Biodistribution of the Radiopharmaceutical Sodium Pertechnetate after Biliopancreatic Bypass with a Duodenal Switch

Study with the purpose to examine the effects of duodenal switch (DS), regularly performed in morbidly obese patients, on biodistribution of sodium pertechnetate in several organs of rats. There was no early or late mortality in either rats groups. The values of percent radioactivity per gram of tissue (%ATI/g), showed no significant difference in liver, stomach, small bowel, duodenum, kidney, heart, bladder, bone and brain, when compared the DS rats with sham and controls rats. A postoperative significant increase (p<0.05) in mean %ATI/g levels was observed in spleen, pancreas and muscle in group DS rats, as compared to group S and C rats. In the lung there was an increase and in thyroid a decrease in mean %ATI/g of DS rats, when compared to sham rats (p<0.05). In conclusion, the biliopancreatic diversion with duodenal switch in rats modified the biodistribution of sodium pertechnetate in thyroid, lung, pancreas, spleen and muscle

Perfuração espontânea de colédoco em adolescente

Spontaneous perforation of the common bile duct is rare. It happens predominantly in children and it is related to obstructive disease of the biliary tract. We present a case of an 18 year-old male patient, with ulcerative rectocolitis associated with malignant tumor of the head of pancreas. The patient developed an acute abdomen syndrome and laparotomy, a spontaneous perforation of common bile duct was evidenced. The authors make a revision of the clinical aspects of that pathology

Accumulation, persistence and effects of indospicine residues in camels fed Indigofera plant

Indospicine (L-2-amino-6-amidinohexanoic acid) is a natural hepatotoxin found in all parts of some Indigofera plants such as I. linnaei and I. spicata. Several studies have documented a susceptibility to this hepatotoxin in different species of animals, including cattle, sheep, dogs and rats, which are associated with mild to severe liver disease after prolonged ingestion. However, there is little published data on the effects of this hepatotoxin in camels, even though Indigofera plants are known to be palatable to camels in central Australia. The secondary poisoning of dogs after prolonged dietary exposure to residual indospicine in camel muscle has raised additional food safety concerns. In this study, a feeding experiment was conducted to investigate the in vivo accumulation, excretion, distribution and histopathological effects of dietary indospicine on camels. Six young camels (2 – 4 year old), weighing 270 − 390 kg were fed daily a roughage diet consisting of Rhodes grass hay and lucerne chaff, supplemented with Indigofera and steam flaked barley. Indigofera (I. spicata) was offered at 597 mg DM/kg body weight (bw)/day designed to deliver 337 µg indospicine/kg bw/day, and fed for a period of 32 days. Blood and muscle biopsies were collected over the period of the study. Concentrations of indospicine in the plasma and muscle biopsy samples were quantitated by validated ultra-performance liquid chromatography−tandem mass spectrometry (UPLC−MS/MS). The highest concentrations in plasma (1.01 mg/L) and muscle (2.63 mg/kg fresh weight (fw)) were found at necropsy (day 33). Other tissues were also collected at necropsy and analysis showed ubiquitous distribution of indospicine, with the highest indospicine accumulation detected in the pancreas (4.86 ± 0.56 mg/kg fw) and liver (3.60 ± 1.34 mg/kg fw); followed by the muscle, heart and kidney. Histopathological examination of liver tissue showed multiple small foci of predominantly mononuclear inflammatory cells. After cessation of Indigofera intake, indospicine present in plasma in the remaining 3 camels had a longer terminal elimination half-life (18.6 days) than muscle (15.9 days), and both demonstrated mono-exponential decreases.

An investigation of the clinical utility of preoperative cardiopulmonary exercise testing in patients undergoing major pancreatic surgery

Pancreaticoduodenectomy with or without adjuvant chemotherapy remains the only modality of possible cure in patients with cancer involving the head of the pancreas and the periampullary region. While mortality rates after pancreaticoduodenectomy have improved considerably over the course of the last century, morbidity remains high. Patient selection is of paramount importance in ensuring that major surgery is offered to individuals who will most benefit from a pancreaticoduodenectomy. Moreover, identifying preoperative risk factors provides potential targets for prehabilitation and optimisation of the patient's physiology before undertaking surgery. In addition to this, early identification of patients who are likely to develop postoperative complications allows for better allocation of critical care resources and more aggressive management high risk patients. Cardiopulmonary exercise testing is becoming an increasingly popular tool in the preoperative risk assessment of the surgical patient. However, very little work has been done to investigate the role of cardiopulmonary exercise testing in predicting complications after pancreaticoduodenectomy. The impact of jaundice, systemic inflammation and other preoperative clinicopathological characteristics on cardiopulmonary exercise physiology has not been studied in detail before in this cohort of patients. The overall aim of the thesis was to examine the relationships between preoperative clinico-pathological characteristics including cardiopulmonary exercise physiology, obstructive jaundice, body composition and systemic inflammation and complications and the post-surgical systemic inflammatory response in patients undergoing pancreaticoduodenectomy. Chapter 1 reviews the existing literature on preoperative cardiopulmonary exercise testing, the impact of obstructive jaundice, perioperative systemic inflammation and the importance of body composition in determining outcomes in patients undergoing major surgery with particular reference to pancreatic surgery. Chapter 2 reports on the role of cardiopulmonary exercise testing in predicting postoperative complications after pancreaticoduodenectomy. The results demonstrate that patients with V˙O2AT less than 10 ml/kg/min are more likely to develop a postoperative pancreatic fistula, stay longer in hospital and less likely to receive adjuvant therapy. These results emphasise the importance of aerobic fitness to recover from the operative stress of major surgery without significant morbidity. Cardiopulmonary exercise testing may prove useful in selecting patients for intensive prehabilitation programmes as well as for other optimisation measures to prepare them for major surgery. Chapter 3 evaluates the relationship between cardiopulmonary exercise physiology and other clinicopathological characteristics of the patient. A detailed analysis of cardiopulmonary exercise test parameters in jaundiced versus non-jaundiced patients demonstrates that obstructive jaundice does not impair cardiopulmonary exercise physiology. This further supports emerging evidence in contemporary literature that jaundiced patients can proceed directly to surgery without preoperative biliary drainage. The results of this study also show an interesting inverse relationship between body mass index and anaerobic threshold which is analysed in more detail in Chapter 4. Chapter 4 examines the relationship between preoperative cardiopulmonary exercise physiology and body composition in depth. All parameters measured at cardiopulmonary exercise test are compared against body composition and body mass index. The results of this chapter report that the current method of reporting V˙O2, both at peak exercise and anaerobic threshold, is biased against obese subjects and advises caution in the interpretation of cardiopulmonary exercise test results in patients with a high BMI. This is particularly important as current evidence in literature suggests that postoperative outcomes in obese subjects are comparable to non-obese subjects while cardiopulmonary exercise test results are also abnormally low in this very same cohort of patients. Chapter 5 analyses the relationship between preoperative clinico-pathological characteristics including systemic inflammation and the magnitude of the postoperative systemic inflammatory response. Obstructive jaundice appears to have an immunosuppressive effect while elevated preoperative CRP and hypoalbuminemia appear to have opposite effects with hypoalbuminemia resulting in a lower response while elevated CRP in the absence of hypoalbuminemia resulted in a greater postoperative systemic inflammatory response. Chapter 6 evaluates the role of the early postoperative systemic inflammatory response in predicting complications after pancreaticoduodenectomy and aims to establish clinically relevant thresholds for C-Reactive Protein for the prediction of complications. The results of this chapter demonstrate that CRP levels as early as the second postoperative day are associated with complications. While post-operative CRP was useful in the prediction of infective complications, this was the case only in patients who did not develop a post-operative pancreatic fistula. The predictive ability of inflammatory markers for infectious complications was blunted in patients with a pancreatic fistula. Chapter 7 summarises the findings of this thesis, their place in current literature and future directions. The results of this thesis add to the current knowledge regarding the complex pathophysiological abnormalities in patients undergoing pancreaticoduodenectomy, with specific emphasis on the interaction between cardiopulmonary exercise physiology, obstructive jaundice, systemic inflammation and postoperative outcomes. The work presented in this thesis lays the foundations for further studies aimed at improving outcomes after pancreaticoduodenectomy through the development of individualised, goal-directed therapies that are initiated well before this morbid yet necessary operation is performed.

Biodistribution of the radiophamarceutical sodium pertechnetate (Na99mTcO4) after massive small bowel resection in rats

To evaluate the biodistribution of sodium pertecnetate (Na99mTcO4) in organs and tissues, the morphometry of remnant intestinal mucosa and ponderal evolution in rats subjected to massive resection of the small intestine. Methods: Twenty-one Wistar rats were randomly divided into three groups of 7 animals each. The short bowel (SB) group was subjected to massive resection of the small intestine; the control group (C) rats were not operated on, and soft intestinal handling was performed in sham rats. The animals were weighed weekly. On the 30th postoperative day, 0.l mL of Na99mTcO4, with mean activity of 0.66 MBq was injected intravenously into the orbital plexus. After 30 minutes, the rats were killed with an overdose of anesthetic, and fragments of the liver, spleen, pancreas, stomach, duodenum, small intestine, thyroid, lung, heart, kidney, bladder, muscle, femur and brain were harvested. The biopsies were washed with 0.9% NaCl.,The radioactivity was counted using Gama Counter WizardTM 1470, PerkinElmer. The percentage of radioactivity per gram of tissue (%ATI-g) was calculated. Biopsies of the remaining jejunum were analysed by HE staining to obtain mucosal thickness. Analysis of variance (ANOVA) and the Tukey test for multiple comparisons were used, considering p<0.05 as signifi cant. Results: There were no signifi cant differences in %ATI-g of the Na99mTcO4 in the organs of the groups studied (p>0.05). An increase in the weight of the SB rats was observed after the second postoperative week. The jejunal mucosal thickness of the SB rats was signifi cantly greater than that of C and sham rats (p<0.05). Conclusion: In rats with experimentally-produced short bowel syndrome, an adaptive response by the intestinal mucosa reduced weight loss. The biodistribution of Na99mTcO4 was not affected by massive intestinal resection, suggesting that short bowel syndrome is not the cause of misleading interpretation, if an examination using this radiopharmaceutical is indicated

Successful Treatment Using Simeprevir, Sofosbuvir and Rituximab of a Severe Form of Hepatitis C Virus-related Mixed Cryoglobulinemia with Cardiac Involvement

Numerous extrahepatic manifestations have been reported in hepatitis C virus (HCV) infection, particularly mixed cryoglobulinemia (MC). MC generally responds to clearance of HCV under pegylated-interferon plus ribavirin treatment. New direct-acting antiviral agents have been licensed for HCV under different combinations but have not been studied in severe forms of MC. Here, we present a case report describing a life-threatening form of MC with multivisceral involvement, which was successfully treated with concomitant rituximab, sofosbuvir and simeprevir. In light of the rapid clinical remission associated with sustained virological response and the excellent side-effect profile, this treatment should be considered as a first-line therapy in severe forms of MC.

Large Morgagni Hernia in an Adult Patient

A 70-year-old woman presented to the emergency department with symptoms of a lower respiratory infection. A chest x-ray showed enlargement of the mediastinal space. The patient was admitted with a respiratory tract infection and started on antibiotic treatment. A computed tomography (CT) scan of the thorax revealed a large diaphragmatic hernia with stomach, large intestine and caudal pancreas lodged in the thoracic cavity. After the antibiotic treatment, the patient became asymptomatic and surgery repair was declined. Morgagni hernia is an uncommon type of congenital diaphragmatic hernia, which may be asymptomatic until late in life or may be present acutely with life threatening conditions.

A biochemical analysis into the co-translational folding of a G protein-coupled receptor; GPR35

The folding and targeting of membrane proteins poses a major challenge to the cell, as they must remain insertion competent while their highly hydrophobic transmembrane (TM) domains are transferred from the ribosome, through the aqueous cytosol and into the lipid bilayer. The biogenesis of a mature membrane protein takes place through the insertion and integration into the lipid bilayer. A number of TM proteins have been shown to gain some degree of secondary structure within the ribosome tunnel and to retain this conformation throughout maturation. Although studies into the folding and targeting of a number of membrane proteins have been carried out to date, there is little information on one of the largest class of eukaryotic membrane proteins; the G-protein-coupled receptors (GPCRs). This project studies the early folding events of the human ortholog of GPR35. To analyse the structure of the 1st TM domain, intermediates were generated and assessed by the biochemical method of pegylation (PEG-MAL). A structurally-similar microbial opsin (Bacterioopsin) was also used to investigate the differences in the early protein folding within eukaryotic and prokaryotic translation systems. Results showed that neither the 1st TM domain of GPR35 nor Bacterioopsin were capable of compacting in the ribosome tunnel before their N-terminus reached the ribosome exit point. The results for this assay remained consistent whether the proteins were translated in a eukaryotic or prokaryotic translation system. To examine the communication mechanism between the ribosome, the nascent chain and the protein targeting pathway, crosslinking experiments were carried out using the homobifunctional lysine cross-linker BS3. Specifically, the data generated here show that the nascent chain of GPR35 reaches the ribosomal protein uL23 in an extended conformation and interacts with the SRP protein as it exits the ribosome tunnel. This confirms the role of SRP in the co-translational targeting of GPR35. Using these methods insights into the early folding of GPCRs has been obtained. Further experiments using site-directed mutagenesis to reduce hydrophobicity in the 1st TM domain of GPR35, highlighted the mechanisms by which GPCRs are targeted to the endoplasmic reticulum. Confirming that hydrophobicity within the signal anchor sequence is essential of SRP-dependent targeting. Following the successful interaction of the nascent GPR35 and SRP, GPR35 is successfully targeted to ER membranes, shown here as dog pancreas microsomes (DPMs). Glycosylation of the GPR35 N-terminus was used to determine nascent chain structure as it is inserted into the ER membrane. These glycosylation experiments confirm that TM1 has obtained its compacted state whilst residing in the translocon. Finally, a site-specific cross-linking approach using the homobifunctional cysteine cross-linker, BMH, was used to study the lateral integration of GPR35 into the ER. Cross-linking of GPR35 TM1 and TM2 could be detected adjacent to a protein of ~45kDa, believed to be Sec61α. The loss of this adduct, as the nascent chain extends, showed the lateral movement of GPR35 TM1 from the translocon was dependent on the subsequent synthesis of TM2.

Behind Recurrent Thromboembolic Events

We describe the case of a 68-year-old man, who presented with an ischemic stroke due to cardiac embolization related to mitral valve endocarditis. Blood cultures were always negative and post-operative valve histology did not show microorganisms. The patient also presented further recurrent peripheral embolic events. These clinical aspects were the first sign of a pancreas adenocarcinoma, which was only diagnosed in the clinical autopsy. In conclusion, these clinical findings of recurrent thromboembolic events with no microorganisms isolated suggests the diagnostic of a marantic endocarditis.

Efeito sacietogênico de um novo inibidor de tripsina da paçoca do amendoim com aumento plasmático de colecistocinina (cck)

Obesity is increasing, reaching epidemic levels in many regions of the world. Studies have shown that consumption of peanuts influences on weight control and this influence may be due to the action of trypsin inhibitors sacietogênica that condition increased plasma colescistocinina (CCK). Moreover, the peanut has other health benefits, and these assignments are guaranteed to increase their production and consumption of several of its products, including the paçoca peanut. The aim of this study was to identify the presence of a trypsin inhibitor in paçoca peanut and evaluate its effect on food intake, weight gain and histomorphological changes in swiss mice (n = 8) and Wistar rats (n = 6). Experimental diets were prepared based on the AIN-93G and supplemented with tack or peanut trypsin inhibitor partially purified paçoca peanut (AHTI). After each treatment, the animals were anesthetized and euthanized, their bloods were collected by cardiac puncture for the determination of CCK and other biochemical parameters (glucose, triglycerides, total cholesterol, high density lipoprotein, low density lipoprotein, glutamic-pyruvic transaminase, glutamic oxaloacetic transaminase and albumin) and their pancreas removed for histologic and morphometric analysis. The supplementation with paçoca peanut and the AHTI showed a decrease of body weight gain and food intake in both mice and rats, due to the satiety, since the animals showed no evidence of impairment of nutritional status conditioned by consumption the AHTI. There were also observed biochemical or morphological important when compared with controls. However, AHTI led to increased secretion of CCK, a peptide sacietogênico. Thus, these results indicate that AHTI present in paçoca peanut, is able to enhance the secretion of plasma CCK and thereby reduce the weight gain associated with lower food intake of experimenta animals

Ação Sacietogênica de um inibidor de tripsina da semente de tamarindo (Tamarindus indica L.)

The seeds are excellent sources of proteinase inhibitors and have been highlighted owing to various applications. Among these applications are those in effect on food intake and weight gain that stand out because of the increasing number of obese individuals. This study evaluated the effects of trypsin inhibitor present in the seed of tamarind (Tamarindus indica L.) reduction in weight gain, biochemical and morphological alterations in Wistar rats. For this, we partially purified a trypsin inhibitor tamarind seed. This inhibitor, ITT2 at a concentration of 25 mg / kg body weight, over a period of 14 days was able to reduce food intake in rats (n = 6) by approximately 47%, causing a reduction in weight gain approximately 70% when compared with the control group. With the evaluation of the in vivo digestibility was demonstrated that the animals lost weight due to satiety, presented by the reduction of food intake, since there were significant differences between true digestibility for the control group (90.7%) and the group treated with inhibitor (89.88%). Additionally, we checked the deeds of ITT2 on biochemical parameters (glucose, triglycerides, total cholesterol, high-density lipoprotein, low-density lipoprotein, glutamic-pyruvic transaminase, glutamic oxaloacetic transaminase, gamma glutamyl transferase albumin, globulin, total protein and C-reactive protein) and these, when assessed in the study groups showed no statistically significant variations. We also evaluate the histology of some organs, liver, stomach, intestine, and pancreas, and showed no changes. And to evaluate the effect of trypsin inhibitor on food intake due to the satiety is regulated by cholecystokinin (CCK) were measured plasma levels, and it was observed that the levels of CCK in animals receiving ITT2 were significantly higher ( 20 + 1.22) than in animals receiving only solution with casein (10.14 + 2.9) or water (5.92 + 1.15). Thus, the results indicate that the effect caused ITT2 satiety, reducing food intake, which in turn caused a reduction in weight gain in animals without causing morphological and biochemical changes, this effect caused by the elevation of plasma levels CCK

Rola fosfodiesterazy 3B w regulacji sekrecji insuliny u szczura (Rattus norvegicus Berkenhout)

Wydział Biologii

Imagiologia dos Tumores malignos do pâncreas

As neoplasias malignas do pâncreas englobam vários tipos histologicos com características ima giológicas e comportamentos que permitem distingui-los entre si numa boa percentagem de situações. Contudo, nem sempre a sua diferenciação se toma possível sem o recurso às técnicas anátomo-patoló gicas, constituindo um grande desafio à imagiologia o diagnóstico diferencial com lesões benignas, com referencia particular às massas inflamatórias. O adenocarcinoma constitui cerca de 95% das neo plasias pancreáticas e é uma das grandes causas de morte por cancro nos países desenvolvidos. As técnicas de imagem aplicadas no diagnóstico e no estadiamento dos principais tumores do pâncreas são muito diversificadas, englobando meios inócuos, como a ecografia, métodos invasivos utilizando técnicas angiográficas ou recurso aos meios endoscópicos para acesso endocavitário. A utilidade de cada uma destas variedades técnicas depende essencialmente do tipo de tumor a estudar, tomando-se fundamental o correcto e o completo conhecimento das possibilidades e limitações de cada uma, com vista à aplicação racional dos meios na imagiologia do pâncreas.

Adenocarcinoma pleomórfico de células giganates de vías biliares(osteoclastoma like)

Las células gigante tipo osteoclásticas (CGTO) del páncreas son una entidad poco frecuente descrito originalmente por Rosaien 1968, caracterizado por osteoclastos, que son células gigantes mononucleares idénticas a las células del estroma observadas en tumores óseos. Desde entonces, hay pocos informes de los tumores que contienen células gigantes en otras localizaciones anatómicas. Las CGTO se pueden distinguir de las células gigantes tipo pleomórficas (CGTP), debido a la falta de un marcado pleomorfismo nuclear asociado. A menudo, un carcinoma de páncreas histológicamente reconocibles acompaña CGTO, dando lugar a un mal resultado. Formas puras de CGTO presentan un mejor pronóstico porque se necesita mucho tiempo para desarrollar metástasis, pero esta forma es muy raros, con pocos casos reportados en la literatura Inglésa. La mayoría de veces se discute el diagnóstico de benignidad de estos tumores basados en la evaluación de inmunohistoquímica. El presente caso se trata de una paciente de sexo femenino de 56 años de edad con cuadro caracterizado por dolor tipo cólico que mejora con antiespasmódicos, de varios meses de evolución, con periodos de remisión y exacerbación. A examen físico presenta: en piel y mucosas ligero tinte subictérico, a nivel abdominal: abdomen doloroso de forma difusa sin viseromegalias o masas palpables

Síntese estereosseletiva da naftotectona

Tese (doutorado)—Universidade de Brasília, Instituto de Química, 2016.