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Valutazione clinico-patologica di primati sottoposti a xenotrapianto renale: determinazione quali-quantitativa della proteinuria
No full textBackground
Immunological and histopathological features in pig-to-primate renal xenotransplantation are widely studied. Only limited data have been reported about clinical-pathological findings in primate recipients of life-supporting renal xenografts.
In the present study we have evaluated the clinical- pathological parameters especially with regard to hematological parameters and biochemestry. In particular, the presence and the significance of quantitative and qualitative proteinuria were evaluated in xenotransplanted non-human primates in which the kidney function is supported exclusivelly by the transplanted organ.
Methods
Eight captive-bred, bilaterally nephrectomized cynomolgus monkeys (Macaca fascicularis), recipient of a life-supporting transgenic porcine kidney, were included in the present study. Donors were α1,3-galactosyltransferase gene-knockout (GTKO) pigs transgenic for human CD39, CD55, CD59 and fucosyltranferase. Primates were subdivided into two groups accordingly to immunosuppressive therapy. The hematological and biochemical parameters primarily involved in evaluation of renal function have been monitored starting 11 days before transplantation until the end of the experimental study. Quantitative and qualitative analysis of proteinuria, evaluated with urinary protein to creatinine ratio (UPC ratio) and sodium dodecyl sulphate-agarose gel electrophoresis (SDS-AGE) respectively, have been performed.
Results
The main hematological and biochemical changes recorded after transplantation were a progressive anemia, a severe and progressive decrease of total proteins. In urine samples, the measurement of UPC ratio was low before transplantation and increased after transplantation. Similarly, SDS-AGE was negative before transplantation but evidenced bands consistent with mixed (i.e. tubular and glomerular) proteinuria in all the samples collected post-transplantation.
Conclusions
The complete evaluation of clinical and pathological condition of primates undergoing renal xenotransplantation, including monitoring of the blood and urine parameters, is an important diagnostic aid in the daily evaluation of these patients and is thought to be helpful to set any supportive care and increase the profile of welfare in animals.
Moreover, the evaluation of UPC ratio and the use of SDS-AGE technique in urine samples of cynomolgus monkeys recipient of a life-supporting transgenic porcine kidney, may be considered a valid, cheap and less time consuming than more sophisticated technique methods in monitoring the proteinuria in post-transplanted period. Nevertheless, proteinuria and presence of LMW proteins can be consistently found in urine after transplantation, independently on the fluctuations of creatinine values and/or of the status of renal functions.Il modello sperimentale di xenotrapianto renale suino-primate non umano, è stato ampiamente studiato dal punto di vista immunologico ed istopatologico. In letteratura sono presenti solo pochi lavori che hanno come principale obbiettivo, la valutazione clinico-patologica dei soggetti riceventi.
Il nostro lavoro è volto a fornire una valutazione clinico-patologica dei soggetti donatori e dei soggetti riceventi mediante monitoraggio dei parametri ematologici e biochimici, le cui variazioni, in queste specie animali ed in queste condizioni sperimentali, non sono mai state oggetto di studio. Inoltre, il monitoraggio della proteinuria e la sua valutazione quali-quantitativa assumono particolare importanza in questi pazienti nei quali, a causa della nefrectomia bilaterale a cui vengono sottoposti, la funzionalità renale è unicamente sostenuta dall’organo trapiantato.
Materiali e metodi
Nel presente lavoro sono stati valutati otto primati bilateralmente nefrectomizzati (Macaca fascicularis) riceventi un rene di suino donatore α1,3-galactosyltransferase gene-knockout (GTKO) e transgenico per le seguenti proteine: CD39, CD55, CD59 e fucosiltranferasi.
I primati sono stati divisi in due gruppi sperimentali a seconda del protocollo immunosoppressivo utilizzato. I parametri ematologici e biochimici, primariamente coinvolti nella funzione renale, sono stati monitorati quotidianamente a partire dal giorno 11 antecedente al trapianto sino alla fine della vita sperimentale dei primati. Lo studio qualitativo e quantitativo delle proteine urinarie, è stato effettuato mediante il rapporto proteine-creatinina urinaria (UPC ratio) ed elettroforesi in sodium dodecyl sulphate-agarose gel electrophoresis (SDS-age).
Risultati
Le principali alterazioni ematologiche e biochimiche osservate nei primati nel periodo post-trapianto sono state un’anemia progressiva ed un marcato e progressivo decremento delle proteine sieriche. Nei campioni d’urina, la valutazione del rapporto UPC, basso nelle valutazioni pre-trapianto, si presentava aumentato nel periodo post-trapianto. Allo stesso modo lo studio elettroforetico in SDS-age dei campioni di urina del periodo post trapianto ha permesso di identificare bande riferibili a proteinuria mista (tubulare e glomerulare), assenti invece nella fase pre-trapianto.
Conclusioni
La valutazione clinico-patologica completa dei primati sottoposti a xenotrapianto renale comprendente monitoraggio di parametri ematologici ed urinari è di importante ausilio diagnostico nella valutazione quotidiana di questi pazienti e si ritiene possa essere d’aiuto per impostare eventuali terapie di supporto ed accrescere il profilo di benessere negli animali.
La valutazione del rapporto UPC e l’uso della metodica di elettroforesi in SDS-age per l’analisi dei campioni urinari provenienti da primati sottoposti a xenotrapianto renale, rappresentano dei mezzi diagnostici poco costosi, validi e sensibili per il monitoraggio della proteinuria post–trapianto. Tuttavia, nel nostro gruppo sperimentale, la proteinuria e la presenza di proteine LMW è stata riscontrata nei campioni dell’immediato post-trapianto, indipendentemente dalle fluttuazioni della creatinina e/o dalla condizione della funzionalità renale
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
Peripheral nerve sheath myxoma. Clinicopathological and immunohistochemical study of a morphologically distinctive myxoid peripheral nerve sheath tumor in the forelimb of a cat
No full textPeripheral nerve sheath tumors (PNST) are a class of nervous system tumors which arise in both schwann
cells and perineural fibroblasts. Benign and malignant PNSTs are reported to occur in all domestic animals.
In cats they represent 3% of all cutaneous and subcutaneous neoplasms. Only in dogs mixoid PNST has
been observed generally localized in the fingers. In humans, PNSTs are rare neoplasms, and nerve sheath
myxomas are a distinct neoplasia most commonly found in limb extremities
A case of spermatic cord B-cell lymphoma relapsing to the brain in a dog
No full text: A 13-year-old, intact male mixed-breed dog was referred to our clinic for lethargy and asthenia following an episode of gastroenteritis. As an incidental finding during abdominal ultrasound, a mass on the right spermatic cord was seen. Cytology of the mass revealed a monomorphic population of large, round cells with a lymphoid appearance. A bilateral orchiectomy was conducted, and histopathology revealed the presence of a B-cell lymphoma in the right spermatic cord. Based on clinical staging, which showed no involvement of other sites, no additional treatment was administered. Recheck evaluations were scheduled for every 3 mo thereafter. Five months after surgery, the dog developed left central vestibular syndrome with a paradoxical right-sided head tilt. An MRI of the brain showed multifocal lesions and, due to a rapidly worsening clinical condition, the dog was humanely euthanized. The histopathology of the brain lesions was consistent with B-cell lymphoma. Key clinical message: This is the first report of a primary spermatic cord lymphoma relapsing to the brain in a dog. Although rare, spermatic cord tumors should be included among the differential diagnoses for masses arising from the spermatic cord. If lymphoma is diagnosed, location to other sites, especially to the central nervous system, should be considered
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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