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S E Weisbrode

Publications and source records attributed to S E Weisbrode.

At least 19 recordsLinked to original sources
PubMed1998

Phenotypic changes in T cell populations during the reactivation of tuberculosis in mice.

The phenotypic changes of T lymphocytes during the reactivation of latent Mycobacterium tuberculosis infection by activation of the hypothalamic-pituitary-adrenal (HPA) axis was monitored using flow cytometric analysis. Subsets of CD4+ and CD8+ lymphocyte populations from the lung, spleen and draining lymph nodes of infected mice were identified based on their differential expression of the cell surface antigens CD44 and CD45RB. Latent infection was characterized by an accumulation of both naive, activated and memory CD4 and CD8 T lymphocytes in the lung and mediastinal lymph nodes. No changes were observed in the spleen of mice with latent infection when compared with uninfected mice. Immediately following the activation of the HPA axis, a reduction in all CD4+ and CD8+ T cells in the lung and mediastinal lymph nodes was observed. This correlated with the reactivation of mycobacterial growth. The decrease was transient for memory and naive CD4 and CD8 T lymphocyte populations in the lung. However, the number of naive CD4 and CD8 T lymphocyte populations in the mediastinal lymph node following reactivation was less than that found in mice with latent infection. These data provide the first characterization of T lymphocyte populations which may be functionally involved in the immunological response to HPA axis-induced reactivation of M. tuberculosis infection.

Animals↗
PubMed1998

Cell trafficking, mediator release, and articular metabolism in acute inflammation of innervated or denervated isolated equine joints.

OBJECTIVES: To describe the acute cellular response, inflammatory mediator release, and effect on chondrocyte metabolism of interleukin 1 beta (IL-1 beta) in isolated innervated or denervated equine metacarpophalangeal joints. ANIMALS: One metacarpophalangeal joint of 24 adult horses. PROCEDURES: The metacarpophalangeal joint was isolated for 6 hours in a pump-perfused, auto-oxygenated, innervated or denervated metacarpophalangeal joint preparation. Isolated joints were assigned to 4 groups: control, control-denervated, inflamed, and inflamed-denervated, and inflammation was induced by intra-articular injection of IL-1 beta. Synovial fluid was collected for cytologic examination and determination of IL (IL)-1 beta, (IL-6), prostaglandin E2 (PGE2), and substance P (SP) values. Synovial membrane was immunostained with SP and nerve-specific enolase (NSE) antibodies. Cartilage was collected for determination of proteoglycan (PG) synthesis and degradation. RESULTS: IL-1 beta induced significant neutrophilic leukocytosis in synovial and synovial membrane. IL-1 beta concentration and returned to baseline by 5.5 hours, but IL-6 concentration significantly increased throughout the study. Total SP content was significantly higher in inflamed joints. There was a significant increase in 24- and 48-hour PG degradation in inflamed innervated joints. CONCLUSION: Cellular response to IL-1 beta was rapid and sustained; joint clearance of IL-1 beta was rapid, and endogenous production of IL-1 beta did not follow. The IL-6 and PGE2 concentrations significantly increased, and SP content was increased in association with inflammation but not denervation. A degradative response of cartilage of IL-1 beta was observed, and was enhanced by innervation. This model was useful for investigation of the articular response to acute inflammation and the influence of denervation in modulating this response.

Animals↗
PubMed1997

Gallium nitrate suppresses lupus in MRL/lpr mice.

Gallium (Ga) nitrate, a drug which prevents a variety of experimental autoimmune diseases, was investigated in a murine model of systemic lupus erythematosus (SLE). In one experiment, female MRL/Mp lpr/lpr (MRL/lpr) mice were randomized into 2 groups of 6: 1) vehicle (trisodium citrate) and 2) Ga. Subcutaneous injections began at 3 weeks of age and continued weekly until the mice were euthanized a week after the thirteenth injection. The loading dose of Ga (calculated as elemental Ga) was 45 mg/kg, followed by 15 mg/kg/week. In another experiment (n = 18) with 3 males and 3 females per group, mice received 1) vehicle, 2) Ga x 1 (one 45 mg/kg dose), and 3) Ga x 13. In the experiment with 12 mice, axillary lymph nodes from Ga-treated mice were significantly smaller than those from vehicle-treated mice (91+/-42 and 360+/-358 mg respectively, mean+/-SD), and spleens as well as lymph nodes from the former showed significantly less lymphoid infiltrate. In the experiment with 18 mice, prescapular lymph nodes weighed 312+/-98, 217+/-52, and 42+/-34 mg, and spleens weighed 732+/-492, 409+/-164, and 192+/-93 mg in the groups which received vehicle, Ga x 1, and Ga x 13 respectively. Control mice had significantly more lymphoid infiltrates in the lungs, spleen, and lymph nodes and, unlike Ga x 13 mice, exhibited glomerulitis and renal vasculitis. Within groups, females developed more severe disease than males. The Ga x 13 group had increased percentages of CD4-bearing and CD8-bearing lymphocytes in lymph nodes and increased CD4-bearing lymphocytes in the spleen, with an increased proliferative response to mitogen stimulation in vitro in lymph nodes, although not in the spleen. The Ga x 13 group also gained less weight and developed osteosclerosis. Although preliminary, our findings suggest that clinical trials with Ga in SLE are merited.

Animals↗
PubMed1997

Endotoxin-induced ileal Vo2-Do2 alterations do not correlate with the severity of ileal injury.

PURPOSE: Altered Vo2-Do2 relationships are most often noted to occur in the setting of sepsis or endotoxin (LPS)-induced systemic organ microvascular injury and are generally thought to be causally linked to that injury. However, we have recently shown that ileal microvascular injury is not associated with altered ileal Vo2-Do2, relationships. Thus, we hypothesized that the severity of LPS-induced systemic organ microvascular injury would not correlate with the development of systemic organ Vo2-Do2 alterations. MATERIALS AND METHODS: To test this hypothesis, we used the in situ autoperfused feline ileal preparation to simultaneously examine microvascular permeability, reflected as the ileal lymph to plasma protein concentration ratio (CL/CP), and ileal Vo2-Do2 relationships 2 hours after intravenous LPS (0.75-2.0 mg/kg; n = 9) and in matching controls (n = 5). RESULTS: As expected, all LPS-treated animals were found to have extensive ileal histological damage and marked increases in the CL/CP compared with controls (0.308 +/- 0.019 v 0.097 +/- 0.009; P < .001). In addition, although the critical Do2 (Do2c) was elevated in the LPS-treated animals relative to controls (34.2 +/- 5.0 v 16.7 +/- 1.4 mL/min/kg; P < .03), there was no correlation between the Do2c and the CL/CP in the LPS-treated animals. Finally, ileal wet to dry weight ratios after LPS did not differ from controls. CONCLUSION: Taken together, these data suggest that factors other than organ injury, as assessed by morphological and permeability alterations, are important in the pathogenesis of altered systemic organ Vo2-Do2 relationships after LPS.

Animals↗
PubMed1997

Ischemia/reperfusion injury to the ileum does not account for the ileal VO2-DO2 alterations induced by endotoxin.

PURPOSE: Endotoxin (lipopolysaccharide [LPS])-induced systemic organ injury leads to disruption of normal systemic organ metabolic processes, which are manifest clinically by signs of accelerated anaerobic metabolism (e.g., tissue acidosis and hyperlactatemia) and altered VO2-DO2 relationships. The association of increased anaerobic metabolism with VO2-DO2 alterations has led to the notion that ischemia/ reperfusion (I/R) injury may be a prerequisite for the development of VO2-DO2 alterations during endotoxemia. However, in contrast to sepsis, in which oxygen consumption is often increased, oxygen consumption is severely decreased after I/R injury. Based on these observations, we hypothesized that I/R injury would result in systemic organ VO2-DO2 alterations, which are distinct from those that occur in sepsis. MATERIALS AND METHODS: We used the in situ autoperfused feline ileal preparation to simultaneously examine microvascular permeability, reflected as the ileal lymph to plasma protein concentration ratio (CL/CP), and ileal VO2-DO2 relationships after either intravenous LPS (2.0 mg/kg; n = 5) or I/R injury (n = 5), and in matching controls (n = 5). RESULTS: As expected, all LPS-treated and I/R-injured animals were found to have extensive ileal histological damage and marked increases in the CL/CP compared with controls (0.315 +/- 0.009 and 0.329 +/- 0.034, respectively, v 0.097 +/- 0.009; P < .001, both comparisons). In addition, the critical DO2 (DO2c) was elevated, and the critical oxygen extraction was decreased in both the I/R and LPS groups relative to controls. However, as initially hypothesized, the VO2 at the critical DO2 was markedly decreased in the I/R group compared with that of the LPS group. CONCLUSIONS: These data indicate that I/R injury is insufficient to account for the systemic organ VO2-DO2 alterations that occur with LPS injury.

Acidosis↗
PubMed1997

Effects of vigorous exercise training and beta-agonist administration on bone response to hindlimb suspension.

The effectiveness of dobutamine (Dob) in preventing bone loss during 14 days of hindlimb suspension (Sus) was tested in exercise-trained (Ex; n = 25) and sedentary (Sed; n = 22) rats (age 155 days). One-half of each group was given Dob (2 mg . kg-1 . day-1) or saline (Sal). Histomorphometric measurements at midfemur revealed a 17% smaller cortical bone area (CBA) and a 32% lower periosteal mineral apposition rate (MAR) in suspended vs. nonsuspended Sed/Sal rats. Dob abolished this decline in CBA in Sed/Sus rats, probably via an attenuation of the decrease in periosteal MAR; similar but nonsignificant effects on cross-sectional moment of inertia were observed. Nonsuspended Ex rats had no change in bone CBA when CBA is indexed to body weight. Sus appeared to uncouple the relationship between soleus weight and CBA. Dob attenuated the 43% decline in soleus weight after Sus in Ex but not in Sed rats. In summary, vigorous Ex before Sus does not affect loss of bone mass due to unloading; Dob effectively maintains CBA in Sed rats subjected to suspension.

Adrenergic beta-Agonists↗
PubMed1997

Biochemical, histochemical, and immunohistochemical characterization of distal tibial osteochondrosis in horses.

OBJECTIVE: To compare the biochemical, histochemical, and immunohistochemical profiles of articular cartilage from horses with naturally acquired distal tibial osteochondrosis (OC) with cartilage from a similar location in clinically normal horses. ANIMALS: 9 affected horses (group 1, 16 OC lesions) and 4 control horses (group 2, 8 normal osteochondral specimens). PROCEDURE: OC specimens were collected during arthroscopic removal of the fragment, and control specimens were collected by aseptic osteotomy. Uronic acid, total protein, total glycosaminoglycan (GAG), chondroitin sulfate (CS), and keratan sulfate (KS) contents were determined. Histomorphologic, histochemical, and immunohistochemical examinations were performed on specimens after snap freezing at -80 C and cryosectioning. Monoclonal antibodies (MAB) 3B3 and 5D4 were applied for location of epitopes of CS and KS, respectively. RESULTS: OC lesions had significantly lower quantity of uronic acid, total GAG, and CS, compared with normal cartilage. OC cartilage had significantly less intense staining with toluidine blue, along with irregular cellularity and tidemark characteristics, compared with normal cartilage. Monoclonal antibodies 3B3 and 5D4 stained OC cartilage, whereas MAB 5D4 did not stain control cartilage. Additionally, MAB 3B3 and 5D4 stained the fibrous tissue that was found firmly attached to the OC lesion located between the parent distal portion of the tibia and OC fragment. CONCLUSION: OC cartilage lesions of the distal intermediate ridge of the tibia in horses are biochemically, histochemically, and immunohistochemically distinct from normal cartilage from the same location. Results may reflect the inability of the chondrocyte of the developing joint to alter matrix components that would allow proper maturation and differentiation into bone.

Animals↗
PubMed1996

Investigation of bone developmental and histopathologic changes from intraosseous infusion.

STUDY OBJECTIVE: To evaluate clinical and cellular changes of bone through the rapid growth phase of development after intraosseous infusion of hypertonic or isotonic solutions at slow or fast infusion rates in a pig model. METHODS: This was a prospective, randomized, partially blinded, comparative study using a porcine model in an urban teaching hospital laboratory with further development in a local farm environment. Sixty pigs weighing 12 to 30 kg were anesthetized and endotracheally intubated, and a no. 15 Jamshidi bone marrow needle was inserted into a front forelimb. Hypertonic (mannitol) or isotonic (saline) solutions of 8 mL/kg were infused through the intraosseous site at a rapid or slow infusion rate. Animals were observed for approximately 6 months, after which they were killed and the front forelimbs harvested for gross pathologic and histologic evaluation. RESULTS: No clinical complications were noted in any of the animal groups. No substantial histologic differences were found between the hypertonic and isotonic groups. Although gross pathologic lesions were found in 32% of the hypertonic groups and in fewer than 5% of the isotonic groups, this difference was not statistically significant. Equal bone changes were found in the slow- and rapid-infusion groups. CONCLUSION: The rate of intraosseous infusion and the osmolarity of the infused fluid did not appear to be related to any gross pathologic or histologic cellular or marrow changes or to any clinical complications in animal development in this study.

Animals↗
PubMed1996

Acid aspiration results in ileal injury without altering ileal V(O2)-D(O2) relationships.

Systemic organ endothelial injury and V(O2)-D(O2) relationship alterations occur frequently in the setting of acute lung injury, and they are believed to play an important role in the pathogenesis of the multiple organ dysfunction syndrome (MODS). However, the relationship, if any, between systemic organ endothelial injury and V(O2)-D(O2) relationship alterations remains unknown. We hypothesized that microvascular endothelial injury and attendant interstitial edema would result in increased diffusion distances for oxygen and altered systemic organ V(O2)-D(O2) relationships. To test this hypothesis, we utilized the in situ autoperfused feline ileal preparation to evaluate ileal V(O2)-D(O2) relationships in control animals (n = 5) and in animals with HCl-induced acute lung and systemic organ injury (n = 5). As expected, ileal endothelial protein permeability (CL/CP) was increased in HCl-injured animals compared to control animals (0.187 +/- 0.024 versus 0.097 +/- 0.009; p < 0.01). However, contrary to our original hypothesis and despite marked morphologic and endothelial protein permeability alterations, ileal V(O2)-D(O2) relationships were not altered in the HCl-injured animals. Moreover, V(O2)-D(O2) relationships in the ileum remained unchanged even when ileal venous pressures were increased to 15 mm Hg. Taken together, these findings do not support an important role for oxygen diffusion limitation in the pathogenesis of altered systemic organ V(O2)-D(O2) relationships.

Animals↗
PubMed1996

Influence of methylprednisolone acetate on osteochondral healing in exercised tarsocrural joints of horses.

OBJECTIVE: To evaluate joint function and healing of surgically created full-thickness articular cartilage defects in exercised horses after intra-articular administration of methylprednisolone acetate (MPA; 120 mg) and sterile saline solution in the contralateral limb. DESIGN: Experimental investigation. SAMPLE POPULATION: 12 healthy, sound, radiographically normal horses with induced full-thickness osteochondral lesions on the medial and lateral trochlear ridges of the tali. PROCEDURE: Two 8.4-mm-diameter full-thickness articular cartilage lesions were created in each tarsocrural joint (12 horses [24 tarsocrural joints]); 1 was in a weight-bearing (WB) position and the other in a less weight-bearing (LWB) position. Each horse was maintained on a standardized exercise protocol (stall rest, days 0-6; walking, days 7-12; and treadmill, days 13-42) and evaluated throughout the study for changes in joint circumferences, synovial fluid, radiographs, lameness, and scintigraphy. 6 horses were euthanatized on day 42, and 6 on day 180. Gross morphometric assessment was performed, using an image analysis system on a projected color slide of the defect. The type of repair tissue, based on gross appearance, was expressed as a percentage of the total defect for each osteochondral defect. Histochemical assessment was performed, using safranin-O staining for proteoglycans and an image analysis system to express the area of stain uptake. Histomorphometric assessment was performed on H&E-stained sections, using an image analysis system. The repair tissue filling the defect was categorized as to tissue type and expressed as a percentage of the total defect area. Synovial membrane specimens were assessed semiquantitatively on H&E-stained sections for changes in character. Significance was established at P < 0.05. RESULTS: Joint circumference was significantly increased in the saline, compared with the MPA-treated, limbs on days 7, 12, and 42. Synovial fluid WBC counts were significantly increased in the MPA-treated limbs on day 42. Gross osteochondral defects had a greater percentage of mature repair tissue in saline-treated joints (30.8% LWB, 23% WB), compared with MPA-treated joints (0% LWB, 0% WB) at 42 days Histomorphometric assessment of the repair tissue indicated significant differences with regard to the quality of repair in the saline-treated (34% fibrous tissue LWB, 19.4% fibrous tissue WB) versus MPA-treated (2.5% fibrous tissue in LWB and WB) joints at 42 days. Microscopically, the percentage of fibrocartilage in the LWB (MPA, 23.7%; saline, 24.8%) was significantly greater than that in the WB (MPA, 14.6%; saline, 15.4%) site at day 180. The MPA-treated limbs had greater villous hyperplasia, edema, and extent of inflammation within the synovial membrane than did saline-treated limbs (days 42 and 180). CONCLUSION: MPA inhibits the development and maturation of repair tissue at 42 days and incites potential long-term (180 days) detrimental synovial membrane inflammation. Furthermore, a single dose of MPA does not cause long-term detrimental effects (180 days) in quality of repair-tissue.

Animals↗
PubMed1995

Metacarpal fracture associated with lymphosarcoma-induced osteolysis in a horse.

A 19-year-old Appaloosa gelding was reluctant to move. Radiography revealed diffuse, permeative lysis of the cortex and subchondral bone of the phalanges, third metacarpal bones, proximal sesamoid bones, radius, carpal bones, tibia, mandible, and nasal bones of the skull. A comminuted fracture of the distal aspect of the left third metacarpal bone was identified on a lateral to medial radiographic view of the left metacarpophalangeal joint. Histologic examination of the first phalanx, third metacarpal bone, and sternum revealed multifocal infiltrates of nodular lymphosarcoma in cortical and subchondral bone. Osteoclastic cavities were apparent in bone trabeculae contiguous with nodular foci of lymphosarcoma. Osteoclastic osteolysis was not evident at bone surfaces that were not directly adjacent to neoplastic cells. Although lymphosarcoma is the most frequent malignant neoplasia encountered in horses, diffuse neoplastic infiltration of cortical and subchondral bone of the appendicular and axial skeleton represents an unusual presentation of lymphosarcoma.

Animals↗
PubMed1995

Metaphyseal bone lesions in young dogs with systemic canine distemper virus infection.

Bone lesions, restricted to the metaphyses of long bones, were observed in young dogs with systemic distemper following experimental and spontaneous infection. Canine distemper virus (CDV) antigen was found immunocytochemically in hematopoietic marrow cells, osteoclasts, osteoblasts and rarely in osteocytes. In experimentally infected dogs, viral antigen was demonstrated in the metaphysis between 5 and 36 days after infection. Associated lesions, characterized by necrosis of osteoclasts, persistence of primary spongiosa and atrophy and necrosis of osteoblasts and marrow cells, were mild and most prominent between 8 and 32 days postinfection. Metaphyseal osteosclerosis (MO) of the long bones, varying from mild to severe, was observed macroscopically in 8 (19%) out of 42 dogs with spontaneous distemper. Affected animals were between 3 and 6 months of age and belonged mainly to the large breeds. In these animals, MO was characterized histologically by persistence of primary spongiosa, loss of bone marrow cells and necrosis of osteoclasts and bone marrow cells varying from mild to severe. Summarized, CDV-associated bone lesions were only transient and there were no indications of viral persistence in bones of dogs experimentally infected with CDV. Although no clinical signs related to the bones were observed, the present study reveals that infection of metaphyseal bone cells is common in young dogs with systemic distemper and occurrence of viral antigen in these cells results in defects in bone modelling.

Animals↗
PubMed1995

Anti-CD18 antibody does not block ileal injury induced by phorbol myristate acetate.

Acute lung injury (ALI) is frequently complicated by systemic microvascular injury. In previous studies, ALI from acid aspiration resulted in ileal microvascular injury. This was due to systemic inflammation and was prevented by MoAb 60.3, an antibody against the CD18 antigen that mediates leukocyte adherence. The present study was designed to test the hypothesis that ileal microvascular injury during phorbol myristate acetate (PMA)-induced systemic inflammation is also blocked by MoAB 60.3. We assessed the injury by measuring the concentration ratios of lymph protein to plasma protein (i.e., CL/CP) at steady-state lymph flows in autoperfused cat ileum preparations. As expected, the CL/CP increased in the ilea of animals given PMA (15 micrograms/kg; n = 5) compared with the ilea of control animals (n = 5) (0.202 +/- 0.024 versus 0.106 +/- 0.010; p = 0.006) and was accompanied by widespread morphologic alterations. Intravenously administering MoAb 60.3 (2 mg/kg) to animals before the PMA infusion (n = 5) yielded a CL/CP value indistinguishable from that of the PMA group (0.222 +/- 0.024 versus 0.202 +/- 0.024; p = NS). These results suggest that CD18-mediated leukocyte adherence is not important in the mechanism of PMA-induced ileal microvascular injury.

Animals↗
PubMed1995

Histologic and immunocytochemical characterization of canine distemper-associated metaphyseal bone lesions in young dogs following experimental infection.

The proximal metaphyses of the humerus of weanling gnotobiotic dogs experimentally infected with canine distemper virus (CDV) were investigated histologically and immunocytochemically between 4 and 41 days after infection. Viral antigen was demonstrated in hematopoietic marrow and bone cells at postinfection day (PID) 5 and PID 7, respectively. Between PID 8 and 27, CDV antigen was abundantly present in marrow cells, osteoclasts, and osteoblasts and less frequently in osteocytes. Immunopositive cells in both osseous tissues and bone marrow declined between PID 29 and PID 36 and were absent by PID 41. Chondrocytes of the growth plate were negative for viral antigen throughout the observation period. In bone, viral antigen was more frequently observed in bone cells of the primary spongiosa than in the secondary spongiosa. There was a strong correlation between occurrence of CDV antigen and osseous changes. Associated metaphyseal bone lesions were mild and most prominent between PID 8 and PID 32. Lesions consisted of necrosis of osteoclasts, which was associated with subsequent persistence of the primary spongiosa (growth retardation lattice). Atrophy and necrosis of osteoblasts and marrow cells were also noted. Infection of metaphyseal bone cells appears to be common in young dogs with experimental systemic distemper. Bone cell infection is preceded by infection of marrow cells, and infected bone cells may experience degeneration and necrosis. This subtle viral effect may result in defects in bone modeling in CDV-infected dogs.

Animals↗
PubMed1995

Histologic evaluation of tissue reactivity and absorption in response to a new synthetic fluorescent pigmented polypropylene suture material in rats.

The degree and type of tissue reactivity and the absorption of a new suture material was determined by implantation within rat gluteal muscles. Amount and type of tissue inflammatory reaction was compared among the new suture material, polypropylene, and coated polyamide. Histologic evaluation of the tissues in which sutures were implanted indicated that the new suture material, polypropylene, and coated polyamide had similar amounts and types of reaction at 30 days or less after implantation, but differed after 30 days. The new suture material and polypropylene had an inflammatory reaction zone measuring less than 25% of the high-power field after 60 days, but the coated polyamide still induced reaction greater than 45% of the field at 90 days. At 60 and 90 days after implantation, the new suture material and polypropylene induced a mature fibrous reaction; the reaction to coated polyamide was either immature fibrous or granulomatous, depending on whether there was rupture of the suture coat. There was no observable absorption of the new suture material at 90 days. This study indicated that the new suture material is nonabsorbable and is minimally reactive in rat muscle. The tissue reactions induced by this suture material are similar to those of polypropylene and significantly less than those induced by coated polyamide after 30 days following implantation.

Animals↗
PubMed1994

Enchondroma in a rhesus monkey.

A 2.5-year-old rhesus monkey was examined because of a bony enlargement of the distal portion of the right tibia. On the basis of radiographic and histologic findings, enchondroma was diagnosed. The tumor enlarged over the next 2 years, but the monkey continued to have normal use of its limb.

Animals↗
PubMed1994

The effects of gallium nitrate on osteopenia induced by ovariectomy and a low-calcium diet in rats.

The effects of gallium nitrate (GN) were evaluated on osteopenia induced by ovariectomy (OVX) and a low-calcium diet (LCD) in Sprague-Dawley rats. Twenty-five rats (300-400 g) were randomized into four groups of 5-7 animals: (I) OVX LCD treated with GN for 22 weeks; (II) OVX LCD treated with GN for 10 weeks; (III) OVX LCD treated with saline; and (IV) sham-operated (SO), normal diet, treated with saline. GN-treated rats received a 30-mg/kg subcutaneous single dose of elemental gallium, followed by 10 mg/kg per week, whereas control animals received an equal volume of saline. All animals were euthanized at 22 weeks. Measurements of bone density and histomorphometry, performed on the proximal portion of the tibia, indicated significant bone loss in all OVX LCD animals. GN-treated rats in group I gained significantly less weight than those in the other groups, and their blood urea nitrogen increased, suggesting a nephrotoxic effect. After discontinuation of GN, rats in group II gained weight at the same rate as those which had received only saline. Bone formation rates in the GN-treated rats were double those of the saline-treated OVX animals and more than 10 times those of SO controls. Although the bone formation rate in GN-treated rats increased, GN had no effect in preventing the loss of bone surface, density and volume induced by OVX LCD. These findings suggest that although GN may enhance osteoblastic activity, this agent alone does not appear effective in the prevention of bone loss induced by OVX LCD.

Analysis of Variance↗