bluuebunny/crossref_metadata_2025 huggingface dataset:
PARALLEL EVOLUTION OF HAND ANATOMY IN KANGAROOS AND VOMBATIFORM MARSUPIALS: FUNCTIONAL AND EVOLUTIONARY IMPLICATIONS
Authors: WEISBECKER VERA , ARCHER MICHAEL
Published: March 2008

Abstract:  The anatomy of the mammalian hand is exposed to an intriguing interplay between phylogeny and function, and provides insights on phylogenetic affinities as well as locomotory habits of extinct species. Within the marsupial order Diprotodontia, terrestrial plantigrade quadrupedalism evolved twice, in the mostly extinct vombatiforms and in extant macropodoids. To assess the influence of functional and phylogenetic signal on the manus in these two clades, manual anatomy and digital proportions in specimens of eight extinct and three extant vombatiforms were investigated and compared with extant macropodoids and extant possums. The results reveal extensive parallelisms in the carpal region of vombatiforms and macropodoids, including flattened distal metacarpal facets, reduction of the palmar process of the hamatum, reduction of mid‐wrist joint curve, extensive hamatum/scaphoid contact, and absence of a lunatum. These transformations appear to be related to stabilization of the wrist for plantigrade locomotion. Vombatiforms are apomorphic in scaphoid and triquetrum anatomy and their metacarpals are much more gracile than in other Diprotodontia. Manual diversity is greater in vombatiforms than in macropodoids, as probably was locomotor diversity. Digital proportions as well as wrist anatomy divide the extinct vombatiforms into species resembling arboreal diprotodontians, whereas others group with terrestrial quadrupedal kangaroos and wombats. The latter is suggested to be owing to plantigrade locomotion and/or large size. Carpal anatomy and digital proportions suggest that a range of earlier diverging vombatiforms may have been arboreal or scansorial. As such, we propose that the ancestor of extant vombatiforms (koalas and wombats) may have been arboreal, an option that deserves consideration in the reconstruction of vombatiform evolution.
TRACE FOSSILS OF CICADAS IN THE CENOZOIC OF CENTRAL PATAGONIA, ARGENTINA
Authors: KRAUSE J. MARCELO , BOWN THOMAS M. , BELLOSI EDUARDO S. , GENISE JORGE F.
Published: March 2008

Abstract:  Hemispherical pan or dish‐shaped trace fossils from the Cenozoic of the Central Patagonia are attributed to the burrowing action of cicadas. A new ichnotaxon, Feoichnus challa igen. et isp. nov. is characterized by its hemispherical shape, mostly subvertical orientation, smoothed internal lining showing knobbly surface texture, and rough and irregular external surface devoid of ornamentation. The wall is composed of a lining plus a layer of soil material consolidated passively by cicada excretions. In other specimens the wall shows a repetition of linings and soil layers reflecting changes in the position of the chambers. Grooves, which represent traces of roots originally related to the feeding activities of cicada nymphs, are located in the wall of many specimens of F. challa. These grooves are subvertical to subhorizontal and show smooth surfaces with longitudinal striations. The cicadan origin of these traces is supported by comparison of the fossils to modern cicada nymph chambers and by laboratory experiments. The most significant characters that emerged from the comparison are the differential preservation of the basal part of the chambers, the interior lining with similar surface texture, and the presence of root traces in the wall and in the interior of the chamber. Additional records of F. challa from the Cretaceous–Pliocene of the USA, the Oligocene of Ethiopia, and the Miocene of the United Arab Emirates and Kenya complete the current information yielded by the known body fossil record to help understand the evolutionary history of cicadas.
NEW DATA ON THE VERTEBRATE ASSEMBLAGE OF FIUME SANTO (NORTH‐WEST SARDINIA, ITALY), AND OVERVIEW ON THE LATE MIOCENE TUSCO‐SARDINIAN PALAEOBIOPROVINCE
Authors: ABBAZZI LAURA , DELFINO MASSIMO , GALLAI GIANNI , TREBINI LUCIANO , ROOK LORENZO
Published: March 2008

Abstract:  This paper reports the results of a study of more than 2400 specimens in the collection of fossil vertebrates from Fiume Santo in north‐west Sardinia. This locality represents the westernmost documentation of the Tusco‐Sardinian palaeobioprovince, which was in existence during the late Tortonian in the North Tyrrhenian area. During the Tortonian, the region that presently corresponds to southern Tuscany and the Sardinian Massif (Central Italy) was occupied by a complex of large islands characterised by endemic vertebrate populations. Morphological features, adaptations and trophic structure (e.g. low diversity and scarce carnivore taxa), mainly in the mammal faunas, attest to a long period of isolation from the continental palaeobioprovinces of the Mediterranean and Central Europe. The greatest numbers of fossil remains of the well‐known endemic Oreopithecus fauna of the so called V0–V2 assemblages, are found at several sites in southern Tuscany (e.g. Montebamboli, Casteani, Baccinello). In Sardinia this endemic fauna occurs only at the Fiume Santo locality, from which 11 taxa have been recognized: Crocodylia indet., Chelonii indet., Oreopithecus bambolii, Mustelidae indet., Eumaiochoerus cf. E. etruscus, Umbrotherium azzarolii gen. et sp. nov., Tyrrhenotragus gracillimus, Bovidae gen. et sp. indet. (?Neotragini), Maremmia cf. M. lorenzi, Etruria viallii gen. et sp. nov., Turritragus casteanensis gen. et sp. nov. Analysis of these fossils and comparison with material from localities in Tuscany has led to a re‐evaluation of the latter and to the description of three new endemic taxa among the ruminants.
LATE HETTANGIAN (EARLY JURASSIC) AMMONITES FROM TASEKO LAKES, BRITISH COLUMBIA, CANADA
Authors: LONGRIDGE LOUISE M. , SMITH PAUL L. , TIPPER HOWARD W.
Published: March 2008

Abstract:  The Taseko Lakes area yields the most diverse and well‐preserved late Hettangian ammonite assemblage in British Columbia. In total, 27 ammonite taxa are described, of which Fergusonites hendersonae, Eolytoceras constrictum and Pseudaetomoceras victoriense are new. Based on this study, Phylloceras cf. asperaense Hillebrandt, Togaticeras togatum (Neumayr), T. aff. goisernense Rakús, Eolytoceras aff. guexi Taylor, Discamphiceras aff. silberlingi Guex, Schlotheimia cf. cuevitensis Hillebrandt and Franziceras aff. graylockense Taylor are newly recognized in the North American Mineralense Zone whereas Nevadaphyllites psilomorphus (Neumayr), N. aff. compressus Guex, Fergusonites hendersonae sp. nov., Eolytoceras chongi Hillebrandt, E. constrictum sp. nov., Paracaloceras spp. A and B, P.? spp., Metophioceras? sp. and Schreinbachites? aff. laqueoides (Hyatt) are newly recognized in the Rursicostatum Zone. Discamphiceras silberlingi, D. sp. nov., Alsatites aff. bipartitus (Hillebrandt), Alsatites sp., Pseudaetomoceras victoriense sp. nov. and Paracaloceras aff. varaense Hillebrandt are newly recognized in both the Mineralense and Rursicostatum zones. The Taseko Lakes fauna allows clear correlations with contemporaneous strata in other areas of North America as well as with the Canadensis Zone and probably the Arcuatum horizon of the South American succession. Broad correlations are also possible with Hettangian or lowest Sinemurian strata in New Zealand and the eastern Tethys. Furthermore, the Taseko Lakes fauna permits correlation of the Mineralense and Rursicostatum zones with the circum‐Mediterranean Marmoreum Zone. Finally, this fauna suggests that the Mineralense Zone and the lower to middle portion of the Rursicostatum Zone in Taseko Lakes are equivalent to the Complanata Subzone whereas the upper portion of the Rursicostatum Zone correlates with the Depressa Subzone of the north‐west European Angulata Zone.
Ambroxol: A CNS Drug?
Authors: Weiser Thomas
Published: March 2008

For almost three decades ambroxol has been used in the therapy of airway diseases. In 2002, ambroxol lozenges were marketed for the treatment of sore throat making use of its local anesthetic effect. Detailed investigations of ambroxol with modern pharmacological methods yielded additional interesting results: ambroxol has been found to have profound effects on neuronal voltage‐gated Na+, as well as Ca2+channels, and to effectively reduce chronic inflammatory and neuropathic pain in rodents. The question was raised whether ambroxol affects the central nervous system (CNS) directly, or whether its effects can be explained solely by a peripheral action. This issue was addressed by reexamining pharmacokinetics, as well as toxicology of ambroxol. It has been concluded that even at the highest clinically used doses ambroxol does not have significant direct effects on the CNS. At clinically relevant plasma concentrations ambroxol either does not penetrate blood‐brain barrier, or its brain levels are too low to cause relevant effects. The analgesic effects of ambroxol by either systemic administration to animals, or by topical application in humans can be explained by ambroxol‐induced blockade of ion channels in peripheral neurons.
GABAA Receptor Subtype‐Selective Efficacy: TPA023, an α2/α3 Selective Non‐sedating Anxiolytic and α5IA, an α5 Selective Cognition Enhancer
Authors: Atack John R.
Published: March 2008

TPA023 and α5IA are structurally related compounds that selectively modulate certain GABAA receptor subtypes. Hence, TPA023 has weak partial agonist efficacy at the α2 and α3 subtypes whereas α5IA has inverse agonist efficacy at the α5 subtype. These efficacy characteristics translate into novel pharmacological profiles in preclinical species with TPA023 being a nonsedating anxiolytic in rats and primates whereas α5IA enhanced cognition in rats but was devoid of the proconvulsant or kindling liabilities associated with nonselective inverse agonists. In vitro and in vivo metabolic studies showed that TPA023 was metabolized via CYP3A4‐mediated t‐butyl hydroxylation and N‐deethylation whereas α5IA was metabolized to produce the hydroxymethyl isoxazole, the latter of which was highly insoluble and caused renal toxicity in preclinical species. In humans, TPA023 had a half‐life in the region of 6–7 h whereas the half‐life of α5IA was 2–2.5 h. TPA023 was clearly differentiated from the nonselective agonist lorazepam in terms of saccadic eye movement and unlike lorazepam, it did not impair either postural stability, as judged by body sway, or cognition. The occurrence of the hydroxymethyl isoxazole metabolite of α5IA in human urine precluded the use of α5IA in prolonged dosing studies. Nevertheless, α5IA was evaluated in an alcohol‐induced cognitive impairment model in healthy normal volunteers and was found to reverse the memory‐impairing effects of alcohol. To date, however, no efficacy data for either TPA023 or α5IA in patient populations has been reported, although at the very least, the preclinical and limited clinical data with TPA023 and α5IA validate the approach of targeting specific GABAA receptors through subtype‐selective efficacy.
High‐ and low‐frequency transcutaneous electrical nerve stimulation delay sciatic nerve regeneration after crush lesion in the mouse
Authors: Baptista Abrahão F. , Gomes Joyce R. S. , Oliveira Júlia T. , Santos Soraia M. G. , Vannier‐Santos Marcos A. , Martinez Ana M. B.
Published: March 2008

Abstract The stimulation of peripheral nerve regeneration has been studied in different ways, including the use of electrical fields. The capacity of this modality to enhance nerve regeneration is influenced by the parameters used, including current type, frequency, intensity, and means of administration. Transcutaneous electrical nerve stimulation (TENS) is a frequently used form of administering electrical current to the body, but its effects on peripheral nerve regeneration are not known. This study assessed the influence of TENS on sciatic nerve regeneration, using a model of crush lesion in the mouse. Mice were stimulated 30 min a day, 5 days a week, for 5 weeks with both high‐ (100 Hz) and low‐ (4 Hz) frequency TENS. Control animals had the sciatic nerve crushed but were not stimulated. Assessment was performed weekly by functional analysis using the Static Sciatic Index for the mouse and at the end of the experiment by light and electron microscopy. The results showed that although there were no differences between the groups regarding the Static Sciatic Index values, TENS led to nerves with morphological signs of impaired regeneration. At light microscopy level, TENS nerves presented more axons with dark axoplasm, signs of edema, and a less organized cytoarchitecture. Electronmicrographs showed fewer and thinner thick myelinated fibers and increased number of Schwann cell nuclei. Myelinated axon diameters and density and diameter of nonmyelinated fibers were not affected by TENS, leading to the conclusion that this regimen of electrical stimulation leads to a delayed regeneration after a crush lesion of the sciatic nerve in the mouse. All these effects were more pronounced on high‐frequency TENS nerves.
Adult Transition From At‐Risk Drinking to Alcohol Dependence: The Relationship of Family History and Drinking Motives
Authors: Beseler Cheryl L. , Aharonovich Efrat , Keyes Katherine M. , Hasin Deborah S.
Published: March 2008

Background:  Prospective studies have not previously examined whether a family history of alcoholism and drinking motives conjointly predict a diagnosed DSM‐IV alcohol abuse or dependence in adults, despite a large literature that each is associated with alcohol consumption. The focus of this study is the conjoint, prospective examination of these risk factors in a 10‐year longitudinal study of adults who were at‐risk drinkers at baseline.

Methods:  Prospective, population‐based cohort of drinkers aged 18 or older from a Northeastern U.S. area initially evaluated for history of alcohol use disorders and drinking motives in 1991 to 1992. New onset dependence was studied in those who never met the criteria for alcohol dependence at baseline (n = 423), and new onset abuse was studied in those who never met the criteria for alcohol abuse at baseline (n = 301) and who did not develop dependence during the follow‐up.

Results:  Family history significantly interacted with 2 baseline drinking motives in predicting new onsets of DSM‐IV alcohol dependence: drinking to reduce negative affect (OR 3.38; 95% CI 1.05, 10.9) and drinking for social facilitation (OR 3.88; CI 1.21, 12.5). Effects were stronger after conditioning the drinking motives on having a positive family history of alcoholism. In contrast, in predicting new onsets of alcohol abuse, drinking motives did not have direct effects or interact with family history.

Conclusions:  Those who drank to reduce negative affect or for social facilitation at baseline were at greater risk of alcohol dependence 10 years later if they also had a family history of alcoholism. These results suggest an at‐risk group that can be identified prior to the development of alcohol dependence. Further, the findings suggest utility in investigating the interaction of drinking motives with measured genetic polymorphisms in predicting alcohol dependence.
A prospective observational cohort safety study of 5106 platelet transfusions with components prepared with photochemical pathogen inactivation treatment
Authors: Osselaer Jean C. , Messe Nathalie , Hervig Tor , Bueno Jose , Castro Emma , Espinosa Aurora , Accorsi Patrizia , Junge Klaus , Jacquet Michele , Flament Jocelyne , Corash Laurence
Published: March 2008

BACKGROUND: Inactivation of pathogens and white blood cells in platelet (PLT) components with amotosalen and UVA light (INTERCEPT, Cerus Europe BV) has entered clinical practice in European blood centers. A prospective cohort study was implemented to characterize the safety profile of this new PLT component in a broad patient population.

STUDY DESIGN AND METHODS: Apheresis or buffy‐coat PLT components were leukoreduced, suspended in approximately 35 percent plasma and 65 percent PLT additive solution, and treated with the INTERCEPT process. Blood centers were requested to complete a safety data form after each transfusion.

RESULTS: Data for 5106 INTERCEPT components administered to 651 patients were monitored. A total of 5051 (98.9%) transfusions and 609 (93.5%) patients had no reported reactions. Fifty‐five (1.1%) transfusions were associated with adverse events, and 42 (0.8%) were possibly, probably, or related to the PLT transfusion. Adverse events occurred in 42 (6.4%) patients, but in only 32 (4.9%) patients was a causal relationship to PLT transfusion established. One reaction was serious, and no deaths were related to PLT transfusion. Among the transfusions reactions, the most frequent clinical events in descending frequency were chills, fever, dermatologic reactions, dyspnea, nausea or vomiting, and hypotension. No episodes of transfusion‐related acute lung injury were reported.

CONCLUSIONS: In this cohort study, 99.2 percent of transfusions were without reactions attributed to PLTs. INTERCEPT PLTs exhibited a safety profile similar to that previously reported for conventional PLT components.
Risk factors for acute, moderate to severe donor reactions associated with multicomponent apheresis collections
Authors: Yuan Shan , Gornbein Jeffrey , Smeltzer Barbara , Ziman Alyssa F. , Lu Qun , Goldfinger Dennis
Published: March 2008

BACKGROUND: Legitimate concerns exist over the safety of donors during multicomponent apheresis collections (MACs), when large volumes of red blood cells (RBCs) and plasma are removed. This study evaluates the predictive value of various donor‐ and procedure‐related variables for moderate to severe donor acute adverse events (AAEs).

STUDY DESIGN AND METHODS: Data on all apheresis donation procedures performed at a large university hospital–based donor center over a 2‐year period were obtained by a review of adverse event forms and procedure logs (Trima Accel 5.1, Gambro BCT). Various donor‐ and procedure‐related variables were compared between procedures that resulted in moderate to severe AAEs and those that did not.

RESULTS: Moderate to severe AAEs occurred in 53 (0.47%) of 11,333 apheresis donation procedures. The majority of events (96.2%) had predominantly features of vasovagal reactions (VVRs). Females were at significantly higher risk (odds ratio [OR] = 2.8, p < 0.0003) compared to males. Donors who experienced AAEs had significantly lower predonation total blood volume (TBV) and hematocrit (Hct) and higher total RBC loss and net fluid loss at the end of the procedures. Total plasma loss alone was not significantly different between the two groups. Total blood loss was significantly higher among donors who experienced AAEs as a percentage of the donor's TBV.

CONCLUSION: Apheresis collections are well tolerated even when multiple components are collected, with a very low overall incidence of moderate to severe AAEs (0.47%). Small, female donors with lower predonation Hct are at higher risk, especially when RBCs are collected.
Using Academic Journals to Help Students Learn Subject Matter Content, Develop and Practice Critical Reasoning Skills, and Reflect on Personal Values in Food Science and Human Nutrition Classes
Authors: Iwaoka Wayne T. , Crosetti Lea M.
Published: March 2008

ABSTRACT:  It has been reported that students learn best when they use a wide variety of techniques to understand the information of the discipline, be it visual, auditory, discussion with others, metacognition, hands‐on activities, or writing about the subject. We report in this article the use of academic journals not only as an aid for students to learn about content knowledge needed in an Experimental Foods course, but also as a way to have students think about and reflect on their own personal values. The topics of these journal entries cover several of the core competencies in the Institute of Food Technologists (IFT) Undergraduate Education Standards for Degrees in Food Science. These are basic principles of food science, as well as address several “Success Skills” (written communication, critical thinking, professionalism, life‐long learning, interaction skills, and organizational skills). While there are no quantitative “measurements” of gains in learning, comments from the students indicate that learning took place, critical reasoning occurred, and personal values were analyzed. A guideline for writing and grading academic journals and a simple rubric for scoring the quality of the writing are included.
Breathing Life into Family Processes: Introduction to the Special Issue on Families and Asthma
Authors: FIESE BARBARA H.
Published: March 2008

This introduction to the special issue dedicated to families and asthma proposes that the study of asthma highlights general systems topics such as integration of individual needs into the group, developmental trajectories of risk and resilience, supportive and destructive patterns of interaction, and the cultural adaptation of family therapy. It briefly introduces papers in the special issue and concludes that asthma can serve as an exemplar in the study of family health due to its comorbidity with mental health problems, potential to affect multiple members of the family, disproportionate influence on low‐income and minority families, and multiple avenues for intervention.
Caregiver Depressive Symptoms and Observed Family Interaction in Low‐Income Children with Persistent Asthma
Authors: CELANO MARIANNE , BAKEMAN ROGER , GAYTAN OSVALDO , SMITH CHAUNDRISSA OYESHIKU , KOCI ANNE , HENDERSON SASSCHON
Published: March 2008

This study examined the relationship between caregiver depressive symptoms and observed parenting behaviors and family processes during interactions among 101 urban, low‐income Africtan American families with children with persistent asthma. Caregivers (primarily female) were assessed on four dimensions (i.e., warmth/involvement, hostility, consistent discipline, relationship quality) in three videotaped interaction tasks (loss, conflict, cohesion). The results indicated that increased depressive symptoms were significantly associated with lower warmth/involvement and synchrony scores and greater hostility scores during the loss and conflict tasks. In the total sample, the highest levels of hostility and the lowest levels of warmth/involvement were found for the conflict task; nevertheless, caregivers with moderate/severe depressive symptoms showed a significantly greater increase in hostility from the loss to the conflict task than caregivers with minimal/mild depressive symptoms. The findings highlight the salience of considering task content in family observational process research to expand our understanding of depressed and nondepressed caregivers' abilities to modulate appropriately their behaviors and affect across various family interactions. Implications for improving asthma management for low‐income children with persistent asthma are discussed, including the utility of multidisciplinary interventions that combine asthma education with family therapy.
Testing the Biobehavioral Family Model in Pediatric Asthma: Pathways of Effect
Authors: WOOD BEATRICE L. , LIM JUNGHA , MILLER BRUCE D. , CHEAH POANN , ZWETSCH TRESSA , RAMESH SUJATHA , SIMMENS SAMUEL
Published: March 2008

This study uses a laboratory‐based multiinformant, multimethod approach to test the hypothesis that a negative family emotional climate (NFEC) contributes to asthma disease severity by way of child depressive symptoms, and that parent‐child relational insecurity mediates the effect. Children with asthma (n=199; aged 7–17; 55% male) reported parental conflict, parent‐child relational security, and depressive symptoms. Parent(s) reported demographics, asthma history, and symptoms. Asthma diagnosis was confirmed by clinical evaluation and pulmonary function tests, with disease severity rated by an asthma clinician according to NHLBI guidelines. Family interactions were evoked using the Family Process Assessment Protocol, and rated using the Iowa Family Interaction Rating Scales. Path analysis indicated a good fit of data to the hypothesized model (χ2[1]=.11,p=.74, NFI=.99, RMSEA=.00). Observed NFEC predicted child depression (β=.19,p<.01), which predicted asthma disease severity (β=.23,p<.01). Relational security inversely predicted depressive symptoms (β=−.40,p<.001), and was not a mediator as predicted, but rather an independent contributor. The findings are consistent with the Biobehavioral Family Model, which suggests a psychobiologic influence of specific family relational processes on asthma disease severity by way of child depressive symptoms.
Family Psychological Factors in Relation to Children's Asthma Status and Behavioral Adjustment at Age 4
Authors: KLINNERT MARY D. , KAUGARS ASTRIDA S. , STRAND MATTHEW , SILVEIRA LORI
Published: March 2008

The objectives of this study were to determine whether family psychosocial factors influenced asthma development by age 4, and whether family factors and early wheezing illness were associated with behavioral adjustment at age 4. Participants were 98 children enrolled in an intervention study at 9–24 months and followed to age 4. Baseline evaluations assessed infants' respiratory illness severity, family psychosocial characteristics, and parental risk factors for asthma development. Active asthma categorization at age 4 utilized both parent report and objective data. Parents completed the Child Behavior Checklist (CBCL). Caregiver single‐parent status, a composite of baseline family stresses, and early wheezing illness severity were associated with active asthma at age 4. The contribution of prenatal smoke exposure and early hospitalization to active asthma varied with racial/ethnic group membership. Maternal mental health and family stresses predicted CBCL scores at age 4, whereas early illness severity and hospitalization were unrelated to CBCL scores. CBCL scores were not elevated for children with active asthma at age 4. Family factors consistent with a negative emotional environment were associated with both active asthma and adjustment problems at age 4, suggesting that both outcomes may be influenced by a common factor.
Family Climate of Routine Asthma Care: Associating Perceived Burden and Mother‐Child Interaction Patterns to Child Well‐being
Authors: FIESE BARBARA , WINTER MARCIA , ANBAR RAN , HOWELL KIMBERLY , POLTROCK SCOTT
Published: March 2008

This preliminary report links the literatures on family asthma management practices and on the characteristics of family interaction patterns thought to influence children's adjustment to a chronic physical illness. Specifically, this study of 60 families with a child with asthma examined the extent to which perceived burden of routine asthma care affected child mental health via its influence on parent‐child interaction patterns. Mothers completed a measure of asthma management routine burden, mother and child were observed in a 15‐minute interaction task, and children completed measures of child anxiety and asthma quality of life (QOL). Perceived routine burden significantly predicted child anxiety and QOL through its effect on mother‐child rejection/criticism. The same pattern did not hold for mother intrusiveness/control. The results are discussed in terms of how overall family climate and regulation of routines affects child well‐being. Implications for clinical practice and limitations of the study are provided.
Elevated ozone modifies the feeding behaviour of the common leaf weevil on hybrid aspen through shifts in developmental, chemical, and structural properties of leaves
Authors: Freiwald V. , Häikiö E. , Julkunen‐Tiitto R. , Holopainen J. K. , Oksanen E.
Published: March 2008

In this study, we tested the impact of moderately elevated ozone (O3) – 1.5 × ambient, equivalent to predicted near‐future ozone concentrations – on the feeding behaviour of the common leaf weevil Phyllobius pyri L. (Coleoptera: Curculionidae), on two hybrid aspen [Populus tremula ×Populus tremuloides (Salicaceae)] clones (clones 55 and 110) differing in ozone sensitivity using the open‐air ozone exposure site in Kuopio, Finland. Three host‐selection tests (test between treatments, test between clones, and test between treatments* clones) with common leaf weevil females were carried out in the laboratory in the 2nd year of ozone exposure. The beetles were offered two (four for the tests between treatments and clones) freshly cut leaf discs from first flush leaves. After 24 h, the beetles were removed and the leaf disc area consumed was measured. In the field, the unfolding of the buds was followed and samples were taken for anatomical and chemical (salicylates, condensed tannins, nitrogen, and water content) leaf analyses. Phyllobius pyri significantly preferred leaves from clone 55 to those from clone 110 in the ambient air treatment, whereas this preference was less evident under elevated ozone. Leaves from ozone‐exposed trees were significantly preferred to leaves grown in ambient air. Our results suggest that the preference of clone 55 and of ozone‐exposed leaves can be explained by phenotypic properties of the plant and prevailing ozone concentration through shifts in leaf development process, phenolic composition, and leaf thickness.
Chinese herbal medicine (Tuhuai extract) exhibits topical anti‐proliferative and anti‐inflammatory activity in murine disease models
Authors: Man Mao‐Qiang , Shi Yuejun , Man Mona , Lee Seung Hun , Demerjian Marianne , Chang Sandra , Feingold Kenneth R. , Elias Peter M.
Published: March 2008

Abstract:  While psoriasis is one of the most common skin disorders in humans, effective, safe and inexpensive treatments are still largely unavailable. Chinese herbal medicine (CHM) has been used for centuries for treating psoriasis and several reports claim that systemic administration of one such CHM, Tuhuai, mainly composed of flos sophorae, smilax glabra roxb and licorice, is effective in psoriasis. However, the mechanisms by which this CHM improves psoriasis are not yet clear. Two universal features of psoriasis are epidermal hyperplasia and inflammation. Moreover, drugs that specifically inhibit epidermal hyperplasia and/or inflammation are widely used to treat psoriasis. Here, we investigated whether topical applications of Tuhuai extract exhibit anti‐proliferative and anti‐inflammatory activities in two murine models of inflammatory dermatoses. To assess Tuhuai’s potential anti‐proliferative effect, we disrupted epidermal barrier function twice‐daily for 4 days in normal hairless mice followed by topical applications of either 1% Tuhuai extract or Vehicle to both flanks immediately after each barrier perturbation. Changes in epidermal proliferation and apoptosis were evaluated by immunohistochemistry and TUNEL staining. To assess the anti‐inflammatory effects of Tuhuai, both irritant (phorbol ester) and acute allergic contact dermatitis (oxazolone) models were used. Whereas topical Tuhuai extract did not alter epidermal proliferation or induce irritation in normal skin, it both reduced epidermal hyperplasia in the epidermal hyperproliferative model, and reduced inflammation in both irritant and allergic contact dermatitis models. As topical Tuhuai extract exhibits anti‐proliferative and anti‐inflammatory properties in a variety of human models of inflammatory dermatoses, Tuhuai could provide an effective, relatively safe and inexpensive therapeutic alternative for the treatment of inflammatory dermatoses, including psoriasis.
K6PC‐5, a novel sphingosine kinase activator, improves long‐term ultraviolet light‐exposed aged murine skin
Authors: Park Hwa‐young , Youm Jong‐Kyung , Kwon Mi Jung , Park Byeong Deog , Lee Seung Hun , Choi Eung Ho
Published: March 2008

Abstract:  Sphingosine‐1‐phosphate (S1P), which is formed by phosphorylation of sphingosine through a process catalysed by sphingosine kinase (SK), is a multifunctional mediator of a variety of cellular responses including proliferation, differentiation, motility, and survival. K6PC‐5, which was recently synthesized as a novel SK activator, is expected to increase S1P levels. Indeed studies have already demonstrated that K6PC‐5 exhibits anti‐aging effects on intrinsic aged murine skin by increasing fibroblasts, collagen synthesis, dermal thickness, and epidermal differentiation. However, photoaging and intrinsic aging have highly different clinical and histopathological properties. In this study, we developed a photoaged murine model by exposing mice that were 56 weeks old to ultraviolet (UV)B and UVA radiation for 8 weeks. We then investigated whether K6PC‐5, as an SK activator, had anti‐aging effects on photoaged murine skin in addition to its effects on intrinsic aged murine skin and determined the mechanism. K6PC‐5 increased dermal collagen density in photoaged skin through increases in fibroblasts and collagen production. Photoaged murine skin treated with K6PC‐5 showed an increase in stratum corneum (SC) integrity with increased corneodesmosome density and an improvement in barrier recovery rate. Matrix metalloproteinase 13 remained unchanged. These results indicate that topical application of K6PC‐5 improves photoaged skin by improving skin barrier and increasing fibroblast count and function. In conclusion, K6PC‐5, as an S1P activator, improves long‐term UV‐exposed aged skin as well as intrinsic aged skin.
Fibulin‐5 accelerates elastic fibre assembly in human skin fibroblasts
Authors: Katsuta Yuji , Ogura Yuki , Iriyama Shunsuke , Goetinck Paul F. , Klement John F. , Uitto Jouni , Amano Satoshi
Published: March 2008

Abstract:  Fibulin‐5 null mice display abnormalities in the elastic fibres in the dermis. We postulated, therefore, that fibulin‐5 might be a regulator of elastic fibre assembly and stability. To clarify the role of fibulin‐5 in elastic fibre formation, we employed in vitro systems that allowed increasing expression of elastic fibre components by gene transduction using retroviral vector constructs. First, the human tropoelastin gene (ELN) was transduced into human dermal fibroblasts, which resulted in elevated gene expression. These cells were then cultured in monolayer, but the overexpression of ELN in this system did not alter the assembly of elastic fibres. However, incubation of fibroblasts with TGF‐β1 resulted in elastic fibre accumulation, and the expression of fibulin‐5 was enhanced by TGF‐β1. Thus, we overexpressed human fibulin‐5 cDNA in dermal fibroblasts using a retroviral vector containing a cytomegalovirus (CMV) promoter. These cells deposited elastic fibres. These results suggest that fibulin‐5 is a critical component in the control of elastic fibre assembly by dermal fibroblasts.
Function and expression of melatonin receptors on human pancreatic islets
Authors: Ramracheya Reshma D. , Muller Dany S. , Squires Paul E. , Brereton Helen , Sugden David , Huang Guo Cai , Amiel Stephanie A. , Jones Peter M. , Persaud Shanta J.
Published: March 2008

Abstract:  Melatonin is known to inhibit insulin secretion from rodent β‐cells through interactions with cell‐surface MT1 and/or MT2 receptors, but the function of this hormone in human islets of Langerhans is not known. In the current study, melatonin receptor expression by human islets was examined by reverse transcription‐polymerase chain reaction (RT‐PCR) and the effects of exogenous melatonin on intracellular calcium ([Ca2+]i) levels and islet hormone secretion were determined by single cell microfluorimetry and radioimmunoassay, respectively. RT‐PCR amplifications indicated that human islets express mRNAs coding for MT1 and MT2 melatonin receptors, although MT2 mRNA expression was very low. Analysis of MT1 receptor mRNA expression at the single cell level indicated that it was expressed by human islet α‐cells, but not by β‐cells. Exogenous melatonin stimulated increases in intracellular calcium ([Ca2+]i) in dissociated human islet cells, and stimulated glucagon secretion from perifused human islets. It also stimulated insulin secretion and this was most probably a consequence of glucagon acting in a paracrine fashion to stimulate β‐cells as the MT1 receptor was absent in β‐cells. Melatonin did not decrease 3′, 5′‐cyclic adenosine monophosphate (cyclic AMP) levels in human islets, but it inhibited cyclic AMP in the mouse insulinoma (MIN6) β‐cell line and it also inhibited glucose‐stimulated insulin secretion from MIN6 cells. These data suggest that melatonin has direct stimulatory effects at human islet α‐cells and that it stimulates insulin secretion as a consequence of elevated glucagon release. This study also indicates that the effects of melatonin are species‐specific with primarily an inhibitory role in rodent β‐cells and a stimulatory effect in human islets.
Fetal/placental regulation of maternal melatonin in rats
Authors: Tamura Hiroshi , Takayama Hisako , Nakamura Yasuhiko , Reiter Russel J. , Sugino Norihiro
Published: March 2008

Abstract:  We investigated how maternal melatonin is regulated in pregnant rats. To examine the involvement of the conceptus (fetus and placenta) in serum melatonin concentrations, the number of conceptuses was experimentally reduced to one on day 7 of pregnancy (1‐conceptus group). Maternal circulating nighttime melatonin levels increased toward day 21 of pregnancy and rapidly decreased to the non‐pregnancy levels after parturition, whereas the maternal serum nighttime melatonin levels of the 1‐conceptus group on day 21 of pregnancy were significantly lower than normal pregnancy bearing dams more than 10 conceptuses. When the fetuses were removed by fetectomy (all fetuses but not the placentae) on day 12 of pregnancy, serum melatonin concentrations were not decreased. To examine the source of circulating maternal melatonin, mRNA expression of N‐acetyltransferase (NAT), which is a late limiting enzyme for melatonin synthesis, was examined in the placenta and fetal pineal. NAT was not expressed in the placenta and was negligible in the pineal gland of the fetus compared with the mother’s pineal gland. To examine the effect of placental hormones on maternal melatonin production, a conditioned medium, which was made by incubating placenta of day 20 of pregnancy with medium, was injected into the 1‐conceptus dams from day 17 to day 20 of pregnancy. Injection of conditioned medium significantly increased serum melatonin concentrations compared with the control values whereas charcoal treatment abolished the stimulatory effect of conditioned medium. In conclusion, maternal circulating melatonin is from the maternal pineal gland and is increased by placental hormones during pregnancy.
Early therapeutic intervention in females with Fabry disease?
Authors: Hughes Derralynn A
Published: March 2008

Anderson–Fabry disease is an X‐linked lysosomal storage disorder resulting from deficiency of α‐galactosidase A. The subsequent accumulation of globotriaosylceramide (Gb3) in cells and tissues of the body has multisystemic effects and significantly impacts upon quality of life and survival of individuals with this condition. In general, Anderson–Fabry disease is more severe in male patients; however, despite X‐linkage, females may develop severe signs and symptoms of the disease, although there is considerable phenotypic heterogeneity, which correlates most closely with age. Histological analyses of biopsies have shown evidence of Gb3storage in the kidney and heart in female patients. Gb3levels are also elevated in the urine of females, although plasma Gb3levels are not reliably elevated. The efficacy of enzyme replacement therapy (ERT) with recombinant human α‐galactosidase A has been demonstrated in females in a clinical trial and in observational studies, including those using data from outcome surveys. Benefits include a reduction in left ventricular mass, stabilization of renal function and improvements in pain and quality of life.

Conclusion: If early intervention with ERT in females is to be advocated, it is necessary to demonstrate not only that females with Anderson–Fabry disease have clinical and biochemical features of α‐galactosidase A deficiency and respond to ERT, but also that early intervention prevents the onset of the later manifestations of the disorder. Any strategy for early therapy should also balance future advantages against any impact on quality of life.
Diagnosis and management of respiratory involvement in Hunter syndrome
Authors: Kamin Wolfgang
Published: March 2008

Respiratory problems are frequently encountered by patients with Hunter syndrome and contribute to the premature mortality seen in individuals with the disease. Progressive deposition of glycosaminoglycans in the soft tissue of the throat and trachea is thought to be responsible for the airway dysfunction and obstruction, which characterize the syndrome. Other physical characteristics, including abnormalities in the shape and structure of the ribs, abdominal organ enlargement, short neck and immobile jaw, further contribute to the respiratory problems. New measurement systems specifically tailored to paediatric patients now allow clinicians to follow the progressive deterioration of lung function, which was previously challenging in this population. Sleep apnoea is another common feature of Hunter syndrome, which can lead to a reduction in oxygen saturation of the blood and severely disrupts sleep. In our clinic, continuous positive airway pressure (CPAP), in which inspired air at elevated pressure is delivered through a specially designed mask, has proved to be effective for reducing sleep apnoea in patients with Hunter syndrome. As a consequence of the anatomical and pathological changes in the upper airways of patients with Hunter syndrome, general anaesthesia – especially intubation – is a difficult and potentially high‐risk procedure. Consequently, such procedures should be performed by an anaesthetist – ideally accompanied by a paediatric pneumologist/intensivist – with experience in managing patients with Hunter syndrome.

Conclusion: Respiratory abnormalities are a major contributor to the premature mortality seen in Hunter syndrome. Treatment of these respiratory problems requires the careful attention of clinicians skilled in the recognition, diagnosis, management and treatment of Hunter syndrome.
Substrate reduction therapy
Authors: Platt Frances M , Jeyakumar Mylvaganam
Published: March 2008

The therapeutic options for lysosomal storage diseases (LSDs) have expanded greatly over the past decade, although for many disorders there is still no effective treatment. Given that the majority of LSDs involve pathological changes in both the brain and peripheral tissues, effective treatment of central nervous system (CNS) and peripheral manifestations still remains a considerable technical challenge. Type 1 Gaucher disease has two approved treatment modalities – enzyme replacement therapy (ERT) and substrate reduction therapy (SRT) – which have unique, independent and potentially complementary mechanisms of action. The availability of these two therapies has greatly increased the options for the effective clinical management of type 1 Gaucher disease. ERT involves the intravenous administration of fully functional enzyme that is taken up by cells and delivered to the lysosome, where it can compensate for the underlying enzyme deficiency. SRT uses an orally available, small molecule drug that inhibits the first committed step in glycosphingolipid biosynthesis. The aim is to reduce the rate of biosynthesis of glycosphingolipids to offset the catabolic defect, restoring the balance between the rate of biosynthesis and the rate of catabolism. SRT also has the potential to treat LSDs with CNS pathology, as the drug in clinical use (miglustat, Zavesca®; Actelion Pharmaceuticals Ltd, Allschwil, Switzerland) crosses the blood–brain barrier. In this review, the current status of SRT for the treatment of Gaucher disease and other LSDs will be discussed, based upon preclinical and clinical studies.

Conclusion: SRT is an oral alternative treatment option for patients with type 1 Gaucher disease unwilling or unable to receive ERT. With the recent reports of clinical improvement/stabilization of CNS manifestations following SRT in patients with Niemann–Pick disease type C, miglustat may also have a role to play in the management of patients with glycosphingolipid storage in the brain. Furthermore, as SRT synergises with other therapeutic modalities, it may also prove to be a key component of combination therapies in the future.
Sensitivity of Petri disease pathogens to hot‐water treatments in vitro
Authors: Gramaje D. , García‐Jiménez J. , Armengol J.
Published: March 2008

Petri disease pathogens (Phaeoacremonium spp. and Phaeomoniella chlamydospora) are able to colonize the vessels in the xylem of grapevine propagating material. Hot‐water treatment (HWT) protocols at 50°C for 30 min have been applied in grapevine nurseries to control these pathogens with variable results. The effect of HWT in vitro at higher temperatures on Pa. chlamydospora, Phaeoacremonium aleophilum and Phaeoacremonium parasiticum isolates was determined by placing conidial suspensions and plugs of agar with mycelia in Eppendorf vials and incubated in hot water at 49, 50, 51, 52, 53 or 54°C for 30, 45 or 60 min. Conidial germination and the colony growth rate decreased with increased temperature and time combinations. Pa. chlamydospora was more sensitive than Phaeoacremonium spp. to the experimental temperatures for all periods of time. Pa. chlamydospora tolerated temperatures of 53°C, while Pm. aleophilum and Pm. parasiticum tolerated temperatures of 54°C, although the treatments above 51–52°C drastically reduced conidial germination and mycelial growth. These results highlight the need to develop HWT using temperatures above 51°C to reduce the incidence of fungal infections and ensure high‐quality propagating material for grapevine growers.
SOFTENING OF PUMPKIN SEEDS (CUCURBITA MOSCHATA) BY ALKALINE MACERATION
Authors: CARAMEZ S.M.B. , STEFANI M. , MEDEIROS J.D. , VIEIRA M.A. , BRÜSKE G.R. , DE FRANCISCO A. , AMANTE E.R.
Published: March 2008

The nutritional value of pumpkin seeds is widely recognized. This article shows that alkaline maceration of pumpkin seed makes them soft and improves their market acceptability as an important source of fiber, unsaturated lipids, minerals and proteins. Microscopic characterization of pumpkin seeds was realized. The results indicate elimination of minerals from the seeds through the delignification process due to the nature of the phenolic compounds eliminated in the maceration liquid. The alkaline maceration process of pumpkin seeds may contribute to a larger consumption of fibers and other nutritive elements from them.

PRACTICAL APPLICATIONS

This work shows that the pumpkin seeds softened by chemical maceration improve sensory preferences, compared to nonmacerated products. Solid waste from pumpkin process can be converted to a new product as a snack rich in fiber and other important compounds, normally discarded as an industrial solid waste.