Retrospective assessment of tolerability and efficacy of zoledronate in the palliative treatment of cancer-bearing dogs.

Zoledronate is a bisphosphonate frequently used for the treatment of hypercalcaemia of malignancy and tumour-associated bone pain in dogs, however, there is a paucity of information regarding its use in veterinary medicine. The aim of this retrospective study was to report the tolerability of zoledronate in the palliative treatment of cancer-bearing dogs and secondarily to to assess the efficacy of zoledronate for the treatment of hypercalcaemia of malignancy. Thirty-seven dogs (22 with tumour-associated bone pain and 15 with hypercalcaemia of malignancy) that received 114 zoledronate infusions were included. Tolerability was assessed by the absence of post-zoledronate hypocalcaemia or other adverse events as defined by Veterinary Cooperative Oncology Group-Common Terminology Criteria for Adverse Events criteria. Efficacy was assessed by comparison of available ionized calcium levels before and after zoledronate administration in hypercalcaemic dogs. In 79% of zoledronate infusions, no adverse events were reported. The majority of adverse events which occurred in the other 21% of infusions could be attributed to concurrent chemotherapy or the underlying neoplastic disease. There was a small but significant increase in creatinine following treatment with zoledronate, however, none of the dogs developed clinically significant renal disease. In eight hypercalcaemic dogs with available ionized calcium following zoledronate administration, ionized calcium decreased rapidly within 7 days following treatment with zoledronate. Zoledronate is well-tolerated with few recorded adverse events, however, monitoring of serum creatinine is advised. Zoledronate seems to be effective in the treatment of hypercalcaemia of malignancy.

Maternal supplementation with cobalt sources, folic acid, and rumen-protected methionine and its effects on molecular and functional correlates of the immune system in neonatal Holstein calves.

Calves born to multiparous Holstein cows fed during the last 30 d of pregnancy 2 different cobalt sources [cobalt glucoheptonate (CoPro) or cobalt pectin (CoPectin)], folic acid (FOA), and rumen-protected methionine (RPM) were used to study neonatal immune responses after ex vivo lipopolysaccharide (LPS) challenge. Groups were (n = 12 calves/group) CoPro, FOA+CoPro, FOA+CoPectin, and FOA+CoPectin+RPM. Calves were weighed at birth and blood collected at birth (before colostrum), 21 d of age, and 42 d of age (at weaning). Growth performance was recorded once a week during the first 6 wk of age. Energy metabolism, inflammation, and antioxidant status were assessed at birth through various plasma biomarkers. Whole blood was challenged with 3 µg/mL of LPS or used for phagocytosis and oxidative burst assays. Target genes evaluated by real-time quantitative PCR in whole blood samples were associated with immune response, antioxidant function, and 1-carbon metabolism. The response in mRNA abundance in LPS challenged versus nonchallenged samples was assessed via Δ = LPS challenged - LPS nonchallenged samples. Phagocytosis capacity and oxidative burst activity were measured in neutrophils and monocytes, with data reported as ratio (percentage) of CD14 to CH138A-positive cells. Data including all time points were subjected to ANOVA using PROC MIXED in SAS 9.4 (SAS Institute Inc.), with Treatment, Sex, Age, and Treatment × Age as fixed effects. A 1-way ANOVA was used to determine differences at birth, with Treatment and Sex as fixed effects. Calf birth body weight and other growth parameters did not differ between groups. At birth, plasma haptoglobin concentration was lower in FOA+CoPro compared with CoPro calves. We detected no effect for other plasma biomarkers or immune function due to maternal treatments at birth. Compared with CoPro, in response to LPS challenge, whole blood from FOA+CoPectin and FOA+CoPectin+RPM calves had greater mRNA abundance of intercellular adhesion molecule 1 (ICAM1). No effect for other genes was detectable. Regardless of maternal treatments, sex-specific responses were observed due to greater plasma concentrations of haptoglobin, paraoxonase, total reactive oxygen metabolites, nitrite, and ß-carotene in female versus male calves at birth. In contrast, whole blood from male calves had greater mRNA abundance of IRAK1, CADM1, and ITGAM in response to LPS challenge at birth. The longitudinal analysis of d 0, 21, and 42 data revealed greater bactericidal permeability-increasing protein (BPI) mRNA abundance in whole blood from FOA+CoPectin versus FOA+CoPro calves, coupled with greater abundance in FOA+CoPro compared with CoPro calves. Regardless of maternal treatments, most genes related to cytokines and cytokine receptors (IL1B, IL10, TNF, IRAK1, CXCR1), toll-like receptor pathway (TLR4, NFKB1), adhesion and migration (ICAM1, ITGAM), antimicrobial function (MPO), and antioxidant function (GPX1) were downregulated over time. Phagocytosis capacity and oxidative burst activity in both neutrophils and monocytes did not differ due to maternal treatment. Regardless of maternal treatments, we observed an increase in the percentage of neutrophils capable of phagocytosis and oxidative burst activity over time. Overall, these preliminary assessments suggested that maternal supplementation with FOA and Co combined with RPM had effects on a few plasma biomarkers of inflammation at birth and molecular responses associated with inflammatory mechanisms during the neonatal period.

Melittin-induced metabolic changes on the Madin-Darby Bovine Kidney cell line / [Mudanças metabólicas induzidas por melitina em células da linhagem Madin-Darby Bovine Kidney]

In this study, the toxic effects of melittin on Madin-Darby Bovine Kidney cells (MDBK) were analyzed with respect to mitochondrial functionality by reduction of MTT and flow cytometry, apoptosis potential, necrosis, oxygen reactive species (ROS) production, lipid peroxidation, and DNA fragmentation using flow cytometry and cell membrane destabilization by confocal microscopy. The toxicity presented dose-dependent characteristics and mitochondrial activity was inhibited by up to 78.24 ±3.59% (P<0.01, n = 6) in MDBK cells exposed to melittin (10µg/mL). Flow cytometry analysis revealed that melittin at 2µg/mL had the highest necrosis rate (P<0.05) for the cells. The lipoperoxidation of the membranes was also higher at 2µg/mL of melittin (P<0.05), which was further confirmed by the microphotographs obtained by confocal microscopy. The highest ROS production occurred when the cells were exposed to 2.5µg/mL melittin (P<0.05), and this concentration also increased DNA fragmentation (P<0.05). There was a significative and positive correlation between the lipoperoxidation of membranes with ROS (R=0.4158), mitochondrial functionality (R=0.4149), and apoptosis (R=0.4978). Thus, the oxidative stress generated by melittin culminates in the elevation of intracellular ROS that initiates a cascade of toxic events in MDBK cells.(AU)

Neste estudo, os efeitos tóxicos da melitina em células Madin-Darby Bovine Kidney (MDBK) foram analisados quanto à funcionalidade mitocondrial, por redução de MTT e citometria de fluxo, potencial de apoptose, necrose, produção de espécies reativas de oxigênio (ROS), peroxidação lipídica e fragmentação de DNA, utilizando-se citometria de fluxo e desestabilização da membrana celular, por microscopia confocal. A toxicidade apresentou características dose-dependentes e a atividade mitocondrial foi inibida até 78,24±3,59% (P<0,01, n = 6) em células MDBK expostas à melitina (10µg/mL). Análises por citometria de fluxo revelaram que a melitina a 2µg/mL apresentou o maior índice necrótico celular (P<0,05). A maior lipoperoxidação de membranas também foi na concentração de 2µg/mL de melitina (P<0,05), o que foi posteriormente confirmado por microscopia confocal. A maior produção de ROS aconteceu quando as células foram expostas a 2,5µg/mL de melitina (P<0,05), e essa concentração também aumentou a fragmentação de DNA (P<0,05). Houve uma significativa correlação positiva entre a lipoperoxidação de membranas e a produção de ROS (R=0,4158), funcionalidade mitocondrial (R=0,4149) e apoptose (R=0,4978). Portanto, o estresse oxidativo gerado pela melitina culminou na elevação de ROS intracelular, que inicia uma cascata de eventos tóxicos nas células MDBK.(AU)

One-carbon, carnitine, and glutathione metabolism-related biomarkers in peripartal Holstein cows are altered by prepartal body condition.

We investigated how prepartal body condition score (BCS) alters key hepatic enzymes associated with 1-carbon, carnitine, and glutathione metabolism and the related biomarkers in liver tissue and plasma of periparturient dairy cows. Twenty-six multiparous Holstein dairy cows were retrospectively selected according to BCS at 4 wk prepartum and divided into high (HighBCS, BCS ≥ 3.50) and normal (NormBCS, BCS ≤ 3.25) BCS groups (n = 13 each). Blood plasma samples were obtained at -30, -10, 7, 15, and 30 d relative to calving. Liver tissue biopsies were performed at -15, 7, and 30 d relative to calving, and samples were used to assess protein abundance via Western blot assay. Cows in the HighBCS group lost ∼1 unit of BCS between -4 and 4 wk around calving, while NormBCS cows lost ∼0.5 unit in the same period. Prepartal dry matter intake (DMI, kg/d) did not differ between groups. Compared with NormBCS cows, HighBCS cows had higher postpartal DMI and milk yield (+5.34 kg/d). In addition, greater overall plasma concentrations of fatty acids and activity of the neutrophil-enriched enzyme myeloperoxidase were observed in HighBCS compared with NormBCS cows. Despite similar reactive oxygen metabolite concentrations in both groups at 30 d, HighBCS cows had lower overall concentrations of ß-carotene and tocopherol, explaining the lower (BCS × Time) antioxidant capacity (ferric reducing ability of plasma). The HighBCS cows also had greater liver malondialdehyde concentrations and superoxide dismutase activity at 30 d. Overall, compared with NormBCS cows, HighBCS cows had lower hepatic protein abundance of the 1-carbon metabolism enzymes cystathionine-ß-synthase, betaine-homocysteine methyltransferase, and methionine adenosyltransferase 1 A (MAT1A), as well as the glutathione metabolism-related enzymes glutathione S-transferase α 4 and glutathione peroxidase 3 (GPX3). A lower protein abundance of glutathione S-transferase mu 1 (GSTM1) at -15 and 7 d was also observed. Regardless of BCS, cows had increased abundance of GSTM1 and GPX3 between -15 and 7 d around calving. A marked decrease of gamma-butyrobetaine dioxygenase 1 from -10 to 7 d in HighBCS compared with NormBCS cows suggested a decrease in de novo carnitine synthesis that was partly explained by the lower abundance of MAT1A. Overall, data suggest biologic links between BCS before calving, milk yield, immune response, and hepatic reactions encompassing 1-carbon metabolism, carnitine, and antioxidant synthesis.

Maternal body condition influences neonatal calf whole-blood innate immune molecular responses to ex vivo lipopolysaccharide challenge.

Managing body condition in dairy cows during the close-up period could alter the availability of nutrients to the fetus during the final growth stages in utero. We investigated how maternal body condition score (BCS) in late pregnancy affected calf whole-blood mRNA abundance and IL-1ß concentrations after ex vivo lipopolysaccharide (LPS) challenge. Thirty-eight multiparous Holstein cows and their calves from a larger cohort were retrospectively grouped by prepartal BCS as normal BCS (≤3.25; n = 22; NormBCS) and high BCS (≥3.75; n = 16; HighBCS). Calf blood samples collected at birth (before receiving colostrum, d 0) and at ages 21 and 42 d (at weaning) were used for ex vivo whole-blood challenge with 3 µg/mL of LPS before mRNA isolation. Target genes evaluated by real-time quantitative PCR were associated with immune response, antioxidant function, and 1-carbon metabolism. Plasma IL-1ß concentrations were also measured. Responses in plasma IL-1ß and mRNA abundance were compared between LPS-challenged and nonchallenged samples. Statistical analyses were performed at all time points using a MIXED model in SAS 9.4. Neither birth body weight (NormBCS = 43.8 ± 1.01 kg; HighBCS = 43.9 ± 1.2 kg) nor colostrum IgG concentration (NormBCS = 70 ± 5.4 mg/mL; HighBCS = 62 ± 6.5 mg/mL) differed between groups. At birth, whole blood from calves born to HighBCS cows had greater mRNA abundance of IL1B, NFKB1, and GSR and lower GPX1 and CBS abundance after LPS challenge. The longitudinal analysis of d 0, 21, and 42 data revealed a BCS × age effect for SOD2 and NOS2 due to lower mRNA abundance at 42 d in the HighBCS calves. Regardless of maternal BCS, mRNA abundance decreased over time for genes encoding cytokines (IL1B, IL6, IL10, TNF), cytokine receptors (IRAK1, CXCR1), toll-like receptor pathway (TLR4, NFKB1), adhesion and migration (CADM1, ICAM1, ITGAM), and antimicrobial function (MPO). Concentration of IL-1ß after LPS challenge was also markedly lower at 21 d regardless of maternal BCS. Overall, results suggested that maternal BCS in late prepartum influences the calf immune system response to an inflammation challenge after birth. Although few genes among those studied were altered due to maternal BCS, the fact that genes related to oxidative stress and 1-carbon metabolism responded to LPS challenge in HighBCS calves underscores the potential role of methyl donors (e.g., methionine, choline, and folic acid) in the early-life innate immune response.

Alterations in immune and antioxidant gene networks by gamma-d-glutamyl-meso-diaminopimelic acid in bovine mammary epithelial cells are attenuated by in vitro supply of methionine and arginine.

Nucleotide-binding oligomerization domain (NOD)-like receptor 1 (NOD1) is a cytosolic pattern recognition receptor with a crucial role in the innate immune response of cells triggered by the presence of compounds such as gamma-d-glutamyl-meso-diaminopimelic acid (iE-DAP) present in the peptidoglycan of all gram-negative and certain gram-positive bacteria. Methionine (Met) and arginine (Arg) are functional AA with immunomodulatory properties. In the present study, we aimed to assess the effect of increased Met and Arg supply on mRNA abundance of genes associated with innate immune response, antioxidant function, and AA metabolism during iE-DAP challenge in bovine mammary epithelial cells (BMEC). Primary BMEC (n = 4 per treatment) were precultured in modified medium for 12 h with the following AA formulations: ideal profile of AA (control), increased Met supply (incMet), increased Arg supply (incArg), or increased supply of Met plus Arg (incMetArg). Subsequently, cells were challenged with or without iE-DAP (10 µg/mL) for 6 h. Data were analyzed as a 2 × 2 × 2 factorial using the MIXED procedure of SAS 9.4. Greater mRNA abundance of NOD1, the antioxidant enzyme SOD1, and AA transporters (SLC7A1 and SLC3A2) was observed in the incMet cells after iE-DAP stimulation. Although increased Met alone had no effect, incMetArg led to greater abundance of the inflammatory cytokine IL-6, and the antioxidant enzyme GPX1 after iE-DAP stimulation. The increased Arg alone downregulated NOD1 after iE-DAP stimulation, coupled with a downregulation in the AA transporters mRNA abundance (SLC7A1, SLC7A5, SLC3A2, and SLC38A9), and upregulation in GSS and KEAP1 mRNA abundance. Overall, the data indicated that increased supply of both Met and Arg in the culture medium were more effective in modulating the innate immune response and antioxidant capacity of BMEC during in vitro iE-DAP stimulation.

Apamin-induced alterations in J774 1. 6 macrophage metabolism / [Alterações induzidas por apamina no metabolismo de macrófagos J774 1. 6]

Among the immune system cells, macrophages have an important role. Apamin, a bee venom constituent, is important in the defense of these insects. Thus, we aimed to evaluate the metabolism of J774 1.6 macrophage cell line when exposed to isolated and purified apamin, using cytotoxicity tests by MTT reduction and analysis by flow cytometry (apoptosis / necrosis, production of reactive oxygen species (ROS), membranous lipoperoxidation (LPO), electrical potential of the mitochondrial membrane (mMP) and DNA fragmentation). None of the tested concentrations (10 to 100µg/mL) were cytotoxic according to MTT reductions. Apoptosis rates decreased at concentrations of 2.5, 5.0, and 10.0µg/mL (P<0.05), while necrosis rates increased (P<0.05). However, rates of healthy cells at the highest tested concentration (10µg/mL) did not differ from control (P>0.05). Apamin did not alter ROS, LPO, or DNA fragmentation. Therefore, all analyzed concentrations (1.25 to 10µg/mL) decreased mMP. Such decrease in apoptosis might be due to a suppression of mitochondrial pro-apoptotic messengers, as this peptide causes no oxidative stress, lipid peroxidation, and DNA damage. Highly sensitive techniques are majorly important for proper interpretation of cellular toxicity mechanisms, combined with routine laboratory methods.(AU)

Das células do sistema imunológico, macrófagos desempenham um papel fundamental. Apamina, constituinte do veneno de abelhas, é importante na defesa destas. Objetivou-se avaliar o metabolismo da linhagem de macrófagos J774 1.6 expostos à apamina isolada e purificada, avaliando-se citotoxicidade por redução de MTT e análise por citometria de fluxo (apoptose / necrose, produção de espécies reativas de oxigênio (EROs), lipoperoxidação membranosa (LPO), potencial elétrico da membrana mitocondrial (MMP) e fragmentação do DNA). Nenhuma concentração testada (10 a 100µg / mL) foi citotóxica. As taxas de apoptose diminuíram nas concentrações 2,5, 5,0 e 10,0µg / mL (P<0,05), enquanto as de necrose aumentaram (P<0,05). Entretanto, as taxas de células saudáveis na maior concentração testada (10µg / mL) não diferiram do controle (P>0,05). A apamina não alterou as ERO, a LPO nem a fragmentação do DNA. Portanto, todas as concentrações analisadas (1,25 a 10µg / mL) diminuíram a mMP. Tal diminuição na apoptose pode ser por uma supressão de mensageiros pró-apoptóticos mitocondriais, já que este peptídeo não causa estresse oxidativo, peroxidação lipídica nem dano ao DNA. Técnicas altamente sensíveis são importantes para adequada interpretação dos mecanismos de citotoxicidade.(AU)

The occurrence of diseases and their relationship with passive immune transfer in Holstein dairy calves submitted to individual management in southern Brazil / Ocorrência de doenças e sua relação com a transferência de imunidade passiva em bezerras Holandês criadas em sistema individual no sul do Brasil

Calves are extremely dependent on colostrum intake for the acquisition of passive immunity. This study aimed to determine the occurrence of diarrhea and respiratory diseases and the impact of Failure of Passive Immune Transfer (FPIT) on the health and zootechnical performance of Holstein dairy calves in individual management. This study has been carried out in five commercial farms in Rio Grande do Sul State, Brazil, from March 2017 to January 2018. In this study, 131 calves were followed from birth to 60 days of age. Total Plasmatic Protein (TPP) has been performed to determine passive immune transfer quality in 53 calves (53/131). A daily clinical follow-up has been accomplished aiming at diagnosing diseases and their incidences, and zootechnical measures such as withers height, width of the croup and weight have been evaluated. FPIT rate was 32.07%, diarrhea occurrence and respiratory diseases were 77.9% and 49.6%, respectively. FPIT increased the chances of calves presenting diarrhea and developing respiratory diseases, but no differences on zootechnical performance were found. The frequency of FPIT is still high and is a factor that corroborated the increased risk for diarrhea and respiratory disease but did not influence the performance of calves in the preweaning phase.(AU)

Bezerras são extremamente dependentes da ingestão de colostro para adquirir imunidade passiva. Este estudo teve o objetivo de determinar os índices de ocorrência de diarreia e de doença respiratória, assim como o impacto da falha na transferência de imunidade passiva (FTIP) no desenvolvimento de doenças e no desempenho zootécnico de bezerras Holandês criadas em sistema individual. O estudo foi desenvolvido em cinco propriedades comerciais no Rio Grande do Sul, Brasil, entre março de 2017 e janeiro de 2018. Assim, 131 bezerras foram acompanhadas, do nascimento aos 60 dias de idade. Em 53 animais, foi realizada avaliação de proteínas plasmáticas totais para determinar a qualidade na transferência de imunidade passiva. Acompanhamento clínico diário foi realizado, a fim de diagnosticar doenças e suas incidências, assim como avaliações zootécnicas, como altura de cernelha, largura de garupa, perímetro torácico e peso. O percentual de FTIP foi 32,07%, a ocorrência de diarreias e de doenças respiratórias foi, respectivamente, 77,9% e 49,6%. A FTIP aumentou as chances de as bezerras apresentarem diarreia e doenças respiratórias, mas não alterou o desempenho zootécnico. Conclui-se que a frequência na FTIP ainda é elevada, fator que corroborou o aumento do risco para as diarreias e doença respiratória. Apesar disso, a FTIP não influenciou no desenvolvimento das bezerras na fase de aleitamento.(AU)

Establishment of heart teams in Portugal.

Whenever several therapeutic options exist, multidisciplinary decision-making is beneficial for the patient and for society at large. The main obstacles to the establishment of heart teams in Portugal are organizational and logistical. Implementing a heart team approach entails definition of the situations requiring multidisciplinary discussion, creation of clear lines of communication, written protocols and obtaining patient informed consent. The European Society of Cardiology guidelines define the clinical scenarios where intervention of the heart team is recommended.

Nutritional status and body composition after 6 months of patients switching from continuous ambulatorial peritoneal dialysis to automated peritoneal dialysis

Our objective was to determine if automated peritoneal dialysis (APD) leads to changes in nutritional parameters of patients treated by continuous ambulatory peritoneal dialysis (CAPD). Twenty-six patients (15 males; 50.5 ± 14.3 years) were evaluated during CAPD while training for APD and after 3 and 6 months of APD. Body fat was assessed by the sum of skinfold thickness and the other body compartments were assessed by bioelectrical impedance. During the 6-month follow-up, 12 patients gained more than 1 kg (GW group), 8 patients lost more than 1 kg (LW group), and 6 patients maintained body weight (MW group). Except for length on dialysis that was longer for the LW group compared with the GW group, no other differences were found between the groups at baseline. After 6 months on APD, the LW group had a reduction in body fat (24.5 ± 7.7 vs 22.1 ± 7.3 kg; P = 0.01), body cell mass (22.6 ± 6.2 vs 21.6 ± 5.8 kg, P = 0.02) and phase angle (5.4 ± 0.9 vs 5.1 ± 0.8 degrees, P = 0.004). In the GW group, body fat (25 ± 7.6 vs 27.2 ± 7.6 kg, P = 0.001) and body cell mass (20.1 ± 3.9 vs 20.8 ± 4.0 kg, P = 0.05) were increased. In the present study, different patterns of change in body composition were found. The length of previous dialysis treatment seems to be the most important factor in determining these nutritional modifications.

Nutritional status and body composition after 6 months of patients switching from continuous ambulatorial peritoneal dialysis to automated peritoneal dialysis.

Our objective was to determine if automated peritoneal dialysis (APD) leads to changes in nutritional parameters of patients treated by continuous ambulatory peritoneal dialysis (CAPD). Twenty-six patients (15 males; 50.5 +/- 14.3 years) were evaluated during CAPD while training for APD and after 3 and 6 months of APD. Body fat was assessed by the sum of skinfold thickness and the other body compartments were assessed by bioelectrical impedance. During the 6-month follow-up, 12 patients gained more than 1 kg (GW group), 8 patients lost more than 1 kg (LW group), and 6 patients maintained body weight (MW group). Except for length on dialysis that was longer for the LW group compared with the GW group, no other differences were found between the groups at baseline. After 6 months on APD, the LW group had a reduction in body fat (24.5 +/- 7.7 vs 22.1 +/- 7.3 kg; P = 0.01), body cell mass (22.6 +/- 6.2 vs 21.6 +/- 5.8 kg, P = 0.02) and phase angle (5.4 +/- 0.9 vs 5.1 +/- 0.8 degrees, P = 0.004). In the GW group, body fat (25 +/- 7.6 vs 27.2 +/- 7.6 kg, P = 0.001) and body cell mass (20.1 +/- 3.9 vs 20.8 +/- 4.0 kg, P = 0.05) were increased. In the present study, different patterns of change in body composition were found. The length of previous dialysis treatment seems to be the most important factor in determining these nutritional modifications.

Palatine mucosa of aging and experimentally induced diabetic aging rabbits: light-microscopic, scanning electron microscopic and transmission electron microscopic qualitative study.

BACKGROUND: Data associating palatine mucosa, microvascular architecture, aging and diabetes mellitus are few, so the aim of the present study was to examine these conditions structurally and ultrastructurally. METHODS: We used 18 female rabbits, aged about 2 years at the beginning of the experiment, distributed into 2 groups: aging diabetic and aging animals, prepared by three different methodologies: light microscopy, scanning electron microscopy and transmission electron microscopy. The samples were stained with hematoxylin-eosin for light microscopy, and for scanning electron microscopy, we used Mercox Cl-2B vascular corrosion casts. For transmission electron microscopy, the specimens were fixed and embedded in Epon 812 resin. RESULTS: Under light microscopy, we noted small amounts of underdeveloped connective papillae and significant flattened areas through the epithelium-connective tissue interface in the aging diabetic group. Larger blood vessels were deeply located in the palatine mucosa, branching off in the direction of the epithelium-connective tissue interface. Capillaries followed the interface contour. In both groups, vascular corrosion casts revealed capillaries sprouting out in disorganized rows but parallel between themselves. 'Hair-pin' capillary loops and convoluted capillary loops were noted. CONCLUSION: The aging diabetic group showed rarefying microvasculature areas with complex tortuous capillary loops. Transmission electron microscopy results showed that the aging diabetic group presented small cytoplasmatic projections directed to the vessel lumen and micropinocytic vesicle, i.e. caveolas. Epithelium-connective tissue interface, connective papillae, microangioarchitecture, and information about endothelial cells alterations were observed in the aging diabetic and aging animals.

Delay in hospital admission of patients with cerebral vein and dural sinus thrombosis.

Factors influencing early hospital admission have been described for several stroke types but not for cerebral vein and dural sinus thrombosis (CVT). CVT is more difficult to diagnose than arterial stroke; delay in hospital admission may postpone CVT treatment. The purposes of this study were: (1) to describe the delay between the onset of symptoms and hospital admission of patients with CVT, and (2) to identify the variables that influence that delay. We registered the interval (days) between the onset of symptoms and hospital admission in 91 consecutive patients admitted to 20 Portuguese hospitals between June 1995 and June 1998. We also studied the impact of admission delay on treatments (prescription of anticoagulants and the number of days elapsed between the onset of symptoms and start of anticoagulation and admission). Median admission delay was 4 days. Twenty-two (25%) patients were admitted within 24 h. Two thirds of the patients were admitted within 7 days and 75% within 13 days. In multiple logistic regression analysis, admission within 24 h was positively associated with mental status disorder (delirium or abulia; OR = 4.59; 95% CI = 1.41-14.89) and negatively associated with headache (OR = 0.03; 95% CI = 0.00-0.32). Presentation as isolated intracranial hypertension was associated with admission delay of more than 4 days (OR = 2.63; 95% CI = 0.97-7.14). Papilloedema was associated with an admission delay of more than 13 days (OR = 4.69; 95% CI = 1.61-13.61). There was no association between admission delay and the proportion of anticoagulated patients. The interval between onset of symptoms and start of anticoagulation was shorter in patients admitted earlier (p = 0.0001, for either admission within 24 h, 4 or 13 days). There is a considerable delay until the clinical picture associated with CVT is recognised as justifying hospital admission, especially when patients present with symptoms identical to isolated intracranial hypertension syndrome.

Angioarchitectural characteristics of the anterodorsal surface of aging and young rabbit tongue: scanning electron microscopy study.

The three-dimensional angioarchitecture of young and aging rabbit tongues were studied using a vascular corrosion cast method. The vascular network of different lingual papillae were observed by scanning electron microscope (SEM). Young animals showed filiform papillae distributed all over considered area, with fungiform ones among them. In comparison to developed specimens, young rabbits demonstrated dense and higher organization of microvascular network.

Long-term prognosis of cerebral vein and dural sinus thrombosis. results of the VENOPORT study.

The purpose of this study was to analyze the long-term mortality, functional recovery and long-term complications of cerebral vein and dural sinus thrombosis (CVDST) admitted to Portuguese hospitals. A follow-up of symptomatic CVDST admitted to Portuguese hospitals since 1980 was performed. Fifty-one patients (retrospective cases) were re-evaluated during 1996; 91 consecutively admitted patients from 6/1995 to 6/1998 were followed up to 1999. In 1996, 4 (8%) of the retrospective cases had died (3 patients died in the acute phase), 4 (8%) could not be reached, 33 (64%) had recovered completely (Rankin 0 or 1) and 3 (6%) were dependent. The prospective cases had a mean follow-up of 1 year: 6 (7%) patients died in the acute phase, one (1%) died during follow-up, 75 (82%) recovered completely, and only 1 (1%) was dependent. For the prospective cases, worsening after admission (OR = 18.2; 95% CI = 2.9-112.4) and encephalopathy as the presenting syndrome (OR = 7.1; 95% CI = 1.2-40.9) predicted death or dependency, while absence of aphasia (OR 6.7, 95% CI = 1.6-33) and no worsening after admission (OR = 5.9; 95% CI = 1.6-20) predicted total recovery. During follow-up of the prospective cases, 4 (5%) patients had thrombotic events, 8 (10%) patients experienced seizures, 9 (11%) complained of severe headaches and 1 patient suffered severe visual loss. The long-term functional prognosis of patients with CVDST was fairly good with complete recovery in the majority of cases. However, these patients had a moderate risk of further thrombotic events and seizures.

[The Internet as a solution facilitating the identification of patients with a suspected acute myocardial infarct]. / A Internet como solução facilitadora da identificação de doentes com suspeita de enfarte agudo do miocárdio.

The current steps for diagnosing heart disease are very time consuming, delaying the correct identification of the problem, therefore, delaying the right treatment. In this study we have developed an experimental method using e-mail in order to identify patients with "rule out myocardial" condition and reduce the time lag for thrombolysis or coronary angioplasty in this clinical setting. Three different locations linked to the Internet by ISDN lines were used. Each line was connected with a computer. A pager and a dedicated phone line were also used. The following steps were performed for each situation: filling out of a questionnaire, ECG recording, questionnaire mailing and ECG by e-mail as attachment, pager warning that an urgent cardiology consultation was requested, including the doctor and patient's phone number, time to open the message and reply by e-mail, phone call for additional comments. A total of 24 attempts of interactive communication were performed. In 22 of those, an answer was obtained in less than 30 minutes. Two failures were recorded. One was due to a delay in the pager message, which did not arrive within the first hour; the second was due to a computer break down. This report shows that it is possible to establish a fast communication between the out patient clinic and the hospital (less than 30 minutes in most cases) at a very low cost and in a simple manner.

Dynamic three-dimensional reconstruction of the heart by transesophageal echocardiography.

OBJECTIVE: To evaluate echocardiography accuracy in performing and obtaining images for dynamical three-dimensional (3D) reconstruction. METHODS: Three-dimensional (3D) image reconstruction was obtained in 20 consecutive patients who underwent transesophageal echocardiography. A multiplanar 5 MHz transducer was used for 3D reconstruction. RESULTS: Twenty patients were studied consecutively. The following cardiac diseases were present: valvar prostheses--6 (2 mitral, 2 aortic and 2 mitral and aortic); mitral valve prolapse--3; mitral and aortic disease--2; aortic valve disease--5; congenital heart disease--3 (2 atrial septal defect--ASD- and 1 transposition of the great arteries-TGA); arteriovenous fistula--1. In 7 patients, color Doppler was also obtained and used for 3D flow reconstruction. Twenty five cardiac structures were acquired and 60 reconstructions generated (28 of mitral valves, 14 of aortic valves, 4 of mitral prostheses, 7 of aortic prostheses and 7 of the ASD). Fifty five of 60 (91.6%) reconstructions were considered of good quality by 2 independent observers. The 11 reconstructed mitral valves/prostheses and the 2 reconstructed ASDs provided more anatomical information than two dimensional echocardiography (2DE) alone. CONCLUSION: 3D echocardiography using a transesophageal transducer is a feasible technique, which improves detection of anatomical details of cardiac structures, particularly of the mitral valve and atrial septum.

[Brazilian Nursing Magazine--a history of resistance]. / Revista brasileira de enfermagem--uma história de resistência.

Part of the conquest of ANEDB, since 1920 the REBEn itself inserting in the professional dispute about the diffusion of the nursing facts. Ought to Edith Magalhães Fraenkel and Rachel Haddock Lobo the inspiration and initiative for the creation, since 1929, within the participation in the I Quadrienal of ICN congress, in Montreal where were discussed facilities, difficulties and advance of nursing newspaper. The ANNAES of nursing, edited by the newspaper "Journal do Brasil--R.J.", in 1932, was the precursor of the REBEn. With her existence, readers, students and Professionals greediness for extend his specifics knowledge, constructors of the historic documentation and the knowledge profession, responsible by the scientific and technologic development and by the concept emission of different period of the Brazilian nursing, has learned to take advantage on his benefits. With more of 50 volumes and 200 edited copies the REBEn has acquired a reference status in the domestic and international of health and human science areas. Already consolidate; spread dissertation results, thesis, and work papers, presented or showed in Brazilian congresses of nursing. It's the most consulted newspaper as source and field scientific investigation. It provides the readers growth, organizer in the editorial process and counselors formation "ad hoc" through the permanent criticism and evaluation.

[The digital image archive--its clinical applications and importance in cardiology consulting by telemedicine]. / Arquivo digital de imagens--aplicações clínicas e sua importância na consultoria cardiológica por telemedicina.

The revolution in digital technology is rapidly changing the world of telecommunications. Its applications to Medicine, and in particular to Cardiology, offer enormous benefits since communication is an essential part of medical practice. The need to improve the management of medical information is critical because of the explosion of medical knowledge, and the need to provide comprehensive documentation on patient care. The availability of a network offers many possibilities for clinical, research and teaching activities. Relevant, up-to-date scientific information is instantly available for analysis and interaction. The authors review the issue of digital communications as well as its potential application to Telemedicine, and present their preliminary experience with digital analysis and storage of echocardiographic images.