PubMed Health⌕ Search

Biomedical subjects

Muhammad Ashraf

Publications and source records attributed to Muhammad Ashraf.

At least 19 recordsLinked to original sources
PubMed2007

Chronic preconditioning: a novel approach for cardiac protection.

Ischemic preconditioning is the most powerful protective mechanism known against lethal ischemia. Unfortunately, the protection lasts for only a few hours. Here we tested the hypothesis that the heart can be kept in a preconditioned state for constant protection against ischemia. In this study we chose BMS-191095 (BMS), a highly selective opener of mitochondrial ATP-sensitive K(+) (mitoK(ATP)) channels. BMS (1 mg/kg ip) was administered to rats every 24 h until 96 h. In other groups, BMS plus wortmannin (WTN, 15 microg/kg ip), an inhibitor of the phosphatidylinositol 3-kinase (PI3-K), or BMS plus 5-hydroxydecanoic acid (5-HD, 5 mg/kg ip), an inhibitor of mitoK(ATP), or BMS plus N(omega)-nitro-L-arginine methyl ester (L-NAME) (30 microg/kg ip), an inhibitor of nitric oxide (NO) synthase, were administered to rats. Rats were then subjected to 30-min left anterior descending coronary artery occlusion and 120-min reperfusion. Cardiac function, infarct size, pathological changes, and apoptosis were assessed at the end of treatments. Saline-treated hearts displayed marked contractile dysfunction and underwent pathological changes. BMS-treated rats showed significant improvement in cardiac function, and infarct size was significantly reduced in BMS-treated hearts. However, protection by BMS was abolished by 5-HD, WTN, or L-NAME. These data demonstrate that hearts can be chronically preconditioned and retain their ability to remain resistant against lethal ischemia and that this protection is mediated by activation of mitoK(ATP) via NO and PI3-K/Akt signaling pathways.

Animals↗
PubMed2007

Moringa oleifera: a food plant with multiple medicinal uses.

Moringa oleifera Lam (Moringaceae) is a highly valued plant, distributed in many countries of the tropics and subtropics. It has an impressive range of medicinal uses with high nutritional value. Different parts of this plant contain a profile of important minerals, and are a good source of protein, vitamins, beta-carotene, amino acids and various phenolics. The Moringa plant provides a rich and rare combination of zeatin, quercetin, beta-sitosterol, caffeoylquinic acid and kaempferol. In addition to its compelling water purifying powers and high nutritional value, M. oleifera is very important for its medicinal value. Various parts of this plant such as the leaves, roots, seed, bark, fruit, flowers and immature pods act as cardiac and circulatory stimulants, possess antitumor, antipyretic, antiepileptic, antiinflammatory, antiulcer, antispasmodic, diuretic, antihypertensive, cholesterol lowering, antioxidant, antidiabetic, hepatoprotective, antibacterial and antifungal activities, and are being employed for the treatment of different ailments in the indigenous system of medicine, particularly in South Asia. This review focuses on the detailed phytochemical composition, medicinal uses, along with pharmacological properties of different parts of this multipurpose tree.

Flowers↗
PubMed2006

In vitro and in vivo effects of bone marrow stem cells on cardiac structure and function.

It is hypothesized that the protection of bone marrow stem cells (BMSCs) on ischemic myocardium might be related to the anti-apoptotic effect via paracrine mechanisms. In this study, a wide array of cytokines including vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF), stromal cell-derived factor-1 (SDF-1) and insulin growth factor-1 (IGF-1) were detected in the BMSCs cultured medium by ELISA. Myocyte apoptosis was assayed by DNA fragmentation and annexin-V staining. Myocardial infarction model was produced by ligation of mouse left anterior descending coronary artery (LAD). Before LAD ligation, mice were myoablated by irradiation and transplanted with bone marrow cells from transgenic mice expressing green fluorescent protein (GFP). After LAD ligation, animals were administered stem cell factor (SCF, 200 mug/day/kg, i.p.) or saline for 6 days. Animals were sacrificed at 4 weeks after SCF treatment. Apoptotic cardiomyocytes were analyzed by TUNEL. Myocardial function was analyzed by echocardiography and pressure-volume system. Bcl-2 protein was analyzed by Western blotting. Our results showed that cultured BMSCs released VEGF, bFGF, SDF-1 and IGF-1. Hypoxia-induced cell apoptosis was diminished in cardiomyocytes co-cultured with BMSCs. Smaller LV dimension and increased LV ejection fraction were seen in SCF-treated animals. SCF significantly reduced cardiomyocytes apoptosis within peri-infarct area and increased up-regulation expression of Bcl-2 in ischemic area. Moreover, conditioned medium from cultured BMSCs also induced up-regulation of Bcl-2 protein in cardiomyocytes. It is concluded that paracrine mediators secreted by BMSCs might be involved in early repair of ischemic heart by preventing cardiomyocytes apoptosis and improving cardiac function.

Animals↗
PubMed2006

Diagnosis of heavy metal contamination in agro-ecology of Gujranwala, Pakistan using cattle egret (Bubulcus ibis) as bioindicator.

The present study investigated the status of heavy metals: Lead (Pb), Cadmium (Cd), Chromium (Cr), Cobolt (Co), Silver (Ag) and Nickle (Ni) residues in egg, regurgitate and sediment samples collected from two colonies of cattle egret (Bubulcus ibis) during the breeding seasons between April and August in 2004 and 2005. The mean concentration of heavy metals in eggs and regurgitates was found higher compared to the maximum residue limit (mrl) standards prescribed by Environmental Protection Agency (EPA). A further comparison was made with a similar study conducted in China. High concentrations of heavy metals have contributed to the altered breeding behaviour of the bird species studied. Based on these findings we suggested a regular monitoring of the spread of these pollutants as these have not yet reached to the sediments.

Animals↗
PubMed2006

Small heat-shock protein Hsp20 attenuates beta-agonist-mediated cardiac remodeling through apoptosis signal-regulating kinase 1.

Chronic stimulation of the beta-adrenergic neurohormonal axis contributes to the progression of heart failure and mortality in animal models and human patients. In cardiomyocytes, activation of the beta-adrenergic pathway has been shown to result in transiently increased expression of a cardiac small heat-shock protein Hsp20. The present study shows that cardiac overexpression (10-fold) of Hsp20 may protect the heart against beta-agonist-induced cardiac remodeling, associated with isoproterenol (50 mug/g per day) infusion for 14 days. Hsp20 attenuated the cardiac hypertrophic response, markedly reduced interstitial fibrosis, and decreased apoptosis. Contractility was also preserved in hearts with increased Hsp20 levels. These beneficial effects were associated with attenuation of the ASK1-JNK/p38 (apoptosis signal-regulating kinase 1/c-Jun NH(2)-terminal kinase/p38) signaling cascade triggered by isoproterenol, whereas there was no difference in either extracellular signal-related kinase 1/2 or Akt activation. Parallel in vitro experiments supported the inhibitory role of Hsp20 on enforced ASK1-JNK/p38 activation in both H9c2 cells and adult rat cardiomyocytes. Immunostaining studies also demonstrated that Hsp20 colocalizes with ASK1 in cardiomyocytes. Taken together, our findings indicate that (1) beta-agonist-induced cardiac injury is associated with activation of the ASK1-JNK/p38 cascade; (2) increased expression of Hsp20 attenuates the induction of remodeling, dysfunction, and apoptosis in response to sustained beta-adrenergic stimulation; and (3) the beneficial effects of Hsp20 are at least partially attributable to inhibition of the ASK1-signaling cascade.

Adrenergic beta-Agonists↗
PubMed2006

Supportive interaction between cell survival signaling and angiocompetent factors enhances donor cell survival and promotes angiomyogenesis for cardiac repair.

Akt is a major cell survival and angiogenic mediator downstream of angiopoietin-1 (Ang-1)/Tie-2 signaling pathway. We hypothesize that transplantation of mesenchymal stem cells (MSCs) co-overexpressing Ang-1 and Akt lead to better prognosis. Ang-1 and Akt genes were adenovirally transduced into MSCs from male Fischer rats. Cytoprotective effects of transgene overexpression in vitro were assessed by exposure of cells to 8 hours of anoxia. TUNEL and measurement of lactate dehydrogenase showed that MSCs co-overexpressing Ang-1 and Akt (MAAs) were more resistant to anoxia as compared with the nontransduced MSCs or those transduced with Ang-1 or Akt alone. For in vivo studies, after permanent coronary artery occlusion, animals were grouped (n=20/group) to receive intramyocardial injections of 70 microL of basal medium without cells (group 1) or containing 3x10(6) nontransduced MSCs (group 2) or MAAs (group 3). Four animals per group were euthanized on 4, 7, and 14 days after cell transplantation for molecular studies. Extensive survival of MAAs was observed in group 3, which continued to co-overexpress transgenes in rat heart at 2 weeks after cell transplantation. Immunohistology at 4 weeks revealed myogenic differentiation of donor cells at the site of cell graft. Blood vessel density was highest in the infarct and periinfarct regions in group 3 (P<0.05). Echocardiography at 4 weeks showed that heart function indices were significantly improved in group 3 (P<0.05), including ejection fraction and fractional shortening as compared with groups 1 and 2. We conclude that supportive interaction between Ang-1 and Akt during MSC transplantation gave better prognosis via enhanced cell survival, improved angiomyogenesis, and restored global cardiac function.

Angiopoietin-1↗
PubMed2006

Evidence for ischemia induced host-derived bone marrow cell mobilization into cardiac allografts.

Mobilized bone marrow stem cells (BMSC) exhibit high degree of plasticity and participate in the repair process in the event of myocardial damage. In this study, we verified the proportional contribution of recipient BMSC in the repair process and identified their specific surface markers. Wild-type (WT) donor female heart was transplanted into abdominal cavity of male rat (Group I). In some of recipient animals, infarction was created by LAD occlusion (Group II). Two weeks later, transplanted female hearts were harvested for histological analysis of the mobilized cells. C-kit, CD31, Ki67 and Y-chromosome were used as markers to identify mobilized cells in the female hearts. Y-chromosome positive cells were found in the donor female cardiac allografts. Acute myocardial infarction (AMI) of recipient heart induced migration of progenitor cells into the lesions of chronic rejection in the allograft. Donor ventricular mass reduction was more pronounced in Group I. Endothelial progenitor cells induced by AMI from male recipient extensively migrated into the cardiac allograft. SDF-1 mRNA levels significantly increased (peak level at 24 h after AMI) in recipient heart. CXCR4 was strongly expressed in the transplanted hearts around the perivascular area. Spontaneous mobilization of hematopoietic progenitor cells (HPCs) occurred in cardiac allografts after creating recipient heart AMI and was detectable until 2 weeks. These data suggests that CXCR4 overexpression enhances vascularization in the damaged myocardium and SDF-1/CXCR4 axis seems particularly important in progenitor cell chemotaxis, homing, engraftment and retention in damaged myocardium. In addition, BMSC attracted to the site of ischemic injury participate in cardiac repair.

Animals↗
PubMed2006

Does exogenous application of salicylic acid through the rooting medium modulate growth and photosynthetic capacity in two differently adapted spring wheat cultivars under salt stress?

In order to assess whether exogenous application of salicylic acid (SA) through the rooting medium could modulate the photosynthetic capacity of two wheat cultivars differing in salinity tolerance, a hydroponic experiment was conducted under greenhouse conditions. Seeds of a salt tolerant (S-24) and a moderately salt sensitive (MH-97) cultivar were germinated at 0 or 150 mM NaCl in Hoagland's nutrient solution containing different levels of salicylic acid (SA) (0, 0.25, 0.50, 0.75 and 1.00 mM) for 7d. Seven-day old wheat seedlings were transferred to hydroponics and grown at 0, or 150 mM NaCl for for further 30 d. Different levels of salicylic acid (SA) were also maintained in the solution culture. After 30 d, four plants out of six were harvested and the remaining plants were left for the estimation of yield attributes Salt stress reduced the growth and grain yield of both cultivars. However, cv. S-24 performed better than MH-97 under salt stress with respect to leaf area, and grain yield. Exogenous application of SA promoted growth and yield, and counteracted the salt stress-induced growth inhibition of salt tolerant S-24, whereas for MH-97 there was no improvement in growth or grain yield with SA application. Of the varying SA levels used, the most effective levels for promoting growth and grain yield were 0.75 and 0.25 mM under normal and saline conditions, respectively. The improvement in growth and grain yield of S-24 due to SA application was associated with improved photosynthetic capacity. Changes in photosynthetic rate due to SA application were not due to stomatal limitations, but were associated with metabolic factors, other than photosynthetic pigments and leaf carotenoids.

Adaptation, Physiological↗
PubMed2006

Bone marrow stem cells prevent left ventricular remodeling of ischemic heart through paracrine signaling.

In this study, we hypothesized that bone marrow stem cells (BMSCs) protect ischemic myocardium through paracrine effects that can be further augmented with preconditioning. In in vitro experiments, cell survival factors such as Akt and eNOS were significantly increased in BMSCs following anoxia. In the second series of experiments following coronary ligation in mice, left ventricles were randomly injected with the following: DMEM (G-1), BMSCs (G-2), and preconditioned BMSCs (G-3). Four days after myocardial infarction, BMSCs were observed within injured myocardium in G-2 and G-3. Apoptotic cardiomyocytes within periinfarct area were significantly reduced in G-3. Four weeks after myocardial infarction, smaller left ventricular (LV) dimension and increased LV ejection fraction were observed in G-3. Infarct area was significantly reduced in G-3. However, GFP+ cardiomyocytes were observed in low numbers within periinfarct area in G-2 and G-3. In conclusion, BMSCs secreted cell survival factors under ischemia, and they prevented apoptosis in cardiomyocytes adjacent to the infarcted area. Preconditioning of BMSCs enhanced their survival and ability to attenuate LV remodeling, which was attributable, in part, to paracrine effects.

Animals↗
PubMed2006

Antioxidant activity with flavonoidal constituents from Aerva persica.

A new flavanone Persinol (1) and the new flavanone glucosides persinosides A (2) and B (3), along with known flavonoids (4 and 5) have been isolated from the ethyl acetate soluble fraction of the whole plants of Aerva persica. Their structures were elucidated on the basis of extensive analysis of nuclear magnetic resonance (1D and 2D-NMR) spectral data. All of them showed profound antioxidative activities by DPPH and cytochrome-c-reduction assays using the HL-60 cell culture system.

Amaranthaceae↗
PubMed2006

Combining pharmacological mobilization with intramyocardial delivery of bone marrow cells over-expressing VEGF is more effective for cardiac repair.

We postulated that combining cell based hVEGF165 gene delivery with cytokine-induced mobilization of bone marrow cells (BMC) may give better prognosis in an infarcted heart. Forty-eight myoabalated female C57BL/6J mice (20-25 g) received 1 x 10(6) BMC from transgenic GFP+ male mice. One month later, acute myocardial infarction (MI) model was developed by coronary artery ligation. Animals were grouped (N = 12) to receive intramyocardial injections of 10 microl DMEM without cells (group 1; group 2) or with 1x10(5) mesenchymal stem cells (MSC) over-expressing hVEGF165 (group 3; group 4). The animals received either cytokine therapy (group 2 and 4) or saline solution (group 1 and 3) for 7 days after MI. Hemodynamic data were obtained 4 weeks after MI using Millar's P-V system and cardiac tissue was harvested for immunohistological studies. We observed regeneration and extensive survival of BMC in and around the infarcted myocardium in groups 3 and 4. Blood vessel density was markedly enhanced in group 4 as compared with groups 1 and 2 in peri-infarct area. Fibrotic area was significantly reduced with improved LV-contractile function in group 2 and 4. LV-systolic and diastolic functions were well-preserved in group 4 as indicated by +dP/dt, -dP/dt and Tau (glantz). We therefore conclude that transplantation of MSC overexpressing VEGF combined with cytokine induced BMC mobilization is superior to either of the monotherapy approach for angiomyogenesis and LV-function recovery.

Animals↗
PubMed2006

A novel 3-d model of chick chorioallantoic membrane for ameliorated studies in angiogenesis.

Decisive indulgence of angiogenesis requires a more holistic assessment and several in vivo assays have been developed that permit a more realistic appraisal of the angiogenic response. One of the most popular assays to study angiogenic activity is the chick chorioallantoic membrane (CAM). Although CAM assay is a vital technique used to study normal and putative angiogenesis, a serious drawback in its utilization is the lack of quantitative assessment of vascularization. In this study, we proposed a new 3-D model of the developing CAM for precise quantification of normal vasculature of CAM from Day 4 to Day 13 of incubation. Image probing technique was used to quantify different 3-D parameters of vascular microarchitecture. A significant increase (P < 0.05) in surface roughness (Sa) was observed at Day 5 of incubation, while highly significant increase (P < 0.01) in Sa values was observed at Day 6 of incubation. Maximum increase (P < 0.001) in Sa values was observed from Day 7 to Day 9 of incubation and slight decrease in Sa values was observed in successive days. Similar results were observed for root mean square values (Sq), absolute heights of the surface (Sz), and amount of lowest valleys (Sy) on CAM. A significant increase (P < 0.05) in developed surface area (Sdr) from Day 5 of incubation, reaching to its maximum (P < 0.01) at Day 9 also was noted. Similarly, significant increase (P < 0.05) in fluid core retention (Sci) illustrates presence of copious fluid in blood vessels. Image probing technique offers a useful modality for visualizing 3-D microvascular architecture of CAM to exaggerate the fine details and reveal the hidden information that can be helpful for precise quantification of angiogenesis. This approach can be used to evaluate the angiogenic and antiangiogenic potential of different biological substances and also can be a valuable independent prognostic indicator in a wide variety of human cancers.

Animals↗
PubMed2006

Cardiac protection by mitoKATP channels is dependent on Akt translocation from cytosol to mitochondria during late preconditioning.

This investigation elucidates the Akt/mitochondrial ATP-sensitive K(+) (mitoK(ATP)) channel signaling pathway in late pharmacological preconditioning, using the mitoK(ATP) channel openers BMS-191095 (BMS) and diazoxide (DE). BMS (1 mg/kg ip) and DE (7 mg/kg ip) alone or BMS plus wortmannin (WTN, 15 microg/kg ip), an inhibitor of phosphatidylinositol 3-kinase, and BMS plus 5-hydroxydecanoic acid (5-HD, 5 mg/kg ip), an inhibitor of mitoK(ATP) channels, were administered to male mice. Twenty-four hours later, hearts were isolated and subjected to 40 min of ischemia and 120 min of reperfusion via Langendorff's apparatus. Both BMS and DE reduced left ventricular end-diastolic pressure and increased left ventricular developed pressure as well as reduced LDH release. Coadministration of BMS and WTN abolished the beneficial effects of BMS on cardiac function. Moreover, BMS and DE accelerated Akt phosphorylation in cardiac tissue as determined by Western blot analysis and also significantly reduced apoptosis compared with ischemic control. WTN significantly suppressed BMS-induced Akt phosphorylation, whereas 5-HD had no effect on Akt phosphorylation in cytosol, and the effect of BMS on apoptosis was abolished. It is concluded that the cardioprotective effect by mitoK(ATP) channels is attributed to the translocation of phosphorylated Akt from cytosol to mitochondria.

Androstadienes↗
PubMed2006

Delineation of cardiac twist by a sonographically based 2-dimensional strain analysis method: an in vitro validation study.

OBJECTIVE: Normal left ventricular contraction involves a twisting component that helps augment stroke volume, the unwinding of which also very usefully contributes to early diastolic filling. Abnormalities of cardiac twist have been related to abnormal cardiac function. We sought to quantify the twisting action using a new sonographically based angle-independent motion-detecting echo method. METHODS: A twist model was developed with a variable-speed motor to rotate a wheel in water bath. A freshly harvested pig heart was mounted on it as a twist phantom. Short axis views were acquired with a GE/VingMed Vivid 7 system (GE Healthcare, Milwaukee, WI) at 3.5 MHz and more than 100 frames/s. Eight different speeds (30-100 cycles/min of winding and unwinding) were studied at 5 degrees of rotation (10 degrees , 20 degrees , 30 degrees , 40 degrees , and 50 degrees ). Data were analyzed off-line for twist analysis with a new 2-dimensional speckle-tracking-based program (2-dimensional strain rate method [2DSR]) embedded in EchoPac software (GE Healthcare). Ten freshly harvested pig hearts were studied in this model. RESULTS: The 2DSR program tracked the twist well (mean determination at 10 degrees = 16.88 degrees +/- 1.81 degrees [SD]; at 20 degrees = 26.5 degrees +/- 1.05 degrees ; at 30 degrees = 36.47 degrees +/- 1.31 degrees ; at 40 degrees = 44.03 degrees +/- 1.39 degrees ; and at 50 degrees = 54.1 degrees +/- 1.96 degrees ). CONCLUSIONS: The 2DSR program can be used to study twisting action of the heart.

Animals↗
PubMed2005

A novel method for the assessment of the accuracy of computing laminar flow stroke volumes using a real-time 3D ultrasound system: In vitro studies.

AIMS: Laminar flow stroke volume (SV) quantification in the ascending aorta or pulmonary artery can provide a measure for determining cardiac output (CO). Comparing flows across different valves can also compute shunt volumes and regurgitant fractions. Quantification methods for 3D color Doppler laminar flow volumes have been developed using reconstructive 3D, but these are cumbersome and time-consuming both in acquisition and measurement. Our study evaluated newly developed color Doppler mapping with real-time live 3D echo to test velocity, spatial and temporal resolution for computing SV. METHODS AND RESULTS: Five rubber tubes (diameters=3.0, 2.25, 2.0, 1.9, 1.7 cm), a freshly dissected porcine aorta (Ao) and a pulmonary artery (PA) (both 2-3 cm diameter) were connected to a pulsatile pump in a water bath. Different SV, from 10 to 80 ml/beat, were studied at pump rates of 40-60 bpm in this phantom model with flow quantified by timed collection. The Nyquist limit was set between 43 and 100 cm/s and frame rate ranged from 14 to 23/s. ECG triggered 3D color Doppler volumes were acquired with a 2-4 MHz probe. The digital scan line data from the 3D volumes, with retained velocity assignments, was exported and analyzed offline by MatLab custom software. Close correlations were found between 3D calculated SV and reference data for all tubes (r=0.98, y=1.14x-1.69, SEE=2.82 ml/beat, p<0.0001). Both Ao and PA flows were also highly correlated with the reference measurements (PA: r=0.98, SEE=3.17 ml/beat; Ao: r=0.99, SEE=3.20 ml/beat). CONCLUSIONS: Real-time 3D color Doppler method could provide an efficient, accurate and reliable method for clinical evaluation and quantification of flow volumes in patients.

Animals↗
PubMed2005

Mechanisms by which K(ATP) channel openers produce acute and delayed cardioprotection.

Mitochondria are being increasingly studied for their critical role in cell survival. Multiple diverse signaling pathways have been shown to converge on the K+-sensitive ATP channels as the effectors of cytoprotection against necrosis and apoptosis. The role of potassium channel openers in regulation and transformation of cell membrane excitability, action potential and electrolyte transfer has been extensively studied. Cardiac mitoK(ATP) channels are the key effectors in cardioprotection during ischemic preconditioning, as yet with an undefined mechanism. They have been hypothesized to couple myocardial metabolism with membrane electrical activity and provide an excellent target for drug therapy. A number of K(ATP) channel openers have been characterized for their beneficial effects on the myocardium against ischemic injury. This review updates recent progress in understanding the physiological role of K(ATP) channels in cardiac protection induced by preconditioning and highlights relevant questions and controversies in the light of published data.

Animals↗