1,720,957 research outputs found
Ostarine and Ligandrol Improve Muscle Tissue in an Ovariectomized Rat Model
No full textIn postmenopausal women, hormonal decline changes muscle function and structure. The non-steroidal selective androgen receptor modulators (SARMs) Ostarine (OS) and Ligandrol (LG) have been shown to increase muscle mass and physical function while showing a relative low risk profile. Information about their effects on muscle structure and metabolism is lacking. To analyze this, two experiments were performed using ovariectomized rats as a standard model for postmenopausal conditions. In each experiment, 3-month old Sprague-Dawley rats were divided into five groups (n = 12 to 15). One group remained intact (Non-OVX), the other four groups were ovariectomized (OVX) and remained untreated for eight (OS Experiment) or nine (LG Experiment) weeks. Thereafter, rats of three of the four OVX groups were treated with OS or LG (with doses of 0.04, 0.4, or 4 mg/kg body weight/day) for 5 weeks. Then, uterus, gastrocnemius, and soleus muscles were weighed, fiber size, capillary density, and enzyme activity (lactate dehydrogenase [LDH], citrate synthase [CS], and complex I) were analyzed. In the LG experiment, intramuscular fat content was determined in the quadriceps femoris muscle. All OS treatments resulted in a higher capillary density in the gastrocnemius and longissimus muscles compared with the Non-OVX and the OVX rats, whereas all LG treatments showed a higher capillary density compared with the Non-OVX group. Muscle fiber size and distribution patterns were not changed under either SARM. The CS activity was higher in the longissimus muscle under OS treatment. LG resulted in a higher activity of CS in the gastrocnemius and of LDH in the longissimus muscle. Both SARMs showed an uterotrophic effect, OS at 4 and 0,4 mg dosages, LG at 4 mg dosage. In sum, beneficial effect on muscle vascularization was observed for both SARMs with a stronger impact for OS. LG showed more effect on muscle metabolism. However, a higher muscle weight and intramuscular fat content observed after LG treatment (4 mg) as well as an uterotrophic effect of both SARMs at higher dosages could be considered as an unfavorable side effects and might be a limitation for their application at these dosages.Open-Access-Publikationsfonds 202
Clinical outcomes and quality of life of patients after surgical treatment of a tibia plateau fracture
No full textAbstract Purpose Tibial plateau fractures are serious and challenging injuries of the knee joint, leading to severe long-term complications and permanent functional impairment of the knee joint. The aim of this study was to evaluate the outcome and quality of life after tibial plateau fracture and possible influencing factors. Methods This retrospective cohort study included patients who underwent surgical treatment for tibial plateau fractures between 2017 and 2020 at the University Medical Center, Göttingen. The endpoints of this study were clinical outcomes, complications, length of hospital stay, sporting ability, and the ability to work. Furthermore, quality of life (SF-36 questionnaire), everyday function (Lysholm Knee Score), subjective self-assessment of satisfaction, and the influence of health insurance status were analyzed. Results A total of 117 patients were included, 55 of whom completed the questionnaires. The mean length of hospital stay was 21 (± 17) days. The most common postoperative complications were wound infection and pseudarthrosis (7.7%). Of the 55 patients who completed the questionnaire, 85.7% regained their ability to work after 28 weeks of incapacity for work. Sporting ability was regained in 31% of the 55 patients. Whereas the subjective satisfaction in our patients was good (56.6% satisfied, 20.8% rather satisfied), the result of the Lysholm score was “poor” on average (mean 63 ± 27) and the SF-36 scores were worse on average compared to the normal population. A correlation between lower BMI and a better outcome was shown by better results in both the Lysholm score and SF-36 dimension (physical functioning). Conclusion Our study could underline that fractures of the tibial plateau are still an injury that have major impact on the quality of life of those affected. We were able to determine increased body weight as a parameter with a negative influence on physical function scores and psychological and emotional well-being. The clinical results were independent of health insurance status in Germany
The influence of the selective androgen receptor modulator Enobosarm on the skeletal muscles in the model organism of the osteoporotic rat
No full textSarkopenie ist eine oft unterdiagnostizierte Erkrankung welche häufig komorbide zur
Osteoporose auftritt. Wir untersuchten die Wirkung des selektiven Androgenrezeptor-
Modulators (SARM) Enobosarm auf die Skelettmuskulatur am Modell der ovariektomierten
Ratte. Drei Monate alte Sprague Dawley Ratten wurden in fünf Gruppen unterteilt. Vier
Gruppen wurden ovarektomiert um postmenopausale Bedingungen zu schaffen. An drei der
ovarektomierten Versuchstiergruppen (SARM 1(n=11), 2(n=10), und 3(n=11)) wurde
Enobosarm in den folgenden Wirkstoffdosierungen 0,04 mg/kg/KG, 0,4 mg/kg/KG und 4,0
mg/kg/KG getestet. Die vierte ovariektomierte Gruppe (OVX (n=9)) diente als kranke, die nicht
ovariektomierte Gruppe fünf (Non OVX (n=10)) als gesunde Kontrollgruppe. Acht Wochen
nach Ovariektomie bekamen die Gruppen SARM 1 bis 3 für insgesamt fünf Wochen eine
Therapie mit Enobosarm über sojafreies Futter. Nach fünfwöchiger Behandlung wurden der M.
Gastrocnemius, M. Soleus, ein Teil des M. Longissimus und die Uteri entnommen, sowie die
jeweiligen Gewichte ermittelt. Aus dem Blut wurden die Kreatinkinase, Magnesium- und
Kalzium-Konzentrationen bestimmt. Aus den Muskelproben wurden mit Hilfe eines Kryotoms
12 μm Dünnschnitte angefertigt und histologische Untersuchungen durchgeführt. Das
Verhältnis von Kapillaren zu Muskelfasern, das Verhältnis der Muskelfasertypen und die
Muskelfasergrößen wurden in Folge bestimmt. Zusätzlich wurden die Enzymaktivitäten der
Citrat-Synthase, Laktatdehydrogenase und Komplex-1 in der Skelettmuskulatur analysiert.
Die Uteri der Gruppen OVX und SARM 1 waren signifikant leichter im Vergleich zu Non
OVX, was sich durch den reduzierten Östrogenspiegel nach Ovariektomie erklären lässt. Die
Uteri der Gruppen SARM 2 und SARM 3 zeigten eine signifikante Gewichtszunahme im
Vergleich zu OVX und SARM 1. Sie haben jedoch nicht das Gewicht der gesunden
Vergleichsgruppe Non OVX erreicht. Dieses spricht für eine dosisabhängige Wirkung am
Uterus über dort vorhandene Androgenrezeptoren. Hinterfragen muss man hier drohende
Langzeitfolgen mit einer im schlimmsten Fall hormonell stimulierten Malignom-Entwicklung
im Bereich des Uterus.
In der Muskulatur, beispielhaft gezeigt am M. Gastrocnemius und M. Longissimus, kam es
unter Therapie zu einer zunehmenden Kapillarisierung. Dieser Effekt stieg mit steigender
Wirkstoffdosierung. Eine zunehmende Angiogenese unter Therapie mit Enobosarm lässt sich
über eine vergleichbare Wirkung von Testosteron erklären.
Es zeigten sich keine signifikanten Änderungen im Verhältnis von Typ-1- zu Typ-2-
Muskelfasern unter Therapie mit Enobosarm. Dieses wurde auch nach Testosteron-Therapie
berichtet. Bezüglich der Muskelfaserflächen und
–durchmesser ergaben die Auswertungen eine tendenzielle Größenzunahme der glykolytischen
Muskelzellen. Von einer Zunahme der Muskelkraft und der fettfreien Körpermasse, unter
Therapie mit SARMs, ist bereits früher berichtet worden. Eine fünf Wochen dauernde Therapie,
wie in unserem Versuch, ist anscheinend nicht ausreichend um einen signifikanten Effekt auf
die Muskelfasergrößen zu erzielen.
Die Aktivität der Citrat-Synthase der Gruppe SARM 3 war im M. Longissimus signifikant
erhöht gegenüber der Gruppe Non OVX. Im Falle der anderen Muskeln konnte eine
tendenzielle Aktivitätssteigerung der CS-Aktivität, v. a. in den Therapiegruppen SARM 2 und
SARM 3 gezeigt werden. Diese spricht wiederum für eine dosisabhängige Wirkung, wie auch
schon beispielhaft am Uterus gezeigt und deutet auf einen aktivitätssteigernden Effekt von
Enobosarm auf den Zellmetabolismus hin. Bezüglich der Laktatdehydrogenase und des
Komplex-1 konnten keine signifikanten Aktivitätsunterschiede nachgewiesen werden. Es
erscheint, dass Enobosarm keinen messbaren Effekt auf die Glykolyse und Atmungskette in
unserem Modell unter den gegebenen Voraussetzungen hat.
In der Analyse des Serums fanden sich keine signifikanten Veränderungen von Magnesium,
Kalzium und der Kreatinkinase (CK). Der fehlende Anstieg der CK-Aktivität spricht gegen
einen durch Enobosarm induzierten Muskelzellschaden. Der Elektrolythaushalt im Serum blieb
ebenfalls unverändert.
Enobosarm zeigte insgesamt eine dosisabhängige anabole Wirkung auf die Skelettmuskulatur
und den Zellmetabolismus. Es kam zu einer verbesserten Blutversorgung der Muskulatur durch
eine zunehmende Kapillarisierung und einer Enzymaktivitätssteigerung (gezeigt an der Citrat-
Synthase). Tendenziell lässt sich ebenfalls eine Größenzunahme der Muskelfasern erkennen.
Bei länger andauernder Therapie wären noch größere Effekte zu erwarten. Diese Effekte
könnten durch die Analyse weiterer Faktoren, wie der vaskulären endothelialen
Wachstumsfaktoren sowie einer Gelelektrophorese der Isoformen der Myosinschwerketten im
Skelettmuskel und einer Analytik der Androgenrezeptoren im Uterus, weiter untersucht
werden. Dieses könnte Gegenstand weiterer Forschungsarbeiten mit Enobosarm sein. Fraglich
stellt sich die perspektivische Zulassung von Enobosarm für die Indikation der Sarkopenie,
Osteoporose und einer komorbiden Sarko-Osteoporose, da das Bestreben der Firma GTx Inc.®
bezüglich einer Zulassung bei Sarkopenie verworfen und auf andere Erkrankungen, wie u. a.
die Tumorassoziierte-Kachexie bei onkologischen Patienten verlagert wurde. Diese Patienten
leiden häufig nicht nur an Sarkopenie, sondern auch an einer Osteoporose. Unsere Studie
bezieht sich jedoch auf die präventive Wirkung bezüglich einer Sarkopenie, am
Modellorganismus der für postmenopausale Bedingungen. Bei ggf. folgenden Studien sollte
dieser Aspekt bedacht werden, auch mit dem Hintergrund weiterer noch unbekannter
Nebenwirkungen an anderen Organen, wie z. B. dem Herzen, dem Uterus und der Leber.Sarcopenia is a often underdiagnosed disease that is usually accomplished osteoporosis. We
examined the effect of the selective androgen receptor modulator (SARM) Enobosarm on the
skeletal muscles, using the ovariectomized rat as a model for postemonopausal conditions.
Three-month-old Sprague Dawley rats where divided into five groups. Four groups were
ovariectomized. In three of the ovariectomized groups (SARM 1(n=11), 2(n=10), und 3(n=11)),
Enobosarm was applied at following doses 0.04 mg / kg / KG, 0.4 mg / kg / KG and 4.0 mg /
kg / KG. The fourth ovariectomized group (OVX) served as a sick control group, whereas the
non-ovariectomized group five (Non OVX) as a healthy control group. Eight weeks after
ovariectomy, groups SARM 1 to 3 received therapy with Enobosarm mixed with soy free feed
for five weeks. After five weeks of treatment, the M. Gastrocnemius, M. Soleus, part of the M.
Longissimus and the Uteri were removed and the weights were determined. Blood was sampled
for the analysis of creatine kinase, magnesium and calcium concentrations. Thin 12 μm sections
of the muscles were made with a cryotome for hystological examinations. The ratio of
capillaries to muscle fibers, the ratio of muscle fiber types and muscle fiber sizes were also
determined. In addition, the enzyme activities of citrate synthase, lactate dehydrogenase and
complex-1 were analyzed in the skeletal muscles.
The uteri of the OVX and SARM 1 groups were significantly lighter compared to non OVX.
That can be explained by the reduced estrogen level after ovariectomy. The uteri of the SARM
2 and SARM 3 groups showed a significant weight gain compared to OVX and SARM 1, but
did not reach the weight of the healthy Non OVX group. This indicates a dose-dependent effect
of Enobosarm on the uterus via the androgen receptors present there. This raises to the question
about long-term influence and development in the worst case, hormone-stimulated malignant
in the uterus.
In Gastrocnemius and Longissimus muscles, there was increasing capillarization during
therapy. This effect enhanced with increasing drug dosage. An increasing angiogenesis during
therapy with SARM can be explained by a comparable effect of testosterone.
There were no significant changes in the ratio of type 1 to type 2 muscle fibers when treated
with Enobosarm. Similarly, it was previously reported after therapy with testosterone.
Regarding the muscle fiber areas and - diameter, the evaluations showed a tendency to increase
the size of the glycolytic cells. An increase in muscle strength and lean body mass during
therapy with SARMs has been reported previously. A five-week therapy, as in our experiment,
apparently is not sufficient to have a significant effect on the muscle fiber size.
The activity of citrate synthase was significantly increased in M. Longissimus in SARM 3 group
compared to the Non OVX group. In other muscles, a tendency to increased activity of CS was
shown in the therapy groups SARM 2 and SARM 3. This points out a dose-dependent effect,
as already shown in the uterus, and indicates an activity-increasing effect of Enobosarm on
muscle cell metabolism. With regard to lactate dehydrogenase and complex-1 activities, no
significant differences could be revealed. It appears that Enobosarm has no measurable effect
on the glycolysis and respiratory chain in our model under the given conditions.
No significant changes in magnesium, calcium and creatine kinase (CK) were found in serum.
The lack of an increase in CK activity speaks against muscle cell damage induced by
Enobosarm. The electrolyte balance also remained unchanged in serum.
Enobosarm showed an overall dose-dependent anabolic effect on skeletal muscles and cell
metabolism. There was an improved blood supply to the muscles through increasing
capillarization and an increase in enzyme activity (shown on the citrate synthase). There is also
a tendency to see an increase in size of the muscle fibers. With a long-term therapy, a stronger
effect could be suggested. These processes could be further analyzed by investigating other
factors, such as the expression of vascular endothelial growth factor, gel electrophoresis of
myosin heavy-chain isoforms in skeletal muscle and analysis of androgen receptors in uterus.
This could be a subject of further research on Enobosarm.
The perspective for the approval of Enobosarm for the indication of sarcopenia, osteoporosis
and comorbid sarco-osteoporosis is questionable since the efforts by GTx Inc.® regarding
approval for sarcopenia have been rejected and shifted to other diseases such as tumorassociated
cachexia in oncological patients. These patients suffer often not only from
sarcopenia, but also from osteoporosis. However, our study was focused on the preventive
effect with regard to sarcopenia in the rat model for postmenopausal conditions. In the
following studies this should be taken into account, if necessary, also other unknown side
effects on the organs, such as heart, uterus and liver could be investigated.2020-03-1
Going Beyond Counting First Authors in Author Co-citation Analysis
Full text linkThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
Variations on the Author
Full text link“Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship
Appropriate Similarity Measures for Author Cocitation Analysis
Full text linkWe provide a number of new insights into the methodological discussion about author cocitation analysis. We first argue that the use of the Pearson correlation for measuring the similarity between authors’ cocitation profiles is not very satisfactory. We then discuss what kind of similarity measures may be used as an alternative to the Pearson correlation. We consider three similarity measures in particular. One is the well-known cosine. The other two similarity measures have not been used before in the bibliometric literature. Finally, we show by means of an example that our findings have a high practical relevance.information science;Pearson correlation;cosine;similarity measure;author cocitation analysis
Dispelling the Myths Behind First-author Citation Counts
Full text linkWe conducted a full-scale evaluative citation analysis study of scholars in the XML research field to explore just how different from each other author rankings resulting from different citation counting methods actually are, and to demonstrate the capability of emerging data and tools on the Web in supporting more realistic citation counting methods. Our results contest some common arguments for the continued
use of first-author citation counts in the evaluation of scholars, such as high correlations between author rankings by first-author citation counts and other citation
counting methods, and high costs of using more realistic citation counting methods that are not well-supported by the ISI databases. It is argued that increasingly available digital full text research papers make it possible for citation analysis studies to go beyond what the ISI databases have directly supported and to employ more
sophisticated methods
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