of them were specifically decreased as a result of chronic sleep loss, including those coding for type I procollagen and dihydrolipoamide acetyltransferase. We also compared sleeping rats to short‐term and long‐term sleep‐deprived rats, and found that acute and chronic sleep loss led to some differences at the molecular level. Several plasticity‐related genes were strongly induced after acute sleep deprivation only, and several glial genes were down‐regulated in both sleep deprivation conditions, but to a different extent. These findings suggest that sustained sleep loss may trigger a generalized inflammatory and stress response in the brain.
Actin‐associated neurabin–protein phosphatase‐1 complex regulates hippocampal plasticity
Authors: Hu Xiao Dong , Huang Qing , Roadcap David W. , Shenolikar Shirish S. , Xia Houhui
Published: August 2006

Protein phosphatase‐1 (PP1) has been implicated in the control of long‐term potentiation (LTP) and depression (LTD) in rat hippocampal CA1 neurons. PP1 catalytic subunits associate with multiple postsynaptic regulatory subunits, but the PP1 complexes that control hippocampal LTP and LTD in the rat hippocampus remain unidentified. The neuron‐specific actin‐binding protein, neurabin‐I, is enriched in dendritic spines, and tethers PP1 to actin‐rich postsynaptic density to regulate morphology and maturation of spines. The present studies utilized Sindbis virus‐mediated expression of wild‐type and mutant neurabin‐I polypeptides in organotypic cultures of rat hippocampal slices to investigate their role in synaptic plasticity. While wild‐type neurabin‐I elicited no change in basal synaptic transmission, it enhanced LTD and inhibited LTP in CA1 pyramidal neurons. By comparison, mutant neurabins, specifically those unable to bind PP1 or F‐actin, decreased basal synaptic transmission, attenuated LTD and increased LTP in slice cultures. Biochemical and cell biological analyses suggested that, by mislocalizing synaptic PP1, the mutant neurabins impaired the functions of endogenous neurabin–PP1 complexes and modulated LTP and LTD. Together, these studies provided the first biochemical and physiological evidence that a postsynaptic actin‐bound neurabin‐I–PP1 complex regulates synaptic transmission and bidirectional changes in hippocampal plasticity.
Antigen‐Specific Therapy Promotes Repair of Myelin and Axonal Damage in Established EAE
Authors: Wang Chunhe , Gold Bruce G. , Kaler Laurie J. , Yu Xiaolin , Afentoulis Michael E. , Burrows Gregory G. , Vandenbark Arthur A. , Bourdette Dennis N. , Offner Halina
Published: August 2006

Inflammation results in CNS damage in multiple sclerosis (MS) and experimental autoimmune encephalomyelitis (EAE), an animal model of MS. It is uncertain how much repair of injured myelin and axons can occur following highly selective anti‐inflammatory therapy in EAE and MS. In this study, SJL/J mice with established EAE were treated successfully with an antigen‐specific recombinant T cell receptor ligand (RTL), RTL401, a mouse I‐As/PLP‐139–151 construct, after the peak of EAE. To define the mechanisms by which late application of RTL401 inhibits EAE, we evaluated mice at different time points to assess the levels of neuroinflammation and myelin and axon damage in their spinal cords. Our results showed that RTL401 administered after the peak of acute EAE induced a marked reduction in inflammation in the CNS, associated with a significant reduction of demyelination, axonal loss and ongoing damage. Electron microscopy showed that RTL‐treated mice had reduced pathology compared with mice treated with vehicle and mice at the peak of disease, as demonstrated by a decrease in continued degeneration, increase in remyelinating axons and the presence of an increased number of small, presumably regenerative axonal sprouts. These findings indicate that RTL therapy targeting encephalitogenic T cells may promote CNS neuroregenerative processes.
Pallister–Killian Syndrome: Multiband FISH of Tetrasomy 12p
Authors: Gerdes Anne‐Marie , Hansen Lars Kjaersgaard , Brandrup Flemming , Soegaard Kirsten , Christoffersen Anja , Rasmussen Kirsten
Published: August 2006

Abstract:  Two patients with mosaicism for tetrasomy 12p are described. One was diagnosed at the age of 14 years with severe mental retardation and other dysmorphologic findings and abnormal skin pigmentation. Chromosome analysis of a blood sample showed a normal female karyotype. A skin biopsy specimen showed mosaicism for a marker chromosome. The other patient was diagnosed prenatally, from a chorionic villus sample, but only in the direct preparation. Mosaicism for a marker chromosome was demonstrated. The ultrasound examination revealed no abnormalities. Multicolor and multiband fluorescence in situ hybridization analyses showed that the marker chromosome was derived from chromosome 12p, which confirmed the diagnosis of Pallister–Killian syndrome in both patients. To our knowledge, this is the first report of the use of these fluorescence in situ hybridization techniques in Pallister–Killian syndrome whereby the nature of the marker chromosome could be confirmed to be derived from chromosome 12p.
Acute Hemorrhagic Edema of Infancy Associated with Herpes Simplex Type 1 Stomatitis
Authors: Garty Ben Zion , Pollak Uri , Scheuerman Oded , Marcus Nufar , Hoffer Vered
Published: August 2006

Abstract:  Acute hemorrhagic edema of infancy is a benign leukocytoclastic vasculitis occurring in children younger than 2 years. The etiology is unknown. Viral or bacterial infections, immunizations, and the use of several medications, mainly antibiotics, may be involved in the pathogenesis. We report the first instance of this disease associated with herpesvirus type 1 stomatitis.
Eccrine Angiomatous Harmartoma in an Infant
Authors: Foshee J. B. , Grau Renee H. , Adelson David M. , Crowson Neil
Published: August 2006

Abstract:  Eccrine angiomatous hamartoma is a nevoid proliferation of eccrine glands and small vessels. It usually presents as a solitary, slow growing nodule, manifesting at birth or in childhood, which can be accompanied by hyperhidrosis and pain on palpation. We report an occurrence in an otherwise healthy 3‐month‐old girl who had multiple, asymptomatic, nodular lesions with a linear arrangement localized to the inguinal fold. We also review the literature on adnexal hamartomas of infancy.
A Unique Presentation of Immuno‐Osseous Dysplasia
Authors: Hubbard V. , Sahota A. , Callahan B. , Carr S. , Paige D.
Published: August 2006

Abstract:  The immuno‐osseous dysplasias are a rare group of conditions in which short‐limbed dwarfism is associated with an immune defect. The best known of these is cartilage hair hypoplasia. However, several reports of other distinct conditions exist, which have been arbitrarily classified on the basis of the immune defect. We present a child with a previously unreported combination of immune and skeletal abnormalities in whom there was an unusual and distinctive skin appearance associated with defective cutaneous elastic fibers. These cutaneous features suggest a unifying link with other immuno‐osseous dysplasia but the combination of immune and skeletal defects exposes weaknesses in the current method of classification.
Vitamin A Deficiency Phrynoderma Associated with Chronic Giardiasis
Authors: Girard Céline , Dereure Olivier , Blatière Véronique , Guillot Bernard , Bessis Didier
Published: August 2006

Abstract:  Phrynoderma is a rare form of follicular hyperkeratosis associated with deficiencies in vitamins A or C or essential fatty acids. We report a 6‐year‐old boy with an unusual presentation of phrynoderma, characterized by multiple minute digitate hyperkeratoses associated with hair casts and related to a severe deficiency in vitamins A and C complicating a chronic intestinal giardiasis. The lesions responded well to oral vitamins A and C combined with albendazole treatment. Vitamin A deficiency‐related phrynoderma is rare in western countries and is usually caused by digestive malabsorption resulting from large intestine resection or pancreatic failure. To our knowledge, this is the first reported instance of phrynoderma related to a chronic intestinal parasitic infection by Giardia intestinalis with intestinal malabsorption as a likely consequence.
Infantile Hemangiopericytoma – Case Report and Literature Review
Authors: Futagami A. , Aoki M. , Iwakiri I. , Hyakusoku H. , Kawamoto M. , Kawana S.
Published: August 2006

Abstract:  Infantile hemangiopericytoma is a rare soft tissue neoplasm of pericytic origin and is almost always benign, despite its worrisome pathologic features. We describe a 2‐month‐old male infant with a soft tissue mass on his right thigh. Histologically, the lesion showed a characteristic hemangiopericytoma‐like vascular pattern, multilobulation, and moderate mitotic activity. These morphologic features were prediagnosed as infantile hemangiopericytoma. However, immunohistochemical and ultrastructural studies revealed a heterogeneous cellular composition, primarily pericytes and endothelial cells, similar to that observed in infantile myofibromatosis.
Prune‐Belly Syndrome in Two Children and Review of the Literature
Authors: Bogart Megan M. , Arnold Holly E. , Greer Kenneth E.
Published: August 2006

Abstract:  Prune‐belly syndrome is a congenital disorder characterized by abdominal wall musculature deficiency, urinary tract anomalies, and bilateral cryptorchidism. Because of the defect in the musculature, the abdominal skin has a peculiar wrinkled appearance. The syndrome is commonly associated with pulmonary, skeletal, cardiac, and gastrointestinal defects. Developmental delays and growth retardation have also been reported. The incidence of prune belly syndrome is approximately 1:40,000 live births. Over 95% of patients are men. Urinary tract disease is the major prognostic factor, with the complications of pulmonary hypoplasia and end stage renal disease resulting in a mortality rate of 60%. Treatment involves surgical correction of the abdominal wall defect and urinary tract abnormalities, early orchiopexy, and supportive management of associated defects.
Patient Burden of Trigeminal Neuralgia: Results from a Cross‐Sectional Survey of Health State Impairment and Treatment Patterns in Six European Countries
Authors: Tölle Thomas , Dukes Ellen , Sadosky Alesia
Published: August 2006

Abstract:  Trigeminal neuralgia (TN) is an uncommon neuropathic condition associated with excruciating facial pain. It is important to determine the effect of TN pain on patient functioning and to characterize relevant pharmacologic treatment patterns and health resource utilization in general practice. Eighty‐two patients with TN were identified in a general practice setting during an observational survey of broad neuropathic pain syndromes in six European countries. Patients answered a questionnaire that included pain severity and interference items from the modified Short Form Brief Pain Inventory (mBPI‐SF), the EuroQol Survey of functioning and well‐being (EQ‐5D), and questions related to current treatment, health status, and resource utilization. Physicians provided information on medications prescribed for TN pain and pain‐related comorbidities (anxiety, depression, and sleep disturbance). The mean patient age was 62.7 ± 15.8 years, 46% were ≥65 years, and 66% of patients had TN >1 year of duration. The mean Pain Severity Index was 4.2 (range 0–10), reflecting moderate pain despite 94% of patients taking prescription medications for their TN pain. Prescription medications included carbamazepine (mean daily dose 534.1 ± 269.8 mg), the recommended first‐line pharmacologic therapy for TN. Pain severity was significantly associated with reduced EQ‐5D health state valuation (P < 0.001) and greater pain interference (mBPI‐SF) (P < 0.001). These findings demonstrate that TN pain presents a substantial patient burden expressed as interference with daily functioning and reduced health status associated with pain severity. This burden may result from both suboptimal management strategies and the frequent resistance of this neuropathic condition to treatment, and suggests a need for more effective pain management strategies.
Visuospatial and Verbal Memory in Chronic Pain Patients: An Explorative Study
Authors: Busch Hillevi , Montgomery William , Melin Bo , Lundberg Ulf
Published: August 2006

Abstract:  Cognitive bias, such as selective memory for pain‐related information, is frequently observed in chronic pain patients and is assessed mostly using verbal material. Beside word lists, the current study used photographs of people presenting pain behaviors to assess memory bias in chronic pain patients. Chronic pain patients were hypothesized to show better recall of pain‐related words and pictures as compared to pain‐free controls. Twenty‐eight female chronic neck patients and 28 pain‐free female controls completed two computerized pictorial memory games and two word recall tasks. Patients and controls performed equally well in the neutral pictorial memory game. In the pain‐related game, patients performed significantly worse than controls. No significant differences were found in the word recall task. The result is discussed in terms of cognitive avoidance.
The Use of Spinal Cord Stimulation in Refractory Abdominal Visceral Pain: Case Reports and Literature Review
Authors: Tiede Jeffrey M. , Ghazi Salim M. , Lamer Tim J. , Obray Jon B.
Published: August 2006

Abstract:  Patients will commonly seek medical attention for refractory abdominal pain. The many causes of abdominal pain include pathologies of the gastrointestinal, genitourinary, musculoskeletal, and nervous systems. Unfortunately, a large number of patients will develop chronic abdominal pain that is recalcitrant to definitive therapies and nonspecific treatments such as cognitive‐behavioral, physical, and pharmacologic therapies. Although spinal cord stimulation is classically used for neuropathic and ischemic conditions, a growing number of reports describe its efficacy in visceral disease. We describe our experience with spinal cord stimulation in two patients with refractory abdominal pain. Although the exact etiology in these complex patients is not defined, it is theorized that visceral hypersensitivity is at least one component. Finally, we will summarize the applicable literature in order to explain a possible mechanism of analgesia in visceral disease.
Assessing the Potential of Bacterial DNA Profiling for Forensic Soil Comparisons*
Authors: Heath Lorraine E. , Saunders Venetia A.
Published: August 2006

ABSTRACT: A pilot study was undertaken to evaluate DNA profiling of the bacterial community in soil as an alternative to geological methods for forensic soil comparisons. Soil samples from three different ecosystems were compared, and the variation within and between ecologically different sites was determined by using terminal restriction fragment (TRF) analysis of 16S ribosomal DNA. Comparison of TRF profiles revealed that samples from within a specific ecosystem (e.g., a field) showed a significantly higher similarity to each other than to those from another ecosystem (e.g., a forest). In addition, some profile features were unique to specific ecosystems. These features may allow the determination of characteristic profiles that will facilitate identification of ecologically different sites, so that a given sample collected from a suspect could be identified as originating from, for example, a field, rather than a forest. The implications of these preliminary findings for forensic investigations are discussed.
Frequencies of Morphological Characteristics in Two Contemporary Forensic Collections: Implications for Identification*
Authors: Komar Debra , Lathrop Sarah
Published: August 2006

ABSTRACT: Positive identification relies on comparison of antemortem and postmortem data. Some identifications are based on morphological features such as fracture, pathological condition, and surgical hardware, despite little literature indicating the frequencies of such traits. This study examines whether such features are sufficiently rare as to be deemed individualizing. Data were collected on two modern North American skeletal collections (N=482 individuals). Presence/absence of features was scored by skeletal element and side. Results indicate that frequencies vary by geographic region (higher frequency of fractures and pathological conditions in New Mexico while individuals in Tennessee were more likely to have surgical interventions), many features such as fractures are remarkably common and that even suites of traits may not be individualizing. Caution is warranted when using written data rather than radiographic comparisons as the primary source of identification. The implications of these findings to missing person databases are also discussed.
The key role of electrophysiology in the diagnosis of visually impaired children
Authors: Van Genderen Maria , Riemslag Frans , Jorritsma Frank , Hoeben Frank , Meire Francoise , Stilma Jan
Published: August 2006

Purpose:  To describe the outcome of specialized electrophysiology in visually impaired children.

Methods:  We carried out a retrospective evaluation of 340 electrophysiological examinations performed in 298 children over a 3‐year period (2001–2003), with regard to demographic data, referral pattern, degree of compliance, and diagnostic results. Electrophysiology was performed without sedation or anaesthesia. In electroretinograms, DTL electrodes were used in combination with online selection of responses. Visual evoked potentials testing was performed with seven active occipital electrodes.

Results:  The mean age of the children was 7 ± 5 years; 72 (24%) of the children were mentally as well as visually impaired. Main reasons for referral were suspected posterior segment disease, abnormal visual development, unexplained low vision, high myopia, and suspected albinism. Compliance was good in 302/340 (88%), partial in 24/340 (7%), and absent in 14/340 (4%) of the examinations. Of the 326 successful procedures, 215 (66%) showed abnormal results. Tapetoretinal dystrophy (22%), opticopathy (16%), congenital stationary night blindness (13%), and cone dystrophy (11%) were the most frequently established diagnoses. Albinism was confirmed in 14 of 24 suspected patients; additionally, unsuspected misrouting was found in six. In 26 (9%) of the patients, a previously established diagnosis was changed.

Conclusions:  In a specialized setting, electrophysiological examinations can be performed successfully in visually impaired children. The results are essential for the final ophthalmological diagnosis and have important consequences for rehabilitation.
Paediatric aphakic glaucoma
Authors: Kirwan Caitriona , O'Keefe Michael
Published: August 2006

Context:  Aphakic glaucoma is a serious, sight‐threatening complication in children who remain aphakic following congenital cataract surgery. The reported incidence varies from 15% to 45% and it has a higher incidence in small eyes and in babies who undergo surgery before 4 weeks of age. Most cases take the form of open‐angle glaucoma. Despite careful monitoring, diagnostic difficulties in children may lead to delayed treatment. Aphakic children require ongoing monitoring, including examinations carried out under general anaesthesia.

Management:  Contrary to earlier optimism, it is unlikely, according to current clinical information, that intraocular lenses provide protection against the development of glaucoma. It is likely that the lower incidence of glaucoma in pseudophakic eyes results from selection bias for lens insertion. Both medical and surgical treatments have a role in glaucoma management. Trabeculectomy with mitomycin C or Seton implantation (glaucoma drainage device) form the mainstay of surgical treatment. The success rate with Seton implants is better in the short term and more promising in the longer term than that of trabeculectomy. Cyclodestructive procedures play a role in refractory glaucoma. Success rates for surgery range from 14% to 44% and many children require additional medical treatment. Children with aphakic glaucoma need lifelong care. Despite our best efforts, many have poor vision, poor glaucoma control and ultimately become blind.
Actinic cheilitis: histopathology and p53
Authors: Neto Pimentel Dalva Regina , Michalany Nilceo , Alchorne Mauricio , Abreu Marilda , Borra Ricardo Carneiro , Weckx Luc
Published: August 2006

Background:  Chronic actinic cheilitis (AC) is a precursor of squamous cell carcinoma (SCC) of the lip.

Objectives:  To evaluate the histopathological characteristics that may help to identify AC more susceptible to carcinomatous transformation, to assess the p53 protein expression in AC, and to determine the value of the p53 expression as a marker of transformation into SCC of the lip.

Methods:  Seventy cases of chronic AC were reviewed, 31 of which were associated with SCCs. The samples were obtained from pathology reports of AC and SCC of the lip. Histopathology and immunohistochemical expression of the p53 protein were evaluated in isolated AC and in AC adjacent to SCC.

Results:  The intensity of the inflammatory infiltrate in the corium was the only histopathological finding significantly associated both with the presence of an invasive tumor and with the degree of epithelial atypia. Most AC (85%) were immunoreactive to the p53 protein. The p53 protein expression in cheilitis was not statistically associated with any other histopathological criteria.

Conclusions:  An intense inflammatory infiltrate in AC was predictive of an adjacent invasive SCC. In this study, the p53 protein immunoreactivity was not a marker of malignant transformation.
Ossifying fibromyxoid tumor of soft parts presenting as a scalp cyst
Authors: Seykora John T. , Kutcher Cynthia , Van De Rijn Matt , Dzubow Leonard , Junkins‐Hopkins Jaqueline , Ioffreda Micheal
Published: August 2006

Background:  Ossifying fibromyxoid tumor of soft parts (OFMT) is a rare mesenchymal neoplasm of intermediate malignant potential. The tumor most commonly occurs on the extremities with a male predominance. We present an unusual case of OFMT occurring as a cystic lesion on the scalp of a female.

Case history:  A 67‐year‐old woman presented with a 6‐year history of a well demarcated cystic scalp mass. Physical examination revealed a slightly movable, multilobular mass of the left parietal scalp which was subsequently excised. Histological evaluation revealed an OFMT comprised of bland, small cells and a thick collagenous capsule containing an incomplete rim of lamellar bone.

Conclusion:  OFMT is an unusual tumor which can usually be considered as having an intermediate risk of malignancy. It generally occurs in the extremities with a male predominance. The clinical differential for a cystic mass on the scalp is broadened by this unusual case of an OFMT.
Expression of cytokeratin subtypes in intraepidermal malignancies: a guide for differentiation
Authors: Aslan Figen , Demirkesen Cuyan , Çağatay Penbe , Tüzüner Nükhet
Published: August 2006

Background:  Among intraepidermal malignancies of epithelial origin, Bowen's disease, bowenoid actinic keratosis (BAK), intraepidermal malignant eccrine poroma (MEP), and Paget's disease may pose diagnostic difficulties.

Methods:  Histologic features and immunohistochemical profiles of 24 cases of Bowen's disease, 21 cases of BAK, 18 cases of intraepidermal MEP, and 11 cases of Paget's disease were analyzed.

Results:  Using multivariate logistic regression test, multinuclear giant cells and solar degeneration were found to be the only histologic parameters of diagnostic help. On the other hand, a widespread positive reaction for CK 5/8, CK 7, CK 19, and negative reaction for CK 10, was a helpful feature in the differentiation of Paget's disease from Bowen's disease and BAK. The widespread and strong expression of CK 10 was seen in almost all cases of Bowen's disease in contrast to BAK. The widespread expression of CK 5/8 and CK 7, and negative reaction for CK 10, was in favor of Paget's disease, compared to intraepidermal MEP. On the other hand, widespread expression of CK 19 was a common finding in intraepidermal MEP, in contrast to Bowen's disease.

Conclusion:  An immunohistochemical panel may provide significant hints on the differentiation of common intraepidermal malignancies, especially in problematic cases.
Rosetoid schwannoma (neuroblastoma‐like) in association with an anetoderma
Authors: Vélez Dolores , Reina Duran Teresa , Pérez‐Gala Silvia , Fernández Javier Fraga
Published: August 2006

Background:  We report an additional case of an extremely uncommon but distinctive histological variant of benign schwannoma, which was previously designated as neuroblastoma‐like schwannoma by Goldblum et al.

Methods:  A 29‐year‐old woman referred to a 6‐year‐history of an atrofic macule. Its clinical appearance was similar to that of an anetoderma.

Results:  A cutaneous biopsy showed findings consistent with a neuroblastoma‐like schwannoma with the following peculiar features: (i) Being fully composed of rosette‐like structures. (ii) Association to an anetoderma.

Conclusions:  Because neither the histological pattern nor the type of tumor allows a differential diagnosis with neuroblastoma, we propose the descriptive term of rosetoid schwannoma. And to our knowledge, this will be the first case reported of rosetoid schwannoma associated to anetoderma.
Onycholemmal carcinoma
Authors: Inaoki Makoto , Makino Eiichi , Adachi Maiko , Fujimoto Wataru
Published: August 2006

A 70‐year‐old Japanese man presented with a 5‐year history of refractory indolent onycholysis of the little finger of the right hand. Roentgenograms did not show involvement of the bone. Histological examination revealed an epithelial tumor consisting of lobular masses varying in size. The tumor was composed of keratinocytes varying in atypicality and showed infiltrative growth into the dermis but not into the phalangeal bone. The tumor had cystic structures composed of eosinophilic amorphous keratin and a surrounding thin layer of keratinocytes. Characteristically, the epithelium in the center of the tumor abruptly changed into amorphous keratin without the formation of intervening keratohyaline granules. From these findings, the mass was diagnosed as onycholemmal carcinoma. Immunohistochemically, the tumor showed a keratin profile comparable to that of the nail bed epithelium and a smaller number of Ki‐67‐positive proliferating tumor cells compared with those of a previous case of onycholemmal carcinoma.
Squamous cell carcinoma arising in an area of long‐standing necrobiosis lipoidica
Authors: Lim Cathy , Tschuchnigg Mark , Lim Jake
Published: August 2006

Background:  Squamous cell carcinoma in an area of chronic ulceration is a well‐documented phenomenon. However, its occurrence arising de novo in an area of necrobiosis lipoidica is rare.

Method:  We report a case in a 53‐year‐old female who presented with a 2 month history of an erythematous nodule occurring in a plaque of necrobiosis lipoidica on the medical aspect of the right lower leg. She had a background of poorly controlled Type 1 diabetes.

Results:  Histopathological findings revealed a well‐differentiated squamous cell carcinoma overlying an area of necrobiosis lipoidica. Treatment was by excision and split‐thickness skin graft.

Conclusion:  Clinicians should be aware of malignant transformation within a plaque of necrobiosis lipoidica. Early detection will allow conservative treatment.
Primary cutaneous histiocyte and neutrophil‐rich CD30+ and CD56+ anaplastic large‐cell lymphoma with prominent angioinvasion and nerve involvement in the forehead and scalp of an immunocompetent woman
Authors: Boudova Ludmila , Kazakov Dmitry V. , Jindra Pavel , Sima Radek , Vanecek Tomáš , Kuntscher Vilem , Vera Vozobulova , Bouda Jiri , Michal Michal
Published: August 2006

Background:  Cutaneous lymphomas co‐expressing CD56 and CD30 are very rare. They share a clinicopathological overlap with natural killer‐ (NK)/T‐cell lymphomas and anaplastic large‐cell lymphomas (ALCLs), two entities with widely disparate clinical behavior.

Methods:  We present a case of an immunocompetent 57‐year‐old Caucasian woman with a rapidly growing, angiodestructive and neuroinvasive primary cutaneous ALCL (PCALCL). The neoplastic population of large anaplastic CD30+ and CD56+ T cells was masked by a massive admixture of histiocytes and neutrophils. The partially ulcerated and pus‐secreting tumor involved the forehead and scalp and was assessed as clinical stage IAE.

Results:  After chemotherapy (cyclophosphamide, doxorubicin, vincristine, and prednisone), the patient achieved a complete remission. Additionally, high‐dose chemotherapy with autologous peripheral blood stem‐cell transplantation was administered as a consolidation of complete remission, in which she has remained for 6 years.

Conclusions:  This is the first CD30+ and CD56+ primary skin lymphoma to be reported on the head. The presented case carries a remarkable combination of clinicopathological features of PCALCL and NK‐/T‐cell lymphoma.
Hypopigmenting agents: an updated review on biological, chemical and clinical aspects
Authors: Solano Francisco , Briganti Stefania , Picardo Mauro , Ghanem Ghanem
Published: August 2006

An overview of agents causing hypopigmentation in human skin is presented. The review is organized to put forward groups of biological and chemical agents. Their mechanisms of action cover (i) tyrosinase inhibition, maturation and enhancement of its degradation; (ii) Mitf inhibition; (iii) downregulation of MC1R activity; (iv) interference with melanosome maturation and transfer; (v) melanocyte loss, desquamation and chemical peeling. Tyrosinase inhibition is the most common approach to achieve skin hypopigmentation as this enzyme catalyses the rate‐limiting step of pigmentation. Despite the large number of tyrosinase inhibitors in vitro, only a few are able to induce effects in clinical trials. The gap between in‐vitro and in‐vivo studies suggests that innovative strategies are needed for validating their efficacy and safety. Successful treatments need the combination of two or more agents acting on different mechanisms to achieve a synergistic effect. In addition to tyrosinase inhibition, other parameters related to cytotoxicity, solubility, cutaneous absorption, penetration and stability of the agents should be considered. The screening test system is also very important as keratinocytes play an active role in modulating melanogenesis within melanocytes. Mammalian skin or at least keratinocytes/melanocytes co‐cultures should be preferred rather than pure melanocyte cultures or soluble tyrosinase.
The Pharmacology of Citalopram Enantiomers: The Antagonism by R‐Citalopram on the Effect of S‐Citalopram*
Authors: Sánchez Connie
Published: August 2006

Abstract: Recent results on the in vivo and in vitro pharmacology of escitalopram are summarised. The exact molecular mechanism by which R‐citalopram inhibits the effect of S‐citalopram on the serotonin transporter remains to be elucidated. Preliminary evidence indicates an effect of R‐citalopram on the association of escitalopram with the high affinity primary site, and on its dissociation from the serotonin transporter, via an allosteric mechanism. Escitalopram can be considered as an allosteric serotonin reuptake inhibitor. This serotonin dual action in binding to two sites on the serotonin transporter (both the primary site and the allosteric site) is hypothesised to be responsible for a longer binding to, and therefore greater inhibition of the serotonin transporter by escitalopram.
The Effect of Vasopressin and Related Compounds at V1aand V2Receptors in Animal Models Relevant to Human Disease*
Authors: Petersen Mads Bjelke
Published: August 2006

Abstract:Vasopressin, a neurohypophyseal peptide hormone, is the endogenous agonist at V1a, V1band V2receptors. The most important physiological function of vasopressin is the maintenance of water homeostasis through interaction with V2receptors in the kidney. Vasopressin and related compounds are used in various clinical settings such as acute variceal bleeding associated with portal hypertension, septic shock,diabetes insipidusand coagulation disorders. The effect in the former two indications relates to the V1areceptor, and in the two latter indications the effect relates to the V2receptor. Vasopressin and related compounds have demonstrated activity in animal models of portal hypertension, sepsis and septic shock,diabetes insipidusand coagulation disorders. The use of the compounds in animal models is reviewed. Generally, the effect of vasopressin and related compounds in animal models reflect the activity in the clinical setting, but in some cases important species differences exist.
Effect of Tetrahydrocurcumin on Lipid Peroxidation and Lipids in Streptozotocin‐Nicotinamide‐Induced Diabetic Rats
Authors: Murugan Pidaran , Pari Leelavinothan
Published: August 2006

Abstract:Hyperlipidaemia is an associated complication of diabetes mellitus. We recently reported that tetrahydrocurcumin lowered the blood glucose in diabetic rats. In the present study, we have investigated the effect of tetrahydrocurcumin, one of the active metabolites of curcumin on lipid profile and lipid peroxidation in streptozotocin‐nicotinamide‐induced diabetic rats. Tetrahydrocurcumin 80 mg/kg body weight was administered orally to diabetic rats for 45 days, resulted a significant reduction in blood glucose and significant increase in plasma insulin in diabetic rats, which proved its antidiabetic effect. Tetrahydrocurcumin also caused a significant reduction in lipid peroxidation (thiobarbituric acid reactive substances and hydroperoxides) and lipids (cholesterol, triglycerides, free fatty acids and phospholipids) in serum and tissues, suggesting its role in protection against lipid peroxidation and its antihyperlipidemic effect. Tetrahydrocurcumin showed a better effect when compared with curcumin. Results of the present study indicate that tetrahydrocurcumin showed antihyperlipidaemic effect in addtion to its antidiabetic effect in type 2 diabetic rats.
The Vasorelaxant Effect of Adrenomedullin, Proadrenomedullin N‐Terminal 20 Peptide and Amylin in Human Skin
Authors: Hasbak Philip , Eskesen Karen , Lind Henrik , Holst Jan , Edvinsson Lars
Published: August 2006

Abstract: In this study we aimed to assess in vivo, the vasodilator effects of adrenomedullin, proadrenomedullin N‐terminal 20 peptide (PAMP) and amylin in human skin vasculature and compare the responses to the effects mediated by the endogenenous neuropeptides calcitonin gene‐related peptide (CGRP) and substance P and to examine the mRNA expression of calcitonin receptor‐like receptor (CL‐R) and receptor‐activity modifying proteins, RAMP1, RAMP 2 and RAMP3 in human subcutaneous arteries. Changes in skin blood flow of the forearm were measured using a Laser Doppler Imager after intradermal injection of the peptides. The mRNA expression was assessed by real‐time reverse transcriptase – polymerase chain reaction (real‐time PCR). CGRP, adrenomedullin and amylin induced concentration‐dependent, long‐lasting increases in skin blood flow. The response to PAMP was shorter in duration appearing similar to the transient response induced by substance P. PAMP (10−6–10−5M) caused distinct itch sensation and local erythema. This effect could be abolished when combining the histamine H1‐receptor antagonist mepyramin and PAMP. Real‐time PCR data showed a higher level of mRNA for RAMP2 than CL‐R, RAMP1 and RAMP3 in the tissue. Though the PCR data demonstrated the presence of mRNA for both CGRP1 and adrenomedullin receptors the rank order of potency (CGRP>adrenomedullin>amylin) for the blood flow increase indicated vasodilatation for these peptides was induced by activation of CGRP1 receptors. Intradermal injection of CGRP, adrenomedullin and amylin induces long lasting dilatation of human skin vasculature by activation of CGRP1 receptors. PAMP induces transient vasodilatation. PAMP but not CGRP, adrenomedullin and amylin causes itch sensation and local erythema. The transient effect on vasodilatation as response to PAMP is discussed.
Effects of Oral L‐Arginine on the Foetal Condition and Neonatal Outcome in Preeclampsia: A Preliminary Report
Authors: Rytlewski Krzysztof , Olszanecki Rafal , Lauterbach Ryszard , Grzyb Anna , Basta Antoni
Published: August 2006

Abstract: Estimation of the influence of oral supplementation with low dose of L‐arginine on biophysical profile, foeto‐placental circulation and neonatal outcome in preeclampsia. Randomized, placebo‐controlled, double‐blind, clinical trial. Oral therapy with 3 g of L‐arginine daily or placebo as a supplement to standard therapy. Eighty‐three preeclamptic women, randomly assigned to the L‐arginine (n=42) or placebo (n=41) groups; [n=30 (L‐arginine) and n=31 (placebo) ended the study, respectively]. Foetal gain chances due to ultrasound biometry, biophysical profile, Doppler velocimetry of pulsatility indices of umbilical and middle cerebral arteries, cerebro‐placental ratio, as well as differences in duration of pregnancy and clinical data of newborn. L‐arginine treatment transitory accelerated foetal gain and improved biophysical profile. Starting from 3rd week of therapy, the umbilical artery pulsatility indices values were significantly lower in L‐arginine than in placebo group. Moreover, treatment with L‐arginine caused significant increase of middle cerebral artery pulsatility indices and cerbro‐placental ratio values. Latency was longer in L‐arginine group. Neonates delivered in the L‐arginine group revealed higher Apgar score. Supplementary treatment with oral L‐arginine seems to be promising in improving foetal well‐being and neonatal outcome as well as in prolonging pregnancy complicated with preeclampsia. However, these benefits require confirmation in more‐powered, larger studies.
Toxicological Studies of Gambogic Acid and its Potential Targets in Experimental Animals
Authors: Guo Qinglong , Qi Qi , You Qidong , Gu Hongyan , Zhao Li , Wu Zhaoqiu
Published: August 2006

Abstract: Acute and chronic toxicity of gambogic acid, a promising novel anticancer agent, was determined using albino mice and Beagle dogs as model animals. Histopathological examination and viscera parameter investigation were also carried out after autopsy. The LD50 of gambogic acid was found to be 45∼96 mg/kg and the 95% confidence limit was determined to be 43.18∼48.45 mg/kg. The results from the chronic toxicity studies demonstrated that the toxicity targets in the experimental animals were liver and kidney. The innocuous dose was established to be 4 mg/kg after administration to dogs for a total of 13 weeks at a frequency of one injection every other day. This dose (4 mg/kg) was approximately 9.6 (body weight) or 5.1 (body surface area) times the dosage (25 mg/60 kg, every other day) recommended for human trials. Our results provide the theoretical foundation for clinical applications of this promising natural anticancer agent and will likely bring about considerable economic and social benefits.
Soleus, plantaris and gastrocnemius VEGF mRNA responses to hypoxia and exercise are preserved in aged compared with young female C57BL/6 mice
Authors: Gavin T. P. , Westerkamp L. M. , Zwetsloot K. A.
Published: August 2006

Aims:  In humans, skeletal muscle capillarization and the vascular endothelial growth factor (VEGF) mRNA response to acute exercise are lower in aged compared with young. The exercise‐induced increase in VEGF mRNA has been proposed to involve hypoxic regulation of VEGF and is believed to be fibre type‐dependent. We hypothesized that attenuated VEGF mRNA responses to hypoxia and exercise with advanced age would be greatest in oxidative vs. glycolytic muscles.

Methods:  3‐ and 24‐month‐old female C57BL/6 mice were exposed to acute hypoxia (FIO2 = 0.06) or performed a single exercise (65% of maximum treadmill running speed) bout. Capillarization and VEGF mRNA were analysed in the soleus, plantaris and gastrocnemius muscles.

Results:  In each muscle, VEGF mRNA was greater in aged compared with young, while the VEGF mRNA response to acute hypoxia or acute exercise was similar between young and aged. Morphological analysis revealed that type IIA fibre percentage and type IIB capillarization in the plantaris were greater and type IIB fibre cross‐sectional area (FCSA) in the gastrocnemius was smaller in aged compared with young.

Conclusions:  These findings suggest that ageing does not impair the potential for non‐pathological angiogenesis in mice and that acute exercise increases VEGF mRNA in the soleus, plantaris and gastrocnemius muscles, which differ considerably in fibre type percentage.
Effect of Diets Formulated with Native Peruvian Plants on Growth and Feeding Efficiency of Red Pacu (Piaractus brachypomus) Juveniles
Authors: Palacios Maria E. , Dabrowski Konrad , Abiado Mary Ann G. , Lee Kyeong‐Jun , Kohler Christopher C.
Published: August 2006

We evaluated the effects of casein‐based semipurified diets, alone or supplemented with native Peruvian plants, on growth, feed efficiency, and histology of the digestive tract of red pacu, Piaractus brachypomus, juveniles over an 8‐wk feeding trial. Three tanks were randomly assigned to one of four casein–gelatin (40:8) diets containing a supplement of 15% wheat meal (control) or an identical level of substitution of three South American native plant as follows: camu‐camu fruit (Myrciaria dubia), aguaje fruit (Mauritia flexuosa), or maca tuber meal (Lepidium meyenii). The fish (initial weight, 2.04 ± 0.06 g) were fed experimental diets at decreasing feeding rates from 4 to 2.6% of body weight. After 8 weeks of feeding, fish fed a diet supplemented with maca meal showed significantly higher (P < 0.05) weight gain, specific growth rate, protein efficiency ratio (PER), apparent net protein utilization (NPU), and instantaneous feed intake than fish fed other diets. Feed conversion ratio (FCR), PER, and NPU in fish fed the casein–gelatin diet supplemented with maca meal were among the best ever reported in the scientific literature, 0.64 ± 0.03, 3.13 ± 0.15 and 23.8 ± 2.0, respectively. The camu‐camu meal had a negative impact on diet palatability and utilization, which resulted in slower growth. The stomach, intestine, pancreas, and pyloric caeca at the start and end of the experiment showed normal differentiation and appearance of cells and tissues. The liver parenchyma showed lipid infiltration and pigment accumulation in all samples at the initiation of the experiment and may be attributed to the period of decreased feed intake prior to the study. At the end of the study, similar histopathologies were recorded in all samples from the control and camu‐camu groups. Normal liver histology (polyhedral hepatocytes with centrally located nuclei) was observed in two of three samples from the maca group and all the samples from the group that was fed the aguaje‐supplemented diet.
Effect of Astaxanthin from Xanthophyllomyces dendrorhous on the Pigmentation of Goldfish, Carassius auratus
Authors: Xu Xueming , Jin Zhengyu , Wang Hongtao , Chen Xiaoming , Wang Caiqing , Yu Shuai
Published: August 2006

Two experiments were conducted to evaluate the addition of astaxanthin from red yeast, Xanthophyllomyces dendrorhous, in the diets of goldfish, Carassius auratus. The first was designed to investigate the distribution of pigments in different tissues of goldfish and the effect of astaxanthin in the diet. The carotenoid concentration of tissues was not homogenous. The content of pigments in fish caudal fin was the highest followed by those of scales and head. Flesh had the least carotenoid deposition. Fish fed the diet containing 60 mg/kg astaxanthin had increased concentration of pigment in its head (22.6%), scales (45.5%), flesh (31.0%), and fin (21.2%), compared to fish fed basal diet (P < 0.05). Sixty parts per million astaxanthin had no effect on the weight gain and survival rate. High‐performance liquid chromatography analysis showed astaxanthin in its esterified form in goldfish. The second experiment was aimed at determining the dietary level of astaxanthin that improved color of goldfish. Goldfish were fed the same diet supplemented with 0, 10, 20, 40, 60, and 80 mg yeast astaxanthin/kg for 60 d. The deposition of carotenoids in goldfish fed diets supplemented with astaxanthin increased significantly (P < 0.05) after 15 d of feeding compared to that of the fish fed the diet without astaxanthin, but the effect of dosage of astaxanthin in the diets on the color of goldfish was not completely evident until Day 60 (P < 0.05). During the period of 15–45 d, the deposition of pigments in fish did not increase significantly (P > 0.05) in any treatment with the exception of the diet with 40 mg yeast astaxanthin/kg.
An Efficient Methodology for Cryopreservation of Spermatozoa of Red Seabream, Pagrus major, with 2‐mL Cryovials
Authors: Liu Qinghua , Li Jun , Zhang Shicui , Ding Fuhong , Xu Xizhang , Xiao Zhizhong , Xu Shihong
Published: August 2006

The aim of this study was to optimize the cryopreservation protocols for the sperm of red seabream, Pagrus major. The 2‐mL cryovials and programmable freezer were employed for cryopreservation. Six extenders, six cryoprotectants in various concentrations ranging from 6 to 20% (v/v), four cooling rates, and three thawing temperatures were evaluated by postthaw sperm motility and fertility. The ratio of sperm to egg for postthaw sperm fertilization trials was experimentally standardized and was optimal at 500:1. The best motility of postthaw sperm (79.4 ± 4.7% to 88.6 ± 8.0%), fertilization rates (89.6 ± 2.9 to 95.6 ± 1.9%), and hatching rates (85.3 ± 5.1% to 91.4 ± 4.3%) were achieved when Cortland extender, dimethyl sulfoxide (15, 18, and 20%) or ethylene glycol (9, 12%) as cryoprotectants, 20 C/min as the cooling rate, and 40 C as the thawing temperature were employed. Moreover, the results on embryonic development were not significantly different between cryopreserved sperm and fresh sperm during incubation process. In conclusion, these methods of cryopreservation of red seabream sperm are suitable for routine aquaculture application and preservation of genetic resources.