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At least 217 records · Page 12Linked to original sources
PubMed2006

Nuclear sphingomyelin pathway in serum deprivation-induced apoptosis of embryonic hippocampal cells.

Sphingomyelin (SM) cycle has been involved in the regulation of proliferation, differentiation, and apoptosis. Increases in ceramide have been found after a larger number of apoptotic stimuli including cytokines, cytotoxic drugs, and environmental stresses. Accumulating evidence suggest that the subcellular localization of ceramide generation is a critical factor in determining the cellular behavior. Since recently enzymes involved in ceramide metabolism such as sphingomyelinase, SM synthase, sphingosine kinase and ceramidase have been found in the nucleus of hepatocyte cells, we have studied first the presence and the physicochemical characteristics of SM metabolism enzymes in nuclei isolated from embryonic hippocampal cells (cell line HN9.10e). The activities of sphingomyelinase and SM-synthase have been assayed and the ceramide production evaluated at different times after serum deprivation in these neurones cultivated in serum-deficient medium. We report that both enzymes are present in the nucleus of embryonic hippocampal cells and differ from those present in the homogenate in optimum pH. After serum deprivation, that induces a time-dependent decrease in cell viability and increase of the cell percentage in G1 phase of the cell cycle, a nuclear sphingomyelinase activation together with SM-synthase inhibition and a consequent increase of nuclear ceramide pool have been demonstrated. No similar enzyme activity modifications in homogenate have been identified. The possible role of nuclear sphingomyelinase/sphingomyelin-synthase balance in serum deprivation-induced apoptosis in the embryonic hippocampal cell is discussed.

Animals↗
PubMed2005

Optimization of a blood pool contrast agent injection protocol for MR angiography.

PURPOSE: To design an ideal first-pass profile for MR angiography (MRA) by optimizing a multiphasic injection protocol based on two experimental animal models. MATERIALS AND METHODS: An equivalent contrast-enhanced (CE) MRA injection protocol was developed with controlled injection modalities (injection rate, volume, and dose) in rabbits and pigs. P792, a blood pool contrast agent, was injected in 17 male New Zealand rabbits and five farm pigs with variable injection schemes (mono- and multiphasic). From the gadolinium (Gd) blood concentration data, a simulation of an MR acquisition was performed to evaluate the impact of such an injection protocol on MR arterial signal and to select the best injection protocol. RESULTS: An empirical relationship between the arterial peak concentration and the injection parameters was found in the rabbits and pigs, allowing precise prediction of the first-pass profile. Of the four injection scheme strategies tested (standard bolus and bi-, tri-, and multiphasic injection protocols), the multiphasic "ramp" injection protocol provided the most optimal contrast agent pharmacokinetics with a durable plateau of concentration. CONCLUSION: Ramp injection protocol provides an optimized first-pass profile for CE-MRA.

Animals↗
PubMed2006

In vivo porcine liver radiofrequency ablation with simultaneous MR temperature imaging.

PURPOSE: To demonstrate in vivo MR-guided temperature mapping during radiofrequency (RF) ablation of the liver with a commercially available RF generator modified to allow simultaneous RF treatment and MRI. MATERIALS AND METHODS: A commercial RF generator was modified using passive filtering to allow the continuous application of the treatment current during MRI studies. A total of six ablations were performed with the device in vivo in three porcine livers, and imaging was concurrently performed using one of two different temperature mapping strategies. RESULTS: MR images acquired during RF ablation demonstrated no noticeable interference from the RF ablation device, which was operated at clinically relevant power levels. Temperature maps showed areas of heating that were consistent with the dimensions of the RF ablation probe, with some asymmetry (likely depending on the orientation of the probe and heat propagation effects), and some differences in heating-spot area stability depending on the specific temperature mapping strategy used. Lesions were visualized on post-ablation imaging and sectioning. CONCLUSION: The feasibility of performing RF ablation with a modified commercial RF generator simultaneously with MRI was demonstrated. Interference-free MR temperature maps were produced with both variable respiratory motion and mechanical ventilation, and showed the extent of heating as the ablation progressed.

Animals↗
PubMed1981

The HBe antigen-antibody system and its relationship to clinical and laboratory findings in 100 chronic HBsAg carriers in Great Britain.

HBeAg or anti HBe were detected using radioimmunoassay in 93 out of 100 British patients who were chronic HBsAg carriers. HBeAg was found more commonly than anti HBe in younger patients and those with higher titres of HbsAg and abnormal liver function tests. HBeAg was present particularly in patients with chronic active hepatitis (26 out of 29) and chronic persistent hepatitis (16 out of 21). Anti HBe was found particularly in healthy carriers (19 out of 27), and patients with cirrhosis (4 out of 8) and hepatocellular carcinoma (7 out of 8). However, the system was of little help in predicting the liver biopsy appearances in the individual patient. During a mean follow-up period of 44 months, 6 of the 62 (9.7%) HBeAg positive carriers converted to anti HBe, a spontaneous seroconversion rate of 2.68% per year.

Adolescent↗
PubMed1981

Effect of CDP-choline on the biosynthesis of phospholipids in brain regions during hypoxic treatment.

Acute administration of CDP-choline (i.p. 100 mg/Kg b.w.), 10 min before the intraventricular injection of labeled precursors, [2-3H] glycerol and [1-14C]-palmitate, was able to correct the impairment caused by hypoxic treatment of lipid metabolism in some brain regions, ie, cerebral hemispheres, cerebellum, and brainstem. After CDP-choline treatment, an increase of the specific radioactivity of total lipids and of phospholipids was observed in mitochondria purified from the three above-mentioned brain regions of the hypoxic animals, while no effect on the other subcellular fractions was found. CDP-Choline had a stimulating effect particularly on the incorporation of both precursors into mitochondrial PC, PE, and polyglycerophosphatides isolated form the three brain regions examined. The results obtained show that the action of CDP-choline in restoring lipid metabolism was more pronounced in brain mitochondria, which, among subcellular fractions, were the most affected by the hypoxic treatment.

Animals↗
PubMed1982

Changes in enzyme activities of glycerolipid metabolism of guinea-pig cerebral hemispheres during experimental hypoxia.

Hypoxic treatment causes changes of some enzymatic activities involved in the glycerolipid metabolism in subcellular fractions of guinea pig cerebral hemispheres. The activity of lysophosphatidylcholine acyltransferase, choline phosphotransferase, glycerol-3-phosphate acyltransferase(s), as well as the activity of triacylglycerol lipase significantly decreased in the microsomes of cerebral hemispheres of animals intermittently exposed to hypoxic treatment for eighty hours. At the same time, a marked activation of microsomal and mitochondrial phospholipase A2 occurred. The changes of the above-mentioned enzymatic activities after the hypoxic treatment correlated well with the increase in the level of brain and blood free fatty acids. The changes also correlated with the decrease of labeled lipid precursors incorporated into lipids of the cerebral hemispheres, observed during oxygen insufficiency.

1-Acylglycerophosphocholine O-Acyltransferase↗
PubMed1983

Axonal transport of glycerophospholipids in regenerating sciatic nerve of the rat during aging.

The effect of age upon the axoplasmic transport of glycerophospholipids has been studied using as a model the regenerating sciatic nerve of young (2-month-old), young adult (6-month-old), middle-aged (16-month-old), and aged (20-month-old) male rats. The right sciatic nerve was crushed 0.5 mm down the incisura ischiadica. Four and nine days after the lesion, a mixture of [2-3H] glycerol and [methyl-14C] choline was bilaterally injected into the spinal cord, at a level of the L4-L5 vertebrae. The animals were killed 18 hr after the isotope injection. Proximal and distal portions of crushed nerve and of contralateral sham-operated ones were dissected and consecutive 5-mm segments were subjected to lipid extraction and analysis. The findings of the present study are summarized as follows: (1) The accumulation of labeled lipid material axonally transported four days after nerve injury was mainly located at the crush site in young, young adult, middle-aged, and aged rats. The accumulation of both 3H-glycerolipids and 14C-choline phospholipids in postcrush segments was markedly higher for young and young adult than for aged rats, four and nine days after crush; (2) the average rate of axonal regeneration, determined between days 4 and 9 following crush injury was 3.6 and 4.2 mm/day for 2-month-old and 6-month-old rats, respectively; it decreased to the value of 2.5 mm/day for 16-20-month-old rats.

Aging↗
PubMed1985

Synthesis of myelin proteins and ultrastructural investigations in regenerating rat sciatic nerve.

Myelin protein synthesis, as well as ultrastructural and morphometric changes in regenerating peripheral nerve, was studied. Sciatic nerves of rats were crushed unilaterally; sham-operated nerves of the contralateral side served as controls. For the in vivo experiments, rats were killed at selected periods after the nerves were crushed (30, 60, 90, and 120 days); seven days prior to killing, the animals were injected intravenously with L-[4,5-3H]leucine. For the in vitro experiments, proximal and distal segments of sciatic nerve and equivalent sham-operated nerves were labeled with 3H-amino acid mixture 90 days after axotomy. Purified myelin was isolated from nerve segments; specific radioactivity and gel electrophoretic patterns of proteins were analyzed. Cross-sectional electron microscope (EM) preparations of proximal, distal, and contralateral segments of nerves also were examined. Results showed that the incorporation of labeled amino acids into total myelin proteins was enhanced significantly in the distal segment of sciatic nerves at all of the periods of regeneration studied. The yield of myelin protein per mm distal nerve segment increased as regeneration proceeded. The remyelination of fibers early after nerve crush was weak, whereas it gradually attained the normal range 90-120 days after axotomy. Morphometric analysis of myelin sheath thickness of regenerating axons was consistent with the data obtained for myelin protein synthesis.

Animals↗
PubMed1990

Effect of low-dose lead acetate exposure on the metabolism of nucleic acids and lipids in cerebellum and hippocampus of rat during postnatal development.

Postnatal exposure (from the second day after birth to 30 days) of rat pups to low levels of lead acetate (50 mg/kg body weight/day), administered by gastric intubation, yielded a maximum blood level of 76.1 micrograms/100 ml, at day 15 of age. Cerebellar and hippocampal lead contents were 8.67 micrograms/100 mg and 11.7 micrograms/100 mg, respectively, at day 30 of age. This lead exposure has been shown to elicit little change in some biochemical parameters in cerebellum and hippocampus. At the three ages investigated (5, 15, and 30 days after birth) there were no alterations of body weight; brain, cerebellum, and hippocampus wet weight; and DNA, RNA, protein and phospholipid content, either in total tissue or in mitochondria. A similar invariance following lead exposure was observed in mitochondrial succinate dehydrogenase and cytochrome oxidase activities. After intraperitoneal administration, the incorporation of [methyl-14C]thymidine into DNA and [5,6-3H]uridine into RNA of cerebellum and hippocampus showed a significant decrease only at day 5, reaching the control value at 15 and 30 days of age. After intraperitoneal injection, [2-3H]glycerol incorporation into total lipids and phospholipids of cerebellum and hippocampus also showed no significant changes in Pb-treated pups compared to controls at all three postnatal ages. We concluded that subclinical lead administration exerts its effect by slowing cell proliferation in the very early growth phase of the brain. It is likely that a metabolic compensative response to subtoxic effect of lead acetate may be brought about in cerebellum and hippocampus during critical phases of nervous system development between days 15 and 30.

Animals↗
PubMed1991

Evidence of proteoglycan/proteoglycan interactions within aggregates.

Nonaggregated proteoglycan monomers, digested fragments of the monomers, as well as link proteins have been shown to self-associate. These associations have not been shown to occur on the aggregate. However, previous reports, using the Kleinschmidt technique of monolayer electron microscopy, have noted proteoglycan subunits on the aggregate that appear to interact, either as branched proteoglycans or as proteoglycan subunits that appear to share the same attachment site on the hyaluronic acid chain. Branching and shared attachments were noted in all aggregates analyzed in this study. Increasing the average space between proteoglycan subunits on the reconstituted aggregate resulted in a significant decrease in branched proteoglycans, indicating either a weak association occurring on the aggregate, or an artifact created by a three-dimensional structure being reduced to a two-dimensional monolayer image. The shared attachments were independent of both the presence of link proteins and changes in spacing between proteoglycans, suggesting a proteoglycan-proteoglycan interaction occurring before aggregation. The interactions were not influenced by proteoglycan concentration at the time of aggregation. Link proteins, however, did increase the number of proteoglycans on the aggregate that could be cross-linked with a bifunctional reagent, suggesting that link proteins facilitate proteoglycan-proteoglycan interactions.

Animals↗
PubMed2002

Photodynamic therapy of vulvar and vaginal condyloma and intraepithelial neoplasia using topically applied 5-aminolevulinic acid.

BACKGROUND AND OBJECTIVES: To determine the feasibility of photodynamic therapy (PDT) of vulvar and vaginal condyloma and intraepithelial neoplasia (VIN, VAIN) and to compare PDT results with conventional treatments. STUDY DESIGN/MATERIALS AND METHODS: Thirty-eight patients with vulvar or vaginal intraepithelial neoplasia (VIN) grade II/III (n = 22) or condyloma (n = 16) had 10% 5-aminolevulinic acid (ALA)-gel applied topically. After 2-4 hours, 80-125 J/cm(2) laser light at a wavelength of 635 nm was applied. PDT was compared to conventional treatments for condyloma (CO(2) laser evaporation) and for VIN III (laser evaporation, surgical excision). RESULTS: The complete clearance rate for condyloma treated by PDT was 66% and the rate for IN was 57% (as determined by biopsy). Of the neoplasia patients, none with hyperkeratotic VIN (n = 4) responded, and only one of four with increased pigmentation cleared. No scarring occurred, and postoperative discomfort lasted 4.9 +/- 3.4 days. Reduced disease-free survival (DFS) was associated with multifocal VIN (P = 0.02, OR 2.17, 95% CI 1.15-4.08), but DFS did not vary with treatment mode. CONCLUSIONS: Although PDT is not equally efficacious for all subgroups, PDT for condyloma and intraepithelial neoplasia appears to be as effective as conventional treatments, but with shorter healing time and excellent cosmetic results.

Administration, Topical↗
PubMed2003

Photodynamic endometrial ablation: morphological study.

BACKGROUND AND OBJECTIVES: Endometriumablation provides an alternative treatment modality to hysterectomy for dysfunctional uterine bleeding (DUB). Its feasibility was demonstrated in animal studies. The purpose of this study was the evaluation of histological changes following photodynamic endometrial ablation in patients. STUDY DESIGN/MATERIALS AND METHODS: 5-Aminolevulinic acid (ALA) was topically applied in three premenopausal and one postmenopausal patient 4-6 hours before laser-illumination. ALA-concentration: 100-400 g/ml, NaOH-titration (pH 5.5). Volume applied, 1.5-2.0 ml; intrauterine balloon-lightdiffuser; wavelength, 635 nm; lightdose, 160 J/cm(2). Hysterectomy was performed 3-152 days after photodynamic ablation. Histological examination was carried out on endometrium sections stained with hematoxylin and eosin (H&E). RESULTS: Necrosis including the full thickness of the endometrium was found 3 days after photodynamic endometrial ablation. Specimens collected after 35 and 152 days did not exhibit fibrosis or adhesions. Foci of preserved endometrium were detected in all patients. CONCLUSIONS: Photodynamic endometrial ablation is selective and does not cause endometrial fibrosis or adhesions.

Adult↗
PubMed2003

Role of p53 and ATM in photodynamic therapy-induced apoptosis.

BACKGROUND AND OBJECTIVES: Photodynamic therapy (PDT) induces cell death through a laser light-activated photosensitizer and is a treatment option for tumors resistant to radio- and chemo-therapy. STUDY DESIGN/MATERIALS AND METHODS: We investigated whether m-THPC-PDT induces cell death by necrosis and/or apoptosis, and whether these responses are modulated by p53 and/or ATM, two cancer-associated genes. Sensitivity of atm(+/+)p53(+/+), atm(+/+)p53(-/-), and atm(-/-)p53(-/-) mouse embryonic fibroblasts to m-THPC-PDT performed at a wavelength of 652 nm was determined by the MTT assay, trypan blue-exclusion, and the TUNEL and caspase3-cleavage apoptosis assays. c-Abl protein level was determined by immunoblotting. RESULTS: m-THPC-PDT rapidly induced cell death in a substantial fraction of cells by p53- and Ataxia telangiectasia mutated (ATM)-independent non-apoptotic processes. However, in the subset of apoptotic cells, apoptosis was reduced by loss of p53 and was even more reduced by the additional loss of ATM. Apoptosis correlated inversely with c-Abl level. CONCLUSIONS: p53 and ATM are not required for necrosis, but may be required for PDT-mediated apoptosis.

Animals↗
PubMed2004

Photodynamic endometrial ablation for the treatment of dysfunctional uterine bleeding: a preliminary report.

BACKGROUND AND OBJECTIVES: To evaluate feasibility and functional effects of photodynamic endometrial ablation (PEA) in patients. STUDY DESIGN/PATIENTS AND METHODS: A total of 15 PEAs has been performed in 11 patients using topically applied 5-aminolevulinic acid (ALA) solutions and a balloon-light diffuser (160 J/cm(2), 635 nm). Uterine bleeding intensity has been determined on a daily basis 3 months prior to and up to 6 months after endometrial ablation using an analogous scale scoring from 1 (spotting) to 6 U (severe bleeding). Statistical analysis by unpaired Student's t-test. RESULTS: The mean number of bleeding units per cycle (n = 44) was 35.7 prior to PEA. The decrease in bleeding units was significant for the months 1-3 (24.4 U per cycle; P = 0.03), but not for the months 4-6 (25.9 U; P = 0.11) following PEA. CONCLUSIONS: PEA is feasible and provides a significant short-term reduction of uterine bleeding.

Adult↗
PubMed2004

Waiting for a liver--hidden costs of the organ shortage.

Discussion about the economics of end-stage liver disease has typically focused on the high cost of liver transplantation, but the management of complications in patients waiting for an organ can also be very expensive. Our research considered the hypothesis that an increase in the number of organ grafts would decrease health care costs in patients with liver disease by eliminating the cost of waiting for an organ. We examined treatment costs for a consecutive series of liver transplant candidates listed at our institution between November 1, 1996 and December 31, 1997. Costs were estimated for inpatient stays, outpatient visits, and posttransplant medications for 2 1/2 years from the date of listing. Of the 58 study patients, 26 (45%) received transplants, 7 of whom died within 2 1/2 years. A total of 11 patients (19%) died while waiting for an organ, and another 21 patients (36%) were still waiting after 2 1/2 years. Pretransplantation costs accounted for 41% of the total cost. Transplanting all 58 candidates without delay through a hypothetical increase in the supply of organs to meet demand would have more than doubled the number of transplantations while increasing costs in this cohort by only 37% (from 123,000 dollars to 169,000 dollars per patient). In conclusion, although an adequate supply of donor organs would not decrease total health care spending for patients with end-stage liver disease, so much money is currently spent on medical management during the waiting period that the savings achieved by transplanting all candidates without delay would offset a large portion of the cost of the additional transplants.

Adolescent↗