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Clinical advantages of dual activity in urticaria.

Urticaria is a common disorder that adversely affects quality of life; work-related and recreational activities are restricted, while rest, sleep, and emotions are seriously disturbed in a significant proportion of patients. The pathogenic mechanisms vary, but cutaneous mast-cell activation with release of histamine and other vasoactive or proinflammatory mediators is thought to be the final common pathway for lesion induction in most cases. A subsequent, but incompletely understood, late-phase allergic reaction seems to prolong the inflammatory process, particularly in certain chronic forms of the disorder. Although histamine is considered an important mediator of urticaria, additional substances, including the cysteinyl leukotrienes (LTs), are putative mediators of the immediate urticarial responses and the inflammatory events that follow in some types of urticaria. A second-generation antihistamine, mizolastine, which exhibits dual activity with selective H1-receptor antagonism and, as shown in animal studies, anti-5-lipoxygenase activity, represents an advance in the treatment of urticaria. It has rapid, potent and sustained action. At the recommended 10-mg dose, mizolastine suppresses the histamine-induced wheal reaction as early as 1 h after oral administration. Compared to placebo, mizolastine significantly reduces overall patient discomfort and pruritus in patients with chronic idiopathic urticaria. Double-blind, placebo-controlled studies have also shown mizolastine to be at least as effective as other second-generation antihistamines. Furthermore, with long-term use of mizolastine over 1 year, a reduction in pruritus and the number of urticarial episodes was maintained with no evidence of tachyphylaxis or tolerance. Mizolastine has also been shown to be an effective treatment for cold-induced urticaria, causing significant delay in the whealing response to the ice-cube test and also reducing the wheal diameter.

Acute Disease↗

In situ cardiac performance of Pacific bluefin tuna hearts in response to acute temperature change.

This study reports the cardiovascular physiology of the Pacific bluefin tuna (Thunnus orientalis) in an in situ heart preparation. The performance of the Pacific bluefin tuna heart was examined at temperatures from 30 degrees C down to 2 degrees C. Heart rates ranged from 156 beats min(-1) at 30 degrees C to 13 beats min(-1) at 2 degrees C. Maximal stroke volumes were 1.1 ml x kg(-1) at 25 degrees C and 1.3 ml x kg(-1) at 2 degrees C. Maximal cardiac outputs were 18.1 ml x kg(-1) min(-1) at 2 degrees C and 106 ml x kg(-1) min(-1) at 25 degrees C. These data indicate that cardiovascular function in the Pacific bluefin tuna exhibits a strong temperature dependence, but cardiac function is retained at temperatures colder than those tolerated by tropical tunas. The Pacific bluefin tuna's cardiac performance in the cold may be a key adaptation supporting the broad thermal niche of the bluefin tuna group in the wild. In situ data from Pacific bluefin are compared to in situ measurements of cardiac performance in yellowfin tuna and preliminary results from albacore tuna.

Adaptation, Physiological↗

Free plasma catecholamine levels in healthy subjects: a basal and dynamic study. The influence of age.

We studied the levels of free plasma noradrenaline (norepinephrine, NE), adrenaline (epinephrine, E), and dopamine (DA) in 143 normal subjects, either basally or, in a part of them, in response to four tests stimulating the sympathoadrenomedullary activity: the tilt-table test (TTT), the cold-pressor test (CPT), the mental-arithmetic test (MAT), and the insulin tolerance test (ITT). In both cases we evaluated the influence of age, which is considered the main physiological variable affecting the peripheral sympathetic activity. A normal distribution of values was observed, in the basal study, only for NE, while E and particularly, DA levels were distributed in an non-homogeneous fashion; a direct correlation was observed between age of subjects and NE levels, while neither E, nor DA levels showed any correlation with the aging process; sex did not influence any of the catecholamines. In the dynamic study, CPT, ITT and, above all, TTT elicited a significant rise in NE levels, while the E release was greatly stimulated by the insulin-induced hypoglycaemia. Neither NE, nor E levels rose after the MAT stimulation. Also in this case, the elderly showed an increased noradrenergic responsiveness when compared with the young subjects, confirming the existence of an 'up-regulation' of the peripheral sympathetic tone in old people.

Adolescent↗

[The role of cortical microtubules in moss protonemal cells during dehydration/rehydration cycle].

Plant cells response to water deficit through a variety of physiological processes. In this work, we studied the function of microtubule cytoskeleton during dehydration/rehydration cycle in moss (Atrichum undulatum) protonemal cells as a model system. The morphological and cytological change of protonemal cells during dehydration and rehydration cycle were first investigated. Under normal conditions, protonemal cells showed bright green colour and appeared wet and fresh. Numerous chloroplasts distributed regularly throughout the cytoplasm in each cell. After dehydration treatment, protonemal cells lost most of their chlorophylls and turned to look yellow and dry. In addition, dehydration caused plasmolysis in these cells. Upon rehydration, the cells could recover completely from the dehydrated state. These results indicated that moss had a remarkable intrinsic ability to survive from the extreme drought stress. Microtubule, an important component of cytoskeleton, is considered to play crucial roles in the responses to some environmental stresses such as cold and light. To see if it is also involved in the drought tolerance, dynamic organization of microtubules in protonemal cells of Atrichum undulatum subjected to drought and rehydration were examined by indirect immunofluorescence combined with confocal lasersharp scanning microscopy. The cortical microtubules were arranged into a fine structure with a predominant orientation parallel to the long axis of the cells in the control cells. After dehydration, the microtubule organization was remarkablly altered and the fine microtubule structure disappeared whereas some thicker cables formed. When the cells were grown under rehydration conditions, the fine microtubule arrays reappeared. These results provided a piece of evidence that microtubules play a role in the cellular responses to drought stress in moss. Furthermore, we analyzed the effects of the microtubule-disrupting agent colchicine on the morphology recovery of the protonemal cells during rehydration process. The cells were incubated with colchicine, followed by drought stress treatment and rehydration in the presence of colchicine to prevent recovery of microtubule organization. Results from immunofluorescence showed that microtubule arrays were broken down into smaller fragments. Compared to the cells treated with drought stress alone, the cells treated with drought stress in the presence of colchicine could not recover after rehydration treatment. The morphology resembled those of the drought treated cells, with obvious plasmolysis phenomena and loss of chlorophyll content. These results support the notion that microtubules were involved in the deccication tolerance mechanism in Atrichum undulatum.

Bryophyta↗

[Physical, chemical and microbiological quality of concentrated orange juices made in Venezuela].

Concentrated fruit juices are a very attractive type of product because of the many advantages they offer for reductions in packing, transportation and storage costs, and in addition, they offer the possibility of consumption outside harvesting time. Due to their potential in the international market, it is necessary to evaluate if they are accomplishing the quality requirements, and to know the different factors that can affect their stability. For this purpose, samples of national products were analyzed for physical, chemical and microbiological characteristics; the diacetyl test was performed as a measure of the sanitary conditions under processing. The samples analyzed comply with the national standards established by the Comision Venezolana de Normas Industriales (COVENIN N(o) 2395-86 Concentrados de frutas para consumo directo). It is advisable to determine the zero tolerant yeasts population because this type of microorganisms are responsible for spoilage whenever cold storage is interrupted, and because they can not be detected by the official procedures used to detect yeasts.

Beverages↗

Safety, tolerability and humoral immune responses after intramuscular administration of a malaria DNA vaccine to healthy adult volunteers.

DNA-based vaccines are considered to be potentially revolutionary due to their ease of production, low cost, long shelf life, lack of requirement for a cold chain and ability to induce good T-cell responses. Twenty healthy adult volunteers were enrolled in a Phase I safety and tolerability clinical study of a DNA vaccine encoding a malaria antigen. Volunteers received 3 intramuscular injections of one of four different dosages (20, 100, 500 and 2500 microg) of the Plasmodium falciparum circumsporozoite protein (PfCSP) plasmid DNA at monthly intervals and were followed for up to twelve months. Local reactogenicity and systemic symptoms were few and mild. There were no severe or serious adverse events, clinically significant biochemical or hematologic changes, or detectable anti-dsDNA antibodies. Despite induction of excellent CTL responses, intramuscular DNA vaccination via needle injection failed to induce detectable antigen-specific antibodies in any of the volunteers.

Adult↗

Radiofrequency capacitive heating of deep-seated tumours using pre-cooling of the subcutaneous tissues: results on thermometry in Dutch patients.

The capacity of a radiofrequency, 13.56 MHz, capacitive hyperthermia system using extensive pre-cooling of the subcutaneous tissue to induce locoregional deep heating has been investigated in 11 patients. Tumour location was presacral in nine--and eccentric towards the lateral side of the pelvis in two patients. For thermometry multiple catheters (mean 2.7) were inserted into the treatment volume. The mean numbers of temperature measuring points per treatment were 9.4 in tumour, 5.5 in muscle and 7.2 in subcutaneous fat. RF energy was applied after 30 min of cooling through two flexible boli perfused with saline water at 5-10 degrees C. Patient tolerance to pre-cooling was very good and after some initial discomfort the patient became rapidly accustomed to the cold water boli. For some patients better temperatures were achieved when the conventional anterior-posterior applicator set-up was replaced by a set-up with an applicator on each lateral side of the patient. As patients can tolerate temperatures within the fat tissue as high as 45.5 degrees C without complaining it appears important to monitor the temperature at the transition of fat to muscle tissue to prevent subcutaneous burns. The study shows that pre-cooling cannot avoid preferential heating at the interface from fat to muscle tissue. In this patient group the quality of the hyperthermia treatment appeared to be rather poor: 60% of the measured tumour temperatures were below 40 degrees D.

Adipose Tissue↗

Hand replantation after 54 hours of cold ischemia: a case report.

A number of case reports and series have reported successful replantation after prolonged periods of ischemia. However, the acceptable range of normothermic and hypothermic ischemic storage remains controversial. There is little question that the tolerance of composite tissue for ischemia is dependent on the quantity of contained skeletal muscle. We report a successful hand replantation after 54 hours of cold ischemia. We believe that this case documents the longest anoxic period yet reported for successful hand replantation. We further believe that the functional results obtained confirm the value of hand replantation even after such a prolonged ischemic interval.

Adolescent↗

Enrichment in Specific Soluble Sugars of Two Eucalyptus Cell-Suspension Cultures by Various Treatments Enhances Their Frost Tolerance via a Noncolligative Mechanism.

A cell-suspension culture obtained from the hybrid Eucalyptus gunnii/Eucalyptus globulus was hardened by exposure to lower temperatures, whereas in the same conditions cells from a hybrid with a more frost-sensitive genotype, Eucalyptus cypellocarpa/Eucalyptus globulus, were not able to acclimate. During the cold exposure the resistant cells accumulated soluble sugars, in particular fructose and sucrose, with a limited increase in cell osmolality. In contrast, the cell suspension that was unable to acclimate did not accumulate soluble sugars in response to the same cold treatment. To an extent similar to that induced after a cold acclimation, frost-hardiness of the cells increased after a 14-h incubation with specific soluble sugars such as sucrose, raffinose, fructose, and mannitol. Such hardening was also observed for long-term cultures in mannitol-enriched medium. This cryoprotective effect of sugars without exposure to lower temperatures was observed in both the resistant and the sensitive genotypes. Mannitol was one of the most efficient carbohydrates for the cryoprotection of eucalyptus. The best hardiness (a 2.7-fold increase in relative freezing tolerance) was obtained for the resistant cells by the cumulative effect of cold-induced acclimation and mannitol treatment. This positive effect of certain sugars on eucalyptus freezing tolerance was not colligative, since it was independent of osmolality and total sugar content.

Journal Article↗

Efficacy of air and liquid cooling during light and heavy exercise while wearing NBC clothing.

BACKGROUND: Studies, to date, have not revealed the extent to which the heat strain of continuous heavy exercise while wearing NBC protective clothing can be reduced by providing liquid- or air-cooling and whether one system is more effective than the other in aiding heat transfer from the body and the clothing. It was of interest to know to what extent present-day cooling technologies can reduce the heat strain of light and heavy exercise in NBC clothing and to compare these reductions to other strategies that have employed changes in clothing design. HYPOTHESIS: It was hypothesized that there would be no difference between the liquid and air cooling systems and that sufficient cooling power would be delivered to the body to reduce the heat strain of heavy exercise to a level similar to that experienced with light exercise when no cooling was provided. METHODS: Eight males performed 6 randomized exposures for a maximum of 3 h at 40 degrees C and 30% relative humidity that involved either light (L) (walking at 3.5 km x h(-1) or heavy (H) (walking at 4.8 km x h(-1) and a 5% grade) exercise while wearing the NBC protective clothing ensemble with no cooling (N), liquid (L) or air (A) cooling. RESULTS: For L exercise, tolerance time was significantly increased from 100 min with N to the maximum of 3 h with either cooling system. There was no difference between L and A cooling in the extent of the changes in rectal temperature, heart rate and heat flow. For H exercise, tolerance time was significantly increased 150% from 57 min with N to 149 min with L and 140 min with A. These latter values for HL and HA were not different from each other but both were significantly greater than L exercise with N. Rectal temperature increased more quickly during HL compared with HA during the first 60 min of exposure but there were no differences between cooling trials for the remainder of the heat exposure. CONCLUSIONS: It was concluded that sufficient cooling power could be delivered to the body to effectively reduce the heat strain of wearing NBC protective clothing during heavy exercise in a hot environment to a level comparable to or slightly lower than that experienced with light exercise and no cooling.

Air↗

Assessment of cold stress.

Cold stress may be present in terms of a risk for skin surface cooling (wind chill), extremity cooling and whole body cooling. Measures of cold stress differ for the various situations. The most common approach, however, has been to apply more or less complex formulas for heat balance calculations. The combined effect of several climatic factors (air temperature, mean radiant temperature, humidity and air velocity) and the activity level determines the cooling power of the environment. The cooling power can be easily converted into a required insulation value, that applies both to parts of the body and to the body as a whole. The value provides information about cold stress in two ways; (a) by specifying necessary behavioural adjustments in terms of required activity level and clothing insulation level, and (b) by quantifying the thermal imbalance and tolerance time, when protection worn does not provide sufficient insulation.

Body Temperature Regulation↗

Accumulation of type I fish antifreeze protein in transgenic tobacco is cold-specific.

Expression of fish antifreeze protein (AFP) genes in plants is a possible means of increasing their frost resistance and freeze tolerance. Initial work involved transfer into tobacco of an AFP gene from winter flounder which codes for the alanine-rich, alpha-helical Type I AFP. Plants were transformed with a gene construct in which the preproAFP cDNA was inserted between the cauliflower mosaic virus 19S RNA promoter and the nopaline synthetase polyadenylation site. Although transgenic plants produced AFP mRNA, no AFP was detected on western blots. Re-evaluation of AFP expression in these transgenic plants showed that AFP accumulated to detectable levels only after exposure of the plant to cold. Extracts of plants incubated at 4 degrees C for 24 h contained a protein which co-migrated with winter flounder proAFP and was cross-reactive to Type I AFP antisera. Two other minor protein bands of slightly higher apparent M(r) also cross-reacted with the antisera and are thought to represent processing intermediates. The proAFP was unique to the transgenic plants and was absent in extracts taken prior to cold exposure. AFP levels increased over the first 48 h of cold incubation then remained stable. Since the alpha-helix content of Type I AFP has been shown to decrease markedly at warmer temperatures, we postulate that Type I AFP stability in transgenic plants is dependent on its secondary structure.

Antifreeze Proteins↗

Use of SAGE technology to reveal changes in gene expression in Arabidopsis leaves undergoing cold stress.

The genes expressed within an organism determine its biological characteristics. Various internal or external factors can modulate these gene expression patterns, which then elicit physiological or pathological changes. We have characterized the global gene expression patterns of Arabidopsis leaves by serial analysis of gene expression (SAGE). A total of 21,280 SAGE tags were sequenced and 12,049 unique tags were identified. Among these, only 3367 tags (27.9%) were matched to the Arabidopsis cDNA or EST database. Functional analysis of annotated tags indicated that a significant proportion of the genes expressed in normal leaves were involved in energy and metabolism, especially in photosynthesis. To systematically analyze differential gene expression profiles under cold stress, a similar SAGE tag library from cold-treated leaves was constructed and analyzed. A comparison of the tags derived from the cold-treated leaves with those identified in the normal leaves revealed 272 differentially expressed genes (P<0.01): 82 genes were highly expressed in the normal leaves and 190 genes were highly expressed in the cold-treated leaves. After cold stress, in general, many of the genes involved in cell rescue/defense/cell death/aging, protein synthesis, metabolism, transport facilitation, and protein destination were induced. They included various COR genes, lipid transfer protein genes, alcohol dehydrogenase, beta-amylase and many novel genes. By comparison, down-regulated genes were mostly photosynthesis related genes involved in energy metabolism. The expression patterns of several cold responsive transcripts identified by SAGE were confirmed by northern analysis. The results presented here will provide valuable information for understanding the mechanisms of the freezing tolerance of plants.

Arabidopsis↗

The effect of epidural anaesthesia with 1% lidocaine on the pressor response to dynamic exercise in man.

1. In order to examine the sensitivity to local anaesthetics of afferent neural feedback from working muscle during dynamic exercise, sixteen subjects cycled for 12 min before and after epidural anaesthesia using 1% lidocaine. The presence of afferent neural blockade was verified by elimination of the blood pressure response to a cold pressor test, laser-induced evoked potentials and increases in pain detection and tolerance thresholds of the foot. Conversely, epidural anaesthesia had no effect on these variables in the unblocked skin areas or on electrically evoked potentials in blocked or unblocked skin. 2. During dynamic exercise, heart rate increased as did mean arterial pressure and cardiac output. Mean arterial pressure remained at the exercise level during post-exercise ischaemia, but heart rate and cardiac output decreased while total peripheral resistance increased. Epidural anaesthesia did not significantly affect these variables during rest, dynamic exercise, post-exercise ischaemia or recovery. 3. The results of this study show that, in order to affect blood pressure during dynamic exercise, epidural anaesthesia must block the pressor response to post-exercise ischaemia. The implication of these data is that complete or almost complete block of group III and/or group IV muscle afferents is necessary to inhibit the pressor response to dynamic exercise in man.

Adult↗

Effects of abscisic acid, low temperature, and plant age on cytoskeleton and phosphorylated proteins.

The effects of exogenous abscisic acid (ABA), low temperature, and seedling age on the content of tubulin, actin, and phosphorylated proteins and the structural organization of microtubules (MTs) in cells of different tissues and organs of winter wheat cultivars contrasting in cold hardiness were studied by immunocytochemical methods using monoclonal (against alpha- and beta-tubulin and actin) and polyclonal (phosphothreonine) antibodies. The leaves and roots of five- and nine-day-old seedlings of three cultivars were characterized by unequal proportion of actin/tubulin proteins. ABA decreased the content of the cytoskeleton and the 60-kD phosphorylated proteins, thus promoting a decrease in the number of MTs and occurrence of a less branched network of weakly fluorescent tubulin components in the cells of the root differentiating zone (which is most responsible for the development of cold hardiness in wheat). Although the cold acclimation of plants (3 degrees C, 7 days) did not change the level of tubulin and actin proteins, it evoked the spatial aggregation of MT, leading to formation of a dense network of tubulin cytoskeleton comprised of thick bundles of intensively fluorescent MTs. In the case of a combined action of the studied factors, low temperatures abolished the hormone effect described above, evoking an increase in the content of the cytoskeletal and 60-kD phosphorylated proteins and MT structures. We suggest that the ABA-induced decrease in the levels of proteins and MTs occurs at the initial stages of plant cold acclimation (3 degrees C, 2-3 days). It may be the signal that triggers the processes of low-temperature adaptation. As the duration of cold acclimation increased (3 degrees C, 7 days), the role of ABA in the formation of plant tolerance decreased. Apparently, in this case other hormone-independent mechanisms of frost hardiness development are triggered, in which the role of the cytoskeleton components and cytoskeleton-associated proteins increases.

Abscisic Acid↗

Water Content during Abscisic Acid Induced Freezing Tolerance in Bromegrass Cells.

Changes in water content and dry weight were determined in control cells and those induced to cold harden in response to abscisic acid (ABA) treatment (7.5 x 10(-5) molar). Bromegrass (Bromus inermis Leyss cv Manchar) cells grown in suspension culture at room temperature (23 degrees C) for 7 days acclimated to -28 degrees C (LT(50)) when treated with ABA, or to -5 degrees C when untreated. ABA significantly reduced cell growth rates at 5 and 7 days after treatment. Growth reduction was due to a decrease in cell number rather than cell size. When the cell water content was expressed as percent water (percent H(2)O) or as grams water per gram dry weight (gram H(2)O/gram dry weight [g DW]), the water content of hardy, ABA-treated cells decreased from 85% to 77% or from 6.4 to 3.3 g H(2)O/g DW in 7 days. Control cell water content remained static at approximately 87% and 7.5 g H(2)O/g DW. However, cell water content, expressed as milligrams water per million cells (milligram H(2)O/10(6) cells), did not differ in ABA-treated or control cells. The dry matter content of ABA-treated cells, expressed as milligram DW/10(6) cells increased to 3.3 milligram/10(6) cells in 7 days, whereas the dry weight of the control cells remained between 1.4 to 2.1 milligrams/10(6) cells. The osmotic potential of ABA-treated cells decreased by the fifth day while that of control cells increased significantly and then decreased by day 7. Elevated osmotic potentials were not associated with increased ion uptake. In contrast to much published literature, these results suggest that cell water content does not decrease in ABA-treated cells during the induction of freezing tolerance, rather the dry matter mass per cell increased. Cell water content may be more accurately expressed as a function of cell number when accompanying changes to dry cell matter occur.

Journal Article↗

Body build and temperature tolerance: an experimental analysis of ecological 'rules'.

According to current anthropological theory, the two factors that primarily determine thermoregulation in human populations are body size and body proportions, and they have found their formulation in the ecological 'rules' of Bergmann and Allen. In order to test the validity of these idea, Buffalo and Fisher rats were submitted to various levels of heat and cold. The two strains were chosen because they demonstrate maximum differences in body size and body proportions in domesticated rats. The experiments lead to the conclusion that Allen's rule has only a limited applicability under conditions of heat and none in cold. However, Bergmann's rule is well substantiated by experimental data in heat and in cold. Nutrition is one of the most important factors influencing thermoregulation, but an extremely high degree of individual variation in temperature tolerance is found even under conditions of maximum homozygosity. The basic physiological processes of thermoregulation are sufficiently similar in human and nonhuman homeotherms to justify the extrapolation from one to the other.

Animals↗