Evaluation of 68Ga-DOTATATE uptake at the pituitary region and the biochemical response to somatostatin analogs in acromegaly.

PURPOSE: Acromegaly is associated with many comorbidities and increased mortality. The first-line treatment is transsphenoidal surgery. However, many patients also need adjuvant drug treatment after surgery. Somatostatin analog (SSA), which suppresses GH secretion by somatotrophs by binding to the SSTR2 receptor, is the first choice. Nevertheless, 50% of patients are partially or totally resistant to SSA, so predictive factors of response are helpful to individualize drug treatment. 68GaDOTATATE PET/CT has emerged as the gold-standard method in the diagnosis and follow-up of gastroenteropancreatic neuroendocrine tumors, which also express SSTR. Our objective was to evaluate whether 68Ga-DOTATATE uptake (SUV max) at the pituitary region of patients on SSA therapy would be useful as a drug response predictor without the need of tumoral tissue. METHODS: Fifteen acromegalics patients on SSA treatment for at least 6 months were underwent to 68Ga-DOTATATE PET/CT at the nuclear medicine service. There was an SSA complete response group (n = 5), defined as GH < 1 µg/L and IFG-1 in the normal range for gender and age, and a group that did not meet these criteria (n = 10). RESULTS: As a result, we did not find out a significantly higher SUV max in the complete response group (p = 0.0576) to SSA. However, we found a significant inverse relationship between postoperative GH values and the SUVmax at the sella turcica (p = 0.0188), probably reflecting tumor SSTR2 expression. CONCLUSION: Thus, after this initial evaluation, 68GaDOTATATE PET/CT should be better studied to assess its usefulness in the follow-up of acromegalic patients.

Oral findings in secondary syphilis.

BACKGROUND: Syphilis is a sexually transmitted disease caused by Treponema pallidum. However, there are of hematogenic and vertical transmission. All health care professionals must be aware of the manifestations of this condition, such as oral lesions. OBJECTIVES: This study to analyze and compare four clinical cases of syphilis that were diagnosed based on lesions in the oral cavity with published literature. MATERIAL AND METHODS: Four patients with a confirmed sorologic and clinical diagnosis of syphilis were examined, confirmated from manifestation of oral lesions together with analysis of serological laboratory tests and histopathological analyses. RESULTS: Lesions were found in classic sites such as lips, tongue and skin. However, there were also lesions on the hard palate, and labial commissure, which correspond to less than 5% of the syphilis oral manifestations. CONCLUSIONS: The practice of unprotected oral sex may result in infection and development of syphilis. The acknowledgment of the oral manifestations of syphilis in all its period of training for health professionals is of basic importance, the association of clinical features, histopathological findings and serological tests are required to complete the diagnosis and correct treatment.

A survey of zoonotic pathogens carried by house mouse and black rat populations in Yucatan, Mexico.

The house mouse (Mus musculus) and the black rat (Rattus rattus) are reservoir hosts for zoonotic pathogens, several of which cause neglected tropical diseases (NTDs). Studies of the prevalence of these NTD-causing zoonotic pathogens, in house mice and black rats from tropical residential areas are scarce. Three hundred and two house mice and 161 black rats were trapped in 2013 from two urban neighbourhoods and a rural village in Yucatan, Mexico, and subsequently tested for Trypanosoma cruzi, Hymenolepis diminuta and Leptospira interrogans. Using the polymerase chain reaction we detected T. cruzi DNA in the hearts of 4·9% (8/165) and 6·2% (7/113) of house mice and black rats, respectively. We applied the sedimentation technique to detect eggs of H. diminuta in 0·5% (1/182) and 14·2% (15/106) of house mice and black rats, respectively. Through the immunofluorescent imprint method, L. interrogans was identified in 0·9% (1/106) of rat kidney impressions. Our results suggest that the black rat could be an important reservoir for T. cruzi and H. diminuta in the studied sites. Further studies examining seasonal and geographical patterns could increase our knowledge on the epidemiology of these pathogens in Mexico and the risk to public health posed by rodents.

Characterization of the gene encoding component C3 of the complement system from the spider Loxosceles laeta venom glands: Phylogenetic implications.

A transcriptome analysis of the venom glands of the spider Loxosceles laeta, performed by our group, in a previous study (Fernandes-Pedrosa et al., 2008), revealed a transcript with a sequence similar to the human complement component C3. Here we present the analysis of this transcript. cDNA fragments encoding the C3 homologue (Lox-C3) were amplified from total RNA isolated from the venom glands of L. laeta by RACE-PCR. Lox-C3 is a 5178 bps cDNA sequence encoding a 190kDa protein, with a domain configuration similar to human C3. Multiple alignments of C3-like proteins revealed two processing sites, suggesting that Lox-C3 is composed of three chains. Furthermore, the amino acids consensus sequences for the thioester was found, in addition to putative sequences responsible for FB binding. The phylogenetic analysis showed that Lox-C3 belongs to the same group as two C3 isoforms from the spider Hasarius adansoni (Family Salcitidae), showing 53% homology with these. This is the first characterization of a Loxosceles cDNA sequence encoding a human C3 homologue, and this finding, together with our previous finding of the expression of a FB-like molecule, suggests that this spider species also has a complement system. This work will help to improve our understanding of the innate immune system in these spiders and the ancestral structure of C3.

Analysis of follicular events in owl monkeys (Aotus azarai infulatus) using B-mode and Doppler ultrasound.

Ultrasound (B-mode) was used to analyze follicular events in 12 trained female owl monkeys (Aotus azarai infulatus). The animals were examined every 48 hours for over 90 days to measure and map follicular growth in both ovaries and to measure (using Doppler velocimetry) local hemodynamic changes during the peri-ovulatory stage. There were 44 follicular growth events, each with two or three follicular waves, and a mean ± SEM interval between events of 17 ± 1.13 days. There were various hemodynamic changes during follicular growth; both vascular resistance index and pulsatility index decreased during the time when the follicle diameter peaked. Thus, both B-mode and Doppler ultrasound were useful for monitoring ovarian follicular events in owl monkeys.

Impact of exposure to positive images on dental anxiety among children: a controlled trial.

AIM: To determine whether exposing children to images of positive dental care would have an effect on their degree of anxiety, assessing anxiety three separate times. STUDY DESIGN: Controlled trial. METHODS: The 70 participants from 4-11 years of age were randomly assigned to one of two conditions. The intervention consisted of viewing positive images of dentistry and dental treatment (n=35). The control condition consisted of dentally neutral images (n=35). OUTCOME MEASURES: Anxiety was assessed using the Venham Picture Test (VPT) prior to the intervention, immediately following the intervention and following the dental appointment. STATISTICS: Statistical analysis (chisquare and Mann-Whitney tests) was conducted blind to group allocation. RESULTS: No significant difference was detected between the scores of the VPT in the two groups at any evaluation time (p>0.05). Dental anxiety at the three evaluation times was not correlated to age. There was no difference in level of anxiety between male and female participants (p>0.05). CONCLUSIONS: Viewing positive images of dentistry and dentists did not have a greater effect on child anxiety in the dental setting than viewing neutral images, however, showed lower rates of anxiety for all children although this was not significant.

[Hybrid-NOTES transvaginal hemi-nephrectomy for duplicated renal collecting system in the adult patient]. / Heminefrectomía NOTES-híbrido transvaginal por duplicidad del sistema colector renal en el paciente adulto.

INTRODUCTION: Duplication of the ureter and renal pelvis is the most common anomaly of the upper urinary tract. Upper pole heminephrectomy is a treatment option when duplication anomalies are associated with ureteral ectopia or ureterocele with an associated nonfunctioning or infected upper pole moiety. MATERIAL AND METHOD: We describe a NOTES hybrid transvaginal upper pole heminephrectomy in a 24 year old with recurrent infections in a poorly functioning right upper pole moiety. The procedure was performed with a bariatric trocar in the vagina, and a multichannel single-port device (Triport, Olympus Surgical) in the umbilicus. An ultrasonic scalpel was used for the heminephrectomy. The specimen was retrieved through the vagina. RESULTS: Operative time was 150 minutes and blood loss 50 cc. One week later the patient developed urinoma at the surgical site and was re-explored laparoscopically. The cut edge of the heminephrectomy defect was fulgurated and a drain placed. The patient recovered uneventfully following re-exploration. CONCLUSIONS: We describe the technique for transvaginal Hybrid-NOTES heminephrectomy. This approach requires further development with respect to instrumentation, and surgical expertise. The combined umbilical and vaginal approached restored triangulation and facilitates dissection, but more experience is required to determine safety, efficacy and reproducibility.

[A novel technique for distal ureterectomy and bladder cuff excision]. / Nueva técnica para la ureterectomía distal y excisión de manguito vesical.

INTRODUCTION: We describe a novel endoscopic approach and provide a literature review for the "en bloc" dissection of the distal ureter and bladder cuff during laparoscopic radical nephroureterectomy using a transvesical single port approach under pneumovesicum. MATERIALS AND METHODS: The procedure was performed in an 80-year old male with a history of gross hematuria due to left renal pelvic TCC and no history of prior bladder TCC. Laparoscopic radical nephroureterectomy was performed and the ureter was dissected down to the bladder and clipped. A single-port device was inserted transvesically and pneumovesicum established. A full thickness incision of the bladder around the ureter was performed with progressive intravesical mobilization of the distal ureter. Subsequently, a water-tight closure of the bladder defect was achieved. The distal ureter, together with the bladder cuff, was then delivered en bloc laparoscopically with the specimen. RESULTS: The operating time (LESS radical nephroureterectomy, RPLND, and bladder cuff excision) was 6hours and 15minutes. The bladder cuff time was 45minutes. There were no intra or postoperative complications and the catheter was removed after 6 days. Histopathological analysis showed kidney-invasive papillary urothelial cancer, pT3 pN0 (0/7) G3. CONCLUSION: The distal ureter and bladder cuff techniques have not yet been standardized. Management of the bladder cuff with a single port is feasible. Additional studies are needed to identify the best approach for management of the distal ureter at the time of laparoscopic nephroureterectomy.

Effects of Bermudagrass hay and soybean hulls inclusion on performance of sheep fed cactus-based diets.

The objective of this experiment was to determine the effects of replacing corn with soybean hulls (SH) or Bermudagrass tifton hay (TH) on performance of sheep fed cactus-based diets. Three ruminally fistulated sheep were used in a 3 x 3 Latin square experiment with 21-day periods. All diets contained 75% spineless cactus (dry matter basis, DM) and formulated to be isonitrogenous. Fiber source had no influence on nutrient intakes except for the intake of neutral detergent fiber (NDF) which was lower (p<0.05) for animals fed corn relative to those fed SH or TH. Time expended in rumination and total chewing time were higher (p<0.05) for animals fed TH than those fed SH or corn. In vivo nutrient digestibilities were similar for all dietary treatments and averaged 69.6%, 74.8%, 69.9%, and 61.8% for DM, organic matter, crude protein, and NDF, respectively. Feeding SH relative to TH and corn decreased ruminal pH (p<0.05) and increased concentration of total volatile fatty acids (p<0.05). However, ruminal NH3-N concentration was higher (p<0.05) for animal fed TH than for those fed SH or corn. Abdominal distension and ruminal biofilm production were greater (p<0.05) in animals fed corn or SH than in those fed TH. It was concluded that replacing corn with SH or TH up to 15% of the diet DM in a cactus-based diet had no effect on nutrient intakes or total tract nutrient utilization. Changes in ruminal fermentation parameters reflected differences in ruminal degradability between the two fiber sources. Bermudagrass tifton hay was more effective than SH in reducing the risk of bloat associated with feeding high levels of spineless cactus to ruminants.

A new anti-loxoscelic serum produced against recombinant sphingomyelinase D Results of preclinical trials

Envenomation by Loxosceles species (brown spider) can lead to local dermonecrosis and to serious systemic effects. The main toxic component in the venom of these spiders is sphingomyelinase D (SMase D) and various isoforms of this toxin are present in Loxosceles venoms. We have produced a new anti-loxoscelic serum by immunizing horses with recombinant SMase D. In the present study, we compared the neutralization efficacy of the new anti-loxoscelic serum and anti-arachnidic serum (the latter serum is used for therapy for loxoscelism in Brazil) against the toxic effects of venoms from spiders of the genus Loxosceles. Neutralization tests showed that anti-SMase D serum has a higher activity against toxic effects of L. intermedia and L. laeta venoms and similar or slightly weaker activity against toxic effects of L. gaucho than that of Arachnidic serum. These results demonstrate that recombinant SMase D can replace venom for anti-venom production and therapy.

Transcriptome analysis of Loxosceles laeta (Araneae, Sicariidae) spider venomous gland using expressed sequence tags

The bite of spiders belonging to the genus Loxosceles can induce a variety of clinical symptoms, including dermonecrosis, thrombosis, vascular leakage, haemolysis, and persistent inflammation. In order to examine the transcripts expressed in venom gland of Loxosceles laeta spider and to unveil the potential of its products on cellular structure and functional aspects, we generated 3,008 expressed sequence tags (ESTs) from a cDNA library. Results: All ESTs were clustered into 1,357 clusters, of which 16.4% of the total ESTs belong to recognized toxin-coding sequences, being the Sphingomyelinases D the most abundant transcript; 14.5% include "possible toxins", whose transcripts correspond to metalloproteinases, serinoproteinases, hyaluronidases, lipases, C-lectins, cystein peptidases and inhibitors. Thirty three percent of the ESTs are similar to cellular transcripts, being the major part represented by molecules involved in gene and protein expression, reflecting the specialization of this tissue for protein synthesis. In addition, a considerable number of sequences, 25%, has no significant similarity to any known sequence. Conclusion: This study provides a first global view of the gene expression scenario of the venom gland of L. laeta described so far, indicating the molecular bases of its venom composition.

Loxosceles spider venom induces the release of thrombomodulin and endothelial protein C receptor: implications for the pathogenesis of intravascular coagulation as observed in loxoscelism.

BACKGROUND: The venom of the spider Loxosceles can cause both local and systemic effects including disseminated intravascular coagulation. AIM: The aim of this study was to investigate the effects of the venom of Loxosceles intermedia (L. intermedia) and the purified Sphingomyelinase D (SMaseD) toxin upon the Protein C (PC) natural anticoagulant pathway. RESULTS: Both the venom and e purified SMaseD reduced the cell surface expression of thrombomodulin (TM) and Endothelial PC Receptor on endothelial cells in culture. The reduction of cell surface expression was caused by cleavage from the cell surface mediated by activation of an endogenous metalloproteinase. Reduction of TM and Endothelial PC Receptor on the surface of these cells resulted in an impaired ability of the cells to assist in the thrombin-induced activation of PC. CONCLUSION: This novel observation gives further insight into the mechanisms of the pathology induced by venom from Loxosceles spiders and may aid the development of a suitable therapy.

Sphingomyelinases D induce direct association of C1q to the erythrocyte membrane causing complement mediated autologous haemolysis.

Bites by Loxosceles spiders can induce severe clinical symptoms, including dermonecrosis, thrombosis, vascular leakage, haemolysis and persistent inflammation. The causative toxin is a sphingomyelinase D (SMase D) that cleaves sphingomyelin into choline and ceramide-1-phosphate. A similar enzyme, showing comparable bioactivity, is secreted by certain pathogenic corynebacteria and acts as a potent virulence factor. We have previously found that SMase D toxins led to an increased susceptibility of human erythrocytes (E) to activation of complement (C) via the classical pathway (CP) in the absence of antibodies. In the present study we have investigated the CP initiating components involved in the haemolysis induced by SMases from Corynebacterium pseudotuberculosis (PLD) and from Loxosceles intermedia venom (P1). When P1 or PLD treated E were incubated with C8-depleted human serum, an increase in C1q, serum amyloid protein (SAP) and C-reactive protein (CRP) binding was observed. While purified C1q, SAP and CRP were found to bind to P1 or PLD treated E, depletion of SAP or CRP from human serum did not prevent C-mediated lysis, suggesting that pentraxins are not involved in the initiation of C-activation. However depletion of C1 lead to a greatly reduced haemolysis, demonstrating that the activation of the CP is caused by direct binding of C1q to the SMase treated cells. Binding of fluid phase C-regulators C4b-binding protein and factor H was also observed, however these C-regulators in conjunction with the membrane bound C-regulators were unable to prevent haemolysis, demonstrating the potency of SMase D facilitated binding of C1 and activation of C.

[Presence of Loxosceles similis Moenkhaus, 1898 (Araneae, Sicariidae) in Serra da Bodoquena, State of Mato Grosso do Sul, Brazil]. / Presença de Loxosceles similis Moenkhaus, 1898 (Araneae, Sicariidae) na Serra da Bodoquena, Estado de Mato Grosso do Sul, Brasil.

The venom of Loxosceles spiders causes dermonecrotic lesion and induces complement-dependent intravascular haemolysis that characterizes a severe systemic effect. In Brazil, L. gaucho, L. intermedia and L. laeta, present in the anthropic environment, have been pointed out as the most important agents of the loxoscelism. Besides these species there are others that, by predominating in the natural environment, have not been evaluated regarding human health risk, as in the case of Loxosceles similis. The development of a research project in Bodoquena Range, for ecological observation and identification of insects of medical interest, enabled the capture of Loxosceles similis specimens in the "Pitangueiras" cave and "Lago Azul" cave, in Bodoquena Range, municipality of Bonito, State of Mato Grosso do Sul, Brazil. The objectives of this study were to define the parameters for identification, environmental features of the habitat of this species, as well as an update of its geographical distribution.

Presença de Loxosceles similis Moenkhaus, 1898 (Araneae, Sicariidae) na Serra da Bodoquena, Estado de Mato Grosso do Sul, Brasil / Presence of Loxosceles similis Moenkhaus, 1898 (Araneae, Sicariidae) in Serra da Bodoquena, State of Mato Grosso do Sul, Brazil

The venom of Loxosceles spiders causes dermonecrotic lesion and induces complement-dependent intravascular haemolysis that characterizes a severe systemic effect. In Brazil, L. gaucho, L. intermedia and L. laeta, present in the anthropic environment, have been pointed out as the most important agents of the loxoscelism. Besides these species there are others that, by predominating in the natural environment, have not been evaluated regarding human health risk, as in the case of Loxosceles similis. The development of a research project in Bodoquena Range, for ecological observation and identification of insects of medical interest, enabled the capture of Loxosceles similis specimens in the [quot ]Pitangueiras[quot ] cave and [quot ]Lago Azul[quot ] cave, in Bodoquena Range, municipality of Bonito, State of Mato Grosso do Sul, Brazil. The objectives of this study were to define the parameters for identification, environmental features of the habitat of this species, as well as an update of its geographical distribution.

O veneno das aranhas do gênero Loxosceles causa lesão dermonecrótica e induz hemólise intravascular dependente de complemento, configurando um quadro clínico de intensa gravidade. No Brasil, as espécies L. gaucho L. intermedia e L. laeta, presentes no ambiente antrópico, têm sido apontadas como principais agentes do loxoscelismo. Além destas, existem outras espécies, que por predominarem no ambiente natural, não têm sido avaliadas quanto ao risco à saúde do homem, como é o caso de Loxosceles similis. O desenvolvimento de projeto de pesquisa, na Serra da Bodoquena, para observações ecológicas e identificação de insetos de interesse médico, possibilitou a captura de espécimens de Loxosceles similis na Serra da Bodoquena, Município de Bonito, Estado do Mato Grosso do Sul, Brasil, nas grutas Pitangueiras e do Lago Azul. Os parâmetros para identificação, características ambientais do habitat da espécie, bem como atualização de sua distribuição geográfica são objetos deste trabalho.

Clinical and pathological assessment of 82 patients with cardiovascular diseases undergoing autopsy at the Hospital das Clínicas of the Faculdade de Medicina de Botucatu from 1988 to 1993.

OBJECTIVE: To evaluated the clinical diagnostic, efficiency for basic death causes in patients dying of circulatory disease and de relative frequency of those diseases. METHODS: Analysis of medical record data of 82 patients, ages from 16 to 84 years old (68 over 40 years old), whose died of circulatory disease and had undergone necropsy in the period from 1988 to 1993 years in the University Hospital of Medicine Faculty of Botucatu-UNESP, Br. RESULTS: The functional class of patients were III or IV, in 78%, and 81.7% needed urgent hospitalization. By the clinical judgment the death were by ischemic heart disease in 32 (21 acute myocardial infarction), Chagas'disease in 12, valvopathy in 11, cardiomyopathy in 7, heart failure with no specification of cardiopathy in 11 and other causes in 9. At the necropsy the death cause was ischemic heart disease in 34 patients, valvopathy in 10, Chagas'disease in 10, cardiomyopathy in 5, and heart failure with no specification of cardiopathy in 2. The concordance taxes were in the same order: 94.6%, 90.0%, 83.3%, 71.4% and 28.5%. CONCLUSION: There was a great efficiency of clinical diagnosis for death cause in a general university hospital. The ischemic heart disease were the main causes of death.

Loxosceles intermedia spider envenomation induces activation of an endogenous metalloproteinase, resulting in cleavage of glycophorins from the erythrocyte surface and facilitating complement-mediated lysis.

Loxosceles is the most venomous spider in Brazil, and envenomation causes dermonecrosis and complement (C)-dependent intravascular hemolysis. The authors studied the mechanism of induction of C-induced hemolysis. Purified Loxosceles toxins rendered human erythrocytes susceptible to lysis by human C but did not have an effect on the E-bound C-regulators DAF, CR1, or CD59. However, incubation with venom toxins caused cleavage of glycophorin from the erythrocyte (E) surface, facilitating C activation and hemolysis. The results suggest that glycophorin is an important factor in the protection of E against homologous C. Cleavage of glycophorin (GP) A, GPB, and GPC occurred at sites close to the membrane but could not be accomplished using purified GPA and purified toxins, demonstrating that cleavage was not an effect of a direct proteolytic action of the Loxosceles toxins on the glycophorins. Inhibition of the cleavage of glycophorins induced by Loxosceles venom was achieved with 1,10-phenanthroline. The authors propose that the sphingomyelinase activity of the toxins induces activation of an endogenous metalloproteinase, which then cleaves glycophorins. They observed the transfer of C-dependent hemolysis to other cells, suggesting that the Loxosceles toxins can act on multiple cells. This observation can explain the extent of hemolysis observed in patients after envenomation. Identification of the mechanism of induction of susceptibility to C-mediated lysis after Loxosceles envenomation opens up the possibility of the development of an effective therapeutic strategy. (Blood. 2000;95:683-691)

Ontogenetic development of Loxosceles intermedia spider venom.

Envenomation by Loxosceles spider has become a public health problem in the South region of Brazil, mainly due to high levels of domiciliary infestation by Loxosceles intermedia spiders. The toxic effects of L. intermedia venom are mostly associated with a 35 kDa protein (F35) which presents complement-dependent haemolytic and dermonecrotic activities. The aim of this study was to detect, through biological and immunochemical assays, the appearance of the main toxic component, F35, during the ontogenetic development of L. intermedia spiders. The toxin appeared in its fully active form in venom of third instar spiderlings; from then on its activity increased throughout development until adulthood. On the other hand, F35 was not detected in extracts of either eggs or spiderlings of the first and second instars.