Plasma CCN2/connective tissue growth factor is associated with right ventricular dysfunction in patients with neuroendocrine tumors

Background  

Carcinoid heart disease, a known complication of neuroendocrine tumors, is characterized by right heart fibrotic lesions. Carcinoid heart disease has traditionally been defined by the degree of valvular involvement. Right ventricular (RV) dysfunction due to mural involvement may also be a manifestation. Connective tissue growth factor (CCN2) is elevated in many fibrotic disorders. Its role in carcinoid heart disease is unknown. We sought to investigate the relationship between plasma CCN2 and valvular and mural involvement in carcinoid heart disease.     

Effectiveness of nonpharmacological and nonsurgical interventions for patients with rheumatoid arthritis: an overview of systematic reviews

Conclusions based on systematic reviews of randomized controlled trials are considered to provide the highest level of evidence about the effectiveness of an intervention. This overview summarizes the available evidence from systematic reviews on the effects of nonpharmacological and nonsurgical interventions for rheumatoid arthritis (RA). Systematic reviews of studies of patients with RA (aged >18 years) published between 2000 and 2007 were identified by comprehensive literature searches. Methodological quality was independently assessed by 2 authors, and the quality of evidence was summarized by explicit methods. Pain, function, and patient global assessment were considered primary outcomes of interest. Twenty-eight systematic reviews were included in this overview. High-quality evidence was found for beneficial effects of joint protection and patient education, moderate-quality evidence was found for beneficial effects of herbal therapy (gamma-linolenic acid) and low-level laser therapy, and low-quality evidence was found for the effectiveness of the other interventions. The quality of evidence for the effectiveness of most nonpharmacological and nonsurgical interventions in RA is moderate to low.     

First reported isolation of Neisseria canis from a deep facial wound infection in a dog

Neisseria canis was isolated in pure culture from a mandibular abscess in a dog. Ultrasound-guided fine-needle aspiration was used to obtain a sample from the abscess. Conventional bacteriological examination techniques followed by 16S rRNA gene sequencing from pure subculture and construction of a phylogenetic tree verified the isolate as N. canis. 16S rRNA sequence analysis revealed that a broader phylogenetic platform is needed in the part of the phylogenetic tree where the canine pathogenic N. canis isolate is located. The canine pathogenic isolate was found to be resistant to cephalexin and trimethoprim.     

Experimental Infection of Reindeer with Cervid Herpesvirus 2

Cervid herpesvirus 2 (CvHV2) has been isolated from reindeer (Rangifer tarandus tarandus), and serological data indicate that in reindeer this virus is endemic in Fennoscandia, Alaska, Canada, and Greenland. CvHV2 has been described as a cause of subclinical genital infections in reindeer, but little information on primary infections exists. In this study, six seronegative and presumably pregnant reindeer were allocated to one of two groups. Two animals were inoculated with CvHV2 intratracheally, and two animals intravaginally, with one control animal in each group receiving sterile water. Mild hyperthermia and serous discharges from the vagina and nose were observed. No abortions were recorded, but one calf died shortly after birth. Inoculated animals seroconverted and had neutralizing antibodies after days 7 to 10 postinfection. CvHV2 was detected by PCR in nasal and vaginal swabs from animals in both groups but could be isolated only from nasal swabs in the respiratory group and from vaginal swabs in the genital group. CvHV2 was detected by PCR in various organs and tissues postmortem. In control animals, the virus could not be isolated in spite of PCR-positive nasal and vaginal swab samples and some degree of positive immunostaining. One of the animals that were inoculated intratracheally developed a hemorrhagic, necrotizing bronchopneumonia, which was CvHV2 positive by PCR and immunohistochemistry. We conclude that CvHV2 can cause systemic infection, that both genital and respiratory inoculations can lead to virus shedding, and that the virus can infect the fetus in utero.Cervid herpesvirus 2 (CvHV2) belongs to the order Herpesvirales, family Herpesviridae, subfamily Alphaherpesvirinae, and genus Varicellovirus (6) and has been isolated from reindeer (Rangifer tarandus tarandus) after reactivation by dexamethasone treatment (11, 26). Serological evidence of CvHV2 or an antigenically related herpesvirus infection has been found in semidomesticated reindeer in Norway (31), in barren-ground caribou (Rangifer tarandus groenlandicus) in Greenland (1), and in Grant''s caribou (Rangifer tarandus granti) in Alaska (9). Recent studies with semidomesticated reindeer in Norway revealed that CvHV2 is endemic, with a relatively high prevalence in the reindeer population (3, 4).Ruminant varicelloviruses are antigenically and genetically closely related, as demonstrated by the gene encoding glycoprotein B (UL27), which shows 84% homology between bovine herpesvirus 1 (BoHV1) and CvHV2 (28). Serological cross-reactions between these viruses have likewise been shown (7, 19, 20, 25). BoHV1 causes infectious bovine rhinotracheitis and infectious pustular vulvovaginitis, as well as encephalitis and abortion, in cattle (12, 24), and such serological cross-reactions may hinder the efficiency of BoHV1 eradication or surveillance programs if similar viruses are circulating.Experimentally, it has been demonstrated that CvHV2 can infect cattle and cause mild rhinotracheitis and induce a serological response, while BoHV1 infection in reindeer causes no clinical signs and only a weak serological response (22, 34). Reactivation was not detected in these cross-infection studies, supporting the notion that herpesvirus species are closely associated with their main respective hosts, as characterized by the ability to establish latency (5). This property is not demonstrated in every case of cross-infection, as recently evidenced by the establishment of latency of elk herpesvirus 1 in cattle (8). However, the genetic and antigenic similarities between these viruses imply that wild ruminants could be considered possible reservoirs for BoHV1 and bovines as reservoirs of alphaherpesviruses from other species (36).Reactivation of BoHV1 usually causes a subclinical infection and the acquired immune response may prevent virus shedding during reactivation. Primary infection, on the other hand, may cause shedding and clinical signs, including abortion or perinatal mortality (12).In experimental reactivation studies with reindeer, CvHV2 has caused asymptomatic genital infections, with virus being excreted in vaginal secretions (11, 35). No information has been published regarding primary infection. Recent field studies demonstrated that CvHV2 is present in the upper respiratory tract, with latency in the trigeminal ganglia, and that it can also be transmitted to the fetus via the placenta (3). The potential of CvHV2 to cause eventual abortion or calves that are born weak remains unknown.In Norway, there were more than 275,000 reindeer in 2006 to 2007, of which almost 90% were semidomesticated and 10% were wild. Reindeer husbandry is of major economical and cultural importance, especially for the local indigenous Saami communities. The registered overall mortality of reindeer in Norway during the 2006 reindeer herding year (1 April 2005 to 31 March 2006) was 37% (2). Attacks by predators are considered the major cause of death, but approximately 11% of the losses are of unknown etiology. Semidomesticated reindeer usually give birth unattended while ranging free, which makes it difficult to assess the contribution of abortion or calves that are born weak to mortality (38).The aim of this study was to carry out experimental infections with CvHV2 in pregnant seronegative reindeer to evaluate the pathogenesis of CvHV2. The clinical signs, different routes of infection (genital and respiratory), possible systemic infection with transmission to calves, and development of the humoral immune response were studied.     

TIMP-3 and MMP-3 contribute to delayed inflammation and hippocampal neuronal death following global ischemia

Hippocampal neuronal death following transient global ischemia in the mouse takes days to occur, providing a potential timeframe for therapeutic intervention. Since matrix metalloproteinase-3 (MMP-3) enhances inflammation and tissue inhibitor of metalloproteinases-3 (TIMP-3) promotes apoptosis in ischemia, we hypothesized that they are involved in neuronal death secondary to transient global ischemia. Timp-3 knockout (T3KO) and wild type (T3WT) mice underwent 30 min bilateral carotid artery occlusion (BCAO), which causes hippocampal neuronal death 7 days after reperfusion. Mice lacking the Timp-3 gene have significantly less astrocytosis, microglial reactivity, MMP-3 activity and neuronal cell death. In addition, T3KO mice had decreased tumor necrosis factor (TNF) receptor-1 (TNFR1) expression and increased TNF-α converting enzyme (TACE) activity. Mmp-3 KO mice with a similar BCAO showed significantly fewer microglial cells, reduced TNF-α expression, and less neuronal death than the Mmp-3 WT. To see if TIMP-3 and MMP-3 cell death pathways were independent, we blocked MMPs with the broad-spectrum MMP inhibitor, BB-94, on days 3 through 6 of reperfusion in T3WT and T3KO mice. BB-94 rescued hippocampal neurons at 7 days in both T3WT and T3KO mice, but significantly fewer neurons died in T3KO mice treated with BB-94. Our results indicate a novel additive role for TIMP-3 and MMP-3 in delayed neuronal death, and show that delayed treatment with MMP inhibitors can be used to reduce hippocampal death.