Literatura académica sobre el tema "Wasting syndrome"

Central neurogenic diabetes insipidus, syndrome of inappropriate secretion of antidiuretic hormone, and cerebral salt-wasting syndrome are secondary events that affect patients with traumatic brain injury. All 3 syndromes affect both sodium and water balance; however, they have differences in pathophysiology, diagnosis, and treatment. Differentiating between hypernatremia (central neurogenic diabetes insipidus) and the 2 hyponatremia syndromes (syndrome of inappropriate secretion of antidiuretic hormone, and cerebral salt-wasting syndrome) is critical for preventing worsening neurological outcomes in patients with head injuries.

AbstractTraumatic brain injury (TBI) is on the rise, especially in today’s fast-paced world. TBI requires not only neurosurgical expertise but also neurointensivist involvement for a better outcome. Disturbances of sodium balance are common in patients with brain injury, as the central nervous system plays a major role in sodium regulation. Hyponatraemia, defined as serum sodium <135 meq/L is commonly seen and is especially deleterious as it can contribute to cerebral oedema in these patients. Syndrome of inappropriate antidiuretic hormone secretion (SIADH), is the most well-known cause of hyponatraemia in this subset of patients. Cerebral Salt Wasting Syndrome (CSWS), leading to renal sodium loss is an important cause of hyponatraemia in patients with TBI. Although incompletely studied, decreased renal sympathetic responses and cerebral natriuretic factors play a role in the pathogenesis of CSWS. Maintaining a positive sodium balance and adequate hydration can help in the treatment. It is important to differentiate between SIADH and CSWS when trying to ascertain a case for patients with acute brain injury, as the treatment of the two are diametrically opposite.

OBJECTIVE: To review the pathophysiology and treatment of HIV wasting syndrome. DATA SOURCES AND STUDY SELECTION: MEDLINE searches (January 1987–September 1997) of the English-language medical literature were conducted. Bibliographies were also selected during a manual review. DATA SYNTHESIS: HIV-related weight loss, often referred to as HIV wasting syndrome, is a common manifestation of advanced HIV infection. Wasting in HIV involves the preferential loss of lean body mass with a paradoxical preservation of body fat. The etiology of wasting appears to be the result of many factors, which may include decreased caloric intake, malabsorption, alterations in energy expenditure and metabolism, cytokine effects, and endocrine dysfunction. Pharmacologic treatment options include appetite stimulants (e.g., dronabinol, megestrol acetate), cytokine inhibitors (e.g., thalidomide, cyproheptadine, ketotifen, pentoxifylline, fish oil, N-acetylcysteine), and anabolic agents (e.g., testosterone, nandrolone, oxandrolone, recombinant human growth hormone). CONCLUSIONS: Wasting associated with HIV has a high morbidity and mortality rate if not adequately managed. Therapeutic strategies include appetite stimulants, cytokine inhibitors, and growth-promoting agents. Selection of the appropriate agent(s) depends on the underlying cause for weight loss, adverse effects, and cost of therapy. OBJETIVO: Revisar la patofisiología y tratamiento del síndrome de desgaste causado por el VIH. FUENTES DE DATOS: Se llevó a cabo una búsqueda de la literatura médica en el idioma inglés utilizando la base de datos del MEDLINE. SÍNTESIS: La pérdida de peso asociado al VIH, también conocido como el síndrome de desgaste, es una manifestación común de la infección avanzada causada por el virus. El desgaste envuelve principalmente la pérdida de masa magra, y paradójicamente la preservación de grasa corporal. La etiología del síndrome de desgaste aparenta ser el resultado de varios factores que pueden incluir la disminución de ingesta calórica, malabsorción, alteración en la utilización de energía, alteración del metabolismo, efectos de las citoquinas, y disfunción endocrina. Las opciones para el tratamiento farmacológico incluyen estimuladores del apetito (dronabinol y acetato de megestrol), inhibidores de citoquinas (talidomida, ciproheptadina, ketotifen, pentoxyfilina, accite de pescado, y N-acetil cisteína), y agentes anabólicos (testosterona, nandrolona, oxandrolona, y la hormona de crecimiento). CONCLUSIONES: La etiología del desgaste asociado a la infección con el VIH es multifactorial. La condición conlieva una alta morbilidad y mortalidad si no es manejada adecuadamente. Las estrategías terapéuticas incluyen la estimulación de apetito, inhibidores de citoquinas y agentes que promueven el crecimiento. La selección de los agentes apropiados dependerá de la causa de la pérdida de peso, los efectos adversos, y el costo de la terapia. Aunque se necesita estudiar la condición más a fondo, la terapia combinada puede ser que resulte ser la modalidad de mayor beneficio para el paciente con el síndrome de desgaste por el VIH. OBJECTIF: Réviser la pathophysiologie et le traitement du syndrome d'émaciation associé au VIH. REVUE DE LITTÉRATURE ET SÉLECTION DES ÉTUDES: Une recherche de la documentation médicale de langue anglaise a été effectuée à l'aide de MEDLINE. Des bibliographies ont aussi été choisies grâce à une révision manuelle. RÉSUMÉ: La perte de poids associée au VIH, souvent appelée le syndrome d'émaciation, est une manifestation fréquente d'une infection avancée au VIH. l'émaciation chez les patients infectés par le VIH entraîne une perte préférentielle du tissu maigre et une conservation du tissu adipeux. l'étiologie du syndrome semble être le résultat de plusieurs facteurs dont l'ingestion calorique, la malabsorption, les modifications au niveau de la dépense énergétique et du métabolisme, les effets des cytokines, et les anormalités endocriniennes. Les options du traitement pharmacologique incluent les stimulants de l'appétit (le dronabinol et l'acétate de mégestrol), les inhibiteurs des cytokines (le thalidomide, la cyproheptadine, le kétotifène, la pentoxifylline, l'huile de poisson, et le N-acétylcystéine), et des agents anabolisants (la testostérone, le nandrolone, l'oxandrolone, et l'hormone de croissance humaine recombinée). CONCLUSIONS: Le syndrome d'émaciation associé au VIH a un taux de morbidité et de mortalité élevé s'il n'est pas adéquatement traité. Les stratégies thérapeutiques incluent les stimulants de l'appétit, les inhibiteurs des cytokines, et les agents stimulant la croissance. La sélection du ou des agents appropriés dépendra de la cause sous-jacente de la perte de poids, des effets indésirables, et du coût de la thérapie.

La síndrome d'aprimament post-deslletament (SAPD) és considerada com una malaltia porcina d'origen multifactorial en la qual el Circovirus porcí tipus 2 (CP2) és l'agent infecciós essencial. L'objectiu de la present tesi doctoral era expandir el coneixement en l'epidemiologia de la infecció per CP2 i el SAPD a través de la realització d'estudis de cas-control a nivell de camp. De manera general, es va investigar la potencial influència de la genètica del CP2, el moment d'infecció del CP2, els anticossos contra CP2 derivats de la immunitat maternal i la resposta humoral dels porcs contra el CP2, en la presentació de la SAPD.
En el primer estudi (estudi I) es van estudiar seqüències de PCV2 de porcs amb diferent condició clínica i patològica. Els resultats van confirmar l'existència de dos genogrups principals i es va proposar la definició de dos genotipus de CP2 (1 i 2). La metodologia suggerida per definir els genotipus està basada en la distribució de la relació p-distància/freqüència de les seqüències de CP2 conjuntament amb anàlisis filogenètics de CP2. Es va observar que el genotipus 1 era predominant en porcs de granges afectades per SAPD. Contràriament, totes les seqüències obtingudes de granges no afectades per la SAPD corresponien al genotipus 2. Així, es va suggerir que el genotipus 1 de CP2 podria ser potencialment més patogènic que el genotipus 2. Addicionalment, es va descriure la presència dels dos genotipus en el mateix moment en porcs individuals procedents de granges afectades per la SAPD.
La present tesi doctoral es va desenvolupar dins del marc del projecte de la Unió Europea (UE) titulat Control de les malalties associades al Circovirus porcí (MACP): Cap a la Millora en la Qualitat i Seguretat Alimentàries (www.pcvd.org), la qual era finançada pel 6è programa marc de la UE. El consorci de la UE d'aquest porjecte va publicar la carta presentada com a addendum de l'estudi I. En aquesta carta es va donar suport a la definició de genotipus proposada, a la vegada que es va proposar la nomenclatura de genotipus a de CP2 (CP2a) i genotipus b (CP2b), corresponent als genotipus 2 i 1, respectivament, per tal d'evitar confusions amb la ja existent diferenciació entre PCV2 i PCV1.
En el segon estudi (estudi II) es van comparar dues tècniques de PCR quantitativa (qPCR) de PCV2. Els resultats mostraven una associació lineal significativa entre les dues tècniques, i un biaix sistemàtic de 1.4 log10 copies of CP2 per mil·lilitre de mostra. Aquesta diferència indicava que la tècnica del laboratori danès generava un resultat sistemàticament més elevat que el generat a través de la tècnica del laboratori espanyol. A més, la tècnica del laboratori danès mostrava major sensibilitat que la tècnica del laboratori espanyol.
En els treballs III i IV es van realitzar estudis longitudinals de tipus cas-control en granges afectades per la SAPD de Dinamarca i Espanya tot utilitzant dissenys similars. Es van observar patrons similars en la dinàmica d'infecció per CP2 tant a Espanya com a Dinamarca, amb un retard en l'edat de presentació de la SAPD a Espanya en comparació a Dinamarca. El diagnòstic individual de la SAPD es va confirmar, mitjançant tests laboratorials, en només la meitat dels porcs en els quals hi havia la sospita clínica. Globalment, els resultats van mostrar que la quantitat de CP2 incrementava concomitantment a la caiguda dels nivells d'anticossos maternals, assolint valors màxims de càrrega vírica en el moment d'aparició dels símptomes clínics. De manera interessant, la reacció de fase aguda (RFA) en porcs afectats per la SAPD s'observava paral·lelament a l'evolució de la virèmia per CP2, suggerint que el CP2 és el principal responsable de l'estat d'inflamació sistèmica que pateixen els porcs afectats per aquesta malaltia. Col·lectivament, els porcs afectats tenien quantitats de CP2 i concentracions de porc-MFA i HPT superiors en sang, excretaven càrregues víriques superiors tant per via nasal com a través de les femtes, i tenien nivells inferiors d'anticossos maternals enfront al CP2 que els porcs que no estaven afectats per la SAPD. Addicionalment, es va observar una menor resposta humoral en els porcs afectats per la SAPD provinents d'Espanya a les 11 setmanes de vida (abans de l'aparició dels símptomes clínics) i en el moment de la necròpsia, suggerint que aquesta circumstància era podria associar-se com a causa més que no pas una conseqüència de la malaltia. D'altra banda, la falta de sensibilitat i/o especificitat observades de les tècniques de qPCR i/o de serologia suggereixen que aquestes tècniques no poden substituir la histopatologia més la detecció de CP2 en teixits per l'establiment del diagnòstic individual de la SAPD. Malgrat això, els resultats indicaven que la qPCR podria ser potencialment útil per diagnosticar la SAPD a nivell poblacional. Addicionalment, els resultats obtinguts donaven suport a la idea que, malgrat que les PFA són marcadors inespecífics d'inflamació, aquestes proteïnes podrien ser marcadors útils de salut, esdevenint una eina potencialment útil per monitoritzar el desenvolupament de la SAPD en estudis epidemiològics o per la valoració de l'eficàcia de vacunes de CP2 a nivell de camp.
Postweaning multisystemic wasting syndrome (PMWS) is considered a multifactorial pig disease in which Porcine circovirus type 2 (PCV2) is the essential infectious agent. The present thesis aimed to expand the epidemiological knowledge on PCV2 infection and PMWS through the realization of case-control field studies. Mainly, the potential influence of PCV2 genetics, the timing of PCV2 infection, the PCV2 maternal derived humoral immunity and the pig humoral response against PCV2 infection in PMWS presentation were investigated.
In the first study consisted in the sudy of PCV2 sequences obtained from pigs with different clinical and pathological conditions. Results further confirmed the existence of two main genogroups and the definition of two PCV2 genotypes (1 and 2) was proposed. The suggested methodology to define PCV2 genotypes is based on the p-distance/frequency distribution of PCV2 sequences together with PCV2 phylogenetic analyses. Genotype 1 was shown to be predominant within pigs coming from PMWS affected farms, while all sequences obtained from non-PMWS affected farms corresponded to genotype 2. Consequently, it was suggested that PCV2 genotype 1 might potentially be more pathogenic than PCV2 genotype 2. In addition, infection of single pigs from PMWS affected farms harbouring both genotypes at the same time was described.
The present thesis was developed within the European Union (EU) project entitled Control of Porcine Circovirus Diseases (PCVD): Towards Improved Food Quality and Safety (www.pcvd.org), which was funded by the EU Sixth Framework Programme. The EU consortium on PCVD published the letter here presented as an addendum of study I. In this letter it was supported the genotype definition, but it was also proposed the nomenclature of PCV2 genotype a (PCV2a) and genotype b (PCV2b), corresponding to genotypes 2 and 1, respectively, in order to avoid potential confusions with the already existent PCV2 and PCV1.
In the second study (Study II) two different real-time quantitative PCR (qPCR) assays were compared. Results showed a significant linear association between the assays, and a systematic difference of 1.4 log10 copies of PCV2 per millilitre of sample. This difference indicated that the assay from the Danish laboratory yielded a higher output than the assay from the Spanish laboratory. Moreover, the Danish assay had higher sensitivity than the Spanish one.
In studies III and IV, longitudinal case-control studies were performed in PMWS affected farms from Denmark and Spain using similar designs. Similar PCV2 infection dynamic patterns were observed in Spain and Denmark, with a delay in PMWS age-presentation in Spain compared to the one in Denmark. Results showed that PCV2 load increased concomitantly to maternal antibody level waning, reaching the maximum viral load concurrently with the development of clinical signs. Interestingly, the acute phase response (APR) in PMWS affected pigs occurred in parallel to PCV2 viremia, suggesting that PCV2 is the main responsible for the systemic inflammatory status suffered by diseased pigs. As a collective, PMWS affected pigs harboured higher PCV2 loads and higher Pig-MAP and HPT concentrations in sera, shed higher viral loads through both nasal secretions and faeces, and had lower level of maternal antibodies against PCV2 than non-PMWS affected pigs. Furthermore, an impaired humoral response was observed in PMWS affected pigs from Spain at 11 weeks of age (prior to the appearence of clinical signs) and at the moment of necropsy, suggesting that this circumstance might be more a cause rather than a consequence of the disease. On the other hand, the lack of sensitivity and/or specificity observed from qPCR and/or serological techniques suggests that those techniques are not able to substitute histopathology plus detection of PCV2 in tissues for the individual PMWS diagnosis. However, results indicated that qPCR might potentially be a reliable technique to diagnose PMWS on a population basis. Additionally, obtained results supported the idea that although APPs are unspecific markers of inflammation, they might be useful indicators of health, becoming a potentially interesting tool to monitor PMWS development in epidemiological studies or in the assessment of the efficacy of PCV2 vaccines in the field.

Weißbüschelaffen (WBA) sind wissenschaftlich häufig genutzte Modelltiere für diverse Humanerkrankungen. Zur Gesunderhaltung dieser Primaten sind grundlegende diagnostische Blutparameter unverzichtbar. Bisher erhobene Daten zeichneten sich jedoch durch große Divergenz aus. Ob Veränderungen in Haltungsbedingungen einen Einfluss auf diese Blutparameter nehmen, ist bis heute unklar. Somit war ein Ziel dieser Arbeit die Erhebung aktueller hämatologischer und klinisch-chemischer Blutparameter von WBA. Zudem wurde der Einfluss der routinemäßigen Umsetzung in eine neue Behausung auf die erhobenen Parameter sowie den Kortisolspiegel im Kot untersucht. Des Weiteren leiden WBA in menschlicher Obhut rezidivierend an gastrointestinalen Erkrankungen, die mittels klinischer Standardparameter allein nicht diagnostizierbar sind. Dabei spielt vor allem die Sensitivität gegenüber Futtermittelinhaltsstoffen (z. B. Gluten) eine Rolle, welche ursächlich im Zusammenhang mit dem Wasting Marmoset Syndrome (WMS) diskutiert wird. Im zweiten Teil der vorliegenden Arbeit sollten deshalb die gastrointestinalen Erkrankungen von in menschlicher Obhut lebenden WBA ätiologisch beleuchtet werden, vor allem hinsichtlich einer möglichen Sensitivität gegenüber Gluten. Im ersten Teil dieser Studie wurden von 54 WBA hämatologische und klinischchemische Richtwerte erhoben. Die ermittelten hämatologischen Blutrichtwerte ähneln denen aus den achtziger Jahren, die Daten der klinischen Chemie nur bedingt: Die Richtwertbereiche von Laktatdehydrogenase, Alaninaminotransferase, Lipase sowie Alkalische Phosphatase und Gesamtbilirubin weichen von den ehemals erhobenen Daten ab. Zudem wurden in der vorliegenden Arbeit geschlechtsabhängige Unterschiede ermittelt: Weibliche Tiere wiesen signifikant höheres mittleres Erythrozytenvolumen und mittleren Hämoglobingehalt des Einzelerythrozyten auf als männliche Tiere, wohingegen bei diesen ein signifikant höheres Gesamt- und Low density lipoprotein- Cholesterol im Vergleich zu weiblichen Affen messbar war. Des Weiteren wurden 16 Tiere über einen vierwöchigen Zeitraum in eine neue Umgebung verbracht, bevor sie in ihre Heimatbehausung zurückkehrten. Durch diese Umsetzung war bei den untersuchten Tieren die Leuko- und Lymphozytenzahl auch vier Wochen nach der Umsetzung erniedrigt. Zeitgleich lag ein erhöhter Kortisolspiegel vor, der im Kot bestimmt wurde. Im zweiten Teil der Studie wurden anhand humandiagnostischer Standards IgAAntikörper (AK) gegen Gliadin (AGA), Gewebstransglutaminase (tTG), deamidiertes Gliadin (ADGA) sowie Glykoprotein 2 (AGP2A) im Plasma von 24 WBA mittels eines ELISAs während glutenhaltiger (Diät 1) und glutenfreier Ernährung (Diät 2) bestimmt. Dabei wurden die klinische Symptomatik von WMS und das Körpergewicht der Tiere ebenfalls untersucht. Zudem erfolgte die Analyse von Kotproben antikörperpositiver Tiere hinsichtlich Qualität und Trockenmassegehalt während Diät 2 und einer darauf folgenden glutenhaltigen Provokationsdiät. Die serologische Diagnostik ergab einen signifikanten Rückgang von AGA, AK gegen tTG und AGP2A während Diät 2 bei Tieren, die nach Diät 1 erhöhte Werte aufwiesen. Diät 2 führte zu einem Rückgang der klinischen Symptome und einer signifikanten Gewichtszunahme bei antikörperpositiven WBA. Die glutenhaltige Provokationsdiät ergab eine verminderte Kotqualität mit einem niedrigeren Trockenmassegehalt. Es wurden im Rahmen dieser Arbeit aktuelle, hämatologische und klinisch-chemische Blutrichtwerte des WBA erhoben. Der durch Umsetzung in eine neue Behausung bedingte Stress ist bei WBA bis vier Wochen lang nachweisbar. Es ist sinnvoll, dies in der zeitlichen Planung wissenschaftlicher Studien zu berücksichtigen, um das Wohlbefinden der Tiere vor Versuchsbeginn sicherzustellen und den Einfluss von Stress auf experimentelle Ergebnisse zu minimieren. Der Nachweis grundlegender, an der Pathogenese der Zöliakie beteiligter Antikörper, in Kombination mit den klinischen Symptomen, deutet auf Glutensensitivität mit ätiologischer Beteiligung an WMS bei WBA hin. Die glutenfreie Ernährung von WBA in menschlicher Obhut ist daher sinnvoll und empfehlenswert
Common marmosets are often used as animal models for human diseases. For their health maintenance, diagnostic blood values are absolutely essential. Previously obtained reference values are characterized by great value-specific differences. Moreover, the influence of routine measures on these blood parameters, e. g. changes in housing conditions, has not been examined yet. Therefore, the first aim of the present study was to update haematological and clinical chemical blood parameters of common marmosets. Further, the influence of stress, caused by relocation to a new housing, on these parameters and the cortisol level in feces was examined. In addition to that, common marmosets under human management are often affected by gastrointestinal diseases, which are difficult to diagnose with basic standard blood values. In this context, sensitivity to nutritional elements, e. g. gluten, plays an important role and is discussed as a potential cause of wasting marmoset syndrome (WMS). In the second part of this study, the recurrent gastrointestinal diseases of common marmosets under human management were aetiologically investigated, with special regard to possible gluten sensitivity. In the first part of this study, blood samples were obtained from 54 female and male common marmosets to evaluate standard values of haematology and clinical chemistry. The determined haematological parameters are similar to the already obtained data, the clinical chemistry values differ somewhat: The enzyme activities of lactate dehydrogenase, alanine aminotransferase and lipase in addition to the ranges of alkaline phosphatase and total bilirubin diverge from the data ascertained in this study. Moreover, female animals presented significantly higher mean corpuscular volume and mean corpuscular haemoglobin than males, whereas male common marmosets showed significantly higher total- and low density lipoprotein-cholesterol, compared to females. Further, 16 animals were relocated to a new environment for a time period of four weeks, before they returned to their home cages. The change of housing caused a decreased leuko- and lymphocyte count in all examined animals that was still measurable four weeks after the relocation. At the same time, an increased fecal cortisol level was determined. The aim of the second study was to investigate the modification of plasma antibodies to gliadin (AGA), tissue transglutaminase (tTG), deamidated gliadin (ADGA) and glycoprotein 2 (AGP2A) during two successive diets in 24 animals: A gluten-containing diet (diet 1) and a gluten-free diet (diet 2). Further, clinical symptoms of WMS and the animals’ body weight were also examined. An analysis of the feces of antibody-positive animals regarding changes in quality and dry matter content was carried out with samples collected during diet 2 and a successive gluten challenge diet of two months duration. The serological diagnostics resulted in a significant decline of AGA, antibodies to tTG and AGP2A during diet 2 in animals that had shown increased antibody concentrations during diet 1. Diet 2 also caused an amelioration of clinical symptoms and an increased body weight in antibody-positive animals. The gluten challenge resulted in a decreased feces quality and a lower fecal dry matter, compared to fecal samples of diet 2. In the context of this dissertation, parameters of haematology and clinical chemistry of the common marmoset were updated. Stress caused by relocation to a new housing was still measurable for a period of four weeks. It is therefore essential to consider this time span in the design of scientific studies to secure animal welfare prior to the study and to reduce the influence of stress on experimental results. In combination with the clinical symptoms, the detection of antibodies that are part of the pathogenesis of coeliac disease in humans strongly suggests gluten sensitivity with an aetiological connection to WMS in common marmosets. Therefore, gluten-free nutrition of common marmosets under human management is highly recommendable

Porcine circovirus type 2 (PCV2) is the primary causative agent of porcine circovirus associated disease (PCVAD), an economically important swine disease that causes wasting in pigs 5-18 weeks of age. There exist two different types of porcine circoviruses: porcine circovirus type 1 (PCV1) was discovered as a contaminant of porcine kidney (PK-15) cells and was determined to be nonpathogenic in swine; whereas porcine circovirus type 2 (PCV2) is pathogenic. A recently released vaccine for PCVAD was generated by inserting the gene encoding the immunogenic capsid protein of PCV2 into the genetic backbone of the non-pathogenic PCV1. This chimeric PCV vaccine, called PCV1-2, was shown to induce protective immunity against PCV2 infection in pigs. The vaccine is currently on the market in a killed form. In order to develop a live version of the vaccine, the genetic stability of the chimeric PCV1-2 vaccine virus was investigated by in vitro and in vivo passaging of the vaccine virus. In vitro passaging of the PCV1-2 vaccine virus was done in a porcine kidney PK-15 cell line. Cells were infected with the PCV1-2 vaccine virus and then serially passaged 11 times. The passaged vaccine viruses recovered from passages 5 and 11 were sequenced, and the sequences were compared to that of the original PCV1-2 vaccine virus. The in vitro serial passage result showed that no mutation occurred during the 11 in vitro passages. The in vivo passaging was done using specific-pathogen-free (SPF) pigs. In in vivo â passage 1â , nine piglets were divided into 3 groups of 3 each: group 1 each inoculated with 200ug of PCV1-2 plasmid, group 2 each with 1Ã 103 TCID50 live PCV1-2 vaccine virus, and group 3 each with 3ml phosphate buffered saline (PBS) buffer as a control. One pig from each group was necropsied at 14, 21, and 28 days post-inoculation (DPI), respectively. A panel of tissue samples including lymph nodes and thymus were collected from each pig. Tissue homogenates from DPI 28 that were positive by PCR for PCV1-2 DNA were used to inoculate new piglets in the in vivo passage 2 experiment. Viruses recovered from passage 2 pigs were subsequently used for inoculation in the in vivo passage 3 experiment. The PCV1-2 vaccine virus DNA from pigs in each passage was amplified and sequenced. The results of the in vivo serial passage experiment showed that, after 3 passages of the PCV1-2 vaccine virus in pigs, there were no new mutations in the viruses recovered from pigs. The PCV1-2 vaccine contained an introduced marker mutation at amino acid position number 79, which is in the capsid region. During the in vivo passaging of the vaccine virus in pigs, this marker mutation quickly reverted back to its original nucleotide. This marker back mutation occurred between DPI 21 and DPI 28 of passage 1 in the PCV1-2 live vaccine virus group, and between DPI 28 of passage 1 and DPI 14 of passage 2 in the PCV1-2 vaccine plasmid group, and remained stable throughout the reminder of the in vivo study. Based upon the results from this study, we conclude that the PCV1-2 chimeric vaccine virus is genetically stable in vitro and in pigs, and thus should serve as a good candidate for a live vaccine against PCV2.
Master of Science

The non-pathogenic porcine circovirus type 1 (PCV1) was originally isolated as a persistent contaminant of the porcine kidney cell line PK-15. Whereas, porcine circovirus type 2 (PCV2) causes postweaning multisystemic wasting syndrome (PMWS) in pigs, which is devastating to the swine industry. My objectives were to determine the effect of maternally derived antibodies on PCV2 infection, assess the role of 2 amino acid substitutions in the PCV2 capsid protein in PCV2 attenuation, evaluate the effect of Rep gene exchange between PCV1 and PCV2 on growth characteristics of a chimeric PCV2, and evaluate the role of open reading frame (ORF) 3 of PCV2 in virus replication and pathogenesis in pigs. Under field conditions, PCV2 infection is widespread and most breeding pigs are seropositive. Assessment of the role of PCV2 maternal antibodies in preventing PCV2 infection in piglets provided evidence that higher levels of maternal antibody provide more protection to piglets. Two amino acid substitutions in the PCV2 capsid protein that enhanced virus replication in vitro and attenuated the virus in vivo were evaluated for their pathogenicity in pigs. The results indicated that P110A and R191S are collectively responsible for virus attenuation. PCV1 replicates better in PK-15 cells and grows at least 1-log titer higher than PCV2. A chimeric PCV with the rep gene of PCV1 replacing that of PCV2 in the genomic backbone of PCV2 replicated more rapidly than PCV1 and PCV2, and more efficiently than PCV2, although to a titer similar to PCV1. The ORF3 of PCV2 is believed to encode a protein involved in apoptosis. The ORF3 start codon was mutated from ATG to GTG and the resulting mutant muPCV2 was infectious in vitro and in pigs; therefore ORF3 is dispensable for virus replication. The pathogenicity of muPCV2 was compared with PCV2 in vivo. Delayed viremia and seroconversion, decreased viral loads, lower level of IgG antibodies, and lower amounts of PCV2 antigen in mesenteric lymph nodes suggested attenuation of muPCV2. However, there was no significant difference in histological or gross lesions in tissues between PCV2- and muPCV2-inoculated groups. The role of ORF3 in attenuation needs to be further elucidated.
Ph. D.

A síndrome de emagrecimento progressivo (SEP) dos calitriquídeos representa importante causa de morbidade e mortalidade de sagüis mantidas em cativeiro. A etiologia dessa síndrome não está estabelecida e suas principais características são emagrecimento progressivo, diarréia, colite, anemia, paralisia dos membros posteriores e alopecia. Com esse estudo pretende-se responder se a síndrome é um processo de má-absorção ou de desnutrição protéico-calórica primária, caracterizar o quadro histológico intestinal de base e a resposta imunológica tecidual local. Foram estudados três grupos de sagüis: 1) 40 doentes com SEP pertencentes ao criadouro Mucky, 2) 9 controles vivos sadios, 3) 8 necrópsias de controles sem SEP. Foi realizado acompanhamento clínico, exame laboratorial das fezes, teste de absorção de D-xilose, avaliação da composição nutricional e digestibilidade da dieta, estudo anatomopatológico, incluindo avaliação semiquantitativa e análise morfométrica do jejuno de sagüis que foram a óbito naturalmente por SEP e dos controles. Os resultados alcançados permitiram caracterizar o perfil dos animais acometidos no nosso meio; os sinais clínicos maiores e menores da síndrome; identificar esteatorréia; o comprometimento da função digestiva e absortiva do intestino delgado dos sagüis com SEP; caracterizar o quadro histopatológico como uma enterite com atrofia semelhante à doença celíaca humana. A associação dos resultados clínicos, laboratoriais e histológicos permitiu definir a SEP como processo de má-absorção, por perda de superfície absortiva de intestino delgado, decorrente de enterite crônica imunomediada, de padrão celíaco-like que leva a progressiva e grave desnutrição secundária dos animais acometidos.
Wasting marmoset syndrome (WMS) is an important cause of morbidity and mortality of marmosets and tamarins kept in captivity. The etiology of this syndrome has not been established and its main features are progressive weight loss, diarrhea, colitis, anemia, hind limb paralysis, and alopecia. The aims of this research were to demonstrate that WMS is a malabsorption process, and to analyze the underlying histological lesion of the intestine and to characterize the local immune response of the small intestine. The sick marmosets (n=40) were compared to live normal controls (n=9) or to necropsied marmosets that died of other diseases than WMS (n=8), regarding clinical follow up, fecal analysis, D-xylose absorption test, evaluation of the nutritional composition and digestibility of the diet, gross and histological examination and morphometric approach of the jejune of wasters and control marmosets. These data revealed general features of WMS under our general captivity conditions, major and minor clinical signs of waster marmosets, impaired absorptive and digestive function of small intestine with steatorrhea and atrophic enteritis similar to celiac disease. The clinical and laboratory data associated with pathology examination demonstrated that WMS is a malabsorption process due to loss of absorptive surface area that results in progressive secondary malnutrition of the waster marmosets. The major immunologic mechanism underlying the celiac-like enteritis of WMS is a T-cell immune mediated response that affects intestine architecture

A Síndrome Multissistêmica do Definhamento do Suíno (SMDS) é uma doença emergente e mundialmente distribuída, que tem trazido sérios prejuízos econômicos para a indústria suinícola. O Circovírus Suíno tipo 2 (PCV2), agente causal da doença, provoca lesões principalmente nos tecidos linfóides, e sugere-se que produza imunossupressão, predispondo o hospedeiro a infecções virais, bacterianas e fúngicas secundárias. Neste trabalho, é descrito um estudo da prevalência e bacteriologia das otites purulentas em suínos apresentando a SMDS, bem como em animais de baixo desenvolvimento e de crescimento normal. No total, foram examinados 385 suínos com idades entre 60 e 130 dias. De 242 animais com a SMDS, 57 (23,5%) apresentaram lesões purulentas no ouvido médio. Dentre 119 animais de baixo desenvolvimento, apenas 1 (0,7%) apresentou a lesão. Não foram detectadas lesões macroscópicas no ouvido médio dos 24 animais com crescimento normal (controles). Os agentes isolados com maior freqüência das lesões foram Arcanobacterium pyogenes, Streptococcus α– hemolíticos e Pasteurella multocida, encontrados em, respectivamente, 37 (43%), 32 (37,2%) e 24 (27,9%) dos 86 ouvidos submetidos à bacteriologia. A alta prevalência de lesões purulentas no ouvido médio de animais com a SMDS sugere que a infecção pelo PCV2 pode tornar o suíno mais suscetível às otites bacterianas. Por outro lado, a prevalência reduzida das lesões em suínos de baixo desenvolvimento sugere que a otite não representa uma causa importante de mau desempenho em suínos nas fases de crescimento e terminação. O isolamento do A. pyogenes, de Streptococcus α- hemolíticos e da P. multocida na maioria das lesões está de acordo com relatos anteriores, confirmando a importância desses organismos como agentes causais da otite média em suínos.
Postweaning Multisystemic Wasting Syndrome (PMWS) is an emerging disease disseminated globally that causes severe losses to the pig industry. Porcine circovirus type 2 (PCV2) is the causal agent of the disease and causes lesions mainly in lymphoid tissue and it is suggested that it can cause immunosuppression, predisposing the host to viral, bacterial and mycotic infections. In the present work we describe a study on prevalence and bacteriology of purulent otitis in pigs with PMWS, as well as in pigs with attrition and pigs with normal growth. A total amount of 385 animals were examined, with ages ranging from 60 to 130 days. Among 242 pigs with PMWS, 57 (23,5%) showed purulent lesions in the middle ear. Among 119 pigs with attrition, only 1 (0,7%) presented the lesion. In 24 control pigs, middle ear lesions were not detected. The agents most frequently isolated from the lesions were Arcanobacterium pyogenes, α–hemolytic Streptococci and Pasteurella multocida, found respectively in 36 (43%), 32 (37,2%) and 24 (27,9%) of 86 ears bacteriologically examined. The high prevalence of purulent lesions found in middle ear of PMWS affected pigs suggests that PCV2 infection can increase susceptibility of swine to bacterial otitis. On the other hand, the small prevalence of lesions in piglets with attrition suggests that otitis does not represent a significant cause for depressed growth in pigs from growing and finishing ages. The isolation of A. pyogenes, α-hemolytic Streptococci and P. multocida from most lesions agrees with previous reports, confirming the importance of these organisms as causal agents in the etiology of otitis media in pigs.

Anorexia-cachexia is a heterogeneous and multifactorial syndrome most likely driven by systemic inflammation and neuroendocrine activation. Key diagnostic features include reduced appetite, weight loss, and muscle wasting. Key clinical problems include management of anorexia without resort to artificial nutritional support, and muscle wasting that cannot be completely arrested/reversed even with such intervention. Assessment should cover domains such as body stores of energy and protein, food intake, performance status, and factors resulting in excess catabolism. Intervention should be early rather than late, informed by the assessment process and focused on a multimodal approach (nutrition, exercise, and pharmacological agents). This chapter aims to discuss these issues and provide (a) the reader with some background principles to classification, (b) a simple approach to patient assessment and a robust algorithm for basic multimodal treatment, and (c) an overview of the evidence base for different pharmacological interventions.

Acute HIV infection is often missed but should be recognized. Most chronically infected individuals are asymptomatic. However, some patients with chronic HIV infection may present with certain clinical and laboratory abnormalities prior to the diagnosis of an opportunistic infection. HIV wasting syndrome is infrequently diagnosed in the era of antiretroviral therapy (ART). Recognition of HIV wasting is important because it carries adverse prognostic implications. Management includes a multifaceted approach, including ART, lifestyle and nutritional support, appetite stimulation, and possibly hormonal agents. The newer antigen–antibody test can detect new HIV infection as early as 15 days after exposure. Screening is important because most chronic HIV infection is asymptomatic.

The metabolic response to critical illness is complex and affects every body system. The first phase of this response is characterized by increased hypothalamic pituitary activity and resistance (decreased response) to effector hormones in many target tissues. Cytokines released in the early stages of such illness may be important as they appear to stimulate the hypothalamic pituitary axis directly as part of this ‘stress response’. This phase is considered ‘adaptive’ (helpful), increasing the availability of glucose, free fatty acids, and amino acids as substrates for vital organs. However, in prolonged illness, the neuroendocrine response is very different with damped hypothalamic responses, leading to a state in which catabolism predominates, leading to what might be termed the critical illness wasting syndrome. The gastrointestinal (GI) failure often associated with prolonged critical illness appears to be due, at least in part, to an altered neuroendocrine environment. The poor nutritional state associated with GI failure exacerbates the catabolic response, prolonging illness and the period of intensive care management required by the patient. The result is increased mortality and, in survivors, a more prolonged recovery/rehabilitation process.

Sodium is the main ion of the extracellular compartments, and it is through control of sodium reabsorption that the kidneys maintain volume homoeostasis and systemic blood pressure. The amount of sodium that is first filtered by the glomerulus and then reabsorbed in the tubule is quite staggering: assuming a glomerular filtration rate of 100 mL/min and a serum sodium concentration of 140 mmol/L, an average-sized person filters about 20,000 mmol of sodium per day, equivalent to the amount in 1.2 kg of cooking salt. In the steady state, the amount of sodium excreted is equal to the amount ingested. An average Western diet contains about 8–10 g of salt per day; a low-salt diet may be around 2 g per day. Under physiological conditions, the tubules reabsorb about 99% of filtered sodium. This enormous task is accomplished by a combination of distinct and sequentially oriented sodium or sodium-coupled transport systems along the nephron and the concerted and parallel action of some of these systems within the kidney. These are described, along with the consequences of disorders of the processes. A diagnostic approach to salt-losing states such as Fanconi, Bartter Gitelman and other syndromes, and hypoaldosteronism, is described.

Mitochondrial disease can affect any organ in the body including the kidney. As increasing numbers of patients with mitochondrial disease are either surviving beyond childhood or being diagnosed in adulthood, it is important for all nephrologists to have some understanding of the common renal complications that can occur in these individuals. Mitochondrial proteins are encoded by either mitochondrial or nuclear DNA (mtDNA and nDNA, respectively); therefore, disease causing mutations may be inherited maternally (mtDNA) or autosomally (nDNA), or can arise spontaneously. The commonest renal phenotype in mitochondrial disease is proximal tubulopathy (Fanconi syndrome in the severest cases); however, as all regions of the nephron can be affected, from the glomerulus to the collecting duct, patients may also present with proteinuria, decreased glomerular filtration rate, nephrotic syndrome, water and electrolyte disorders, and renal tubular acidosis. Understanding of the relationship between underlying genotype and clinical phenotype remains incomplete in mitochondrial disease. Proximal tubulopathy typically occurs in children with severe multisystem disease due to mtDNA deletion or mutations in nDNA affecting mitochondrial function. In contrast, glomerular disease (focal segmental glomerulosclerosis) has been reported more commonly in adults, mainly in association with the m.3243A<G point mutation. Co-enzyme Q10 (CoQ10) deficiency has been particularly associated with podocyte dysfunction and nephrotic syndrome in children. Underlying mitochondrial disease should be considered as a potential cause of unexplained renal dysfunction; clinical clues include lack of response to conventional therapy, abnormal mitochondrial morphology on kidney biopsy, involvement of other organs (e.g. diabetes, cardiomyopathy, and deafness) and a maternal family history, although none of these features are specific. The diagnostic approach involves acquiring tissue (typically skeletal muscle) for histological analysis, mtDNA screening and oxidative phosphorylation (OXPHOS) complex function tests. A number of nDNA mutations causing mitochondrial disease have now been identified and can also be screened for if clinically indicated. Management of mitochondrial disease requires a multidisciplinary approach, and treatment is largely supportive as there are currently very few evidence-based interventions. Electrolyte deficiencies should be corrected in patients with urinary wasting due to tubulopathy, and CoQ10 supplementation may be of benefit in individuals with CoQ10 deficiency. Nephrotic syndrome in mitochondrial disease is not typically responsive to steroid therapy. Transplantation has been performed in patients with end-stage kidney disease; however, immunosuppressive agents such as steroids and tacrolimus should be used with care given the high incidence of diabetes in mitochondrial disease.

Malnutrition in cardiac and critical illness is associated with a compromised clinical outcome. The aim of nutrition therapy is to prevent these complications and particularly to attenuate lean tissue wasting and the loss of muscle force and of physical function. During the last decade, several well-powered randomized controlled nutrition trials have been performed. Their results challenge the existing nutrition practices in critically ill patients. Enhancing the nutritional intake and the administration of specialized formulations failed to evoke clinical benefit. Some interventions even provoked an increased mortality or a delayed recovery. These unexpected new findings might be, in part, caused by an important leap forward in the methodological quality in the recent trials. Perhaps reversing early catabolism in the critically ill patient by nutrition or anabolic interventions is impossible or even inappropriate. Nutrients effectively suppress the catabolic intracellular autophagy pathway. But autophagy is crucial for cellular integrity and function during metabolic stress, and consequently its inhibition early in critical illness might be deleterious. Evidence from large nutrition trials, particularly in acute cardiac illness, is scarce. Nutrition therapy is therefore focused on avoiding iatrogenic harm. Some enteral nutrition is administered if possible and eventually temporary hypocaloric feeding is tolerated. Above all, the refeeding syndrome and other nutrition-related complications should be prevented. There is no indication for early parenteral nutrition, increased protein doses, specific amino acids, or modified lipids in critical illness.

Phyllodes tumors (PTs) of the breast correspond to about 1% of women’s breast tumors. Predominantly, benign has a high rate of local recurrence. The diagnosis is usually clinical, showing up as a voluminous tumor. Treatment, in most cases, is surgical alone; chemotherapy and radiotherapy are still uncertain on PT. Treatment based on arterial embolization of the tumor prior to surgery to improve morbidity is a practice that is rarely used, but this technique can be suggested as a saving measure. M.C.J.S., female, 39 years old, in 2013, presented with a nodule in the left breast, measuring 4 cm, mobile, painless, oval, which did not retract the skin. A nodulectomy was performed, with an anatomopathological diagnosis of benign PT. In 2015, there was a new recurrence, with a small volume, and the surgical margin was enlarged. In 2016, the patient evolved with a local recurrence of about 9 cm, being opted for neoadjuvant chemotherapy and radiotherapy and a total left mastectomy. In 2017, the left breast reconstruction with prosthesis placement was performed. In 2018, the patient was admitted to the mastology clinic of the Hospital Guilherme Álvaro (Santos, SP), with a new tumor recurrence, in the left axillary region, with only 3 months of evolution, and after chemotherapy treatment for regression in another service, without clinical improvement. The tumor measured about 36 cm in the left axillary region. It was then opted for radiotherapy for tumor regression. After 25 sessions, the patient returned with a tumor of the same dimensions; she was emaciated with a decline in her general condition, local pain, and unable to move her left upper limb. The patient was hospitalized for clinical stabilization and interdisciplinary planning for appropriate management. After attesting to the failure of the attempt to regress the tumor size with systemic treatment and failure to stabilize the tumor progression with radiotherapy, with no clinical improvement, the patient began to increasingly decline in general condition due to great wasting syndrome. In August 2018, after surgical planning, a tumor angiography was performed, and the poor vascularization of the tumor was noted, which after the radiotherapy had a necrotic clinical aspect, being opted for a surgical approach to the lesion. The autonomized Tram technique, with increased blood supply by an arterial and venous microvascular anastomosis of the deep inferior epigastric artery, was deprecated for covering the surgical wound. The procedure was done the week before the surgery. Two days before surgery, tumor embolization was performed via catheterization, with the application of intratumoral hemostatic gelfoam and with immediate radiological result of a section of the blood flow in the tumor. On the day after the procedure, the patient’s main complaint was a pain in the tumor bed, which was easily controlled with nonsteroidal anti-inflammatory drugs. The surgery was performed on August 24, 2018, with a tumor excision that compromised a large part of the adjacent musculature; there was no major bleeding and the procedure lasted for about 8 h, with the surgical wound being covered by flaps I, II, III, and IV of the Tram. The main postoperative complications were chronic left arm lymphedema and difficulty in mobilizing it, without other significant complications.