Zygomycosis due to Mucor racemosus Associated with a Circovirus Infection in a Blue Tit (Cyanistes caeruleus).

In spring 2014, several wild passeriform garden birds were found severely ill or dead, all with severe periocular swellings. A blue tit (Cyanistes caeruleus) showing severe depression was humanely destroyed and sent for necropsy examination. In this bird, the lower eyelids were sagging, red and oedematous. Microscopical examination revealed marked infiltration of the eyelid tissue with fungal hyphae (stained by periodic acid-Schiff) without any inflammatory reaction. Polymerase chain reaction followed by sequencing identified Mucor racemosus and a so far unknown circovirus. The circovirus infection in this bird might have induced immunosuppression and thus facilitated the fungal infection. To our knowledge this is the first report of ocular M. racemosus infection associated with circovirus infection in a bird.

High prevalence of Mycobacterium genavense within flocks of pet birds.

Mycobacterium genavense is regarded as the primary cause of mycobacteriosis in psittaciform and passeriform birds, which are commonly kept as pets. In humans, Mycobacterium genavense is especially pathogenic for young, old, pregnant and immunocompromised people (YOPIs). In birds, only few studies, mainly case reports, exist and there is still little e information about occurrence and relevance of this zoonotic pathogen. In this first pilot study concerning the prevalence of Mycobacterium genavense within flocks of naturally infected pet birds, real-time PCR examinations of 170 individual passeriform and psittaciform birds, including commonly kept budgerigars, lovebirds and zebra finches as well as gold finches and weaver finches, were conducted to determine the infection rate in six different aviaries. Antemortem examinations of faeces and cloacal swabs were compared with postmortem examinations of tissue samples to evaluate the reliability of antemortem diagnostics. Additional ophthalmologic examinations were performed to evaluate their diagnostic potential. Molecular examinations for viral co-infections, including circovirus, polyomavirus and adenovirus, were conducted to identify potential risk factors. PCR results revealed a detection prevalence of Mycobacterium genavense in the flocks varying from 3% to 91% based on postmortem testing, while antemortem diagnostics of faecal samples and swabs showed 64% discrepant (false negative) results. Ophthalmologic examinations were not useful in identifying infected birds within the flocks. Viral co-infections, especially with polyomavirus, were common. It has to be assumed that Mycobacterium genavense infections are widespread and underdiagnosed in companion birds. Viral infections might be an important risk factor. There is urgent need to improve antemortem diagnostics.

Most preschool children hospitalised for acute rhinosinusitis had orbital complications, more common in the youngest and among boys.

AIM: This study established the incidence of acute rhinosinusitis and related orbital complications in tertiary care in Stockholm County and surveyed the clinical outcomes. METHODS: This was a population-based, retrospective, observational study, from July 1, 2003 to June 30, 2007, of the hospital admissions records of 213 children up to five years old, with a diagnosis of sinusitis and related complications. RESULTS: Preseptal cellulitis was present in 171 of the 213 admissions, which equated to an incidence of orbital complications due to acute rhinosinusitis of 36 per 100 000 people per year (95% confidence interval 26-49). Postseptal complications occurred in seven cases. The incidence rate ratio for hospitalisation of children less than two years old with rhinosinusitis compared with children aged 2-5 years was 2.8 (95% confidence interval 1.8-4.4). The incidence among boys was 53 per 100 000 people per year and 36 per 100 000 people per year for girls, and the incidence rate ratio was 1.5 (95% confidence interval 1.0-2.3). The most common bacterial finding was Streptococcus pneumoniae. CONCLUSION: Most children hospitalised for acute rhinosinusitis had an orbital complication, and this was more common in children under the age of two years and boys. Severe postseptal complications were rare.

Efficient isolation of avian bornaviruses (ABV) from naturally infected psittacine birds and identification of a new ABV genotype from a salmon-crested cockatoo (Cacatua moluccensis).

Avian bornaviruses (ABV) have been discovered in 2008 as the causative agent of proventricular dilatation disease (PDD) in psittacine birds. To date, six ABV genotypes have been described in psittacines. Furthermore, two additional but genetically different ABV genotypes were recognized in non-psittacine birds such as canary birds and wild waterfowl. This remarkable genetic diversity poses a considerable challenge to ABV diagnosis, since polymerase chain reaction (PCR) assays may fail to detect distantly related or as yet unknown genotypes. In this study we investigated the use of virus isolation in cell culture as a strategy for improving ABV diagnosis. We found that the quail fibroblast cell line CEC-32 allows very efficient isolation of ABV from psittacine birds. Isolation of ABV was successful not only from organ samples but also from cloacal and pharyngeal swabs and blood samples collected intra vitam from naturally infected parrots. Importantly, using this experimental approach we managed to isolate a new ABV genotype, termed ABV-7, from a salmon-crested cockatoo (Cacatua moluccensis). Phylogenetic analysis showed that ABV-7 is most closely related to the psittacine genotypes ABV-1, -2, -3, and -4 and clearly distinct from genotypes ABV-5 and -6. Our successful identification of ABV-7 emphasizes the necessity to consider the high genetic diversity when trying to diagnose ABV infections with high reliability and further shows that classical virus isolation may represent a useful diagnostic option, particularly for the detection of new ABV genotypes.

Use of a Real Time PCR for detecting subspecies of Babesia canis.

This paper reports the development and use of a Real Time PCR for detection of Babesia canis canis, B. canis rossi, and B. canis vogeli in endemic areas of Brazil. The sequences of the internal transcribed spacer (ITS) of several organisms were aligned and five primers and four probes were designed for amplification of a fragment (around 125 bp) which differentiates subspecies of B. canis. Blood samples collected from dogs living in farms in three distinct rural regions within the State of Minas Gerais (Lavras, Belo Horizonte and Nanuque) were tested. Blood samples had been collected during a dry season (Lavras, n=100; Belo Horizonte, n=50; Nanuque, n=102); the dogs were re-sampled in the subsequent rainy season (Lavras, n=71; Belo Horizonte, n=29; Nanuque, n=66). From each sample, DNA was extracted and Giemsa stained smears were microscopically examined for direct detection of Babesia parasites. B. canis vogeli was the only subspecies found, with an overall prevalence of 9.9% during the dry season and 10.8% during the rainy season. Dogs living in Nanuque and Belo Horizonte showed significantly higher prevalence rates than those living in Lavras (13.7%, 12.0% and 5.0%, respectively). The Real Time PCR developed proved to be appropriate to detect B. canis subspecies in endemic areas.

Integrating science and business models of sustainability for environmentally-challenging industries such as secondary lead smelters: a systematic review and analysis of findings.

Secondary lead smelters (SLS) represent an environmentally-challenging industry as they deal with toxic substances posing potential threats to both human and environmental health, consequently, they operate under strict government regulations. Such challenges have resulted in the significant reduction of SLS plants in the last three decades. In addition, the domestic recycling of lead has been on a steep decline in the past 10 years as the amount of lead recovered has remained virtually unchanged while consumption has increased. Therefore, one may wonder whether sustainable development can be achieved among SLS. The primary objective of this study was to determine whether a roadmap for sustainable development can be established for SLS. The following aims were established in support of the study objective: (1) to conduct a systematic review and an analysis of models of sustainable systems with a particular emphasis on SLS; (2) to document the challenges for the U.S. secondary lead smelting industry; and (3) to explore practices and concepts which act as vehicles for SLS on the road to sustainable development. An evidence-based methodology was adopted to achieve the study objective. A comprehensive electronic search was conducted to implement the aforementioned specific aims. Inclusion criteria were established to filter out irrelevant scientific papers and reports. The relevant articles were closely scrutinized and appraised to extract the required information and data for the possible development of a sustainable roadmap. The search process yielded a number of research articles which were utilized in the systematic review. Two types of models emerged: management/business and science/mathematical models. Although the management/business models explored actions to achieve sustainable growth in the industrial enterprise, science/mathematical models attempted to explain the sustainable behaviors and properties aiming at predominantly ecosystem management. As such, there are major disconnects between the science/mathematical and management/business models in terms of aims and goals. Therefore, there is an urgent need to integrate science and business models of sustainability for the industrial enterprises at large and environmentally-challenging industrial sectors in particular. In this paper, we offered examples of practices and concepts which can be used in charting a path towards sustainable development for secondary lead smelters particularly that the waste generated is much greater outside the industrial enterprise than inside. An environmentally-challenging industry such as secondary lead smelters requires a fresh look to chart a path towards sustainable development (i.e., survivability and purposive needs) for all stakeholders (i.e., industrial enterprise, individual stakeholders, and social/ecological systems). Such a path should deal with issues beyond pollution prevention, product stewardship and clean technologies.

Avian influenza A virus monitoring in wild birds in Bavaria: occurrence and heterogeneity of H5 and N1 encoding genes.

To define avian influenza virus prevalence in wild birds in Bavaria, 12,930 tracheal, cloacal swabs or tissue samples from various waterfowl species were screened between January 2006 and December 2007. In 291 (2.3%) birds, genomes of influenza A viruses were detected by reverse transcription real-time PCR (rRT-PCR) targeting the matrix protein genes. Furthermore, solitary H5 hemagglutinin or N1 neuraminidase encoding genes were identified in 35 (0.3%) apparently healthy birds; whereas highly pathogenic (HPAI) H5N1 virus genomes were only diagnosed in dead wild birds (n = 93; 0.7%) found across this federal state region. In this study, multiple import events for H5N1 viruses were confirmed during 2006 and 2007. In addition, our findings argue against an existing HPAI H5N1 reservoir in aquatic birds in Bavaria. By contrast, phylogenetic analyses of the H5 or N1 sequences of low pathogenic avian influenza (LPAI) viruses revealed a marked diversity and multiple genetic lineages. This diversity of LPAI H5 and N1 subtype components indicates the existence of LPAI HA and NA gene pools which differ from the Bavarian HPAI H5N1. Moreover, the hemagglutinin amino acid differences between LPAI H5 viruses of a western European genotypic lineage observed in wild birds suggest a continuous evolution of LPAI viruses in Bavaria.

Evidence-based integrated environmental solutions for secondary lead smelters: pollution prevention and waste minimization technologies and practices.

An evidence-based methodology was adopted in this research to establish strategies to increase lead recovery and recycling via a systematic review and critical appraisal of the published literature. In particular, the research examines pollution prevention and waste minimization practices and technologies that meet the following criteria: (a) reduce/recover/recycle the largest quantities of lead currently being disposed of as waste, (b) technically and economically viable, that is, ready to be diffused and easily transferable, and (c) strong industry interest (i.e., industry would consider implementing projects with higher payback periods). The following specific aims are designed to achieve the study objectives: Aim 1 - To describe the recycling process of recovering refined lead from scrap; Aim 2 - To document pollution prevention and waste management technologies and practices adopted by US stakeholders along the trajectory of LAB and lead product life cycle; Aim 3 - To explore improved practices and technologies which are employed by other organizations with an emphasis on the aforementioned criteria; Aim 4 - To demonstrate the economic and environmental costs and benefits of applying improved technologies and practices to existing US smelting operations; and Aim 5 - To evaluate improved environmental technologies and practices using an algorithm that integrates quantitative and qualitative criteria. The process of identifying relevant articles and reports was documented. The description of evidence was presented for current practices and technologies used by US smelters as well as improved practices and technologies. Options for integrated environmental solutions for secondary smelters were introduced and rank ordered on the basis of costs (i.e., capital investment) and benefits (i.e., production increases, energy and flux savings, and reduction of SO(2) and slag). An example was provided to demonstrate the utility of the algorithm by detailing the costs and benefits associated with different combinations of practices and technologies. The evidence-based methodology documented in this research reveals that it is technically and economically feasible to implement integrated environmental solutions to increase lead recovery and recycling among US smelters. The working example presented in this research can be confirmed with US stakeholders and form the basis for implementable solutions in the lead smelter and product industries to help reverse the overall trend of declining life-cycle recycling rates.

Canine babesiosis caused by Babesia canis vogeli in rural areas of the State of Minas Gerais, Brazil and factors associated with its seroprevalence.

This epidemiological survey on canine babesiosis was carried out in three distinct rural regions (Lavras, Belo Horizonte and Nanuque) of the State of Minas Gerais, Brazil. Ticks and blood samples were collected during a dry season (Lavras, n=92; Belo Horizonte, n=50; Nanuque, n=102) and the subsequent rainy season (Lavras, n=71; Belo Horizonte, n=28; Nanuque, n=66) from dogs living on farms. Plasma samples were analyzed by the indirect fluorescent antibody test for detection of anti-Babesia canis vogeli antibodies. DNA was extracted from blood of serologically positive dogs and molecular characterization of Babesia species was performed. Rhipicephalus sanguineus, Amblyomma cajennense and Boophilus microplus were the tick species identified in all regions. In Lavras, in addition to those tick species, A. tigrinum and A. ovale were also identified. The most prevalent tick species was A. cajennense (35.3%), followed by R. sanguineus (19%) and B. microplus (4.0%). Dogs living in Nanuque region were more heavily infested with ticks than dogs living in Belo Horizonte and Lavras regions. The overall frequency of anti-B. c. vogeli antibodies in the canine population in rural areas of Minas Gerais was 28.7%, with prevalence rates of 49.0% in Nanuque, 34.0% in Belo Horizonte and 3.3% in Lavras. The age of the animals and tick infestation were associated with seroprevalence of B. c. vogeli. The sequence analysis showed that B. c. vogeli was the only Babesia species present in all three regions. This study showed different rates of prevalence and incidence of canine babesiosis among the three rural regions sampled in Minas Gerais State. The results point to the importance of canine babesiosis in rural areas and to the need for further studies related to its transmission and maintenance in nature.

An exploratory study of lead recovery in lead-acid battery lifecycle in US market: an evidence-based approach.

BACKGROUND: This research examines lead recovery and recycling in lead-acid batteries (LAB) which account for 88% of US lead consumption. We explore strategies to maximize lead recovery and recycling in the LAB lifecycle. Currently, there is limited information on recycling rates for LAB in the published literature and is derived from a single source. Therefore, its recycling efforts in the US has been unclear so as to determine the maximum opportunities for metal recovery and recycling in the face of significant demands for LAB particularly in the auto industry. OBJECTIVES: The research utilizes an evidence-based approach to: (1) determine recycling rates for lead recovery in the LAB product lifecycle for the US market; and (2) quantify and identify opportunities where lead recovery and recycling can be improved. METHODS: A comprehensive electronic search of the published literature was conducted to gather information on different LAB recycling models and actual data used to calculate recycling rates based on product lifecycle for the US market to identify strategies for increasing lead recovery and recycling. RESULTS: The electronic search yielded five models for calculating LAB recycling rates. The description of evidence was documented for each model. Furthermore, an integrated model was developed to identify and quantify the maximum opportunities for lead recovery and recycling. Results showed that recycling rates declined during the period spanning from 1999 to 2006. Opportunities were identified for recovery and recycling of lead in the LAB product lifecycle. CONCLUDING REMARKS: One can deduce the following from the analyses undertaken in this report: (1) lead recovery and recycling has been stable between 1999 and 2006; (2) lead consumption has increased at an annual rate of 2.25%, thus, the values derived in this study for opportunities dealing with lead recovery and recycling underestimate the amount of lead in scrap and waste generated; and (3) the opportunities for maximizing lead recovery and recycling are centered on spent batteries left with consumers, mishandled LAB sent to auto wreckers, slag resulting from recycling technology process inefficiencies, and lead lost in municipal waste.

Glutamate release from adult primary sensory neurons in culture is modulated by growth factors.

The aim of this study was to examine possible modulatory effects of some trophic molecules, i.e. nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF) and basic fibroblast growth factor (bFGF), on potassium (K(+))-, bradykinin (BK)- or capsaicin (CAPS)-evoked release of glutamate (GLU) from dorsal root ganglion (DRG) neurons in vitro. BK (0.5 and 1 microM) induced a dramatic and significant increase in glutamate release. Neither CAPS nor K(+) (60 mM) produced any significant increase of GLU release vs. basal levels during a 5-min stimulation. The BK-evoked release of GLU was almost completely blocked by HOE 140, a selective BK2-receptor antagonist at high doses. Basal release of GLU was significantly reduced in cultures grown in the presence of bFGF, whereas BDNF and NGF had no significant effect. Incubation with growth factors generally decreased the BK-stimulated GLU release, an effect most pronounced for bFGF, which completely blocked BK-stimulated release. The rise in intracellular [Ca(2+)] following stimulation with BK (100 nM-1 microM), potassium (60 mM) or ATP (10 microM) was also studied using a Ca(2+)-sensitive indicator, Fura-2, in cultures grown in basal medium with or without bFGF. None of the bFGF-treated cells exhibited strong Ca(2+) responses to BK or ATP stimulation, while 10-20% of the responding cells grown in basal medium exhibited strong responses. The K(+)-induced increase of [Ca(2+)] did not vary between the different groups. The present findings suggest that sensory neurotransmission involving glutamate may be modulated by growth factors and that regulation of intracellular Ca(2+) homeostasis may be a contributing factor.

Safety and efficacy of suture-mediated closure after percutaneous coronary interventions.

Percutaneous coronary interventions (PCI) performed with concomitant use of heparin and platelet inhibitors are safe procedures with reported vascular complication rates of approximately 6.1%. EPILOG investigators demonstrated that utilizing a low-dose heparin regimen with abciximab, along with early sheath removal, vascular access-related bleeding was significantly lower than that reported in EPIC. Recently, a suture-mediated closure (SMC) device has been reported to be safe, appears effective, and may improve patient comfort by allowing early ambulation. We conducted a retrospective analysis (January 1999 to March 2000) of complication frequencies among PCI patients who underwent SMC and those who had manual compression (non-SMC). Furthermore, we compared the overall rates of complications to patients who underwent PCI prior to the introduction of SMC (1995-1998). When comparing the current cohort to the historical cohort, there was a significant decrease in the number of retroperitoneal bleeds (0.3% vs. 0.9%; P = 0.003), hematomas (5% vs. 9%; P < 0.001), pseudoaneurysms (1.2% vs. 2.7%; P < 0.001), and need for vascular surgery (0.9% vs. 2.8%; P < 0.001). There was no difference in the number of arterio-venous fistulas and a slight increase in transfusion needs (12% vs. 10%; P = 0.03). Within the current cohort, there was no difference in the vascular complications between SMC and non-SMC PCI patients, although there were lower rates of pseudoaneurysms (0.5% vs. 1.8%; P = 0.02) and transfusion requirements (72/880 vs. 132/874; P < 0.001). These results suggest that the complication rates for SMC are not different and may be lower when compared to non-SMC patients after PCI. At our institution, the practice of early sheath removal and less aggressive heparin dosing has led to a decrease in vascular complication rates and a 66% reduction in vascular surgeries on post-PCI patients. Because of the limitations of retrospective analyses, further studies will be necessary to confirm these findings.

Antinociceptive effects after intrathecal administration of phosphodiester-, 2'-O-allyl-, and C-5-propyne-modified antisense oligodeoxynucleotides targeting the NMDAR1 subunit in mouse.

In the present study, we have compared the antinociceptive effect of three different types of antisense oligodeoxynucleotides targeting the N-methyl-D-aspartate (NMDA) R1-subunit in mice. The probes were administrated intrathecally three times during a period of 5 days (1, 5 or 25 microg/injection), followed by evaluation using the formalin test. The antinociceptive effect was correlated to in vitro receptor binding in spinal cord sections. The tissue distribution was studied after a single injection of fluorescein-conjugated probes. The phosphodiester probe showed superficial tissue penetration after 30 min and disappeared within 2 h. The probe did, however, significantly reduce both receptor binding in laminae I and II (by 36-44% compared to saline) as well as pain behavior (32% compared to saline), without apparent side effects. The mismatched probe was ineffective at 25 microg, while some reductions in receptor binding and pain behavior were seen after 5 microg. The C-5-propyne-modified phosphorothioate probe showed pronounced tissue penetration and cellular uptake as soon as 30 min after injection which was still detectable after 24 h. Immediately after injection of the highest dose, long-lasting hind-limb paralysis was observed. Receptor binding was reduced but not in a dose-related manner. Pain behavior was significantly reduced by 40% following 25 microg of antisense probe but not after lower doses or 25 microg of mismatched probe. The 2'-O-allyl-modified probe did not significantly reduce receptor binding or pain behavior. Thus, only the phosphodiester probe showed a significant correlation between reduction in pain behavior and receptor binding. These findings demonstrate that antisense technology is associated with specificity problems, but still could provide a valuable tool to study the role of different target proteins in the drug discovery process.

Enhanced inotropic response to dobutamine in strength-trained subjects with left ventricular hypertrophy.

To determine whether strength-trained individuals with physiological concentric left ventricular (LV) hypertrophy exhibit enhanced inotropic responses to catecholamines, we studied 11 bodybuilders, aged 33.0 +/- 2 (SE) yr old, and 10 sedentary healthy subjects, aged 31.3 +/- 2.4 yr old, at baseline and during infusion of incremental doses of dobutamine after atropine. The bodybuilders had larger LV mass, posterior wall and septal wall thicknesses, and wall thickness-to-radius ratio, assessed with two-dimensional echocardiography, than did the sedentary subjects. There was a significant correlation between LV mass and lean body mass irrespective of training status. Baseline LV fractional shortening was similar in the two groups. There was a greater inotropic response to dobutamine in the strength-trained individuals, as evidenced by a steeper slope of the fractional shortening-end-systolic wall stress relationship with a higher y-axis intercept and by a shallower end-systolic wall stress-end systolic diameter relationship without changes in end-diastolic diameter. The heart rate response to dobutamine was attenuated in the strength-trained athletes. There was a significant correlation (r = 0.604, P < 0.05) between the inotropic sensitivity to dobutamine and LV mass normalized for lean body mass in the bodybuilders. The data suggest that concentric LV physiological hypertrophy in the resistance-trained individuals is associated with enhanced inotropic but not chronotropic responses to catecholamines.

Enhanced endothelium-dependent vasodilation in older endurance-trained men.

We hypothesized that abnormal endothelium-dependent vasodilation (EDD) found in older otherwise healthy subjects can be attenuated with long-term endurance training. Ten endurance-trained men, 68.5 +/- 2.3 yr old, and 10 healthy sedentary men, 64.7 +/- 1.4 yr old, were studied. Aerobic exercise capacity (VO(2 max)), fasting plasma cholesterol, insulin, and homocysteine concentrations were measured. Master athletes had higher VO(2 max) (42 +/- 2.3 vs. 27 +/- 1.4 ml. kg(-1). min(-1), P < 0.001), slightly higher total cholesterol (226 +/- 8 vs. 199 +/- 8 mg/dl, P = 0.05), similar insulin, and higher homocysteine (10.7 +/- 1.3 vs. 9.2 +/- 1.4 micromol/ml, p = 0.02) concentrations. Brachial arterial diameter, determined with vascular ultrasound, during the hyperemic response was greater in the master athletes than in controls (P = 0.005). Peak vasodilatory response was 109.1 +/- 2 vs. 103.6 +/- 2% (P < 0.05) in the athletes and controls, respectively. Endothelium-independent vasodilation in response to nitroglycerin was similar between the two groups. The increased arterial diameter during the hyperemic response correlated significantly with the VO(2 max) in the entire population (r = 0.66, P < 0.002). Our results suggest that long-term endurance exercise training in older men is associated with systemic enhanced EDD, which is even detectable in the conduit arteries of untrained muscle.

Effects of endurance exercise training on left ventricular systolic performance and ventriculoarterial coupling in patients with coronary artery disease.

BACKGROUND: Endurance exercise training can increase left ventricular (LV) ejection fraction during dynamic exercise in coronary artery disease. This adaptation may be mediated by altered cardiac loading conditions rather than an improvement in intrinsic LV systolic function. To minimize these confounding effects, we used isometric handgrip exercise to assess the training-induced changes in LV systolic function and ventriculoarterial coupling. METHODS: Twenty-six patients (52 +/- 2 years of age) trained for 12 months. LV function was assessed with radionuclide ventriculograpy. RESULTS: LV systolic reserve (the change in LV ejection fraction from rest to handgrip exercise) increased from -7.32 +/- 1.2 to -3.4 +/- 1.1 (P =. 033) without acute changes in end-diastolic volume or the effective arterial load. LV end-systolic elastance increased 37% (P =.039) during handgrip exercise. Resting end-diastolic volume increased and the effective arterial load decreased after training. CONCLUSIONS: Data suggest that in coronary artery disease adaptations to exercise training include a lower effective arterial load and an increase in EDV at rest, with an improvement in LV systolic function detectable only during afterload stress.

The effect of NGF, BDNF and bFGF on expression of galanin in cultured rat dorsal root ganglia.

Peripheral nerve injury causes a marked change in expression of the neuropeptide galanin in dorsal root ganglion (DRG) neurons. We have used DRG cell cultures to study whether growth factors, especially nerve growth factor (NGF), play a role in this regulation. Adult rat DRG cultures seem to represent a suitable model for this study, since the neurons are axotomized during culture preparation and are known to survive independently of added neurotrophic factors. The effect of NGF, brain derived neurotrophic factor (BDNF) and basic fibroblast growth factor (bFGF) was studied on the expression of galanin and galanin message-associated peptide (GMAP)-like immunoreactivities using immunohistochemistry, as well as of prepro-galanin (ppGAL) mRNA levels using radioactive and non-radioactive in situ hybridization. The results show that 100, but not 20 or 50 ng/ml NGF, as well as 10 ng/ml BDNF cause a 40% decrease in the number of GMAP expressing neurons in 72 h cell cultures. A 50% decrease was observed after treatment with 10 ng/ml bFGF. The high dose needed and the modest effect suggest that NGF is not a major factor involved in galanin regulation, whereas BDNF and bFGF may have a role. Moreover, the strong upregulation of galanin/GMAP and ppGAL mRNA levels in the untreated cultures indicates that DRG neurons in vitro have a phenotype similar to DRG neurons after axotomy, i.e. a phenotype distinctly different from normal DRG neurons.

Acquired von Willebrand's disease: a concise review.

Acquired von Willebrand's disease (AvWD), an adult-onset bleeding diathesis, has most commonly been found in patients with an underlying lymphoproliferative disease or monoclonal gammopathy. Other malignancies, autoimmune diseases, hypothyroidism, and drugs have also been associated with AvWD. We have included an illustrative case history of a patient with a bleeding diathesis consistent with AvWD and a monoclonal gammopathy who required emergent cardiac surgery. Our review of the literature determined that most cases of AvWD are due to a circulating antibody that combines with the high molecular weight multimers (HMWM) of von Willebrand factor (vWF). These vWF multimer-antibody complexes are subsequently cleared from the circulation either by the reticuloendothelial system or by adsorption onto tumor cells. Clearance of the HMWM of vWF thus results in extremely low functional levels and variable antigenic levels. Mixing studies which are traditionally used to diagnose factor inhibitors are useful only if removal of vWF-antibody complexes can be accomplished in vitro. Treatment with intravenous immunoglobulin has recently been shown to be the most effective therapy for patients with an underlying lymphoproliferative disorder or monoclonal gammopathy. This therapeutic strategy is based on the observed immune complex clearance phenomenon that appears to be operative in most cases. Other AvWD-associated diseases require treatment specifically directed at the underlying disorder.