Biomedical subjects

J Heller

Publications and source records attributed to J Heller.

At least 55 records · Page 3Linked to original sources

PubMed2000

Improved biocompatibility of a viscous bioerodible poly(ortho ester) by controlling the environmental pH during degradation.

The poly(ortho ester), POE, used in this investigation, is a viscous bioerodible polymer (8 kDa), which rapidly degrades into a triol and an acidic by-product, acetic acid. In order to improve biocompatibility, we have evaluated the addition of various basic excipients, such as sodium acetate, hydroxyapatite, calcium carbonate and magnesium hydroxide, which buffered and neutralized the acidic degradation product and prolonged the polymer lifetime and drug release. This decrease of POE degradation rate results in a decreased rate of formation of the acidic by-product. Similarly, a POE of higher molecular weight (14 kDa) has been tested. Sodium acetate was too hydrophilic to affect the drug release and the biocompatibility of the polymer, whereas the presence of magnesium hydroxide markedly prolonged the drug release and improved the acceptability of the polymer. The increased molecular weight POE did not improve biocompatibility and a similar but delayed, inflammatory reaction was observed.

Animals↗

PubMed2000

The role of nitric oxide in the reduction of protein kinase C-induced contractile response in aortae from rats with portal hypertension.

BACKGROUND/AIMS: Protein kinase C plays a role in the regulation of vascular cell contraction but its activity may be reduced by nitric oxide. In portal hypertension, the exact mechanism by which nitric oxide induces vascular hyporeactivity to vasoconstrictors is unclear. The aim of this study was to investigate the role of the interaction of nitric oxide and protein kinase C in the vascular reactivity in isolated aortae from portal vein-stenosed rats. METHODS/RESULTS: The contractile response to phorbol 12,13-dibutyrate, a protein kinase C activator, was significantly reduced in portal vein-stenosed aortae compared to sham-operated aortae. Preincubation with N-nitro-L-arginine or endothelium removal enhanced the response to phorbol 12,13-dibutyrate. The hyporesponsiveness to phorbol 12,13-dibutyrate in portal vein-stenosed rat aortae was only corrected after endothelium removal. The time course of contractions induced by phorbol 12,13-dibutyrate showed that the contraction was maintained for 2 h in sham-operated aortae and decreased to baseline in portal vein-stenosed rat aortae. This decrease was inhibited by N-nitro-L-arginine preincubation or endothelium removal. Protein kinase C downregulation caused a more marked reduction of phenylephrine-induced contraction in portal vein-stenosed aortae than in sham-operated aortae. The time course of total nitric oxide synthase activity in the presence of phorbol 12,13-dibutyrate showed a decrease in nitric oxide synthase activity after 30 min in both groups. Nitric oxide synthase activity remained stable for 120 min in sham-operated aortae but returned to basal level in portal vein-stenosed aortae. CONCLUSIONS: Hyporeactivity to vasoconstrictors in portal vein-stenosed rat aortae may be due, in part, to a decrease in protein kinase C activation caused by nitric oxide overproduction.

Animals↗

PubMed2000

Effects of lipopolysaccharide on TNF-alpha production, hepatic NOS2 activity, and hepatic toxicity in rats with cirrhosis.

BACKGROUND/AIMS: Septic shock results in high mortality in patients with cirrhosis. Nitric oxide synthase 2 (NOS2) is induced by bacterial lipopolysaccharides (LPS) and plays a major role in the inflammatory response to bacterial infections. Little is known about the regulation of NOS2 in cirrhosis under septic conditions. Thus, the aim of this study was to determine tissue NOS2 activity, serum nitrate and tumor necrosis factor (TNF-alpha) levels and hepatic toxicity in cirrhotic rats after LPS administration. METHODS: Serum nitrates, TNF-alpha and transaminases were determined after LPS-administration in rats with secondary biliary cirrhosis and in sham-operated rats. Liver, lung, aortic and peritoneal macrophage NOS2 activities were determined by converting L[14C] arginine into L[14C] citrulline in a calcium free medium. Nitrate and TNF-alpha production were determined in a culture medium of peritoneal macrophages after in vivo LPS administration. RESULTS: LPS (1.5 mg/kg) induced 50% mortality in cirrhotic rats and no mortality in sham-operated rats. After LPS, TNF-alpha, nitrate and transaminase levels were significantly higher in cirrhotic rats compared to sham-operated rats. After LPS administration, there were no differences in NOS2 activity in the aorta, lungs, or peritoneal macrophages of the two groups, whereas NOS2 activity was significantly higher in the cirrhotic liver compared to the normal liver. CONCLUSIONS: In rats with cirrhosis, LPS administration induces higher mortality, hepatic toxicity, hepatic NOS2 activation and TNF-alpha release than in sham-operated rats. These results confirm the harmful role of septic shock in liver disease.

Animals↗

PubMed2000

Poly(ortho esters) - their development and some recent applications.

Poly(ortho esters) have been under development since the early 1970s and four families of such polymers have been described. Of most interest are poly(ortho ester) III and poly(ortho ester) IV. Poly(ortho ester) III is a semisolid material that has been shown to be highly biocompatible and is currently being investigated as an adjunct to glaucoma filtering surgery and other ocular applications. However, the polymerization is difficult to control and is not readily scaled up. Poly(ortho ester) IV can be easily prepared in a highly reproducible manner, is very stable provided moisture is rigorously excluded and has also been shown to be highly biocompatible. It is currently under development for a variety of applications, such as ocular delivery, protein release, post-operative pain treatment and post-operative cancer treatment.

Animals↗

PubMed2000

A poly(ortho ester) designed for combined ocular delivery of dexamethasone sodium phosphate and 5-fluorouracil: subconjunctival tolerance and in vitro release.

A viscous hydrophobic poly(ortho ester) (POE) has been developed as a biocompatible, biodegradable sustained release system for selected cases of glaucoma filtering surgery. Dexamethasone and 5-fluorouracil (5-FU) are frequently administered together post-operatively, for their anti-fibroblastic and anti-inflammatory properties, respectively. A combined sustained release of both drugs could be advantageously used. Drug release kinetics were studied using specially designed thermostated cells. Subconjunctival tolerance was evaluated on New Zealand albino rabbits by clinical evaluation. Due to its basicity, the addition of dexamethasone sodium phosphate (DEX-P) stabilized the polymer and prolonged 5-FU in vitro release from 2 to 4 days. Both therapeutic agents were released concomitantly, according to a linear profile. The presence of 5-FU only slightly affected the overall subconjunctival tolerance of POE in rabbits, whereas the addition of DEX-P markedly improved POE tolerance by reducing the hyperemia of the conjunctiva to a minimal grade.

Animals↗

PubMed2000

Processing and properties of two different poly (ortho esters).

Processing and properties of two structurally different poly (ortho esters) (POE) and their in vitro behavior have been compared. One POE was a copolymer of diketene acetal 3,9-diethylidene-2,4,8,10-tetraoxaspiro[5.5]undecane, trans-cyclohexanedimethanol and polyacetal. The other POE was a copolymer of diketene acetal 3,9-diethylidene-2,4,8,10-tetraoxaspiro[5.5]undecane, trans-cyclohexanedimethanol and trans-cyclohexanedimethanol-dilactide. The polyacetal POE was also used as a matrix incorporating two different model drugs, caffeine and furosemide. Both polymers were ultrasonically molded into slabs. The lactide modified POE was also melt-extruded into rods and self-reinforced using a solid state die-drawing technique. The initial strength values of both ultrasonically molded and extruded samples were close to those of non-oriented poly lactic acids. Self-reinforcing increased the shear strength, bending strength and modulus of the rods from 41.7+/-1.7 MPa to 66.7+/-2.3 MPa, from 78.5+/-22.8 MPa to 183+/-23 MPa and from 2.5+/-0.3 GPa to 4.4+/-0.3 GPa, respectively. In vitro hydrolysis of samples was studied either in phosphate buffer saline (PBS) or in simulated body fluid (SBF) at 37 degrees C. Samples degraded faster in unchanged PBS than in PBS changed weekly. The total in vitro strength retention time was relatively short varying from 14 days to 42 days depending on the processing method and polymer type. Samples retained their wet weight at initial level for a longer time but dry weight started to decrease already after the first in vitro week. Polymers or degradation products crystallized in SBF but remained amorphous when hydrolyzed in PBS. Some of the devices showed evidence of surface erosion, and the processing method affected the erosion. The storage time of these polymers was found to be limited. However, both polymers were found to be of interest in bone fixation and tissue engineering.

Journal Article↗

PubMed2000

Changes in protein kinase C isoforms in association with vascular hyporeactivity in cirrhotic rat aortas.

BACKGROUND & AIMS: Although protein kinase C (PKC) alterations may play a role in the abnormal reactivity of cirrhotic rat aortas, its isoforms and cellular distribution are unknown. We therefore studied the protein expression and cellular distribution of PKC isoforms and their activation in cirrhotic rat aortas. METHODS: Endothelium-denuded aortas from control and cirrhotic rats were examined. Immunoblots were performed with PKC isoform-specific antibodies. Aortic reactivity was determined for phorbol myristate acetate and phenylephrine after PKC down-regulation. RESULTS: PKC-alpha expression was reduced in both the cytosolic and membrane fractions in cirrhotic aortas. Trace amounts of PKC-beta were detected in cirrhotic aortas. PKC-delta was detected in the cytosolic fraction of control and cirrhotic aortas. PKC-zeta was detected in the membrane fraction in control aortas and in the cytosolic fraction in cirrhotic aortas. Phorbol myristate acetate and phenylephrine triggered translocation of PKC-alpha and PKC-delta isoforms from the cytosol to the membrane in control aortas; in cirrhotic aortas, only PKC-alpha was translocated. Aortic reactivities were reduced after PKC down-regulation. PKC-alpha and -delta activities were reduced in cirrhotic aortas. CONCLUSIONS: These results suggest that a change in PKC isoforms may be responsible in part for the abnormal reactivity and intracellular transduction through the PKC pathway in cirrhotic rat aortas.

Animals↗

PubMed2000

Role of aortic nitric oxide synthase 3 (eNOS) in the systemic vasodilation of portal hypertension.

BACKGROUND & AIMS: In portal hypertension, the mechanisms responsible for nitric oxide (NO) overproduction and vasodilation have not yet been clearly identified. One hypothesis is that NO synthase (NOS) 3 is overactivated because of shear stress in endothelial cells caused by hyperkinetic circulation. The aim of this study was to evaluate aortic NOS3 after a reduction of blood flow by long-time beta-adrenoceptor antagonist administration. METHODS: Propranolol or atenolol was administered by gavage in portal vein-stenosed and sham-operated rats. The vascular reactivity of thoracic aortic rings to phenylephrine, total aortic NOS activity, and aortic NOS3 messenger RNA and protein expressions were studied. RESULTS: After propranolol or atenolol administration, the aortic hyporesponse returned to normal in portal vein-stenosed rats. Total aortic NOS activity was higher in portal vein-stenosed aortas and significantly decreased after beta-blocker administration. Aortic NOS3 expressions were more marked in portal vein-stenosed aortas than in controls, but NOS3 expressions were reduced after propranolol administration. CONCLUSIONS: In portal hypertension, aortic NOS3 activity and expressions are enhanced but return to normal after beta-blocker administration. These results suggest that in portal hypertension, increased shear stress, related to high blood flow, induces enhanced aortic NOS3.

Adrenergic beta-Antagonists↗

PubMed2000

Evidence for an endothelium-derived hyperpolarizing factor in the superior mesenteric artery from rats with cirrhosis.

In cirrhosis, in splanchnic arteries, endothelium-dependent relaxation may persist even if overactive nitric oxide synthase (NOS) and cyclooxygenase (COX) are inhibited. In normal arteries, a significant endothelium-dependent relaxation to acetylcholine persists after NOS/COX inhibition. This relaxation is caused by smooth muscle cell (SMC) membrane hyperpolarization, which is sensitive to a combination of the potassium channel blockers apamin and charybdotoxin, and is mediated by an endothelium-derived hyperpolarizing factor (EDHF). The aim of this study was to detect EDHF and evaluate its pathophysiologic role in isolated superior mesenteric arteries from cirrhotic rats. Arterial rings were obtained and exposed to N(w)-nitro-L-arginine (L-NNA, a NOS inhibitor) and indomethacin (a COX inhibitor). Acetylcholine-induced membrane potential responses and concentration-response curves to the relaxant of acetylcholine were obtained with and without apamin plus charybdotoxin. Acetylcholine-induced responses were measured in certain rings from endothelium-denuded arteries. Contractions caused by the alpha(1)-adrenoceptor agonist phenylephrine were obtained in cirrhotic and normal rings with and without apamin and charybdotoxin. Significant acetylcholine-induced, endothelium-dependent, apamin- and charybdotoxin-sensitive, SMC membrane hyperpolarization and relaxation were found. An apamin- and charybdotoxin-sensitive hyporesponsiveness to the contractile action of phenylephrine was found in cirrhotic rings. In conclusion, in cirrhotic rats, in the superior mesenteric artery exposed to NOS/COX-inhibitors, an EDHF exists that may replace NOS/COX products to induce endothelium-dependent arterial relaxation.

Acetylcholine↗

PubMed2000

Effect of intrarenal infusion of angiotensin-(1-7) in the dog.

Angiotensin-(1-7), (Ang-(1-7)), a metabolite of Ang II and /or Ang I, was infused into the renal artery (i.r.a) of anesthetized dogs in order to demonstrate its possible direct renal action. The dose administered, 15 Ig/kg BW/min in isotonic saline (0.072 ml/kg BW/min) throughout the experiment, did not influence the systemic arterial pressure and water and sodium excretion from the contralateral noninfused kidney. Renal blood flow (RBF) was measured by an electromagnetic flowmeter, glomerular filtration rate (GFR) by (exogenous) creatinine clearance. In other groups of animals, either EXP 3174, an AT-1 receptor antagonist alone (30 Ig/kg BW/ min) or together with Ang-(1-7) (15 Ig/kg BW/min), were infused. In the last group, the AT-2 receptor antagonist PD 123319, 10 Ig/kg BW/min, was added to the infusion of Ang-(1-7). A small but significant decrease of RBF from 4.51+/-0.32 to 3.8+/-0.29 ml/g BW/min occurred after Ang-(1-7); this decrease was very similar when PD 123319 was added. However, an increase to 4.98+/-0.34 ml/g BW/min was seen after the addition of EXP 3174 to the i.r.a. infusion of Ang-(1-7); this increase was similar to the increase observed after EXP 3174 alone (5.21+/-0.33; p<0.02 in both cases). A very small but significant increase in GFR was seen after Ang-(1-7) + EXP 3174 or after the AT-1 blocker alone (0.64+/-0.049 and 0.62+/-0.05 vs. 0.6+/-0.05 ml/g BW/min in the Time Control Group, p<0.01 and 0.05, respectively). Water, sodium and urea excretion rates were increased in all groups infused with Ang-(1-7); after the combination of Ang-(1-7) + EXP 3174, all increases were higher than after every substance alone; however, statistical significance (p<0.05) was reached in sodium excretion values only. Potassium excretion rates were increased just in those groups in which EXP 3174 was present in the infusion fluid. In summary, Ang-(1-7) i.r.a. infusion in the dog is followed by increases in water, sodium and urea (but not potassium) excretion rates, highly probably of tubular origin. This effect is not completely blocked by the AT-1 - and not at all by the AT-2 receptor antagonist - thus indirectly suggesting another receptor could play a role. A small decrease in RBF disappears after EXP 3174, thus indicating an AT-1 receptor action.

Angiotensin I↗

PubMed2000

[Role of the kidney in long-term regulation of blood pressure and the development of hypertension].

Evidence about the crucial role of the kidney in the development and maintenance of the "essential" hypertension (i.e. hypertension which is accompanied with the absence of any pathological change in any of body organs) and in the regulation of "normal" blood pressure level (BP) has been accumulated. Blood pressure is expressed as a product of cardiac output (CO) and total peripheral resistance (TPR). TPR almost entirely depends on the volume of the extracellular fluid (ECFV): With increasing volume BP rises and vice versa. ECFV--due to intensive maintenance of the osmolality--almost entirely depends on the total amount of sodium in the organism. This amount is not determined by the intake of salt, which is in every civilized population always higher than necessary. Sodium balance is therefore critically determined by the output of sodium, which is carried out almost entirely by the kidney. The output depends on the quantity of the glomerular filtration and on the tubular reabsorption. Under normal circumstances, the increased sodium intake is accompanied by an increased excretion via the mechanism called "pressure natriuresis". It is based on the prompt increase of sodium excretion after an increase of BP, resulting from the increased sodium intake. Mechanism of such elevated excretion is not clear; lot of evidence has been accumulated for the existence of a humoral principle produced within the kidney. Such assumption is supported by experiments in which a kidney is transplanted from a hypertonic donor to a normotensive recipient: hypertension in the recipient develops. Similarly, kidney grafting from a normotensive animal corrects the hypertension in an originally hypertensive recipient. Important role of the renin-angiotensin (RAS) and nitric oxide (NO) systems is often stressed in this context. If kidney is unable to excrete the ingested amount of sodium at the normal BP, blood pressure must rise and the shift of the pressure-natriuresis curve to the right is the necessary consequence. If these conditions are long lasting, hypertension develops soon and becomes "fixed" by rebuilding the resistance arteries architecture.

Animals↗

PubMed2000

[Experimental ischemic renal injury--effect of surgical technique and the protective effect of a nonpeptide angiotensin II antagonist (losartan)].

Experimental renal ischaemic injuries are typically produced by temporary closure of the renal artery. In rats, two different methods of such temporary closure of the renal artery were compared: snaring of the artery by tourniquet, and clamping by a microsurgical bulldog clamp. The consequences of ischaemic periods 60, 90 and 120 minutes were evaluated. In different experimental series, the potential protective effect of non-peptic AT1 angiotensin II receptor antagonist losartan on postischaemic renal injury was evaluated. The seven-day survival and the degree of functional renal damage (according to the plasma levels of creatinine and urea) were analyzed 24 hours and 7 days after experimental renal ischaemia. Ischaemia, produced by the tourniquet led to a more significant renal damage than ischaemia caused by clamping of the renal artery by a microclamp (higher 7-day mortality rate, higher postischaemic plasma levels of creatinine and urea). Losartan decreased the consequences of renal ischaemia caused by the tourniquet, but did not change the outcome of renal ischaemia produced by microsurgical bulldog clamps. We found, that not only the duration of ischaemia and pharmacology, but even the surgical technique of producing renal ischaemia are important factors in experimental studies evaluating ischaemic renal damage. These findings provide evidence of the role of angiotensin II in postischaemic renal injury by a renal tourniquet. This particular mechanism is probably not involved, when renal artery is gently temporarily closed by a bulldog microclamp.

Angiotensin II↗

PubMed2000

Energy cost and cardiorespiratory demands of nunchaku exercise.

BACKGROUND: The purpose was to examine the energy cost and cardiorespiratory demands of nunchaku exercise, one of the martial arts performed with an instrument. METHODS: Nine male martial art practitioners (age 26.4 (+/-SD) 3.4 years, VO2max 54.1+/-9.0 ml x kg(-1)x min(-1)) completed three nunchaku exercise trials, lasting 20 sec, 1 min and 5 min. Cardiorespiratory response was followed by the Cosmed K4 portable respiratory analysis system. MEASURES: Oxygen consumption (VO2) was determined during pre-exercise rest, the exercise period and the recovery phase (10-15 min), and energy release from lactate (La) production was calculated assuming that an increase of 1 mmol x l(-1) corresponds to aVO2 of 3 ml O2 (di Prampero 1981). RESULTS: The overall energy cost of nunchaku exercise attained 76+/-16 kJ (229+/-48 kJ x min(-1)), 98+/-23 kJ and 271+/-72 kJ (54+/-14 kJ x min(-1)) for the 20 sec, 1 min and 5 min nunchaku exercise, respectively. From the point of view of the energy sources (alactic, lactic and oxidative), 20-sec performance was essentially "anaerobic alactic" (69:15:16%), 1 min exercise "alactic-oxidative" (49:16:35%) and 5-min performance an "oxidative" exercise workload (17% alactic: 6% lactic: 77% oxidative, respectively). The intensity of the exercise, on the average, corresponded to 43, 49 and 56% of VO2max and 69, 72 and 76% of HRmax, for the 20 sec, 1 min and 5 min exercises, respectively. CONCLUSIONS: Nunchaku exercise elicits high alactic and oxidative energy sources, but its demand for anaerobic glycolytic pathway seem to be relatively low, regardless the duration of the exercise. The energy cost (EC) for 20-sec to 5-min lasting exercise may be described by power function EC=10.84.t(-0.522) (n=24, r2=0.95), where EC is in kJ x min(-1) x kg(-1) and t in seconds.

Adult↗

PubMed1999

Concomitant and controlled release of dexamethasone and 5-fluorouracil from poly(ortho ester).

A viscous bioerodible and hydrophobic poly(ortho ester) has been developed as a biocompatible, sustained drug release system for an ophthalmic application in intraocular proliferative disorders. The combination of wound healing modulators such as 5-fluorouracil and dexamethasone is a major advantage since these drugs act at different stages of these diseases. Since 5-fluorouracil is an acidic, water-soluble compound and dexamethasone exists in three chemical forms, i.e. the water-insoluble base, the highly hydrophobic acetate ester or the basic phosphate salt, it was of interest to investigate whether the physicochemical properties of the drugs have an influence on their release rates, and whether a concomitant and sustained release of both 5-fluorouracil and dexamethasone could be achieved. It has been found that lipophilicity and acidobasicity play a major role in controlling drug release rates and polymer degradation. The combination of 5-fluorouracil and dexamethasone phosphate allows a sustained and concomitant release of both drugs, due to the basic characteristics of the corticosteroid which stabilize the polymer. This system appears to be promising for concomitant and controlled drug delivery aimed at the pharmacological treatment of intraocular proliferative disorders.

Anti-Inflammatory Agents, Non-Steroidal↗

PubMed1999

Technical note: biomechanical analysis of two absorbable fracture fixation pins after long-term canine implantation.

The design requirements for bioabsorbable fracture fixation devices for specific applications are as yet unknown. Therefore, a range of initial mechanical properties and degradation kinetics may provide developers with additional choices for the design of absorbable fracture fixation devices. This study evaluated the changes in push-out strength, polymer mechanical properties, and bone mechanical properties of self-reinforced poly(glycolide) (SR-PGA) and poly(ortho ester) (POE) fracture fixation pins implanted into the canine femoral canal for 18 months. Mechanical testing indicated that SR-PGA pins had degraded to a pasty consistency by 3 months, showing complete loss of all mechanical properties. Meanwhile, POE pins showed a simultaneous linear decrease in both compressive strength and stiffness to almost zero by the end of the study period, suggesting that these devices were undergoing surface erosion. However, changes in specimen diameter, which would support this mechanism, were not apparent. The decrease in polymer density after 12 months suggests that there was an increase in bulk erosion for POE devices. This was further supported by the observation of internal polymer resorption noticed in specimen cross-sections after 18 months. This observation appears to be related to the method of polymer processing; hot-compression molding of fine powdered polymer. The appearance of grain boundaries would provide a path for water to penetrate into the bulk polymer and cause autocatalysis in the interior of the implant.

Absorption↗

PubMed1999

In vitro and in vivo comparison of bulk and surface hydrolysis in absorbable polymer scaffolds for tissue engineering.

This article describes preliminary in vitro and in vivo studies comparing bulk and surface hydrolysis in absorbable polymer scaffolds proposed for tissue engineering of bone. The two polymers systems used were a bulk hydrolyzing 50:50 poly(DL-lactide-co-glycolide) (PLGA) and a surface hydrolyzing self-catalytic poly(ortho ester) (POE). Polymer scaffolds were exposed to physiological saline at body temperature and changes in polymer mass loss and inherent viscosity were monitored over time. New bone formation and local tissue response were evaluated by implanting scaffold disks of both polymer systems into non-critical-size calvarial defects in rabbits. New bone formation was determined by bone mineral density measurements, and local tissue response was determined by qualitative histology. Preliminary results confirmed that one of the main design characteristics for absorbable polymers in tissue engineering of bone, coordination of controlled polymer mass loss with new tissue formation, appeared to be achieved better using a surface hydrolyzing POE, rather than with a bulk hydrolyzing 50:50 PLGA. Bone mineral density at 6 and 12 weeks was an average 25% higher in the surface hydrolyzing scaffold. Unfortunately, the amount of bone formed was so inconsequential that this observation is of little relevance. Use of a water-soluble signaling factor such as basic fibroblast growth factor (bFGF) failed to increase bone formation. The histological response of these two polymer systems was similar and unaffected by the presence or absence of bFGF. The persistence of structural integrity for self-catalytic POE scaffolds after 6 and 12 weeks implantation, while 50:50 PLGA scaffolds had partially collapsed after 6 weeks, suggests surface hydrolyzing scaffolds may have some advantage over bulk hydrolyzing scaffolds in resisting normal in vivo stresses when used in a calvarial defect.

Animals↗

PubMed1999

Abnormal regulation of aortic NOS2 and NOS3 activity and expression from portal vein-stenosed rats after lipopolysaccharide administration.

Hyporeactivity to vasoconstrictors in aortae from portal vein-stenosed rats is associated with an increased activity of endothelial NO synthase (NOS3). In contrast, during sepsis, which is common in cirrhosis, vascular hyporeactivity is associated with an induction of inducible NOS2. The aim of this study was to investigate the in vitro reactivity to phenylephrine and the regulation of NOS2 and NOS3 in aortae from portal vein-stenosed rats after lipopolysaccharide (LPS) administration. Aortic vascular reactivity for phenylephrine, aortic NOS activity, and NOS2 and NOS3 protein expression were determined 5 hours after intravenous LPS or saline administration. Moreover, aortic NOS activity was measured after 5-hour in vitro incubation in LPS. LPS induced a significantly smaller decrease in aortic tension in portal vein-stenosed than in sham-operated rats. Under baseline conditions, aortic NOS activity and NOS3 protein expression were higher in portal vein-stenosed than in sham-operated rats, and NOS2 protein expression was not detected in aortae from either group. After LPS administration, NOS activity and NOS2 protein expression increased significantly less in portal vein-stenosed than in sham-operated rat aortae. Similar results were obtained after in vitro incubation with LPS. Endothelium removal or NOS3 inhibition with the calmodulin inhibitor, W7, increased NOS activity in the aortae of portal vein-stenosed rats after LPS incubation. In conclusion, in aortae of portal vein-stenosed rats exposed to LPS, no further decrease in aortic reactivity to phenylephrine was observed, and the induction of NOS2 was down-regulated. Endothelium removal or calmodulin inhibition inhibits NOS3 overactivity and leads to normalized NOS2 activation after LPS in aortae from portal vein-stenosed rats.

Animals↗

PubMed1999

Functional Equations in Binocular Space Perception.

A general theory of the relationship of binocular visual space to physical space is formulated within a conjoint measurement framework. Psychophysically motivated invariance relations induce various functional equations. Another class of functional equations arises if we additionally assume the validity of a different psychophysical theory that is based on a formula suggested by A. A. Blank. We solve and interpret most of these equations and point out an unsolved problem. The obtained results lead to a measurement-theoretic foundation of the psychophysical assumptions underlying the Luneburg theory of binocular vision. They also contribute to clarifying the relationship between the presented general theory and Blank's approach. Copyright 1999 Academic Press.

Journal Article↗