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Selective portal clamping to minimize hepatic ischaemia-reperfusion damage and avoid accelerated outgrowth of experimental colorectal liver metastases.

BACKGROUND: Temporary vascular clamping during local ablation for colorectal liver metastases increases destruction volumes. However, it also causes ischaemia-reperfusion (IR) injury to the liver parenchyma and accelerates the outgrowth of microscopic tumour deposits. The aim of this study was to investigate the effects of selective portal clamping on hepatocellular damage and tumour growth. METHODS: Mice carrying pre-established hepatic colorectal micrometastases underwent either simultaneous clamping of both the portal vein and the hepatic artery or selective clamping of the portal vein to the median and left liver lobes for 45 min. Sham-operated mice served as controls. Hepatic injury and tumour growth were assessed over time. RESULTS: Standard inflow occlusion resulted in a rise in liver enzymes, a local inflammatory response and hepatocellular necrosis. The outgrowth of pre-established micrometastases was accelerated three- to fourfold in clamped compared with non-clamped liver lobes (27.4 versus 7.8 per cent, P < 0.010). Conversely, selective portal clamping induced minimal liver injury, tissue inflammation or hepatocellular necrosis, and completely stopped the accelerated outgrowth of micrometastases. CONCLUSION: Selective portal clamping does not induce liver tissue damage or accelerate micrometastasis outgrowth and may therefore be the preferable clamping method during local ablative treatment of hepatic metastases.

Animals↗

Detection of impaired left ventricular function in coronary artery disease with acceleration index in the first derivative of the transthoracic impedance change.

In order to detect impaired left ventricular (LV) function in coronary artery disease (CAD) patients using acceleration index (Ac) of impedance cardiography (ICG), exercise ICG was performed in 29 patients with chest pain but without CAD (Group 1) and 21 patients with CAD (Group 2), and their resting values were compared with 30 healthy controls (Group 3). The acceleration index, which reflects indirectly aortic blood flow acceleration, was calculated as the ratio of dZ/dtmax to its accelerating time (AT). At rest, the values for Ac in Groups 1, 2, and 3 were 23 +/- 10, 15 +/- 6, and 36 +/- 13 omega/s2, respectively. There were significant differences between Group 1 versus 3, 2 versus 3, and 1 versus 2 (all p less than 0.001). At maximal exercise, Ac showed the largest percent change among the various indices used in this study. An increase of 198% for Group 2 was markedly lower than that of 250% in Group 1 (40 +/- 14 vs. 68 +/- 24 omega/s2, p less than 0.001). With a value of less than or equal to 40 omega/s2, Ac can detect the CAD patients, with a sensitivity of 62% and specificity of 90%, superior to stress ECG using CM5 lead. It is concluded that: (1) Ac is the sole index capable of distinguishing not only between the normals and diseased groups, but also between CAD patients and suspected CAD cases at rest. (2) Ac is a remarkably sensitive index for detecting impaired LV function at maximal exercise. (3) Exercise ICG is useful for predicting CAD from the population predisposing to CAD.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Acceleration and delay of puberty in female mice via urinary chemosignals: age of the urine stimulus.

Five experiments were conducted to test the effects of the age of urine on the acceleration and delay of puberty in female mice resulting from treatment with urinary chemosignals. The chemosignal in the urine of male mice that accelerates female puberty was not affected by remaining exposed to the air at room conditions for up to 7 days, or when dried in air and reconstituted with water. The chemosignal in the urine of grouped female mice that delays puberty in females and the chemosignal present in the urine of pregnant and lactating female mice that accelerates female puberty were affected to varying degrees by exposure to room conditions; at 5-to-7 days of exposure the urine samples lost their capacity to delay or accelerate sexual maturation. These results are in agreement with earlier work indicating that the male chemosignal is not volatile, whereas the substances in urine from grouped females and pregnant or lactating females are more volatile. The results also have implications for interpretations of how the urinary chemosignals may affect the population biology of house mice under natural conditions.

Animals↗

Genetic requirements for acceleration of diabetes in non-obese diabetic mice expressing interleukin-2 in islet beta-cells.

Diabetes was dramatically accelerated in non-obese diabetic (NOD) transgenic mice that expressed interleukin-2 (IL-2) in their beta cells. A single cross to C57BL/6 completely prevented this effect and a further backcross to the NOD genetic background showed that at least two diabetes susceptibility loci (Idd1s and Idd3/10s) were required for the diabetes acceleration T cells activated to islet antigens were not circulating in the mice. The accelerating effect of IL-2 was present; but decreased, in NOD mice that lacked CD8+ T cells as well as in NOD SCID mice. The implications are that in the NOD genetic background, the production of cytokines, such as IL-2, by islet-specific CD4+ T cells can lead to beta cell damage and diabetes and that CD8+ T cells may have a role in accelerating diabetes onset.

Animals↗

Acceleration of invasive activity via matrix metalloproteinases by transfection of the estrogen receptor-alpha gene in endometrial carcinoma cells.

It is well known that the functions of reproductive organs are regulated by sex steroids and their receptors and it is hypothesized that the progression of neoplasms that originate from the reproductive organs is influenced by them. However, the correlation between sex steroids and tumor progression, especially tumor invasion, is not well known in endometrial carcinoma. In our study, we focused on the influence of estrogen and its receptor in invasion and matrix metalloproteinases (MMPs), which are known to be important in tumor invasion, as well as on endometrial carcinoma cells. The growth of Ishikawa cells, to which an estrogen receptor-alpha expressing vector was transfected, was accelerated by 17 beta-estradiol as was the acceleration of the expression of cyclin D1. By invasion assay, in conditions with 17 beta-estradiol, the invasiveness of Ishikawa cells was enhanced. Furthermore, according to the accelerated invasiveness, the expression of MMP-1, -7 and -9 and Ets-1 was enhanced. These results suggest that activation of ER-alpha by estrogen results in tumor progression by stimulating cell growth and invasiveness via acceleration of the expression of MMPs.

Blotting, Western↗

Formation of apatite on poly(alpha-hydroxy acid) in an accelerated biomimetic process.

Bonelike apatite coating was formed on poly(L-lactic acid) films and poly(glycolic acid) scaffolds within 24 h through an accelerated biomimetic process. The ion concentrations in the simulated body fluid (SBF) were nearly 5 times of those in the human blood plasma. The apatite formed was characterized by using scanning electron microscopy (SEM), energy dispersive X-ray spectroscopy (EDX), X-ray diffraction (XRD), and Fourier transform infrared spectroscopy (FTIR). The apatite formed in 5SBFs was similar in morphology and composition to that formed in the classical biomimetic process using SBF or 1.5SBF and similar to that of natural bone. This indicated that the biomimetic apatite-coating process could be accelerated by using concentrated simulated body fluid at 37 degrees C. Besides saving time, the accelerated biomimetic process is particularly significant to biodegradable polymers. Some polymers that degrade too fast to be coated with apatite by a classical biomimetic process (e.g., PGA) could be coated with bonelike apatite in an accelerated biomimetic process.

Apatites↗

Analysis of puberty-accelerating pheromones.

Two experiments were performed to test putative puberty-accelerating pheromones. In the first experiment, 37 weanling female house mice of the ICR strain were exposed to 1 of the following 3 treatments: an airborne mixture of 0.05 M isoamylamine and 0.05 M isobutylamine, fresh male mouse urine, or distilled water, as the control. Neither the amine mixture nor the male urine accelerated first estrus in the mice following airborne exposure to these compounds. In the second experiment, 37 weanling female mice of the same strain were exposed to the same chemicals as in the first experiment by direct contact to the oro-nasal groove. The mixture of isoamylamine and isobutylamine did not accelerate puberty, but direct contact with the male urine accelerated puberty as evidenced by uterine weights.

Administration, Intranasal↗

Microwave-accelerated cytochemical stains for the image analysis and the electron microscopic examination of light microscopy diagnostic slides.

Recent studies in our laboratories have shown how microwave (MW) irradiation can accelerate a number of tissue-processing techniques, especially staining, to aid in the preparation of single specimens on glass microscope slides or coverslips for examination by light microscopy (and electron microscopy, if required) for diagnostic purposes. Techniques have been developed, which give permanently stained preparations, that can be studied initially by light microscopy, their areas of interest mapped, and computer-automated image analysis performed to obtain quantitative information. This is readily performed after MW-accelerated staining with silver methenamine by the Giammara-Hanker PATS or PATS-TS reaction. This variation of the PAS reaction gives excellent markers for specific infectious agents such as lipopolysaccharides for gram-negative bacteria or mannans for fungi. It is also an excellent stain for glycogen and basement membranes and an excellent marker for type III collagen or reticulin in the endoneurium or perineurium of peripheral nerve or in the capillary walls. Our improved MW-accelerated Feulgen reaction with silver methenamine for nuclear DNA is useful to show the nuclei of bacteria and fungi as well as of cells they are infecting. Improved coating and penetration of tissue surfaces by thiocarbohydrazide bridging of ruthenium red, applied under MW-acceleration, render biologic specimens sufficiently conductive for SEM so that sputter coating with gold is unnecessary. The specimens treated with these highly visible electron-opaque stains can be screened with the light microscope after mounting in polyethylene glycol (PEG) and the structures or areas selected for EM study are mapped with a Micro-Locator slide. After removal of the water soluble PEG the specimens are remounted in the usual EM media for scanning electron microscopy (SEM) or transmission electron microscopy (TEM) study of the mapped areas. By comparing duplicate smears from areas of infection, such as two coverslips of buffy coat smears of blood from a patient with septicemia, the microorganisms responsible can occasionally be classified for antimicrobial therapy long before culture results are available; gram-negative bacteria are positive with the Giammara-Hanker PATS-TS stain, and gram-positive bacteria are positive with the SIGMA HT40 Gram stain. The gram-positive as well as gram-negative bacteria are both initially stained by the crystal violet component of the Gram stain. The crystal violet stain is readily removed from the gram-negative (but not the gram-positive) bacteria when the specimens are rinsed with alcohol/acetone. If this rinse step is omitted, the crystal violet remains attached to both gram-negative and gram-positive bacteria. It can then be rendered insoluble, electron-opaque, and conductive by treatment with silver methenamine solution under MW-irradiation. This metallized crystal violet is a more effective silver stain than the PATS-TS stain for a number of gram-negative spirochetes such as Treponema pallidum, the microbe that causes syphilis.

Acquired Immunodeficiency Syndrome↗

Studies on intracellular transport of secretory proteins in the rat exocrine pancreas. V. Kinetic studies on accelerated transport following caerulein infusion in vivo.

The previous finding that intracellular transport of secretory proteins in the rat exocrine pancreas is accelerated by in vivo stimulation with a pancreatic secretagogue has been further analyzed. Using a radioassay for discharge of newly synthesized proteins, the rate of release was compared in control and prestimulated lobules. In control preparations discharge occurred with an initial lag period of 30 minutes and a maximum after two hours of incubation. After in vivo infusion of 5 x 10(-8) g/hr. caerulein for 24 h in vitro discharge started after 10 minutes of in vitro incubation and attained a maximal rate after one hour. Using the same radioassay and several inhibitors of intracellular transport and granule discharge, it could be demonstrated that both processes were reduced to the same extent in controls and in lobules with accelerated transport. To obtain direct evidence for the degree of acceleration of the different transport steps between rough endoplasmic reticulum, Golgi complex and zymogen granules, the respective subcellular fractions of these organelles prepared and characterized ultrastructurally and biochemically. The rate of disappearance of newly formed proteins from rough microsomes and the appearance in smooth microsomes and zymogen granules were significantly increased after in vivo stimulation. The data substantiate an acceleration of the regular transport steps by the secretagogue. There was no indication that a high level of secretory activity leads to a rerouting of secretory proteins or to an omission of one of the regular steps in intracellular transport.

Amylases↗

Retardation of cerebral dopamine turnover after morphine withdrawal and its enhanced acceleration by acute morphine administration in rats.

To clarify the effects of withdrawal from chronic morphine treatment on cerebral dopamine (DA) turnover, we have measured the alpha-methyl-p-tyrosine (alpha MT)-induced depletion of DA in five brain areas of male Wistar rats given morphine twice daily for 40 or 60 days. After the last morphine dose (50 or 70 mg/kg) the rats were withdrawn for 1, 2 or 4 days. In order to study the development of tolerance some of the rats were challenged with 10 mg/kg of morphine. Withdrawal of morphine retarded the alpha MT-induced DA depletion in the limbic forebrain and after long enough chronic treatment in the striatum, too. The challenge dose of morphine accelerated the cerebral DA depletion slightly less in rats withdrawn for 1 day from 60-day chronic morphine treatment than in rats treated chronically with saline, but it enhanced the DA depletion more in rats withdrawn from morphine for 2 and 4 days than in chronic saline rats. This enhancement was clearest in rats withdrawn for 4 days from 60-day treatment. Thus withdrawal from morphine seems to sensitize the rats to the DA depletion accelerating effect of morphine. Our results show that repeated administration of morphine creates no marked tolerance to the DA depletion accelerating effect of morphine. In contrast, the dopaminergic neurones of the chronically treated rats seem to depend on continuous morphine administration for their normal functioning. Furthermore, the retarded DA turnover after discontinuation of morphine treatment seems to sensitize the dopaminergic neurones to the DA depletion accelerating effect of morphine.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

The effects of the distribution of training on learning feedback-assisted cardiac acceleration.

In order to test a hypothesis derived from a motor skills learning model of cardiac acceleration control, groups of subjects were given biofeedback training for four sessions to learn cardiac acceleration under four different training schedules: (1) all sessions in one day, (2) daily sessions, (3) sessions every other day, and (4) weekly sessions. Ability to accelerate heart rate both with and without feedback was determined at each session. Also ability to accelerate heart rate without feedback was determined 1 week after the last training session as a measure of retention. Although there was highly significant (p less than.0001) evidence of heart rate control both with and without feedback, there were no differences in degree of control attributable to distribution of training sessions. There was, however, a trend (p less than .10) for subjects trained under the most distributed training schedule (weekly) to show more retention than subjects trained under a less distributed schedule (daily).

Adolescent↗

Interleukin 1 mediated acceleration of type II collagen-induced arthritis: effects of anti-inflammatory or anti-arthritic drugs.

We previously demonstrated that treatments with rIL-1 beta accelerated the onset and progression of CIA in mice. In the present study, it was observed that IL-1 also enhanced the development of CIA in rats. Like the mouse model, maximal incidence (80-100%) of arthritis occurred within 7 days after the first treatment with IL-1 in rats. Thus, the acceleration of CIA by IL-1 (IL-1 CIA) may be an improved model for the rapid screening of anti-inflammatory and/or anti-arthritic drugs. As a first step to determining the utility of the IL-1 CIA model as a drug screen, we examined the ability of various known anti-inflammatory and anti-arthritic drugs to modify the IL-1 mediated enhancement of CIA in both rats and mice. The results of these studies showed that when analyzed in the IL-1 CIA model, rats and mice exhibited differences in their responses to several of these drugs. For example, dexamethasone, cyclophosphamide, azathioprine, various non-steroidal anti-inflammatory drugs (NSAIDs) as well as methotrexate were found active in the IL-1 CIA of rats. By contrast, the NSAIDs were found to be less effective in suppressing the IL-1 accelerated disease in mice. In both rats and mice, cyclosporine A and several disease modifying anti-arthritic drugs failed to the prevent the development of CIA that was potentiated by IL-1. Thus, in the IL-1 CIA model NSAIDs appeared to be less active in mice than rats. In conclusion, because of the shorter latent period required for the development of arthritis in the IL-1 treated animals, the IL-1 accelerated CIA model in both mice and rats may be useful for screening anti-inflammatory or anti-arthritic compounds.

Animals↗

Erythromycin accelerates solid emptying at the expense of gastric sieving.

Erythromycin accelerates gastric emptying by inducing antral contractions similar to phase III of interdigestive MMC. These powerful contractions are capable of forcing coin-sized indigestibles out of the stomach. In contrast, fed motility is associated with submaximal contractions that fragment (trituration) and propel solids while retaining large (> 0.5 mm) pieces for further size reduction (gastric sieving). In this study, using dogs with duodenal fistulas, we tested the hypothesis that erythromycin-induced acceleration of gastric emptying resulted in the passage of inadequately triturated (> 0.05 mm) chunks of solids into the duodenum. We found that gastric emptying was accelerated by erythromycin (vs 0.15 M NaCl control, P < 0.05). However, the percentage of chyme collected in the > 0.5-mm fraction was much greater (P < 0.01) in the erythromycin-treated experiments (63 +/- 9%) than the controls (7 +/- 1%). Correspondingly, while a fine gruel was passed during controls, under erythromycin infusion, most of the solids were emptied as large chunks virtually unchanged from the swallowed pieces. We conclude that erythromycin accelerates gastric emptying at the expense of gastric sieving.

Animals↗

The induction of accelerated murine amyloid with human splenic extract. Probable role of amyloid enhancing factor.

Amyloid enhancing factor (AEF) is derived from the tissues of pre-amyloidotic and amyloidotic animals and, when transferred, greatly accelerates amyloid induction in the recipient murine models. It has also been reported that similarly accelerated amyloid induction can be achieved in mice by injection of human splenic homogenates from patients with amyloidosis. The present study has attempted to characterize further the mechanism of this "heterologous transfer of amyloid". Treatment of mice with the "tissue homogenate" or the "AEF extract" of AA-, AL- and A prealbumin-laden human spleens followed by daily subcutaneous casein injections induced amyloidosis in an accelerated fashion. The resultant amyloid deposits in mice had strongly positive immunohistochemical reactions with anti-mouse AA, and negative reaction with anti-human AA or anti-human prealbumin. The results lend support to the idea that accelerated amyloid induction in the recipient mice is unlikely to be due to transfer of human amyloid substance, but rather to formation of "native" murine amyloid under the influence of a human AEF factor similar to or identical with AEF described in mouse-to mouse transfer models.

Amyloid↗

Selective lymph node dissection following hyperfractionated accelerated radio-(chemo-)therapy for advanced head and neck cancer.

BACKGROUND: 2-year results of a German multicenter randomized trial showed that accelerated chemoradiation with MMC/5-FU to 70.6 Gy is more effective than accelerated radiation to 77.6 Gy alone at equivalent levels of acute and late radiation morbidity. Frequency, histopathology and impact on local tumor control of selective lymph node dissection were analyzed. PATIENTS AND METHODS: Between February 1996 and October 2000 at Tübingen University 42 randomized patients plus 45 non-randomized patients with stage III/IV MO head and neck cancer were treated according to this protocol. After completion of hyperfractionated accelerated (chemo-)radiation a selective lymph node dissection was performed, if the primary tumor was in complete remission and clinical plus computed tomography proved residual lymph node disease. 17 of 38 patients with residual node metastasis underwent uni- or bilateral selective node dissection, the remaining patients had residual primary tumors, clinical deterioration or refused neck dissection. RESULTS: After a median follow-up of 26 months, the Kaplan-Meier analysis showed a 2-year overall survival of 49%, disease-specific survival of 64% and loco-regional tumor control of 60%, respectively. 3-year loco-regional tumor control in randomized patients was 52% compared to 58% in non-randomized patients (log rank p = 0.23). 2-year loco-regional tumor control in stage cT4cN0 was 76% compared to 57% in cT2-4 cN1-3 tumors. Subgroup analysis of patients with involved nodes revealed a 2-year loco-regional tumor control of 74% after complete remission of primary tumor and neck disease, 53% after complete remission of primary tumor and partial remission of neck disease. In patients with selective lymph node dissection loco-regional tumor control was 62%. Histopathological examination showed viable tumor in eight of 17 patients. CONCLUSIONS: Selective lymph node dissection of residual neck masses after completion of hyperfractionated accelerated radio-(chemo-)therapy is likely to contribute to loco-regional tumor control in advanced head and neck cancer.

Adult↗

Hyperglycemia attenuates erythromycin-induced acceleration of solid-phase gastric emptying in healthy subjects.

BACKGROUND: Acute hyperglycemia has been associated with delayed gastric emptying of solid foods in healthy control subjects. Erythromycin has been found to be a gastrointestinal prokinetic agent in humans. We examined whether acute steady-state hyperglycemia reduces the erythromycin-induced acceleration of gastric emptying of a solid meal after a fasted state in healthy subjects. METHODS: Twelve healthy subjects ate standard solid meals that had been radiolabeled. Gastric emptying was measured by scintigraphy during normoglycemia (5-8.9 mmol/L glucose) and hyperglycemia induced by intravenous glucose (16-19 mmol/L glucose) after administration of placebo or 200 mg of erythromycin intravenously. Emptying was measured randomly on 4 different days. RESULTS: Administration of erythromycin during normoglycemia or induced hyperglycemia compared with placebo accelerated the gastric emptying of the solid meal but did not completely normalize the delay caused by hyperglycemia versus normoglycemia (p < 0.001). In both conditions, erythromycin versus placebo significantly reduced the lag-phase duration (9.7 +/- 2.3 min and 22.0 +/- 3.9 min vs. 38.3 +/- 5.7 min and 49.5 +/- 6.0 min, respectively; p < 0.001), gastric emptying of the half meal (39.2 +/- 4.0 min and 52.0 +/- 7.1 min vs. 75.7 +/- 11.8 min and 94.0 +/- 13.4 min, respectively; p < 0.001), and the percentage of meal retained in the stomach 120 min postprandially (p < 0.001). CONCLUSION: The erythromycin-induced acceleration effect on gastric emptying was related to the plasma glucose level. Hyperglycemia might have chosen a cholinergic antagonist pathway that delayed gastric emptying of solids. Even though induced hyperglycemia inhibited gastric emptying, erythromycin accelerated the gastric emptying rate through two distinct pathways: cholinergic and noncholinergic.

Adult↗

MR imaging of the cervical spine: assessment of image quality with parallel imaging compared to non-accelerated MR measurements.

To compare the quality of cervical spine MR images obtained by parallel imaging [generalized autocalibrating partially parallel acquisition (GRAPPA)] with those of non-accelerated imaging, we conducted both phantom studies and examinations of ten volunteers at 1.5Tesla with a dedicated 12-element coil system and a head-spine-neck coil combination. Acquisitions included axial T2-weighted (T2w) images with both methods, and sagittal T2w and T1w images in vivo with the latter coil combination. Non-accelerated MRI with two averages and GRAPPA (acceleration factor 2) with two averages (GRAPPA/2AV, time reduction of approximately 50%) and four averages (GRAPPA/4AV) were compared. In the phantom, the signal-to-noise ratio of the GRAPPA/2AV was lower than that of the other two settings. In vivo, the image inhomogeneity (non-uniformity, NU) was significantly higher in T2w GRAPPA/2AV than in both other settings, and in T1w GRAPPA/2AV compared to GRAPPA/4AV. Subjectively, the delineation of anatomical structures was sufficient in all sequences. Only the spinal cord was considered to be better delineable on the non-accelerated T1w sequence compared to GRAPPA/2AV. In part, GRAPPA/4AV performed better than the other settings. The subjective image noise was lowest with GRAPPA/4AV. In cervical spine MRI, the examination time can be reduced by nearly 42% with GRAPPA, while preserving sufficient image quality.

Cervical Vertebrae↗

Accelerated endothelialization model for the study of Dacron graft healing.

Accelerated endothelialization was studied by creating a vascular tissue environment around porous Dacron grafts. Three study groups, each containing 10 dogs, were divided equally into 2- and 4-week implant periods, with 8 mm x 6 cm knitted Dacron grafts implanted in the abdominal aorta. Grafts in group 1, the control group, were implanted conventionally. In group 2 each implanted graft was completely wrapped in a resected segment of the autogenous inferior vena cava, with its intima against the wall. In group 3 the adventitial side of the vein was wrapped against the wall. The vein wrap produced accelerated endothelialization as follows: endothelial-like cell coverage scores at 2 and 4 weeks were, respectively, 78% and 98% for group 2 and 80% and 95% for group 3, compared to only 14% and 50% for group 1 (p < 0.05). The neointima, which contained smooth muscle cells, was formed as early as 2 weeks in the vein-wrapped grafts. There were no differences in the speed of healing or in healing patterns according to whether the intimal or the adventitial side of the inferior vena cava was placed against the graft. Histologic findings did not support the hypothesis that accelerated flow surface endothelialization results in direct migration of endothelial cells from the intima of the vein wrap, and there was no clear correlation between the surface endothelial-like cell coverage and microostia. To gain further insight into why accelerated healing occurs in this model, earlier observations accompanied by molecular biology analysis are needed, and vein wrap studies provide a method of comparison for this work.

Animals↗