Diabetes mellitus-related morphoquantitative changes in the celiac ganglion neurons of the dog

Diabetes mellitus is the most common endocrine disturbance of domestic carnivores and can cause autonomic neurological disorders, although these are still poorly understood in veterinary medicine. There is little information available on the quantitative adaptation mechanisms of the sympathetic ganglia during diabetes mellitus in domestic mammals. By combining morphometric methods and NADPH-diaphorase staining (as a possible marker for nitric oxide producing neurons), type I diabetes mellitus-related morphoquantitative changes were investigated in the celiac ganglion neurons in dogs. Twelve left celiac ganglia from adult female German shepherd dogs were examined: six ganglia were from non-diabetic and six from diabetic subjects. Consistent hypertrophy of the ganglia was noted in diabetic animals with increase of 55% in length, 53% in width, and 61.5% in thickness. The ordinary microstructure of the ganglia was modified leading to an uneven distribution of the ganglionic units and a more evident distribution of axon fascicles. In contrast to non-diabetic dogs, there was a lack of NADPH-diaphorase perikarial labelling in the celiac ganglion neurons of diabetic animals. The morphometric study showed that both the neuronal and nuclear sizes were significantly larger in diabetic dogs (1.3 and 1.39 times, respectively). The profile density and area fraction of NADPH-diaphorase-reactive celiac ganglion neurons were significantly larger (1.35 and 1.48 times, respectively) in non-diabetic dogs compared to NADPH-diaphorase-non-reactive celiac ganglion neurons in diabetic dogs. Although this study suggests that diabetic neuropathy is associated with neuronal hypertrophy, controversy remains over the possibility of ongoing neuronal loss and the functional interrelationship between them. It is unclear whether neuronal hypertrophy could be a compensation mechanism for a putative neuronal loss during the diabetes mellitus. (C) 2007 Elsevier Ltd. All rights reserved.

Cardiovascular and autonomic phenotype of db/db diabetic mice

The db/db mice serve as a good model for type 2 diabetes characterized by hyperinsulinaemia and progressive hyperglycaemia. There are limited and conflicting data on the cardiovascular changes in this model. The aim of the present study was to characterize the cardiovascular and autonomic phenotype of male db/db mice and evaluate the role of angiotensin II AT(1) receptors. Radiotelemetry was used to monitor 24 h blood pressure (BP) in mice for 8 weeks. Parameters measured were mean arterial pressure (MAP), heart rate (HR) and their variabilities. In 8-week-old db/db mice, the MAP and BP circadian rhythms were not different from age-matched control mice, while HR and locomotor activity were decreased. With ageing, MAP gradually increased in db/db mice, and the 12 h light values did not dip significantly from the 12 h dark periods. In 14-week-old mice, MAP was increased during light (101 +/- 1 versus 117 +/- 2 mmHg, P < 0.01; control versus db/db mice) and dark phases (110 +/- 1.7 versus 121 +/- 3.1 mmHg, P < 0.01; control versus db/db mice). This increase in MAP was associated with a significant increase in plasma angiotensin-converting enzyme activity and angiotensin II levels. Chronic treatment with losartan (10 mg kg(-1) day(-1)) blocked the increase in MAP in db/db mice, with no effect in control animals. Spectral analysis was used to monitor autonomic cardiovascular function. The circadian rhythm observed in systolic arterial pressure variance and its low-frequency component in control mice was absent in db/db mice. There were no changes in HR variability and spontaneous baroreflex sensitivity between control and db/db mice. The results document an age-related increase in MAP in db/db mice, which can be reduced by antagonism of angiotensin II AT(1) receptors, and alterations in autonomic balance and components of the renin-angiotensin system.

Effects of exercise training on autonomic dysfunction management in an experimental model of menopause and myocardial infarction

Objective: The aim of this study was to investigate the effects of exercise training on cardiovascular autonomic dysfunction in ovariectomized rats submitted to myocardial infarction. Methods: Female Wistar rats were divided into the following ovariectomized groups: sedentary ovariectomized (SO), trained ovariectomized (TO), sedentary ovariectomized infarcted (SOI), and trained ovariectomized infarcted (TOI). Trained groups were submitted to an exercise training protocol on a treadmill (8 wk). Arterial baroreflex sensitivity was evaluated by heart rate responses to arterial pressure changes, and cardiopulmonary baroreflex sensitivity was tested by bradycardic and hypotension responses to serotonin injection. Vagal and sympathetic effects were calculated by pharmacological blockade. Results: Arterial pressure was reduced in the TO in comparison with the SO group and increased in the TOI in relation to the SOI group. Exercise training improved the baroreflex sensitivity in both the TO and TOI groups. The TOI group displayed improvement in cardiopulmonary reflex sensitivity compared with the SOI group at the 16 mu g/kg serotonin dose. Exercise training enhanced the vagal effect in both the TO (45%) and TOI (46%) animals compared with the SO and SOI animals and reduced the sympathetic effect in the TOI (38%) in comparison with the SOI animals. Significant correlations were obtained between bradycardic baroreflex responses and vagal (r = -0.7, P < 0.005) and sympathetic (r = 0.7, P < 0.001) effects. Conclusions: These results indicate that exercise training in ovariectomized rats submitted to myocardial infarction improves resting hemodynamic status and reflex control of the circulation, which may be due to an increase in the vagal component. This suggests a homeostatic role for exercise training in reducing the autonomic impairment of myocardial infarction in postmenopausal women.

Autonomic impairment after myocardial infarction: Role in cardiac remodelling and mortality

P>1. Impairmant of baroreflex sensitivity (BRS) has been implicated in the reduction of heart rate variability (HRV) and in the increased risk of death after myocardial infarction (MI). In the present study, we investigated whether the additional impairment in BRS induced by sinoaortic baroreceptor denervation (SAD) in MI rats is associated with changes in the low-frequency (LF) component of HRV and increased mortality rate. 2. Rats were randomly divided into four groups: control, MI, denervated (SAD) and SAD + MI rats. Left ventricular (LV) function was evaluated by echocardiography. Autonomic components were assessed by power spectral analysis and BRS. 3. Myocardial infarction (90 days) reduced ejection fraction (by similar to 42%) in both the MI and SAD + MI groups; however, an increase in LV mass and diastolic dysfunction were observed only in the SAD + MI group. Furthermore, BRS, HRV and the LF power of HRV were reduced after MI, with an exacerbated reduction seen in SAD + MI rats. The LF component of blood pressure variability (BPV) was increased in the MI, SAD and SAD + MI groups compared with the control group. Mortality was higher in the MI groups compared with the non-infarcted groups, with an additional increase in mortality in the SAD + MI group compared with the MI group. Correlations were obtained between BRS and the LF component of HRV and between LV mass and the LF component of BPV. 4. Together, the results indicate that the abolishment of BRS induced by SAD in MI rats further reduces the LF band of HRV, resulting in a worse cardiac remodelling and increased mortality in these rats. These data highlight the importance of this mechanism in the prognosis of patients after an ischaemic event.

Novel OTOF mutations in Brazilian patients with auditory neuropathy

The OTOF gene encoding otoferlin is associated with auditory neuropathy (AN), a type of non-syndromic deafness. We investigated the contribution of OTOF mutations to AN and to non-syndromic recessive deafness in Brazil. A test for the Q829X mutation was carried out on a sample of 342 unrelated individuals with non-syndromic hearing loss, but none presented this mutation. We selected 48 cases suggestive of autosomal recessive inheritance, plus four familial and seven isolated cases of AN, for genotyping of five microsatellite markers linked to the OTOF gene. The haplotype analysis showed compatibility with linkage in 11 families (including the four families with AN). Samples of the 11 probands from these families and from seven isolated cases of AN were selected for an exon-by-exon screening for mutations in the OTOF gene. Ten different pathogenic variants were detected, among which six are novel. Among the 52 pedigrees with autosomal recessive inheritance (including four familial cases of AN), mutations were identified in 4 (7.7%). Among the 11 probands with AN, seven had at least one pathogenic mutation in the OTOF gene. Mutations in the OTOF gene are frequent causes of AN in Brazil and our results confirm that they are spread worldwide. Journal of Human Genetics (2009) 54, 382-385; doi: 10.1038/jhg.2009.45; published online 22 May 2009

Spastic Paraplegia, Optic Atrophy, and Neuropathy: New Observations, Locus Refinement, and Exclusion of Candidate Genes

SPOAN is an autosomal recessive neurodegenerative disorder which was recently characterized by our group in a large inbred Brazilian family with 25 affected individuals. This condition is clinically defined by: 1. congenital optic atrophy; 2. progressive spastic paraplegia with onset in infancy; and 3. progressive motor and sensory axonal neuropathy. Overall, we are now aware of 68 SPOAN patients (45 females and 23 males, with age ranging from 5 to 72 years), 44 of which are presented here for the first time. They were all born in the same geographic micro region. Those 68 patients belong to 43 sibships, 40 of which exhibit parental consanguinity. Sixty-one patients were fully clinically evaluated and 64 were included in the genetic investigation. All molecularly studied patients are homozygotes for D11S1889 at 11q13. This enabled us to reduce the critical region for the SPOAN gene from 4.8 to 2.3 Mb, with a maximum two point lod score of 33.2 (with marker D11S987) and of 27.0 (with marker D11S1889). Three genes located in this newly defined critical region were sequenced, but no pathogenic mutation was detected. The gene responsible for SPOAN remains elusive.

Autonomic job scheduling policy for grid computing

Autonomic middleware services will play an important role in the management of resources and distributed workloads in emerging distributed computing environments. In this paper, we address the problem of autonomic grid resource scheduling and propose a scheduling infrastructure that is capable of self-management in the face of dynamic behavior inherent to this kind of systems.

Toward self discovery for an autonomic cluster

Nondedicated clusters are currently at the forefront of the development of high performance computing systems. These clusters are relatively intolerant of hardware failures and cannot manage dynamic cluster membership efficiently. This report presents the logical design of an innovative self discovery service that provides for automated cluster management and resource discovery. The proposed service has an ability to share or recover unused computing resources, and to adapt to transient conditions autonomically, as well as the capability of providing dynamically scalable virtual computers on demand.

Building autonomic clusters : a response to IBM’s autonomic computing challenge

IBM has announced Autonomic Computing as one of its Grand Challenges. A list of characteristics was generated to describe an autonomic computing system. Many researchers and research group have responded positively to the challenge by initiating research around one or two of the characteristics identified by IBM as the requirements for Autonomic Computing. We have addressed the IBMrsquos request to contribute to the challenge by building an autonomic operating system that possesses nearly all IBM characteristics. This paper contains our response to the IBMrsquos Autonomic Computing Challenge.

Building autonomic clusters: a response to IBM's autonomic computing challenge

IBM has announced Autonomic Computing as one of its Grand Challenges. A list of characteristics was generated to describe an autonomic computing system. Many researchers and research group have responded positively to the challenge by initiating research around one or two of the characteristics identified by IBM as the requirements for Autonomic Computing. We have addressed the IBMs request to contribute to the challenge by building an autonomic operating system that possesses nearly all IBM characteristics. This paper contains our response to the IBMs Autonomic Computing Challenge.

Cluster operating system support for parallel autonomic computing

The aim of this paper is to show a general design of autonomic elements and initial implementation of a cluster operating system that moves parallel processing on clusters to the computing mainstream using the autonomic computing vision. The significance of this solution is as follows. Autonomic Computing was identified by IBM as one of computing's Grand Challenges. The human body was used to illustrate an Autonomic Computing system that possesses self-knowledge, self-configuration, self optimization, self-healing, and self-protection, knowledge of its environment and user friendliness properties. One of the areas that could benefit from the comprehensive approach created by the autonomic computing vision is parallel processing on non-dedicated clusters. Many researchers and research groups have responded positively to the challenge by initiating research around one or two of the characteristics identified by IBM as the requirements for autonomic computing. We demonstrate here that it is possible to satisfy all Autonomic Computing characteristics.

The development of a wisdom autonomic grid

It is not a simple matter to develop an integrative approach that exploits  synergies between knowledge management and knowledge discovery in   order to monitor and manage the full lifecycle of knowledge and provides  services quickly, reliably and securely. One of the main problems is the heterogeneity of the involved resources that represent knowledge. Data mining systems produce knowledge in a form meant to be understandable  to machines and on the other hand in knowledge management systems the  priority is placed on the readability and usability of knowledge by humans.  The Semantic Web is a promising platform to unify this heterogeneity and, in conjunction with novel techniques for Web Intelligence it could offer more  then just knowledge - wisdom. The Wisdom Autonomic Grid is an original proposal of a knowledge based Grid that is able to configure and reconfigure itself under varying and unpredictable conditions and optimize its working, performs something akin to healing and provides self-protection, as  visioned in the IBM Autonomic Computing initiative. This paper presents an original framework for creating advanced applications to integrate  knowledge discovery and knowledge management in the Autonomic Grid  and Web environments.

Service migration in autonomic service oriented grids

The introduction of Web services into grids helped to address their two main obstacles to be embraced by business and industry, heterogeneity and useability. However, many problems are still open, e.g., grid reconfiguration, reliability and computing optimization. We argue here that a mechanism that could help solving these problems is Web Service migration, a part of automatic and transparent brokerage. Web service migration presents a number of new requirements not addressed in traditional process migration, being the outcome of Web services specific configuration of hosts and application servers, and availability of Web services / resources state. In this paper we report on our study into the development of a Web service migration facility focused on providing migration of services in a Service Oriented Grid environment. We present a novel approach to Web service migration, embodied in a System Management Broker, which is transparent, interoperable and flexible. We take the requirements of Web services into consideration when discovering suitable destination hosts and match services to suitable grid resources which are able to fulfil the needs of the service. We discuss a number of experiments conducted with different types of grid and Web service applications to highlight the feasibility and effectiveness of our migration facility and demonstrate how our facility significantly improves Service Oriented Grids.

Transparent and autonomic rollback-recovery in cluster systems

Cluster systems provide an excellent environment to run computation hungry applications. However, due to being created using commodity components they are prone to failures. To overcome these failures we propose to use rollback-recovery, which consists of the checkpointing and recovery facilities. Checkpointing facilities have been the focus of many previous studies; however, the recovery facilities have been overlooked. This paper focuses on the requirements, concept and architecture of recovery facilities. The synthesized fault tolerant system was implemented in the GENESIS system and evaluated. The results show that the synthesized system is efficient and scalable.

Autonomic system management in mobile grid environments

Mobile device integration in grid environments is a challenge for many researchers. Due to the transient nature of mobile devices, service management is a critical, but often overlooked area of research. We propose a distributed broker responsible for the autonomic management of grid services. The broker provides self discovery and negotiation, self configuration and self healing for SOA based mobile grids. In this paper the design and prototype implementation of the broker is presented and the importance of autonomic grid service management is shown.