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Cardiovascular reactivity to psychological stress may enhance subsequent pain sensitivity.

Stress-induced physiological reactivity has been shown to correlate with indexes of pain sensitivity, but it has not been demonstrated whether such reactivity can affect subsequent levels of pain threshold, tolerance and self-reported severity. The present study examined whether the degree of physiological reactivity (i.e., blood pressure and heart rate) elicited during an initial psychological stressor could be shown to influence indexes of pain sensitivity during subsequent pain induction. Fifty-two undergraduate men and women were assigned randomly to one of two conditions: perform mental arithmetic (MA) and then undergo a cold pressor task (CP; MA/CP) or vice versa (CP/MA). Subjects were divided into low/high mean arterial pressure (MAP) and low/high heart rate (HR) groups based on reactivity to MA. Principal analyses showed 'condition x MAP reactor group' interactions for pain threshold (F(1,48) = 7.38; P < 0.009) and tolerance (F(1,48) = 9.63; P < 0.003). Post hoc tests revealed that high MAP reactors in the MA/CP condition showed lower pain threshold and tolerance during CP than low MAP reactors in the same condition, while high and low MAP reactors in the CP/ MA condition did not differ. Thus, cardiovascular reactivity during psychological stress may contribute to increased sensitivity to subsequent painful stimulation.

Adolescent↗

Plasma exchange for cold agglutinin hemolytic anemia.

Two patients with advanced lymphoma, chronic cold agglutinin disease refractory to conventional therapy and severe, progressive anemia were treated with exchange plasma transfusion. Both experienced significant reduction in titers. The first patient, in whom the procedure was done manually, died with widespread lymphoma without achieving apparent clinical benefit. The second patient was exchanged using the Aminco Celltrifuge, with improvement in in vitro compatibility tests and transfusion tolerance. The technical details of continuous-flow centrifugation exchange plasma transfusion are described.

Aged↗

Low temperature responses of Nothofagus dombeyi and Nothofagus nitida, two evergreen species from south central Chile.

Nothofagus dombeyi (Mirb.) Blume and Nothofagus nitida (Phil.) Krasser are closely related evergreen trees native to south central Chile. Nothofagus dombeyi is a pioneer in habitats subject to high daytime irradiances and nighttime freezing temperatures and has a wider altitudinal and latitudinal distribution than N. nitida, which is restricted to more oceanic climates. We postulated that N. dombeyi has a greater cold-acclimation capacity, expressed as a greater capacity to maintain a functional photosynthetic apparatus at low temperatures, than N. nitida. Because cold-acclimation may be related to the accumulation of cryoprotective substances, we investigated relationships between ice nucleation temperature (IN), freezing temperature (FT), and the temperature causing injury to 50% of the leaf tissues (LT(50)) on the one hand, and concentrations of total soluble carbohydrates (TSC), starch and proline on the other hand. Observations were made throughout a seasonal cycle in adults and seedlings in the field and in seedlings in the laboratory under cold-acclimation inductive and non-inductive conditions. In adults, LT(50) values were lower in N. dombeyi than in N. nitida, suggesting that N. dombeyi is the more frost tolerant species. Adults of both species tolerated freezing in autumn and winter but not in spring and summer. In the fall and winter, seedlings of N. dombeyi had a much lower LT(50) than those of N. nitida. Nothofagus nitida seedlings, in autumn and winter, exhibited freezing avoidance mechanisms. Although elevated TSC and proline concentrations may contribute to freezing tolerance in adults of both species, an increase in proline concentration is unlikely to be the dominant frost tolerance response in adults because proline concentrations were higher in N. nitida than in N. dombeyi. In seedlings, however, there were large differences in proline accumulation between species that may account for the difference between them in freezing tolerance. Starch concentration in both species decreased during winter. Chlorophyll fluorescence indicated that maximal photochemical efficiency (F(v)/F(m)) remained at optimal values (~0.8) throughout the year. The effective photochemical efficiency of PSII (PhiPSII) and relative electron transport rates (ETR(r)) decreased in winter in both species. In seedlings, fluorescence parameters were more affected in winter in N. nitida than in N. dombeyi. We concluded that adults and seedlings of N. dombeyi are hardier than adults and seedlings of N. nitida, which is consistent with its wider latitudinal and altitudinal distribution.

Chile↗

Kappa antinociceptive activity of spiradoline in the cold-water tail-flick assay in rats.

Spiradoline (U62066E) a racemic mixture of the two enantiomers U63639(+) and U63640(-), appears to have kappa opioid receptor activity, but the contribution of each enantiomer toward this activity is still in question. To determine the activity of each enantiomer in comparison to the racemic mixture, the three forms were tested in the cold-water tail-flick (CWTF) assay in male Sprague-Dawley rats. Antinociception by spiradoline was completely antagonized by naloxone 0.50 mg/kg, a dose five times that required to antagonize antinociception by fentanyl in this same assay. In a second series of tests, fentanyl-induced antinociception was markedly reduced, while spiradoline-induced antinociception was essentially unchanged. in methadone-tolerant animals. Of the enantiomers, only U63640 produced antinociception, whereas U63639 failed to affect the nociceptive response. Additionally, spiradoline failed to produce antinociception in animals pretreated with norbinaltorphimine (kappa receptor specific), but antinociception was not affected in animals pretreated with beta-funaltrexamine (mu receptor specific). These results show that spiradoline is a full antinociceptive agonist in the CWTF assay and that the effects of the drug are mediated through kappa opioid receptors.

Analgesics↗

Common cold and influenza symptom management: the use of pharmacokinetic considerations to predict the efficacy of a twice-daily treatment for colds and flu.

OBJECTIVE: The objective of the two pharmacokinetic studies reported here was to compare the relative bioavailability of an ibuprofen/pseudoephedrine modified-release capsule with each of the active ingredients given alone as standard formulations. STUDY DESIGN: Evaluation of two open, randomised, cross-over studies, one single dose and one multiple dose, in healthy male volunteers. METHODS: Healthy volunteers were randomised in a cross-over design to single or multiple doses of a combination of ibuprofen (600 mg) plus pseudoephedrine (90 mg) in a slow-release formulation and the individual active products alone as standard formulations; ibuprofen 400 mg, pseudoephedrine 60 mg. RESULTS: The single-dose study demonstrated that the bioavailabilities of ibuprofen and pseudoephedrine achieved with the slow-release formulation were not significantly different from those with standard tablets of each ingredient alone. In addition, mean plasma levels of ibuprofen predictive of clinical efficacy were achieved within 0.5-1 h and lasted for 10-12 h thereafter. The time required to reach clinically effective blood levels of pseudoephedrine was longer, starting at approximately 2 h. However, the plasma levels predicted that the clinical effect would then last for at least a further 12 h. Trough levels from the multiple-dose study showed that clinically relevant analgesic and decongestant plasma levels were maintained for 24 h during twice-daily dosing. The slow-release formulation was well tolerated with only mild adverse events. CONCLUSIONS: Blood levels would predict that the present slow-release formulation of ibuprofen plus pseudoephedrine should offer reliable day and night control of cold and flu and sinus symptoms and be associated with a favourable safety profile.

Adolescent↗

Changes in membrane lipid and free fatty acid composition during low temperature preconditioning against SO2 injury in coleus.

The effects of a low temperature (13 degrees C) treatment known to provide protection against sulphur dioxide (SO2) injury were assessed on leaf lipid composition in two cultivars of Coleus blumei Benth, found previously to differ in sensitivity to SO2 and other environmental stresses. After 5 days growth at 13 degrees C, there were significant differences in membrane lipid fatty acid composition as well as in free fatty acid (FFA) levels between SO2-sensitive 'Buckley Supreme' ('BS') and SO2-insensitive 'Marty' ('M'). Molecular species of chloroplast galactolipids in 'M' contained increased levels of linolenic acid (18:3). In the leaf FFA pools, the saturated components, palmitic (16:0) and stearic (18:0) acids, were predominant at 20 degrees C. After temperature hardening at 13 degrees C, the total amount of FFAs decreased in 'M' but increased in 'BS.' These modifications in lipid composition suggest an additional mechanism for cultivar differences in tolerance to SO2 and other stressors in coleus.

Cold Temperature↗

Chilling invokes different morphologies in two Salmonella enteritidis PT4 strains.

The reduction in chemical preservatives in food processing has resulted in more refrigerated (chilled) products. However, the effect of chilling on Salmonella enteritidis PT4 isolates has received relatively little attention. This study investigates the effect of chilling on two Salm. enteritidis PT4 isolates, denoted E and I. These isolates differ in their tolerance to heat, acidification, survival on surfaces, and behaviour in animal models. E routinely shows greater tolerance and pathogenicity than I. Chilling invokes profound cell elongation and heterogeneity in E which corresponded to a 90% sublethal injury; neither such substantial cell elongation nor significant injury was seen in I. The ability to recover resistance to desoxycholate coincided with a reduction to normal cell size. Incomplete cell division and failure of the septum to form is a likely hypothesis for cell elongation although outer membrane changes could be responsible. Possible links are suggested between cell elongation of the hat- and acid-tolerant strain and pathogenicity.

Acridine Orange↗

Dark chilling inhibition of photosynthesis and symbiotic nitrogen fixation in soybean during pod filling.

The growth stage of a soybean [Glycine max (L.) Merrill] plant may influence its physiological response to dark chilling. Opposed to vegetative development, the intense nutrient and energy requirements of the developing seeds during pod filling could cause additional chilling damage and decreased recovery capacity. Previously, we investigated dark chilling tolerance during vegetative development in two soybean genotypes, 'Maple Arrow' and 'Fiskeby V' and consistently found that photosynthesis and symbiotic nitrogen fixation (SNF) was less affected by dark chilling in 'Maple Arrow'. In this study we describe the dark chilling response of the same genotypes during pod filling. Our aim was to establish whether the potential selection criteria for dark chilling tolerance, identified during vegetative development, was equally sensitive during pod filling. The results indicate that photosynthesis is less affected by dark chilling in 'Maple Arrow' than in 'Fiskeby V', not only during vegetative development, but also during the critical reproductive stage of pod filling. 'Fiskeby V' also lacks the ability to restore normal photosynthetic capacity during an extended recovery treatment. The decrease of nodule ureide content indicates that SNF was inhibited to a similar extent in both genotypes. Nodule ureide content was reduced more than stem ureide content, suggesting that the former is a more sensitive indicator of chilling stress effects on SNF. The results indicate that certain photosynthetic and fluorescence parameters are sensitive indicators of dark chilling tolerance throughout plant development and should prove valuable in future breeding programmes aimed at increasing the chilling tolerance of soybean.

Carbon Dioxide↗

A combination of the Arabidopsis DREB1A gene and stress-inducible rd29A promoter improved drought- and low-temperature stress tolerance in tobacco by gene transfer.

The transcription factor DREB1A/CBF3 specifically interacts with the dehydration responsive element (DRE/CRT) and induces expression of genes involved in environmental stress tolerance in Arabidopsis: Overexpression of DREB1A improved drought- and low-temperature stress tolerance in tobacco. The stress-inducible rd29A promoter minimized the negative effects on the plant growth in tobacco. Furthermore, we detected overexpression of stress-inducible target genes of DREB1A in tobacco. These results indicate that a combination of the rd29A promoter and DREB1A is useful for improvement of various kinds of transgenic plants that are tolerant to environmental stress.

Acclimatization↗

Metabolism and temperature regulation in young harbor seals Phoca vitulina richardi.

Metabolism and the ability to regulate core and peripheral temperatures under a variety of ambient conditions were studied in five unrestrained pups (less than 5 wk old) and four 3- to 5-mo-old harbor seals. Pups born with nonlanugo (adultlike) hair and little fat were able to swim in 5 degrees C water for several hours without becoming hypothermic. They were also found to tolerate 5 degrees C air temperature with the fur wet and exposed to a 35-knot wind. Basal metabolism in pups averaged 0.8 ml O2 g-1 h-1, which is 2.6 times the predicted value for an adult mammal of the same weight. Lower critical temperature in air was about 3 degrees C. Oxygen uptake in 3- to 5-mo-old seals under basal conditions was 0.5 ml g-1 h-1. Minimal thermal conductance values were .02 and .015 ml O2 g-1 h-1 degrees C-1 in pumps and 3- to 5-month-old seals, respectively. Appendages, and to a lesser extent the skin on the torso, cooled appreciably at lower air temperatures, and the flippers were kept just above freezing in subzero air. Tissue insulation provided by low peripheral temperatures and a high resting metabolic rate enable newborn and developing harbor seals to tolerate the low temperatures encountered in their natural environment.

Animals↗

[Method of forecasting maximal bearable time at low temperature for humans].

Theoretical and experimental studies helped to elaborate a method defining maximal time for humans to tolerate low ambient temperatures with consideration of the physical activity and clothing, wind speed. Methodic approaches suggested enable various services to forecast the maximal time for humans to tolerate low temperatures during the work in critical conditions.

Adult↗

Abscisic acid-induced heat tolerance in Bromus inermis Leyss cell-suspension cultures. Heat-stable, abscisic acid-responsive polypeptides in combination with sucrose confer enhanced thermostability.

Increased heat tolerance is most often associated with the synthesis of heat-shock proteins following pre-exposure to a nonlethal heat treatment. In this study, a bromegrass (Bromus inermis Leyss cv Manchar) cell suspension cultured in a medium containing 75 microM abscisic acid (ABA) without prior heat treatment had a 87% survival rate, as determined by regrowth analysis, following exposure to 42.5 degrees C for 120 min. In contrast, less than 1% of the control cells survived this heat treatment. The heat tolerance provided by treatment with 75 microM ABA was first evidenced after 4 d of culture and reached a maximum tolerance after 11 d of culture. Preincubation with sucrose partially increased the heat tolerance of control cells and rendered ABA-treated cells tolerant to 45 degrees C for 120 min (a completely lethal heat treatment for control cells). Comparative two-dimensional polyacrylamide gel electrophoresis of cellular protein isolated from heat-tolerant cells identified 43 ABA-responsive proteins of which 26 were heat stable (did not coagulate and remained soluble after 30 min at 90 degrees C). Eight heat-stable, ABA-responsive proteins ranging from 23 to 45 kD had similar N-terminal sequences. The ABA-responsive (43-20 kD), but none of the control heat-stable, proteins cross-reacted to varying degrees with a polyclonal antibody directed against a conserved, lysine-rich dehydrin sequence. A group of 20- to 30-kD heat-stable, ABA-responsive proteins cross-reacted with both the anti-dehydrin antibody and an antibody directed against a cold-responsive winter wheat protein (Wcs 120). In ABA-treated cells, there was a positive correlation between heat- and pH-induced coagulation of a cell-free homogenate and the heat tolerance of these cells. At 50 degrees C, control homogenates coagulated after 8 min, whereas cellular fractions from ABA-treated cells showed only marginal coagulation after 15 min. In protection assays, addition of heat-stable, ABA-responsive polypeptides to control fractions reduced the heat-induced coagulation of cell-free homogenates. Sucrose (8%) alone and control, heat-stable fractions enhanced the thermostability of control fractions, but the most protection was conferred by ABA-responsive, heat-stable proteins in combination with sucrose. These data suggest that stress-tolerance mechanisms may develop as a result of cooperative interactions between stress proteins and cell osmolytes, e.g. sucrose. Hypotheses are discussed implicating the role of these proteins and osmolytes in preventing coagulation and denaturation of cellular proteins and membranes.

Abscisic Acid↗

Evidence of correlations between mast-cell histamine and beta-endorphin (ir) from NIL-pituitary in the homeostasis.

This study was designed to characterize physiological events related to a single or repeated experimental anaphylactoid reactions (by Compound 48/80) in non-stressed or cold-restrained rats. Acute treatment with Compound 48/80 (1 mg/kg, i.p.) increases Beta-endorphin(ir) content in the neurointermediate lobe (NIL) of rat pituitary. Moreover, repeated treatment with Compound 48/80 showed tolerance effects. These animals, exposed to stressful conditions, exhibited a fully evident paw oedema following carrageenin oedema-test, whereas saline-pretreated rats, under the same experimental conditions, showed reduced local inflammation. Since Compound 48/80 produces characteristic, systemic, anaphylactoid reaction in the rat, with a very high degree of selectivity in its action, our results suggest that mast-cell histamine and Beta-endorphin from NIL pituitary are involved in the body's reactivity to stressful stimuli.

Animals↗

Effectiveness of tizanidine in neuropathic pain: an open-label study.

The purpose of this research trial is to assess the effectiveness and tolerability of tizanidine in neuropathic pain. In an open-label study, patients with neuropathic pain received 1 to 4 mg of tizanidine once daily for 7 days, followed by weekly dose escalation of 2 to 8 mg to his/her effective or maximum tolerated dose or a maximum of 36 mg over an 8-week period. Treatment effects were assessed, using average weekly pain scores as well as biweekly scores for patient global assessment of pain relief, the neuropathic pain scale, and wisconsin brief pain inventory. Frequency and severity of adverse events were examined also. Twenty-three patients were enrolled. The mean average weekly pain score at baseline was 6.9, which decreased by 1.7 points at the end of week 8 to 5.2 (p < or =.01). A total of 15 patients (68%) reported that their pain relief was improved or much improved with tizanidine therapy, and 2 of these patients became completely pain-free. The following neuropathic pain qualities were significantly lower at week 8 compared with baseline: intense, sharp, hot, dull, cold, sensitive, unpleasant, and deep pain. There was a significant decline in pain quantity and interference of pain on quality of life from baseline to week 8. The mean effective or maximum tolerated dose was 23 mg/day (range 6 to 36 mg/day). Side effects consisted primarily of dizziness/lightheadedness (52%), drowsiness (48%), fatigue/weakness (43%), dry mouth (39%), gastrointestinal upset (30%), and sleep difficulty (22%). One patient developed significant elevation in liver function tests (LFTS) With symptoms at week 4. Tizanidine therapy was discontinued. LFTS returned to normal in 3 weeks. Tizanidine might be an effective treatment for neuropathic pain, offering an alternative for patients poorly responsive to other medications. A larger, randomized placebo-controlled trial is recommended. In addition, comparative studies with alternative agents should be sought.

Journal Article↗

Selective brain cooling in desert animals: the camel (Camelus dromedarius).

1. Animals living in the Arabian desert are subjected to extremely high temperatures during the day in summer and very cold nights in winter. They have developed various adaptive mechanisms in order to cope with these severe heat conditions. 2. The camel (Camelus dromedarius), like many other land animals, resorts to selective brain cooling when it is subjected to heat stress. 3. This mechanism protects the heat-sensitive brain tissue from heat stress and at the same time increases the animals' tolerance to high temperatures. 4. The blood cooled in the nasal cavity by evaporative heat loss is diverted to the brain sinuses via the nasal and angular veins. 5. In the cavernous sinus, the arterial blood in the carotid rete is cooled by the cold venous blood before entering the brain. This will lead to significant cooling of the brain tissue. 6. Active myogenic tone was mainly observed in the facial, nasal and angular oculi veins of the camels head. This tone was found to be sensitive to small changes in temperature in the range 33-45 degrees C. 7. The facial veins constricted, while the nasal and angular oculi veins relaxed to increasing temperatures. This leads to a coursing of cold venous return to the brain's sinuses for selective brain cooling. 8. It is concluded that this myogenic vasoactive mechanism is a major factor in the control of blood flow in the facial area of the camel during heat stress.

Animals↗

Pangenome-wide identification and expression analysis of the chalcone synthase (CHS) gene family in five yellowhorn spp.

Chalcone synthase (CHS) is a pivotal enzyme in flavonoid biosynthesis involved in plant development, defense, and secondary metabolism. Xanthoceras sorbifolium (yellowhorn) is a medicinal and ornamental species with high resistance to environmental stresses, but its CHS gene family remains uncharacterized. We performed a pangenome-wide identification of CHS genes across five yellowhorn genomes (Xzs4, Xwf8, Xjg, Xg11, and Xzg2). Across the five yellowhorn genomes, 27 CHS genes were identified and classified into four core pangenes, present in all five genomes, and two dispensable genes, present only in a subset of genomes. Phylogenetic analysis grouped these genes into three major clades, and chromosomal mapping and duplication analyses identified four tandemly duplicated gene pairs under purifying selection. The analyses of conserved structural features, including protein motifs and exon-intron organization, together with promoter cis-regulatory elements and gene ontology annotation, further indicated the potential involvement of CHS genes in flavonoid biosynthesis and stress-responsive mechanisms. Gene expression profiling identified significant upregulation of Xg11_CHS1 and Xg11_CHS3 under cold and drought stress, with tissue-specific expression patterns. These findings provide valuable insights into the evolution, functional diversification, and stress-responsive roles of the CHS gene family, identifying candidate genes for future studies targeting stress tolerance and flavonoid biosynthesis in yellowhorn.

Acyltransferases↗

Methodology and safety considerations in the production of an intravenous immunoglobulin preparation.

Intravenous immunoglobulins are biologic substances and differ in many respects from chemical pharmaceuticals. To produce a safe and efficacious preparation, special points must be considered. Careful screening procedures and excluding high-risk donor populations reduce the risk of transmitting viral disease from the starting material. With plasma fractionation the immunoglobulins are purified, and safety is further improved by eliminating potentially remaining viruses. Cold ethanol-fractionation methods have proved to be safe and economical. Anticomplementary aggregates, responsible for anaphylactoid reactions in agammaglobulinemic patients, are removed to achieve intravenous tolerance. Enzymatic digestion or chemical modifications impair the efficacy of the preparation. Ion-exchange adsorption removes immunoglobulin subpopulations. Mild acid treatment at pH 4 yields a safe product with intact potency. Optimal stability is ensured by freeze-drying. A fine net of quality controls virtually guarantees a safe preparation.

Humans↗

Reduced peripheral vascular symptoms in elderly patients treated with alpha-methyldopa--a comparison with propranolol.

A multicentre study of 6-10 weeks duration was performed in 60 ambulant hypertensive patients aged over 60 years to compare the efficacy of methyldopa and propranolol with particular reference to the occurrence of cold extremities and sleep disturbances. Blood pressure was effectively controlled by both drugs being reduced from a mean of 180/108 mmHg to 161/93 with methyldopa and 180/108 to 162/94 with propranolol. More patients treated with methyldopa (74%) achieved the target diastolic blood pressure of 95 mmHg or below compared with those treated with propranolol (58%). Side effects were more frequent in the propranolol group necessitating the withdrawal of four patients from the study. Only one patient on methyldopa was withdrawn. The incidence of cold extremities was significantly greater with propranolol. The occurrence of sleep disturbances was similar in both groups. In this group of elderly patients methyldopa was better tolerated than propranolol.

Aged↗