Muscarinic modulation of endogenous noradrenaline release from adrenergic terminals in the guinea-pig colon

1 The present study examined the role of muscarinic receptors in the modulation of noradrenaline (NA) release in the guinea-pig isolated distal colon. The spontaneous endogenous NA overflow assayed by HPLC-ED was taken as an index of NA release from enteric noradrenergic nerve terminals. 2 Physostigmine (10 μm ) significantly enhanced spontaneous endogenous NA overflow. Hyoscine (muscarinic antagonist), (R)-(-)-trihexyphenidyl and telenzepine (M₁-selective antagonists), and 11[[2-[(diethylamino)methyl]-1-piperydil]acetyl]-5,11-dihydro-6H-pyrido[2,3-b][1,4]benzodiazepine-6-one (AF-DX 116, M₂-selective antagonist) inhibited NA overflow in a concentration dependent manner, with the following EC₅₀ values: 131.74 (18.19–953.96), 101.62 (58.83–175.60), 150 (60–330), 30 (5–170) nm , respectively. 4-diphenylacetoxy-N-methylpiperidine methiodide (4-DAMP, M₁- and M₃- selective antagonist) had no significant effect up to 100 μm . 3 The muscarinic agonist oxotremorine inhibited NA overflow in a concentration dependent manner, with an EC₅₀ value of 0.67 (0.30–1.51) μm . The response to oxotremorine was inhibited by muscarinic antagonists with the following order of potency: hyoscine = (R)-(-)-trihexyphenidyl = telenzepine > 4-DAMP >> AF-DX 116. 4 In the presence of 3 μm tetrodotoxin (TTX), the effect of oxotremorine and 4-DAMP was unchanged, while hyoscine, (R)-(-)-trihexyphenidyl, telenzepine and AF-DX 116, instead of inhibiting, significantly enhanced NA overflow. 5 The present results indicate that, in the guinea-pig colon, endogenous acetylcholine sustains spontaneous NA release by activating muscarinic receptors possibly located on interneurones. In addition, inhibitory muscarinic receptors may exist on adrenergic terminals.     

Management of headache in emergency room

Neurological Sciences - Headache is one of the most common symptoms that leads patients to the emergency room (ER) and is often related to diseases requiring prompt diagnosis and immediate...     

Partial k-space reconstruction in single-shot diffusion-weighted echo-planar imaging.

Partial k-space sampling is frequently used in single-shot diffusion-weighted echo-planar imaging (DW-EPI) to reduce the TE and thereby improve the SNR. However, it increases the sensitivity of the technique to bulk rotational motion, which introduces a phase gradient across the tissue that shifts the echo in k-space. If the echo is displaced into the high spatial frequencies, conventional homodyne reconstruction fails, causing intensity oscillations across the image. Zero-padding, on the other hand, compromises the image resolution and may cause truncation artifacts. We present an adaptive version of the homodyne algorithm that detects the location of the echo in k-space and adjusts the center and width of the homodyne filters accordingly. The adaptive algorithm produces artifact-free images when the echo is shifted into the high positive k-space range, and reduces to the standard homodyne algorithm in the absence of bulk motion.     

Increased serum levels of soluble interleukin-2 receptor in patients with systemic lupus erythematosus and rheumatoid arthritis

In this study we investigated the serum levels of a released soluble form of the interleukin-2 receptor (sIL-2R) in 42 patients with rheumatoid arthritis and in 12 cases of systemic lupus erythematosus. Data were evaluated in relationship to the clinical phase and compared with those observed in normal controls (N=56) and in osteoarthritis (N = 7). Increased levels were observed in both rheumatoid arthritis (mean ± SE, 604±49 U/ml) and systemic lupus erythematosus (1438±481 U/ml). These values were significantly higher than in control (256±15 U/ml;P<0.001) and in osteoarthritis (298±33 U/ml;P<0.001) groups. In addition, the highest values were associated with the active phases of both rheumatoid arthritis (active vs inactive, 771±78 vs 451±39 U/ml;P<0.001) and systemic lupus erythematosus (active vs inactive, 2108±489 vs 499±75 U/ml;P<0.001). Our findings suggest that the detection of sIL-2R in rheumatoid arthritis and in systemic lupus erythematosus may represent a good marker of disease activity, which indirectly indicates the ongoing activation and/or proliferation of immunoreactive cells which are involved in the pathogenetic events of these autoimmune conditions.     

Excitability of the soleus H-reflex arc during walking and stepping in man

Summary In eight normal subjects, the excitability of the soleus (Sol) H-reflex was tested in parallel with Sol length changes, EMGs of leg and thigh muscles and ground contact phases, during three different pacing movements: bipedal treadmill walking, single limb treadmill walking, and single-limb stepping on one spot. A computerized procedure was used which compensated for changes in stimulus effectiveness that occurred during free motion. In the three paradigms examined, significant excitability modulations were observed with respect to a control level determined in standing weight-bearing position. During bipedal treadmill walking, excitability was decreased in the early stance, maximally enhanced in the second half of the stance, and again decreased during the end-stance and the whole swing phase, with a minimum value around the toe off period. The main modulation pattern was retained during single-limb treadmill walking. During single-limb stepping on one spot, the stance-phase increase in excitability and the swing phase depression were still present. However, in the second half of the swing phase, reflex responsiveness returned to reference level, which was maintained during the subsequent contact period. Moreover, a decrease in reflex excitability was detected around the mid-stance. The time course of the described modulations was only partly correlated with the EMG and length changes of the Sol muscle. Furthermore, in the three movements tested, during the early stance phase, the excitability of the H-reflex arc did not correspond to the one expected on the basis of the available H-reflex studies performed under static conditions. It is suggested that, at least in certain stride phases (e.g. around the early contact period), an active regulation affects the transmission in the Sol myotatic arc during the pacing movements investigated.     

Reduced platelet glutamate uptake in Parkinson's disease

Summary. Defects in mitochondrial enzymes have been found not only in substantia nigra, but also in platelets from Parkinson's Disease (PD) patients, suggesting a systemic impairment of energy metabolism. Since platelets present an energy-dependent glutamate uptake similar to that described in central nervous system, glutamate uptake was determined in platelets from 34 PD patients and 21 age-related normal controls, as Na⁺-dependent [³H]glutamate influx; glutamate level was also analyzed by reverse-phase HPLC. A 50% reduction of glutamate uptake (p < 0.001) was observed in idiopathic PD patients, respect to controls and secondary parkinsonian syndromes. The decrease correlated with the severity of PD, measured by the UPDRS (r = −0.54; P < 0.05). Glutamate level was increased in platelets of PD patients, but was not correlated to the uptake decrease. Both phoenomena may be explained by the modifications of mitochondrial enzymes described in platelets, which could be used as a peripheral model of glutamatergic function in PD. Received October 7, 1998; accepted January 7, 1999     

Human olfactory sensitivity for bourgeonal and male infertility: a preliminary investigation

Olfactory receptor (OR) expression is also present in the sperm cells and could mediate sperm chemotaxis. OR1D2 was the first OR expressed in the testis demonstrated to be involved in chemotaxis and to be expressed also in the nose with a similar behavior. Bourgeonal is the OR1D2 most potent known agonist. Infertility affects ~15 % of couples in western countries and sometimes it is unexplained. This pilot study compared the bourgeonal olfactory thresholds, the ability of sperm to sense the bourgeonal and the frequency of 13 single nucleotide polymorphisms (SNPs) of OR1D2 gene in nine males suffering of unexplained infertility with a control group of 15 healthy males. The mean olfactory threshold for bourgeonal was statistically different between the study group (10.5 ± 3.7; median 12.3) and the control group (14.0 ± 2.8; median 15.5) (p = 0.006). Statistical analysis showed a significantly higher percentage of spermatozoa that migrated toward the capillaries filled with bourgeonal in the control group compared to the study group (p < 0.0001). Sperm migration was equally inhibited in both groups of subjects when, together with bourgeonal, capillaries were filled with undecanal, a strong bourgeonal inhibitor (p = 0.42). The 13 SNPs of OR1D2 revealed a statistically significant difference for allele and genotype frequency of rs769423 in study group versus control group (p = 0.02). The present preliminary study seems to confirm the important role of OR1D2 both in nose and spermatozoa and may explain the idiopathic infertility of the study group. Further studies on larger series are mandatory to confirm our preliminary evidence.     

Evaluation of regional myocardial systolic and diastolic function using ECG-gated Sestamibi scintigraphy Preliminary results in patients with and without coronary artery disease

Sestamibi allows ECG-gated acquisition and similarly to radionuclide angiography a time-activity curve from a defined myocardial region can be derived and analysed. Diastolic (peak relaxation velocity) and systolic (per cent thickening) functional parameters from Sestamibi ECG-gated acquisition were obtained; this data were compared in 10 patients with radionuclide angiographic data (peak filling rate and ejection fraction, respectively). A high correlation was found between peak relaxation velocity and peak filling rate (r = 0.792), while no significant correlation was found between thickening and ejection fraction (r=0.577). Sestamibi parameters were calculated in 15 patients with known or suspected coronary artery disease and compared with those obtained in 10 normal subjects. In regions supplied by stenotic vessels the average values of peak relaxation velocity and thickening were significantly lower than those obtained in control subjects in the corresponding vascular territory. The average regional values of the diastolic parameter were significantly lower than the corresponding normal range also in regions with preserved systolic function, i.e. with thickening values within 1SD from the mean value of normals.In conclusion, from the ECG-gated acquisition of Sestamibi regional diastolic and systolic functional parameter may be derived; this completes the spectrum of information that can be obtained by a single injection of tracer.Abbreviations EDc end-diastolic counts - EDV end-diastolic volume - EF% ejection fraction - ESc end-systolic counts - ESV end-systolic volume - PFR peak filling rate - PRV peak relaxation velocity - TH% percent thickening