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1.
At variance with the earlier belief that mitochondrial genomes are represented by circular DNA molecules, a large number of organisms have been found to carry linear mitochondrial DNA. Studies of linear mitochondrial genomes might provide a novel view on the evolutionary history of organelle genomes and contribute to delineating mechanisms of maintenance and functioning of telomeres. Because linear mitochondrial DNA is present in a number of human pathogens, its replication mechanisms might become a target for drugs that would not interfere with replication of human circular mitochondrial DNA.  相似文献   

2.
Recovery from prolonged anesthesia might be compromised in elderly patients. Desflurane (DES) may be particularly well suited to achieve a rapid postoperative recovery because of its low lipid solubility. Postoperative recovery was compared in 45 elderly patients randomized to receive either DES, isoflurane (ISO), or propofol (PRO) to maintain anesthesia. Anesthesia was induced with PRO, vecuronium, and fentanyl and maintained with N2O, fentanyl, and the study drug. Times from end of anesthesia to tracheal extubation, eye opening and hand squeezing on command, and ability to state name and date of birth were recorded. Sedation and psychometric evaluation were tested 0.5, 1, 1.5, 2, and 24 h postoperatively. Results are given as means +/- SD. Differences among were analyzed by chi2 or analysis of variance. P < 0.05 compared with DES was considered significant. After a prolonged anesthesia (199 +/- 57 min with DES), immediate recovery times were significantly shorter with DES than with ISO or PRO (times to eye opening: 5.6 +/- 3.4 min, 11.5 +/- 8.4 min, and 11.9 +/- 7.6 min; times to extubation: 6.9 +/- 3 min, 13.1 +/- 8.9 min, 9.9 +/- 6.5 min for DES, ISO, and PRO, respectively). Intermediate recovery, as measured by psychometric testing, sedation levels, and time to discharge from the postanesthesia care unit, was similar in the three groups. In this study, DES provided a transient advantage compared with ISO or PRO with respect to early recovery after prolonged general anesthesia in elderly patients. IMPLICATIONS: Recovery from prolonged anesthesia can sometimes be problematic in elderly patients. We evaluated 45 elderly patients who received either desflurane, isoflurane, or propofol for anesthesia. We found that desflurane provided a transient advantage in terms of postoperative recovery, but whether this difference is clinically important remains to be demonstrated.  相似文献   

3.
BACKGROUND: Sevoflurane has a lower blood:gas partition coefficient than isoflurane, which may cause a more rapid recovery from anesthesia; it also might cause faster emergence times than for propofol-based anesthesia. We evaluated a database that included recovery endpoints from controlled, randomized, prospective studies sponsored by Abbott Laboratories that compared sevoflurane to isoflurane or propofol when extubation was planned immediately after completion of elective surgery in adult patients. METHODS: Sevoflurane was compared to isoflurane in eight studies (N=2,008) and to propofol in three studies (N=436). Analysis of variance was applied using least squares method mean values to calculate the pooled mean difference in recovery endpoints between primary anesthetics. The effects of patient age and case duration also were determined. RESULTS: Sevoflurane resulted in statistically significant shorter times to emergence (-3.3 min), response to command (-3.1 min), orientation (-4.0 min) and first analgesic (-8.9 min) but not time to eligibility for discharge (-1.7 min) compared to isoflurane (mean difference). Times to recovery endpoints increased with increasing case duration with isoflurane but not with sevoflurane (patients receiving isoflurane took 4-5 min more to emerge and respond to commands and 8.6 min more to achieve orientation during cases longer than 3 hr in duration than those receiving sevoflurane). Patients older than 65 yr had longer times to orientation, but within any age group, orientation was always faster after sevoflurane. There were no differences in recovery times between sevoflurane and propofol. CONCLUSIONS: Recovery from sevoflurane was 3-4 min faster than with isoflurane in all age groups, and the difference was magnified in longer-duration surgical cases (> 3 hr).  相似文献   

4.
The tegument of herpes simplex virus type 1 (HSV-1) virus particles is a complex assemblage of virus proteins whose relative proportions within virions are essentially constant for a particular strain of virus. To examine the processes controlling incorporation into the tegument, we constructed a HSV-1 recombinant that expresses two copies of gene UL49, which encodes the major tegument protein VP22. One copy specifies the unmodified form of VP22 under the control of the native promoter while the second expresses an epitope-tagged version of the protein via the human cytomegalovirus immediate early promoter. In cells infected with the recombinant virus, the overall levels of VP22 synthesized were about fivefold higher than those for wild-type virus, due to the high levels of expression of tagged protein. Analysis of virus particles revealed that the amount of VP22 in the tegument was approximately two- to threefold higher in recombinant virions and L-particles than in particles produced by wild-type virus. These results provide the first evidence that, for certain proteins, the level of polypeptide synthesis can act as a controlling factor for the amount of protein incorporated into tegument.  相似文献   

5.
Light affects the circadian axis in at least two ways. It can cause the acute suppression of pineal melatonin synthesis, and/or a phase-shift of the circadian oscillator. As recent evidence has suggested that extraocular light exposure may cause phase-shifts of the circadian clock, we have investigated whether suppression of melatonin can be induced by the same type of light exposure. In the first study subjects' eyes were exposed to white light (2250 lux for 30 mins) via a fibre optic cable. As expected, suppression of nighttime plasma melatonin levels (61 +/- 6%) was observed. In the second study, light of the same quality but higher intensity (14,000 or 67,500 lux for 180 mins) was delivered in the same manner to the popliteal region behind the subjects' knees, whilst shielding their eyes. No suppression of plasma melatonin levels (4 +/- 7%) was detected in any of the subjects. Thus, extraocular photoreception, if it exists in mammals, does not affect the suprachiasmatic nucleipineal pathway.  相似文献   

6.
The coexistence of S100beta with calcitonin gene-related peptide (CGRP), substance P (SP), somatostatin (SOM), nicotinamide adenosine dinucleotide phosphate-diaphorase (NADPH-d), and tyrosine hydroxylase (TH) was examined in the glossopharyngeal and vagal sensory ganglia. S100beta immunoreactive (-ir) neurons in the jugular and petrosal ganglia frequently colocalized CGRP- or SP-ir, whereas S100beta-ir neurons in the nodose ganglion infrequently contained CGRP- or SP-ir. No S100beta-ir neurons in the jugular and petrosal ganglia showed SOM-ir while the small number of SOM-ir neurons in the nodose ganglion colocalized S100beta-ir. Many neurons in the nodose ganglion colocalized S100beta-ir and NADPH-d activity, whereas S100beta-ir neurons in the jugular and nodose ganglia infrequently contained NADPH-d activity. S100beta- and TH-ir were frequently colocalized in nodose ganglion but not in petrosal or jugular ganglion neurons. These findings suggest relationships between S100beta and specific putative transmitters in functions of subpopulations of vagal and glossopharyngeal sensory neurons.  相似文献   

7.
We have designed a microdialysis technique to measure acetylcholinesterase (AChE) activity in the cortex of freely moving rats while simultaneously measuring the release of acetylcholine (ACh). Our approach was validated using ethyl S-2-di-isopropylaminoethyl-phosphonothiolate (VX), an irreversible inhibitor of AChE and comparing inhibition measured by this 'in vivo' method with traditional post-mortem assays of AChE activity 120 min after an intraventricular injection of VX. Maximum inhibition of AChE occurred 30 min after injection and was followed by a slow recovery. ACh release reached its maximum 60 min after treatment and then decreased towards normal levels. This method offers a new way to develop medications against poisoning with anticholinesterasic neurotoxic and allows the evaluation of the effects of cholinergic drugs for the treatment of Alzheimer's disease.  相似文献   

8.
Autocrine stimulation of growth factor receptors by autonomously produced ligands regulates different aspects of cellular transformation and progression. In several tumors, including gliomas, multiple autocrine systems are activated and may exert different functions in the malignant transformation process. The c-kit proto-oncogene is widely expressed in human gliomas, and it may be activated by its co-expressed ligand, stem cell factor (SCF). Studies in glioma cell lines as well as different tumor types suggest the possibility of intracellular interactions of c-kit with SCF. Although c-kit and SCF may not play a primary and causal role in the initiation and progression of glial tumors they may still be contributing factors in glioma biology. It can be hypothesized that the parallel activation of several autocrine systems including some of which have found less attention in gliomas, such as c-kit/SCF, could compromise the efficacy of therapies targeting different autocrine loops. A better understanding of the multiplicity and mechanisms of autocrine stimulation has implications for the development of new therapies interfering with autocrine tumor cell growth.  相似文献   

9.
BACKGROUND: We determined the effect of oral ingestion of sucrose polyester, which was approved as a fat replacer in the United States, on gallbladder motility and on the release of cholecystokinin, the hormone that mediates gallbladder emptying. OBJECTIVE: Our objective was to measure effects of sucrose polyester on gallbladder emptying and cholecystokinin release. DESIGN: Eight healthy volunteers (3 men and 5 women) drank 60 mL sucrose polyester, digestible fat, or saline solution in a balanced crossover design on 3 separate days. RESULTS: Mean (+/-SEM) gallbladder emptying, when integrated over time, was low in response to both sucrose polyester (-150 +/- 214 mL x 120 min) and saline solution (-89 +/- 123 mL x 120 min). In contrast, there was marked emptying in response to digestible fat (1069 +/- 253 mL x 120 min). Sucrose polyester did not affect plasma cholecystokinin concentrations (-9.3 +/- 15.0 pmol x 120 min/L), whereas digestible fat resulted in a significant increase (89.5 +/- 44.8 pmol x 120 min/L, P = 0.014) compared with saline solution (-3.0 +/- 13.8 pmol x 120 min/L). CONCLUSIONS: Ingestion of sucrose polyester, in contrast with digestible fat, did not stimulate gallbladder emptying or release of cholecystokinin.  相似文献   

10.
We studied the effect of premedication (1 microgram/kg fentanyl and 0.04 mg/kg midazolam 5 min before induction of anesthesia) on airway reactivity and hemodynamic stability during inhaled induction using desflurane in 10 ambulatory surgical patients. Eight patients who were anesthetized without premedication served as the controls. Induction and emergence were rapid and unaffected by premedication. End-tidal and inspired concentrations of desflurane at loss of consciousness were significantly reduced by premedication (10.1% end-tidal/14.1% inspired, no premedication, vs. 5.3% end-tidal/8.9% inspired, premedication). Airway irritability was markedly attenuated by premedication (100% no premedication versus 30% premedicated), as was apnea (37.5% no premedication versus 0% premedicated). We observed an increase in mean arterial blood pressure and heart rate after loss of consciousness (mean arterial pressure 103 vs 121 mm Hg, heart rate 73 vs 100 bpm) in the unpremedicated patients, whereas both groups demonstrated a decrease in mean arterial blood pressure with no change in heart rate when baseline values were compared to those at incision (103 vs 74 mm Hg, no premedication, 99 vs 81 mm Hg premedicated). Patient acceptability was satisfactory and unchanged by premedication. We recommend the use of such premedication when desflurane is used during the induction of anesthesia.  相似文献   

11.
Handling rat pups by removing them from the nest during the preweaning period has been shown to influence brain and behavioral development. The authors hypothesized that handling rats with perinatal (Day 4) medial frontal cortex removals might attenuate behavioral deficits and reverse dendritic atrophy associated with such an injury. On the day after surgery, pups were removed from the nest for 15 min, 3 times per day until weaning. Animals were tested as adults in the Morris water task and on skilled reaching. Handled animals showed no improvement in behavioral performance. The handling procedure led to a decrease in dendritic length in parietal cortex, but spine density was unchanged. No therapeutic advantage was observed following the preweaning handling of brain-injured rats. (PsycINFO Database Record (c) 2010 APA, all rights reserved)  相似文献   

12.
Epidemiologic studies indicated that tea consumption reduces the risk of cardiovascular disease. We assessed the effect of green or black tea consumption on resistance of low-density lipoprotein (LDL) to oxidation ex vivo and on serum lipid concentrations in healthy volunteers. In a 4-wk parallel comparison trial, 45 volunteers consumed 900 mL (6 cups) mineral water, green tea, or black tea/d. Blood samples drawn while subjects were fasting were obtained before and after the study. The effect on resistance of subsequently isolated LDL to oxidation of adding green or black tea extract to plasma was investigated in an in vitro experiment. Consumption of 900 mL (6 cups) green or black tea/d did not affect serum lipid concentrations, resistance of LDL to oxidation, or markers of oxidative damage to lipids in vivo, although consumption of green tea slightly increased total antioxidant activity of plasma. The in vitro experiment showed that resistance of isolated LDL to oxidation increased only after incubation of plasma with very high amounts of green or black tea. These amounts, when converted to tea catechin concentrations, were much higher than those expected in vivo. We conclude that daily consumption of 900 mL (6 cups) green or black tea/d for 4 wk had no effect on serum lipid concentrations or resistance of LDL to oxidation ex vivo. Future research should focus on mechanisms by which tea flavonoids may reduce the risk of cardiovascular disease other than by increasing the intrinsic antioxidant status of LDL.  相似文献   

13.
Despite improvement in early diagnosis, surgical techniques, and general patient care, most deaths of cancer patients result from metastases. Recent studies have revealed that cytokines produced by cancer cells or by stromal cells play an important role into development the cancer metastasis. The formation of a cancer metastasis involves several major steps: 1) extensive vascularization; 2) local invasion; 3) adherence either to capillary endothelial cells or to subendothelial basement membrane; 4) extravasation; and 5) proliferation. In colon cancer, several cytokines such as growth factors, inflammatory cytokines, and angiogenic factors have been confirmed to be involved in each step of metastasis. This paper summarizes the involvement of cytokines in the development of invasion and metastasis in colon cancer.  相似文献   

14.
This prospective, randomised study compared total intravenous anaesthesia (TIVA) and inhalation anaesthesia with respect to endocrine stress response, haemodynamic reactions, and recovery. METHODS. The investigation included two groups of 20 ASA I-II patients 18-60 years of age scheduled for orthopaedic surgery. For premedication of both groups, 0.1 mg/kg midazolam was injected IM. Patients in the propofol group received TIVA (CPPV, PEEP 5 mbar, air with oxygen FiO2 33%) with propofol (2 mg/kg for induction followed by an infusion of 12-6 mg/kg.h) and fentanyl (0.1 mg before intubation, total dose 0.005 mg/kg before surgery, repetition doses 0.1 mg). For induction of patients in the isoflurane-group, 5 mg/kg thiopentone and 0.1 mg fentanyl was administered. Inhalation anaesthesia was maintained with 1.2-2.4 vol.% isoflurane in nitrous oxide and oxygen at a ratio of 2:1 (CPPV, PEEP 5 mbar). For intubation of both groups, 2 mg vecuronium and 1.5 mg/kg suxamethonium were injected, followed by a total dose of 0.1 mg/kg vecuronium. Blood samples were taken through a central venous line at eight time points from before induction until 60 min after extubation for analysis of adrenaline, noradrenaline (by HPLC/ECD), antidiuretic hormone (ADH), adrenocorticotropic hormone (ACTH), and cortisol (by RIA). In addition, systolic arterial pressure (SAP) heart rate (HR), arterial oxygen saturation (SpO2), and recovery from anaesthesia were observed. RESULTS. Group mean values are reported; biometric data from both collectives were comparable (Table 1). Plasma levels of adrenaline (52 vs. 79 pg/ml), noradrenaline 146 vs. 217 pg/ml), and cortisol (82 vs. 165 ng/ml) were significantly lower in the propofol group (Table 2, Figs. 1 and 3). Plasma levels of ADH (4.8 vs. 6.1 pg/ml) and ACTH (20 vs. 28 pg/ml) did not differ between the groups (Table 2, Figs 2 and 3). SAP (128 vs. 131 mmHg) was comparable in both groups, HR (68/min vs. 83/min) was significantly lower in the propofol group, and SpO2 (97.1 vs 97.4%) showed no significant difference (Table 3). Recovery from anaesthesia was slightly faster in the propofol group (following of simple orders 1.9 vs. 2.4 min, orientation with respect to person 2.4 vs. 3.4 min, orientation with respect to time and space 2.8 vs. 3.7 min), but differences failed to reach statistical significance. CONCLUSIONS. When compared with isoflurane inhalation anaesthesia, moderation of the endocrine stress response was significantly improved during and after TIVA with propofol and fentanyl. Slightly shorter recovery times did not lead to an increased stress response. With respect to intra- and postoperative stress reduction, significant attenuation of sympatho-adrenergic reaction comparable SAP and reduced HR, sympatholytic and hypodynamic anaesthesia with propofol and fentanyl seems to be advantageous for patients with cardiovascular and metabolic disorders. For this aim, careful induction and application of individual doses is essential.  相似文献   

15.
BACKGROUND: Omeprazole is known to have an effect on Helicobacter pylori in vivo. One opinion is that H. pylori "migrates" from the antrum to the corpus in response to omeprazole therapy. METHODS: To determine whether H. pylori migrates in response to omeprazole, we assessed the presence of H. pylori in the antrum and corpus in duodenal ulcer patients receiving omeprazole for 4 wk. Culture and histological examination of antral biopsies (Genta stain) were performed before patients received omeprazole, at the end of therapy, and 4-6 wk later. The end points were presence or absence of H. pylori and the number of H. pylori colonies per biopsy. RESULTS: Seventy-two patients had H. pylori in both the antrum and corpus at entry and 4-6 wk after ending therapy. Three general patterns were prevalent at the end of omeprazole therapy: antrum- and corpus-positive (54%), antrum-negative and corpus-positive (24%), both antrum- and corpus-negative (21%), and one patient had antrum-positive with corpus-negative (1%). Evaluation of the number of colonies per biopsy in those who remained H. pylori-positive in both the antrum and corpus throughout showed that the number of H. pylori decreased in both the antrum and corpus during therapy (507 +/- 60 vs. 225 +/- 51, p < 0.01 and 415 +/- 58 vs. 290 +/- 46 0.1) for antrum and corpus, respectively, and tended to return to pre-therapy levels 4-6 wk later. The number of H. pylori in the corpus also decreased in the antrum-negative and corpus-positive group during therapy with omeprazole (433 +/- 87 vs. 185 +/- 61, p < 0.05). In most of the patients studied, the number of H. pylori in the corpus was less posttreatment than it was pretreatment. The decrease in H. pylori load was also reflected in the development of false-negative urea breath tests. CONCLUSIONS: Omeprazole is detrimental to H. pylori in both the antrum and the corpus; migration from the antrum to the corpus in response to omeprazole is a myth.  相似文献   

16.
In our previous studies aimed at designing appropriate strategies to accelerate recovery of the immune system after irradiation, we found that the hematopoietic cytokine recombinant murine (rmu) interleukin (IL)-3 was able to induce differentiation and growth of thymocytes and splenic T and B lymphocytes in mice exposed to x-rays (200-500 cGy). The recovery, however, was complete at 7 days only after a dose of 200 cGy, whereas 2, 3, and 4 weeks were necessary to achieve full recovery after 300, 400, and 500 cGy, respectively. These studies were extended to investigate the effects of another hematopoietic cytokine, recombinant human (rhu) IL-11, a bone marrow stromal-derived cytokine, administered together with IL-3 to irradiated mice. The synergistic effect of the two cytokines was evident when relatively small doses of rhu IL-11 were injected with an optimal dose of rmu IL-3.  相似文献   

17.
18.
INTRODUCTION: Arm abduction of 90 degrees during injection of local anesthetic followed by adduction of the arm has been recommended traditionally to favor proximal distribution of local anesthetic and extension of the blockade in the brachial plexus by the axillary route. A recent study demonstrated that there are no clinical or radiological differences between axillary blockades performed with abduction or adduction. OBJECTIVE: To compare the extension of sensory blockade in axillary anesthesia performed with adduction or abduction. MATERIAL AND METHODS: Forty patients were randomly distributed in two groups, 20 in the adduction group and 20 in the abduction group. The axillary catheter was inserted 3 cm in the proximal direction and a mixture of 40 ml of 1.5% mepivacaine without adrenaline and 4 ml of 8.4% bicarbonate soda was injected into each patient. RESULTS: No statistically significant differences in extension of sensory blockade, including circumflex, musculocutaneous and radial nerve blockade, were observed. CONCLUSIONS: Axillary rotation of the arm is not a determining factor in sensory blockade in brachial plexus anesthesia by the axillary route.  相似文献   

19.
Networks of interstitial cells of Cajal embedded in the musculature of the gastrointestinal tract are involved in the generation of electrical pacemaker activity for gastrointestinal motility. This pacemaker activity manifests itself as rhythmic slow waves in membrane potential, and controls the frequency and propagation characteristics of gut contractile activity. Mice that lack a functional Kit receptor fail to develop the network of interstitial cells of Cajal associated with Auerbach's plexus in the mouse small intestine and do not generate slow wave activity. These cells could provide an essential component of slow wave activity (for example, a biochemical trigger that would be transferred to smooth muscle cells), or provide an actual pacemaker current that could initiate slow waves. Here we provide direct evidence that a single cell, identified as an interstitial cell of Cajal by light microscopy, electron microscopy and expression of Kit mRNA, generates spontaneous contractions and a rhythmic inward current that is insensitive to L-type calcium channel blockers. Identification of the pacemaker of gut motility will aid in the elucidation of the pathophysiology of intestinal motor disorders, and provide a target cell for pharmacological treatment.  相似文献   

20.
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