Endogenous inhibitory system in pain

Electrical stimulation of several brain sites produces profound analgesia in humans, and inhibits nocifensor reflexes in animal studies. Responses of the dorsal horn nociceptive neurons evoked by stimulation onto the receptive fields are also inhibited by brain stimulation. These brain sites are Periaqueductal Gray Matter (PAG), Nucleus Raphe Magnus (NRM), Nucleus Reticularis magnocellularis (NRmc), Locus Coeruleus (LC), Lateral Hypothalamus, and others. We have explained in a general way the mechanism of these stimulation produced analgesia. The mechanism of PAG stimulation analgesia is partly due to an activation of serotonin containing neurons which descend from NRM to the spinal dorsal horn and activated by PAG stimulation. Activation of NRM neurons may produce inhibition of the nociceptive neurons of the dorsal horn by the mechanism of direct postsynaptic inhibition. Currently there is no evidence to support the theory of presynaptic inhibition. Endogenous opioid peptides do not play an important role in PAG stimulation analgesia. On the other hand, the mechanism of NRmc or LC stimulation analgesia may be due to an activation of noradrenaline containing neurons which similarly inhibit the dorsal horn nociceptive neurons in the spinal cord. At present, it still remains unknown whether endogenous opioid peptides play an important role in this type of analgesia.     

Localization of epileptogenic foci using a simple reference-subtraction montage to document small interchannel time differences

We present a modified EEG montage that detects small interchannel time differences and assists in localizing the epileptogenic focus. Regions with apparently synchronous epileptic discharges are displayed simultaneously in referential and subtraction derivations. The subtraction derivation is a bipolar configuration of two regions of interest that are not necessarily adjacent. The referential derivation reveals the polarity, voltage, and morphology of the two discharges, and the subtraction derivation detects asynchrony; the combined reference-subtraction derivation thus indicates the region that is activated first.     

Neuroradiological analysis of small infarcts in deep subcortical structure detected by CT

We studied angiographic findings of 56 patients who were diagnosed as lacunar infarcts in the basal ganglia or deep subcortical white matter based on clinical symptomatology and brain computed tomography. In 26 patients with CT lesions less than 15 mm in diameter, only eight (31%) showed minor angiographic findings. In 30 patients with lesion of 15 mm or more, however, 22 (73%) had abnormal angiographic findings. Fourteen of the 22 patients had minor irregularities, three had 25-75% stenosis, five had 75% less than stenosis at the bifurcation of the common carotid artery or the horizontal portion of the middle cerebral artery. Our findings support the notion that a small lesion on CT can result from an occlusion of the perforating artery itself and a larger lesion is much related to the major vessel or heart diseases, i.e., emboli from the parent artery or heart, obstruction of perforators at their origin by an atheromatous plaque of the horizontal portion of the middle cerebral artery, or terminal zone infarct due to hemodynamically significant stenotic lesion. In patients with a larger deep infarct on CT, further investigation of the arteries in the carotid-axis and heart is important for determination of therapeutic indication.     

Silent period induced by cutaneous stimulation.

An electrical stimulus applied to a cutaneous nerve during isometric muscle contraction causes a suppression of EMG activity (silent period) followed by a rebound. The extent of inhibition is related to the stimulus intensity as the silent period is more evident when stimulation is perceived as painful. The silent period is present in different limb and cranial muscles after stimulation of the same cutaneous nerve and in the same muscle after stimulation of distant cutaneous nerves. It also occurs synchronously in antagonist muscles. Within the silent period induced after cutaneous stimulation the maximal inhibition on the opponens pollicis motor neuron pool, as tested by the motor response evoked after transcranial cortical stimulation, occurs between 50 and 70 msec. Using the double stimulus technique to study the recovery cycle, the silent period is present at interstimulus intervals as low as 100 msec, and does not habituate with trains of stimuli at frequencies up to 5 Hz. Our results suggest that motor neuron inhibition from nociceptive stimulation may be mediated by Renshaw cells directly activated by high threshold cutaneous afferents.     

Neoplastic meningitis.

Neoplastic meningitis appears to be increasing in frequency with improvements in the treatment of many cancers. It is most often recognized in patients with leukemia, breast cancer, lymphomas, and small-cell cancer of the lung, although it may be seen with virtually any malignancy. Treatment should include intrathecal chemotherapy, radiation therapy to symptomatic areas of the CNS, and optimal therapy of the systemic cancer. New efforts are underway to decrease the toxicity and improve the efficacy of antineoplastic therapy for this devastating complication of cancer.     

Ubiquitin in motor neuron disease: study at the light and electron microscope.

Several neurodegenerative diseases, including motor neuron disease (MND), are characterized by formation of abnormal cytoskeleton-derived inclusions which contain ubiquitin (Ubq). We have studied the distribution of Ubq in 26 cases of MND with light and electron microscopic immunocytochemistry. Ubiquitin-positive inclusions were found in neurons of anterior horns in most cases of amyotrophic lateral sclerosis (ALS) but were not present in other forms of MND. Ubiquitin immunoreactivity was observed in 10-15 nm intraneuronal filaments, which were not stained by antibodies to neurofilaments, and on dense bodies of dystrophic neurites throughout the neuropil of anterior horns and pyramidal tracts. Data analysis showed a trend toward lower percentage of Ubq-positive neurons in cases with longer duration of illness or lower number of neurons. A high percentage of Ubq-positive inclusions occurred in cases with an aggressive clinical course, suggesting that ubiquitination takes place at early stages of the disease.     

Intrafollicular blood flow during human ovulation.

Transvaginal ultrasonography with color flow mapping has been used to study changes in intrafollicular blood flow and morphology during follicular rupture and presumed ovulation in one human volunteer. Detailed monitoring started on day 11 of the menstrual cycle and the follicle began to rupture at 14.30 on day 13. This event was preceded by a defined rise and peak in the level of immunoreactive serum luteinizing hormone (LH) by 42 h and 17 h 20 min, respectively. Blood vessels were clearly visible in the inner ring of the follicle (the granulosa layer) at the time of the LH peak and part of the granulosa (probably containing the oocyte) started to detach before the follicle ruptured. The maximum value for the peak blood velocity in the inner vessels was observed 10 s after the start of follicular rupture and there was a concurrent increase in the impedance to blood flow, as reflected by the resistance index and the pulsatility index. The follicle took 14 min 29 s to empty and the corpus haemorrhagicum started to form about 1 min later. These preliminary data suggest that intrafollicular angiogenesis and changes in blood flow can be monitored by a relatively non-invasive technique. Changes in vascularity might be used to predict imminent ovulation and could possibly be identified or modified biochemically to help achieve or avoid a pregnancy.     

Human alpha-fetoprotein and its purification by chromatography on immobilized estrogens.

Human alpha-fetoprotein (AFP) was isolated from human abortive tissue by biospecific chromatography on immobilized estrogens. The most effective sorbents were: estrone-0-3-hemisuccinyl-hexamethylenediamine-Sepharose CL 4B and diethylstilbestrol-diasoanisole-sulfonyl-oxyethyl-Sepharose CL 4B. As elution solution the most optimum was 10% buffered aqueous butanol. Taking into consideration the data obtained, one can conclude that AFP in human biological fluids is bound to immobilized estrogens. Butanol extraction deestrogenizes AFP, and as a result human AFP acquires affinity to immobilized estrogens. During rechromatography on immobilized diethylstilbestrol, it was possible to obtain AFP preparations of about 95% purity. The present results provide the opportunity to work out new methodological approaches to human AFP isolation using biospecific chromatography on immobilized estrogens.     

New indole alkaloid glycosides from Nauclea orientalis

Two new indole alkaloid glycosides, 10-hydroxystrictosamide and 6'-O-acetylstrictosamide, as well as the known alkaloids strictosamide and vincosamide were isolated from the leaves of Nauclea orientalis L. The structures of the isolated compounds were determined using spectroscopic methods, mainly 1D- and 2D-NMR spectroscopy.