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Great adaptability of brown adipose tissue mitochondria to extreme ambient temperatures in control and cold-acclimated gerbils as compared with mice.

1. The gerbil (Gerbillus campestris) is a desert rodent able to tolerate high (38 degrees C) and low (-20 degrees C) ambient temperatures, probably due to both its low resting metabolic rate in hot environment and its high peak metabolic rate in cold. 2. Measurement of mitochondrial state IV respiration and cytochrome-oxidase activity (COX) were made in interscapular brown adipose tissue (IBAT), liver and hind limb muscles of gerbils and mice of nearly equal body mass, acclimated for 4 weeks at cold ambient temperature (CA) or reared at thermoneutrality (TN). 3. The most striking difference between these two animal species appears to be in IBAT mitochondria: in TN animals, the level of state IV respiration and COX activity was lower in gerbils than in mice, but the cold acclimation-induced increase in these parameters was greater in gerbils than in mice. 4. Alternatively, in gerbils as in mice, cold acclimation induced a reduction in muscle mitochondrial COX activity. No important change due to cold acclimation was observed in liver mitochondria, either in gerbils or in mice. 5. As compared with mice, the lower state IV respiration in IBAT mitochondria from TN gerbils may explain their low RMR, whereas the higher COX activity of IBAT mitochondria from CA gerbils may explain their higher PMR. 6. As a result of this great adaptability of BAT mitochondria, the gerbil seemed to be able to live in a wide range of ambient temperatures in its natural habitat.

Acclimatization↗

[Aortic aneurysm in horseshoe kidney--special diagnosis and therapy].

The co-existence of horseshoe kidney (HSK) and abdominal aortic aneurysm (AAA) is rare and demands a special diagnostic workup and a meticulous surgical procedure. Ten patients with HSK associated with AAA are reported. All underwent aortic replacement with successful preservation of multiple renal arteries. One patient died at the 7th postoperative day from myocardial infarction. HSK does not represent a contraindication for aortic repair. Angiography for identification of aberrant renal arteries and classification into three types for surgical management is mandatory. In type I and II we recommend a standard midline transperitoneal approach. Only in type III does a thoraco-abdominal approach seem favourable. The aortic reconstruction should be performed with tube grafts, if possible. Aberrant renal arteries are reattached directly to the prosthesis. Dissection of renal isthmus should be avoided. Temporary cold renal perfusion is indicated to extend the ischemic tolerance time. As repair of a ruptured AAA in patients with HSK may be quite difficult and time consuming, we recommend more liberal indications for aneurysm surgery in patients with HSK.

Adult↗

Stress-induced accumulation of glycerol in the flesh fly, Sarcophaga bullata: evidence indicating anti-desiccant and cryoprotectant functions of this polyol and a role for the brain in coordinating the response.

Nondiapausing larvae of the flesh fly, Sarcophaga bullata, responded to several forms of short-term environmental stress (low temperature, anoxia and desiccation) by accumulating glycerol. Elevation of this polyol, regardless of the type of stress that induced accumulation, conferred cold resistance: larvae with high glycerol levels were 3-4 times more tolerant of a 2h exposure to -10 degrees C than unstressed larvae. Protection against low temperature injury, as well as dehydration, was also attained by injection of exogenous glycerol into third instar larvae. This artificially induced cold hardiness was only temporary: when glycerol-injected larvae were exposed to -10 degrees C immediately after injection, survival was high, but none survived if they were injected and then held at 25 degrees C for 2 days before the -10 degrees C exposure. Larvae ligated behind the brain immediately after low temperature exposure failed to accumulate glycerol, but glycerol did accumulate in larvae ligated 6-24h after cold treatment, thus implying a critical role for the brain in initiating glycerol production. Interestingly, a much shorter exposure (2h) to low temperature was sufficient to reduce the maximum rate of water loss. Collectively, these observations suggest that multiple pathways may be exploited in response to stress: one pathway is most likely associated with rapid cold hardening (RCH) which generates immediate protection, and a second pathway remains activated for a longer period to enhance the initial protection afforded by glycerol.

Animals↗

The consequences of experimentally induced and chronic unilateral pain: reflections of hemispheric lateralization of emotion.

In a series of three studies with right handed subjects, left side pain is tolerated less well than right side pain with a cold pressor, and results in greater emotional disturbance, both with a cold pressor and in chronic pain patients. In the second study where comparisons are made with non-stimulated controls, acute left side pain results in higher state anxiety scores than controls; right side pain and control groups are comparable. The differences between the reactions to left and right side pain are consistent with activation of the emotional properties of the hemisphere contralateral to the painful stimulation.

Adult↗

Induction of synthesis of an antimicrobial peptide in the skin of the freeze-tolerant frog, Rana sylvatica, in response to environmental stimuli.

An extract of skin taken from specimens of the freeze-tolerant wood frog, Rana sylvatica, that were collected from cold (<7 degrees C) ponds and maintained at 5 degrees C lacked detectable antimicrobial activity. In contrast, an extract of skin taken from specimens maintained at 30 degrees C for 3 weeks under laboratory conditions contained a high concentration (approximately 4 nmol/g) of a single antimicrobial peptide of the brevinin-1 family (FLPVVAGLAAKVLPSIICAVTKKC). The peptide inhibited growth of Escherichia coli (minimum inhibitory concentration 45 microM) and Staphylococcus aureus (minimum inhibitory concentration 7 microM). The data suggest that synthesis of the peptide is induced when the animal is in an environment that promotes the growth of microorganisms consistent with a role in the animal's defense strategy.

Adaptation, Physiological↗

Liver ischemic preconditioning: a new strategy for the prevention of ischemia-reperfusion injury.

Ischemic preconditioning renders the liver more tolerant to ischemia-reperfusion injury in warm and cold ischemia-reperfusion models. In general, the application of a 5 to 10-minute period of ischemia followed by 10 minutes of reperfusion confers early effective protection to the liver. Mechanisms responsible for this endogenous protective effect include: (1) transient nitric oxide production during liver preconditioning; (2) diminution of toxic reactive species generated on reperfusion; (3) remote effect on extrahepatic organs such as lung, kidney, and pancreas; (4) preservation of energy metabolism during ischemia; and (5) involvement of nuclear transcription factor and others.

Animals↗

Environmental effects on thermoregulation and nutrition of horses.

Horses are reared in all types of weather. Temperatures as diverse as -40 degrees C to 40 degrees C are tolerated by horses. The nutrient requirement most influenced by cold weather is energy. In cold weather, feeding good quality hays free-choice is usually sufficient for mature horses in good body condition. Grain may have to be fed when poor quality hays are used. Hot weather (greater than 30 degrees C) necessitates heat loss to maintain body core temperature. Horses sweat to reduce body heat. Heat stress can be minimized by feeding diets that reduce the heat increment. Use of grain and fat in the diet, which have a lower heat increment than fibrous feeds such as hays, may benefit horses in hot climates. Wind or precipitation necessitate protection to minimize chilling in cold weather and discomfort in hot weather. However, it is a moot point whether horses will use shelters under these circumstances.

Animal Nutritional Physiological Phenomena↗

Deep ocean environmental biotechnology

Major recent advances in deep-sea biotechnology have come in the form of continuing discoveries of novel microorganisms, unexpected genetic diversity, and new natural products of potential relevance to human health or environmental bioremediation. Continuing explorations of submarine hydrothermal vent environments have yielded new hyperthermophiles (maximal growth at 90 degreesC or greater) and more evidence that elevated hydrostatic pressure stabilizes cells and enzymes at high temperature. Vent samples have also yielded new mesophiles (optimal growth near 30 degreesC) that produce heparin-like exopolysaccharides or express extraordinary tolerance (removal by precipitation) of heavy metals. From the cold deep sea have come new findings of unexpected microbial diversity and the promise of industrially useful enzymes or secondary metabolites. New classes of predictive models are emerging to guide future exploration of microbial diversity in the deep ocean.

Journal Article↗

Once daily mometasone furoate aqueous nasal spray is as effective as twice daily beclomethasone dipropionate for treating perennial allergic rhinitis patients.

BACKGROUND: Perennial allergic rhinitis is chronic and persistent, may lead to a constellation of secondary complaints including sinusitis, mouth-breathing, and some symptoms resembling a permanent cold, and often requires constant medical intervention. Well-tolerated nasal corticosteroids, alone or in combination with antihistamines, have been found to be very effective in treating this condition. OBJECTIVE: To compare the effectiveness and tolerability of mometasone furoate aqueous suspension, a new once daily nasal spray, to placebo vehicle and to beclomethasone dipropionate, administered twice daily, in patients with perennial allergic rhinitis. METHODS: This was a randomized, double-blind, placebo-controlled, double-dummy, parallel group study, in 427 patients age 12 years and older at 24 centers in Canada and Europe. Patients allergic to at least one perennial allergen, confirmed by medical history, skin testing, and adequate symptomatology were eligible to receive one of the following regimens for 3 months: mometasone furoate, 200 micrograms only daily; beclomethasone dipropionate, 200 micrograms twice daily (400 micrograms total dose); or placebo vehicle control. The primary efficacy variable was the change from baseline in total AM plus PM diary nasal symptom score over the first 15 days of treatment. RESULTS: Three hundred eighty-seven patients were valid for efficacy. For the primary efficacy variable, mometasone furoate was significantly (P < or = .01) more effective than placebo and was indistinguishable from beclomethasone dipropionate. Similar trends were seen among individual symptoms, physician symptom evaluations, and therapeutic response. There was no evidence of tachyphylaxis. All treatments were well tolerated. CONCLUSIONS: Mometasone furoate nasal spray adequately controls symptoms of perennial allergic rhinitis, offers the advantage of once daily treatment, and is well tolerated.

Administration, Intranasal↗

A downshift in temperature activates the high osmolarity glycerol (HOG) pathway, which determines freeze tolerance in Saccharomyces cerevisiae.

The molecular mechanisms that enable yeast cells to detect and transmit cold signals and their physiological significance in the adaptive response to low temperatures are unknown. Here, we have demonstrated that the MAPK Hog1p is specifically activated in response to cold. Phosphorylation of Hog1p was dependent on Pbs2p, the MAPK kinase (MAPKK) of the high osmolarity glycerol (HOG) pathway, and Ssk1p, the response regulator of the two-component system Sln1p-Ypd1p. However, Sho1p was not required. Interestingly, phosphorylation of Hog1p was stimulated at 30 degrees C in cells exposed to the membrane rigidifier agent dimethyl sulfoxide. Moreover, Hog1p activation occurred specifically through the Sln1 branch. This suggests that Sln1p monitors changes in membrane fluidity caused by cold. Quite remarkably, activation of Hog1p at low temperatures affected the transcriptional response to cold shock. Indeed, the absence of Hog1p impaired the cold-instigated expression of genes for trehalose- and glycerol-synthesizing enzymes and small chaperones. Moreover, a downward transfer to 12 or 4 degrees C stimulated the overproduction of glycerol in a Hog1p-dependent manner. However, hog1Delta mutant cells showed no growth defects at 12 degrees C as compared with the wild type. On the contrary, deletion of HOG1 or GPD1 decreased tolerance to freezing of wild-type cells preincubated at a low temperature, whereas no differences could be detected in cells shifted directly from 30 to -20 degrees C. Thus, exposure to low temperatures triggered a Hog1p-dependent accumulation of glycerol, which is essential for freeze protection.

Active Transport, Cell Nucleus↗

Comparative effects of University of Wisconsin and Euro-Collins solutions on pulmonary mitochondrial function after ischemia and reperfusion.

BACKGROUND: The aim of this study was to compare the effects of Euro-Collins and University of Wisconsin solutions on pulmonary mitochondrial function after cold ischemia and subsequent warm reperfusion. METHODS: Seventeen pigs underwent lung harvesting after classical lung flush with either University of Wisconsin or Euro-Collins solutions. The mitochondria were isolated from fresh swine lungs, from swine lungs subjected to 24 hr of cold ischemia, and from swine lungs subjected to 24 hr of ischemia followed by 30 min of subsequent ex vivo reperfusion at 37 degrees C with Krebs-Henseleit buffer solution and air ventilation. Mitochondrial oxidative phosphorylation parameters were determined in isolated mitochondria by in vitro measurement of oxygen consumption rates. During reperfusion, the lung function was assessed by the pulmonary aerodynamic parameters and the pulmonary vascular resistance. RESULTS: Relative to controls, mitochondria submitted to cold ischemia showed an alteration in the oxidoreductase activities of the respiratory chain. However, the yield of oxidative phosphorylation was conserved. After reperfusion, pulmonary mitochondria underwent a significant worsening in the oxidoreductase activities of the respiratory chain, and a decrease in the respiratory control and the efficiency of oxidative phosphorylation. Meanwhile, the reperfused lungs showed evidence of early dysfunction, assessed by the aerodynamic parameters and pulmonary vascular resistance. In this model, there was no advantage of University of Wisconsin solution over Euro-Collins solution. CONCLUSIONS: The mild mitochondrial alterations after cold ischemia were not sufficient to explain the limited tolerance of lung to ischemia. After reperfusion, the mitochondrial damage was more severe and could be involved in the posttransplant lung dysfunction.

Adenosine↗

Effect of carvedilol and metoprolol on blood pressure, blood flow, and vascular resistance.

Carvedilol and metoprolol were given for 4 weeks in a double-blind study to patients with essential hypertension. The effects on blood pressure were measured and hemodynamic alterations were assessed by forearm venous plethysmography before and after chronic administration, and 2 h after an acute dose before and during chronic therapy. Carvedilol (50 mg/day) reduced supine and erect blood pressure, and pulse rate similar to the reduction with metoprolol (100 mg b.i.d.). There was a tendency for forearm blood flow to rise and for forearm resistance to fall with both drugs. When administered acutely, there was no fall in pulse rate with carvedilol compared to the fall with metoprolol when on placebo or active therapy. The blood pressure fall with acute administration was similar with both drugs when not on treatment, but when on chronic therapy, there was no fall with metoprolol but a marked fall with carvedilol. In this circumstance, vascular resistance rose with metoprolol but not with carvedilol. No effect of either drug on a modified cold presser test was observed. Both drugs were well tolerated and there were no significant side effects except for an excessive fall in blood pressure in one patient on carvedilol. Plasma renin activity (PRA) fell with both drugs and there was a tendency for both plasma potassium and plasma uric acid to rise. Carvedilol was well tolerated and reduced blood pressure successfully.

Adrenergic beta-Antagonists↗

Efficacy of Fat Mobilisation System (FMS) in the treatment of obesity and its utility in the resolution of gynecological problems related to overweight.

In industrialised countries the problem of overweight affects more than 50% of the adult population. Knowledge acquired over the past years has replaced the principally esthetic concept of obesity with the notion of a multifactorial pathology, the outcome of an imbalance in the individual's energy balance caused by an excessive food intake as well as an inadequate energy consumption. The Fat Mobilisation System (FMS), which is able to activate a fat clearance process following cold local application, has proved a valuable and well tolerated tool capable of influencing the entire system responsible for obesity. A group of 109 patients of both sexes, aged between 15 and 71 years old, with problems of overweight and/or figure faults linked to the localised accumulation of fat, underwent out-patient treatment in the form of bandaging with elasticated bandages soaked in active solution able to lower body temperature by 2-3 degrees C. The results were satisfactory in all cases. In particular, a group of 24 women (10 of a childbearing age, 7 in premenopause and 7 in menopause), in whom overweight was associated with gynecological problems, were evaluated by Department A of the Department of Gynecology and Obstetrics at the University of Turin. An improvement in gynecological symptoms was achieved in parallel to weight loss in all patients.

Adipose Tissue↗

[A new beta-2 sympathomimetic drug with longer effectiveness. Comparison with current beta-2 sympathomimetic drugs in therapy of bronchial asthma in childhood].

Inhaled beta-2-agonists are well established for the treatment of bronchial asthma. Treatment in childhood asthma has to take into account the longer night rests and intensive physical activity of the children. The new inhaled beta-2-agonist Formoterol meets these aspects because of the long lasting efficacy. In addition, compliance is increased by easy handling and rare application. Effects of Formoterol in children derived from several studies are presented. In single dose studies, Formoterol (12, 24 mcg) showed a rapid onset of action and in comparison to salbutamol and fenoterol a four-fold respectively two-fold longer lasting spasmolytic effect. The protective effect against unspecific stimuli was comparable but significantly longer. This protection was even more pronounced with a higher dose (24 micrograms). Long-term studies over three months showed that Formoterol (2 x 12 micrograms/day) improved lung function and asthmatic symptoms and protected against histamine and cold-air challenge throughout the study. Formoterol was well tolerated and additional medication could be reduced. Furthermore, we accomplished a high acceptance of treatment with Formoterol for both children and their parents.

Adrenergic beta-Agonists↗

[Liver resection under occlusion of hepato-duodenal ligaments. Renunciation of a textbook opinion].

The belief that the hepatoduodenal ligament should only be clamped for 5-10 min, then the clamp released for a shorter or longer period, can no longer be upheld. The author's clinical investigations have shown that continous clamping up to 20 min can be tolerated by the liver without adverse effect. The authors consider a clamping time of 30-40 min tolerable particularly if the liver is cooled by pouring cold Ringer's solution over it. In one case, splenic capsule rupture was a complication of clamping the hepatoduodenal ligament.

Duodenum↗

Decrease in plasma glucose concentration during storage at -20 degrees C.

We measured glucose concentrations with the Beckman Glucose Analyzer, before and after storage at -20 degrees C for various intervals, in 228 plasma samples from oral glucose tolerance tests on 17 normal subjects and 21 patients with impaired carbohydrate tolerance, and also in 82 control samples collected daily, after overnight fast, from seven insulin-dependent diabetics. We found a significantly (p < 0.001) positive relation between storage interval and percentage decrease in glucose concentration. Evidently, the longer plasma is stored, the greater the decrease in glucose.

Blood Glucose↗

Are poor metabolisers of sparteine/debrisoquine less pain tolerant than extensive metabolisers?

It has recently been shown that O-demethylation of the opioid drug codeine to morphine depends on the sparteine/debrisoquine oxygenase (CYP2D6) which in man exhibits genetic polymorphism. Morphine may be an endogenously formed substance in mammalians. Therefore, it may be hypothesized that the final step in an endogenous synthesis of morphine from codeine also depends on CYP2D6. CYP2D6, which is present in the liver and presumably also in the brain, is not expressed in subjects who are poor metabolisers of the sparteine/debrisoquine type. We have determined sensitivity to painful stimuli in 94 extensive metabolisers and 82 poor metabolisers of sparteine in 2 phasic (pain thresholds to heat and pressure) and 1 tonic (cold pressor test) experimental pain model. Extensive and poor metabolisers did not differ significantly in the 2 phasic pain models neither with respect to pain detection nor pain tolerance thresholds. However, for the cold pressor test, peak pain ratings and area under the pain rating-time curve during 2 min were significantly higher in poor than in extensive metabolisers (P = 0.0024 and 0.044). Furthermore, a substantially higher fraction of poor metabolisers prematurely withdrew their hand from the ice water during the cold pressor test due to intolerable pain (32 vs. 18%, P = 0.0545). We conclude that poor metabolisers of sparteine may be less tolerant to tonic pain than extensive metabolisers, and we hypothesize that this may be related to an inherited defect in endogenous synthesis of morphine via CYP2D6 in the brain.

Adult↗

[Intraoperative protection of free microsurgical transfer flaps: "cold storage" in HTK-1 solution].

There is a rule of thumb that an ischaemia time of 6 hours should not be exceeded when preserving a free flap. Microsurgical reconstructions sometimes require a long operation time and a long tolerance of ischaemia of the free flap. Using Bretschneider's HTK solution for the intraoperative cold storage of free flaps with a temperature of 5-7 degrees C, an ischaemia time of 12 hours should not affect the free flap, and hence the time limit of the ischaemic tolerance looses its importance. Based on Bretschneider's research results of cardioplegia and of the ischaemic tolerance of the kidney and the liver, we chose the HTK solution for the intraoperative protection of free microsurgical flaps.

Cardioplegic Solutions↗