CLINICAL AND EXPERIMENTAL PHARMACOLOGY AND PHYSIOLOGY, Issue 4 2007
Zhi-Jiang Huang
SUMMARY 1Torsades de pointes (TDP) is a severe adverse effect during the clinical use of dofetilide, a selective blocker of the rapid component of the delayed rectifier potassium channel (IKr). The present study was designed to test whether CPU228, a derivative of dofetilide with calcium (Ca2+) antagonist properties, could reduce TDP without reducing the blockade of IKr. 2The incidence of TDP in a rabbit model and the effective refractory period (ERP) were measured and compared for dofetilide and CPU228. Suppression of IKr and the L-type Ca2+ current (ICa,L) and the Ca2+ transients of isolated cardiomyocytes were investigated by whole-cell patch-clamp and Fluo-3 dye spectrophotometry. 3The incidence of TDP was greatly reduced by CPU228 relative to dofetilide, occurring in only one of six rabbits compared with five of six rabbits following dofetilide (P < 0.05). In isolated atria, prolongation of ERP by CPU228 was less than that of dofetilide and no reverse frequency dependence was observed. Negative inotropism by CPU228 was significant against positive inotropism by dofetilide. CPU228 inhibited both IKr and ICa,L currents and the IC50 for ICa,L inhibition was 0.909 µmol/L. At 3 µmol/L, CPU228 significantly suppressed the Ca2+ transients. 4CPU228 is able to block ICa,L, contributing to decreased TDP, while also blocking IKr activity. By combined blockade of IKr and ICa,L, CPU228 shares the property of complex Class III anti-arrhythmic agents. [source]

Studies on dentin grafts to bone defects in rabbit tibia and mandible; development of an experimental model

DENTAL TRAUMATOLOGY, Issue 1 2009
Lars Andersson
This property may possibly be used as an alternative or supplement to bone grafting to defective areas after trauma prior to treatment with osseointegrated implants. Hence, the objective of this study was to investigate if dentin can be used as a graft in bone defects in an experimental rabbit model. Materials and Methods:, Eight New Zealand White Rabbits were used to prepare bone cavities either in the angle of the mandible or tibia. Six of the eight tibial and six of the eight mandibular bone defects were filled with dentin blocks from human premolars which were extracted for orthodontic treatment. Two mandibular and two tibial bone cavities were used as controls and all the rabbits were sacrificed after 3 months. Radiographic and histological examinations were performed. Results:, There was a difference in healing pattern between the mandibular and tibial defects. In the mandible, the dentin blocks were resorbed to a larger extent and more often surrounded by fibrous tissue, probably due to the fact that the dentin blocks were mobile because of the thin mandibles and muscular activity in that area. Only some dentin blocks were ankylosed with the mandibular bone. In the tibia however, all dentin blocks were fused to bone over a large area. Osseous replacement resorption was seen. In control cavities, bone formation was seen but was never complete. No signs of inflammatory changes were seen in any fused grafts. Conclusions:, Dentin grafts have a potential to be incorporated in bone without inflammation and can be used as bone inducer and later replaced by bone. Thus, rabbit tibia served as a better model for further studies of this phenomenon when compared to the mandible. [source]

Arousal, but not nursing, is necessary to elicit a decreased fear reaction toward humans in rabbit (Oryctolagus cuniculus) pups

DEVELOPMENTAL PSYCHOBIOLOGY, Issue 3 2003
Péter Pongrácz
Abstract Rabbits that are handled at the time of feeding during the first week postpartum show reduced fear of humans later in their lives as compared to unhandled controls. Effective handling has been shown to be confined to a sensitive period. Our study aimed to investigate if feeding itself (provided by a second doe, 6 hr after the standard nursing time) affects the levels of fear of humans later in life. Our results showed that (a) the prenursing state of excitement is only characteristic of the standard nursing and is not elicited by a second feeding 6 hr past the usual nursing time, repeated daily across the first week postpartum; and (b) handling linked to a second feeding 6 hr after the standard nursing does not reduce fear responses toward humans at weaning. We conclude that the aroused state, per se, is essential for the reduction of a rabbit's fear response toward humans provoked by early handling. © 2003 Wiley Periodicals, Inc. Dev Psychobiol 43: 192,199, 2003. [source]

Amplitude and Velocity of Mitral Annulus Motion in Rabbits

ECHOCARDIOGRAPHY, Issue 4 2004
Li-ming Gan M.D., Ph.D.
Objective: During recent years, the amplitude and the maximal systolic velocity of the mitral annulus motion (MAM) have been established as indices of the left ventricular systolic function and the maximal diastolic velocity of the annulus motion has been suggested as an index of diastolic function. The main aims of the present study were to investigate the feasibility of these techniques in rabbits and to investigate age-related changes concerning these variables. Methods: Twenty-one New Zealand white rabbits were investigated by echocardiographic M-mode and pulsed tissue Doppler. One subgroup (I) included 11 still-growing, 3.0 ± 0.2 month-old, animals and another group (II) included 10 young grown up rabbits, 12.1 ± 1.5 months old. Results: The amplitude (4.8 ± 0.6 and 3.5 ± 0.3 mm, respectively) and maximal systolic (98 ± 14 and 66 ± 7 mm/s, respectively) and diastolic (111 ± 21 and 80 ± 12 mm/s, respectively) velocities of the MAM were significantly (P < 0.001) higher in group I than in group II, despite a bigger heart in the animals in the latter group. A coefficient of variation of <5% was found for both inter- and intraobserver variability for both amplitude and velocities. Conclusions: The amplitude and velocities of MAM are easily recorded in rabbits with excellent reproducibility and the changes with age seem to be very similar to those in humans. These noninvasive M-mode and tissue Doppler methods are therefore suitable for the investigation of left ventricular function in experimental studies in rabbits. (ECHOCARDIOGRAPHY, Volume 21, May 2004) [source]

Mimicking Natural Nursing Conditions Promotes Early Pup Survival in Domestic Rabbits

ETHOLOGY, Issue 3 2000
Gérard Coureaud
In the wild rabbit, Oryctolagus cuniculus, mother,young relationships are based on restricted, once-per-day nursing interactions. Correspondingly, pups have evolved an efficient strategy of energy saving. Here we investigate under breeding conditions, whether matching or not, the once-daily nursing visit by the rabbit females has an effect on pup survival and growth. Two nursing regimen were applied to 89 primiparous (P) and to 78 multiparous (M) does: (a) one that matched the once daily nursing pattern (closed nest-box during the whole day except for a few minutes devoted to nursing) and (b) one that did not match it (24 h free nest access). In P females, the controlled nest access resulted in lower mortality between birth and weaning (8.1%) as compared to the free nest-access (18%). This effect was recorded from postnatal d 3,4 onwards. Both treatments induced different death causes (starvation (63%) in controlled-access regimen, and wounds and nest-soiling (29%) in free-access regimen). While both experimental nest-access regimens differentially affected pup survival in P or M females, they were without influence on pup growth rate in does of either parity. It is concluded that repeated nest visits by the female increase risks of injury to pups, and of out-of-time pup activation or sucking, and that, more generally, it plays against the ethophysiologigal strategy of biomass conservation evolved by rabbit newborns. The fact that the nest-access regimen no longer affected pup survival from the second parity suggests that the behaviour of multiparous does more adequately models the offspring demands. [source]

Influence of Different Surface Machining Treatments of Magnesium-based Resorbable Implants on the Degradation Behavior in Rabbits,

ADVANCED ENGINEERING MATERIALS, Issue 5 2009
Nina Von Der Höh
The surface of magnesium,calcium implants (MgCa0.8) was differently treated which resulted in cylinders with smooth, sand-blasted, or threaded surface. These cylinders were implanted into the medial femoral condyle of New Zealand White rabbits. The degradation behavior and the reaction of the organism were assessed by clinical compatibility, radiographs, and µ -computed tomography. [source]

Route of Administration Differentially Affects Fevers Induced by Gram-Negative and Gram-Positive Pyrogens in Rabbits

EXPERIMENTAL PHYSIOLOGY, Issue 3 2002
T. Cartmell
We have investigated the febrile responses of New Zealand White rabbits to a Gram-negative pyrogen (bacterial lipopolysaccharide (LPS) from Salmonella typhosa), commonly associated with systemic infection, and a Gram-positive pyrogen (Staphylococcus aureus), more frequently associated with superficial soft tissue infection, each administered via one of four different routes (intravenous, intramuscular, subcutaneous or intraperitoneal) at each of three different doses (LPS: 0.1, 1 and 10 ,g kg,1; S. aureus: 1.5 × 107, 1.5 × 108 and 1.5 × 109 cell walls kg,1). Intravenous administration of LPS evoked rapid, dose-dependent biphasic fever. Injection of LPS by the other routes also evoked dose-dependent fever. However, these fevers were monophasic, had increased latency of onset, and were of lower amplitude. It is important to note that a dose of approximately 10 and 100 times that of the standard intravenous dose was required to produce a similar peak rise in temperature when administered subcutaneously and intraperitoneally, respectively. Intravenous injection of the highest dose of S. aureus evoked dose-dependent biphasic fever, with short latency of onset, which was very similar to that induced by intravenous LPS. At lower doses, intravenous S. aureus induced monophasic fever. No fever occurred when the same doses of S. aureus were administered by any other route. We conclude that any of the four routes may be used for the study of LPS-induced fever, provided that the doses are adjusted. However, studies of S. aureus -induced fever, and detection of contamination with either pyrogen, requires intravenous injection. [source]

A colony immunoblotting method for quantitative detection of a Bifidobacterium animalis probiotic strain in human faeces

JOURNAL OF APPLIED MICROBIOLOGY, Issue 6 2000
H. Duez
A colony immunoblotting method has been developed to allow detection of the probiotic Bifidobacterium animalis strain DN-173 010 in human faecal samples. Rabbits were immunized with heat-killed DN-173 010 bacteria resulting in the production of an antiserum highly specific for bacteria belonging to Bif. animalis species. Of the 89 strains representative of 29 different bifidobacterial species tested, only the 15 strains of the Bif. animalis species could be detected with the antiserum. In Western immunoblotting the serum reacts with a protein of 45-kDa apparent molecular weight. None of the bacteria classically encountered in human faecal samples and able to grow on non-selective Columbia blood agar (enterobacteria, Bacteroides or Lactobacillus for instance) reacted with the antiserum. Taking advantage of the high specificity of the antiserum and of the absence of Bif. animalis bacteria in faeces samples of five human volunteers, we demonstrated that strain DN-173 010 survives the intestinal transit. Being based on a combination of semiselective cultivation and colony immunoblotting techniques, the method allowed detection of the Bif. animalis strain even when it represented only one thousandth of the total bifidobacterial population. [source]

Noggin Inhibits Postoperative Resynostosis in Craniosynostotic Rabbits,

JOURNAL OF BONE AND MINERAL RESEARCH, Issue 7 2007
Gregory M Cooper PhD
Abstract Inhibition of bone formation after surgery to correct craniosynostosis would alleviate the need for secondary surgeries and decrease morbidity and mortality. This study used a single dose of Noggin protein to prevent resynostosis and improve postoperative outcomes in a rabbit model of craniosynostosis. Introduction: Craniosynostosis is defined as the premature fusion of one or more of the cranial sutures, which causes secondary deformations of the cranial vault, cranial base, and brain. Current surgical intervention involves extirpation of the fused suture to allow unrestricted brain growth. However, resynostosis of the extirpated regions often occurs. Several bone morphogenetic proteins (BMPs), well-described inducers of ossification, are involved in bone healing. This study tested the hypothesis that a postoperative treatment with Noggin, an extracellular BMP inhibitor, can inhibit resynostosis in a rabbit model of human familial nonsyndromic craniosynostosis. Materials and Methods: Thirty-one New Zealand white rabbits with bilateral coronal suture synostosis were divided into three groups: (1) suturectomy controls (n = 13); (2) suturectomy with BSA in a slow-resorbing collagen vehicle, (n = 8); and (3) suturectomy with Noggin in a slow-resorbing collagen vehicle (n = 10). At 10 days of age, a 3 × 15-mm coronal suturectomy was performed. The sites in groups 2 and 3 were immediately filled with BSA-loaded gel or Noggin-loaded gel, respectively. Serial 3D-CT scan reconstructions of the defects and standard radiographs were obtained at 10, 25, 42, and 84 days of age, and the sutures were harvested for histological analysis. Results: Radiographic analysis revealed that Noggin-treated animals had significantly greater coronal suture marker separation by 25 days and significantly greater craniofacial length at 84 days of age compared with controls. 3D-CT analysis revealed that Noggin treatment led to significantly greater defect areas through 84 days and to increased intracranial volumes at 84 days of age compared with other groups. Histological analysis supported CT data, showing that the untreated and BSA-treated groups had significant healing of the suturectomy site, whereas the Noggin-treated group had incomplete wound healing. Conclusions: These data support our hypothesis that inhibition of BMP activity using Noggin may prevent postoperative resynostosis in this rabbit model. These findings also suggest that Noggin therapy may have potential clinical use to prevent postoperative resynostosis in infants with craniosynostosis. [source]

Recombinant newcastle disease virus capsids displaying enterovirus 71 VP1 fragment induce a strong immune response in rabbits

JOURNAL OF MEDICAL VIROLOGY, Issue 8 2006
Lalita Ambigai Sivasamugham
Abstract The complete VP1 protein of EV71 was truncated into six segments and fused to the C-terminal ends of full-length nucleocapsid protein (NPfl) and truncated NP (NPt; lacks 20% amino acid residues from its C-terminal end) of newcastle disease virus (NDV). Western blot analysis using anti-VP1 rabbit serum showed that the N-terminal region of the VP1 protein contains a major antigenic region. The recombinant proteins carrying the truncated VP1 protein, VP11,100, were expressed most efficiently in Escherichia coli as determined by Western blot analysis. Electron microscopic analysis of the purified recombinant protein, NPt-VP1,100 revealed that it predominantly self-assembled into intact ring-like structures whereas NPfl-VP1,100 recombinant proteins showed disrupted ring-like formations. Rabbits immunized with the purified NPt-VP1,100 and NPfl-VP1,100 exhibited a strong immune response against the complete VP1 protein. The antisera of these recombinant proteins also reacted positively with authentic enterovirus 71 and the closely related Coxsackievirus A16 when analyzed by an immunofluorescence assay suggesting their potential as immunological reagents for the detection of anti-enterovirus 71 antibodies in serum samples. J. Med. Virol. 78:1096,1104, 2006. © 2006 Wiley-Liss, Inc. [source]

Local injection of thrombin-related peptide (TP508) in PPF/PLGA microparticles,enhanced bone formation during distraction osteogenesis

JOURNAL OF ORTHOPAEDIC RESEARCH, Issue 4 2008
Yan Wang
Abstract We have previously demonstrated that injections of the thrombin-related peptide, TP508, into the lengthening gap have significantly enhanced bone consolidation in a rabbit model of distraction osteogenesis. This study was to further test the effect of a single TP508 injection in slow release preparation on bone formation during distraction osteogenesis. Rabbits had left tibiae lengthened unilateral lengthener at rate of 1.4 mm/day for 6 days. TP508 was injected into as the following: Group 1, TP508 in saline; Group 2, in PPF/PLGA [poly(propylene fumarate)/poly(D,L -lactic- co -glycolic acid)] microparticles; and Group 3, dextran gel only. All the animals were killed 2 weeks after lengthening. On radiographies, more bone was formed in the two TP508-treated groups at first and secnd week postlengthening than that of the control Group 3. Microcomputed tomography (microCT) at 2 weeks indicated that the most advanced bone formation and remodeling was seen in Group 2. The mean volumetric BMD of the regenerates was significantly higher in the TP508 treated groups compared to the control group (p,<,0.05). Histological evaluations supported the radiographic and the microCT results. In conclusion, we have demonstrated that a single injection of small amount of TP508 (300 µg) at the end of lengthening phases has significantly enhanced bone consolidation process in a rabbit model of distraction osteogenesis. The delivery of TP508 in PPF/PLGA microparticles appears to lead to a better quality bone formation over the saline delivery, further examinations are needed to confirm if PPF/PLGA microparticles may be desirable drug delivery form in augmenting bone formation. © 2007 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 26:539,546, 2008 [source]

SIAM-Like Phenomenon Caused by Low Doses of Alcohol

ALCOHOLISM, Issue 2010
Akiko Shimamoto
Background:, Swift increase in alcohol metabolism (SIAM) is usually evoked by a large dose of ethanol, which is often demonstrated by an abrupt increase in oxygen uptake. SIAM was induced by low doses of ethanol and evaluated by pharmacokinetic analyses of ethanol and its metabolites. Methods:, Rabbits were initially administered 1.0 g/kg of ethanol solution and the same dose was given to the bolus group 6 hours after the first injection. The infusion group was administered 0.25 g/kg/h of ethanol 2 hours after the first injection. Blood concentrations of ethanol, acetaldehyde, and acetate were then determined and comparisons were made using pharmacokinetic parameters. Results:, A significantly higher ethanol elimination rate was observed after re-administration of ethanol to the bolus group. Other pharmacokinetic parameters were unaffected. The concentration at steady state (Css) for the infusion group was stable. A significantly higher level of mean residence time (MRT) in blood acetaldehyde was observed for the bolus group, whereas no MRT changes were observed for the infusion group. A significantly higher level of blood acetate Css was observed after re-administration of ethanol to the bolus group, following the changes in area under concentration and MRT. No Css changes were observed for the infusion group. The Css of acetate at stage 2 was significantly higher for the bolus group, compared to the infusion group. Conclusion:, Low doses of ethanol enhanced alcohol metabolism in rabbits, according to a pharmacokinetic analysis of circulating ethanol concentrations. Simultaneous analyses of its metabolites followed the kinetic of ethanol. [source]

Alcohol-Induced Electrical Remodeling: Effects of Sustained Short-Term Ethanol Infusion on Ion Currents in Rabbit Atrium

ALCOHOLISM, Issue 10 2009
Roman Laszlo
Background:, In some patients, above-average alcohol consumption before occurrence of atrial fibrillation (AF) in terms of a "holiday heart syndrome" (HHS) can be determined. There is evidence that long before development of apparent alcohol-induced cardiomyopathy, above-average alcohol consumption generates an arrhythmogenic substrate which abets the onset of AF. Changes of atrial current densities in terms of an electrical remodeling after sustained short-term ethanol infusion in rabbits as a potential part of HHS pathophysiology were examined in this study. Methods:, Rabbits of the ethanol group (EG) received sustained short-term intravenous alcohol infusion for 120 hours (during infusion period, blood alcohol level did not fall below 158 mg/dl), whereas NaCl 0.9% was infused in the placebo group (PG). Using patch clamp technique in whole-cell mode, atrial current densities were measured and compared between both groups. Results:, Ethanol infusion did not alter current densities of Ito [58.7 ± 5.0 pA/pF (PG, n = 20 cells) vs. 53.9 ± 5.0 pA/pF (EG, n = 24)], Isus [11.3 ± 1.4 pA/pF (PG, n = 20) vs. 10.2 ± 1.0 pA/pF (EG, n = 24)], and IK1 [,1.6 ± 0.3 pA/pF (PG, n = 17) vs. ,2.0 ± 0.3 pA/pF (EG, n = 22)]. However, alcohol infusion resulted in a remarkable reduction of ICa,L current densities [,28.4 ± 1.8 pA/pF (PG, n = 20) vs. ,15.2 ± 1.4 pA/pF (EG, n = 22)] and INa [,75.4 ± 3.6 pA/pF (PG, n = 17) vs. ,35.4 ± 4.4 pA/pF (EG, n = 21)], respectively. Conclusion:, Sustained short-term ethanol infusion in rabbits alters atrial current densities. HHS might be favored by alcohol-induced atrial electrical remodeling. [source]

Functional characteristics of antibodies induced by Arg-gingipain (HRgpA) and Lys-gingipain (Kgp) from Porphyromonas gingivalis

MOLECULAR ORAL MICROBIOLOGY, Issue 4 2001
T. Nakagawa
Arginine-specific gingipain (HRgpA) and lysine-specific gingipain (Kgp), enzymes produced by Porphyromonas gingivalis, may be candidates for an anti,P. gingivalis vaccine. The purpose of our study was to determine whether HRgpA and Kgp have opsonic target sites and whether these sites are available and accessible on intact P. gingivalis cells. Rabbits were used to generate polyclonal antibodies to both proteins. Animals were immunized and immunoglobulin G (IgG) fractions were isolated from preimmune and immune sera. Functional characteristics of the antibodies were assessed by determining antibody titers by enzyme-linked immunosorbent assay (ELISA), generating Western immunoblots, and measuring antibody enhancement of P. gingivalis opsonization, phagocytosis and killing by polymorphonuclear leukocytes (PMN) of intact cells of strains of P. gingivalis representative of the four serotypes. Strains studied included 33277 (serotype A), A7A1,28 (serotype B), W50 (serotype C) and 381 (serotype D). Both HRgpA and Kgp induced high titers of IgG antibody. Anti-HRgpA and anti-Kgp bound to both HRgpA and Kgp demonstrating a large proportion of shared antigenic epitopes. The two antibodies bound equally well to all four P. gingivalis serotypes with titers ranging from 77 to 205 ELISA units when compared to preimmune IgG set at 1 ELISA unit. The immunoblot patterns of binding of the two antibodies to HRgpA and Kgp and to sonicates of the four P. gingivalis serotypes were virtually identical. Both antibodies detected components in HRgpA at 27, 35 and 45 kDa and in Kgp at 27, 32, 35, 40 and 55 kDa. The antibodies also detected components at or near these same positions in addition to multiple high molecular mass components in the cell sonicates of P. gingivalis. Both proteins induced antibodies that significantly enhanced opsonization as assessed by chemiluminescence, with values ranging from 130 mV to 375 mV for anti-HRgpA IgG and from 240 mV to 475 mV for anti-Kgp IgG. Both antibodies significantly enhanced PMN-mediated bacterial killing of the four P. gingivalis serotypes, although the percentage of killing varied among the serotypes (24,81% for anti-HRgpA and 37,89% for anti-Kgp). Thus, both HRgpA and Kgp express opsonic target sites and induce high titers of antibodies that opsonize and enhance killing of all four serotypes of P. gingivalis. These two proteins appear to be potential candidate antigens for an anti,P. gingivalis vaccine. [source]

Fimbriae of Porphyromonas gingivalis induce opsonic antibodies that significantly enhance phagocytosis and killing by human polymorphonuclear leukocytes

MOLECULAR ORAL MICROBIOLOGY, Issue 3 2001
Q. Fan
Porphyromonas gingivalis has been strongly implicated in the pathogenesis of human periodontitis. Fimbriae mediate adherence and colonization of the oral cavity by this organism and may, therefore, have potential for use as antigen in an anti,P. gingivalis vaccine. The purpose of our study was to determine whether P. gingivalis fimbriae have opsonic target sites and whether they are accessible on the cell surfaces and cross-reactive among P. gingivalis fimbrial types and serotypes. Rabbits were immunized with a vaccine. The antiserum reacted with a 43-kDa fimbrillin monomer and a 43-kDa component in whole-cell sonicates of P. gingivalis 33277, but it showed only very weak reactivity in the 43-kDa region of Western blots of a whole-cell sonicate of strain DPG3, a mutant that does not express functional fimbriae. The antibody enhanced chemiluminescence approximately six-fold relative to preimmune serum values and significantly enhanced phagocytosis and killing of P. gingivalis 33277 by human polymorphonuclear leukocytes. Peak opsonic activity was observed at week 6 followed by a plateau that remained until week 16. The fimbria-deficient mutant DPG3 did not bind antifimbrial antibody and was not opsonized, whereas strain 381, the parent of the mutant, was opsonized. The specific antibody bound to and opsonized P. gingivalis strains 33277 and 381 (fimbria type I) but not W50, A7A-1-28, 9-14K-1 or FAY-19M-1 (fimbrial types II,V). Specific antibody bound to strain 2561 (fimbrial type I) but, as assessed by chemiluminescence, did not opsonize it. While fimbriae have opsonic target sites that are accessible on P. gingivalis cell surfaces, the relevant opsonic target sites do not appear to be shared across serotypes or fimbrial types. Thus, a vaccine containing, as antigen, fimbrial protein from a single P. gingivalis strain would likely be ineffective against infections by P. gingivalis strains expressing other fimbrial types. [source]

Inhibition of p38 MAPK improves intestinal disturbances and oxidative stress induced in a rabbit endotoxemia model

NEUROGASTROENTEROLOGY & MOTILITY, Issue 5 2010
S. Gonzalo
Abstract Background, Lipopolysaccharide (LPS) decreases intestinal contractility and induces the release of reactive oxygen species, which play an important role in the pathogenesis of sepsis. p38 mitogen-activated protein kinase (MAPK) can be activated by a variety of stimuli such as LPS. The aims of this study were: (i) to investigate the role of p38 MAPK in the effect of LPS on (a) the acetylcholine, prostaglandin E2 and KCl-induced contractions of rabbit duodenum and (b) the oxidative stress status; (ii) to localize the active form of p38 in the intestine. Methods, Rabbits were injected with (i) saline, (ii) LPS, (iii) SB203580, a specific p38 MAPK inhibitor or (iv) SB203580 + LPS. Duodenal contractility was studied in an organ bath. SB203580 was also tested in vitro. The protein expression of p-p38 and total p38 was measured by Western blot and p-p38 was localized by inmunohistochemistry. The formation of products of oxidative damage to proteins (carbonyls) and lipids (MDA+4-HDA) was quantified in intestine and plasma. Key Results, ACh, PGE2 and KCl-induced contractions decreased with LPS. LPS increased phospho-p38 expression and the levels of carbonyls and MDA+4-HDA. SB203580 blocked the effect of LPS on the ACh, PGE2 and KCl-induced contractions in vivo and in vitro and the levels of carbonyls and MDA+4-HDA. P-p38 was detected in neurons of the myenteric plexus and smooth muscle cells of duodenum. Conclusions & Inferences, Lipopolysaccharide decreases the duodenal contractility in rabbits and increases the production of free radicals. p38 MAPK is a mediator of these effects. [source]

Detection of the Sm31 antigen in sera of Schistosoma mansoni, infected patients from a low endemic area

PARASITE IMMUNOLOGY, Issue 1 2010
G. S. SULBARÁN
Summary Schistosoma mansoni cathepsin B (Sm31) is a major antigen from adult worms that circulates in the blood of infected patients (Li et al., Parasitol Res 1996; 82: 14,18). An analysis of the Sm31 sequence (Klinkert et al., Mol Biochem Parasitol 1989; 33: 113,122) allowed the prediction of seven hydrophilic regions that were confirmed to be exposed on the surface of a 3D model of Sm31; the species specificity of these regions was checked using BLAST analysis. The corresponding peptides were chemically synthesized in polymerazible forms using the t-Boc technique. Rabbits developed a high humoral response against these peptides as tested by a multiple antigen blot assay; it recognized native Sm31 in crude S. mansoni extracts and as circulating antigen in sera of S. mansoni-infected patients by western blot. Relevant antigenic determinants were located at the N- and C-terminus sequences. Antibodies against these regions recognized the native enzyme in an ELISA-like assay called cysteine protease immuno assay in which the immunocaptured enzyme was revealed by the intrinsic cathepsin B hydrolytic activity of Sm31. The method successfully and specifically detected Sm31 in sera of infected individuals, most of them (83·3%) with light infections, offering a rationale for the development of parasite enzyme capture assays using anti-synthetic peptide antibodies for possible use in the diagnosis of schistoso,iasis. [source]

Low doses of silver nitrate induce pleurodesis with a limited systemic response

RESPIROLOGY, Issue 6 2009
Evaldo MARCHI
ABSTRACT Background and objective: Both talc and 0.5% silver nitrate have been shown to induce effective pleurodesis. However, acute adverse systemic inflammatory effects have been described with both agents. The aim of this study was to assess in rabbits the systemic effects associated with a new technique of pleurodesis using repeated low doses of 0.1% silver nitrate. Methods: Rabbits were injected intrapleurally through a chest tube with 0.1% silver nitrate at 0, 24 and 48 h. Other groups received a single injection of 0.5% silver nitrate or 400 mg/kg of talc. Blood samples were collected at 24, 48 and 72 h, and at 7 days, and cytological and biochemical measurements were performed. After 28 days, the presence of macroscopic pleural adhesions and microscopic pleural fibrosis in the pleural cavity were evaluated. Results: Both talc and 0.5% silver nitrate caused significant increases in blood neutrophils, serum LDH, IL-8, transforming growth factor-, and CRP in comparison with control at almost all time points, whereas sequential doses of 0.1% silver nitrate only increased LDH and CRP in the first 24 h and transforming growth factor-, at all time points. All groups showed efficient pleurodesis, with no differences in pleural adhesions or fibrosis. Conclusions: Sequential doses of 0.1% silver nitrate produced efficient pleurodesis in rabbits, with a low systemic inflammatory response in comparison with 400 mg/kg of talc or 0.5% silver nitrate. [source]

Effects of melatonin on the oxidant/antioxidant status and lung histopathology in rabbits exposed to cigarette smoke

RESPIROLOGY, Issue 4 2006
Mehmet UNLU
Objectives and background: To evaluate the effects of cigarette smoking on the histopathology and the oxidant/antioxidant status of the lungs and to test the potential antioxidant benefits of melatonin on these induced changes. Methodology: Rabbits were exposed to cigarette smoke in a glass chamber for 1 h daily for 1 month with or without intraperitoneal melatonin injection. A melatonin control group was given intraperitoneal melatonin only. A control group was exposed to clean air only. At the end of 1 month, animals were sacrificed and lung tissues were examined histopathologically. Blood levels of protein sulphydryls, carbonyls, prostaglandin F2, (PGF2,), malondialdehyde (MDA), glutathione peroxidase and superoxide dismutase (SOD) were measured. Results: Intraparenchymal vascular congestion and thrombosis, intraparenchymal haemorrhage, respiratory epithelial proliferation, number of macrophages in the alveolar and bronchial lumen, alveolar destruction, emphysematous changes and bronchoalveolar haemorrhage scores were significantly increased in rabbits exposed to cigarette smoke compared with the control group. Protein sulphydryls and SOD levels were significantly decreased; carbonyls, PGF2, and MDA levels were significantly increased in the smoke exposed rabbits. Administration of melatonin to rabbits exposed to cigarette smoke caused a reduction in the bronchoalveolar haemorrhage score and blood carbonyls levels. Other parameters were unaffected by melatonin. Conclusion: Exposure to cigarette smoke causes severe histopathological changes and negatively affects the oxidant/antioxidant status in the lungs of rabbits. A low daily dose of melatonin has some protective effects on histopathological changes and oxidant/antioxidant status of the lungs in smoke exposed rabbits. [source]

Comparing transforming growth factor beta-2 and fibronectin as pleurodesing agents

RESPIROLOGY, Issue 4 2001
Y. C. GARY LEE
Background: We have recently demonstrated that transforming growth factor beta-2 (TGF-,2) can produce effective pleurodesis. Whether this effect can be reproduced by the use of its downstream proteins is not known. This study compared the effectiveness of TGF-,2 and fibronectin in inducing pleurodesis in rabbits. Methodology: New Zealand white rabbits (1.5,2.0 kg) were given 1.7 ,g of TGF-,2 (n = 5) or 2.0 mg of cellular fibronectin (n = 4) intrapleurally via a chest tube. The induced pleural fluid was collected and analyzed. The rabbits were sacrificed after 14 days. The pleurodesis was graded macroscopically from 1 (none) to 8 (symphysis > 50%). Results: All rabbits in the TGF-,2 group developed effective pleurodesis while none in the fibronectin group had scores > 2 (pleurodesis scores 7.0 ± 0.6 vs 1.3 ± 0.3, P < 0.001). Rabbits that received TGF-,2 produced large amounts of pleural fluid initially (< 4 days). Microscopically, the pleura of rabbits in the TGF-,2 group showed prominent spindle cell proliferation and collagen deposition, but no significant inflammation or mesothelial proliferation. Pleural tissues of rabbits in the fibronectin group had occasional thin collagen deposits only. The intrapleural administration of 2.0 mg of fibronectin, a downstream product of TGF-,, did not induce effective pleurodesis, as did the intrapleural administration of TGF-,2. Conclusions: The present study suggests that the mechanism by which TGF-,2 induces pleurodesis is not predominantly dependent on the production of fibronectin. [source]

Masticatory Loading, Function, and Plasticity: A Microanatomical Analysis of Mammalian Circumorbital Soft-Tissue Structures

THE ANATOMICAL RECORD : ADVANCES IN INTEGRATIVE ANATOMY AND EVOLUTIONARY BIOLOGY, Issue 4 2010
Eldin Ja, arevi
Abstract In contrast to experimental evidence regarding the postorbital bar, postorbital septum, and browridge, there is exceedingly little evidence regarding the load-bearing nature of soft-tissue structures of the mammalian circumorbital region. This hinders our understanding of pronounced transformations during primate origins, in which euprimates evolved a postorbital bar from an ancestor with the primitive mammalian condition where only soft tissues spanned the lateral orbital margin between frontal bone and zygomatic arch. To address this significant gap, we investigated the postorbital microanatomy of rabbits subjected to long-term variation in diet-induced masticatory stresses. Rabbits exhibit a masticatory complex and feeding behaviors similar to primates, yet retain a more primitive mammalian circumorbital region. Three cohorts were obtained as weanlings and raised on different diets until adult. Following euthanasia, postorbital soft tissues were dissected away, fixed, and decalcified. These soft tissues were divided into inferior, intermediate, and superior units and then dehydrated, embedded, and sectioned. H&E staining was used to characterize overall architecture. Collagen orientation and complexity were evaluated via picrosirius-red staining. Safranin-O identified proteoglycan content with additional immunostaining performed to assess Type-II collagen expression. Surprisingly, the ligament along the lateral orbital wall was composed of elastic fibrocartilage. A more degraded organization of collagen fibers in this postorbital fibrocartilage is correlated with increased masticatory forces due to a more fracture-resistant diet. Furthermore, the lack of marked changes in the extracellular composition of the lateral orbital wall related to tissue viscoelasticity suggests it is unlikely that long-term exposure to elevated masticatory stresses underlies the development of a bony postorbital bar. Anat Rec, 293:642,650, 2010. © 2010 Wiley-Liss, Inc. [source]

A VEGF Trap Inhibits the Beneficial Effect of bFGF on Vasoreactivity in Corporal Tissues of Hypercholesterolemic Rabbits

THE JOURNAL OF SEXUAL MEDICINE, Issue 9 2008
Donghua Xie MD
ABSTRACT Introduction., Hypercholesterolemia causes a decrease in normal corporal tissue vasoreactivity in a preclinical model of erectile dysfunction. Previous studies have shown that intracorporal injection (ICI) of basic fibroblast growth factor (bFGF) reverses some of the detrimental vasoreactivity effects of hypercholesterolemia and increases vascular endothelial growth factor (VEGF) expression. Aim., We sought to determine whether the beneficial effects of bFGF are VEGF-mediated. Methods., A total of 32 New Zealand white rabbits were fed a 1% cholesterol diet for 6 weeks and randomly divided into four groups (N = 8/group). Group 1 received a 2.5 µg bFGF ICI and 2.5 × 1011 viral particle unit (vpu) of adenovirus encoding ,-galactosidase (Ad,-gal) ICI, 10 days later. Group 2 received a 2.5 µg bFGF ICI and 2.5 × 1011 vpu of adenovirus encoding soluble VEGF receptor (VEGFR) (AdsVEGFR, a VEGF trap) ICI, 10 days later. Group 3 received phosphate buffered saline solution (PBS) ICI and 2.5 × 1011 vpu Ad,-gal ICI, 10 days later. Group 4 received PBS ICI and 2.5 × 1011 vpu AdsVEGFR ICI, 10 days later. Main Outcome Measures., The corpus cavernosum was harvested for vasoreactivity studies 10 days post viral injection. The effective dose of 50% maximum relaxation was determined. VEGF levels were assessed by enzyme-linked immunosorbent assay. Total and phoshorylated Akt and endothelial nitric oxide were analyzed by Western blot. Results., Endothelium-dependent vasoreactivity was significantly greater in Group 1 vs. all other groups. The VEGF trap eliminated the beneficial effects of bFGF on endothelium-dependent vasoreactivity and decreased Akt and nitric oxide phosphorylation. Conclusions., These data demonstrate that VEGF activity contributes much of the therapeutic modulation of bFGF-mediated vasoreactivity in corporal tissue. Xie D, Findley CM, Greenfield JM, Pippen AM, Kontos CD, Donatucci CF, and Annex BH. A VEGF trap inhibits the beneficial effect of bFGF on vasoreactivity in corporal tissues of hypercholesterolemic rabbits. J Sex Med 2008;5:2069,2078. [source]

Contractile Changes of the Clitoral Cavernous Smooth Muscle in Female Rabbits with Experimentally Induced Overactive Bladder

THE JOURNAL OF SEXUAL MEDICINE, Issue 5 2008
Soon-Chul Myung MD
ABSTRACT Introduction., Recently, growing clinical evidence has suggested that sexual dysfunction is more prevalent in women with overactive bladder (OAB). Aims., However, there has been no basic research to clarify the relationship between OAB and female sexual dysfunction. Therefore, we investigated this issue using a rabbit model of OAB. Methods., Twenty-seven New Zealand white female rabbits were randomly divided into the OAB and control groups. Main Outcome Measures., The contractile responses of clitoral cavernous strips to K+, phenylephrine (PE), Bay K 8644, and endothelin (ET)-1, and the relaxation responses of acetylcholine (ACh), sodium nitroprusside (SNP), and Y-27632 to PE-induced contraction by measuring isometric tension. Results., The contractile responses to K+, PE, Bay K 8644, and ET-1 were significantly more increased in the OAB group in a dose-dependant manner than in the control group (P < 0.05), and the responses to ET-1 were more prominent than those to the remaining substances (P < 0.01). The increased contractile responses to ET-1 were blocked by BQ123 (ETA receptor antagonist) but not by BQ788 (ETB receptor antagonist). Clitoral cavernosal strips from the OAB group were more difficult to relax than those from the control group in terms of ACh- and SNP-induced relaxation (P < 0.05). The Y-27632-induced relaxant responses to PE- and ET-1-induced contraction were less prominent in the OAB group than in the control group. Conclusions., The results of this study provide evidence that female OAB may deteriorate clitoral engorgement, which is associated with a greater force generation by increased calcium sensitization and subsequently decreased of relaxation. The activation of ET and Rho-kinase system may be crucial to negatively effect the clitoral smooth muscle relaxation in experimentally induced OAB animal model. But whether these vasomotor effects are revived in human clitoris is still debatable. Myung S-C, Lee M-Y, Lee S-Y, Yum S-H, Park S-H, and Kim S-C. Contractile changes of the clitoral cavernous smooth muscle in female rabbits with experimentally induced overactive bladder. J Sex Med 2008;5:1088,1096. [source]

Developing a Rabbit Model of Rhinogenic Chronic Rhinosinusitis,

THE LARYNGOSCOPE, Issue 6 2008
Kai-Li Liang MD
Abstract Objective: The purpose of this study was to develop a rabbit model of rhinogenic chronic rhinosinusitis (CRS). Methods: New Zealand white rabbits were used and divided into two groups. In group A rabbits, a piece of Merocel (Medtronic-Xomed, Jacksonville, FL) was inserted into one nasal cavity and the other was left undisturbed as control. In group B rabbits, 1 ,g phorbol 12-myristate 13-acetate (PMA) was injected into bilateral nasal lateral walls and then a piece of Merocel (Medtronic-Xomed) was inserted into one nasal cavity. At week 2, the Merocel (Medtronic-Xomed) was removed, and computed tomography (CT), nasoendoscopy, and cultures were performed. All examinations were repeated at week 12. Rabbits that had purulent discharge in nasal cavities and sinuses opacification shown in CT scans were diagnosed as having rhinosinusitis. Rabbits with CRS were randomly allocated to receive intravenous ceftriaxone (50 mg/kg/day) for 28 days or nothing. All rabbits with CRS received CT scans, nasoendoscopy, and cultures at week 16. Results: At week 12, CRS had developed in two controlled nasal cavities, six nasal cavities inserted with Merocel (Medtronic-Xomed), six nasal cavities injected with phorbol 12-myristate 13-acetate (PMA), and seven both PMA-injected and Merocel- (Medtronic-Xomed) inserted nasal cavities. Seven of nine treated CRS sides were clear of opacification after treatment. All non-treated CRS sides had persistent diseases at week 16. There was a significant difference in the CRS incidence (P = .00043) and culture rates (P = .027) between treated and non-treated CRS nasal cavities. Conclusions: Our study developed a rabbit model of rhinogenic CRS. This model is easily performed and is reversible by treatment. [source]

Morphology of Testes from Transgenic Rabbits: Histological and Ultrastructural Aspects

ANATOMIA, HISTOLOGIA, EMBRYOLOGIA, Issue 1 2010
P. Chrenek
Summary The aim of this study was to compare morphological characteristics of testes from transgenic (the WAP-hFVIII gene) and non-transgenic rabbits with emphasis on the histological and ultrastructural aspects. Samples of testes from both groups were fixed and embedded into Durcupan ACM for transmission electron microscopy. For histological analysis, semi-thin toluidine blue-stained sections were evaluated under a Jenaval light microscope. Male fertility was tested based on egg fecundity and blastocyst yield; transgene transmission was proved using PCR assay. Spermatogenesis in rabbit testes had not been destroyed both in transgenic and non-transgenic rabbits. No significant differences were found in the occurrence of individual cell organelles of the Sertoli cells in transgenic and non-transgenic rabbits. The ultrastructure of Leydig cells in testes of transgenic and non-transgenic rabbits was rather similar. No differences in the occurrence of individual organelles of Leydig cells between transgenic and non-transgenic males were found. These results were in concert with fertilizing capacity of transgenic spermatozoa. The presented status of organelles in this study indicates functional activity of the analysed cells. [source]

The Distribution of the Cardiac Veins in Angora Rabbits (Oryctolagus cuniculus)

ANATOMIA, HISTOLOGIA, EMBRYOLOGIA, Issue 4 2007
S. Bahar
Summary This study was carried out to describe the ramifications of the cardiac veins of Angora rabbit. For this purpose, a total of 16 adult healthy Angora rabbits of both sexes, 1.5,2 years of age, were used. The great, middle, right cardiac veins ran in a subepicardial course and opened into the left cranial vena cava, but some tributaries of the right cardiac veins sometimes also joined various portions of the right atrium. The smallest cardiac veins followed subendocardially and terminated in the right chambers of the heart. Based on their origin, course and frequency, it was concluded that the smallest cardiac veins are primarily responsible for the drainage of the interventricular septum. Results from this study are thought to shed light on further heart-related medical studies, and to contribute considerably to the present anatomical knowledge of the cardiac veins in this species. [source]

Ultrastructural Morphometry of Mammary Gland in Transgenic and Non-transgenic Rabbits

ANATOMIA, HISTOLOGIA, EMBRYOLOGIA, Issue 6 2006
S. Dragin
Summary The mammary gland of transgenic animals has been used for the production of recombinant proteins of therapeutic and nutraceutical use. The objective of this study was to compare the ultrastructure of transgenic and non-transgenic rabbit mammary gland tissue. New Zealand White transgenic rabbits were obtained by breeding non-transgenic rabbits with transgenic founder rabbits containing a whey acidic protein-human factor VIII (WAP-hFVIII) transgene integrated into their genome. Samples of mammary gland tissue from lactating rabbit females were isolated by surgical procedures. These samples were examined by optical and electron microscopy and photographs were taken. Measurements of ultrastructural organelles were made from digital images of the mammary cells. No differences were found in the cellular structure of mammary tissue, but significant differences t(0.001) in the relative volume of mitochondria and vacuoles between transgenic and non-transgenic mammary gland epithelium were observed. [source]

Morphological Investigation of Carotid Body and Its Arteries in Rabbits

ANATOMIA, HISTOLOGIA, EMBRYOLOGIA, Issue 5 2002
E. Unur
Summary The purpose of this study was to determine the morphology of the rabbit carotid body and its artery at the light microscopy level. The carotid body was situated between the internal and external carotid arteries after the bifurcation point of the common carotid artery. The carotid body was usually found to be a single, ovoid tissue mass but, in some cases it consisted of two or three parts. More carotid bodies were supplied by a single carotid body artery (glomic artery) which arose from the common carotid artery or the internal or external carotid arteries near the bifurcation point of the common carotid artery. In only one case were there two arteries which arose from opposite sides of the external carotid artery at its origin. There was a distinguishable sinus (glomic sinus) at the origin of the glomic artery. This artery had a thin wall with elastic laminae in the sinus area which become thinner distal to the sinus. [source]

Repair of mandible defect with tissue engineering bone in rabbits

ANZ JOURNAL OF SURGERY, Issue 11 2005
Zhi Li
Background: The aim of the present study was to investigate the effect of tissue engineering bone composed of bone marrow-derived osteoblasts and demineralized bone in repairing mandible defect. Methods: Bone marrow-derived osteoblasts of 20 rabbits were cultured and seeded into scaffold of allogeneic demineralized bone to construct tissue engineering bone graft in vitro, which was used to repair the 10 × 5-mm bone defect made in the same rabbit mandible edge. Implant of demineralized bone alone was as the control. Rabbits were killed according to the schedule: five after 2 weeks, five after 4 weeks, five after 8 weeks, five after 12 weeks, and the implants were harvested for gross, radiographic, and histological observation. Results: New bone formation at the margin region of defect and osteogenesis at the centre were observed in the implant of tissue engineering bone, and the bone formation pattern included osteogenesis, osteoconduction, and osteoinduction. In the implant of demineralized bone alone, the major bone formation pattern was ,creeping substitute'. Conclusions: The tissue engineering bone graft constructed by autogenous bone marrow-derived osteoblasts and allogeneic demineralized bone was better than demineralized bone alone in bone formation capability, which might be an ideal graft for bone defect repair. [source]

Continuous occurrence of both insufficient neovascularization and elevated vascular permeability in rabbit proximal femur during inadequate repair of steroid-associated osteonecrotic lesions

ARTHRITIS & RHEUMATISM, Issue 10 2009
Ge Zhang
Objective To examine the features of the intraosseous vasculature, the size of the marrow stem cell pool (MSCP), and expression of vascular endothelial growth factor A (VEGF) during inadequate repair of steroid-associated osteonecrotic lesions in rabbits. Methods Steroid-associated osteonecrosis was induced in male rabbits. At 0, 1, 2, 4, and 6 weeks postinduction, vascularization and permeability indices were quantified by dynamic magnetic resonance imaging (MRI). In addition, the size of the MSCP in the hematopoietic and mesenchymal compartments was determined, and marrow mononuclear cells expressing specific surface markers for endothelial progenitor cells or periendothelial mural precursor cells were counted. At various time points after the rabbits were killed, the proximal femora were dissected to examine the intraosseous vasculature by angiography, histomorphometry, and ultramorphology. In addition, osteonecrotic lesion repair and marrow VEGF expression were evaluated. Results Lesion formation without repair was observed at 2 weeks after induction of steroid-associated osteonecrosis. Rabbits displaying destructive repair (DR+) and those displaying reparative osteogenesis (DR,) from 4 weeks to 6 weeks postinduction were identified. From week 2 to week 6, the vascularization index was significantly lower in DR+ rabbits compared with DR, rabbits, whereas the permeability index was significantly higher in DR+ rabbits compared with DR, rabbits. The features of the intraosseous vasculature determined by angiography, histomorphometry, and ultramorphology were consistent with those determined by dynamic MRI. The MSCP size and number of marrow mononuclear cells expressing specific surface markers were all significantly lower in DR+ rabbits than in DR, rabbits from week 1 to week 6. The increased VEGF expression at 2 weeks was maintained through week 6 in DR+ rabbits, whereas VEGF expression decreased in DR, rabbits from week 2 to week 6. Conclusion Continuous occurrence of both insufficient neovascularization and elevated vascular permeability is accompanied by a continuously low- level MSCP and uncontrolled VEGF expression during inadequate repair of steroid-associated osteonecrotic lesions. [source]