bluuebunny/crossref_metadata_2025 huggingface dataset:
Insight into the molecular mechanisms of glucocorticoid receptor action promotes identification of novel ligands with an improved therapeutic index
Authors: Schäcke Heike , Rehwinkel Hartmut , Asadullah Khusru , Cato Andrew C. B.
Published: June 2006

Abstract: Glucocorticoids are highly effective in the therapy of inflammatory and autoimmune disorders. Their beneficial action is restricted because of their adverse effects upon prolonged usage. Topical glucocorticoids that act locally have been developed to significantly reduce systemic side effects. Nonetheless, undesirable cutaneous effects such as skin atrophy persist from the use of topical glucocorticoids. There is therefore a high medical need for drugs as effective as glucocorticoids but with a reduced side‐effect profile. Glucocorticoids function by binding to and activating the glucocorticoid receptor that positively or negatively regulates the expression of specific genes. Several experiments suggest that the negative regulation of gene expression by the glucocorticoid receptor accounts for its anti‐inflammatory action. This occurs through direct or indirect binding of the receptor to transcription factors such as activator protein‐1, nuclear factor‐κB or interferon regulatory factor‐3 that are already bound to their regulatory sites. The positive action of the receptor occurs through homodimer binding of the receptor to discrete nucleotide sequences and this possibly contributes to some of the adverse effects of the hormone. Glucocorticoid receptor ligands that promote the negative regulatory action of the receptor with reduced positive regulatory function should therefore show improved therapeutic potential. A complete separation of the positive from the negative regulatory activities of the receptor has so far not been possible because of the interdependent nature of the two regulatory processes. Nevertheless, considerable improvement in the therapeutic action of glucocorticoid receptor ligands is being achieved through the use of key molecular targets for screening novel glucocorticoid receptor ligands.
Morphogenesis of dermal–epidermal junction in a model of reconstructed skin: beneficial effects of vitamin C
Authors: Marionnet Claire , Vioux‐Chagnoleau Corinne , Pierrard Cécile , Sok Juliette , Asselineau Daniel , Bernerd Françoise
Published: June 2006

Abstract:  In skin, cohesion between the dermis and the epidermis is ensured by the dermal–epidermal junction which is also required for control of epidermal growth and differentiation. Here we showed that addition of vitamin C optimized the formation of the dermal–epidermal junction in an in vitro human reconstructed skin model leading to a structure closer to that of normal human skin. Compared with controls, vitamin C treatment led to a better organization of basal keratinocytes, an increase in fibroblast number and a faster formation of the dermal–epidermal junction. Vitamin C also accelerated deposition of several basement membrane proteins, like type IV and VII collagens, nidogen, laminin 10/11, procollagens I and III, tenascin C and fibrillin‐1 at the dermal–epidermal junction. The mechanism of action of vitamin C was investigated by quantitative polymerase chain reaction in fibroblasts and keratinocytes respectively. Vitamin C effects passed in part through an increase in col I alpha1, col III alpha1 and fibrillin‐1 mRNA levels. Effects on the other markers appeared to happen at the translational and/or post‐translational level, as illustrated for tenascin C, col IV alpha2 and col VII alpha1 mRNA levels which were reduced by vitamin C in both cell types.
Experimental scoliosis in melatonin‐deficient C57BL/6J mice without pinealectomy
Authors: Machida Masafumi , Dubousset Jean , Yamada Thoru , Kimura Jun , Saito Masashi , Shiraishi Tateru , Yamagishi Masaaki
Published: June 2006

Abstract:  The etiology of idiopathic scoliosis is unknown. Scoliosis with many characteristics closely resembling those seen in idiopathic scoliosis has been produced in young chickens and bipedal rats after pinealectomy. In this study, we induced experimental scoliosis in C57BL/6J mice without pinealectomy and melatonin treatment suppressed the development of scoliosis. A total of 100 mice were divided into four groups: 20 quadrupedal mice served as controls; 30 mice underwent resection of two forelegs and tail at 3 wk of age (bipedal mice); the remaining 20 quadrupedal and 30 bipedal mice received intraperitoneal melatonin (8 mg/kg BW) at 19:00 hr daily. Before killing, blood samples were collected in the middle of dark cycle and melatonin levels were measured by radioimmunoassay. Spine X‐ray and helical 3D‐CT were examined after killing at 5 months of age. The bipedal mice without a tail were able to walk with standing posture, whereas the quadrupedal mice did not walk with standing posture. In C57BL/6J mice, the serum melatonin was reduced to nearly zero; however, the normal level was restored in both bipedal and quadrupedal mice after the injection of melatonin. Scoliosis with rib humps developed in 29 of 30 bipedal and in five quadrupedal mice. None of mice with melatonin treatment developed scoliosis. The results suggest that melatonin deficiency in bipedal mice appears to play crucial role for development of scoliosis. Also the restoration of melatonin levels prevents the development of scoliosis.
Decreased intramuscular blood flow in patients with lateral epicondylitis
Authors: Oskarsson E. , Gustafsson B.‐E. , Pettersson K. , Aulin K.Piehl
Published: June 2006

The purpose of this pilot study was to investigate intramuscular microcirculation in extensor carpi radialis brevis (ECRB) in patients with lateral epicondylitis. Ten patients with unilateral epicondylitis, mean duration of symptoms of 39 (12–96) months participated. The diagnosis was based on clinical examination and none was under treatment for the last 6 months. Isometric handgrip strength, 2‐pinch grip strength and muscle strength during radial deviation and dorsal extension were determined. Functional perceived pain was evaluated by a modified behaviour rating scale and perceived pain during contraction by visual analogue scale. Intramuscular and skin blood flow was recorded by a laser‐Doppler flowmetry system technique (LDF) during stable temperature condition. Intramuscular blood flow was significantly lower in the affected side, 22.7±9.8 perfusion units (PU), as compared with 35.2±11.9 PU in the control side (P=0.01). There was no difference in skin blood flow or temperature between the affected and the control side. A positive correlation was found between the duration of symptoms and the difference in intramuscular blood flow between the affected and the control arm (r=0.65, P=0.06). The present data indicate that decreased microcirculation and anaerobic metabolism in ECRB may contribute to the lateral epicondylitis symptoms.
Therapeutic effect of passive mobilization exercise on improvement of muscle regeneration and prevention of fibrosis after laceration injury of rat
Authors: Hwang J. H. , Ra Y. J. , Lee K. M. , Lee J. Y. , Ghil S. H.
Published: June 2006

OBJECTIVE: To evaluate the muscle healing effect of passive mobilization exercises after a laceration injury.

DESIGN: Randomized‐controlled trial.

SETTING: Basic science laboratory.

ANIMALS: Male Sprague–Dawley rats (N=36), age ranging from 8 to 10 weeks and weight ranging from 300 to 400 g.

INTERVENTION: The bilateral gastrocnemius muscles were lacerated. The left‐leg muscles were used as the study groups and the right side was used as the control (lacerated muscles without any treatment, n=8). In the exercise group (n=24), passive mobilization exercise (15 min/day) was performed for 5 days starting from different time points (2, 7, and 14 days postlaceration). The decorin group (n=8) was injected with decorin (50 μg at 14 days postlaceration), which is a well‐known antifibrotic agent. Four animals were used as the normal controls, in which only the muscle strength was evaluated. All the animals were killed 4 weeks after the laceration.

MAIN OUTCOME MEASURES: The histologic characterization of muscle regeneration (hematoxylin and eosin staining, number and diameter of the centronucleated, regenerating myofibers), muscle fibrosis (vimentin‐positive area, Masson modified trichrome staining positive area), and muscle strength (analysis of fast twitch strength).

RESULTS: The level of fibrosis was more than 50% lower in the exercise and decorin groups than in the control (P<0.05). The decorin group showed the highest number of regenerated, new myofibers, and the highest muscle strength. All of the exercise groups, regardless of the starting time of exercise, also showed significant improvement in regeneration and strength. However, the exercise group starting 14 days after the laceration showed the best results.

CONCLUSIONS: Stretching exercises after a muscle laceration injury has a strong antifibrotic effect, as much as a well‐known antifibrotic agent, decorin. According to the results, the best time to begin stretching exercises is 14 days after laceration for antifibrosis and muscle regeneration.
Electromyographic analysis of traditional and nontraditional abdominal exercises: implications for rehabilitation and training
Authors: Escamilla R. F. , Babb E. , Dewitt R. , Jew P. , Kelleher P. , Burnham T. , Busch J. , D'Anna K. , Mowbray R. , Imamura R. T.
Published: June 2006

BACKGROUND AND PURPOSE: Performing nontraditional abdominal exercises with devices such as abdominal straps, the Power Wheel, and the Ab Revolutionizer has been suggested as a way to activate abdominal and extraneous (nonabdominal) musculature as effectively as more traditional abdominal exercises, such as the crunch and bent‐knee sit‐up. The purpose of this study was to test the effectiveness of traditional and nontraditional abdominal exercises in activating abdominal and extraneous musculature.

SUBJECTS: Twenty‐one men and women who were healthy and between 23 and 43 years of age were recruited for this study.

METHODS: Surface electromyography (EMG) was used to assess muscle activity from the upper and lower rectus abdominis, external and internal oblique, rectus femoris, latissimus dorsi, and lumbar paraspinal muscles while each exercise was performed. The EMG data were normalized to maximum voluntary muscle contractions. Differences in muscle activity were assessed by one‐way, repeated‐measures analysis of variance.

RESULTS: Upper and lower rectus abdominis, internal oblique, and latissimus dorsi muscle EMG activity were highest for the Power Wheel (pike, knee‐up, and roll‐out), hanging knee‐up with straps, and reverse crunch inclined 30°. External oblique muscle EMG activity was highest for the Power Wheel (pike, knee‐up, and roll‐out) and hanging knee‐up with straps. Rectus femoris muscle EMG activity was highest for the Power Wheel (pike and knee‐up), reverse crunch inclined 30°, and bent‐knee sit‐up. Lumbar paraspinal muscle EMG activity was low and similar among exercises.

DISCUSSION AND CONCLUSION: The Power Wheel (pike, knee‐up, and roll‐out), hanging knee‐up with straps, and reverse crunch inclined 30° not only were the most effective exercises in activating abdominal musculature but also were the most effective in activating extraneous musculature. The relatively high rectus femoris muscle activity obtained with the Power Wheel (pike and knee‐up), reverse crunch inclined 30°, and bent‐knee sit‐up may be problematic for some people with low back problems.
Gamma loop dysfunction in the quadriceps femoris of patients who underwent anterior cruciate ligament reconstruction remains bilaterally
Authors: Konishi Y. , Aihara Y. , Sakai M. , Ogawa G. , Fukubayashi T.
Published: June 2006

Purpose of this study was to investigate the effects of anterior cruciate ligament (ACL) repair on the γ loop of the bilateral quadriceps femoris (QF). Maximal voluntary contraction (MVC) of knee extension and integrated electromyogram (I‐EMG) of vastus medialis (VM), vastus lateralis (VL), and rectus femoris (RF) were examined in uninjured and injured limbs of 18 patients and 10 normal subjects, before and after 20‐min vibration applied to the QF. Mean percentage changes were calculated as: (pre‐vibration value−post‐vibration value)/pre‐vibration value × 100. Patients were divided into two groups: short‐term‐group (tested ≤12 months after ACL repair, n=8), long‐term‐group (tested ≥18 months after ACL repair, n=10). Mean percentage changes of the four groups were compared with those of controls. Results indicated that changes of MVC and I‐EMG on the uninjured and injured sides in short‐term‐group in response to vibration were significantly different from those of controls. There were no significant differences between uninjured sides in long‐term and control groups. MVC and I‐EMG of VM and RF of injured side in patients in the long‐term‐group in response to vibration were not different from those of controls.

From these results, we concluded that this abnormality of the γ loop in both injured and uninjured sides did not recover despite ACL reconstruction. However, the abnormality in uninjured side might recover ≥18 months after repair.
Relationship between efficiency and pedal rate in cycling: significance of internal power and muscle fiber type composition
Authors: Hansen E. A. , Sjøgaard G.
Published: June 2006

Cycling was performed to test the following two hypotheses: (1) muscular efficiency is unrelated to pedal rate (61, 88, and 115 r.p.m.) for a group of subjects with a wide range of slow twitch (ST) fibers in spite of decreasing whole‐body efficiency and (2) muscular efficiency correlates positively with % ST muscle fibers, and this correlation is more pronounced at low pedal rates than at high pedal rates.

Whole‐body gross efficiency decreased from 20–22% at 61 r.p.m. to 15–18% at 115 r.p.m. Mean muscular efficiency for all subjects (n=16) was ∼26%, with delta efficiency being constant and muscular efficiency (taking internal power into account) slightly increasing with pedal rate. Muscular efficiency correlated positively (R2=0.25) with % ST fibers (21–97% ST in m. vastus lateralis) at 115 r.p.m. while not at 61 and 88 r.p.m.

In conclusion, the decrease in whole‐body gross efficiency with increasing pedal rate was not explained by a decrease in muscular efficiency, and supported increase in internal power to account for the increase in metabolic power with increasing pedal rate. Furthermore, differences between individuals in muscle fiber type composition affected muscular efficiency, which correlated positively with % ST muscle fibers during fast pedalling.
Two‐Year Clinical Evaluation of Repair versus Replacement of Composite Restorations
Authors: Gordan Valeria V. , Shen Chiayi , Riley Joseph , Mjör Ivar A.
Published: June 2006

Purpose:  To investigate the effectiveness of alternative treatments to the replacement of resin‐based composite (RBC) restorations through a prospective longitudinal cohort clinical study.

Materials and Methods:  Forty patients aged 27 to 77 years (mean=55) with 88 RBC restorations, with one or more features that deviated from ideal, participated in the study. They were assigned to five treatment groups: repair (N=25), sealing of defective margins (N=13), resurfacing (N=18), replacement (N=16), and the no‐treatment group (N=16). The replacement and no‐treatment groups served as comparison groups and received random assignment. Two clinicians examined the quality of the restorations (N=88) prior to the assigned treatment, and at subsequent recalls (1 and 2 years) using a modified Ryge criteria (Alfa, Bravo, and Charlie, meaning clinically excellent, clinically acceptable with one or more features that deviated from ideal, and clinically unacceptable, respectively) that observed (1) color, (2) marginal adaptation, (3) anatomic form, (4) surface roughness, (5) marginal staining, (6) bulk discoloration, (7) contact, (8) secondary caries, (9) postoperative sensitivity, and (10) luster.

Results:  At 1‐ and 2‐year recalls, 66 (75%) and 58 (66%) restorations were examined. Kruskal‐Wallis Test showed significant differences for marginal adaptation and marginal staining for both 1‐ and 2‐year recall exams (p < .05). The repair, sealant, and replacement groups presented significant improvement when compared with the no‐treatment group for marginal adaptation. The repair and replacement groups showed superior results when compared with the no‐treatment group for marginal staining.

Conclusion:  RBC restorations that present less‐than‐ideal marginal adaptation and stained margins are better off being repaired.

clinical significance

Repair of resin‐based composite (RBC) restorations is a conservative option for treatment of RBC restorations with inadequate marginal adaptation and marginal staining.
The Eagles of Romanticism
Authors: Ferber Michael
Published: July 2006

In English, German, French, and Russian poetry of 1750 to 1850 the eagle surpasses the nightingale and the lark as a symbol of the poet, the poetic genius, or the creative imagination. They flock so thickly in that period, and were seen so seldom before and after, that they can be taken as definitive of Romanticism. Pindar likened himself to an eagle, but the modern trend gets its main boost, it seems, from Gray, who calls Pindar “the Theban eagle” for the sovereign flight of his odes. This essay surveys dozens of poets in seven languages who adopted the image. Sometimes, notably with Victor Hugo, the image stands for the supreme command of genius; among others it represents the helpless “rapture” of enthusiasm – hence the Ganymede theme. Some poets, particularly women, modestly compare themselves to lesser winged things unable to fly like eagles (recycling Horace’s poem on Pindar the swan); yet others see the poet as an eagle caged, wounded, or ill. All this on the face of it is odd, since eagles, unlike nightingales and larks, are not songbirds; traditionally they are the lords of the avian world, and dangerous predators. But Romantic poets plume themselves as the new sovereigns of the imaginative skies.
Transdermal nicotine patch enhances type I collagen synthesis in abstinent smokers
Authors: Sørensen Lars T. , Jorgensen Lars N. , Zillmer Rikke , Vange Jakob , Hemmingsen Ulla , Gottrup Finn
Published: June 2006

Cigarette smokers deposit less collagen, expressed as hydroxyproline, in granulation tissue than nonsmokers. We studied the effect of abstinence from smoking and transdermal nicotine patches on deposition of hydroxyproline, proline, type I procollagen, and total proteins. Fifty‐four healthy smokers were studied during 10 days of smoking and again from days 10 to 20 following smoking cessation. After the first 10 days of abstinence they were randomized to double‐blind treatment with transdermal nicotine patches of 25 mg/day or placebo for a period of 10 days. During this period and during smoking, an expanded polytetrafluoroethylene tube was implanted into the subcutis. Following removal of the implant, total amino acids and peptides were extracted. Hydroxyproline and proline were analyzed by high‐pressure liguid chromatography, type I procollagen was analyzed by enzyme‐linked immunoassay, and total proteins were determined colorimetrically. In the 39 subjects who complied with the study protocol, abstinence from smoking did not affect the deposition of hydroxyproline, proline, type I procollagen, or total protein in the implants. During abstinence, the type I procollagen level increased by 18% in the transdermal nicotine patches group and decreased by 10% in the placebo group (p<0.05). We conclude that 20 days of abstinence from smoking does not affect collagen deposition in granulation tissue. However, in abstinent smokers, transdermal nicotine patches appears to increase type I collagen synthesis.
Cytokines and growth factors in wound drainage fluid from patients undergoing incisional hernia repair
Authors: Di Vita Gaetano , Patti Rosalia , D'Agostino Pietro , Caruso Giuseppe , Arcara Matteo , Buscemi Salvatore , Bonventre Sebastiano , Ferlazzo Viviana , Arcoleo Francesco , Cillari Enrico
Published: June 2006

Knowing the dynamics of growth factor and cytokine secretion within the site of a surgical operation is important, as they play a crucial role in the pathophysiology of wound healing and are a target for modifying the repair response. The aim of this study was to evaluate the production of several cytokines and growth factors in the drainage wound fluid from patients undergoing incisional hernia repair: namely, interleukin (IL)‐6, IL‐10, IL‐1α, IL‐1 ra, interferon‐γ, vascular endothelial growth factors and basic fibroblast growth factor. Ten female patients with abdominal midline incisional hernia undergoing surgical repair were included in this study. In all cases, a closed‐suction drain was inserted in the wound below the fascia and removed on postoperative day 4. Wound fluid was collected on postoperative days 1–4 and the amount was recorded each time. Growth factors and cytokines production was evaluated as the whole amount produced over a 24‐hour period. In all patients, the amount of drain fluid from surgical wounds was more copious the first day after surgery, it decreased significantly afterward. The presence of all cytokines was highest on postoperative day 1, decreasing over the following days. More specifically, the production of IL‐1 ra, IL‐6, IL‐1α, and IL‐10 on postoperative day 1 fell sharply on postoperative days 3 and 4, whereas, after an initial reduction, interferon‐γ showed an increase from day 2 onward. Vascular endothelial‐derived growth factor production increased progressively after the operation reaching statistical significance only on day 4. As for basic fibroblast growth factor, it showed an opposite pattern: it was higher on postoperative day 1 decreasing thereafter. This analysis of cytokine and growth factor production in the drain fluid will lead us to a better evaluation of the events that follow a surgical wound and to a better understanding of the healing process.
Time course analysis of hypoxia, granulation tissue and blood vessel growth, and remodeling in healing rat cutaneous incisional primary intention wounds
Authors: Lokmic Zerina , Darby Ian A. , Thompson Erik W. , Mitchell Geraldine M.
Published: June 2006

Hypoxia and the development and remodeling of blood vessels and connective tissue in granulation tissue that forms in a wound gap following full‐thickness skin incision in the rat were examined as a function of time. A 1.5 cm‐long incisional wound was created in rat groin skin and the opposed edges sutured together. Wounds were harvested between 3 days and 16 weeks and hypoxia, percent vascular volume, cell proliferation and apoptosis, α‐smooth muscle actin, vascular endothelial growth factor‐A, vascular endothelial growth factor receptor‐2, and transforming growth factor‐β1 expression in granulation tissue were then assessed. Hypoxia was evident between 3 and 7 days while maximal cell proliferation at 3 days (123.6±22.2 cells/mm2, p<0.001 when compared with normal skin) preceded the peak percent vascular volume that occurred at 7 days (15.83±1.10%, p<0.001 when compared with normal skin). The peak in cell apoptosis occurred at 3 weeks (12.1±1.3 cells/mm2, p<0.001 when compared with normal skin). Intense α‐smooth muscle actin labeling in myofibroblasts was evident at 7 and 10 days. Vascular endothelial growth factor receptor‐2 and vascular endothelial growth factor‐A were detectable until 2 and 3 weeks, respectively, while transforming growth factor‐β1 protein was detectable in endothelial cells and myofibroblasts until 3–4 weeks and in the extracellular matrix for 16 weeks. Incisional wound granulation tissue largely developed within 3–7 days in the presence of hypoxia. Remodeling, marked by a decline in the percent vascular volume and increased cellular apoptosis, occurred largely in the absence of detectable hypoxia. The expression of vascular endothelial growth factor‐A, vascular endothelial growth factor receptor‐2, and transforming growth factor‐β1 is evident prior, during, and after the peak of vascular volume reflecting multiple roles for these factors during wound healing.
Expression of intracellular filament, collagen, and collagenase genes in diabetic and normal skin after injury
Authors: Rodgers Kathleen E. , Ellefson Dolph D. , Espinoza Theresa , Hsu Ya‐hsuan , DiZerega Gere S. , Mehrian‐Shai Ruty
Published: June 2006

Reports have shown differences in gene expression in the skin of diabetic and normal mice both at baseline and after injury. Cluster analysis identified distinct expression patterns within intermediate filaments and extracellular proteins. This report addresses the effect of diabetes and injury on the expression of keratin‐associated proteins, keratin complexes, procollagen, and collagenase (matrix metalloproteinase; MMP) genes. At baseline keratin‐associated proteins and keratin complexes gene expression was increased in diabetic mice. After surgery, the level of expression for keratin‐associated proteins and keratin complexes genes decreased in diabetic mice, but did not change in normal mice. If the expression of a procollagen gene differed between diabetic and normal mice, the expression was lower in diabetic mice. Procollagen gene expression was elevated after skin excision compared with noninjured skin. At baseline, the level of MMP and tissue inhibitor of metalloproteinase gene expression was comparable between mouse strains. With injury, the expression of several MMP genes was increased in both mouse strains, but to higher levels in diabetic mice. At day 7, the level of MMP‐9 activity in granulation tissue was elevated. This alteration may contribute to delayed healing in diabetic mice. Therefore, differences in gene expression exist between mouse strains and can assist in understanding of physiological manifestations, including delayed healing, in diabetic mice.
Contraction of myofibroblasts in granulation tissue is dependent on Rho/Rho kinase/myosin light chain phosphatase activity
Authors: Tomasek James J. , Vaughan Melville B. , Kropp Bradley P. , Gabbiani Giulio , Martin Michael D. , Haaksma Carol J. , Hinz Boris
Published: June 2006

During wound healing and fibrocontractive diseases fibroblasts acquire a smooth muscle cell‐like phenotype by differentiating into contractile force generating myofibroblasts. We examined whether regulation of myofibroblast contraction in granulation tissue is dominated by Ca2+‐induced phosphorylation of myosin light chain kinase or by Rho/Rho kinase (ROCK)‐mediated inhibition of myosin light chain phosphatase, similar to that of cultured myofibroblasts. Strips of granulation tissue obtained from rat granuloma pouches were stimulated with endothelin‐1 (ET‐1), serotonin, and angiotensin‐II and isometric force generation was measured. We here investigated ET‐1 in depth, because it was the only agonist that produced a long‐lasting and strong response. The ROCK inhibitor Y27632 completely inhibited ET‐1–promoted contraction and the phosphatase inhibitor calyculin elicited contraction in the absence of any other agonists, suggesting that activation of the Rho/ROCK/myosn light chain phosphatase pathway is critical in regulating in vivo myofibroblast contraction. Membrane depolarization with K+ also stimulated a long‐lasting contraction of granulation tissue; however, the amount of force generated was significantly less compared to ET‐1. Moreover, K+‐induced contraction was inhibited by Y27632. These results are consistent with inhibition of myosin light chain phosphatase by the Rho/ROCK signaling pathway, which would account for the long‐duration contraction of myofibroblasts necessary for wound closure.
Effect of recombinant human fibroblast growth factor‐2 on intramuscular ectopic osteoinduction by recombinant human bone morphogenetic protein‐2 in rats
Authors: Kakudo Natsuko , Kusumoto Kenji , Kuro Atsuyuki , Ogawa Yutaka
Published: June 2006

To clarify the effects of recombinant human fibroblast growth factor‐2 (rhFGF‐2) on the osteoconduction ability of recombinant human bone morphogenetic protein‐2 (rhBMP‐2) in vivo, rhBMP‐2 (2 μg) was mixed with different doses of rhFGF‐2 (0, 16, 80, 400, or 2,000 ng), and implanted into the lower leg muscle of rats using type I collagen as a carrier. Twenty‐one days later, ectopic neoplastic bones had bone mineral content, bone area, and bone mineral density measured by means of dual energy X‐ray absorptiometry and imaged by soft X‐ray. The values for alkaline phosphatase activity and calcium content were determined, and histology obtained. In the group treated with rhFGF‐2 at 16 ng, alkaline phosphatase activity, calcium content, bone mineral content, bone area, and bone mineral density were the greatest of all treatment groups, and the richest trabeculae were histologically observed in this group. In the groups treated with rhFGF‐2 at 80, 400, or 2,000 ng, bone formation was suppressed in a dose‐dependent manner. These results indicate that rhFGF‐2 promotes ectopic rhBMP‐2‐related osteoinduction at a low concentration (16 ng) in vivo, and that it suppresses osteoinduction at a higher amount (>80 ng).
Measurement of optical properties to quantify healing of chronic diabetic wounds
Authors: Weingarten Michael S. , Papazoglou Elisabeth , Zubkov Leonid , Zhu Linda , Vorona Greg , Walchack Adam
Published: June 2006

Measurement of scattering and absorption characteristics of tissue by near infrared spectroscopy may provide a clinically applicable, quantitative method of assessing healing of diabetic wounds. Twenty SICH‐1 hairless rats were divided into a control group and a streptozotocin‐induced diabetic group. Full‐thickness wounds were made on the dorsal surface of each animal. Wounds were examined using a near infrared device with three wavelengths of incident light. Amplitude and phase of scattered light were obtained at four different source detector distances at each wavelength. The probe was positioned at six different locations. Tissue absorption and scattering coefficients were calculated from amplitude and phase data. Wound dimensions were calculated by cross and parallel polarization. Thirty‐eight wounds were evaluated during the experiment. Wound size decreased at twice the rate in the control animals, whereas the average absorption coefficient was higher by a factor of two while the average value of the reduced scattering coefficient was 30% higher in the diabetic wounds. During healing, both scattering and absorption coefficients increased faster in the diabetics. Higher absorption in diabetic rats suggests impaired blood flow. Scattering may reflect tissue disorganization observed in delayed wound healing. We conclude that near infrared spectroscopy may differentiate between healing diabetic and nondiabetic wounds.
Changes in canine ionised calcium under three storage conditions
Authors: Brennan S. F. , O’Donovan J. , Mooney C. T.
Published: June 2006

Objectives:To determine the ionised calcium concentration following aerobic collection of blood and to compare ionised calcium concentration and pH of heparinised whole blood and plasma at 48 hours following collection under three different storage conditions to assess if ionised calcium concentration can be measured retrospectively.

Methods:Blood was collected from 17 dogs for analysis of ionised calcium concentration and pH using a Rapidpoint 400 (Bayer) blood gas analyser. Blood was collected into a commercial preheparinised syringe and into a plain syringe, with subsequent transfer to a commercially available heparinised sample tube. Samples were analysed within 10 minutes, and the remainder was divided for storage. One aliquot was set‐aside at room temperature for 48 hours, and the other was immediately centrifuged and the plasma divided for storage at room temperature and at 4°C for 48 hours each. In all samples, ionised calcium concentration and pH were measured again at 48 hours after storage.

Results:There was no significant difference in ionised calcium concentration or pH between anaerobically and aerobically collected heparinised whole blood analysed within 10 minutes of collection. At 48 hours, ionised calcium concentrations had decreased under all storage conditions irrespective of the direction of pH change.

ClinicalSignificance:Ionised calcium concentration can be measured in aerobically collected samples within 10 minutes and at 48 hours after collection under the conditions described.
Interpretation of palaeoweathering features and successive silicifications in the Tertiary regolith of inland Australia
Authors: Thiry Médard , Milnes Anthony R. , Rayot Véronique , Simon-CoinÇon Régine
Published: June 2006

Detailed studies of morphological, micromorphological and geochemical characteristics of silcretes in the deep bleached and weathered regolith across a large area of inland Australia have provided a new interpretation of the history of the regolith and its climatic and morphological evolution during the Tertiary. Pedogenic silcretes have distinctive morphological and mineralogical features caused by a succession of phases of silica dissolution and recrystallization resulting from multiple episodes of water infiltration and percolation under alternately wet and dry climates. These are the oldest of the regolith features. Deep, bleached profiles formed over a wide area in a variety of substrates ranging from Precambrian granites to Palaeozoic sandstones, Cretaceous sediments and Tertiary deposits, and represent the second major stage in regolith development. These profiles, in which kaolinite coexists with gypsum, alunite and opal, formed by reaction of the substrates with saline groundwaters, the water-table levels of which progressively fell over the region. Extensive networks of termite burrows constructed to great depth in the bleached regolith followed the water tables down. The climate was warm and dry with a high water deficit. Groundwater silcretes formed near-horizontal lenses and pods of porcellanite and jasper in the bleached regolith. They preserve the primary fabric of the host rock. Groundwater silcretes post-date the construction of termite burrows and were formed during a rise in groundwater tables across the landscape, in places to near-surface environments in broad landscape depressions. The climate was more humid but the presence of gypsum during silicification demonstrates that the groundwaters were still saline. Red–brown hardpans are the youngest silicification features and represent periods of successive infiltration and percolation, and waterlogging, during high rainfall or flood events. They are confined to low regions in the landscape. Mineralogical and geochemical analysis of the bleached profiles, together with geochemical modelling, suggests that ferrolysis is the most likely cause of acidity in groundwater leading to the development of the bleach profiles and/or alunite. Present-day groundwater tables are both at low levels and sulphate-rich. It is possible that acidic alteration leading to bleaching is still active around the extensive playa landscapes in the region.
Sequence architecture of ancient rocky shorelines and their response to sea-level change: an Early Jurassic example from South Wales, UK
Authors: Sheppard T. Huw
Published: June 2006

The sea-cliffs of Ogmore-by-Sea in Glamorgan, South Wales, expose a succession of Early Jurassic nearshore carbonates that drape rocky palaeoplatforms. A sequence-stratigraphic interpretation allows the recognition of four retrogradationally stacked parasequences, the internal facies architecture of each of which is controlled by the bathymetry and geometry of the underlying shore platforms. Preserved facies are interpreted as representative of foreshore, shoreface and offshore environments. Supratidal facies are absent, but representative storm-terrace clast assemblages are preserved in all lithofacies as a result of the cannibalization of the backshore during periods of shoreline retreat driven by sea-level rise. Biostratigraphical calibration allows the reconstruction of sea-level history and the correlation of regionally important flooding surfaces in the Rhaetian–Sinemurian of Southern Britain with the position of the contemporary shoreline. This suggests that platform incision in South Wales occurred several million years before the onset of major deposition; superseding deposits above ancient rock shore platforms may therefore not be representative of the environment in which coastal incision took place. As one of the best examples of its kind, the rockshore at Ogmore acts as a deposystem model for ancient rocky shores worldwide.
Fate of calcite, apatite and feldspars in an ombrotrophic peat bog, Black Forest, Germany
Authors: Le Roux Gaël , Laverret Emmanuel , Shotyk William
Published: June 2006

The distribution of primary minerals in a peat profile was investigated in a dated core (
210
Pb,
14
C) taken from the upper part of an ombrotrophic bog. Using XRD, the most abundant minerals present in the peat were those of the local granite, suggesting that the dust entering the bog is mainly of local origin. Apatite and calcite are restricted to the top 8 cm of the profile, which suggests rapid dissolution. The release of P by apatite dissolution is possibly the main source of plant-available P to the oligotrophic waters. In contrast, quartz and feldspars appear to be preserved for thousands of years despite the low pH and abundance of organic acids. This study suggests that ombrotrophic peat bogs could be valuable archives of aluminosilicate deposition since the Late Glacial.
Structure and evolution of hydrothermal vent complexes in the Karoo Basin, South Africa
Authors: Svensen Henrik , Jamtveit BjØrn , Planke Sverre , Chevallier Luc
Published: June 2006

The Karoo large igneous province, formed at
c
. 183 Ma, is characterized by the presence of voluminous basaltic intrusive complexes within the Karoo Basin, extrusive lava sequences and hydrothermal vent complexes. These last are pipe-like structures, up to several hundred metres in diameter, piercing the horizontally stratified sediments of the basin. Detailed mapping of two sediment-dominated hydrothermal vent complexes shows that they are composed of sediment breccias and sandstone. The breccias cut and intrude tilted host rocks, and are composed of mudstone and sandstone fragments with rare dolerite boulders. Sandstone clasts in the breccias are locally cemented by zeolite, which represents the only hydrothermal mineral in the vent complexes. Our data document that the hydrothermal vent complexes were formed by one or a few phreatic events, leading to the collapse of the surrounding sedimentary strata. We propose a model in which hydrothermal vent complexes originate in contact metamorphic aureoles around sill intrusions. Heating and expansion of host rock pore fluids resulted in rapid pore pressure build-up and phreatic eruptions. The hydrothermal vent complexes represent conduits for gases and fluids produced in contact metamorphic aureoles, slightly predating the onset of the main phase of flood volcanism.
The Professional Development of an Entomologist
Authors: Michener Charles D.
Published: June 2006

An account of the development of biological interest, and specifically interest in bees, by Charles D. Michener. Included topics are the role of graduate students and the relationship between behavioral studies and systematics. Sections are (a) upbringing, including initiation of biological interests, (b) early studies of bees, (c) student work at the University of California, Berkeley, (d) work at the American Museum of Natural History and in the U.S. Army, and (e) work at the University of Kansas, especially wild bee behavior and bee systematics.
Surviving the Breakup: The DNA Damage Checkpoint
Authors: Harrison Jacob C. , Haber James E.
Published: June 2006

In response to even a single chromosomal double-strand DNA break, cells enact the DNA damage checkpoint. This checkpoint triggers cell cycle arrest, providing time for the cell to repair damaged chromosomes before entering mitosis. This mechanism helps prevent the segregation of damaged or mutated chromosomes and thus promotes genomic stability. Recent work has elucidated the molecular mechanisms underlying several critical steps in checkpoint activation, notably the recruitment of the upstream checkpoint kinases of the ATM and ATR families to different damaged DNA structures and the molecular events through which these kinases activate their effectors. Chromatin modification has emerged as one important component of checkpoint activation and maintenance. Following DNA repair, the checkpoint pathway is inactivated in a process termed recovery. A related but genetically distinct process, adaptation, controls cell cycle re-entry in the face of unrepairable damage.
Cellular Responses to DNA Damage: One Signal, Multiple Choices
Authors: Su Tin Tin
Published: June 2006

DNA double-strand breaks (DSBs) produce a number of cellular responses, some mutually exclusive. Depending on where on the chromosome it occurs, a DSB may become preserved inside a telomere or eliminated by repair. A cell may arrest division via checkpoint activation to fix DSBs or commit suicide by apoptosis. What determines the outcome: to bury, fix, or succumb to DNA DSBs? With this question in mind, we review recent data on cellular responses to DSBs.
Dense Matter in Compact Stars: Theoretical Developments and Observational Constraints
Authors: Page Dany , Reddy Sanjay
Published: June 2006

▪ Abstract  We review theoretical developments in studies of dense matter and its phase structure of relevance to compact stars. Observational data on compact stars, which can constrain the properties of dense matter, are presented critically and interpreted.
Molecular cloning and functional characterization of novel zinc transporter rZip10 (Slc39a10) involved in zinc uptake across rat renal brush-border membrane
Authors: Kaler P. , Prasad R.
Published: June 2006

Previously, in our laboratory a 40-kDa zinc transporter protein was purified and functionally reconstituted in proteoliposomes (Kumar R, Prasad R. Biochim Biophys Acta 1419: 23–32, 1999). Furthermore, we now report the identification of Slc39a10 cDNA encoding the 40-kDa zinc transporter protein by isolating a cloned DNA complementary to zinc transporter mRNA. cDNA was constructed from immunoenriched mRNA encoding the zinc transporter. cDNA was inserted into pBR322 using poly(dC)- poly(dG) tailing. Escherichia coli DH5α cells were transformed, and colonies were screened for zinc transporter cDNA by insertional inactivation. Plasmid DNA was purified from the ampicillin-sensitive clones, and the cDNA was sequenced from both strands. A basic local alignment research tool (BLAST) search of cDNA revealed that it belongs to the Slc39 gene family of zinc transporters and was designated as Slc39a10. Zinc transporter protein deduced on the basis of cDNA sequence was named rZip10 and consists of 385 amino acids with 9 predicted transmembrane domains. The Slc39a10 gene was abundantly expressed in both rat and human tissues. Increased extracellular zinc concentration resulted in upregulation of Slc39a10 in LLC-PK1cells expressing rZip10, which was downregulated at higher zinc concentrations. These cells accumulated more zinc than control cells. rZip10-mediated zinc uptake activity was time-, temperature-, and concentration-dependent and saturable which followed Michaelis-Menten kinetics with a Kmof 19.2 μM and Vmaxof 50 pmol·min−1·mg protein−1. This activity was competitively inhibited by cadmium with Kiof 91 μM. rZip10-mediated zinc uptake was inhibited by COOH group-modifying agents such as DCC. Immunofluorescence studies showed that rZip10 localizes to the plasma membrane of LLC-PK1cells.
Nocturnal polyuria in monosymptomatic nocturnal enuresis refractory to desmopressin treatment
Authors: Kamperis K. , Rittig S. , Jørgensen K. A. , Djurhuus J. C.
Published: June 2006

The transition from day to night is associated with a pronounced decline in diuresis with reductions in the amount of excreted water, electrolytes, and other end products of our metabolism. Failure to do so leads to a large urine output at night, a condition known as nocturnal polyuria, encountered in a large proportion of children with nocturnal enuresis. The aim of this study was to clarify the mechanisms responsible for the nocturnal polyuria seen in enuretics with inadequate response to desmopressin (dDAVP). Forty-six enuretics (7–14 yr of age) and fifteen age-matched controls were admitted for a 24-h protocol with standardized fluid and sodium intake, comprising urine collections, blood sampling, and blood pressure monitoring. We included patients with severe enuresis (5 ± 1 wet nights/wk) showing <50% reduction in wet nights on dDAVP. We characterized the patients on the basis of their nocturnal urine production. The children with nocturnal polyuria excreted larger amounts of sodium and urea at night than nonpolyurics and controls. Solute-free water reabsorption as well as urinary arginine vasopressin and aquaporin-2 excretion were normal in polyurics, and no differences were found in atrial natriuretic peptide, angiotensin II, aldosterone, and renin levels. Urinary prostaglandin E2(PGE2) excretion was significantly higher in polyurics. The nocturnal polyuria in children with dDAVP-resistant nocturnal enuresis seems to be the result of augmented sodium and urea excretion. The high urinary PGE2levels found in these children point toward a role for increased prostaglandin synthesis in the pathogenesis of enuresis-related polyuria.
Lung Function in β-Thalassemia Patients: A Longitudinal Study
Authors: Piatti G. , Allegra L. , Fasano V. , Gambardella C. , Bisaccia M. , Cappellini M.D.
Published: June 2006

Patients with β-thalassemia often present with a restrictive pattern at pulmonary function tests (PFTs) due to several pathogenetic factors. However, the long-term evolution is unknown. We performed a longitudinal study of pulmonary function in asymptomatic, non-smoking patients with β-thalassemia major and intermedia. We looked for temporal changes in lung function and characteristics that would predict the development of PFT abnormalities. In 1996, 18 patients with major β-thalassemia (9 males and 9 females; age range: 18–35 years) and 11 patients with intermediate β-thalassemia (5 males and 6 females; age range: 25–51 years) underwent clinical assessment and PFT, including body plethysmography and gas transfer study (carbon monoxide diffusion capacity, DLCO). Patients were reassessed in 2003. An echocardiographic evaluation was also obtained to exclude pulmonary hypertension. In 55.5% of major and 45.4% of intermediate β-thalassemia patients, a restrictive pattern was found in 1996; in 2003 only 38.8 and 27.2% of patients, respectively, exhibited total lung capacities below the predicted values. DLCO was unchanged in both groups of patients, being reduced in 5 thalassemia major patients and within the normal range in intermediate patients. We conclude that asymptomatic patients with β-thalassemia have a high prevalence of PFT abnormalities, but without significant increases over time. An improvement may be observed when good control of the iron balance is reached with optimal chelation therapy.
Acute Abdomen by Varicella Zoster Virus Induced Gastritis after Autologous Peripheral Blood Stem Cell Transplantation in a Patient with Non-Hodgkin’s Lymphoma
Authors: Scholl S. , Hocke M. , Höffken K. , Sayer H.G.
Published: June 2006

We report on a 54-year-old male patient with an aggressive T cell non-Hodgkin’s lymphoma with abdominal manifestation undergoing autologous peripheral blood stem cell transplantation after high-dose chemotherapy in April 2003. About 4 months after transplantation, he developed severe upper abdominal pain. Ultrasound examination, X-ray, computed tomography of the abdomen and cardiac diagnostics could not explain the symptoms. While empiric therapy with high-dose acyclovir was started, we could document herpetic lesions in the gastric antrum by endoscopy. The epigastric pain rapidly decreased within several days after the start of acyclovir therapy. No herpetic skin lesions were observed at any time during the disease. This report demonstrates the importance of viral-induced gastritis in the differential diagnosis of severe abdominal pain in patients receiving autologous peripheral blood stem cell transplantation.