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Biomedical subjects

H Sadeghi

Publications and source records attributed to H Sadeghi.

At least 19 recordsLinked to original sources

Isolation and structure elucidation of a new potent anti-neoplastic diterpene from Dendrostellera lessertii.

Two diterpene esters were isolated from Dendrostellera lessertii. These compounds were identified as compound I (12-O-benzoyl-3,5-hydroxy-6,7-epoxy-resiniferonol-9,13,14-orthobenzoate) and compound 11 (12-O-benzoyl-5-hydroxy-6,7-epoxy-resiniferonol-9,13,14-orthodecanoate). Cytotoxicity evaluation of these two compounds, using seven different cancerous cell lines, indicated that compound I with IC50 of 5-25 nmol, is 2.5 times more active than compound II. Using flow cytometry technique, it was found that treatment of the most responsive cells (K562) with compound I inhibited the progression of cells through G1 phase by almost 20% compared to the untreated cells.

Antineoplastic Agents, Phytogenic↗

Effect of body morphology on standing balance in adolescent idiopathic scoliosis.

OBJECTIVES: The objective of this study was to determine the effect of body somatotype on standing balance in girls with adolescent idiopathic scoliosis (AIS) who are under observation but not wearing a body brace. DESIGN: In all, 74 girls participated in this study to form the able-bodied (n = 36) and the AIS (n = 38) groups, having an average age of 13 yrs. Quiet standing balance was tested using a force platform. Afterward, subjects in each group were divided according to their dominant body somatotype, namely endomorphs (fatness), mesomorphs (muscular), or endomorphic ectomorphs (lean). RESULTS: The center of pressure measured in the anteroposterior position was closer to the heels for the AIS ectomorphic group by approximately 14 mm (P = 0.00497). Only the AIS mesomorphic group displayed a statistically significant 12-mm shift to the right in their center of pressure (P = 0.01211) compared with the able-bodied girls of the same morphotype. In the endomorphic group, the sway area was statistically higher for the scoliotic subjects (P = 0.00839). The distances traveled by the AIS subjects were all statistically longer for all three body morphologic somatotypes. CONCLUSION: Different postural responses seem to be dependent on body somatotypes. The endomorphic AIS girls had a larger sway area than their able-bodied counterparts while maintaining a similar center of pressure position. The AIS ectomorphic girls had a tendency to lean further back than a comparable able-bodied group. This could be emphasizing a hypokyphotic trunk attitude and increasing the risk of spinal deformity progression. The AIS mesomorphic subjects characterized by a large muscular and bony structure had a tendency to position their center of mass more to their right, indicating less postural adaptability and a stiffer trunk.

Adolescent↗

Synthesis and calcium antagonist activity of 1,4-dihydropyridines containing phenylaminoimidazolyl substituents.

Alkyl ester analogues of nifedipine, in which the ortho-nitrophenyl group at position 4 is replaced by 2-methylthio-1-phenylamino-5-imidazolyl substituent, were synthesized and evaluated as calcium-channel antagonists using the high K(+) contraction of guinea-pig ileal longitudinal smooth muscle. The results for the symmetrical esters showed that in the series of alkyl esters increasing the length of methylene chain in C-3 and C-5 ester substituents for more than two methylene units decreases activity. In the phenylalkyl ester series increasing the length of methylene chain also decreases activity. The results demonstrate that most of the compounds had similar activity to the reference drug nifedipine. In addition, two compounds, 5b and 5f were more active than the nifedipine.

Aniline Compounds↗

Main functional roles of knee flexors/extensors in able-bodied gait using principal component analysis (I).

This study was undertaken to demonstrate how principal component analysis (PCA) can be used to detect the main functional structure of actions taken by knee flexors/extensors during able-bodied gait. PCA was applied as a classification and curve structure detection method for knee sagittal muscle moment developed during walking of 20 young, healthy male subjects. Over 90% of the information provided by the first three principal components (PCs) was chosen for further biomechanical interpretation. PCA was able to identify the three main functional contributions of knee sagittal muscle moment during able-bodied gait, namely control balance, foot clearance/limb preparation and shock absorption.

Adolescent↗

Knee flexors/extensors in gait of elderly and young able-bodied men (II).

In this study the fundamental tasks of muscle activity at the knee during gait in elderly and young able-bodied subjects were identified using principal component analysis (PCA). Role discrepancies between the older and younger subjects for the actions executed by the knee flexors and extensors during the gait cycle were also investigated. The t-test for independent groups was applied to determine significant differences between spatio-temporal and peak muscle moment parameters (P<0.05). PCA as a multivariate classification and curve structure detection method was applied to the sagittal knee muscle moment curves of twenty elderly (72 +/-5.5 years) and twenty young (25 +/- 8.1 years) subjects. The first three principal components (PCs) which accounted for 80% (older) and 93% (younger) of the information were retained for further analysis. Providing stable locomotion was recognised as a major task of the knee in the older subjects, while for the younger subjects the knee contributed to both balance and propulsion. Supporting the body during single limb support should be considered the only common task at the knee level in elderly and young subjects' gait. The lack of muscle power for propulsion might be the reason for not identifying the knee extensor muscle roles in the first three major tasks during elderly gait. Functional asymmetry can be considered the result of a different ordering of the functional roles of the muscles acting at the knee level in elderly and young subjects.

Adolescent↗

Functional roles of ankle and hip sagittal muscle moments in able-bodied gait.

OBJECTIVE: The main objectives of this study on able-bodied gait were (a) to identify the main functions of the ankle and hip muscle moments and their contribution to support and propulsion tasks, and (b) to illustrate the interaction between the ankle and hip moment activities. DESIGN: Twenty young, able-bodied male subjects walked along a 13 m path at a freely chosen speed. BACKGROUND: Functional contributions of the ankle and hip muscles and their interactions in achieving support and propulsion tasks during gait are still subject to controversy. METHODS: Principal component analysis was applied as a curve structure detection method to identify the main functional characteristics of the ankle and hip muscle moments. The first two principal components which contained over 70% and 85%, respectively, of the information in the ankle and hip moment curves revealed their functional tasks. Ankle versus hip moment plots was used to illustrate the interactions between muscles acting at the hip and ankle in the sagittal plane. Correlation coefficient and covariance calculations quantified the interaction between the ankle and hip moments. RESULTS: The first principal component revealed that the main role of the ankle and hip is to keep the body from collapsing. The second principal component is associated with the functional contribution of both ankle plantarflexors and hip flexors during the propulsion phase (50-60% of the gait cycle). High coordination (r=0.82) between the ankle and hip moments was observed. CONCLUSION: Maintaining body support against gravity was identified as the first functional task of the ankle plantarflexors and hip extensors, while contribution to propulsion was recognised as the second major role for the ankle plantarflexors and hip flexors. RELEVANCE: Identifying the main roles of the muscles acting at the hip and ankle during able-bodied walking provides better insight into how pathological gait should be evaluated.

Adult↗

Muscle power compensatory mechanisms in below-knee amputee gait.

OBJECTIVE: This three-dimensional and bilateral gait study on five below-knee amputees was undertaken to demonstrate the following: (1) how hip muscle powers can compensate for the lack of ankle function on the amputated side; and (2) how these compensatory mechanisms can influence muscle power activities in the sound limb. DESIGN: Gait data were assessed by an eight-camera high-speed video system synchronized to two force plates. The three-dimensional mechanical muscle powers were calculated at the joints of the lower limbs. Significant differences between each limb were determined using the Student's t test for paired data with P < 0.05. RESULTS: In the absence of ankle plantar flexor power, hip extensors and flexors as well as hip external rotators became the major power generators, whereas hip abductors and adductors and knee extensors muscle powers became the main source of absorption. For the sound limb, increased hip extensor activity was observed, accompanied by less hip abduction-adduction activity. CONCLUSIONS: Perturbations in below-knee amputee gait affected the hip muscle powers on the amputated side in all three planes, although the hip frontal plane balance was modified in the sound limb.

Adult↗

Lower limb muscle power relationships in bilateral able-bodied gait.

OBJECTIVE: The purpose of this study was to test the hypothesis that limb propulsion is mainly associated with the interaction of a number of muscle power bursts developed throughout the stance phase and that the control actions are mainly achieved by the contralateral limb through different power-burst interactions. We also hypothesized that the power activities of the propulsion limb would be related to those of the control limb. DESIGN: Sixty gait trials of 20 subjects with dominant right hands and right legs were chosen for analysis. Each trial represents a performance of an able-bodied gait. Data were assessed using an eight-camera, high-speed, video-based system synchronized to two force plates. The muscle powers and their related mechanical energies were calculated at each joint and in each plane of the lower limbs by use of an inverse dynamic technique. The Pearson correlation method was used to determine the relationships within each limb by use of the data identified by principal component analysis, whereas a canonical correlation analysis was performed to illustrate the interaction between the limbs. RESULTS: Gait propulsion was an activity initiated by the hip shortly after heel-strike and maintained throughout the stance phase. Control was the main task of the left limb as evidenced by the power absorption bursts at the hip and knee. The left limb power generations were generally secondary to control activities and were possibly involved in adjustments to correct the other limb's propulsion. Interlimb interaction further emphasized the functional relationship between forward progression and control tasks developed by each limb and highlighted the importance of the frontal and transverse plane actions during gait. CONCLUSION: These results do not support the hypothesis that the ankle was a major contributor to forward progression.

Adult↗

Distinct categories of immunologic changes in frail elderly.

Immune changes and their relationships in a frail elderly population (N=116, age 70-103, median 86 years) were defined in comparison to a healthy younger group. Previous immune studies in the elderly have generally focused on one or few parameters without correlation analyses. Furthermore, the study populations have been active elderly in relatively small numbers. A total of 33 immune parameters representing many aspects of the immune system were quantified. Most changes in the frail elderly were parallel to those reported in active elderly. A classification tree analysis revealed that increased plasma activation markers (neopterin and sTNF-R) and increased CD28 expression on CD8 T cells and proliferative response separated the aged and control populations. Statistical procedures utilizing principal components analyses, partial correlations and exploratory factor analyses all indicated that immunologic parameters in frail elderly are grouped in three major clusters of immunologic results. These involved (a) increased plasma levels of neopterin and sTNF receptor indicating elevated IFNgamma and TNF cytokine activity; (b) increased proportion of mature (CD45RO) versus naïve (CD45RA) T cells; and (c) a diverse group of related changes including impaired proliferative response, reduced T cells, CD28 and CD25 expression, B cell percentage and lower CD4:CD8 ratios and increased HLA-DR expression. These findings emphasize that several different groups of immune parameters but not 33 independent immune changes, occurred in the aged population.

ADP-ribosyl Cyclase↗

Symmetry and limb dominance in able-bodied gait: a review.

As one of the most universal of all human activities, gait in the able-bodied has received considerable attention, but many aspects still need to be clarified. Symmetry or asymmetry in the actions of the lower extremities during walking and the possible effect of laterality on gait are two prevalent and controversial issues. The purpose of this study was to review the work done over the last few decades in demonstrating: (a) whether or not the lower limbs behave symmetrically during able-bodied gait; and (b) how limb dominance affects the symmetrical or asymmetrical behavior of the lower extremities. The literature reviewed shows that gait symmetry has often been assumed, to simplify data collection and analysis. In contrast, asymmetrical behavior of the lower limbs during able-bodied ambulation was addressed in numerous investigations and was found to reflect natural functional differences between the lower extremities. These functional differences were probably related to the contribution of each limb in carrying out the tasks of propulsion and control during able-bodied walking. In current debates on gait symmetry in able-bodied subjects, laterality has been cited as an explanation for the existence of functional differences between the lower extremities, although a number of studies do not support the hypothesis of a relationship between gait symmetry and laterality. Further investigation is needed to demonstrate functional gait asymmetry and its relationship to laterality, taking into consideration the biomechanical aspects of gait.

Biomechanical Phenomena↗

Reduction of gait data variability using curve registration.

Timing in peak gait values shifts slightly between gait trials. When averaged, the standard deviation (S.D.) in gait data may increase due to this inter-trial variability unless normalization is carried out beforehand. The objective of this study was to determine how curve registration, an alignment technique, can reduce inter-subject variability in gait data without perturbing the curve characteristics. Twenty young, healthy men participated in this study each providing a single gait trial. Gait was assessed by means of a four-camera high-speed video system synchronized to a force plate. A rigid body three-segment model was used in an inverse dynamic approach to calculate three-dimensional muscle powers at the hip, knee and ankle. Curve registration was applied to each of the 20 gait trials to align the peak powers. The mean registered peak powers increased by an average of 0.10 +/- 0.13 W/kg with the highest increases in the sagittal plane at push-off. After performing curve registration, the RMS values decreased by 13.6% and the greatest reduction occurred at the hip and knee, both in the sagittal plane. No important discontinuities were reported in the first and second derivatives of the unregistered and registered curves. Curve registration did not have much effect on the harmonic content. This would be an appropriate technique for application prior to any statistical analysis using able-bodied gait patterns.

Adult↗

Principal component analysis of the power developed in the flexion/extension muscles of the hip in able-bodied gait.

This study was undertaken to demonstrate how principal component analysis (PCA) can be used: (a) to detect the main functional structure of actions taken by hip extensors and flexors during two consecutive gait cycles of able-bodied subjects, and (b) to determine whether or not symmetrical behaviour exists between right and left hip muscle power activity. Twenty young, healthy male subjects walked along a 13 m path at a freely-chosen speed. Applying curve structure detection methods such as PCA to walking patterns can provide insight into the functional tasks accomplished by the lower limbs of able-bodied and disabled subjects. PCA was applied as a classification and curve structure detection method to hip sagittal muscle power calculated for the right and left lower limbs. Over 70% of the information provided by the first four principal components (PCs) was chosen for further biomechanical interpretation. PC1 for both right and left sides mainly described the action taken by the hip extensors/flexors corresponding to the vertical component of ground force on the respective limbs during mid-stance. Propulsion and limb preparation were identified as the second and third tasks attributed to right hip muscle power, while between limb co-ordination was recognised as the second and third functional tasks of the left hip extensors/flexors. Balance was identified as the fourth main functional contribution of the hip extensors/flexors at the right limb while for the left limb, these muscles were mainly responsible for preparing the limb to enter into new gait cycle. PCA was able to identify the four main functional contributions of hip sagittal muscle power during able-bodied gait. PCA was also able to examine the existence of functional asymmetry in gait by highlighting different task priorities at the hip level for the right and left lower limbs.

Adult↗

Anti-inflammatory actions of 15-deoxy-delta 12,14-prostaglandin J2 and troglitazone: evidence for heat shock-dependent and -independent inhibition of cytokine-induced inducible nitric oxide synthase expression.

In this study, the anti-inflammatory actions of the peroxisome proliferator-activated receptor (PPAR)-gamma agonists 15-deoxy-delta 12,14-prostaglandin J2 (15-d-delta 12,14-PGJ2) and troglitazone have been examined. Treatment of RAW 264.7 cells and CD-1 mouse peritoneal macrophages with lipopolysaccharide (LPS) + interferon-gamma (IFN-gamma) results in inducible nitric oxide synthase (iNOS), inducible cyclooxygenase (COX-2) and interleukin-1 (IL-1) expression, increased production of nitric oxide, and the release of IL-1. In a concentration-dependent manner, 15-d-delta 12,14-PGJ2 inhibits each of these proinflammatory actions of LPS + IFN-gamma, with half-maximal inhibition at approximately 0.5 microg/ml and complete inhibition at 1-5 microg/ml. The inhibitory actions of 15-d-delta 12,14-PGJ2 on LPS + IFN-gamma-induced inflammatory events are not associated with the inhibition of iNOS enzymatic activity or macrophage cell death, but appear to result from an inhibition of iNOS and IL-1 transcription. In addition, the anti-inflammatory actions of 15-d-delta 12,14-PGJ2 are not limited to peritoneal macrophages, as 15-d-delta 12,14-PGJ2 prevents TNF-alpha + LPS-induced resident islet macrophage expression of IL-1beta and beta-cell expression of iNOS stimulated by the local release of IL-1 in rat islets. 15-d-delta 12,14-PGJ2 appears to be approximately 10-fold more effective at inhibiting resident islet macrophage activation (in response to TNF + LPS) than IL-1-induced nitrite production by beta-cells. Two mechanisms appear to be associated with the antiinflammatory actions of both 15-d-delta 12,14-PGJ2 and troglitazone: 1) the direct inhibition of cytokine- and endotoxin-stimulated iNOS and IL-1 transcription; and 2) the inhibition of IL-1 signaling, an event associated with PPAR-gamma agonist-induced activation of the heat shock response (as assayed by heat shock protein 70 expression). These findings indicate that the PPAR-gamma agonists, troglitazone and the J series of prostaglandins, are potent anti-inflammatory agents that prevent cytokine- and endotoxin-stimulated activation of peripheral and resident tissue macrophages and cytokine-induced iNOS expression by beta-cells by the inhibition of transcriptional activation and induction of the heat shock response.

Animals↗

Contributions of lower-limb muscle power in gait of people without impairments.

BACKGROUND AND PURPOSE: Although gait asymmetry in rehabilitation has been documented, little is known about propulsion and control tasks performed by each limb and how these tasks are managed between the lower limbs. The purpose of this study was to test the hypothesis that the leading limb contributes mainly to forward progression, whereas the trailing limb provides control and propels the lower limb to a lesser extent. SUBJECTS: Nineteen men with an average age of 26.2 years (SD=3.2, range=21-34) and no history of orthopedic ailments participated in the study. METHODS: Muscle power was determined using an 8-camera high-speed video system synchronized with 2 force plates. The principal-component analysis method was applied to reduce and classify 52 gait variables for each limb, and Pearson correlations were used to determine the interactions within the data sets for each limb. RESULTS: Gait propulsion was initiated by the hip of the leading limb shortly after heel-strike and was maintained throughout the stance phase. Control was the main task of the trailing limb, as evidenced by the power absorption bursts at the hip and knee. CONCLUSION AND DISCUSSION: Within-limb interaction further emphasized the functional relationship between forward progression and control tasks and highlighted the importance of frontal- and transverse-plane actions during gait.

Adult↗

O-Glycosylation of the V2 vasopressin receptor.

The human V2 vasopressin receptor contains one consensus site for N-linked glycosylation at asparagine 22 in the predicted extracellular amino terminal segment of the protein. This segment also contains clusters of serines and threonines that are potential sites for O-glycosylation. Mutagenesis of asparagine 22 to glutamine abolished N-linked glycosylation of the V2 receptor (N22Q-V2R), without altering its function or level of expression. The N22Q-V2R expressed in transfected cells migrated in denaturing acrylamide gels as two protein bands with a difference of 7000 Da. Protein labeling experiments demonstrated that the faster band could be chase to the slower one suggesting the presence of O-linked sugars. Sialidase treatment of membranes from cells expressing the N22Q-V2R or of immunoprecipitated metabolically labeled V2R accelerated the migration of the protein in acrylamide gels demonstrating the existence of O-glycosylation, the first time this type of glycosylation has been found in a G protein coupled receptor. Synthesis of metabolically labeled receptor in the presence of 1 mM phenyl-N-acetyl-alpha-D-galactosaminide, a competitive inhibitor of N-acetyl-alpha-D-galactose and N-acetylneuraminic acid transferases, also produced a receptor that migrated faster in denaturing gels. Serines and threonines present in the amino terminus were analyzed by alanine scanning mutagenesis to identify the acceptor sites. O-glycosylation was found at most serines and threonines present in the amino terminus. Because the disappearance of a site opened the availability of others to the transferases, the exact identification of the acceptor sites was not feasible. The wild type V2R expressed in HEK 293, COS, or MDCK cells underwent N- and O-linked glycosylation. The mutant V2R bearing all serine/threonine substitutions by alanine at the amino terminus yielded a receptor functionally indistinguishable from the wild type protein, whose mobility in polyacrylamide gels was no longer affected by sialidase treatment.

Amino Acid Sequence↗

Transient phosphorylation of the V1a vasopressin receptor.

The V1a arginine vasopressin receptor (V1aR) expressed in HEK 293 cells was phosphorylated after binding to arginine vasopressin (AVP). The phosphate was incorporated very rapidly into the protein but remained attached for a very short time despite the continuous presence of hormone. The extent of phosphorylation depended upon the concentration of AVP suggesting the involvement of G-protein-coupled receptor kinases. Protein kinase C (PKC) contributed to V1aR phosphorylation as demonstrated by the fact that inhibition of the kinase decreased the amount of phosphate incorporated into the receptor. However, PKC activity was not responsible for the transient nature of V1aR phosphorylation. The hormone-free receptor could be phosphorylated by phorbol ester-activated PKC. Although the phosphorylation was transient, the phosphate groups incorporated remained on the receptor protein longer than those incorporated after AVP treatment. PKC phosphorylation of unoccupied V1aR was not sufficient to promote sequestration. Vasopressin also promoted sequestration of about 80% of the surface receptor, but measurements of the rate of accumulation of inositol phosphates in the sustained presence of the ligand did not reveal a significant desensitization of coupling to phospholipase C activity. The addition of a V1aR antagonist inhibited the sustained accumulation of inositol phosphates establishing that the sustained stimulation of PLC was mediated by receptors located on the cell surface. The transient character of V1aR phosphorylation seemed intrinsic to the receptor protein rather than a consequence of signaling within the cell, and receptor sequestration appeared to be responsible for the desensitization observed in HEK 293 cells.

Arginine Vasopressin↗

Inspiratory flow limitation in children with bronchopulmonary dysplasia.

The objective of this study was to compare pulmonary function tests of children with bronchopulmonary dysplasia (BPD) and asthma, and to evaluate children with BPD for evidence of upper airway obstruction. This is a case-control retrospective study of pulmonary function tests (PFTs) of 11 children with BPD between 5 and 8 years of age who were followed by pediatric pulmonologists, and of 32 age- and height-matched children with asthma. The median forced vital capacity (FVC), forced expiratory volume in one second (FEV1), and peak expiratory flow (PEF) were significantly lower in the BPD group (0.86 L, 0.79 L, 120 L/min) than in the asthmatic group (1.34 L, 1.21 L, 155 L/min; P = 0.002, P = 0.007, P = 0.004, respectively). Both groups were equally hyperinflated (median thoracic gas volume 155% of predicted values in the BPD compared to 152% predicted in the asthma group; P = 0.67), and both groups showed decreases in air-trapping after a bronchodilator. The ratios of forced expiratory flow at 50% of the FVC to forced inspiratory flow at 50% of the FVC (FEF50%/FIF50%) and FEV1 to PEF (FEV1/PEF) were used to assess upper airway obstruction and were higher in children with BPD than asthma (P = 0.0001 and P = 0.035, respectively). We conclude that pulmonary function of children with BPD who are still symptomatic after 5 years of age is different from age-matched children with asthma, and the children with BPD demonstrate significant inspiratory flow limitations.

Asthma↗

Incidence and prognostic value of electrocardiographic abnormalities after heart transplantation.

BACKGROUND: The improvement of surgical techniques and the use of immunosuppressive drugs within the past 15 years has made heart transplantation an increasingly performed procedure and an accepted treatment for end-stage cardiac failure. HYPOTHESIS: The aim of this study was to describe the changes of the 12-lead electrocardiogram (ECG) after heart transplantation and to determine their prognostic value on complications such as rejection or graft coronary artery disease during follow-up. METHODS: The ECGs of 62 consecutive patients were analyzed for 5 years at follow-up periods of 1, 2, 3, 6 months and yearly after transplantation. RESULTS: The most prevalent abnormality was the presence of complete or incomplete right bundle-branch block (RBBB). New RBBB appeared in 69% (43/62) of the patients, mainly during the first month (21/43). There was no left bundle-branch block. We detected nine episodes of supraventricular arrhythmias: one atrial fibrillation, six atrial flutter, one junctional tachycardia, one orthodromic tachycardia on a Wolff-Parkinson-White syndrome; all appearing during the first 3 months. Three of the six episodes of atrial flutter occurred during an episode of acute rejection. There was no relation between RBBB and the gender and age of recipients and donors, nor with the graft ischemic time and the pretransplantation hemodynamic values. Right bundle-branch block was not associated with acute rejection nor with graft coronary artery disease. CONCLUSION: The ECG abnormalities after heart transplantation have no predictive value on the long-term evolution. Right bundle-branch block is very frequent and is not associated with adverse prognosis.

Adult↗