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Tissue inhibitor of metalloproteinases-1 (TIMP-1) modulates neuronal death, axonal plasticity, and learning and memory.

The tissue inhibitor of metalloproteinases-1 (TIMP-1) belongs to a family of multifunctional proteins that inhibit matrix metalloproteinases (MMPs), but also regulate cell growth, proliferation, migration and apoptosis in non-nervous tissues. We had previously reported that kainate (KA)-mediated excitotoxic seizures induce the expression of TIMP-1 in resistant neurons and reactive astrocytes of the rat CNS, but the functional implications of these changes had not been elucidated. In the present work we used a targeted gene null mutation in mice to investigate in vivo the involvement of TIMP-1 in neuronal death and axonal sprouting following KA. We found no differences in seizure behaviour between the wild-type (WT) and the TIMP-1 knock-out (KO) mice, without any compensation by other TIMPs, at least at the mRNA level. However, the TIMP-1 KO mice were resistant to excitotoxicity and did not undergo the typical mossy fibre sprouting observed in WT mice. The lack of TIMP-1 paradoxically hampered the increase in the activity of MMPs observed in the seizing WT mice. In addition, we demonstrate that learning and memory are impaired in untreated KO mice. In conclusion, this study provides the first in vivo evidence for the implication of TIMP-1 in neuronal death and axonal sprouting in a pathological situation, but also suggests the involvement of TIMP-1 in the synaptic mechanisms underlying learning and memory in physiological conditions. More generally, these data support the idea that the control of proteolysis is instrumental for pathological and physiological processes in the brain.

Animals↗

Central control of the cardiovascular and respiratory systems and their interactions in vertebrates.

This review explores the fundamental neuranatomical and functional bases for integration of the respiratory and cardiovascular systems in vertebrates and traces their evolution through the vertebrate groups, from primarily water-breathing fish and larval amphibians to facultative air-breathers such as lungfish and some adult amphibians and finally obligate air-breathers among the reptiles, birds, and mammals. A comparative account of respiratory rhythm generation leads to consideration of the changing roles in cardiorespiratory integration for central and peripheral chemoreceptors and mechanoreceptors and their central projections. We review evidence of a developing role in the control of cardiorespiratory interactions for the partial relocation from the dorsal motor nucleus of the vagus into the nucleus ambiguus of vagal preganglionic neurons, and in particular those innervating the heart, and for the existence of a functional topography of specific groups of sympathetic preganglionic neurons in the spinal cord. Finally, we consider the mechanisms generating temporal modulation of heart rate, vasomotor tone, and control of the airways in mammals; cardiorespiratory synchrony in fish; and integration of the cardiorespiratory system during intermittent breathing in amphibians, reptiles, and diving birds. Concluding comments suggest areas for further productive research.

Afferent Pathways↗

Antennae on transmitters on penguins: balancing energy budgets on the high wire.

The effect of externally mounted antennae on the energetics of penguins was studied by mounting various antennae on a transducer fixed to a model Magellanic penguin Spheniscus magellanicus to determine drag, run at speeds of up to 2 m s(-1) in a swim canal. For rigid antennae set perpendicular to the water flow, measured drag increased with increasing swim speed. Increasing antenna length (for lengths between 100 and 200 mm) or diameter (for diameters between 1 and 4 mm) resulted in accelerating increased drag as a function of both antenna length and diameter. Where antennae were positioned at acute angles to the water flow, drag was markedly reduced, as was drag at higher speeds in flexible antennae. These results were incorporated in a model on the foraging energetics of free-living Magellanic penguins using data (on swim speeds, intervals between prey encounters, amount ingested per patch and dive durations) derived from previously published work and from a field study conducted on birds from a colony at Punta Norte, Argentina, using data loggers. The field work indicated that free-living birds have a foraging efficiency (net energy gain/net energy loss) of about 2.5. The model predicted that birds equipped with the largest rigid external antennae tested (200 mm x 3 mm diameter), set perpendicular to water flow, increased energy expenditure at normal swim speeds of 1.77 m s(-1) by 79% and at prey capture speeds of 2.25 m s(-1) by 147%, and ultimately led to a foraging efficiency that was about 5 times less than that of unequipped birds. Highly flexible antennae were shown to reduce this effect considerably. Deleterious antenna-induced effects are predicted to be particularly critical in penguins that have to travel fast to capture prey. Possible measures taken by the birds to increase foraging efficiency could include reduced travelling speed and selection of smaller prey types. Suggestions are made as to how antenna-induced drag might be minimized for future studies on marine diving animals.

Animals↗

Injuries and considerations in masters aquatics sports.

Masters level athletes in all aquatic sports challenge healthcare professionals, providing them with many opportunities to test their sports medicine training. Along with sports-specific injuries, the medical professional must factor in physiologic differences due to aging and even the older athlete's basic motivation to pursue the sport--which differs greatly from that of younger swimmers. Organized Masters programs, complete with national and international championships, are growing in Masters Diving, Masters Synchronized Swimming, Masters Swimming, and Masters Water Polo.

Aging↗

Refractive change in response to acute hyperbaric stress in refractive surgery patients.

PURPOSE: To determine whether acute hyperbaric stress affects visual acuity or refractive power after keratorefractive surgery. SETTING: Clinical multiplace hyperbaric chamber and ophthalmology clinic, University of California, San Diego, California, USA. METHODS: This prospective convenience sample study included 3 groups: 3 patients who had had bilateral myopic radial keratotomy (RK); 2 who had had bilateral myopic laser in situ keratomileusis (LASIK); and 4 control subjects who had no previous corneal refractive surgery or ocular pathology but had a myopic refractive error (-1.25 to -8.38 diopters [D]) similar to that in the treated patients before refractive surgery. One additional patient had had unilateral LASIK only and was included in the LASIK and control groups. Best spectacle-corrected visual acuity (BSCVA), manifest spherocylindrical refractive error, and intraocular pressure were measured at baseline, at 4 atmospheres absolute (atm abs), and on return to ambient pressure. Corneal pachymetry and keratometry were measured at baseline and on return to ambient pressure. RESULTS: The mean BSCVA changed from 0.06 logMAR (20/25 Snellen equivalent) at baseline to 0.10 logMAR (20/25) at 4 atm abs in the RK group and from 0.00 logMAR (20/20) to -0.06 logMAR (20/15) in the LASIK group; it did not change in the control group. The mean refractive error changed from 0.25 D at baseline to 0.50 D at 4 atm abs in the RK group, from -0.90 to -1.02 D in the LASIK group, and from -4.58 to -4.53 D in the control group. CONCLUSIONS: Acute hyperbaric stress did not appear to alter refractive power after corneal surgery.

Adult↗

Isoproterenol accelerates decompression sickness and death after saturation dives in swine.

BACKGROUND: Disabled submarine (DISSUB) survivors are expected to achieve inert gas tissue saturation that would likely cause severe decompression sickness (DCS). Rescue procedures in a DISSUB scenario cannot accommodate a staged decompression and the availability of recompression treatment chambers is limited. Alternatives to the standard recompression procedures for treating DCS are needed. Experimentally, isoproterenol has successfully addressed many underlying physiological concerns expected to result in cardiopulmonary DCS in this group. HYPOTHESIS: We hypothesized that isoproterenol would reduce the incidence of cardiopulmonary DCS in a saturation dropout model. METHODS: Yorkshire swine (21.8 +/- 1.68 kg) were fitted with an external jugular catheter and compressed to 4.33 ATA in a dry chamber for 22 h. They were infused with isoproterenol (0.002 mg x kg(-1)) while still at depth and returned to the surface without decompression stops. They received additional infusions every 10 min throughout a 2-h observation period. Signs of DCS were recorded to the nearest minute. RESULTS: Isoproterenol administration resulted in a significant increase in the incidence of severe cardiopulmonary DCS (13/34 control vs. 12/18 isoproterenol) and death from DCS (10/34 control vs. 11/18 isoproterenol). There was no difference in the incidence of severe neurological DCS. CONCLUSIONS: Administering isoproterenol as an intervention/treatment for DCS significantly increases the risk of cardiopulmonary DCS and death following saturation dropout in 20-kg swine. As an adjunctive therapy or alternative to staged decompression, isoproterenol in the dose regimen delivered here is not expected to improve outcome in a DISSUB mass casualty scenario.

Adrenergic beta-Agonists↗

Topographic electroencephalographic studies in a hyperbaric environment--specific reference to high pressure nervous syndrome.

Hyperbaric chamber dives at various equivalent depths below sea level, i.e. 7, 14, 19 and 31 atmosphere absolute (ATA) with helium-oxygen or helium-nitrogen-oxygen have been performed at the Japan Marine Science and Technology Center. A two-dimensional (topographic) display of the scalp EEG was used during simulated underwater experiments to determine; 1) Whether there are any characteristic EEG patterns in high pressure nervous syndrome (HPNS), 2) the relationship between the EEG changes and the compression rate, and 3) the relationship between the EEG changes and the characteristic signs and symptoms of HPNS. A two-way analysis of variance and a distribution analysis technique revealed that the topographic brain patterns depended on the diving depth and indicated the most affected brain areas during compression and decompression. Significant correlations between the diving depth and the EEG potentials were observed at different brain locations. Alpha waves showed a diffuse cortical distribution. Theta wave activity was more localized in the frontal midline region. These waves developed paroxysmally in relatively brief bursts supplanting or intermixing with normal background EEG rhythms. In our subjects, frontal midline theta activity was associated mostly with some of the characteristic features of HPNS, such as a transient episode of laughter or euphoria at depths greater than 21 ATA. An intimate correlation between frontal midline theta wave and laughter was observed. Frontal midline theta waves may be related to emotional activities induced by helium under high pressure. There were significant individual variations in susceptibility and subjective signs and symptoms. The EEG is of great value in studying man's physiological reactions in an undersea environment and also very important in selecting divers who are relatively more tolerant of a severe hyperbaric environment.

Adult↗

Cornea-contact lens interaction in the aquatic environment.

PURPOSE: A large population of ametropic scuba divers wear contact lenses. We discuss optics and corneal physiology, as well as the types of contact lenses that are appropriate for underwater activities. METHODS: We reviewed an extensive body of literature to formulate guidelines to aid the contact lens fitter in satisfying individual sport diver's needs. RESULTS: Optical factors such as image displacement and light wave-length shifts require that contact lenses for underwater use be suitably modified. Underwater images appear nearer and larger (requiring greater accommodation) and are made up almost exclusively of the short wavelength end of the spectrum. Correction of presbyopia, in particular, is influenced by these factors. For example, presbyopic contact lens-corrected myopes require greater near adds underwater than when viewing the same objects in air. In general, presbyopes should consider monovision correction to facilitate underwater visual tasks. Although divers wearing rigid gas permeable contact lenses run the risk of more corneal problems than soft lens wearers if conservative ascents are not adhered to, there are no compelling reasons to change lens types in patients who are already fully adapted. Soft contacts, while very stable on the eye during diving, present a greater risk of lens contamination by sea or fresh water exposure. However, the latter problems are easily overcome by using disposable soft lenses. CONCLUSION: In this paper, we present several suggestions for lens material, modifications required for underwater ametropia correction, and wearing modalities for the sport divers. An understanding of the dramatic changes that impact the properties of light, corneal physiology, and visual perception which accompany the diver below the surface will enable the contact lens fitter to design a lens appropriate to the needs of the individual patient.

Contact Lenses, Hydrophilic↗

Onboard acoustic recording from diving northern elephant seals.

This study was the first phase in a long-term investigation of the importance of low-frequency sound in the aquatic life of northern elephant seals, Mirounga angustirostris. By attaching acoustic recording packages to the backs of six translocated juveniles, the aim was to determine the predominant frequencies and sound levels impinging on them, and whether they actively vocalize underwater on their return to their rookery at Ano Nuevo, California, from deep water in Monterey Bay. All packages contained a Sony digital audio tape recorder encased in an aluminum housing with an external hydrophone. Flow noise was minimized by potting the hydrophone in resin to the housing and orienting it posteriorly. The diving pattern of four seals was recorded with a separate time-depth recorder or a time-depth-velocity recorder. Good acoustic records were obtained from three seals. Flow noise was positively correlated with swim speed, but not so high as to mask most low-frequency sounds in the environment. Dominant frequencies of noise impinging on the seals were in the range 20-200 Hz. Transient signals recorded from the seals included snapping shrimp, cetacean vocalizations. boat noise, small explosive charges, and seal swim strokes, but no seal vocalizations were detected. During quiet intervals at the surface between dives, the acoustic record was dominated by respiration and signals that appeared to be heartbeats. This study demonstrates the feasibility of recording sounds from instruments attached to free-ranging seals, and in doing so, studying their behavioral and physiological response to fluctuations in ambient sounds.

Acoustics↗

Intravascular bubble composition in guinea pigs: a possible explanation for differences in decompression risk among different gases.

Differences in risk of decompression sickness (DCS) that have been observed among inert gases may reflect differences in gas solubility or diffusivity or both. A higher risk gas might generate a larger volume of evolved gas during decompression, thereby increasing the probability of DCS. If this hypothesis is correct, the composition of bubbles that develop during decompression should reflect such gas differences. Unanesthetized guinea pigs were compressed to depths ranging from 250 to 350 fsw with air, He-O2 (21% O2) or one of a number of N2-He-O2 or N2-Ar-O2 mixtures (21% O2). Animals were held at depth from 15 to 60 min, then decompressed slowly (60 fsw/min) or rapidly (less than 15 s) to 5 fsw. If severe DCS developed, as judged by changes in physiologic variables, death usually occurred quickly. Gas/blood samples were then immediately withdrawn from the right atrium or the inferior vena cava, and the gas phase analyzed for He, N2, Ar, O2, and CO2 via gas chromatography. Bubbles from all dives contained 5-9% CO2, 1-4% O2, with the balance inert gas. Bubbles after N2-He-O2 dives contained substantially more N2 than He (up to 1.9 times more) compared to the dive mixture; bubbles after N2-Ar-O2 dives contained more Ar than N2 (up to 1.8 times more). For N2-He-O2 dives, the actual inert gas makeup of bubbles was dependent on the time-at-depth and the decompression profile. Results may reflect differences among He, N2, and Ar in tissue solubility/diffusivity and gas exchange rates, and support the rank order of increasing DCS risk (He less than N2 less than Ar) and rate of gas exchange (N2 less than He) observed previously during rat dives.

Animals↗

Stress inoculation training for smoke divers and free fall lifeboat passengers.

The effects of 1 h stress inoculation training on subjective experience, performance, and physiological activation were studied in two fear-provoking situations. In the free fall lifeboat situation, the experimental group reported higher acceptance of the free fall lifeboat concept after the training course than the control group. In the smoke diving situation, the experimental group reported less need of success and reported learning self confidence instead of skills more often than the control group and received less help from the instructor during diving. However, the experimental group reported higher anxiety than the control group during training. There were no differences between groups in saliva cortisol values in either of the two experiments. Effects of stress inoculation training are explained in terms of expectancy theory.

Adaptation, Psychological↗

Human erythrocyte superoxide dismutase activity during deep diving.

As the practical use of high pressure oxygen (HPO) in clinical medicine and the offshore industries accelerates, knowledge of its toxic nature becomes essential. In this study, divers' erythrocyte superoxide dismutase (SOD) activity was monitored during high pressure exposure and shown to decrease on average by 20% at depths greater than 150 m. Assay of total red cell SOD protein and activity established that the recorded SOD activity decrement was by loss of immuno-measurable enzyme. No evidence of intra-cellular Heinz bodies was observed. An increase of intra-membrane lipid peroxidation products, within physiological limits, was found, particularly in the denser cell fractions. Using previously in vivo pressure stressed cells, experiments at increasing O2 pressures educed that human red blood cells were oxygen "resistant" up to ten times the normal atmospheric pressure, 0.021 MPa (0.21 bar). Thereafter, a loss in SOD enzyme activity occurred with hemolysis during the in vitro decompression procedure.

Diving↗

Seadragon VI: a 7-day dry saturation dive at 31 ATA. I. Objectives, design, and scope.

Seadragon VI dive was designed to determine the effects on humans of a prolonged exposure to a 31 ATA, dry helium-oxygen environment. The specific objectives were to study a) circadian changes in renal-endocrine function, including a comprehensive characterization of nocturia; b) cardiovascular-endocrine responses to a 90 degree tilt; c) erythrocyte functions, including intracellular organic phosphates and the Donnan ratio for chloride; and d) blood enzyme profiles. The experiment was conducted over a period of 30 d in September and October 1984 at the Japan Marine Science and Technology Center, Yokosuka. Following a 5-d predive control period at 1 ATA in air, 4 male divers spent 7 d at 31 ATA in a helium-oxygen environment, and then returned to 1 ATA air after 12 d of decompression. They stayed an additional 3 d inside the chamber for postdive control measurements. The chamber temperature was maintained at 27-28 degrees C during pre- and postdive periods, 31-32 degrees C at 31 ATA, and 28-31 degrees C during decompression. At 31 ATA, PO2 and PCO2 of the chamber gas were maintained at approximately 225 and 2 mmHg, respectively. In this introductory paper, physical and physiologic characteristics of individual subjects, the major daily activity schedule, daily caloric intake, and the scope of investigation are presented.

Adult↗

The Irving-Scholander legacy in polar physiology.

The pioneer arctic and cold environment studies of Laurence Irving and Per Scholander, undertaken during the middle decades of the 20th century, have had a wide ranging and major influence on the direction and character of experimental research on polar species. Their investigations included comparative studies of metabolism, insulation, and acclimatization of mammals and birds in arctic Alaska and the tropics. Freezing, supercooling, and antifreeze research included fishes, insects, and plants. They examined the special problems of cooling in appendages of mammals and birds and the potential for acclimatization of these structures by repeated cold exposure. Studies of cold exposure in human populations considered possible adaptive reactions. Their research on diving mammals opened a vast new area for studies with attention to asphyxial tolerance and temperature regulation. A lesser-known accomplishment was an innovative approach to recovery of ancient atmospheric gases from polar ice fields, an approach that was stimulated by original investigations of frozen insect larvae and gas permeability through ice.

Adaptation, Physiological↗