Assessment of bone quality, quantity, and turnover with multiple methodologies at multiple skeletal sites.
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Absorptiometry, Photon↗
Biomedical subjects
S Majumdar
Publications and source records attributed to S Majumdar.
Direct measures of trabecular bone architecture from MR images.
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Aged↗
Effects of prostaglandin E2 and nitric oxide inhibitors on the expression of interleukin-10, interleukin-12 and MHC class-II molecules in Mycobacterium microti-infected and interferon-gamma-treated mouse peritoneal macrophages.
Mycobacterium microti-infected mouse peritoneal macrophages produced high amounts of prostaglandin E2 (PGE2) and nitric oxide (NO) when activated with interferon-gamma (IFN-gamma). In order to understand the relation between PGE2 and NO production and the expression of interleukin-12 (IL-12), interleukin-10 (IL-10) and MHC class-II (Ia) molecules by M. microti-infected and IFN-gamma-stimulated macrophages, we analyzed the level of these molecules in the presence or absence of PGE2 and NO inhibitors. Addition of NG-methyl-L-arginine (L-NMA) and indomethacin (IM) caused a significant increase in IL-12 level (2.6- and 1.9-fold, respectively) whereas IL-10 level decreased by 88 and 56%, respectively, relative to M. microti-infected and IFN-gamma-treated control macrophages. Enhanced PGE2 and NO upregulated IL-10 expression and down-regulated IL-12 and MHC class-II (Ia) expression in M. microti-infected and IFN-gamma-treated mouse peritoneal macrophages.
Animals↗
Role of phospholipid transfer protein in rabbit lung development.
A 36-kDa phospholipid transfer protein (PLT-P(R)), which preferentially transfers phosphatidyl choline (PC) compared to phosphatidyl inositol (PI), was purified 827-fold from rabbit lung homogenate. Incorporation of cholesterol in unilamellar vesicles reduced the PC transfer activity of PLTP(R). Dipalmitoyl phosphatidyl choline uptake by alveolar type II cells was increased in the presence of the protein, and further enhanced in the presence of surfactant liposomes. However, a decrease in uptake was noted with cholesterol in host membranes. Incorporation of PI into host membranes had a low stimulatory effect on the process. All these effects were more pronounced in adult type II cells compared to premature, term and 3-day-old pups.
1,2-Dipalmitoylphosphatidylcholine↗
The temporal changes of trabecular architecture in ovariectomized rats assessed by MicroCT.
To study the short- and long-term effects of estrogen deficiency on trabecular bone, three-dimensional measurements of proximal tibiae of ovariectomized rats were performed by micro-computed tomography (MicroCT). New three-dimensional (3D) techniques were employed to characterize the trabecular architecture from 0 to 110 days post-ovariectomy (OVX). These new methods no longer assume a plate or rod model of bone, but calculate trabecular thickness, separation, and number and their distribution by placing maximal spheres into the 3D representation of the structure. The model type of bone was quantified with the Structure Model Index (SMI). Utilizing these methods we found a rapid loss of trabecular bone in the first week after OVX. After the first week bone mass declined further, although the rate of loss was lower. In addition there was a complete change in model type from plate-like to rod-like within 7 days post-OVX, and then a very constant SMI after 12 days. After an initial thinning of trabecular structure, further bone loss seems to occur through removal of trabeculae, while the trabecular plate thickness remains constant. The heterogeneity of the network could be quantified by intra-individual standard deviation of local separations, which showed a stair-like progression, with a plateau between 12 and 60 days post-OVX. This study provides new insights into ovariectomy-related changes in cancellous bone structure evaluated by 3D MicroCT. In addition, these data suggest that the rapid change of model from plate-like to rod-like post-OVX may potentially introduce biases in the parameters that are determined using model-based algorithms, and these biases may modify the impact of age-related or therapeutic changes.
Analysis of Variance↗
Rapid non-destructive quantitative estimation of urania/thoria in mixed thorium uranium di-oxide pellets by high-resolution gamma-ray spectrometry.
A non-destructive technique using high-resolution gamma-ray spectrometry has been standardised for quantitative estimation of uranium/thorium in mixed (ThO2-UO2) fuel pellets of varying composition. Four gamma energies were selected; two each from the uranium and thorium series and the time of counting has been optimised. This technique can be used for rapid estimation of U/Th percentage in a large number of mixed fuel pellets from a production campaign.
Radiation Monitoring↗
Toxico-kinetics, recovery, and metabolism of napropamide in goats following a single high-dose oral administration.
Toxicokinetic behavior, recovery and metabolism of napropamide (a pre-emergent herbicide) and its effect on Cytochrome P(450) of liver microsomal pellet were studied following a single high-dose oral administration of 2.5 g kg(-1) and continuous (7 days) oral administration of 500 mg kg(-1) in black Bengal goat. Napropamide was detected in blood at 15 min and the maximum quantity was recovered at 3 h after administration. The absorption rate constant (Ka) value was low indicating poor absorption from the gastrointestinal tract. High elimination half-life (t(1/2) beta) and low body clearance (Cl(B)) values coupled with higher transfer of compound from tissue to central compartment (K(21)) suggest that napropamide persisted in the blood for a long time, i.e., after 72 h of oral administration. The recovery percentage of napropamide, including metabolites, from goats varied from 75.94 to 80.08 and excretion of the parent compound through feces varied from 18.86 to 21.59%, indicating that a major portion of the orally administered napropamide was absorbed from the gastrointestinal tract of goat. Napropamide significantly increased the Cytochrome P(450) content of liver microsomal pellet. The recovery of metabolites from feces, urine, and tissues ranged from 4.2--6.2, 40.81--49.42, and 2.7--11.6%, respectively, during a 4--7 day period. The material balance of napropamide (including metabolites) following a single high-dose oral administration at 2.5 g kg(-1) during 4--7 days after dosing was found to be in the range of 75--80%.
Absorption↗
Selective impairment of protein kinase C isotypes in murine macrophage by Leishmania donovani.
Leishmania donovani, an obligate intracellular parasite resides and multiplies within macrophage of the reticuloendothelial system. The intracellular signalling mechanism involved in the impaired oxidative response in leishmaniasis has not yet been clearly established. Generation of superoxide anion (O2-) is supposed to be the first line of host defence during microbial invasion. We found a substantial inhibition of superoxide anion generation in parasitized macrophages, which was just the reverse in case of macrophages challenged with Lipophosphoglycan (LPG) deficient attenuated leishmanial parasite UR-6. The generation of O2- essentially needs the prior activation of protein kinase C (PKC) mediated phosphorylation events. Our study proposed that phosphorylation of 67, 54, 47 and 36 kDa proteins was attenuated during infection. This was supported by PKC activity study, where Ca-dependent PKC activity was inhibited but, Ca-independent PKC activity was enhanced. This result was further confirmed by using isotype specific pseudosubstrate inhibitors of Ca-dependent PKC beta and Ca-independent PKC zeta. Application of beta-pseudosubstrate could not alter the Ca-dependent PKC activity but zeta-pseudosubstrate inhibited the Ca-independent PKC activity in infected macrophages. Our immunoblot analysis with specific antibody against PKC beta and PKC zeta isotypes showed down regulation of PKC beta-II expression with concomitant induction of PKC zeta. Such inhibition of Ca-dependent PKC beta was reversed in macrophages treated with UR-6. Taken together, our observations revealed that infection with L. donovani selectively attenuates both the expression and activity of Ca-dependent PKC beta.
Animals↗
Generation of ceramide in murine macrophages infected with Leishmania donovani alters macrophage signaling events and aids intracellular parasitic survival.
In the present study, we examined the involvement of intracellular ceramide in host pathogen interaction of BALB/c mouse peritoneal macrophages infected with the obligate intracellular protozoan, Leishmania donovani. Our findings indicate that the level of intracellular ceramide was enhanced as a result of the in vitro infection. While the elevated ceramide was largely due to de novo synthesis, activation of the sphingomyelinases was also observed. The enhanced ceramide was responsible for the downregulation of classical PKC activity, upregulation of calcium independent atypical PKC-zeta expression and activity of calcium independent PKC. Ceramide also impaired the phosphorylation of MAPK. Evidently, ceramide suppressed the generation of nitric oxide during leishmanial infection and also facilitated the survival of leishmanial parasites in the intramacrophageal milieu. These data present newer insight to the signaling events in leishmania-infected murine macrophages, which might offer ceramide as a new therapeutic target in the future.
Animals↗
Modulation of acid secretion in common bile duct ligation-related gastropathy in Wistar rats.
BACKGROUND: Portal hypertensive gastropathy is associated with fundic gland atrophy, resulting in a decrease in chief and parietal cells, and diminished acid secretion. METHODS: Acid secretion by isolated parietal cells was measured (acridine orange retention), along with the levels of various second messengers (intracellular Ca(2+), cyclic adenosine monophosphate and protein kinase C) in the common bile duct, ligated portal hypertensive rats and compared with sham-operated controls. RESULTS: There was a significant decrease in the response of isolated parietal cells to the secretagogues histamine and carbachol. This resulted in the blunted acid secretion in the common bile duct ligated group. In addition, all the second messengers studied were significantly decreased as compared with the sham-operated controls. CONCLUSION: These results suggest that the blunted acid secretory response in the portal hypertensive rat is caused by an alteration in the intracellular signal transduction mechanism.
Acridine Orange↗
Intracellular cytokines in cells of necrotic tissue from patients with acute pancreatitis.
OBJECTIVE: To determine the alterations in intracellular cytokine responses in necrotic pancreatic tissue obtained on debridement from patients with acute pancreatitis. DESIGN: Laboratory study. SETTING: Teaching hospital, India. MATERIAL: Necrotic tissue obtained at necrosectomy from 34 patients with alcohol-induced or biliary pancreatitis (n = 17 in each) and at autopsy from 12 controls. INTERVENTIONS: Histopathological evaluation; measurement of intracellular content of the cytokines interleukin (IL)-2, IL-4, IL-10 and IFN-gamma in CD4+ and CD8+ T lymphocytes and IL-6 and IL-12 in CD14+ monocytes. MAIN OUTCOME MEASURES: Intracellular content of the measured cytokines. RESULTS: CD4+ and CD8+ T cells and CD14+ monocytes responded to in vitro stimulation of mitogens and synthesised cytokines to varying degrees in the three groups. The heterogeneous cytokine response pattern did not show a typical type 1/type 2 polarised model. CONCLUSIONS: This profile suggests that the cells retain the capacity to modulate their phenotype in response to local conditions at the effector site. These results could be taken into consideration when designing new and specific treatments for modifying the immune inflammatory response.
Acute Disease↗
Does the trabecular bone structure depicted by high-resolution MRI of the calcaneus reflect the true bone structure?
RATIONALE AND OBJECTIVES: The purpose of this study was to compare trabecular bone structure parameters assessed with high-resolution magnetic resonance imaging (HR-MRI) with those determined in specimen sections. METHODS: High-resolution MR images were obtained for 30 calcaneus specimens with a three-dimensional, T1-weighted spin-echo sequence (spatial in-plane resolution 0.195 mm, slice thicknesses of 0.3 and 0.9 mm). Thirty-eight sections were obtained from the specimens, and contact radiography was performed. In the corresponding sections, structural parameters analogous to bone histomorphometry were determined. RESULTS: Significant correlations between MRI-derived structural parameters and those derived from macro pathological sections were found: r values of up to 0.75 were obtained (P < 0.01). The highest correlations were found for apparent bone volume/total volume and trabecular thickness. Image thresholding techniques showed a significant impact on these correlations (P < 0.01). The thinner MR sections were less susceptible to the different thresholding algorithms. CONCLUSIONS: Trabecular bone structure depicted by HR-MR images is significantly correlated with that shown in macro sections (P < 0.01); however, a number of limitations have to be considered, including the substantial impact of thresholding techniques and slice thickness.
Aged↗
Fractal analysis of bone X-ray tomographic microscopy projections.
Fractal analysis of bone X-ray images has received much interest recently for the diagnosis of bone disease. In this paper, we propose a fractal analysis of bone X-ray tomographic microscopy (XTM) projections. The aim of the study is to establish whether or not there is a correlation between three-dimensional (3-D) trabecular changes and two-dimensional (2-D) fractal descriptors. Using a highly collimated beam, 3-D bone X-ray tomographic images were obtained. Trabecular bone loss was simulated using a mathematical morphology method. Then, 2-D projections were generated in each of the three orthogonal directions. Finally, the model of fractional Brownian motion (fBm) was used on bone XTM 2-D projections to characterize changes in bone structure that occur during disease, such a simulation of bone loss. Results indicate that fBm is a robust texture model allowing quantification of simulations of trabecular bone changes.
Bone and Bones↗
Immunomodulatory role of interleukin-10 in visceral leishmaniasis: defective activation of protein kinase C-mediated signal transduction events.
Leishmania donovani, an intracellular protozoan parasite, challenges host defense mechanisms by impairing the signal transduction of macrophages. In this study we investigated whether interleukin-10 (IL-10)-mediated alteration of signaling events in a murine model of visceral leishmaniasis is associated with macrophage deactivation. Primary in vitro cultures of macrophages infected with leishmanial parasites markedly elevated the endogenous release of IL-10. Treatment with either L. donovani or recombinant IL-10 (rIL-10) inhibited both the activity and expression of the Ca2+-dependent protein kinase C (PKC) isoform. However, preincubation with neutralizing anti-IL-10 monoclonal antibody (MAb) restored the PKC activity in the parasitized macrophage. Furthermore, we observed that coincubation of macrophages with rIL-10 and L. donovani increased the intracellular parasite burden, which was abrogated by anti-IL-10 MAb. Consistent with these observations, generation of superoxide (O2-) and nitric oxide and the release of murine tumor necrosis factor-alpha were attenuated in response to L. donovani or rIL-10 treatment. On the other hand, preincubation of the infected macrophages with neutralizing anti-IL-10 MAb significantly blocked the inhibition of nitric oxide and murine tumor necrosis factor-alpha release by the infected macrophages. These findings imply that infection with L. donovani induces endogenous secretion of murine IL-10, which in turn facilitates the intracellular survival of the protozoan and orchestrates several immunomodulatory roles via selective impairment of PKC-mediated signal transduction.
Adjuvants, Immunologic↗
Involvement of nitric oxide in the antiaggregatory effect of enalapril.
This study was conducted to examine the effects of single dose enalapril (1.6 mg/kg) on platelet aggregation alone and after an intravenous bolus dose of the nitric oxide synthase (NOS) inhibitor N-nitro-L-arginine (L-NNA; 40 mg/kg). Blood samples were collected before and 1, 2 and 6 h after the administration of drugs in rhesus monkeys. Enalapril was administered via a nasogastric tube while L-NNA was administered by the intravenous route. Platelet aggregation was stimulated with adenosine diphosphate (ADP) in platelet rich plasma (PRP). Enalapril significantly inhibited platelet aggregation with a peak effect at 6 h. Upon administration of L-NNA, there was a significant increase in the percentage of platelet aggregation. This effect was partially antagonized by enalapril. The present study demonstrates that enalapril may possess antiaggregatory effects, which may be mediated via nitric oxide mechanisms.
Adenosine Diphosphate↗
The skeletal structure of insulin-like growth factor I-deficient mice.
The importance of insulin-like growth factor I (IGF-I) for growth is well established. However, the lack of IGF-I on the skeleton has not been examined thoroughly. Therefore, we analyzed the structural properties of bone from mice rendered IGF-I deficient by homologous recombination (knockout [k/o]) using histomorphometry, peripheral quantitative computerized tomography (pQCT), and microcomputerized tomography (muCT). The k/o mice were 24% the size of their wild-type littermates at the time of study (4 months). The k/o tibias were 28% and L1 vertebrae were 26% the size of wild-type bones. Bone formation rates (BFR) of k/o tibias were 27% that of the wild-type littermates. The k/o bones responded normally to growth hormone (GH; 1.7-fold increase) and supranormally to IGF-I (5.2-fold increase) with respect to BFR. Cortical thickness of the proximal tibia was reduced 17% in the k/o mouse. However, trabecular bone volume (bone volume/total volume [BV/TV]) was increased 23% (male mice) and 88% (female mice) in the k/o mice compared with wild-type controls as a result of increased connectivity, increased number, and decreased spacing of the trabeculae. These changes were either less or not found in L1. Thus, lack of IGF-I leads to the development of a bone structure, which, although smaller, appears more compact.
Animals↗
Trabecular structure assessment in lumbar vertebrae specimens using quantitative magnetic resonance imaging and relationship with mechanical competence.
The purpose of this study was to use quantitative magnetic resonance imaging (MRI; high-resolution [HR] and relaxometry) to assess trabecular bone structure in lumbar vertebrae specimens and to compare these techniques with bone mineral density (BMD) in predicting stress values obtained from mechanical tests. Fourteen vertebral midsagittal sections from lumbar vertebrae L3 were obtained from cadavers (aged 22-76 years). HR images with a slice thickness of 300 microm and an in-plane spatial resolution of 117 microm2 x 117 microm2 were obtained. Transverse relaxation time T2' distribution was measured by using an asymmetric spin-echo (ASE) sequence. Traditional morphometric measures of bone structure such as apparent trabecular bone fraction (app. BV/TV), apparent trabecular bone number (app. Tb.N), apparent trabecular bone separation (app. Tb.Sp), and apparent trabecular bone thickness (app. Tb.Th) as well as the directional mean intercept length (MIL) were calculated. Additionally, BMD measurements of these sections were obtained by dual-energy X-ray absorptiometry (DXA) and biomechanical properties such as directional stress values (to fracture) were determined on adjacent specimens. With the exception of T2', all morphological parameters correlated very well with age, BMD, and stress values (R between 0.79 and 0.92). However, in the direction perpendicular to the magnetic field, T2' values enhanced the adjusted R2 correlation value with horizontal (M/L) stress values in addition to BMD from 0.70 to 0.91 (p < 0.05).
Adult↗
Risk factors for kernicterus in term babies with non-hemolytic jaundice.
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Asphyxia Neonatorum↗