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PubMed2004

Neurogenesis response to hypoxia-induced cell death: map kinase signal transduction mechanisms.

Hypoxic stress induces apoptosis of hippocampal CA1 neurons while selectively sparing those in CA2-3. Proliferation and differentiation of local stem cells may potentially replace lost neurons. We examined MAP kinase signaling regulation of these dual responses. Rat organotypic hippocampal cultures were exposed to hypoxia for up to 6 h followed by reoxygenation. JNKs and ERKs were maximally activated by 4 h, returning approximately to basal levels by 6 h. Apoptosis of CA1 neurons was maximal by 6-h hypoxia, although JNK activation had returned to basal levels. A neuroprotective protein, JNK-interacting protein 1 (JIP1), an inhibitor of JNK-mediated apoptosis, was reduced by 6-h hypoxia and markedly decreased by 24-h reoxygenation in CA1 neurons as was DENN/MADD, which also modulates JNK-mediated cell death. A second peak of ERK1 activation occurred at 24-h reoxygenation and declined to control levels by 48 h. Stem cells were detected by antinestin and cell proliferation confirmed with anti-PCNA immunohistochemistry and BrdU incorporation. With U0126, an inhibitor of ERK activation, BrdU labeling was strikingly reduced implicating ERKs in the proliferation response. Antidoublecortin (DCX), which detects neural progenitor cells, colabeled a subset of BrdU-positive cells that extended from the dentate granule neurons into CA1. Astrocytes were colabeled with BrdU. Thus, hypoxia concurrently triggered both JNK and ERK signaling, and with reoxygenation, ERK1 activation and stem cell proliferation followed by neuronal progenitor cell differentiation and targeted migration to the site of pyramidal neuronal loss.

Animals↗
PubMed1993

Macropinosome maturation and fusion with tubular lysosomes in macrophages.

Macropinosomes formed by addition of recombinant macrophage colony-stimulating factor (rM-CSF) to mouse macrophages migrate centripetally and shrink, remaining detectable by phase microscopy for up to 15 min. This longevity allowed us to study how macropinosomes age. Macropinosomes were pulse labeled for 1 min with fixable fluorescein dextran (FDx10f), a probe for fluid phase pinocytosis, and chased for various times. To quantify changes in their antigenic profile, pulse-labeled macropinosomes of different ages were fixed and stained for immunofluorescence with a panel of antibodies specific for the transferrin receptor (TfR), the late endosome-specific, GTP-binding protein rab 7 or lysosomal glycoprotein A (lgp-A), and the percentage of antibody positive, FDx10f-labeled macropinosomes was scored. Some newly formed macropinosomes were positive for TfR, but few were rab 7 or lgp-A-positive. With intermediate chase times (2-4 min), staining for rab 7 and lgp-A increased to > 60%, while TfR staining declined. After a long chase (9-12 min), rab 7 staining returned to low levels while lgp-A staining remained at a high level. Thus, macropinosomes matured by progressive acquisition and loss of characteristic endocytic vesicle markers. However, unlike a maturation process, their merger with the tubular lysosomal compartment more nearly resembled the incorporation of a transient vesicle into a pre-existing, stable compartment. Shortly after their formation, FDx10f-labeled macropinosomes contacted and merged with Texas red dextran (TRDx10)-labeled tubular lysosomes. This occurred in two steps: macropinosomes acquired lgp-A first, and then several minutes later the cation-independent mannose-6-phosphate receptor (CI-MPR) and markers of lysosomal content (cathepsin L or pre-loaded TRDx10), all apparently derived from tubular lysosomes. Thus, macropinosome progress through macrophages showed features of both the maturation and vesicle shuttle models of endocytosis, beginning with a maturation process and ending by merger into a stable, resident lysosomal compartment.

Animals↗
PubMed1992

Equine haptoglobin: isolation, characterization, and the effects of ageing, delivery and inflammation on its serum concentration.

Haptoglobin (Hp) was isolated from equine serum by ammonium sulphate precipitation, anion-exchange chromatography and gel filtration. Equine Hp which migrated to the alpha 2-globulin region in electrophoresis, contained 2 fractions with molecular weights (NW) of 108,000 and 105,000, and each fraction consisting of 2 subunits. Quantitative measurement of Hp in equine serum was performed by the single radial immunodiffusion method using anti-equine Hp serum. In clinically normal horses, the highest concentration of serum Hp was found in newborn foals and a high value was maintained until 12 months of age. The concentration then decreased with age. Normal Hp values were 5.25 +/- 2.36 mg/ml in foals (less than or equal to 12 months old), 2.19 +/- 1.54 mg/ml in adult horses (greater than or equal to 18 months old) and 3.62 +/- 0.81 mg/ml in all horses. Serum Hp concentration in mares during the perinatal period in comparison with the normal adult female was high for 4 months pre-partum, a passing increase at delivery, and then decreased at 2 weeks post-partum returning to normal within 1 month of delivery. In horses with experimentally-induced inflammation, serum Hp concentration began to increase immediately after treatment and reached the highest value, 1.5 to 9 times higher than those of pre-treatment at 2 to 5 days, then decreased within 4 weeks. It was also elevated in most cases of horses with clinically inflammatory signs.

Aging↗
PubMed1995

Proliferation and hypertrophy of liver cells surrounding islet grafts in diabetic recipient rats.

The liver offers an adequate site for the metabolic function of pancreatic islet implants. Little is known about the effects of the islet grafts on the host organ. This study examines liver tissue of normal or streptozotocin (STZ)-diabetic rats at different intervals following intraportal injection of syngeneic islets. Implantation of 800-islet-grafts, containing 0.9 million beta cells, normalized overt diabetes within 14 days. This period of metabolic normalization was characterized by a specific sequence of alterations in the implant area. During the first days after transplantation, islet cells migrated into the liver lobules, whereby tight hepatocyte-islet cell contacts were established. Hepatocytes surrounding grafts showed massive lipid accumulation and hypertrophy (cellular profile area 603 +/- 72 microns 2 in diabetic islet recipients vs. 382 +/- 42 microns 2 in diabetic controls; P < .005). The implant area also contained significantly more liver cells in proliferative activity than hepatic tissue in normal controls (bromodeoxyuridine labeling index of peri-islet hepatocytes 6.2%, 4.6%, and 0.9% on posttransplantation days 2, 4, and 14, respectively, compared with 0.02% in normal controls). The cellular hypertrophy and hyperplasia explain the sudden increase in liver weight of diabetic recipients (from 8.0 +/- 1.1 g to 13.8 +/- 2.2 g on posttransplantation day 2; P < .005). Both alterations can be attributed to the massive local discharge of insulin in an insulin-deficient organ containing an excess of extra-cellular nutrients. Progressive revascularization of the implant sites and overall metabolic normalization are thought to explain the return of a normal liver histology by the third week after transplantation. In conclusion, intraportal islet grafts exert profound effects on the liver of diabetic rat recipients. The morphological features of the implant sites may serve as markers for the function of the islet grafts as well as for the adaptive capacity of the recipient liver.

Animals↗
PubMed1995

'Firm' versus 'soft' double pigtail ureteric stents: a randomised blind comparative trial.

It is generally considered that 'firm' double pigtail ureteric catheters, while easier to insert and less prone to migration, may cause more patient discomfort than the 'softer' variety of stent. Objective support for these perceptions is however lacking. The aim of this study was to compare firm and soft stents regarding their ease of insertion, positional stability, biocompatibility and patient tolerance. 155 patients were randomised to receive 'firm' (polyurethane, n = 78) or 'soft' (Sof-Flex, n = 77) stents. Ease and mode of insertion was recorded at time of initial placement. Positional stability, degree of bladder inflammation, stent encrustation and patient tolerance were recorded at the time of removal. Patient tolerance was assessed by symptom score in double-blind fashion. Results showed no significant difference in ease of insertion, positional stability, degree of bladder inflammation or stent encrustation between the two groups. There was a significantly higher incidence of dysuria, renal and suprapubic pain in the firm stent group. There was no significant difference in the incidence of urgency, frequency, nocturia or haematuria. Normal activity and return to work were reported in 67 and 45% of patients with soft and firm stents, respectively. The data indicates that patient tolerance appears to be related to the softness of the stent material.

Biocompatible Materials↗
PubMed2002

LEX032, a novel recombinant serpin, protects the brain after transient focal ischemia.

This investigation examined the effectiveness of a serine protease inhibitor (LEX032) when used as a cerebral protective agent after ischemia. Focal cerebral ischemia in the rat was produced by intravascular occlusion of the middle cerebral artery for a period of 30 min. Just prior to thread withdrawal (i.e., reperfusion), rats received an iv bolus administration of either vehicle or LEX032 (50 mg/kg), an optimal dose chosen based on previous studies. Somatosensory evoked potentials (SSEP's) were monitored prior to, during, and for a period of 60 min after removal of occlusion. The animals were allowed to recover for 24 h after the ischemic insult. Cortical activity in the occluded region, as assessed by SSEPs, returned much sooner in the LEX032-treated animals (10 +/- 6 min) than in the untreated animals (40 +/- 25 min). On a scale ranging from 0 to 3, with three indicating the most severely injured, the LEX032 animals had a significantly better neurologic score (1.0 +/- 0.9) than the untreated animals (2.3 +/- 0.5) 24 h after ischemia. The improved neurobehavior was related to a 55% reduction in brain injury as assessed by TTC staining. LEX032-treated animals had significantly (P < 0.01) smaller infarcts (115 +/- 40 mm3) compared to vehicle-treated animals (263 +/- 13 mm3). In a separate group of animals (n = 6/group), leukocyte infiltration, as evaluated by tissue myeloperoxidase activity (MPO U/g tissue wt), was also significantly (P < 0.05) lower in the LEX032-treated animals (1.4 +/- 0.3) compared to vehicle-treated animals (3.6 +/- 0.7). This data demonstrates that LEX032 reduces brain injury and suggests that serine protease inhibitors may reduce ischemia/reperfusion injury by decreasing leukocyte activation and migration.

Animals↗
PubMedDate not supplied

Endografting of the thoracic aorta:.

BACKGROUND: Thoracic aortic dissections, ruptures, fistulae, and aneurysms pose a unique surgical challenge. Traditional repair of thoracic aortic aneurysms involves thoracotomy with graft interposition. Despite advances in perioperative care and both total and partial cardiopulmonary bypass, conventional surgery carries a significant morbidity and mortality. Principal complications include bleeding, paraplegia, stroke, cardiac events, pulmonary insufficiency, and renal failure. Recent enthusiasm for innovative endovascular therapies to treat aortic disease has spurred many centers to investigate endoluminal grafting of the thoracic aorta. Early reports on endovascular repair using custom made "first generation devices" demonstrated the technique to be feasible with a mortality and morbidity comparable to open repair. METHODS AND RESULTS: From February 2000 to February 2001, endovascular stent graft repair of the thoracic aorta was performed in 46 patients (mean age 70; 29 male and 17 female) using the Gore Excluder. Twenty-three patients (50%) had atherosclerotic aneurysms, fourteen patients (30%) had dissections, three patients (7%) had aortobronochial fistulas, three patients (7%) had pseudoaneurysms, two patients (4%) had traumatic ruptures, and one patient (2%) had a ruptured aortic ulcer. Patient characteristics, procedural variables, outcomes, and complications were recorded. All patients were followed with chest CT scans at 1, 3, 6, and 12 months. Mean follow up was 9 months ranging from 1 to 15 months. All procedures were technically successful. There were no conversions. Average duration of the procedure was 120 minutes. Average length of stay was 6 days, but most patients left the hospital within 4 days (64%) after endoluminal grafting. Overall morbidity was 23%. Two patients (4%) had endoleaks that required a second procedure for successful repair. Two patients (4%) died in the immediate postoperative period. There were no cases of paraplegia. At follow-up, one patient had an endoleak found the day after the procedure and another patient had an endoleak 6 moths post procedure. Both were treated successfully with additional stent grafts. There were no cases of migration. One patient died of a myocardial infarction 6 months after graft placement. The Gore Excluder device was voluntarily recalled on February 26, 2001. Therefore, from June 2000 to January 2001, 37 patients underwent endovascular stent graft repair of the thoracic aorta for various disease entities using our customized thoracic graft (Endomed). Twenty-seven patients (73%) had aneurysms, six (16%) had dissections, two (5%) had pseudoaneurysms, one (2%) had a traumatic transection, and one patient (2%) had an embolizing ulcer. Patients were followed with CT scans at 1, 3, 6, and 12 months. All procedures were technically successful. There were no conversions. The average age was 68 years.(17-87). And the male and female ratio was 24/13. One patient died in the operating room from iliac rupture and one died from embolization/stroke in the immediate postoperative period. Two patients died within 30 days from comorbid factors. The total 30-day mortality was 10%. Two patients had endoleaks. One returned to the operating room and needed an additional cuff. The other had a small leak in a proximal dissection that is being followed. There were no cases of paraplegia. CONCLUSION: Thoracic endoluminal grafting is a safe and feasible alternative to open graft repair and can be performed successfully with good results. Early data suggest that an endoluminal approach to these disease entities maybe favorable to open resection and graft replacement. Technical details of Endoluminal stent grafting of the thoracic aorta for different disease entities have been discussed at length.

Adult↗
PubMed1957

The metamorphosis of visual systems in the sea lamprey.

The life cycle of the sea lamprey, Petromyzon marinus, includes two metamorphoses. At the end of a period spent as a blind larva, buried in the mud of streams, a first metamorphosis prepares it to migrate downstream to the sea or a lake for its growth phase. Then, following a second metamorphosis, it migrates upstream as a sexually mature adult to spawn and die. The downstream migrants have a visual system based upon rhodopsin and vitamin A(1), whereas that of the upstream migrants is based upon porphyropsin and vitamin A(2). The livers contain vitamin A(1) at all stages. The sea lamprey therefore exhibits a metamorphosis of visual systems, like those observed earlier among amphibia. The presence of porphyropsin in this member of the most primitive living group of vertebrates, as in fishes and amphibia, supports the notion that porphyropsin may have been the primitive vertebrate visual pigment. Its association with fresh water existence throughout this range of organisms also is consistent with the view that the vertebrate stock originated in fresh water. The observation that in the life cycle of the lamprey rhodopsin precedes porphyropsin is not at variance with the idea that porphyropsin is the more primitive pigment, since this change is part of the second metamorphosis, marking the return to the original environment. The observation that in lampreys, fishes, and amphibia, porphyropsin maintains the same general association with fresh water, and rhodopsin with marine and terrestrial habit, suggests that a single genetic mechanism may govern this association throughout this wide span of organisms.

Animals↗
PubMed1999

Population substructure and isolation by distance in three continental regions.

Isolation by distance and divergence from a shared population history are two sources of population substructure. Isolation by distance erases population history as populations approach migration-drift equilibrium, while diverging populations descended from a single ancestral population will accumulate genetic differences with time. Here I investigate how much of the worldwide genetic diversity from Jorde et al.'s ([1997] Proc. Natl. Acad. Sci. USA 94:3100-3103) 60 tetranucleotide short tandem repeat (STR) data can be explained by isolation by distance. I use Slatkin's measure of population substructure, R(ST), principal components analyses, and Mantel tests to investigate the pattern of genetic diversity at both the intercontinental and intracontinental levels. Geographic distance accounts for almost 60% of world-wide interpopulation genetic relationships. Within continents, the correlations are less, although not significantly so because of wide confidence intervals. These results suggest that populations have not reached migration-drift equilibrium and that there is information in STR data to reconstruct population history. The level of population substructure worldwide is consistent with previous observations, but at the intracontinental level substructure is less. When one examines diversity against distance from the centroid, one sees excess heterozygosity in Africa, a pattern also noted by Stoneking et al. ([1998] Genome Research 7:1061-1071). A larger effective population size in Africa could explain the excess diversity. Greater gene flow in Africa is an unlikely explanation because the African R(ST) value is slightly larger than the Asian and European R(ST)s, pointing to less gene flow and greater substructure among African populations. Furthermore, there are differences in patterns between heterozygosity and allele size variance. Heterozygosity has a higher correlation with distance from the centroid than does allele size variance, and this may reflect demographic history. Kimmel et al. ([1998] Genetics 148:1921-1930) have shown that after a population expansion heterozygosity returns to equilibrium more quickly than does allele size variance. The contrasting patterns between heterozygosity and allele size variance may reflect different times after an expansion. However, simulations and further work need to be done to more thoroughly investigate the possibility that these data reflect population expansions.

Alleles↗
PubMed1978

The origin, kinetics, and characteristics of the Kupffer cells in the normal steady state.

Enzymatic digestion with pronase and DNAase was used to isolate Kupffer cells from mouse liver. The characteristics of these cells were found to be similar to those of peritoneal macrophages, except that in the initial suspension the percentage of Kupffer cells with Fc receptors was low, C receptors were absent and the ingestion of opsenized bacteria was very poor, because of the effect of pronase on the cell membrane. After 24 h incubation in vitro all these characteristics return. The in vitro and 1 h-pulse [(3)H]thymidine labeling of the Kupffer cells is low (0.8 and 1 percent, respectively) indicating that in essence these cells do not divide. It was also shown that the small percentage of in vitro labeled Kupffer cells was recently derived from the circulation. After an intravenous injection of zymosan the in vitro labeling index of the Kupffer cells increased 16-fold, but it was proven that these dividing cells were immature mononuclear phagocytes very recently recruited from the bone marrow. The labeling of Kupffer cells aider one or four injections of [(3)H]thymidine reached a peak of 10.4 percent at 48 h or 24.1 percent at 60 h, respectively, indicating that these cells are derived from labeled monocytes. Further evidence for this conclusion was obtained by the absence of an increase of labeled Kupffer cells during treatment with hydrocortisone, which causes a monocytopenia during which no circulating monocytes are available to migrate to the tissues. Labeling studies in animals X-irradiated with hind-limb shielding gave a Kupffer cell labeling index of 5-10 percent of the normal values, which confirms their bone marrow origin. A quantitative study on the production of labeled monocytes in the bone marrow and their transit through the circulation showed that in the normal steady state at least 56.4 percent of the monocytes leaving the circulation become Kupffer cells. Considering the Kupffer cells as kinetically homogeneous this gives a mean turnover time of the total population of Kupffer cells of 21 days.

Animals↗
PubMed1993

Malaria and mobility in Thailand.

This paper examines the relationship between malaria transmission and migration in three northern Thai villages. Data and observations indicate that land-poor families forced into swidden farming have greater contact with the primary vectors in Thailand--which breed in small pools in forested areas and shady clearings on hilly scrub terrain. Once infected, migrants from an endemic locus can introduce the parasite into an area with no transmission but potent vectors, thus becoming the cause of explosive epidemics; equally, non-immunes carrying out agricultural activities in or across forest and border areas can themselves be subject to seasonal morbidity. In addition to agricultural activities on clearings near forested areas, clandestine forest activities and cross border traffic contributes to the high prevalence of malaria in Thai border villages. Illegal economic activities--logging, poaching, cattle and goods smuggling--interferes with vector suppression campaigns and prompt detection of infected cases, and ultimately increases human infection not only within the mobile population, but also within the passive population of villages to which the migrants return periodically. Control measures therefore need to take into account the economic pressures which determine a high degree of mobility, the ethnic diversity of the groups which depend on fringe activities for their economic welfare, and the difficult geography of the areas in which they live. As long as economic circumstances forcing human-vector contact receives inadequate attention, better alternatives to current vector control campaigns (which are not effective amongst migrants) are not tried and malaria transmission continues.

Agriculture↗
PubMed1985

Requirements for restitution of the surface epithelium of frog stomach after mucosal injury.

In frog fundic mucosae mounted in Ussing chambers, exposure to luminal 1 M NaCl for 10 min caused a sharp immediate decrease in potential difference, resistance, short circuit current, and acid secretion, but within 4-6 h these readings had returned toward control values. After initial severe destruction of surface epithelial cells, gradual morphologic restitution occurred within 4-6 h. A Ca2+-free nutrient solution and 4 mM ethylenediaminetetraacetic acid administered after injury prevented both physiologic and morphologic restitution. A Ca2+-free nutrient solution administered alone after injury prevented physiologic recovery, but although narrow gaps and lack of tight junctions were found between some cells, there was near-complete epithelial cell coverage. The addition of 2 mM Ca2+ to these tissues 3 h after injury effected rapid recovery of electrophysiologic parameters and a complete closure of the intercellular spaces. Cytochalasin B (3 X 10(-3) M nutrient) prevented physiologic recovery and mucosal restitution. Neither cycloheximide nor colchicine had any effect on the normal process of restitution. Autoradiography of [3H]thymidine incorporation showed no increase in labeling within 4 h of hyperosmolar injury. We conclude that adequate Ca2+ is required for complete restitution of gastric mucosa after hyperosmolar injury, and that restitution occurs by migration of persisting viable gastric pit cells.

Animals↗
PubMed2005

Pivotal role of endogenous tachykinins and the NK1 receptor in mediating leukocyte accumulation, in the absence of oedema formation, in response to TNFalpha in the cutaneous microvasculature.

Tachykinins including substance P (SP) are well known to play a role in influencing oedema formation and leukocyte accumulation during tissue insult and inflammation. Cutaneous inflammatory models to characterize a TNFalpha-dependent mechanism where endogenous SP act via the NK1 receptor to promote leukocyte accumulation in the absence of oedema formation were used. We found that TNFalpha induced dose-dependent leukocyte accumulation at 4 h, which returned towards basal levels at 8 h in NK1+/+ mice. This response was absent in both the NK1+/+ mice treated with an NK1 receptor antagonist and NK1-/- mice. At the highest dose IL-6 induced a significant accumulation in NK1+/+ and NK1-/- mice but IL-12 was ineffective. SP induced skin oedema but none of the cytokines did. Either co-injection of SP with low dose of TNFalpha (0.3 pmol/site) or SP previously injected (30 min) to TNFalpha evoked a significant increase in MPO activity when compared with that induced by the cytokine alone. In contrast, SP injected i.d. 3.5 h after TNFalpha failed to produce additive response. Control, but not capsaicin-pretreated rats (to deplete sensory nerves), exhibited a marked increase in MPO activity in response to TNFalpha. Histological analysis showed that TNFalpha caused tissue infiltrate of leukocytes in NK1+/+ mice, whilst leukocytes accumulated at intravascular sites in NK1-/- mice, but did not appear to emigrate, suggesting a defect in trans-endothelial migration. Interestingly, monocytes in addition to neutrophils accumulated 4 h post TNFalpha injection. In conclusion, the NK1 receptor plays a functional role in mediating leukocyte accumulation independently of the historically important NK1 mediated oedema formation. It seems that TNFalpha directly activates sensory nerve in addition to its chemoattractant activity. The NK1 receptor agonist influences the accumulation of monocytes in addition to that of PMN by 4 h, thus revealing an important influence of the NK1 receptor on TNFalpha mediated events in mouse skin.

Albumins↗
PubMed2003

Dental caries in South Pacific populations: a review.

Dental caries (tooth decay) was uncommon in Pacific Island communities before European trading and migration expanded into the Region. The etiology of this oral microbial disease is a consequence of changed diets, food preparation and lifestyle. In particular, the easy availability of a high level of frequent dietary supplementation with refined sucrose (sugar) and carbohydrates is the key factor in the etiology of tooth decay. While tooth decay initially developed as a health problem in the more accessible Pacific islands over a century ago, it has spread increasingly as trading, travel and cash economies have developed to include even the more geographically remote communities. In this review selected epidemiological data are presented to show the magnitude, variation and secular changes in the prevalence of tooth decay in different communities. Tooth decay in conjunction with the historically endemic adult gum diseases poses a major public health problem in terms of pain, premature loss of teeth and the need for oral rehabilitation. Implementation and monitoring of caries control programs is a priority need in most communities. It is impractical to consider a return to indigenous diets and lifestyles as a strategy for caries prevention. Instead promotion of proven modern community preventive programmes, notably appropriate use of fluorides, 'fissure sealants' together with control of excessive consumption of diets rich in refined sugar is required if a significant increase in the levels of tooth decay is to be avoided.

Cooking↗
PubMed1988

[Foreign immigration in contemporary France].

Immigration trends in France since 1946 are first reviewed. The author notes that immigration peaked in the period prior to the oil crisis of the early 1970s. Tighter immigration controls adopted in 1974 have affected the characteristics of the immigrant population concerning intention to return to country of origin, length of stay, and reuniting of family members. Consideration is also given to immigrant characteristics by nationality, unemployment among foreigners, and fertility differentials. "The second part of the article examines the new terms of the immigration problem (the alternative between the foreigners' integration and the maintainance of the immigrant statute) and the programs to be proposed." (SUMMARY IN ENG)

Acculturation↗
PubMed1998

Effect of aging on neointima formation and hyaluronan, hyaluronidase and hyaluronectin production in injured rat aorta.

Few studies have examined the effect of aging on arterial wall response to injury, and the results are discordant. Moreover, the effect of aging on hyaluronan synthesis in injured vessels is unknown. The aim of this present study was to determine the effect of aging on neointima formation and hyaluronan (HA), hyaluronidase and hyaluronectin production in injured rat aorta. Aorta was analysed in sham-operated rats (group D0) and 14 (D14) and 28 (D28) days after injury using biochemical and immunohistochemical techniques. Uninjured aorta of old rats was more thickened than that of young rats; it showed a decreased number of arterial smooth muscle cells (ASMC) and was characterized by HA accumulation in the intima and increased hyaluronidase activity. Intima-media wet weight was significantly increased in young rats at D14 and D28 but remained unchanged in old rats. DNA content was significantly enhanced at D14 in both young and old rats. DNA decreased slightly in young rats at D28 but significantly in old rats to return to control level. HA content and hyaluronidase activity in the intima-media were markedly increased in young rats at D14 (+148% and +116% respectively) but slightly in old rats (+23% and +15% respectively). Both HA and hyaluronidase activity continued to increase at D28, but remained more produced in young rats. The immunohistochemical analysis showed the formation of a thickened neointima in young rats, which was associated with strong expression of HA and HN. Neointima of old rats was reduced; it also showed strong expression of HA and HN but their distributions were different from those observed in neointima of young rats. In conclusion, aorta of old rats showed an increased amount of HA in the intima and elevated activity of hyaluronidase. Injury induced formation of a significant neointima in young rats but not in old rats. This was correlated with more HA and hyaluronidase production in injured aorta of young rats. As HA is considered to increase extracellular matrix space and to promote ASMC proliferation and migration, our findings suggest that HA may be implicated in intima thickening with age and after injury.

Aging↗
PubMedDate not supplied

Bilateral implantation of low-profile interbody fusion cages: subsidence, lordosis, and fusion analysis.

BACKGROUND CONTEXT: The use of interbody fusion cages as a treatment for degenerative disc disease has become widespread. Low-profile cages have been developed to allow a closer fit when implanting bilateral cages in patients with smaller vertebral bodies. Some surgeons feel the open design also allows better bone contact and visualization. This is particularly true when two low-profile cages are used adjacent to one another. Because of the open design of low-profile interbody fusion cages, there has been concern regarding such issues as subsidence, lordosis and fusion rates. PURPOSE: This retrospective review of paired bilateral reduced profile interbody fusion cages was completed to assess changes in subsidence, lordosis and fusion. As a secondary goal, patient outcomes were measured to determine overall health since surgery and the patient's satisfaction with the spine surgery, in an attempt to assess the effect of the outcome variables cited supra. STUDY DESIGN: This was a retrospective evaluation of patients who underwent anterior lumbar interbody fusion with low-profile interbody fusion cages. PATIENT SAMPLE: Seventy-one consecutive patients who underwent bilateral implantation of low-profile interbody fusion cages were evaluated. OUTCOME MEASURES: A patient self-evaluation, which included a Short Form (SF)-36 and questions regarding patient satisfaction were administered to patients who were at least 1 year postoperative. Subsidence and lordosis measurements were completed. Fusion was assessed by the operating surgeon. METHODS: Low-profile interbody fusion cages (BAK/Proximity, Centerpulse Spine-Tech, Inc., Minneapolis, MN) were implanted bilaterally in at least one level from L3-L4 to L5-S1. Most patients had degenerative disc disease with leg and back pain that was not responsive to conservative treatment and demonstrated segmental instability or collapse. A small percentage of patients had either a degenerative spondylolisthesis (7.0%) or an isthmic spondylolisthesis (4.2%). Autograft harvested from the iliac crest was used in all cases. Demographic, surgical and follow-up data were retrospectively collected from patient charts. A clinical outcome questionnaire that included an SF-36 as well as questions regarding patient satisfaction was either mailed to each patient who was at least 1 year postsurgery or given to patients to complete at their 1-year visit. Patients were routinely followed radiographically before surgery, immediately after surgery and at 3, 6, 12 and 24 months after surgery. Fusion was assessed by the operating surgeon using lateral radiographs often in conjunction with a thin-slice computed tomography (CT) scan. Criteria for a successful fusion were lack of motion, anterior bridging bone and lack of lucencies on flexion/extension X-rays and/or contiguous bone through the cage using a thin-cut sagittal CT scan. Lateral X-rays on each patient were also measured for subsidence and lordosis changes. RESULTS: A total of 71 patients (45 men, 26 women) with a mean age of 43.4 years (range, 25 to 74) were evaluated. Thirty-six percent of the patients were smokers, and 96% were worker's compensation patients. Thirty-two percent of the patients had previous lumbar surgery. A total of 100 operative levels were evaluated. There were 45 one-level, 23 two-level and three three-level cases. Forty-nine percent were level L5-S1, 43% were L4-L5 and 8% were L3-L4. The mean duration of symptoms was 31.5 months. Mean surgical time, mean blood loss and mean hospital stay were 139 minutes, 186 cc and 3.34 days, respectively. There were no intraoperative or postoperative complications attributable to the construct and no cases of cage migration or collapse. Patients who were at least 1-year postsurgery and had follow-up X-rays or had undergone a CT scan at this time point were evaluated for fusion status. Sixty-three patients were assessed for fusion. Fifty-four (86%) of these patients were determined to have a solid fusion. Mean time to fusion was 10 months. Fusion was assessed as solid only if all operative levels were fully fused. Mean subsidence of the anterior region was 1.97 mm, whereas the mean subsidence of the posterior region was 0.82 mm. Lordosis was unchanged at all surgical levels with mean lordosis in L3-L4 decreasing only slightly from 13 degrees before surgery to 12 degrees after surgery. L4-L5 and L5-S1 showed only slight increases in lordosis changing from 17 to 18 degrees at L4-L5 and from 17 to 19 degrees at L5-S1. These changes were not statistically significant. The clinical outcome questionnaires had a return rate of 68%. Of the 48 patients who completed the questionnaire, 75% responded that they were happy with the surgical results and would definitely recommend the surgery to a friend. Sixty-seven percent agreed that surgery met their expectations or that surgery improved their condition enough that they would go through it again for the same outcome. The results of the SF-36 portion of the survey revealed that the physical and mental composite scores were within normal range of the US population that has experienced back pain or sciatica. CONCLUSION: Bilateral implantation of low-profile cages in this patient population led to satisfactory outcomes. Subsidence and changes in lordosis were minimal. Fusion rates were good, especially for one-level cases. Patient satisfaction was relatively high, considering the population consisted of 96% worker's compensation cases. With proper surgical technique, bilateral low-profile cages can be used effectively to treat patients with degenerative disc disease.

Health Status↗
PubMed2002

The involvement of matrix metalloproteinases in basement membrane injury in a murine model of acute allergic airway inflammation.

BACKGROUND: Airway remodelling in asthma such as subepithelial fibrosis is thought to be the repair process that follows the continuing injury as of chronic airway inflammation. However, how acute allergic inflammation causes tissue injury in the epithelial basement membrane in asthmatic airways remains unclear. Matrix metalloproteinases (MMPs) capable of degrading almost all of the extracellular matrix components have been demonstrated to be involved in cell migration through the basement membrane in vivo and in vitro. OBJECTIVE: We investigated the alterations of matrix construction and the role of MMPs in matrix degradation in the subepithelium during acute allergic airway inflammation. METHODS: Airway inflammation, the ultrastructure of the subepithelium and injury of types III and IV collagen in tracheal tissues from ovalbumin (OVA)-sensitized mice after OVA inhalation with or without the administration of tissue inhibitor of metalloproteinase-2 (TIMP-2) and dexamethasone were evaluated by cell counting in bronchoalveolar lavage (BAL) fluids, electron microscopy and immunohistochemistry, respectively. RESULTS: The disruption of the lamina densa and matrix construction and the decrease of the immunoreactivity for type IV collagen in subepithelium were observed in association with the accumulation of inflammatory cells in airways 3 days after OVA inhalation. This disorganization of the matrix components in the subepithelium, as well the cellular accumulation, was abolished by the administration of TIMP-2 and dexamethasone. The immunoreactivity for type IV collagen in the subepithelium in OVA-inhaled mice returned to the level of that in saline-inhaled mice 10 days after inhalation in association with a decrease of the cell numbers in the BAL fluid. The immunoreactivity for type III collagen was changed neither 3 nor 10 days after OVA inhalation. CONCLUSION: These results suggest that epithelial basement membrane gets injured by, at least in part, MMPs as a consequence of cell transmigration through the membrane during acute allergic airway inflammation.

Acute Disease↗