Use of 2-dimensional speckle-tracking echocardiography to assess left ventricular systolic function in dogs with systemic inflammatory response syndrome

Background: Early identification of systolic dysfunction in dogs with systemic inflammatory response syndrome (SIRS) potentially could improve the outcome and decrease mortality. Objective: To compare 2-dimensional speckle tracking (2D-STE) with 2-dimensional (2D) and M-mode echocardiography in the evaluation of systolic function in SIRS dogs. Animals: Seventeen SIRS and 17 healthy dogs. Methods: Prospective observational case-control study. Each dog underwent physical examination, conventional echocardiography, 2D-STE, and C-reactive protein measurement. Results: Dogs with SIRS had lower 2D-STE ejection fraction (X4D-EF; 44 ± 8 versus 53 ± 8; P =.003), endocardial global longitudinal strain (ENDO-G-Long-St; -14.6 ± 3.2 versus -18.5 ± 4.1; P =.003), and normalized left ventricular diameter in diastole (1.38 ± 0.25 versus 1.54 ± 0.17; P =.04) and systole (0.85 ± 0.18 versus 0.97 ± 0.11; P =.03) as compared to healthy dogs. Simpson method of disks (SMOD) right parasternal EF (55 ± 9 versus 60 ± 6; P =.07) and end systolic volume index (ESVI; 23 ± 10 versus 21 ± 6; P =.61), SMOD left apical EF (59 ± 9 versus 59 ± 6; P =.87) and ESVI (20 ± 8 versus 22 ± 6; P =.25), fractional shortening (FS; 34 ± 5 versus 33 ± 4; P =.39), M-mode EF (64 ± 7 versus 62 ± 5; P =.35), and ESVI (23 ± 11 versus 30 ± 9; P =.06) were not significantly different between SIRS and control group, respectively. Conclusion and Clinical Importance: Speckle tracking X4D-EF and ENDO-G-Long-St are more sensitive than 2D and M-Mode FS, EF, and ESVI in detecting systolic impairment in dogs with SIRS

Novel effect of nefopam preventing cGMP increase, oxygen radical formation and neuronal death induced by veratridine

Nefopam hydrochloride is a potent analgesic compound that possesses a profile distinct from that of opiods or anti-inflammatory drugs. Previous evidence suggested a central action of nefopam but the detailed mechanisms remain unclear. Here we have used cultured cerebellar neurons to test the hypothesis that nefopam may modulate voltage sensitive sodium channel (VSSC) activity. Nefopam (100 microM) effectively prevented NMDA receptor-mediated early appearance (30 min) of toxicity signs induced by the VSSC activator veratridine. Delayed neurotoxicity by veratridine occurring independently from NMDA receptor activation, was also prevented by nefopam. In contrast, excitotoxicity following direct exposure of neurons to glutamate was not affected. Neuroprotection by nefopam was dose-dependent. 50% protection was obtained at 57 microM while full neuroprotection was achieved at 75 microM nefopam. Veratridine-induced sodium influx was completely abolished in nefopam-treated neurons. Intracellular cGMP and oxygen radical formation following VSSC stimulation by veratridine were also effectively prevented by nefopam. Our data are consistent with an inhibitory action of nefopam on VSSC and suggest that nefopam may modulate the release of endogenous glutamate following activation of these channels. This novel action of nefopam may be of great interest for the treatment of neurodegenerative disorders involving excessive glutamate release and neurotransmission

Nefopam, an analogue of orphenadrine, protects against both NMDA receptor-dependent and independent veratridine-induced neurotoxicity

Nefopam hyghochloride is a potent analgesic compound commercialized in most Western Europe for 20 years, which possesses a profile distinct from that of opioids or anti-inflammatory drugs. Previous evidence suggested a central action of nefopam but the detailed mechanisms remain unclear. While, nefopam structure resembles that of orphenadrine, an uncompetitive NMDA receptor antagonist, here we report that differently from orphenadrine, nefopam (100 microM) failed to protect cultured cerebellar neurons from excitotoxicity following direct exposure of neurons to glutamate. Moreover, nefopam failed to displace MK-801 binding to hippocampal membranes. Nefopam effectively prevented NMDA receptor-mediated early appearance (30 min) of toxicity signs induced by the voltage sensitive sodium channel (VSSC) activator veratridine. The later phase (24 h) of neurotoxicity by veratridine occurring independently from NMDA receptor activation, was also prevented by nefopam. Nefopam effect was not mimicked by the GABA receptor agonist muscimo

Multiple sclerosis and HERV-W/MSRV: A multicentric study

We designed a large multicentric study to analyse the presence of MSRV particles in blood and CSF of a large cohort of patients and controls from different European areas. 149 MS patients and 153 neurological and healthy controls were selected from Sardinia, Spain, Northern-Italy and Sweden. To avoid biological and inter-assay variability MSRV was detected within a single laboratory through nested and real-time PCR assays specific for pol and env genes. MSRV detection in blood and CSF of MS patients and controls in populations of different ethnicity gave significant differences (p<0.05 compared to neurological controls and <0.001 compared to healthy controls). The presence and viral load of MSRV are significantly associated with MS as compared to neurological and healthy controls in all ethnic groups

A study of the relationship between muscle length, tension-time area and stiffness in cat areflexic soleus

The relationship between muscle length and both tension-time area and stiffness were studied in the isolated cat soleus muscle during tetanic isometric contraction at different stimulus rates. The results show that: 1. The area subtending the tension curve remains constant in a range of 8-10 mm of muscle length, for stimulation frequencies between 15 and 66 Hz. 2. The muscle stiffness, measured using different amplitude stretches, remains constant over changes in muscle length of 10 mm. 3. The stiffness is higher for smaller stretches than for larger ones. The data therefore show an approximately constant tension-time area and no significant changes in stiffness for variations in muscle length that exceed the physiological length variations during quiet standing. These results are discussed in the context of postural mechanisms

Peripheral mononeuropathy affects hypothalamic and splenocyte beta-endorphin levels but not immune function in the rat

Beta-endorphin and substance P levels were measured in the hypothalamus of rats 14 days after chronic constriction injury of right sciatic nerve. Furthermore, beta-endorphin concentrations in splenocytes, phytoemoagglutinin-induced proliferation of splenocytes, and natural killer activity were assessed. We observed a significant increase of beta-endorphin and substance P hypothalamic levels, and a significant decrease of beta-endorphin concentrations in the immune cells. In contrast, the peripheral mononeuropathy did not affect the immune function. This study presents a picture of central and peripheral peptide changes consistent with a painful condition, but different from what previously observed in rats which underwent peripheral nerve deafferentation or stressful condition

A horseradish peroxidase study of afferent projections to nucleus reticularis thalami in the cat

Afferent projections from both the reticular formation and the thalamic relay nuclei to nucleus reticularis thalami (R) were studied using the HRP technique. Injections were performed in different regions of the nucleus. Numerous labelled cells were found ipsilaterally in the lateral geniculate nucleus (GL) following HRP injections in dorsolateral regions of R and in the ventrobasal complex (VB) following HRP injections in the ventral regions. No labelling of brain stem reticular structures was ever found. These results provide evidence for direct projections from the VB and GL nuclei to R. The functional meaning of this data is discussed in relation to previous anatomical and neurophysiological findings. The hypothesis of a significant role of R in feedback circuits modulating sensory information seems to be supported

Rough annealing by two-step clustering, with application to neuronal signals.

Analysis of neuronal signals by clusterin

Effects of the bisphosphonate ibandronate on hyperalgesia, substance P, and cytokine levels in a rat model of persistent inflammatory pain

The anti-inflammatory and analgesic properties of different bisphosphonates have been demonstrated in both animal and human studies. Ibandronate is a third-generation bisphosphonate effective in managing different types of bone pain. In this study we investigated its effects in a standard pre-clinical model of inflammatory pain. We evaluated the effects of a single injection of different doses (0.5, 1.0, and 2.0 mg/kg i.p.) of ibandronate on inflammatory oedema and cutaneous hyperalgesia produced by the intraplantar injection of complete Freund's adjuvant (CFA) in the rat hind-paw. In addition, we measured the effects of this drug (1.0 mg/kg i.p.) on hind-paw levels of different pro-inflammatory mediators (PGE-2, SP, TNF-alpha, and IL-1beta). We also measured the levels of SP protein and of its mRNA in the ipsilateral dorsal root ganglia (DRG). Ibandronate proved able to reduce the inflammatory oedema, the hyperalgesia to mechanical stimulation, and the levels of SP in the inflamed tissue as measured 3 and 7 days following CFA-injection. This drug significantly reduced the levels of TNF-alpha and IL-1beta only on day 7. On the other hand, the levels of PGE-2 in the inflamed hind-paw were unaffected by the administration of this bisphosphonate. Finally, ibandronate blocked the overexpression of SP mRNA in DRG induced by CFA-injection in the hind-paw. These data help to complete the pharmacodynamic profile of ibandronate, while also suggesting an involvement of several inflammatory mediators, with special reference to substance P, in the analgesic action of this bisphosphonate