Thrombolysis in Patients Aged over 80 Years Is Equally Effective and Safe

BACKGROUND: Despite stroke's high prevalence in the elderly, intravenous thrombolysis is licensed in Europe only for patients younger than 80 years old. We aimed to compare the functional outcomes and complication rates in patients older versus younger than 80 years old treated with intravenous thrombolysis. METHODS: A retrospective observational study of patients who received intravenous thrombolysis in a stroke unit between January 1, 2009, and June 30, 2012, was conducted. Variables were compared between 2 subgroups (≤80 and >80 years). RESULTS: Overall, 512 patients underwent intravenous thrombolysis, of which 13.1% were over 80 years. The mean age was 65.4 years in the younger subgroup and 82.9 years in the older subgroup. Prior independence rates did not differ between the subgroups. Prevalence of atrial fibrillation and cardioembolic stroke was higher in the older subgroup (P = .004 and .026). Only 3% of the elderly with atrial fibrillation were taking oral anticoagulants. Symptoms-to-needle time was lower in the older subgroup (P = .048). Stroke severity was higher in patients over 80 years (P = .026). There was significant improvement in the National Institutes of Health Stroke Scale score 7 days after intravenous thrombolysis (P < .001) in both subgroups. The proportion of patients with 3 months' favorable outcome and independence, hemorrhagic transformation, and mortality rates were similar in both subgroups. CONCLUSIONS: Elderly patients' benefits and outcomes from intravenous thrombolysis treatment were identical to the younger subgroup without excess hemorrhagic transformation or mortality. These results favor the use of intravenous thrombolysis in patients over 80 years.

Rates of spread of marine pathogens

Epidemics of marine pathogens can spread at extremely rapid rates. For example, herpes virus spread through pilchard populations in Australia at a rate in excess of 10 000 km year(-1), and morbillivirus infections in seals and dolphins have spread at more than 3000 km year(-1). In terrestrial environments, only the epidemics of myxomatosis and calicivirus in Australian rabbits and West Nile Virus in birds in North America have rates of spread in excess of 1000 km year(-1). The rapid rates of spread of these epidemics has been attributed to flying insect vectors, but flying vectors have not been proposed for any marine pathogen. The most likely explanation for the relatively rapid spread of marine pathogens is the lack of barriers to dispersal in some parts of the ocean, and the potential for long-term survival of pathogens outside the host. These findings caution that pathogens may pose a particularly severe problem in the ocean. There is a need to develop epidemic models capable of generating these high rates of spread and obtain more estimates of disease spread rate.

Introduced mammals in Australian rangelands: Future threats and the role of monitoring programmes in management strategies

In the present paper, we have provided an initial assessment of the current and future threats to biodiversity posed by introduced mammals (predators and herbivores) inhabiting the Australian rangelands, exploring trends in populations and options for management. Notably, rabbits have declined in recent years in the wake of rabbit haemorrhagic disease, populations of feral camels have increased dramatically and foxes appear to have moved northwards, thereby threatening native fauna within an expanded range. Following on, we developed a framework for monitoring the impacts of introduced mammals in the Australian rangelands. In doing so, we considered the key issues that needed to be considered in designing a monitoring programme for this purpose and critically evaluated the role of monitoring in pest animal management. Finally we have provided a brief inventory of current best-practice methods of estimating the abundance of introduced mammal populations in the Australian rangelands with some comments on new approaches and their potential applications.

Simultaneous detection and differentiation of human Polyomaviruses JC and BK by a rapid and sensitive PCR-ELAHA assay and a survey of the JCV subtypes within an Australian population

Human polyomaviruses JCV and BKV can cause several clinical manifestations in immunocompromised hosts, including progressive multifocal leukoencephalopathy (PML) and haemorrhagic cystitis. Molecular detection by polymerase chain reaction (PCR) is recognised as a sensitive and specific method for detecting human polyomaviruses in clinical samples. In this study, we developed a PCR assay using a single primer pair to amplify a segment of the VP1 gene of JCV and BKV. An enzyme linked amplicon hybridisation assay (ELAHA) using species-specific biotinylated oligonucleotide probes was used to differentiate between JCV and BKV. This assay (VP1-PCR-ELAHA) was evaluated and compared to a PCR assay targeting the human polyomavirus T antigen gene (pol-PCR). DNA sequencing was used to confirm the polyomavirus species identified by the VP1-PCR-ELAHA and to determine the subtype of each JCV isolate. A total of 297 urine specimens were tested and human polyomavirus was detected in 105 specimens (35.4%) by both PCR assays. The differentiation of JCV and BKV by the VP1-PCR-ELAHA showed good agreement with the results of DNA sequencing. Further, DNA sequencing of the JCV positive specimens showed the most prevalent JCV subtype in our cohort was 2a (27%) followed by 1b (20%), 1a (15%), 2c (14%), 4 (14%) and 2b (10%). The results of this study show that the VP1-PCR-ELAHA is a sensitive, specific and rapid method for detecting and differentiating human polyomaviruses JC and BK and is highly suitable for routine use in the clinical laboratory. (C) 2004 Wiley-Liss, Inc.

Suspected hexamine intoxication in a dog

An eight-month-old Labrador Retriever was presented with urinary incontinence and haematuria. Recent history suggested that the dog had access to solid fuel hexamine tablets, ingesting a dose of 6g/kg. Clinical signs, laboratory investigation and ultrasonographic findings were supportive of chemically-induced cystitis and a diagnosis of suspected hexamine intoxication was made. The dog recovered uneventfully and it is unlikely that the insult will be carcinogenic.

Ebola virus glycoprotein GP is not cytotoxic when expressed constitutively at a moderate level

Transient expression of Ebola virus (EBOV) glycoprotein GP causes downregulation of surface proteins, cell rounding and detachment, a phenomenon believed to play a central role in the pathogenicity of the virus. In this study, evidence that moderate expression of GP does not result in such morphological changes was provided. It was shown that GP continuously produced in 293T cells from the Kunjin virus replicon was correctly processed and transported to the plasma membrane without affecting the surface expression of beta 1 and alpha 5 integrins and major histocompatibility complex I molecules. The level of GIP expression in Kunjin replicon GP-expressing cells was similar to that observed in cells infected with EBOV early in infection and lower than that produced in cells transfected with plasmid DNA, phCMV-GP(1) expressing GP from a strong promoter. Importantly, transient transfection of Kunjin replicon GIP-expressing cells with GIP-coding plasmid DNA resulted in overexpression of GP, which lead to the downregulation of surface molecules and massive rounding and detachment of transfected cells. Here, it was also demonstrated that cell rounding and downregulation of the surface markers are the late events in EBOV infection, whereas synthesis and massive release of virus particles occur at early steps and do not cause significant cytotoxic effects. These findings indicate that the synthesis of EBOV GP in virus-infected cells is controlled well by several mechanisms that do not allow GP overexpression and hence the early appearance of its cytotoxic properties.

PCR detection and analysis of Pasteurella multocida from the tonsils of slaughtered pigs in Vietnam

A total of 36 tonsil swab samples were collected from healthy swine prior to slaughter at the abattoirs in Can tho and Tien giang provinces of Southern Vietnam, The presence of Pasteurella multocida in these samples was detected by the combination of direct cultivation and isolation, mouse inoculation and the polymerase chain reaction (PM-PCR). P. multocida was detected in 16 samples by PCR, with 17 strains ultimately isolated. All samples were negative for serogroup B by HSB-PCR and conventional serotyping, with isolates identified as A:3, D:1 or D:3. In addition, all samples were determined to be negative for the P. multocida toxin (PMT). Characterisation of isolated P, multocida by REP-PCR and biotyping revealed nine distinct REP profiles and seven biotypes among the 17 isolates. Some correlation was seen with P. multocida isolated from a previous Australian outbreak of acute swine pasteurellosis, and those isolated from fowl cholera outbreaks in Vietnamese poultry. (C) 2000 Elsevier Science B.V. All rights reserved.

Atividade antiofídica do decocto das folhas de jatropha gossypiifolia l. frente o veneno de bothrops jararaca

Antiophidic activity from decoct of Jatropha gossypiifolia L. leaves against Bothrops jararaca venom. Snakebites are a serious worldwide public health problem. In Latin America, about 90 % of accidents are attributed to snakes from Bothrops genus. Currently, the main available treatment is the antivenom serum therapy, which has some disadvantages such as inability to neutralize local effects, risk of immunological reactions, high cost and difficult access in some regions. In this context, the search for alternative therapies to treat snakebites is relevant. Jatropha gossypiifolia L., a medicinal plant popularly known in Brazil as “pinhão-roxo”, is very used in folk medicine as antiophidic. So, the aim of this study is to evaluate the antiophidic properties of this species against enzymatic and biological activities from Bothrops jararaca snake venom. The aqueous leaf extract of J. gossypiifolia was prepared by decoction. The inhibition studies were performed in vitro, by pre-incubation of a fixed amount of venom with different amounts of extract from J. gossypiifolia for 60 min at 37 °C, and in vivo, through oral or intraperitoneal treatment of animals, in different doses, 60 min before venom injection. The proteolytic activity upon azocasein was efficiently inhibited, indicating inhibitory action upon metalloproteinases (SVMPs) and/or serine proteases (SVSPs). The extract inhibited the fibrinogenolytic activity, which was also confirmed by zymography, where it was possible to observe that the extract preferentially inhibits fibrinogenolytic enzymes of 26 and 28 kDa. The coagulant activity upon fibrinogen and plasma were significantly inhibited, suggesting an inhibitory action upon thrombin-like enzymes (SVTLEs), as well as upon clotting factor activators toxins. The extract prolonged the activated partial thromboplastin time (aPTT), suggesting an inhibitory action toward not only to SVTLEs, but also against endogenous thrombin. The defibrinogenating activity in vivo was efficiently inhibited by the extract on oral route, confirming the previous results. The local hemorrhagic activity was also significantly inhibited by oral route, indicating an inhibitory action upon SVMPs. The phospholipase activity in vitro was not inhibited. Nevertheless, the edematogenic and myotoxic activities were efficiently inhibited, by oral and intraperitoneal route, which may indicate an inhibitory effect of the extract upon Lys49 phospholipase (PLA2) and/ or SVMPs, or also an anti-inflammatory action against endogenous chemical mediators. Regarding the possible action mechanism, was observed that the extract did not presented proteolytic activity, however, presented protein precipitating action. In addition, the extract showed significant antioxidant activity in different models, which could justify, at least partially, the antiophidic activity presented. The metal chelating action presented by extract could be correlated with SVMPs inhibition, once these enzymes are metal-dependent. The phytochemical analysis revealed the presence of sugars, alkaloids, flavonoids, tannins, terpenes and/or steroids and proteins, from which the flavonoids could be pointed as major compounds, based on chromatographic profile obtained by thin layer chromatography (TLC). In conclusion, the results demonstrate that the J. gossypiifolia leaves decoct present potential antiophidic activity, including action upon snakebite local effects, suggesting that this species may be used as a new source of bioactive molecules against bothropic venom.

Efeito da Olmesartana na resposta inflamatória em modelo de mucosite intestinal em ratos

Intestinal Mucositis is inflammation and/or ulceration of mucosa of the gastrointestinal tract caused by anticancer therapies. Histologically, villous atrophy, damage to enterocytes and infiltration of inflammatory cells. Methotrexate (MTX) is a compound that depletes dihydrofolate pools and is widely used in the treatment of leukemia and other malignancies. The aim of this study was to evaluate the effect of Olmesartan (OLM), an angiotensin II receptor antagonist, on an Intestinal Mucositis Model (IMM) induced by MTX in Wistar rats. IMM was induced via intraperitoneal (i.p.) administration of MTX (7 mg/kg) for three consecutive days. The animals were pretreated with oral OLM at 0.5, 1 or 5 mg/kg or with vehicle 30 min prior to exposure to MTX, for three days. Small intestinal (duodenum, jejunum and ileum) homogenates were assayed for levels of the IL-1β, IL-10 and TNF-α cytokines, malondialdehyde and myeloperoxidase activity. Additionally, immunohistochemical analyses of MMP-2, MMP-9, COX-2, RANK/RANKL and SOCS-1 and confocal microscopy analysis of SOCS-1 expression were performed. Treatment with MTX+OLM (5 mg/kg) resulted in a reduction of mucosal inflammatory infiltration, ulcerations, vasodilatation and hemorrhagic areas (p<0.05) as well as reduced concentrations of MPO (p<0.001) and the pro-inflammatory cytokines IL-1β and TNF-α (p<0.01), and increase antiinflammatory cytosine IL-10 (p,0.05). Additionally, the combined treatment reduced expression of MMP-2, MMP-9, COX-2, RANK and RANKL (p<0.05) and increased cytoplasmic expression of SOCS-1 (p<0.05). Our findings confirm the involvement of OLM in reducing the inflammatory response through increased immunosuppressive signaling in an IMM. We also suggest that the beneficial effect of Olmesartan treatment is specifically exerted during the damage through blocking inflammatory cytosines.

Avaliação dos efeitos tóxicos in vitro e in vivo do extrato hidroetanólico dos frutos de Genipa americana L. (Rubiaceae) em camundongos Swiss

The therapeutic use of medicinal plants has contributed since antiquity in a beneficial way for health. However, many species lacks of scientific evidence which provide basis for their use in therapeutic practice. In this context is the Genipa americana L. species (Rubiaceae), popularly known as jenipapo and used to treat syfilis, ulcer and hemorrhagic disturbs. It's also used against bruising, as tonic and as aphrodisiac. Due this species lacks toxicological studies, the aim of this study was to evaluate the toxicity in vivo (acute and sub-chronic toxicity) and in vitro (cytotoxicity) of the hydroethanolic extract from G. americana fruits. The hydroethanolic extract of G. americana fruits was prepared by maceration. A preliminary phytochemical analysis was performed to assess the presence of secondary metabolites in the extract. The cytotoxicity study of the extract (0.1, 1.0, 10, 100 and 1000 mg / 100 ul) were performed against normal cells (3T3) and tumor (786-0, HepG2 and B16), analyzed by the MTT assay. To evaluate the acute (single dose of 2000 mg / Kg) and subchronic (100, 500 and 1000 mg / kg for 30 days) toxicity Swiss mice of both sexes were used. At the end of the experiment, blood samples and organs were collected for analysis. Data between groups were compared by t test or ANOVA with Dunnett's post-test with 5% significance level. The phytochemical study of the extracts mainly indicated the presence of iridoids. Results for cytotoxicity tests showed up to 70% inhibition of B16 cell line at a dose of 1000 mg / 100 ul, and up to 29% inhibition of 786-0 at a dose of 10 ug / 100 ul. The extract did not cause death in 3T3 and HepG2 cells. During the in vivo assays, there were no animal deaths. Analysis of blood samples revealed that the animals submitted to the evaluation of acute toxicity had changes in AST and ALT, and that the animals evaluated for subchronic toxicity showed changes in the relative wet weight of the kidney and plasma urea concentration. No differences were observed between groups on histopathological evaluation of the collected organs. Despite the changes found in the in vivo toxicity tests, using the criteria described by the OECD Guidelines, it is suggested that the hydroethanolic extract of the fruits of the G. americana is classified as low toxicity. The cytotoxicity of the extract suggests that they have potential against melanoma cell lines (B16).

Avaliação dos efeitos tóxicos in vitro e in vivo do extrato hidroetanólico dos frutos de Genipa americana L. (Rubiaceae) em camundongos Swiss

The therapeutic use of medicinal plants has contributed since antiquity in a beneficial way for health. However, many species lacks of scientific evidence which provide basis for their use in therapeutic practice. In this context is the Genipa americana L. species (Rubiaceae), popularly known as jenipapo and used to treat syfilis, ulcer and hemorrhagic disturbs. It's also used against bruising, as tonic and as aphrodisiac. Due this species lacks toxicological studies, the aim of this study was to evaluate the toxicity in vivo (acute and sub-chronic toxicity) and in vitro (cytotoxicity) of the hydroethanolic extract from G. americana fruits. The hydroethanolic extract of G. americana fruits was prepared by maceration. A preliminary phytochemical analysis was performed to assess the presence of secondary metabolites in the extract. The cytotoxicity study of the extract (0.1, 1.0, 10, 100 and 1000 mg / 100 ul) were performed against normal cells (3T3) and tumor (786-0, HepG2 and B16), analyzed by the MTT assay. To evaluate the acute (single dose of 2000 mg / Kg) and subchronic (100, 500 and 1000 mg / kg for 30 days) toxicity Swiss mice of both sexes were used. At the end of the experiment, blood samples and organs were collected for analysis. Data between groups were compared by t test or ANOVA with Dunnett's post-test with 5% significance level. The phytochemical study of the extracts mainly indicated the presence of iridoids. Results for cytotoxicity tests showed up to 70% inhibition of B16 cell line at a dose of 1000 mg / 100 ul, and up to 29% inhibition of 786-0 at a dose of 10 ug / 100 ul. The extract did not cause death in 3T3 and HepG2 cells. During the in vivo assays, there were no animal deaths. Analysis of blood samples revealed that the animals submitted to the evaluation of acute toxicity had changes in AST and ALT, and that the animals evaluated for subchronic toxicity showed changes in the relative wet weight of the kidney and plasma urea concentration. No differences were observed between groups on histopathological evaluation of the collected organs. Despite the changes found in the in vivo toxicity tests, using the criteria described by the OECD Guidelines, it is suggested that the hydroethanolic extract of the fruits of the G. americana is classified as low toxicity. The cytotoxicity of the extract suggests that they have potential against melanoma cell lines (B16).

Cerebrovascular dysfunction in the presence of chronic inflammation

Background: Patients with autoimmune disease have increased incidence of stroke. Hemorrhagic stroke (HS) is associated with loss of cerebrovascular function, leading to micro-vessel burst, and hemorrhage. We believe chronic inflammation is involved in loss of cerebrovascular function and HS. We established a hypertensive-arthritis model in spontaneously hypertensive rats (SHR) fed either standard rodent diet (0.59% NaCl) (RD) or high salt diet (4% NaCl) (HSD) and compared them to non-inflamed SHR. Methods: Complete Freund’s adjuvant (CFA) was injected into the left paw to induce mono-arthritis. Blood pressure and inflammation was monitored. At endpoint, animals were sacrificed and evaluated for HS while middle cerebral artery (MCA) was isolated for functional studies. Results: HS was observed in 90% of CFA-treated groups. The MCA of arthritic RD-SHR exhibited decreased ability to undergo pressure dependent constriction (PDC). All HSD-SHR showed a decreased response to PDC. However, arthritic HSD-SHR also demonstrated a diminished response to vasoactive peptides. Conclusion: HS occurring with CFA injection corresponds with loss of MCA function. Chronic HSD appears to further exacerbate vascular dysfunction in the MCA.

Trajetórias e fatores associados a qualidade de vida de mães de recém-nascidos pré-termos de muito baixo peso até três anos após o parto

Preterm birth is a public health problem worldwide. It holds growing global incidence rates, high mortality rates and a risk of the long-term sequelae in the newborn. It is also poses burden on the family and society. Mothers of very low birth weight (VLBW) preterm infants may develop psychological disorders, and impaired quality of life (QoL). Factors related to mothers and children in the postpartum period may be negatively associated with the QoL of these mothers. The aim of this study was to assess factors possibly associated with the QoL of mothers of VLBW preterm newborns during the first three years after birth. Mothers of VLBW preterm answered the World Health Organization Quality of Life (WHOQOL)-bref and the Beck Depression Inventory (BDI) in five time points up to 36 months postpartum, totalizing 260 observations. The WHOQOL–bref scores were compared and correlated with sociodemographic and clinical variables of mothers and children at discharge (T0) and at six (T1), twelve (T2), 24 (T3) and 36 (T4) months after the delivery. We used the Kruskal Wallis test to compared scores across different time points and correlated WHOQOL-bref scores with the sociodemographic and clinical variables of mothers and preterm infants. Multiple linear regression models were used to evaluate the contribution of these variables for the QoL of mothers. The WHOQOL–bref scores at T1 and T2 were higher when compared to scores in T0 in the physical health dimension (p = 0.013). BDI scores were also higher at T1 and T2 than those at T0 (p = 0.027). Among the maternal variables that contributed most to the QoL of mothers, there were: at T0, stable marital union (b= 13.60; p= 0.000) on the social relationships dimension, gestational age (b= 2.38; p= 0.010) in the physical health dimension; post-hemorrhagic hydrocephalus (b= -10.05; p= 0.010; b= -12.18; p= 0.013, respectively) in the psychological dimension; at T1 and T2, Bronchopulmonary dysplasia (b= -7.41; p= 0.005) and female sex (b= 8,094; p= 0.011) in the physical health dimension and environment, respectively. At T3, family income (b= -12.75’ p= 0.001) in the environment dimension, the SNAPPE neonatal severity score (b= -0.23; p= 0.027) on the social relationships dimension; at the T4, evangelical religion (b= 8.11; p= 0.019) and post-hemorrhagic hydrocephalus (b: -18.84 p: 0.001) on the social relationships dimension. The BDI scores were negatively associated with WHOQOL scores in all dimensions and at all times points: (-1.42 ≤ b ≤ -0.36; T0, T1, T2, T3 and T4). We conclude that mothers of preterm infants VLBW tend to have a transient improvement in the physical well-being during the first postpartum year. Their quality of life seems to return to levels at discharge between two and three years after delivery. The presence of maternal depressive symptoms and diagnosis of post-hemorrhagic hydrocephalus or BDP are factors negatively associated with the QoL of mothers. Social, religious and economic variables are positively associated with the QoL of mothers of VLBW preterm.