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[Indicators of articular cartilage degeneration in synovial fluid].

Detection of proteoglycans in biological fluids is a perspective method for the evaluation of the degree of catabolic processes in articular cartilage. The demand of accuracy and specificity of detection of substructures of the degradation products of the cartilaginous matrix, with the perspective of routine large scale examinations, restricts available possible methods practically only to the use of immunochemical methods. In the present investigation in the inhibitory ELISA test polyclonal antibodies with a double specificity in relation to basic structures of the cartilage--proteoglycans--were used. The highest concentrations of degradation products of proteoglycans in punctates of synovial fluid were found in diseases where the clinical picture is dominated by repeated attacks of the joints with longer remission periods, and where the attack is stimulated, usually by stimuli of an intermittent systemic or exogenous character (gout, reactive arthritis incl. Reiter's syndrome, Lyme disease).

Antigen-Antibody Reactions↗

Behavioral and electrophysiological effects of peptides related to lipotropin (beta-LPH).

Both C-terminal fragments of lipotropin (beta-LPH) (endorphins) and N-terminal fragments (e.g., ACTH 4-10) delayed extinction of pole-jumping avoidance behavior in rats. After subcutaneous injection Met5-enkephalin appeared to be as active as ACTH 4-10 whereas beta-LPH 61-69, alpha- and beta-endorphin were more potent in delaying extinction of pole-jumping avoidance behavior (approximate ED50 of alpha-endorphin 4 x 10(-11) M rat.) However, the potency of beta-LPH 61-69 and alpha-endorphin appeared to be approximately the same whereas that of beta-endorphin was less than that of ACTH 4-10 after intraventricular administration (approximate ED50 of alpha-endorphin 0.2 x 10(-11) M rat). alpha-Endorphin and ACTH 4-10, administered subcutaneously in a dose which markedly delayed extinction of pole-jumping avoidance behavior, had only slight effects on open field behavior and on responsiveness to electric footshock. A 5 times higher dose of both peptides facilitated passive avoidance behavior. Morphine in two doses significantly delayed extinction of pole-jumping avoidance behavior but the effect was not dose dependent. The specific opiate antagonist naltrexone, however, markedly facilitated extinction of the avoidance response. ACTH 4-10, alpha- and beta-endorphin and a behaviorally potent ACTH 4-9 analog (Org 2766) restored pole-jumping avoidance behavior of rats pretreated with naltrexone. Treatment with a similar dose of naltrexone blocked beta-endorphin-induced analgesia. These results suggest that the influence of peptides related to C-terminal and N-terminal fragments of lipotropin on extinction of avoidance behavior may be dissociated from those exerted on opiate receptor sites. Subcutaneously injected beta-LPH 61-69 or intraventricularly administered beta-endorphin induced a shift from lower to higher frequencies of hippocampal theta rhythm during paradoxical sleep in the same way as that found after ACTH 4-10. This effect is interpreted as indicating an increased arousal state in certain midbrain limbic structures. This may, as has been postulated for ACTH 4-10, alter the motivational value of environmental stimuli (e.g., aversive stimulation).

Adrenocorticotropic Hormone↗

[The electrophysiological characteristics of the compensatory and restorative processes in the central nervous system of neurosurgical patients in relation to the lateralization of the injury].

The authors studied the functional condition of the brain during the restorative period after operative damage to one of the hemispheres. In the early stages of the restorative period in neurosurgical patients with a slow rhythm afferent stimuli (rhythmic light stimulation) induced the appearance of a marked alpha-rhythm, which is evidence of restoration of the functional condition of the cortical and subcortical structures taking part in the generation of this rhythm. Such dynamic changes in the condition of the structures may be considered as a manifestation of their activation and evaluated as a favourable prognostic sign. Data were obtained which characterized the features of the restorative-compensatory process depending on which hemisphere, right or left, the damage was inflicted. According to the indices of the various rates of EEG, high-frequency waves of beta-range prevailed in the intact left hemisphere on the 12th-25th day; this phenomenon was not recorded in an intact right hemisphere in damage to the left hemisphere.

Adaptation, Physiological↗

Dynamic infrared functional mapping of the cerebral cortex.

Although many neuroimaging methods (computer tomography, H+ and isotope clearance, [14C]deoxyglucose utilization, potential-sensitive dyes, electroencephalogram and magnetoencephalogram-mapping, nuclear magnetic resonance tomography, single photon emission computer tomography, and positron emission tomography) are now being used to map brain structure and function, there still exists a need for a new approach that is functional, dynamic, remote, and noninvasive, and that also has reasonable sensitivity and spatial and temporal resolution. Such a method is described here. Thermoencephaloscopy (TES), based on thermovision and digital image processing techniques, is a method of neuroimaging consisting of recording through the intact skull the very weak changes in infrared radiation that are connected with brain activity. The parameters of the method are: temperature sensitivity of 0.002 degrees C, instrumental spatial resolution of 70 microns pixel-1, and instrumental temporal resolution of 40 ms (enabling up to twenty-five maps to be produced per second). The distribution over the rat cerebral cortex of local, multiple, and modally and regionally specific thermoresponses to various sensory stimuli, direct cortical stimulation, and associative learning (conditioning), have been studied, as well as the spreading of thermowaves over the brain cortex. The underlying mechanisms which form the basis of the technique of TES, such as joule heating, local changes in brain metabolism and local cerebral blood flow, as well as the formation of thermodipoles, are discussed.

Animals↗

Sensory deprivation and the ophthalmic patient.

1. Ophthalmic patients with reduced visual acuity and mobility restrictions are potentially at risk for developing cognitive, sensory and behavioral disturbances with sensory deprivation. 2. Each individual has an optimum level of stimulation that varies with circumstances such as age, time of day, amount of recent stimulation, anxiety, fatigue, pain, or illness. The body strives to maintain a homeostatic balance of stimulation. 3. Sensory stimuli must be meaningful, varied, and of sufficient quantity and intensity to maintain arousal. 4. Nursing care of ophthalmic patients should include individual assessment of the appropriateness of environmental stimuli, and plans to prevent sensory deprivation experiences or alleviate symptoms if they occur.

Aged↗

Species variation in the site and mechanism of the neuromuscular effects of diadonium in rodents.

The unusually wide, 80-fold species variation observed by others (1,2) in the neuromuscular (NM) potency of diadonium, a nondepolarizing muscle relaxant (MR), between cat and man suggested that the site and mechanism of its NM effect may vary in different species. To obtain information on this question, the NM potency of diadonium and the reversibility of its NM effect by neostigmine and/or 4-aminopyridine (4AP) was investigated on the in vitro phrenic nerve--hemidiaphragm preparations of rats, mice and guinea pigs. The concentration of diadonium that caused 90% NM block (IC90) was much greater in guinea pigs, 1.74 +/- 0.02 and 1.28 +/- 0.01 mu, when the preparations were stimulated with single stimuli at 0.1 Hz or with 0.1 s trains of 50 Hz tetani every 10 s, respectively, than in rats (IC90 = 62.4 +/- 0.89 and 52.1 +/- 1.00 microM) or mice (IC90 = 51.9 +/- 0.98 and 44.4 +/- 0.22 microM). In guinea pigs, the NM blocking effect of diadonium could be antagonized by neostigmine. This indicates that in this species the NM blocking effect of diadonium is primarily caused by inhibition of the interaction of acetylcholine (ACh), released by the nerve impulse, with the cholinergic receptors (cholinoceptors) of the postjunctional membrane (p.j.m.). By contrast, in rats and mice diadonium was not antagonized by neostigmine but was reversed by 4-aminopyridine. This suggests that in these species, in contrast to other nondepolarizing MR, diadonium does not inhibit NM transmission postsynaptically, but by inhibiting the positive nicotinic feedback mechanism of mobilization of ACh from reserve depots to release sites, causes a presynaptic NM block.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetylcholine↗

Association between gelatinase release and increased plasma membrane expression of the Mo1 glycoprotein.

Mo1, a glycoprotein heterodimer (gp 155,95) that functions as an adhesion promoting molecule and as the C3bi receptor of human myeloid cells, is expressed in increased amounts in the plasma membrane after exposure of polymorphonuclear leukocytes (PMNs) to various stimuli. Previous studies have suggested that secondary granules represent an intracellular pool of Mo1 that, upon degranulation, fuse with the plasma membrane resulting in a tenfold increase in surface expression of Mo1. To determine the intracellular location of Mo1, we monitored Mo1 expression by immunofluorescence and compared it to the release of myeloperoxidase (MPO, a marker for the primary granules), vitamin B12 binding protein (B12BP, secondary granules), and gelatinase (gelatinase-containing organelles) following exposure to various stimuli. Human neutrophils stimulated with 20 mmol/L fluoride for 16 minutes exhibited a twofold increase in Mo1 expression and gelatinase release but no enhanced release of primary or secondary granular contents. In a similar fashion, incubation of cells at 37 degrees C for five minutes with 7.5 X 10(-9) to 10(-6) mol/L N-formyl-methionyl-leucyl-phenylalanine (FMLP) resulted in significant increases in both surface Mo1 expression (three- to fivefold) and gelatinase release (five- to eightfold) without significant release of either MPO or B12BP. In addition, both the fluoride and FMLP experiments demonstrated that Mo1 up-modulation alone is not sufficient to activate superoxide (O2-) production. These data indicate that at least one intracellular storage pool of Mo1 is the gelatinase-containing organelles and that their fusion with the plasma membrane results in increased expression of Mo1 on the cell surface.

Fluorides↗

Matching behavior in the young infant.

Infants as young as 2--6 weeks have been reported to exhibit matching behavior in response to seeing an adult model tongue protrusion and certain other acts. Matching behavior to the tongue model declines by 12 weeks. The present study was designed to investigate whether (1) this matching behavior represents selective imitation or a released response that can be elicited by a broad but delimited class of incentive stimuli and (2) stimulation of tongue protrusion enhances the response and delays its decline. 24 infants were observed at 6, 10, and 14 weeks. A moving pen and ball were as effective as the tongue model in eliciting tongue protrusion at 6 weeks, while a dangling ring elicited as much hand opening and closing as the hand model at 14 weeks. After the 6-week visit, 12 of the infants were exposed to the tongue model daily. This intervention delayed the decline of matching behavior to the tongue model at 14 weeks. Also, experimental infants responded selectively to the tongue model, while the pen continued to be an effective releaser of tongue protrusions among controls.

Arousal↗

[The value of renin determination in the diagnosis of hypertension].

Primary aldosteronism and renovascular hypertension are two different diseases in which renin determinations are necessary for establishment of diagnosis or therapeutic procedure. Low renin values which are not stimulated by acute stimuli combined with elevated plasma aldosterone concentrations confirm the diagnosis of primary aldosteronism. When in a patient with proven renal artery stenosis a significant difference in renal venous renin activity is observed between the two kidneys, a connection between hypertension and renal artery stenosis is likely when in addition the renin secretion of the unaffected kidney is suppressed. A favourable outcome for surgery can be predicted when the individual clinical picture in such a case is also considered. A similar view also holds for the connection between hypertension and unilateral small kidney not due to renal artery stenosis. In essential hypertension the plasma renin level makes it possible to a certain extent to predict whether a patient will benefit from diuretics or from beta-blocking agents. Despite this experience, however, renin determinations are not indicated in every case of essential hypertension. It has not been proven that the prognosis of this disease is improved by renin oriented monotherapy rather than by effective treatment with other antihypertensive agents.

Adrenergic beta-Antagonists↗

Synthesis and pharmacological activity of befuraline (N-benzo[b]furan-2-ylcarbonyl-N'-benzylpiperazine), a new antidepressant compound.

The methods of synthesis and the pharmacological evaluation of a new non-tricyclic antidepressant drug, N-benzo[b]furan-2-ylcarbonyl-N'-benzylpiperazine (befuraline), are reported. The chemical structure of befuraline is clearly different from that of the tricyclic antidepressant drugs. While the gross behavior in animals remains unaffected, the central nervous system depressed by reserpine, tetrabenazine or perphenazine is activated by even small doses of this novel compound. Exploratory activity is prolonged, and performance in operant behavior tests and in the conditioned avoidance response is improved by befuraline, indicating increased alertness, attentiveness and the capacity to react to environmental stimuli. High doses stimulate the CNS, causing EEG desynchronization. Befuraline displays an aggression-inhibiting activity; without having a sedative effect on the animals' normal behavior, it inhibits fighting behavior. The central anticholinergic effect of befuraline is negligible. No apomorphine or tryptamine potentiation is observed and hexobarbital anesthesia is not influenced. The peripheral autonomic nervous system, with the exception of the nictitating membrane in cats, is not affected by befuraline. It has a biphasic effect on the norepinephrine induced contraction of isolated guinea pig seminal vesicle and of isolated cat spleen slices. Although the mechanism of action is as yet not clear, it is assumed that, in addition to a direct influence on the central adrenergic structures, the inhibition of norepinephrine and serotonin uptake and the inhibition of phosphodiesterase are responsible for the drug's effect. Befuraline has no undesirable effects on either the peripheral autonomic nervous system or the cardiovascular system, and it does not affect the normal gross behavior of animals. Because these favorable therapeutic aspects are coupled with low toxicity, befuraline may provide a new alternative in the treatment of depression.

Animals↗

Pathophysiology of airway obstruction in horses: a review.

Obstruction of the upper and lower airways is common in horses. In the upper airway, paresis of abductor muscles of the nares and larynx allows inspiratory collapse of soft tissues, which is accentuated by factors increasing upper airway resistance and by high inspiratory flow rates. Intrapulmonary airway obstruction occurs due to accumulation of secretions, release of chemical mediators in response to a variety of stimuli, and parasympathetic stimulation of airways. Obstruction of large airways increases the work of breathing, whereas obstruction of small airways may cause no measurable increase in resistance but does cause uneven distribution of ventilation and hypoxemia, especially during exercise. Poor collateral ventilation accentuates gas exchange problems in the horse with airway obstruction and may be a factor causing intrapulmonary hemorrhage during racing.

Airway Obstruction↗

Dehydration and fluid balance: central effects of angiotensin.

Central effects of dehydration are stimulated by osmotic stimuli, the reduced input of volume receptors, and angiotensin II. The subfornical organ (SFO) and organum vasculosum laminae terminalis (OVLT) have become accepted as putative receptor sites for angiotensin II in the brain. The exact quantitative relationship between the hours of water deprivation and the amount of angiotensin generated peripherally and whether that amount is sufficient to induce thirst centrally have not been established, but there is no question that when animals are dehydrated their angiotensin levels rise and the animals are thirsty. Attempts to block centrally the contribution of angiotensin II to thirst have been variable and cholinergic inputs have to be blocked at the same time. Various stimuli for thirst interact in a parallel fashion, and when one stimulus is blocked the other stimuli are still effective. Plasma angiotensin II may induce natural thirst, but how it enters the brain still remains to be explained. Although the SFO and OVLT have no blood-brain barrier, the blood supply to these organs acts as a limited perfusion system whereby blood-borne proteins cannot diffuse far from the capillary bed. A second set of receptors is found on the ventricular surface of the OVLT, as shown by fluorescence labeled angiotensin II. The connection between the SFO and OVLT was cut by discrete knife cuts. Drinking to angiotensin II intraventricularly was not significantly altered but the pressor response was reduced by 50%. These results can be explained by a circuit for drinking passing down below the level of the knife cut and a separate pressor pathway passing dorsally through the area that was cut by the knife. Thirst and pressor neural circuits beginning with angiotensin receptors could explain some of the data accumulated with the AV3V syndrome that occurs when the OVLT and nucleus medianas are destroyed.

Angiotensin II↗

[Role of dominant motivation in producing the effects of electric stimulation of hypothalamo-limbic structures].

The experiments were made on cats with electrodes chronically implanted in the hypothalamus and the amygdala. The effects of electrical stimulation of the points from which the food reactions were initially evoked, were transformed into an avoidance reaction, if stimulation was applied in surroundings where the animals had previously received pain stimuli. Defensive reactions to stimulation of the hypothalamus and amygdala changed to alimentary reactions if the same stimulation was presented to hungry cats in conditions of repetitive feeding. A conclusion has been drawn that the elements of the hypothalamo-limbic structures have plastic properties and may be involved in different forms of behaviour, depending on current motivation and learning.

Amygdala↗

[Hyperplastic Brunner glands and chronical renal insufficiency (author's transl)].

Enlarged Brunner glands (EBG) are an occasional finding in upper gastro-intestinal barium studies. The clinical manifestations vague upper abdominal symptoms or bleeding are rare. Brunner gland secretion is stimulated by different stimuli but especially by secretin. In our report E.B.G. has been observed in 9/15 chronically hemodialysed patients. This uncommon frequence of E.B.G. can be related to the high blood levels of secretin found in patients with chronic renal failure. E.B.G. could explain some of the gastro-intestinal complications occuring in these patients.

Adult↗

Essential involvement of interleukin-8 (IL-8) in acute inflammation.

Neutrophil infiltration into inflammatory sites is one of the hallmarks of acute inflammation. Locally produced chemotactic factors are presumed to mediate the sequence of events leading to the infiltration at inflammatory sites. Interleukin-8 (IL-8), a novel leukocyte chemotactic activating cytokine (chemokine), is produced by various types of cells upon stimulation with inflammatory stimuli and exerts a variety of functions on leukocytes, particularly, neutrophils in vitro. However, no definitive evidence has been presented on its role in recruiting and activating neutrophils in the lesions of various types of inflammatory reactions. We administered a highly specific neutralizing antibody against IL-8 in several types of acute inflammatory reactions, including lipopolysaccharide (LPS)-induced dermatitis, LPS/IL-1-induced arthritis, lung reperfusion injury, and acute immune complex-type glomerulonephritis. Anti-IL-8 treatment prevented neutrophil-dependent tissue damage as well as neutrophil infiltration in these conditions. These results suggest that IL-8 plays a causative role in acute inflammation by recruiting and activating neutrophils.

Animals↗

Quantitative measurements of eye movements in a patient with Tullio phenomenon.

The Tullio phenomenon consists of vestibular symptoms on exposure to high-intensity acoustic stimuli, reflecting pathological stimulation of semicircular canals or otoliths. We report a patient with posttraumatic Tullio phenomenon to illustrate how precise measurement of eye movements during auditory stimulation, using the magnetic search coil technique, may characterize movements that are not clinically apparent or easily measured by other means. Such measurements in patients with surgically verified lesions may further elucidate the mechanisms responsible for this phenomenon.

Acoustic Stimulation↗

Ionic currents underlying developmental regulation of repetitive firing in Aplysia bag cell neurons.

We have investigated the developmental regulation of the ability to fire repetitively in the bag cell neurons of Aplysia californica, a neuronal system in which the behavioral effects of repetitive firing are well characterized. Adult bag cell neurons exhibit an afterdischarge, consisting of prolonged depolarization and repetitive firing, which causes the release of several peptides from these neurons that induce egg-laying behaviors. Afterdischarge can be triggered in vitro by a variety of stimuli, including electrical stimulation and exposure to the potassium channel blocker tetraethyl ammonium chloride (TEA). In contrast to adults, juvenile neurons did not exhibit afterdischarge in response to pleural-abdominal connective shock or TEA. Juvenile neurons did exhibit, however, prolonged depolarizations in the presence of TEA, perhaps reflecting the anlage of the mechanism responsible for afterdischarge in the adult. To investigate developmental mechanisms underlying the regulation of repetitive firing, we compared ionic currents in adult and juvenile bag cell neurons. We found that during the period in which these neurons acquire the capacity to fire repetitively, a number of currents are regulated: (1) three K+ currents decrease (Ca2+)-dependent K+ and two components of voltage-dependent delayed-rectifier K+ current); (2) A-type K+ current increases; and (3) two Ca2+ currents increase (basal and PKC-activated). This pattern is consistent with the increase in the ability to fire repetitively that we observe during maturation: our results indicate that developmental control of repetitive firing in this system is accompanied by selective regulation of specific ionic currents which, after maturation, play important roles in generating the afterdischarge and triggering egg-laying behaviors.

Animals↗

[Cardiac pacing in tachycardiac arrhythmias].

Cardiac pacing may be useful in the management of supraventricular and ventricular tachycardias. Prophylactically, recurrent ectopic tachycardias may be prevented by atrial or ventricular pacing for a sustained period at a rate faster than the spontaneous rate, but slower than the rate of the tachycardia being suppressed. Moreover, the pacemaker permits the dosage of antiarrhythmic agents to be increased until the recurrent arrhythmias are completely controlled. Therapeutically, supraventricular tachycardias may be terminated by (1) overdrive suppression, (2) delivery of a single stimulus or two serial stimuli or repetitive stimulation at a rate slower than the tachycardia (competitive stimulation) and (3) orthorhythmic stimulation. Today, implantable units exist. Advantages and disadvantages as well as risks of pacing in patients with tachycardias, are discussed.

Electric Stimulation↗