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PubMed1990

Failure of a knee prosthesis accelerated by shedding of beads from the porous metal surface.

A 61-year-old man who received a porous-metal-coated knee implant returned eight months later with chronic synovitis, instability, and loosening of his artificial joint. Subsequently, metal beads were detected in the joint space and soft tissues and were also embedded in the articulating surface of the tibial component. There was scoring of the tibial surface, and polyethylene wear particles were noted in the synovial and fibroconnective-tissue membranes, which had formed beneath the tibial component. Many particles were seen inside giant cells and macrophages. Failure in this case was probably accelerated by the granulomatous response in the soft tissue to wear particles. There was osteolysis rather than new bone growth at the interface with the tibial component. Analysis indicated that poor bead-bonding strength may have initiated the problem. Careful appraisal of the outcome from use of beaded porous-metal-coated devices and assurance of their adequate bonding strength are essential for further progress.

Foreign Bodies↗

PubMed1992

Reverse brain drain in South Korea: state-led model.

Korea's reverse brain drain (RBD) has been an organized government effort, rather than a spontaneous social phenomenon, in that various policies and the political support of President Park, Chung-Hee were instrumental in laying the groundwork for its success. Particular features of Korea's RBD policies are the creation of a conducive domestic environment (i.e., government-sponsored strategic R & D institution-building, legal, and administrative reforms), and importantly, the empowerment of returnees (via, i.e., exceptionally good maternal benefits, guarantees of research autonomy). President Park played the cardinal role in empowering repatriates at the expense of his own civil bureaucracy, and his capacity for such patronage derived from Korea's bureaucratic-authoritarian political system. Returning scientists and engineers directly benefitted from this political system as well as Park's personal guardianship. For Park, empowerment of returning "brains" was necessary to accomplish his national industrialization plan, thereby enhancing his political legitimacy in domestic politics. An alliance with the R & D cadre was functionally necessary to successfully consolidate strong presidential power, and politically nonthreatening due to the particular form of "pact of domination" in Korea's power structure. RBD in Korea will continue in the near future given Korea's drive for high technology, and the remarkable expansion of local industrial and educational sectors. Korea's future RBD, however, needs to pay closer attention to the following 4 problems: research autonomy; equality issues; skill-based repatriation of technicians and engineers rather than Ph.Ds; and subsidies to small and medium industry for RBD.

Asia↗

PubMed1987

Effect of citric acid and lyophilized autologous plasma on healing following periodontal flap surgery in monkeys.

The purpose of this histologic, histometric, and autoradiographic study was to examine the effect of citric acid conditioning and lyophilized autologous plasma (LAP) application on healing following periodontal flap surgery. Mucoperiosteal flaps were elevated in six rhesus monkeys using the modified Widman flap procedure. A total of 24 quadrants were treated, each included the first and second premolar and first and second molar teeth. Cementum was removed from the exposed root surfaces, and reference notches were inscribed into the roots at the alveolar bone margin. Two treatment modalities were employed: (1) surgery plus citric acid conditioning, to serve as control and (2) surgery plus citric acid followed by LAP application (400 mg/ml saline). Flaps were returned to their preoperative positions and sutured. Animal sacrifices were scheduled to provide observations 3, 7, 14, 21, 28, and 45 days after surgery. Each monkey received an intravenous injection of tritiated thymidine, 1 microCi/gm of body weight, 1 hour before it was killed. Tissue specimens were processed for evaluation following standard procedures. Histologically, tissue sections were examined for: (1) proliferation and attachment of epithelium, (2) organization and maturation of periodontal fibers, (3) inflammatory cell types, (4) presence or absence of new cementum deposition, and (5) degree of vascularity of the tissues. For histometric evaluation, the radicular notches were used as reference points. The distances examined histometrically were: (1) from the root surface notch to the alveolar bone crest, (2) from the root surface notch to the apical extent of the junctional epithelium, and (3) from the free gingival margin to the apical extent of the junctional epithelium. For autoradiographic evaluation labeled cells were counted in five spatial compartments at 400 X magnification: (1) oral epithelium, (2) crevicular area, (3) supracrestal connective tissue, (4) coronal periodontal membrane, and (5) coronal bone marrow. For each the histometric and autoradiographic evaluation involved a total of 36 tissue sections per quadrant (9 sections per tooth). Tooth and quadrant means were obtained for each monkey. The plasma-treated and control quadrants were compared at each time point by the paired t test. N = 2 monkeys were used for each comparison. Histologic results showed that in teeth that were acid-conditioned after root planing, the epithelium often migrated apically reaching the radicular notch. Those teeth that were conditioned and subsequently treated with LAP demonstrated fiber attachment to the planed root surface and little or no epithelial downgrowth.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

PubMed1996

Conversion of failed or complicated vertical banded gastroplasty to gastric bypass in morbid obesity.

BACKGROUND: Previous studies have documented a significantly better we weight loss for gastric bypass (GBP) than for vertical banded gastroplasty (VGB). Additional problems associated with VBG include intractable vomiting or gastroesophageal (GE) reflux, intragastric migration of the polypropylene band, staple line disruption, or inadequate weight loss due to excessive ingestion of high-calorie liquid or soft carbohydrates. PATIENTS AND METHODS: Fifty-eight morbidly obese patients underwent conversion from VBG to GBP for either weight-loss failure (15) or complications of VBG (43), including 2 who where referred with anastomotic leaks and peritonitis, 3 with band erosion, 15 with staple line disruption, and 23 with stomal stenosis, of whom 6 had severe GE reflux, with a Barrett's esophagus in 1. RESULTS: Percentage of excess weight loss in the 53 patients followed up for at least 1 year after conversion increased from 36% +/- 24% to 67% +/- 18%, and in the 15 "sweets eaters" from 20% +/- 19% to 70% +/- 19% (both P <0.001), was equal to weight loss after primary GBP, and was reasonably constant over 8 years in those patients who could be contacted for follow-up, although average follow-up after 5 years was only 45% All patients had resolution of GE reflux symptoms immediately after surgery and for at least 1 year or at last contact. Complications of conversion included 2 anastomotic leaks with major wound infections (1 in a referred patient requiring emergency subtotal gastrectomy following a VBG leak), 3 staple line disruptions (2 subclinical), 3 small-bowel obstructions, and 20 marginal ulcers or stomal stenoses (all responded to endoscopic balloon dilation or acid reduction therapy). Hemoglobin, calcium, and vitamin B12 levels remained within normal levels with prophylactic supplementation in patients who returned for follow-up evaluation. CONCLUSIONS: These data support the efficacy of conversion to GBP in morbidly obese patients with a failed or complicated VBG.

Gastric Bypass↗

PubMed2004

Epidural abscess and discitis complicating instrumented posterior lumbar interbody fusion: a case report.

STUDY DESIGN: A case of epidural abscess and discitis following instrumented PLIF using a single carbon fiber interbody cage is presented. OBJECTIVE: To describe a previously unreported complication of epidural abscess and discitis following posterior lumbar interbody fusion using a single carbon fiber cage. SUMMARY OF BACKGROUND DATA: Various complications have been reported with PLIF. These include graft migration, pseudarthrosis, implant subsidence, epidural hemorrhage, incidental durotomy, arachnoiditis, transient or permanent neurologic deficits, persistence of pain, and wound infections. There are no reported cases of epidural abscess or refractory discitis associated with PLIF. METHODS: A 35-year-old infantryman on active duty with chronic low back pain and single-level lumbar disc degeneration underwent instrumented PLIF after reporting no improvement with 3 years of extension-based physical therapy and nonsteroidal pain medications. His back pain was reported improved at 6 weeks after surgery. At 12 weeks after surgery, he presented to the emergency department with intense back pain and fevers. Laboratory data were remarkable for elevated erythrocyte sedimentation rate (118) and C-reactive protein (38). Initial imaging studies, including a lumbar MRI, did not demonstrate any abnormalities. The patient continued to spike fevers, and a repeat lumbar MRI 1 week later clearly demonstrated the presence of an epidural abscess at the level of the PLIF surgery. The patient was treated with surgical debridement and epidural abscess drainage. The interbody cage was left in place. Surgical cultures identified Staphylococcus aureus as the pathogen, and the patient was placed on intravenous vancomycin. During the ensuing 3 weeks, his clinical symptoms worsened and his radiographs demonstrated lucency in the region of his interbody cage. Repeat debridement was performed, and his interbody cage and pedicle screw instrumentation were removed 4 months after initial surgery. RESULTS: The disc space infection resolved following removal of the implants. Radiographs at 6 months after instrumentation removal demonstrated solid bilateral posterolateral arthrodesis. The patient returned to active duty 1 year after his initial surgery, reporting that his back pain was reduced compared with his preoperative level. CONCLUSIONS: There is a paucity of literature on epidural abscess and discitis as complications associated with PLIF. In this case, the infection persisted despite surgical debridement and intravenous antibiotics. The patient ultimately required removal of the interbody implant and posterior instrumentation. The patient developed solid posterolateral arthrodesis despite the presence of deep infection, which led to early implant removal 4 months after the initial surgery. This case underscores the potential importance of concomitant posterolateral fusion, particularly following wide laminectomy and facetectomy required for PLIF.

Adult↗

PubMed2003

Transcutaneous electrogastrography in the perioperative period in patients undergoing laparoscopic cholecystectomy and laparoscopic non-adjustable gastric banding.

BACKGROUND: Transcutaneous electrogastrography (EGG) is a non-invasive method of examination that allows monitoring of gastric myoelectric activity. The goal of this prospective study was to describe changes in gastric motility in the early postoperative period in extremely obese patients, who underwent planned surgery--Laparoscopic Non-Adjustable Gastric Banding (LNGB) and to establish the specificity of observed differences for this intervention. PATIENTS AND METHODS: Myoelectric gastric activity was evaluated in the perioperative period in 20 extremely obese patients undergoing LNGB. The results of monitoring up to +24 h after the intervention were compared to a group of 15 healthy volunteers, and to a group of 20 patients undergoing laparoscopic cholecystectomy (LC). The recording was performed in both the patient and control groups 24 h before the operation and +5 h, +24 h and +48 h after the surgery, both in the fasting state and after stimulation with a liquid bolus. The data were recorded using the Microdigitrapper device and analyzed using the spectral analysis and Fourier transformation. RESULTS: The finding characteristic in the early postoperative period was a decrease in frequency of both spontaneous and stimulated gastric contractions (bradygastria) at +5 h after the intervention, that was followed by rapid return to baseline activity. In patients after LNGB, the normalization of motility was seen within 24 h, and in patients after LC within 48 h after the intervention. Tachygastria was not found in any patient who did not have complications, but on the contrary it was found in both patients with significant dyspepsia after LC. CONCLUSIONS: In the early postoperative period after LNGB, significant changes in myoelectric gastric activity were seen and were characterized by transient bradygastria. Comparison with the reference group of patients after LC shows that the intensity and duration of basal and stimulated bradygastria has a non-specific relationship with the extent of tissue trauma caused by the intraabdominal surgery. It is not specific for the gastric banding itself. The method of measuring the basal stimulated EGG potentials can be used in routine surgical practice as an auxiliary method for evaluation of the functional status of the gastrointestinal tract after intraabdominal surgery.

Adult↗

PubMedDate not supplied

Peritoneal macrophage cholesteryl ester content as a function of plasma cholesterol in rats.

Cholesterol accumulation in macrophages that have migrated in the subintimal space leads to foam cell formation, which is believed to be one of the initiating events in atherosclerosis. In this study we investigated the effect of cholesterol feeding on peritoneal monocyte/macrophage cholesterol content and peritoneal cavity lipoprotein composition in rats. A cholesterol (2%) and cholic acid (1%) diet caused significant hypercholesterolemia in plasma, and at the same time the cholesterol content of peritoneal monocytes/macrophages was increased. At day 7, the cellular cholesteryl ester content had risen to 30.1 micrograms/mg cellular protein from a baseline value of 9.2 micrograms/mg. The unesterified cholesterol content also increased by 56%. At this time, acyl-coenzyme A:cholesterol acyltransferase (ACAT) activity was doubled, whereas neutral and acidic cholesteryl ester hydrolase activities were unchanged. Reversal to the regular chow diet after 7 days of the cholesterol-enriched diet normalized plasma cholesterol levels as well as peritoneal monocyte/macrophage cholesteryl ester content. ACAT activity also decreased toward normal levels. Analysis of the d less than 1.21 g/ml peritoneal lipoproteins isolated by ultracentrifugation revealed the presence, in both normal and hypercholesterolemic rats, of apolipoprotein A-I-rich lipid complexes with pre-beta mobility on agarose gel electrophoresis. The size of the peritoneal lipoproteins was smaller than that of plasmatic high density lipoproteins, and their chemical composition was also different from that of the major plasma lipoproteins. The cholesteryl ester content of peritoneal lipoproteins increased after feeding of the cholesterol-enriched diet. In conclusion, our results show that cholesterol feeding leads to rapid accumulation of cholesteryl esters in monocytes/macrophages. As soon as plasma cholesterol levels are returned to normal, cellular cholesterol content is also normalized.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1995

Evaluation of hemostatic and fibrinolytic alterations associated with daily administration of low-molecular-weight heparin for a 12-week period.

The PTCA procedure fails in 30-50% of patients due to late restinosis, meaning that this is a problem of 100,000-150,000 people per year in the USA alone. It has been found that heparin and low-molecular-weight heparin (LMWH) have an inhibitory effect on smooth muscle cell (SMC) proliferation and migration, the major causes of restinosis. However, little is known about the toxicity and side effects of these drugs when used for a long period as may be required for prophylaxis of PTCA restinosis. To investigate possible side effects, non-human primates received daily injections of 1 mg/kg s.c. LMWH (Mono-Embolex) over a 12-week period. The hemostatic system was monitored through measurement of ACT-celite, APTT, Heptest, TT(10U/mL), TFPI, Anti-IIa activity, Anti-Xa activity, ACA-Heparin, AT III, factor VIII R:Ag, fibrinogen, and thrombomodulin levels. Elisa tests for t-PA, PAI-1, u-PA, FgDP, TDP, and D-Di levels were used for measurements of fibrinolytic activity. Increased values of ACT, APTT, Heptest, TT, Anti-IIa, Anti-Xa, ACA-Heparin, and TFPI were observed four hours after LMWH injections. AT III, vWFAg, fibrinogen and thrombomodulin showed no change from the pre-study baseline. An accumulation effect was seen in the APTT and Heptest over the 12 weeks. After the first week the blood levels of Anti-IIa activity remained elevated at 20% inhibition rather than 0% 24 hrs after drug administration. This activity slowly decreased after discontinuation of drug. The Anti-Xa blood level activity remained elevated at 40% inhibition 24 hrs after drug administration 2 weeks into the study, and this activity was detectable even 2 weeks after cessation of drug administration. There was increasing activity of the fibrinolytic system with LMWH treatment. After two weeks t-PA increased two-fold to 6 ng/mL but returned to baseline at six weeks. There was a corresponding increase of the TDP but not a clear increase in D-Di and FgDP. The increase of u-PA was limited to the first days of LMWH treatment only. The PAI-1 activity increased gradually over the entire study period. No bleeding complications occurred throughout the study. The long-term administration of Mono-Embolex as projected for the use in the prophylaxis of restinosis following PTCA appears to be safe for patients.

Animals↗

PubMed2005

Using stable isotopes to study resource acquisition and allocation in procellariiform seabirds.

Some procellariiform seabirds use a dual strategy for provisioning their chicks by alternating short (ST) and long (LT) foraging trips. Parent birds gain mass during LT but they lose mass while increasing the chick feeding frequency during ST. Self-feeding during LT is crucial for the success of ST because firstly most of the energy used during ST is likely to be derived from the energy stored during LT and secondly self-feeding during ST is presumed to be negligible. Self-feeding by adult procellariiforms is thus a key issue to understand allocation processes but it is still poorly known. We tested these predictions by using the stable isotope (delta(15)N and delta(13)C) technique on birds' plasma and prey with the short-tailed shearwater Puffinus tenuirostris breeding at Tasmania as a model. Parent shearwaters returning to the colony after a LT have an Antarctic/subantarctic delta(13)C signature in their plasma (-23.8 per thousand), thus indicating that they fed in cold waters, far away from their breeding colony, for their own maintenance. Parent birds returning to the colony after a ST also have a distant Antarctic/subantarctic delta(13)C signature in their plasma (-24.3 per thousand), thus verifying that self-feeding is negligible during ST and that birds fast at that time, using energy stores built up in cold waters. Plasma delta(15)N values of adults (8.8 per thousand) indicates they mainly prey upon zooplankton-eating organisms, probably mesopelagic myctophid fishes. A simple isotopic mixing model estimates that they consume by mass 87% myctophids and 13% subantarctic krill when self-feeding. Finally and as expected, the carbon isotopic signature of chick plasma (-22.2 per thousand) was intermediate between those of high- and low-latitude marine organisms and is thus in agreement with chicks being fed with a large diversity of prey species caught by adult birds from Antarctic to Tasmanian waters. One main consequence of this system is that reproduction of a Tasmanian species is controlled by resources available at great distances from the breeding colony that drive allocation decisions of parent birds.

Animal Migration↗

PubMed1997

Postembryonic changes in the structure of the olfactory bulb of the chinook salmon (Oncorhynchus tshawytscha) across its life history.

Juvenile chinook salmon (Oncorhynchus tshawytscha) memorize odors characteristic of their natal stream, then use these imprinted olfactory cues to return to that same stream years later as sexually mature adults. In a preliminary effort to identify neuroanatomical changes in the salmon olfactory system that may underlie these behavioral capabilities, the structure of the olfactory bulb (OB) was studied at three developmental periods across the life history: in early juvenile development (0.1-4 months of age), in late juvenile development (11-16 months), and as spawning adults (48 months). Using antibodies that selectively label primary olfactory afferents (anti-keyhole limpet hemocyanin), combined with a thionin counterstain, the telencephalon (TEL), OB, and two of the bulb's laminar components, the olfactory nerve-glomerular layer (ONL-GL) and inner cell layer (ICL), could be easily identified. Laminar organization and relative volume (i.e. percent of OB comprised by ONL-GL or ICL) were then compared across groups, and absolute volumes of the OB, ONL-GL, and ICL were compared to that of the TEL at each stage. Three age-related processes were observed across the life history. First, a rapid increase in organizational and structural maturity of the OB was found to be confined to early juvenile life. Second, an increase in OB, ONL-GL, and ICL volume, relative to TEL volume, was found to occur across the entire life history. Lastly, the composition of the OB itself changed, in that an increase in the relative volume of the ONL-GL, and a decrease in that of the ICL, were observed across the life history. Taken together, these results indicate that the OB of young salmon matures dramatically while the fish is still in the freshwater phase of its life history. Then, during migration to the ocean and growth to the adult stage, the volume of the OB, relative to that of the telencephalon, and the relative volume of the input layer of the bulb, both undergo a marked, continuous increase. These changes in the structure, and presumably the function, of the olfactory bulb of salmon may be important in the behavioral phenomena of olfactory imprinting as juveniles and homing as adults.

Age Factors↗

PubMed2000

Gene expression of TGF-beta, TGF-beta receptor, and extracellular matrix proteins during membranous bone healing in rats.

Poorly healing mandibular fractures and osteotomies can be troublesome complications of craniomaxillofacial trauma and reconstructive surgery. Gene therapy may offer ways of enhancing bone formation by altering the expression of desired growth factors and extracellular matrix molecules. The elucidation of suitable candidate genes for therapeutic intervention necessitates investigation of the endogenously expressed patterns of growth factors during normal (i.e., successful) fracture repair. Transforming growth factor beta1 (TGF-beta1), its receptor (Tbeta-RII), and the extracellular matrix proteins osteocalcin and type I collagen are thought to be important in long-bone (endochondral) formation, fracture healing, and osteoblast proliferation. However, the spatial and temporal expression patterns of these molecules during membranous bone repair remain unknown. In this study, 24 adult rats underwent mandibular osteotomy with rigid external fixation. In addition, four identically treated rats that underwent sham operation (i.e., no osteotomy) were used as controls. Four experimental animals were then killed at each time point (3, 5, 7, 9, 23, and 37 days after the procedure) to examine gene expression of TGF-beta1 and Tbeta-RII, osteocalcin, and type I collagen. Northern blot analysis was used to compare gene expression of these molecules in experimental animals with that in control animals (i.e., nonosteotomized; n = 4). In addition, TGF-beta1 and T-RII proteins were immunolocalized in an additional group of nine animals killed on postoperative days 3, 7, and 37. The results of Northern blot analysis demonstrated a moderate increase (1.7 times) in TGF-beta1 expression 7 days postoperatively; TGF-beta1 expression returned thereafter to near baseline levels. Tbeta-RII mRNA expression was downregulated shortly after osteotomy but then increased, reaching a peak of 1.8 times the baseline level on postoperative day 9. Osteocalcin mRNA expression was dramatically downregulated shortly after osteotomy and remained low during the early phases of fracture repair. Osteocalcin expression trended slowly upward as healing continued, reaching peak expression by day 37 (1.7 times the control level). In contrast, collagen type IalphaI mRNA expression was acutely downregulated shortly after osteotomy, peaked on postoperative days 5, and then decreased at later time points. Histologic samples from animals killed 3 days after osteotomy demonstrated TGF-beta1 protein localized to inflammatory cells and extracellular matrix within the fracture gap, periosteum, and peripheral soft tissues. On postoperative day 7, TGF-beta1 staining was predominantly localized to the osteotomized bone edges, periosteum, surrounding soft tissues, and residual inflammatory cells. By postoperative day 37, complete bony healing was observed, and TGF-beta1 staining was localized to the newly formed bone matrix and areas of remodeling. On postoperative day 3, Tbeta-RII immunostaining localized to inflammatory cells within the fracture gap, periosteal cells, and surrounding soft tissues. By day 7, Tbeta-RII staining localized to osteoblasts of the fracture gap but was most intense within osteoblasts and mesenchymal cells of the osteotomized bone edges. On postoperative day 37, Tbeta-RII protein was seen in osteocytes, osteoblasts, and the newly formed periosteum in the remodeling bone. These observations agree with those of previous in vivo studies of endochondral bone formation, growth, and healing. In addition, these results implicate TGF-beta1 biological activity in the regulation of osteoblast migration, differentiation, and proliferation during mandibular fracture repair. Furthermore, comparison of these data with gene expression during mandibular distraction osteogenesis may provide useful insights into the treatment of poorly healing fractures because distraction osteogenesis has been shown to be effective in the management of these difficult clinical cases.

Animals↗

PubMed1994

Highly prevalent falciparum malaria in north west Guyana: its development history and control problems.

After being absent from North West Guyana for over two decades, falciparum malaria returned in force in 1986 and soon developed a high prevalence affecting a large share of the region's inhabitants. This falciparum upsurge was accompanied by a significant rise in the number of vivax cases that helped bring the annual parasite index to figures ranging from 260 positive smears per 1,000 inhabitants in 1986 to 973 in 1988 and 776 in 1991. The chloroquine-resistant P. falciparum strain responsible apparently travelled from the area of the Rupununi River in Southern Guyana to the more northern Cuyuni/Mazaruni/Potaro area in 1985, and from there was brought into the North West Region, probably by itinerant miners. Circumstances leading to the present endemic demonstrate how transient populations, resistant parasites, and economic restraints can interfere with malaria control, and how rapidly high malaria prevalences can establish themselves in receptive tropical areas vulnerable to attack.

Adolescent↗

PubMed2005

Endogenous nitric oxide modulates small intestinal nutrient transit and activity in healthy adult humans.

OBJECTIVE: Nitric oxide (NO) mechanisms have been shown to modulate fasting small intestinal motility in humans, but a role in the regulation of human postprandial small intestinal motility has not been assessed. The aim of this study was to evaluate the effect of the NO synthase inhibitor NG-monomethyl-L-arginine (L-NMMA) on the regulation of small intestinal nutrient transit and postprandial small intestinal motility in healthy humans. MATERIAL AND METHODS: Seven healthy male volunteers (18-27 years) underwent antroduodenal manometry recordings for 4 h on 2 occasions after intraduodenal instillation of a 500 KJ [120 Kcal] test meal. The meal was administered 15 min after the commencement of a 60-min intravenous infusion of L-NMMA (4 mg kg-1 h-1) or saline (0.9%). Studies were separated, performed in randomized order and >3 days apart. The frequency and amplitude of duodenal pressure waves together with time to return of fasting motility (phase III) was determined. On each day, small intestinal transit was measured using a lactulose breath test. RESULTS: The test meal interrupted fasting small intestinal motility in all subjects. The time to recurrence of fasting motility following its postprandial disruption was similar (L-NMMA versus saline 1.6+/-0.2 h versus 1.9+/-0.1 h; p>0.05). Duodenocaecal transit was delayed by infusion of L-NMMA compared with saline (L-NMMA versus saline 92.1+/-3.9 min versus 66.4+/-6.4 min; p<0.005). Infusion of L-NMMA significantly increased the frequency (L-NMMA versus saline 50.4+/-6.6 versus 34.8+/-5.5 waves per 30 min; p<0.05) and amplitude (L-NMMA versus saline 20.4+/-1.5 versus 15.5+/-1.1 mmHg; p<0.01) of duodenal pressure waves. CONCLUSIONS: These data suggest that endogenous NO may play a role in the regulation of small intestinal nutrient transit by regulating small intestinal motility in healthy individuals.

Adolescent↗

PubMed2004

Genotoxicity of environmental air pollution in three European cities: Prague, Kosice and Sofia.

The genotoxic potential of extractable organic matter (EOM) associated with the respirable particulate matter (PM <10 microm) of atmospheric pollution has been determined in three European cities--Prague (Czech Republic, two monitoring sites, Libus and Smíchov), Kosice (Slovak Republic) and Sofia (Bulgaria) using the alkaline single-cell gel electrophoresis (the comet assay). The EOM samples were extracted by dichloromethane from ambient airborne particles collected daily (24 h intervals) during 3-month sampling periods in winter and summer seasons. The human metabolically competent cell line Hep G2 was used as a test system and benzo[a]pyrene (BaP), a known carcinogen, was applied as a positive control (internal standard) in each electrophoretic run. Two-hour exposure of Hep G2 cells to equivalent EOM concentrations ranging from 5 to 150 microg EOM/ml resulted in a linear dose-dependent increase of DNA migration (r > 0.9, P < 0.01). A less significant dose-response (r = 0.61) was only induced by the EOM sample from the locality Prague-Libus (PRG-LB) in the winter. Generally, a 1.5 to four-fold increase of DNA strand breaks over the background control level was determined in EOM-exposed cells. In order to compare the genotoxic potential of individual EOMs, a mathematical model was used to correct the 'real' data. No substantial location- or season-related differences were found in EOM genotoxicity (EOM microg/ml), except for the EOM sample from Sofia, collected in the summer. This EOM sample induced a nearly two-fold lower level of DNA damage in comparison with other EOMs. On the other hand, clear statistically significant location- and season-related differences (P < 0.001) in ambient air genotoxicity were determined when the EOM quantity per cubic meter of air (microg/m3) was taken into account. In that case, the genotoxicity of winter air pollution was six- to 10-fold higher in comparison with summer air. The air pollution genotoxicity in individual localities rose during the winter season in the order: PRG-LB < Kosice < Prague-Smíchov (PRG-SM) < Sofia, while during the summer season the highest ambient air genotoxicity was revealed in the locality Prague-Smíchov and approximately equal air pollution genotoxicity was determined among localities Prague-Libus, Kosice and Sofia (PRG-LB approximately Kosice approximately Sofia < PRG-SM). The greatest overall air pollution genotoxicity was determined in the locality Sofia during the winter season. In a time course study to evaluate the kinetics of DNA strand break rejoining it was shown that the level of DNA strand breaks in EOM-exposed cells has returned to near the background level within 24 h after the treatment.

Air Pollutants↗

PubMed1999

Participation of a chloride conductance in the subthreshold behavior of the rat sympathetic neuron.

The presence of a novel voltage-dependent chloride current, active in the subthreshold range of membrane potential, was detected in the mature and intact rat sympathetic neuron in vitro by using the two-microelectrode voltage-clamp technique. Hyperpolarizing voltage steps applied to a neuron held at -40/-50 mV elicited inward currents, whose initial magnitude displayed a linear instantaneous current-voltage (I-V) relationship; afterward, the currents decayed exponentially with a single voltage-dependent time constant (63.5 s at -40 mV; 10.8 s at -130 mV). The cell input conductance decreased during the command step with the same time course as the current. On returning to the holding potential, the ensuing outward currents were accompanied by a slow increase in input conductance toward the initial values; the inward charge movement during the transient ON response (a mean of 76 nC in 8 neurons stepped from -50 to -90 mV) was completely balanced by outward charge displacement during the OFF response. The chloride movements accompanying voltage modifications were studied by estimating the chloride equilibrium potential (E(Cl)) at different holding potentials from the reversal of GABA evoked currents. [Cl(-)](i) was strongly affected by membrane potential, and at steady state it was systematically higher than expected from passive ion distribution. The transient current was blocked by substitution of isethionate for chloride and by Cl(-) channel blockers (9AC and DIDS). It proved insensitive to K(+) channel blockers, external Cd(2+), intracellular Ca(2+) chelators [bis-(o-aminophenoxy)-N,N,N',N'-tetraacetic acid (BAPTA)] and reduction of [Na(+)](e). It is concluded that membrane potential shifts elicit a chloride current that reflects readjustment of [Cl(-)](i). The cell input conductance was measured over the -40/-120-mV voltage range, in control medium, and under conditions in which either the chloride or the potassium current was blocked. A mix of chloride, potassium, and leakage conductances was detected at all potentials. The leakage component was voltage independent and constant at approximately 14 nS. Conversely, gCl decreased with hyperpolarization (80 nS at -40 mV, undetectable below -110 mV), whereas gK displayed a maximum at -80 mV (55.3 nS). Thus the ratio gCl/gK continuously varied with membrane polarization (2.72 at -50 mV; 0.33 at -110 mV). These data were forced in a model of the three current components here described, which accurately simulates the behavior observed in the "resting" neuron during membrane migrations in the subthreshold potential range, thereby confirming that active K and Cl conductances contribute to the genesis of membrane potential and possibly to the control of neuronal excitability.

Animals↗

PubMed1988

The development of cholinergic neurons.

Motoneuron precursors acquire some principles of their spatial organization early in their cell lineage, probably at the blastula stage. A predisposition to the cholinergic phenotype in motoneurons and some neural crest cells is detectable at the gastrula to neurula stages. Cholinergic expression is evident upon cessation of cell division. Cholinergic neurons can synthesize ACh during their migration and release ACh from their growth cones prior to target contact or synapse formation. Neurons of different cell lineages can express the cholinergic phenotype, suggesting the importance of secondary induction. Early cholinergic commitment can be modified or reversed until later in development when it is amplified during interaction with target. Motoneurons extend their axons and actively sort out in response to local environmental cues to make highly specific connections with appropriate muscles. The essential elements of the matching mechanism are not species-specific. A certain degree of topographic matching is present throughout the nervous system. In dissociated cell culture, most topographic specificity is lost due to disruption of local environmental cues. Functional cholinergic transmission occurs within minutes of contact between the growth cone and a receptive target. These early contacts contain a few clear vesicles but lack typical ultrastructural specializations and are physiologically immature. An initial stabilization of the nerve terminal with a postsynaptic AChR cluster is not prevented by blocking ACh synthesis, electrical activity, or ACh receptors, but AChR clusters are not induced by non-cholinergic neurons. After initial synaptic contact, there is increasing deposition of presynaptic active zones and synaptic vesicles, extracellular basal lamina and AChE, and postjunctional ridges over a period of days to weeks. There is a concomitant increase in m.e.p.p. frequency, mean quantal content, metabolic stabilization of AChRs, and maturation of single channel properties. At the onset of synaptic transmission, cell death begins to reduce the innervating population of neurons by about half over a period of several days. If target tissue is removed, almost all neurons die. If competing neurons are removed or additional target is provided, cell death is reduced in the remaining population. Pre- or postsynaptic blockade of neuromuscular transmission postpones cell death until function returns.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

PubMed1983

Immunoregulation in experimental disseminated histoplasmosis: flow microfluorometry (FMF) studies of the Thy and Lyt phenotypes of T lymphocytes from infected mice.

Previous studies have shown that mice infected i.v. with 6 X 10(5) yeast phase Histoplasma capsulatum (Hc) develop suppressed immune responses during weeks 1 to 4 of infection but that by weeks 8 to 12 of infection these responses return to normal. In this study total and differential cell counts showed that as early as the third day of infection there was a marked reduction in the number of lymphocytes recovered from the peripheral blood, bone marrow, and thymus of infected animals. Concomitantly, there was an increase in the number of splenic lymphocytes. By day 28 both the total and differential cell counts were similar in both infected and normal animals. Flow microfluorometric (FMF) studies comparing the Thy-1.2, Lyt-1, Lyt-2, and surface immunoglobulin (slg) phenotypes of lymphocytes from normal and infected mice were performed. Between days 5 and 7 the thymocytes from infected mice displayed a higher relative fluorescence intensity (RFI) of the Thy-1.2 marker than normal thymocytes, whereas at day 10, the RFI was less than that of normal thymic lymphocytes. Between days 7 and 10 of infection the RFI of the Lyt-2 marker was less on thymocytes from Hc-infected mice; however, there was no change in the Lyt-1 marker. Examination of these lymphocyte markers in blood, spleen, and mesenteric lymph nodes showed that there were decreases in the RFI of both the Thy-1.2 and Lyt-2 between days 5 and 10 of infection. No changes were observed in the Lyt-1 or slg markers. By day 28 there were no differences between the normal and infected mice with respect to any surface marker in any of the organs studied. In other experiments, the effect of adrenalectomy before infection on these surface markers was studied. Absolute numbers of Thy-1.2+, Lyt-1+, and Lyt-2+ cells were significantly increased in the spleen and significantly decreased in the thymus and peripheral blood of infected mice relative to normal controls. These studies suggest that there is a migration of cells from the thymus, blood, and bone marrow to the spleens of mice with disseminated Hc infection.

Adrenalectomy↗

PubMed2007

Detecting female precise natal philopatry in green turtles using assignment methods.

It is well established that sea turtles return to natal rookeries to mate and lay their eggs, and that individual females are faithful to particular nesting sites within the rookery. Less certain is whether females are precisely returning to their natal beach. Attempts to demonstrate such precise natal philopatry with genetic data have had mixed success. Here we focused on the green turtles of three nesting sites in the Ascension Island rookery, separated by 5-15 km. Our approach differed from previous work in two key areas. First, we used male microsatellite data (five loci) reconstructed from samples collected from their offspring (N = 17) in addition to data for samples taken directly from females (N = 139). Second, we employed assignment methods in addition to the more traditional F-statistics. No significant genetic structure could be demonstrated with F(ST). However, when average assignment probabilities of females were examined, those for nesting populations in which they were sampled were indeed significantly higher than their probabilities for other populations (Mann-Whitney U-test: P < 0.001). Further evidence was provided by a significant result for the mAI(C) test (P < 0.001), supporting greater natal philopatry for females compared with males. The results suggest that female natal site fidelity was not sufficient for significant genetic differentiation among the nesting populations within the rookery, but detectable with assignment tests.

Animal Migration↗