Distribution of intranasal instillations in mice: effects of volume, time, body position, and anesthesia

Intranasal instillation techniques are used to deliver various substances to the upper and lower respiratory tract (URT and LRT) in mice. Here, we quantify the relative distribution achieved with intranasal delivery of a nonabsorbable tracer, (99m)Tc-labeled sulfide-colloid. Relative distribution was determined by killing mice after instillation and quantifying the radioactivity in dissected tissues using gamma scintigraphy. A significant effect of delivery volume on relative distribution was observed when animals were killed 5 min after instillation delivered under gas anesthesia. With a delivery volume of 5 microl, no radiation was detected in the LRT; this increased to a maximum of 55.7 +/- 2.5% distribution to the LRT when 50 microl were delivered. The majority of radiation not detected in the LRT was found in the URT. Over the course of the following 1 h, radiation in the LRT remained constant, while that in the URT decreased and appeared in the gastrointestinal tract. Instillation of 25 microl into anesthetized mice resulted in 30.1 +/- 6.9% distribution to the LRT, while only 5.3 +/- 1.5% (P < 0.05) of the same volume was detected in the LRT of awake mice. Varying the body position of mice did not affect relative distribution. When using intranasal instillation, the relative distribution between the URT and LRT and the gastrointestinal tract is heavily influenced by delivery volume and level of anesthesia.     

Brain stimulation: feeling the buzz

A recent study demonstrates that artificially generated patterns of brain activity are surprisingly easy to sense. Brain areas that differ substantially in their functional specialization are remarkably similar in their ability to support this awareness.     

More than a feeling: discovering, understanding, and influencing mechanosensing pathways

The ability of cells to extract biophysical information from their extracellular environment and convert it to biochemical signals is known as mechanotransduction. Here we detail three passive, 'inside-out' mechanotransduction mechanisms with an emphasis on the mechanosensing pathways involved in creating these signal: Rho/ROCK, stretch-activated channels, and 'Molecular Strain Gauges.' We also examine how molecular tools have been used to perturb these pathways to better understand their interconnectivity. However, perturbing pathways may have unintended confounding effects, which must also be addressed. By discovering and understanding mechanosensitive pathways, the ability to influence them for clinical applications increases.     

Armor morphology and reproductive output in threespine stickleback,Gasterosteus aculeatus

Synopsis The threespine stickleback, Gasterosteus aculeatus, is an extensively armored fish inhabiting both marine and fresh waters across its holarctic distribution. Marine fish nearly always possess a full complement of bony lateral plates running from just behind the head to the tail, and a robust pelvic girdle complex. These armor features appear to constrain lateral and ventral abdominal distention, and therefore clutch volume. Freshwater populations in many areas exhibit variable reduction in lateral plate number, and in some regions the pelvic girdle is also reduced or lost. Freshwater populations also vary in the degree of abdominal distention exhibited by gravid females. We tested whether reduction in armoring might be correlated with increased clutch volume using five populations from the Cook Inlet area of Alaska. The hypothesis that populations having reduced pelvic girdle complexes would have greater size-adjusted clutch volumes was not supported. In fact, our two full-pelvic populations as a group had larger volumes. Similarly, size-adjusted clutch volumes were not related to pelvic phenotype within either of our two pelvic-reduced populations, nor to lateral plate morph within a fifth population. Other factors that may explain the interpopulation differences in clutch volume in threespine stickleback include body shape, food quantity and quality, intensity of predation, and even behavior. Except for a preliminary analysis of body shape, these possibilities remain unexplored. The concept of phenotypic integration suggests that these factors should be analyzed as a suite rather than individually.     

Breathing and feeling: Capnography and the individually meaningful psychological stressor

This article briefly discusses capnography and the use of individually meaningful psychological stressors (IMPS) to provoke episodes of acute hyperventilation. Guidelines are provided on history taking, and a strategy for using IMPS with ongoing capnographic monitoring is described, together with a proposal for diagnostic criteria. Diagnosis of hyperventilation using IMPS and capnography can help to demonstrate that feelings, breathing, and symptoms are all interlinked, and may help to suggest appropriate targets for therapy.     

Face to face: meaning, feeling and perception in Amazonian welcoming ceremonies

Some welcoming ceremonies practised by indigenous peoples of the Amazon have been considered events that enable the establishment of a social link between potential enemies. The studies do not, however, indicate how the shift from latent hostility to a social relationship occurs. They only refer to the 'magical act' produced through the significant exchange during the dialogues that take place at the key moment of the ceremony. Examining the perceptual interaction of the Candoshi welcoming ceremony and not merely the text of the dialogue, this article attempts to incorporate into the analysis the intensity of the affective dimension which governs these rituals, which can help to explain how such rituals provide the participants with the confidence to initiate a social relationship.     

DNA topology: feeling the pulse of a topoisomerase

The action of individual type II DNA topoisomerases has been followed in real time by observing the elastic response of single DNA molecules to sequential strand passage events. Micromanipulation methods provide a complementary approach to biochemical studies for investigating the mechanism of DNA topoisomerases.     

Peptidergic innervation in the rat carotid body after 2, 4, and 8 weeks of hypocapnic hypoxic exposure

The distribution and abundance of neuropeptide-containing nerve fibers were examined in the carotid bodies of rats exposed to hypocapnic hypoxia (10% O2 in N2) for 2, 4, and 8 weeks. The carotid bodies after 2, 4, and 8 weeks of hypoxic exposure were enlarged by 1.2-1.5 times in the short axis, and 1.3-1.7 times in the long axis in comparison with the normoxic control ones. The enlarged carotid bodies contained a number of expanded blood vessels. Mean density per unit area (10(4) microm2) of substance P (SP) and calcitonin gene-related peptide (CGRP) immunoreactive fibers was transiently high in the carotid bodies after 4 weeks of hypoxic exposure, and decreased significantly to nearly or under 50% after 8 weeks of hypoxic exposure. Density of vasoactive intestinal polypeptide (VIP) immunoreactive fibers increased significantly in all periods of hypoxic exposure observed, and was especially high in the carotid bodies after 4 weeks of hypoxic exposure. Density of neuropeptide Y immunoreactive fibers was unchanged in the carotid bodies during hypoxic exposure. These characteristic changes in the density of SP, CGRP, and VIP fibers in the carotid bodies after 4 weeks of hypoxic exposure suggest that the role of these neuropeptide-containing fibers may be different in the carotid bodies after each of three periods of hypoxic exposure, and that the peptidergic innervation after 8 weeks of hypoxic exposure may show an acclimatizing state.     

Effect of training on treadmill performance,aerobic capacity,and body responses to acute cold exposure

An attempt was made to test the hypothesis that regular physical activity at the anaerobic threshold can stimulate an increase in the amount of brown or beige body fat, which can manifest itself in increased lactate utilization during exercise and increased reactivity in response to acute regional cooling. The methods used in the study included the ramp test; regional acute cold exposure; measurement of gas exchange; lactate and glucose in the blood; heart rate; heart rate, blood pressure, and respiration variability at rest and during standard functional tests; infrared thermal imaging; and statistical methods of analysis of results. Training of ten physically active volunteers (7 males and 3 females) on a treadmill at a speed corresponding to 75–80% of personal maximum oxygen consumption \(\left( {V_{O_{2\max } } } \right)\) for 30 min 3 times per week at a fixed ambient temperature of 21–22°C for 6 weeks resulted in a significant (from 19 to 39%) increase in exercise duration in the ramp test, whereas \(V_{O_{2\max } }\) changed, on average, only slightly. The increase in the anaerobic threshold power was associated with a sharp slowdown in the accumulation of lactate during the ramp test. The lactate utilization rate during the recovery period, on the contrary, increased. In general, work efficiency during test load significantly increased. Noticeable changes in the condition and responses to the standard functional tests of the autonomic system were not found, as judged by the heart rate variability, blood pressure, and respiration variability at rest and during orthostatic tests and imposed breathing rhythm. The functional response of the body to acute cold exposure (1-min cooling of the feet in ice water) did not change after a cycle of training, both in terms of metabolism (oxygen consumption, etc.) and the skin temperature dynamics in the areas of most probable location of brown adipose tissue (BAT). These data do not confirm our previous hypothesis (2010) about the function of BAT as a universal homeostatic instrument in the body. Probably, if the formation of the beige adipose tissue is stimulated by physical activity and hormone irisin, produced by muscles, this tissue is involved in lactate utilization but is not involved in the thermoregulatory responses.     

Scaling the physiological effects of exposure to radiofrequency electromagnetic radiation: consequences of body size

We have demonstrated that a comparative analysis of the physiological effects of exposure of laboratory mammals to radiofrequency electromagnetic radiation (RFR) may be useful in predicting exposure thresholds for humans if the effect is assumed to be due only to heating of tissue. The threshold specific absorption rate (SAR) necessary to affect a thermoregulatory parameter shows an inverse and linear relationship to body mass. The inverse relationship between threshold SAR and body mass is attributed to a surface area: body mass relationship. In comparison to small mammals, relatively large mammals have a reduced capacity to dissipate an internal heat load passively, and are therefore physiologically more sensitive to RFR exposure. The threshold for a thermoregulatory response depends on the type of response measured, species, ambient temperature, etc. By extrapolation, it can be shown that a SAR of only 0.2-0.4 W/kg is required to promote a thermoregulatory response in a mammal with a body mass of 70 kg (e.g. weight of adult human). The specific absorption rate bioeffects data collected from laboratory mammals can be related by means of a simple power formula: threshold SAR (W/kg) = aMb, where M is body mass in kg, a is a constant and b is equal to approximately -0.5. Through this equation we have illustrated that a threshold SAR measured in a species weighing 100 g would be 10 times greater than that of a species weighing 10 000 g. Accordingly, a relatively low SAR that is physiologically ineffective in small mammals may be stressful to larger species.     

Effects of cold exposure on gaseous metabolism and body composition in the rat

1. Exposure of rats to a temperature of 1 degree C resulted in a temporary decline in respiratory quotient to a minimum on the 4th day of exposure, with subsequent recovery. 2. Metabolism stabilized after 4-6 days of cold exposure. 3. Body composition was determined for control rats and rats exposed to 2 or 23 degrees C for 2 weeks. 4. Animals kept at 2 degrees C had a lower fat content than other groups, with a higher iodine value. 5. Mineral content indicated that bone growth continued during cold exposure.     

Effect of exposure to physical loading, hypoxia and hyperthermia on factors of the cellular anti-infection protection of the body

Examinations of 146 healthy males aged 20-25 years have shown that moderate exercise stimulates the function of peripheral macrophages. The same effect is produced by exercise in combination with a single exposure to hypoxia. On the contrary, combined exposure to exercise, hypoxia and hyperthermia leads to the development of a tendency towards the suppression of macrophagal phagocytosis. The functional loading of the body induces deep transformation of the structure of the correlative characteristics of phagocytosis and hemogram.     

On the role of anesthesia on the body/brain temperature differential in rats

Different anesthetics often produce distinctly different effects on blood flow, oxygen consumption and other physiological parameters in animal studies. We investigated the influence of two common anesthetics—alpha-chloralose and chloral hydrate—on the body-core/brain temperature differential in rats. The results indicate a remarkable difference of 4.34±0.64 °C (mean±SD) in the body-core/brain-cortical temperature differential observed under alpha-chloralose anesthesia compared to a relatively smaller differential of 2.73±0.40 °C under chloral hydrate anesthesia in rats. Temperature gradients within the brain are around 0.3 °C/mm in both cases. Thus, the anesthetic utilized has the potential to markedly influence brain temperature and therefore other important physiological parameters in the brain.     

The structure, growth and formation of bones in toxic exposure of the body to pesticides and antioxidant therapy]

In the experiment performed on 175 white male rats by means of a complex of morphological, biochemical and biomechanical methods peculiarities of structure, growth, outline formation and mineralization of the skeletal bones have been investigated under a toxic lesion of the organism with pesticides (chlorophose and keltan) and at a simultaneous administration of antioxidants of various groups (tocopherol, ionol, sodium selenit). Osteotoxic effect of the pesticides, manifested as an inhibition of bone growth, as a disbalance of mineral saturation and their composition, as a decrease in indices of firmness is leveled by means of therapeutic doses of the antioxidants. The stabilizing effect of the antioxidant applied correlates to the manifestation of the pesticides osteotoxic effect, to the ability of their cumulation in the organism and is directly connected with the supposed mechanism of damaging effect to the organism and/or cell. The expressiveness of the toxic effect of the chemical poison, in its turn, is defined not only by the dose, mechanism and duration of the effect, but by age peculiarities of the organism and by functional state of its reactivity. When the poisons are applied for a long time, in order to level their osteotoxic effect, a multiple increase of therapeutic doses of the antioxidants and a combined potentiation of their effect are necessary.