Ventricular arrhythmias among patients with implantable cardioverter-defibrillator during the COVID-19 pandemic.

Background: Coronavirus Disease-2019 (COVID-19) has been associated with myocardial injury and higher risk of arrhythmic complications. However, no reports are available about the effect of the ongoing pandemic on arrhythmias in patients at risk. Objective: To describe the effect of COVID-19 pandemic on arrhythmic burden among high-risk patients. Methods: This is a cross-sectional study on the incidence of ventricular arrhythmia (VA) during the pandemic outbreak (study period), compared to the same timeframe in 2019 (reference period). Inclusion criteria were age (>18 years) and having an implantable cardiac defibrillator (ICD). Results: Among 455 patients enrolled (mean age 64.9 ± 15.7 years; 25.1% females and 39.6% with CRTD), in the study period, 45 (9.9%) patients experienced a total of 86 VA; 8 patients (1.7%) required antitachycardia-pacing (ATP) and 6 (1.3%) at least one shock. In the reference period, a total of 69 events occurred in 36 patients (7.9%). Six patients (1.3%) required ATP and three (0.7%) at least one shock. The number of patients that suffered from any arrhythmic events in the study period (9.9% vs 7.9%) did not significantly differ from the reference period (χ2 = 1.09, P = .29). The main predictor of VA during the COVID-19 pandemic was the previous history of any ICD therapy (OR = 3.84, P < .001). Conclusions: No evidence of an increase of arrhythmic burden was found during the COVID-19 pandemic among patients with an ICD.

Cardiac arrhythmias and In-hospital mortality amongst patients with takotsubo cardiomyopathy: A retrospective study in an Italian population.

BACKGROUND: Takotsubo cardiomyopathy (TTC) is an acute non-ischemic cardiomyopathy classically associated with an intense emotional or physiologic trigger. Data on the relationship between arrhythmias and mortality in TTC have been limited by small sample sizes. The aim of this study is to assess the impact of ventricular and atrial arrhythmias and advanced atrioventricular block on in-hospital mortality in a large inpatient population with TTC. METHODS: Data was obtained from the Italian National Healthcare System Databank from 2009 to 2016. Patients with TTC were identified using diagnosis codes and clinical characteristics were collected, with a primary outcome of mortality. Univariate and multivariate logistic regression analyses were used to identify significant predictors for mortality, and patients with TTC were further analyzed according to sex and age. RESULTS: There were 10,861 patients with TTC; 91.7% were women (9959) and the mean age was 70.7 +/- 11.9 years. The mortality rate was 2.2%; while 1.2% of patients had ventricular arrhythmias, 10.0% had atrial arrhythmias, and 1.3% had advanced atrioventricular block. Male sex, increased age and ventricular arrhythmias were predictors of mortality. In a sex-stratified analysis, ventricular arrhythmias and advanced age remained independent predictors for mortality in women. CONCLUSION: In this large retrospective analysis, male sex and the presence of ventricular arrhythmias are strong predictors of mortality in patients hospitalized with TTC.

Clinical experience of a chronic urticaria referral university center.

Summary: Objective. Describing routine procedures, clinical profile and evolution of patients treated in a chronic urticaria CU reference center of a university hospital. Methods. Retrospective analysis of clinical records and database of CU patients registered between March 2011 and February 2016 in a reference center. Besides demographic characteristics, disease duration, comorbidities, angioedema, thyroid lab tests, urticaria subtypes, provocation tests, UAS and CUQ2oL scores were recorded. Patients with 3 or more visits were included in analysis regarding the first and last visits, to evaluate pharmacological treatment and differences of UAS/CUQ2oL scores, antihistamines anti H1 dosages and need of other medications, according urticaria subtypes. Results.During the study, 252 patients were attended, 200 with CU, including 162 women, median age 45 years, perc 25 - 75 = 27 - 58, and median duration of symptoms before diagnosis 24 months, perc 25 - 75 = 9 - 60. Regarding the etiology, 166 (83%) patients had chronic spontaneous urticaria (CSU), 34 (17%) had isolated chronic inducible urticaria (CIndU) and 66 (33%), CSU with CIndU. Among the 123 patients followed up for 3 or more visits, first prescription to 106 (86.2%) patients was monotherapy with anti-H1, and associations with other medications were prescribed to 17 (13.8%). At the last visit, 94 (76.5%) received antihistamines, and 29 (23.5%) used associations. Patients with CSU + CIndU + ASST positive need more association of anti-H1 with other medications than patients with CSU + CIndU and only CIndU (÷2 = 7.998; p 0.01). Between first and last visits, CUQ2oL mean scores changed from 35.7 (± 21.9) to 22.6 (± 21.0) (Z = -4.833 p less than 0.000). Conclusions.Most of the patients presented CSU, frequently associated with CIndU. There was an improvement in the patients' quality of life during the follow-up period. All patients were treated with antihistamines and there was a great need for doses above the standardized and also for combination with other medications, especially in patients with concomitance of urticaria subtypes.

Evaluation of the frequency of non-motor symptoms of Parkinson's disease in adult patients with Gaucher disease type 1.

BACKGROUND: Gaucher disease (GD) is caused by deficiency of beta-glucocerebrosidase (GCase) due to biallelic variations in the GBA1 gene. Parkinson's disease (PD) is the second most common neurodegenerative condition. The classic motor symptoms of PD may be preceded by many non-motor symptoms (NMS), which include hyposmia, rapid eye movement (REM) sleep behavior disorder, constipation, cognitive impairment, and depression. Population studies have identified mutations in GBA1 as the main risk factor for idiopathic PD. The present study sought to evaluate the prevalence of NMS in a cohort of patients with GD type 1 from Southern Brazil. METHODOLOGY: This is an observational, cross-sectional study, with a convenience sampling strategy. Cognition was evaluated by the Montreal Cognitive assessment (MoCa), daytime sleepiness by the Epworth Scale, depression by the Beck Inventory, constipation by the Unified Multiple System Atrophy Rating Scale, and REM sleep behavior disorder by the Single-Question Screen; hyposmia by the Sniffin' Sticks. Motor symptoms were assessed with part III of the Unified Parkinson's Disease Rating Scale. All patients were also genotyped for the GBA1 3'-UTR SNP (rs708606). RESULTS: Twenty-three patients (female = 13; on enzyme replacement therapy = 21, substrate reduction therapy = 2) with a mean age of 41.45 ± 15.3 years (range, 22-67) were included. Eight patients were found to be heterozygous for the 3'-UTR SNP (rs708606). Fourteen patients (8 over age 40 years) presented at least one NMS; daytime sleepiness was the most frequent (n = 10). Two patients (aged 63 and 64, respectively) also presented motor symptoms, probably drug-related. CONCLUSIONS: NMS were prevalent in this cohort. We highlight the importance of a multidisciplinary follow-up focusing on earlier diagnosis of PD, especially for patients with GD type 1 over the age of 40.

Food protein-induced enterocolitis syndrome in children: what's known? What's new?

Summary: Food protein-induced enterocolitis syndrome (FPIES) is an under-recognized and frequently misdiagnosed non-IgE mediated food allergy syndrome. Affected infants show gastrointestinal symptoms few hours after ingestion of the incriminating food. Pathophysiology of FPIES has not yet been clearly defined and needs further characterization. The common allergy tests are not helpful for this disorder and tests for food specific IgE are usually negative. A diagnostic oral food challenge (OFC) is the method to confirm the diagnosis of FPIES. This review summarizes what is known about epidemiology, pathophysiology, clinical characteristics and diagnosis and what's new about therapeutic options of FPIES.

Serum levels of proteins and acute-phase proteins in captive emus (Dromaius novaehllandieae) of different ages / Teores séricos de proteínas, inclusive proteínas de fase aguda, em emus (Dromaius novaehollandiae) de diferentes faixas etárias e criados em cativeiro

Protein electrophoresis is a relatively simple technique that allows separating serum protein fractions, and provides important information in the investigation and diagnosis of several diseases. This study determined the levels of acute-phase proteins in the serum of healthy, captive emus (Dromaius novaehollandiae). Animals were divided into two groups (n=11 in each) based on age, with 1-year-old and 4-year-old emus. Acute-phase proteins were separated by SDS-PAGE. Ceruloplasmin, transferrin, albumin, haptoglobin, acidic glycoprotein, IgA, and IgG were detected in the serum of all animals. Protein profiles varied significantly with age (P<0.05). Individuals in the 4-year-old emus group had higher values of ceruloplasmin, transferrin, albumin, haptoglobin, and acidic glycoprotein, compared with the group with 1-year-old animals, showing the role of age in the protein profile of this species. Reference values for acute-phase proteins in healthy emus may be useful in the evaluation of health status and in the diagnosis of diseases affecting the species.(AU)

A eletroforese de proteínas é um método relativamente simples, que permite a separação das proteínas do plasma em frações. Sua interpretação fornece informações importantes para a investigação e o diagnóstico de inúmeras doenças. O objetivo deste estudo foi o de determinar a concentração das proteínas de fase aguda no soro de emus (Dromaius novaehollandiae) hígidos e criados em cativeiro. As aves foram separadas em dois grupos: grupo 1: (n=11), aves com um ano de idade; grupo 2: (n=11), aves com quatro anos de idade. As proteínas de fase aguda foram separadas por eletroforese em gel de poliacrilamida (SDS-PAGE). Identificaram-se as proteínas ceruloplasmina, transferrina, albumina, IgG, haptoglobina, glicoproteína ácida, IgA e IgG no soro de todos os emus. Houve diferença (P<0.05) entre os traçados eletroforéticos em função da faixa etária. As aves do grupo 2 apresentaram valores superiores de ceruloplasmina, transferrina, albumina, haptoglobina e glicoproteína ácida quando comparadas às aves do grupo 1. Conclui-se que o perfil eletroforético de emus sofre alterações conforme a idade analisada. O estabelecimento de valores de referência para as proteínas de fase aguda de emus hígidos poderá auxiliar estudos futuros na avaliação da saúde assim como no diagnóstico de doenças em emus.(AU)

Nutritional Status and Body Composition in Patients With Hepatic Glycogen Storage Diseases Treated With Uncooked Cornstarch—A Controlled Study

Abstract Hepatic glycogen storage diseases (GSDs) are genetic diseases associated with fasting hypoglycemia. Periodic intake of uncooked cornstarch is one of the treatment strategies available for those disorders. For reasons that are still not clear, patients with hepatic GSDs may be overweight. Aims: To assess nutritional status and body composition in patients with hepatic GSDs receiving uncooked cornstarch. Methods: The sample included 25 patients with hepatic GSD (type Ia = 14; Ib = 6; III = 3; IX? = 1; IX? = 1), with a median age of 11.0 years (interquartile range [IQR] = 9.0-17.5), matched by age and gender with 25 healthy controls (median age = 12.0 years, IQR = 10.0-17.5). Clinical, biochemical, and treatment-related variables were obtained from medical records. Nutritional status and body composition were prospectively evaluated by bioelectrical impedance. Results: Patients and controls did not differ with regard to age and gender. Height was significantly reduced in patients (median = 1.43 m, IQR = 1.25-1.54) in comparison to controls (median = 1.54 m, IQR = 1.42-1.61; P = .04). Body mass index for age z-score and fat mass percentage were higher in patients (median = 1.84, IQR = 0.55-3.06; and 27.5%, IQR = 22.6-32.0, respectively) than in controls (median = 0.86, IQR = ?0.55 to 1.82; P = .04 and 21.1%, IQR = 13.0-28.3; P = .01, respectively). When patients were stratified by type, those with GSD Ia had significantly higher adiposity (median fat mass = 28.7%, IQR = 25.3-32.9) than those with GSD III and GSD IX?/? (median fat mass = 20.9%, IQR = 14.9-22.6; P = .02). Conclusions: Our findings suggest that patients with hepatic GSD on treatment with cornstarch, especially those with GSD Ia, exhibit abnormalities in nutritional status and body composition, such as short stature and a trend toward overweight and obesity.

Rare disease landscape in Brazil: report of a successful experience in inborn errors of metabolism.

Brazil is a country of continental dimensions, with many social inequalities. The latter are reflected on its health system, which comprises a large public component called SUS, a small paid health insurance component and a third very small private component, in which patients pay personally for medical services. Seventy five percent of the population depends on SUS, which thus far does not provide adequate coverage for genetic medical procedures. In 2014, SUS introduced the "Policy for the Integral Attention to Subjects with Rare Diseases", establishing guidelines for offering diagnosis and treatment. The policy defines the two main axes, genetic and non-genetic rare diseases. In this fashion, public genetic services in SUS will be installed and funded not by themselves, but as part of the more general policy of rare diseases. Unfortunately, up to now this policy is still depending on financial allowances to be effectively launched. In this article, our intention was to describe activities developed in the area of inborn errors of metabolism by a Brazilian reference center. In spite of the lack of support of SUS, thousands of Brazilian families affected by rare genetic metabolic disorders, and many health professionals from all regions of Brazil, already have benefited from the services, training programs and research projects provided by this comprehensive center.

Thuya occidentalis CH12 como tratamento alternativo da papilomatose canina / Thuya occidentalis CH12 as an alternative treatment to dog papilomatosis

RESUMO A papilomatose é uma doença de natureza crônica e pode causar tumores epiteliais e na mucosa. Não possui predileção por sexo, raça ou idade, mas comumente aparece em animais jovens. As lesões papilares ocorrem principalmente na mucosa bucal, nos lábios, língua e da faringe, além destes, também são encontradas na forma ocular e cutânea. Este estudo teve como objetivo relatar a eficácia da Thuya occidentalis CH12, uma medicação homeopática de uso comum, no tratamento de cães com papilomatose. Os resultados positivos puderam ser vistos, em alguns casos, já na primeira semana do tratamento, em outros, após vinte dias, e o desaparecimento total das lesões, na maioria dos casos, ocorreu com quinze dias. Alicerçada no princípio da similitude, a homeopatia apóia-se na observação experimental de que toda substância capaz de provocar determinados sintomas em uma pessoa sadia, é capaz de curar estes mesmos sintomas em uma pessoa enferma. A Thuya occidentalis provou ser eficiente contra lesões de papilomavírus canina, e apresentou resultados rápidos e com um valor econômico acessível.

ABSTRACT The papillomatosis is a disease of chronic nature and can cause epithelial and mucosa tumors. . It may affect any gender, race or age but is most common in young animals. The papillary lesions occur mainly on the oral mucosa, in the lips, tongue and pharynx, besides appearing also in the eeyes and skin. This study aimed to report the effectiveness of the Thuya occidentalis CH12 , a homeopathic medication commonly used in the treatment of dogs with papillomatosis . The positive results could be noticed, in some cases, even in the first week of treatment , or after twenty days, with the total remission of the lesions occurring in most of the cases within fifteen days . Founded based on the similarity principle, the homeopathy relies on the experimental observation that any substance capable of causing certain symptoms in a healthy person can cure these same symptoms in a sick person. The Thuya occidentalis proved to be effective against canine papillomavirus lesions, and with fast results at an affordable economic value.

Establishment of peritoneal liquid electrophoretogram from healthy horses and horses submitted to experimentally induced intestinal obstruction / Estabelecimento do eletroforetograma do líquido peritoneal de equinos hígidos e daqueles submetidos à obstrução intestinal experimental

The initial inflammatory stages of the colic syndrome include changes known as acute phase response. The aim of this study was to contribute with the establishment of reference values concerning the electrophoretogram of peritoneal liquid from healthy horses and horses submitted to experimentally induced intestinal obstruction. Twenty-one horses were allotted in four groups: duodenal obstruction (DG), ileum obstruction (IG), left-dorsal colon obstruction (MG), and control group (CG). Peritoneal liquid was sampled before obtruction (T0), with 3 hours of obstruction (T3) and 6, 30, 102 and 174 hours after desobstructing (T6, T30, T102 and T174, respectively). Total protein levels were determined by the biuret method and protein fractions were obtained by SDS-PAGE electrophoresis. The acute phase proteins (APP) identified were Immunoglobulin-A, ceruloplasmin, transferrin, albumin, α1-antitrypsin, heavy and light chains of immunoglobulin-G, haptoglobin, α1-acid glycoprotein and a still unnamed protein, which was called P24. There was no difference (P>0.3) in protein levels among groups, although a significant difference (P>0.05) was observed between distinct experimental moments in each group evidencing a higher response of the APP in the obstructed groups. The APP fractioning of the peritoneal liquid was standardized to establish a standard curve for healthy equines and those submitted to induced intestinal obstruction. Moreover, it was verified that the SDS-PAGE electrophoresis was sensitive and effective to help diagnose abdominal inflammatory processes...

Na cólica equina, os estágios iniciais da inflamação incluem alterações denominadas resposta de fase aguda. O objetivo deste estudo foi contribuir para o estabelecimento de valores de referência do proteinograma do líquido peritoneal de equinos hígidos e daqueles submetidos à obstrução intestinal experimental. Vinte e um animais foram distribuídos nos grupos: obstrução de duodeno (GD), íleo (GI), cólon dorsal esquerdo (GM) e controle instrumentado (GC). As colheitas das amostras de líquido peritoneal foram realizadas antes (T0), durante as obstruções (T3) e após as desobstruções (T6, T30, T102 e T174 horas). A proteína total foi determinada pelo método do biureto, e as frações proteicas obtidas por eletroforese em SDS-PAGE. Identificaram-se as proteínas de fase aguda (PFA): IgA, ceruloplasmina, transferrina, albumina, α1-antitripsina, cadeias pesada e leve de imunoglobulina-G, haptoglobina, alfa-1-glicoproteína ácida e uma proteína nominalmente não identificada, que foi chamada P24. Não houve diferença (P>0.3) nas concentrações proteicas entre os grupos, somente entre tempos dentro de cada grupo (P>0.05), evidenciando uma resposta maior das PFA dos grupos obstruídos. O fracionamento eletroforético das PFA, presentes no líquido peritoneal, foi padronizado de modo a estabelecer a curva-padrão para equinos hígidos e para aqueles submetidos à obstrução intestinal; ademais, verificou-se que o referido fracionamento proteico mostrou-se sensível e eficaz no auxílio ao diagnóstico de processos inflamatórios abdominais...

Reproductive efficiency of adult and prepubertal goats subjected to repeated follicular aspiration / Eficiência reprodutiva em cabras adultas e pré-púberes após repetidas sessões de aspiração folicular

The objective of this study was to assess the reproductive response of adult and prepubertal goats subjected to repeated laparoscopic ovum pick-up (LOPU). The study animals were divided into two groups, specifically, adult nanny goats (GA, n=10) and prepubertal nanny goats (GP, n=10), which were subjected to estrous synchronization and ovarian stimulation for LOPU. Both groups underwent six LOPU procedures at seven-day intervals and were subsequently subjected to controlled mating and pregnancy diagnosis to evaluate their future fertility. The study showed a reduction in the number of follicles visualized and in the amount and quality of the oocytes that were recovered and exposed to in vitro maturation. As indicated by the fertility test, however, no complications were found during the laparoscopic procedures that would impair the reproductive future of the animals. Therefore, a viable number of oocytes were obtained even with the decreased reproductive efficiency, proving that repeated LOPUs do not interfere with the reproductive of adult and prepubertal nanny goats. These results indicate a positive aspect of this procedure, allowing for increasing reproductive performance of this kind, when used for the production in vitro.

O objetivo deste estudo foi avaliar a resposta reprodutiva de cabras adultas e pré-púberes submetidas a repetidas aspirações foliculares por videolaparoscopia (LOPU). Os animais do estudo foram divididos em dois grupos, especificamente cabras adultas (GA, n = 10) e pré-púberes (GP, n = 10), que foram submetidas a sincronização de estro e estimulação ovariana para LOPU. Ambos os grupos foram submetidos a seis procedimentos LOPU em intervalos de sete dias e foram posteriormente submetidos à monta controlada e posterior diagnóstico de gestação para avaliar sua fertilidade. O estudo mostrou uma diminuição do número de folículos visualizados, na quantidade e na qualidade dos oócitos que foram recuperados e expostos à maturação in vitro. Tal como indicado pelo teste de fertilidade, no entanto, não foram observadas grandes complicações durante os procedimentos laparoscópicos que pudessem prejudicar o futuro reprodutivo dos animais. Portanto, foi obtido um número de oócitos viáveis, mesmo com a diminuição da eficiência reprodutiva, provando que repetidas LOPU não interferem na reprodutividade de animais adultos e pré-púberes. Estes resultados indicam um aspecto positivo desse procedimento, possibilitando um aumento da eficiência reprodutiva dessa espécie quando utilizado para a produção in vitro.

Assessment of Basal Metabolic Rate and Nutritional Status in Patients with Gaucher Disease Type III.

UNLABELLED: Gaucher disease type III (GD III) is a rare form of GD characterized by neurological involvement and severe systemic disease. The objective of this study was to assess the nutritional status and energy metabolism of patients with GD III. METHODS: The basal metabolic rate (BMR, measured by indirect calorimetry) and anthropometric parameters (height, weight, body mass index (BMI), and arm circumference) of three patients with GD III (p.L444P/L444P genotype) were assessed at different time points. The clinical severity of GD was assessed by means of physical examination, laboratory tests, imaging findings, and the severity scores proposed by Zimran (SSI) and Davies (SSNI). RESULTS: The measured BMR of patients 1 (age 14 years, not on enzyme replacement therapy (ERT), SSI score 33, SSNI score 14.5), 2 (age 17 years, on ERT, SSI score 33, SSNI score 16), and 3 (age 20 years, on ERT, SSI score 33, SSNI score 7.5) was, respectively, 47%, 72%, and 15% higher than that estimated by the Harris-Benedict equation. Patients with a more severe phenotype had more marked hypermetabolism. Patients 1 and 2 had BMI-for-age z scores of -1.09 and -1.39, respectively, and height-for-age z scores of -4.27 and -3.02, respectively; patient 3 had a BMI of 24.7 kg/m(2). CONCLUSION: All three patients showed hypermetabolism; however, the two patients with the highest BMR had more severe GD and were malnourished. Additional studies are warranted to assess whether hypermetabolism may be a biomarker of disease severity in GD.

Identification of hydrocarbon sources in contaminated soils of three industrial areas.

The present paper deals with identification of hydrocarbon sources in contaminated soil of three tank farms located in north, central and south Italy. Parent polycyclic aromatic hydrocarbons (naphthalene through benzo(g,h,i)perylene) and n-alkanes (n-C10 through n-C36) were determined. The study of source assignments was carried out by their distribution patterns, their diagnostic ratios, and determination of less-commonly used markers. The data show anthropogenic and biogenic origin of n-alkanes and petrogenic and pyrolytic sources of PAHs. Multiple sources of hydrocarbons, that were not considered in the preliminary environmental assessments, are identified. The application of a multi-criteria approach allows to locate petroleum pollution sources that affect the study sites. The results demonstrate that the application of a multi-criteria approach for source identification is a key point to assess environmental damage and prove that an accurate study of source identification has to be performed. The suggested methodology is a useful tool to manage contaminated sites and to plan appropriate interventions of clean up.

Tumour microenvironment and radiation response in sarcomas originating from tumourigenic human mesenchymal stem cells.

BACKGROUND: Resistance to radiation therapy remains a serious impediment to cancer therapy. We previously reported heterogeneity for clonogenic survival when testing in vitro radiation resistance among single-cell derived clones from a human mesenchymal cancer stem cell model (hMSC). Here we aimed to determine whether this heterogeneity persisted in tumours established from these clones, and whether the response to radiation treatment was principally governed by cell-intrinsic qualities or by factors pertaining to the tumour microenvironment, such as the degree of hypoxia and vascularization. METHODS: Immune-deficient female mice were implanted on the backs with cells from one of the clones. The subsequent tumours were subjected to either radiation treatment or had the tumour microenvironment assayed, when they reached 400 mm³. Radiation was given as a single fraction of 0-15 Gy and the degree of tumour control and time to three times the treatment volume were noted. Tumours used for the microenvironmental assay had intratumoral hypoxia measured by the Eppendorf oxygen electrode and pimonidazole staining, and the extent of vascularization determined by a microvasculature density assay using endothelial-specific staining. RESULTS: All microenvironmental assays indicated a similar degree of hypoxia and vascularization for the selected clones. Nonetheless, the tumours responded differently to radiation treatment since the BB3 clone displayed tumour control at 5, 10 and 15 Gy, whereas tumour control was not seen below 15 Gy with the CE8 clone. CONCLUSION: For tumours that displayed similar degrees of oxygenation and vascularization, the clone-specific in vitro radiation resistance could predict the in vivo response to radiation treatment. These results favor the hypothesis that intrinsic genetic factors can govern radiation resistance in this cancer stem cell model.

Tumourigenicity and radiation resistance of mesenchymal stem cells.

BACKGROUND: Cancer stem cells are believed to be more radiation resistant than differentiated tumour cells of the same origin. It is not known, however, whether normal nontransformed adult stem cells share the same radioresistance as their cancerous counterpart. MATERIAL AND METHODS: Nontumourigenic (TERT4) and tumourigenic (TRET20) cell lines, from an immortalised mesenchymal stem cell line, were grown in culture prior to irradiation and gene expression analysis. Radiation resistance was measured using a clonogenic assay. Differences in gene expression between the two cell lines, both under nontreated and irradiated conditions, were assessed with microarrays (Affymetrix Human Exon 1.0 ST array). The cellular functions affected by the altered gene expressions were assessed through gene pathway mapping (Ingenuity Pathway Analysis). RESULTS: Based on the clonogenic assay the nontumourigenic cell line was found to be more sensitive to radiation than the tumourigenic cell line. Using the exon chips, 297 genes were found altered between untreated samples of the cell lines whereas only 16 genes responded to radiation treatment. Among the genes with altered expression between the untreated samples were PLAU, PLAUR, TIMP3, MMP1 and LOX. The pathway analysis based on the alteration between the untreated samples indicated cancer and connective tissue disorders. CONCLUSION: This study has shown possible common genetic events linking tumourigenicity and radiation response. The PLAU and PLAUR genes are involved in apoptosis evasion while the genes TIMP3, MMP1 and LOX are involved in regulation of the surrounding matrix. The first group may contribute to the difference in radiation resistance observed and the latter could be a major contributor to the tumourigenic capabilities by degrading the intercellular matrix. These results also indicate that cancer stem cells are more radiation resistant than stem cells of the same origin.

Cancer stem cell overexpression of nicotinamide N-methyltransferase enhances cellular radiation resistance.

BACKGROUND: Cancer stem cells are thought to be a radioresistant population and may be the seeds for recurrence after radiotherapy. Using tumorigenic clones of retroviral immortalized human mesenchymal stem cell with small differences in their phenotype, we investigated possible genetic expression that could explain cancer stem cell radiation resistance. METHODS: Tumorigenic mesenchymal cancer stem cell clones BB3 and CE8 were irradiated at varying doses and assayed for clonogenic surviving fraction. Altered gene expression before and after 2 Gy was assessed by Affymetric exon chip analysis and further validated with q-RT-PCR using TaqMan probes. RESULTS: The CE8 clone was more radiation resistant than the BB3 clone. From a pool of 15 validated genes with altered expression in the CE8 clone, we found the enzyme nicotinamide N-methyltransferase (NNMT) more than 5-fold upregulated. In-depth pathway analysis found the genes involved in cancer, proliferation, DNA repair and cell death. CONCLUSIONS: The higher radiation resistance in clone CE8 is likely due to NNMT overexpression. The higher levels of NNMT could affect the cellular damage resistance through depletion of the accessible amounts of nicotinamide, which is a known inhibitor of cellular DNA repair mechanisms.

Leucogram and serum acute phase protein concentrations in queens submitted to conventional or videolaparoscopic ovariectomy / Leucograma e concentrações séricas de proteínas de fase aguda de gatas submetidas à ovariectomia convencional ou por videolaparoscopia

Thirty health queens were submitted to ovariectomy by conventional technique or by videolaparoscopy. In order to study the intensity of inflammatory response by means of acute phase protein analysis and white blood cell count, serum samples were taken before and until 144 hours after the surgical procedures. The protein concentrations that were significantly increased 24 hours after surgical procedures were: ceruloplasmin, hemopexin, haptoglobin, and α1-acid glycoprotein, 69.8 percent, 103.5 percent, 117.3 percent, and 199.0 percent, respectively, for conventional ovariectomy; and 22.3 percent, 46.1 percent, 79.8 percent, and 74.6 percent, respectively, for laparoscopic ovariectomy. Therefore, inflammatory response was more intense in queens submitted to conventional ovariectomy. Results indicate that the increase or decrease in acute phase proteins, as well as in white blood cells count, may be useful in the evaluation of inflammatory response induced by these surgical procedures.

Trinta gatas, saudáveis, foram submetidas à ovariectomia pela técnica convencional e por videolaparoscopia. Amostras de sangue foram obtidas com o objetivo de verificar a intensidade da resposta inflamatória por meio da análise das concentrações de proteinas de fase aguda e contagem de leucócitos antes e até 144 horas após procedimento cirúrgico. As proteínas que apresentaram aumento significativo 24 horas após a cirurgia foram: ceruloplasmina, hemopexina, haptoglobina e α1-glicoproteína ácida, 69,8 por cento, 103,5 por cento, 117,3 por cento e 199,0 por cento, respectivamente, para ovariectomia convencional, e 22,3 por cento, 46,1 por cento, 79,8 por cento e 74,6 por cento, respectivamente, para ovariectomia por videolaparoscopia. A resposta inflamatória foi mais evidente nas gatas submetidas à ovariectomia convencional. Os resultados mostram aumento e diminuição na concentração de proteínas de fase aguda e na contagem de leucócitos, podendo ser utilizados na avaliação da resposta inflamatória induzida por procedimentos cirúrgicos.

Características celulares e bioquímicas do líquido peritoneal de equinos submetidos à obstrução experimental do duodeno, íleo e cólon maior / Cellular and biochemical characteristics of peritoneal fluid of equines submitted to experimental obstruction of duodenum, ileum, and large colon

Estudaram-se as características macroscópicas, bioquímicas e citológicas do líquido peritoneal de equinos submetidos a um modelo experimental de obstrução intestinal em 24 animais, distribuídos em grupos: de controle instrumentado (GI), de obstrução do duodeno (GII), de obstrução do íleo (GIII) e de obstrução do cólon maior (GIV). As amostras de líquido peritoneal foram colhidas antes da cirurgia (T0), durante as obstruções (T60i-T180i) e após as desobstruções (T60ri-T7º ). Durante o período obstrutivo, não foram observadas alterações significativas nos parâmetros bioquímicos e citológicos avaliados no líquido peritoneal dos animais. Após as desobstruções, apenas os animais de GII e GIII apresentaram resposta inflamatória mais intensa, caracterizada por maior contagem global e diferencial de leucócitos e dos valores de proteína total, fibrinogênio, lactato e fósforo inorgânico. As alterações laboratoriais não foram associadas a sinais clínicos indicativos da presença de processo inflamatório abdominal, demonstrando que os resultados da análise do líquido peritoneal, apesar de auxiliarem no acompanhamento da evolução do processo de cura, não devem ser utilizados isoladamente na elaboração do diagnóstico e do prognóstico de complicações no pós-operatório de equinos com cólica.

The macroscopic, biochemical, and cytological characteristics of peritoneal fluid of equines submitted to intestinal obstruction using an experimental model were evaluated. Twenty-four animals were distributed in four groups: instrumented control (GI), duodenum obstruction (GII), ileum obstruction (GIII), and large colon obstruction (GIV). Peritoneal fluid samples were collected before the surgery (T0), during the obstruction (T60i-T180i), and after unblocking procedures (T60ri-T7º ). During obstructive period, significant alterations were not observed in biochemical and cytological examination of peritoneal fluid of all animals. After unblocking procedure, animals from GII and GIII presented intense inflammatory response characterized by higher global and differential leukocytes counts, as well as in fibrinogen and total protein concentrations; lactate and inorganic phosphorus concentrations in peritoneal fluid were also increased. The laboratory alterations were not associated with clinical signs, indicative of the abdominal inflammatory process presence. Results showed that analyses of peritoneal fluids can be used as support in the evolution of healing process. However, they can not be isolated used for a diagnosis and prognosis of equine postoperative complications.

Evaluation of creatine kinase (CK) and aspartate aminotransferase (AST) activities after laparoscopic or conventional ovariectomy in queens.

Creatine kinase (CK) and aspartate aminotransferase (AST) are mainly muscle-specific enzymes, which can be associated with muscle tissue damage. The aim of this study was to assess the activities of CK and AST during the postoperative period, after conventional (G1) and videolaparoscopic ovariectomy (G2), in queens. A further group (G3) was subjected to anaesthesia only. Results demonstrate that there were significant differences between groups. The highest levels of CK were recorded in G1, however at a confidence level of p<0.05 there was no significant difference between groups during the first 6 hours after surgery. A significant (p<0.05) increase of CK values was identified between 0 h and 3 h in both groups (G1 and G2). Regarding AST activity there was no significant variation between groups, but again there was a significant difference between values at 0 h and 3h after surgery. In conclusion, ovariectomy performed by videolaparoscopy seems to cause less muscle damage when compared to the conventional method.

Validation of criteria for selective his bundle and para-hisian permanent pacing.

BACKGROUND: His Bundle (HB) pacing is a valid alternative to right ventricular pacing for patients with preserved His-ventricle conduction who are candidates for permanent stimulation. Permanent pacing in the HB area enables Selective HB pacing (SHBP) or para-Hisian pacing (PHP) to be achieved. The aim of our study was to draw up a set of easy criteria to differentiate and validate the two kinds of stimulations according to the pacing output and the ECG/EKG signals. METHODS AND RESULTS: From February to July 2005, 17 patients eligible for a pacemaker (PM) procedure underwent implantation with the Medtronic SelectSecure lead (Medtronic, Minneapolis, MN, USA) screwed into the HB area.SHBP was defined when the intrinsic QRS was equal, in both duration and morphology, to the paced QRS, the His-Ventricular (H-V) interval was equal to Pace-Ventricular interval (Vp-V) and, at low output, only the HB was captured, while increasing the output resulted in both the HB and right ventricular (RV) being captured (widening of QRS at high output). Conversely, PHP was defined when the intrinsic QRS differed from the paced one, either in morphology or in duration and, at high output, both the RV and HB were captured (non-SHBP), while decreasing the output resulted in losing HB capture (widening of QRS at low output). According to these criteria, SHBP was achieved in 11 patients, while in the remaining 6, PHP was obtained. No adverse events were reported. CONCLUSIONS: The above criteria enabled SHBP and PHP to be validated easily and clearly. A longer follow-up will be needed in order to ascertain whether the clinical outcome of these two approaches differs.