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PubMed2003

Regulatory pathways in lacrimal gland epithelium.

Tears are a complex fluid that continuously cover the exposed surface of the eye, namely the cornea and conjunctiva. Tears are secreted in response to the multitude of environmental stresses that can harm the ocular surface such as cold, mechanical stimulation, physical injury, noxious chemicals, as well as infections from various organisms. Tears also provide nutrients and remove waste from cells of the ocular surface. Because of the varied function of tears, tears are complex and are secreted by several different tissues. Tear secretion is under tight neural control allowing tears to respond rapidly to changing environmental conditions. The lacrimal gland is the main contributor to the aqueous portion of the tear film and the regulation of secretion from this gland has been well studied. Despite multiple redundencies in pathways to stimulate secretion from the lacrimal gland, defects can occur resulting in dry eye syndromes. These diseases can have deleterious effects on vision. In this review, we summarize the latest information regarding the regulatory pathways, which control secretion from the lacrimal gland, and their roles in the pathogenesis of dry eye syndromes.

Animals↗
PubMed2006

ATP stimulates interleukin-6 production via P2Y receptors in human HaCaT keratinocytes.

We evaluated the role of ATP in functions of human HaCaT keratinocytes. ATP was released from HaCaT cells by changing the culture medium. Reverse transcription-polymerase chain reaction analysis revealed that HaCaT cells expressed multiple P2 purinergic receptor mRNAs. UTP was the most potent agonist to increase the intracellular Ca2+ concentration ([Ca2+]i). UTP and ATP caused the accumulation of [3H]inositol phosphates, suggesting that UTP binds to the Gq/11-coupled P2Y receptor. UTP increased IL-6 mRNA and protein levels, and the increases were inhibited by a P2 purinergic receptor antagonist (suramin, 300 microM). While a protein kinase C inhibitor (GF109203X, 10 microM) was without effect, an intracellular free Ca2+ chelator (BAPTA-AM, 50 microM) suppressed UTP-mediated IL-6 induction. These results suggest that 1) ATP is released from HaCaT cells upon physical stimulation and may act as an autocrine molecule, and 2) the stimulation of P2Y receptors causes IL-6 production via mRNA expression through [Ca2+]i elevation.

Adenosine Triphosphate↗
PubMed1992

Effects of simulated microgravity (HDT) on blood fluidity.

Exposures to microgravity and head-down tilt (HDT) produce similar changes in body fluid. This causes an increase in hematocrit that significantly affects hemorheological values. Lack of physical stimulation under bed rest conditions and the relative immobility of the crew during spaceflight also affects the blood fluidity. A group of six healthy male subjects participated as volunteers, and blood samples were collected 10 days before, on day 2 and day 9, and 2 days after the HDT phase. Blood rheology was quantified by plasma viscometry, red cell aggregability, and red cell deformability. A reduced red cell deformability, an indication of the diminished quality of the red blood cells, was measured under HDT conditions that finally led to the so-called "space flight anemia." Enhanced red cell membrane fragility induced by diminished physical activity and an increase in hemoglobin concentration are responsible for this effect. Plasma viscosity is reduced as a result of diminished plasma proteins. However, despite the reduction in plasma proteins, including fibrinogen, alpha 2-macroglobulin, and immunoglobulin M, red cell aggregation was enhanced, principally because of the increase in hematocrit. Our results of hemorheological alterations under HDT conditions may help to elucidate the formerly documented hematologic changes during spaceflight.

Adult↗
PubMed1995

Effects of fluid-induced shear on articular chondrocyte morphology and metabolism in vitro.

This study tested the effects of fluid-induced shear on high density monolayer cultures of adult articular chondrocytes. Fluid-induced shear (1.6 Pa) was applied by cone viscometer to normal human and bovine articular chondrocytes for periods of 24, 48, and 72 hours. At 48 and 72 hours, fluid-induced shear caused individual chondrocytes to elongate and align tangential to the direction of cone rotation. Fluid-induced shear stimulated glycosaminoglycan synthesis by 2-fold (p < 0.05) and increased the length of newly synthesized chains in human and bovine chondrocytes. In human chondrocytes, the hydrodynamic size of newly synthesized proteoglycans also was increased. After 48 hours of fluid-induced shear, the release of prostaglandin E2 from the chondrocytes was increased 10 to 20-fold. In human chondrocytes, mRNA signal levels for tissue inhibitor of metalloproteinase increased 9-fold in response to shear compared with the controls. In contrast, mRNA signal levels for the neutral metalloproteinases, collagenase, stromelysin, and 72 kD gelatinase, did not show such major changes. This study demonstrated that articular chondrocyte metabolism responds directly to physical stimulation in vitro and suggests that mechanical loading may directly influence cartilage homeostasis in vivo.

Aged↗
PubMedDate not supplied

Intracellular calcium response to directly applied mechanical shearing force in cultured vascular endothelial cells.

We studied the responses of cultured endothelial cells to mechanical shearing force directly applied to those cells in vitro to determine changes in the concentration of intracellular calcium ion (Ca++), one of the factors that transfers information within the cell. Cultured bovine fetal aortic endothelial cells containing the Ca++ fluorescence indicator, Fura-2, were rubbed with a latex balloon in a specially designed system, and changes in the fluorescence of Fura-2 caused by this shear stimulation were determined by photometric fluorescence microscopy. Immediately after shear stimulation, the concentration of Ca++ in the cells was increased and reached a peak (511 +/- 165 nM, n = 12) within 15 seconds after stimulation. After the peak, the concentration was gradually restored to the resting level (55 +/- 17 nM, n = 12). The magnitude of the Ca++ response was dependent on the intensity of the shear force applied. Analysis of fluorescence images of Fura-2 revealed that the cells showed this Ca++ reaction without being injured or desquamated, although there were slight differences in the degree and duration of reaction among cells. This reaction appeared even when the cells were placed in the air with no contact with the fluid. This result suggests that neither the fluid flow associated with the balloon movement nor chemical substances in the fluid are involved in the reaction, but that pure physical force alone is responsible for the Ca++ reaction. Further, it suggests that endothelial cells have the ability to perceive such physical stimulation as shear force and to transfer this information to the interior of the cell via changes in the intracellular Ca++ concentration.

Animals↗
PubMed1989

[Biofeedback training and functional electrostimulation for improving incontinence in children with anal atresia].

Eleven children with anal incontinence following a pull-through operation for anorectal agenesis (4 low, 7 high anomalies) were treated with a conservative continence training program (optic/acoustic biofeedback, transcutaneous electrical stimulation, physical therapy, contraction exercises and sensibility training). All patients with one exception showed subjective and objective improvement of continence. Sphincter contraction increased by 80% in high and by 40% in low anomalies. For a short time electrostimulation provided an improvement of up to 20% in sphincter pressure. One additional success was improved coordination. Beside surgical therapy and other methods continence training is always indicated.

Adolescent↗
PubMed1997

Aging and sexuality.

Recent research suggesting that a high proportion of men and women remain sexually active well into later life refutes the prevailing myth that aging and sexual dysfunction are inexorably linked. Age-related physiological changes do not render a meaningful sexual relationship impossible or even necessarily difficult. In men, greater physical stimulation is required to attain and maintain erections, and orgasms are less intense. In women, menopause terminates fertility and produces changes stemming from estrogen deficiency. The extent to which aging affects sexual function depends largely on psychological, pharmacological, and illness-related factors. In this article I review the physiological sex-related changes that occur as part of the normal aging process in men and women. I also summarize the effects on sexual function of age-related psychological issues, illness factors, and medication use. An understanding of the sexual changes that accompany normal aging may help physicians give patients realistic and encouraging advice on sexuality. Although it is important that older men and women not fall into the psychosocial trap of expecting (or worse, trying to force) the kind and degree of sexual response characteristic of their youth, it is equally as important that they not fall prey to the negative folklore according to which decreased physical intimacy is an inevitable consequence of the passage of time.

Adaptation, Psychological↗
PubMed1997

Modelling the effects of increased physical activity on coronary heart disease in England and Wales.

OBJECTIVE: To investigate the use of computer models as tools for policy makers in evaluating physical activity interventions aimed at reducing deaths from coronary heart disease (CHD). DESIGN: The cell-based computer model Prevent, adapted to simulate risk factor interventions for an English and Welsh population, was used to simulate the effect of two strategies for increasing physical activity levels in respect of CHD mortality over 25 years. The first strategy involved a 25% increase in the proportion of 15-64 year olds who were moderately active, while the second strategy involved a similar increase in the proportion who were vigorously active. The effects of focusing on narrower age ranges and on people at different initial activity levels were also explored. MAIN RESULTS: The simulations showed a small reduction in the CHD death rates--less than 0.15% and 0.06% for men and women respectively. The strategies would postpone up to 12,100 deaths over 25 years, comparable to the effect of a 2% reduction in smoking prevalence. The strategies seemed as if they would be more effective if they concentrated on men rather than women, on those over 45 years of age as opposed to all or younger age groups, and on the least active members of the population rather than those already taking some exercise. CONCLUSION: The use of computer modelling for stimulating physical activity strategies has shown that concentrating these interventions on older sedentary men will produce the greatest health gain, but efforts to encourage smoking cessation may be more effective in terms of years of life saved.

Adolescent↗
PubMed2003

[Stress urinary incontinence: an overview on actual surgical trends].

Stress urinary female incontinence (IUS) is an unpleasant symptom describing a loss of urine during physical exertion; genuine stress incontinence (GSI) is a socially unacceptable, involuntary loss of urine in absence of detrusor activity from the urethra associated with sudden cough or strain. The incidence of IUS is less than 10% in reproductive-age women but may approach 10-20% in postmenopausal women. The IUS pathophysiology is connected with two specific mechanisms: the urethral-bladder sliding out of anatomical area involves the normal system of endobladder/intraabdominal pressures, with a loss of urine; the second mechanism involves the damaged urethral sphincteric function, with a reduction of the urethral closure pressure and a urinary loss after minimal physical stimulation. The IUS medical therapy is troublesome and often inefficient, and the only approved effective measures are the surgical procedures, actually reserved for cases of unsuccessful medical therapy; surgical treatments can be classified according to the access as: vaginal, abdominal, associated and complex. They intend to reposition the urethral-bladder sliding in its normal intra-abdominal position, to allow equal transmission of increased intraabdominal pressure to the bladder and the proximal urethra. In the scientific literature there are more than one hundred surgical procedures for IUS correction, but the IUS surgical approach is anyway the actual gold standard therapy.

Adult↗
PubMed2005

Housing-related activity in rats: effects on body weight, urinary corticosterone levels, muscle properties and performance.

The cage systems commonly used for housing laboratory rats often result in sedentary and overweight animals, as a consequence of restricted opportunities for physical activity combined with ad libitum feeding. This can have implications both for animal well-being and for the experimental outcome. Physical activity has several known positive effects on health and lifespan, and physical fitness might therefore be incorporated into the animal welfare concept. The aim of this study was to investigate if and how pen housing affects the physical activity and fitness of rats. Thirty-two juvenile male Sprague-Dawley rats were randomly assigned to two different housing systems for a 4-week period. Sixteen rats were kept individually in standard Makrolon type III cages (42x26x18 cm) furnished with black plastic tubes (singly-housed, SI). The remaining rats were kept in groups of eight, housed in large floor pens (150x210 cm), which were furnished with various objects to increase environmental complexity (pen-housed, PH). The body weight gain, and food and water intake of the rats were measured. During weeks 3 or 4, home cage behaviour, urinary cortiosterone/creatinine ratios (CO/CR), and muscle strength on an inclined plane, were measured. Enzyme activities and glycogen content were measured in tissue samples from m. triceps brachii taken after euthanization at the end of the study. There were no significant differences between groups for food and water intake, but PH rats weighed 14% less than SI rats after 4 weeks, and PH rats also had a more diverse behavioural pattern than SI rats. PH rats had significantly higher oxidative capacity (28% more citrate synthase (CS)) and greater glycogen content (28%) in their muscle samples than SI rats. The PH rats performed significantly better on the inclined plane, both in the muscle strength test (mean angle 75+/-0.5 degrees for PH rats and 69+/-0.4 degrees for SI rats) and the endurance strength test (mean time 233+/-22 s for PH rats and 73+/-14 s for SI rats). There was a negative correlation between body weight and results on the inclined plane for the PH rats. There were no significant differences between housing types with respect to CO/CR ratios. In conclusion, the large pen represents an environment that stimulates physical activity and more varied behaviour, which should be beneficial for the welfare of the animal.

3-Hydroxyacyl CoA Dehydrogenases↗
PubMed1993

The development of synaptic function and integration in the central auditory system.

The development of inhibitory synaptic transmission is difficult to assess because the afferents usually arise from intrinsic neurons that are difficult to stimulate independently. The postnatal maturation of excitatory and inhibitory synaptic function was compared in the gerbil lateral superior olive (LSO), where it is possible to stimulate physically discrete afferent projections. Intracellular recordings obtained in a brain slice preparation revealed that transmission was prominent at birth. The EPSPs and IPSPs were up to 2 orders of magnitude longer than in more mature animals. Brief trains of electrical stimulus pulses led to a temporal summation of postsynaptic potentials (PSPs) in 1-14 d animals resulting in prolonged depolarizations or hyperpolarizations. In neonates, the depolarization could exceed 1 sec following a 70 msec stimulus train. The IPSPs in neonates were often of sufficient amplitude to evoke a rebound depolarization or action potential. The number of converging afferents was estimated from the quantized increases in PSP size. There was a significant decrease with age, suggesting that both inhibitory and excitatory afferents were eliminated during the first 3 postnatal weeks. The integration of action potentials with IPSPs was examined with conjoint stimuli to the two afferent pathways, and demonstrated that the effective IPSP duration decreased approximately 20-fold during the first 3 postnatal weeks. The magnitudes and durations of electrical stimulus-evoked PSPs suggest that spontaneous discharge of afferents to the LSO could have a substantial impact on their development, even prior to the response to airborne sound at 12 d. Furthermore, the synaptic responses obtained at 12-14 d postnatal indicated that both amplitude and temporal processing remain compromised. These immature synaptic properties would be expected to compound the inadequacies present in the cochlea and cochlear nucleus.

Animals↗
PubMed2006

Meniett clinical trial: long-term follow-up.

OBJECTIVE: To delineate 2-year efficacy of Meniett device therapy in people with classic, unilateral, Ménière's disease unresponsive to traditional medical treatment. DESIGN: A 2-year long-term unblinded follow-up after a prior randomized, placebo-controlled, multicenter clinical trial of the Meniett device for Ménière's disease. SETTING: Follow-up was performed remotely by using diaries and questionnaires mailed to the data coordinating center by the participants. Those who failed to mail their diaries were interviewed by telephone. PARTICIPANTS: Sixty-one study participants agreed to use the Meniett device and report their symptoms for 2 years. All had active, unilateral cochleovestibular disease. Outcomes are available for 58 participants; 2 were unavailable for follow-up and 1 was excluded because of a concurrent condition that precluded Meniett device use. INTERVENTIONS: Participants were advised to adhere to a low-sodium diet, use the Meniett device 3 times daily, and maintain a patent tympanostomy tube in the affected ear. Diuretic and vestibular suppressant medications were used as needed. MAIN OUTCOME MEASURES: Outcomes were based on the participants' daily diary, questionnaires, and telephone interviews. Three different analyses were prepared: tracking of vertigo frequency throughout the study, comparison of vertigo frequency before and at the end of Meniett device use (American Academy of Otolaryngology-Head and Neck Surgery Foundation reporting guideline), and Kaplan-Meier estimates of vertigo remission and recurrence. RESULTS: Vertigo levels gradually improved for most but not all participants. American Academy of Otolaryngology-Head and Neck Surgery Foundation class A (remission) or class B (greatly improved) results occurred in 67% (39/58) of participants, and class F (dropped out to receive surgical therapy) results occurred in 24%. Of the 44 nondropout participants, 39 (89%) had American Academy of Otolaryngology-Head and Neck Surgery Foundation group A or B outcomes. People who went into remission were highly likely (80%) to remain in remission long term; participants who achieved remission (20/43; 47%) did so within the first year of follow-up. CONCLUSIONS: Use of the Meniett device was associated with a significant reduction in vertigo frequency in about two thirds of the participants, and this improvement was maintained long term. Therapy with the Meniett device is a safe and effective option for people with substantial vertigo uncontrolled by medical therapy.

Adult↗
PubMed1997

Organization of somatosensory cortex and distribution of corticospinal neurons in the eastern mole (Scalopus aquaticus).

The somatotopic organization of somatosensory cortex of the eastern mole (Scalopus aquaticus) was explored with multiunit microelectrode recordings from middle layers of cortex. The recordings revealed the presence of at least parts of two systematic representations of the body surface in the lateral cortex. One of the representations appears to be primary somatosensory cortex (S1), and it contained cytochrome oxidase dark regions, separated by light septa that formed isomorphs with some body parts. The rostral portion of this presumptive S1 cortex contained a face representation with a series of barrel-like cytochrome oxidase dark ovals that corresponded to the vibrissae on the snout. In caudolateral S1, light septa outline the palm and digits of the forepaw. Cortex caudal to S1, in the expected region of auditory cortex, responded to vibration, suggesting a modification of auditory cortex. Injections of wheat germ agglutinin-horseradish peroxidase into the cervical enlargement of the spinal cord revealed two dense foci of cortical cells that project to the spinal cord. The focus medial to the face region in S1 may correspond to primary motor cortex (M1). The second focus was coextensive with the somatosensory representation of the forelimb and the trunk in S1. The dense corticospinal projections from the forelimb representation of S1 and motor cortex may reflect sensorimotor specializations related to digging behaviors in moles.

Animals↗
PubMed1988

Diagnosis and treatment of typical and atypical forms of lipopigment storage disorders.

Lipopigment storage disorders are common lysosomal diseases of unknown etiology. Four classic types have been delineated on a clinical basis, focused on the age of onset, visual and retinal impairment, epilepsy and progressive loss of mental and motor abilities. Lipopigments with ultrastructural characteristics distinct from lipofuscin accumulate mostly in the nerve cells but in many other cell types as well. Excess dolichol can be demonstrated in tissues and urine, but no primary accumulating substrate has been identified. Many cases with atypical features or course cannot be currently classified. Medical treatment includes, in all types, prevention of aspiration pneumonia with fundoplication and gastrostomy and avoidance of carbamazepine. In Spielmeyer-Vogt, Vitamin E and appropriate mental and physical stimulation improve the patient's quality of life.

Diagnosis, Differential↗
PubMed1988

Preduodenal mechanisms in initiating gallbladder emptying in man.

The existence of preduodenal phases of gallbladder emptying in normal volunteers was investigated by evaluating the effect of sham feeding a sandwich (chew and spit) (n = 15), the sight and smell of food followed by sham feeding a cooked meal (n = 15), and gastric distension (intragastric balloon tube) (n = 9) on gallbladder emptying and comparing these responses with those after ingestion of a standard meal (n = 14). A control group given no intestinal stimuli were studied to determine the frequency of spontaneous emptying during fasting (n = 18). 99mTc-EHIDA (2,6 diethylphenylcarbamoylmethyliminodiacetic acid) was used as the biliary tracer. The frequency of gallbladder emptying during fasting was 0.0045/min. Thus, in any 20 min period emptying occurred spontaneously in only about 1 in 11 volunteers. Significant emptying (greater than 5 per cent over 20 min) occurred in 8 out of 15 volunteers after sham feeding a sandwich (P less than 0.001 versus control), in 8 out of 15 volunteers after sham feeding a cooked meal (P = 1.0 versus sandwich sham feed, n.s.), in 6 out of 9 volunteers after gastric distension (P less than 0.001 versus control) and in 14 out of 14 volunteers after meal ingestion. The rate of emptying was significantly greater in the gastric distension and meal ingestion groups compared with other groups (P less than 0.05). However, the emptying rate after sham feeding was not significantly different from spontaneous gallbladder emptying (P greater than 0.05, n.s.). There was no significant difference in time to onset of emptying between the four stimulus groups (P greater than 0.05, n.s.). These results suggest that pre-duodenal stimuli can evoke gallbladder emptying in man, although the precise physiological significance of this phenomenon remains to be established.

Adolescent↗
PubMed1988

Connections of the corpus cerebelli in the thornback guitarfish, Platyrhinoidis triseriata (Elasmobranchii): a study with WGA-HRP and extracellular granule cell recording.

The neuronal connections of the cerebellar corpus in the guitarfish Platyrhinoidis triseriata were investigated by WGA-HRP injections and extracellular recording of sensory evoked electrical activity. Injections of WGA-HRP into the corpus resulted in retrograde labeling of the following cell groups bilaterally: pretectal and accessory optic nuclei, interstitial nucleus of Cajal, nucleus ruber, oculomotor and possibly trochlear nucleus, central (periaqueductal) gray, nucleus H, reticular formation of the midbrain, cerebellar nucleus, caudal part of nucleus F, tentatively locus coeruleus and subcoeruleus field, octaval and trigeminal nuclei, intermediate octavolateralis nucleus, medial inferior reticular formation, lateral reticular nucleus, and spinal cord. Unilaterally labeled cells were seen in the contralateral inferior olive, which was found to project in sagittal zones onto the molecular layer of the corpus. Terminal fields of efferent Purkinje cell axons were labeled over the ipsilateral cerebellar nucleus exclusively. Purkinje cells in different parts of the corpus project topographically onto subdivisions of the nucleus. Mapping of evoked electrical multiple unit activity recorded from the granule cell layer of the corpus shows separate visual and tactile areas, mostly confined to the anterior and posterior lobes, respectively. Granule cells within the tactile area also responded to lateral line stimuli and, at two distinct medial locations in the caudal and rostral parts of the posterior lobe, to weak electric field stimulation in the bath. The body surface is somatotopically represented in the tactile area, but discontinuities in the map might indicate that the somatotopy is "fractured".

Animals↗