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Biomedical subjects

Muhammad Ashraf

Publications and source records attributed to Muhammad Ashraf.

At least 37 records · Page 2Linked to original sources
PubMed2005

Bone marrow cell transplantation in clinical perspective.

The deficit in left ventricular performance in an ischemically damaged heart is characterized by depletion of functioning cardiomyocytes. The problem is accentuated by the inadequate intrinsic repair mechanism of the heart. Recent progress in regenerative medicine has paved way for an outside intervention to support the limited on-going reparative process in the heart through transplantation of cells with myogenic and/or angiogenic potential. The functional plasticity of bone marrow derived stem cells has been exploited for cardiac repair. The early experiences in proof-of-concept animal studies and phase-1 clinical trials have been encouraging and suggest the safety, feasibility and potential of this approach. We critically review the literature in depth to elucidate the progress in this field together with discussion of the problems and controversies that need to be addressed in order to fully exploit the potential of bone marrow stem cell transplantation with clinical relevance.

Animals↗
PubMed2005

Bone marrow stem cells in the infarcted heart.

Conventionally, the heart is perceived as a terminally differentiated organ, which is incapable of regeneration. Adult stem cell transplantation is aimed at replenishing the myocyte number to compensate for the cardiomyocyte loss during the process of cardiomyocyte necrosis following infarction. More recently, the focus has been shifted on the use of autologous skeletal myoblasts and bone marrow derived stem cells. Here, we have reviewed some interesting aspects of the fast emerging field of bone marrow derived stem cell therapy for cardiac repair.

Animals↗
PubMed2005

Bone marrow stem cell transplantation for cardiac repair.

Cardiomyocytes respond to physiological or pathological stress only by hypertrophy and not by an increase in the number of functioning cardiomyocytes. However, recent evidence suggests that adult cardiomyocytes have the ability, albeit limited, to divide to compensate for the cardiomyocyte loss in the event of myocardial injury. Similarly, the presence of stem cells in the myocardium is a good omen. Their activation to participate in the repair process is, however, hindered by some as-yet-undetermined biological impediments. The rationale behind the use of adult stem cell transplantation is to supplement the inadequacies of the intrinsic repair mechanism of the heart and compensate for the cardiomyocyte loss in the event of injury. Various cell types including embryonic, fetal, and adult cardiomyocytes, smooth muscle cells, and stable cell lines have been used to augment the declining cardiomyocyte number and cardiac function. More recently, the focus has been shifted to the use of autologous skeletal myoblasts and bone marrow-derived stem cells. This review is a synopsis of some interesting aspects of the fast-emerging field of bone marrow-derived stem cell therapy for cardiac repair.

Bone Marrow Transplantation↗
PubMed2005

Use of Corel Photo-Paint for chromosome karyotyping: an inexpensive, semiautomatic approach.

Karyotyping has become an important component of cytogenetic analysis. Both manual and automatic karyotyping procedures are in use all over the world, but both have drawbacks. Manual karyotyping is inexpensive, but highly time-consuming and labor-intensive. Automatic karyotyping, on the other hand, saves time but is expensive and also does not always provide consistent or reliable results. Thus, in order to cope with these problems, a semiautomatic approach for karyotyping was developed. In this technique, a commonly used graphics software program, Corel Photo-Paint, is used for karyotyping. With this technique one can cut, paste, move, rotate, and arrange the chromosomes to form a karyotype. In addition, one can increase the resolution and sharpness of chromosome bands, which facilitates the classification of chromosomes. The comparative advantages of this semiautomatic approach are discussed in detail.

Journal Article↗
PubMed2005

Trace metals analysis in selected pharmaceutical multimineral formulations.

Twelve pharmaceutical multimineral formulations, marketed in Pakistan by various multinational and national pharmaceutical manufacturers were analyzed for calcium, copper, iron, magnesium, manganese, potassium and zinc contents using atomic absorption spectrophotometric (AAS) technique. Generally, the Ca, Fe, K and Mg contents were normal to higher range compared with the labeled quantity. The Cu, Mn and Zn contents were low in most of the formulations when compared with the labeled amounts. Potassium was quantified in some formulations where it was not labeled this may be due to the excepients that may have been used in the formulations. The high contents like iron, calcium may also be due to the contamination or excepients used in the preparation of these drugs.

Calcium↗
PubMed2004

Differentiation of bone marrow stromal cells into the cardiac phenotype requires intercellular communication with myocytes.

BACKGROUND: Bone marrow stromal cells (BMSCs) have the potential to differentiate into various cells and can transdifferentiate into myocytes if an appropriate cellular environment is provided. However, the molecular signals that underlie this process are not fully understood. In this study, we show that BMSC differentiation is dependent on communication with cells in their microenvironment. METHODS AND RESULTS: BMSCs were isolated from green fluorescent protein (GFP)-transgenic mice and cocultured with myocytes in a ratio of 1:40. Myocytes were obtained from neonatal rat ventricles. The differentiation of BMSCs in coculture was confirmed by immunohistochemistry, electron microscopy, and reverse transcription-polymerase chain reaction. Before coculturing, the BMSCs were negative for alpha-actinin and exhibited a nucleus with many nucleoli. After 7-day coculture with myocytes, some BMSCs became alpha-actinin-positive and formed gap junctions with native myocytes. However, BMSCs separated from myocytes by a semipermeable membrane were still negative for alpha-actinin. Transdifferentiated myocytes from BMSCs were microdissected from cocultures by laser captured microdissection to determine the changes in gene expression. BMSCs cocultured with myocytes expressed mouse cardiac transcription factor GATA-4. CONCLUSIONS: When cocultured with myocytes, BMSCs can transdifferentiate into cells with a cardiac phenotype. Differentiated myocytes express cardiac transcription factors GATA-4 and myocyte enhancer factor-2. The transdifferentiation processes rely on intercellular communication of BMSCs with myocytes.

Animals↗
PubMed2004

Contribution of Akt and endothelial nitric oxide synthase to diazoxide-induced late preconditioning.

The opening of mitochondrial ATP-sensitive K+ (mitoK(ATP)) channels has a significant role in delayed ischemic preconditioning, and nitric oxide (NO) is a well-known trigger for its activation. However, the source of NO remains unknown. Phosphorylation of endothelial NO synthase (eNOS) increases NO production and reduces apoptosis through the Akt signaling pathway. To elucidate the Akt signaling pathway involved in the opening and antiapoptotic effect of mitoKATP channel during delayed pharmacological preconditioning, the mitoKATP channel opener diazoxide (DE, 7 microg/kg i.p.) alone or DE plus Nomega-nitro-L-arginine methyl ester (L-NAME, 30 microg/kg i.v.), an inhibitor of NOS, or wortmannin (WTN, 15 microg/kg i.v.), an inhibitor of phosphatidylinositol 3'-kinase (PI3 kinase), was administered to wild-type (WT) or eNOS(-/-) mice during DE treatment. Twenty-four hours later, hearts were isolated and subjected to 40 min ischemia and 30 min reperfusion (I/R). The effect of DE and other interventions on hemodynamic, terminal dUTP nick-end labeling staining and biochemical changes during I/R was assessed in mouse hearts. Treatment with DE resulted in a 2.2-fold increase in phosphorylation of Akt and a significant increase in eNOS and inducible NOS (iNOS) proteins. Akt is upstream of NOS and the mitoKATP channel as simultaneous pretreatment of WTN with DE abolished phosphorylation of Akt, which was not affected by L-NAME and 5-hydroxydecanoate. In hearts treated with DE, cardiac function was significantly improved after I/R, and apoptosis was also significantly decreased. WTN abolished the antiapoptotic effect of DE. Similarly, S-methylisothiourea, a specific iNOS inhibitor, when given to eNOS(-/-) mice that were pretreated with DE completely abolished the beneficial effects of DE on reduction of apoptotic death. DE was partially effective in eNOS(-/-) mice against the ischemic injury. It is concluded that DE activates Akt through the PI3 kinase signaling pathway and iNOS and eNOS is downstream of Akt.

Animals↗
PubMed2004

Anthelmintic activity of Artemisia brevifolia in sheep.

This paper describes the in vitro and in vivo anthelmintic activity of Artemisia brevifolia in comparison with levamisole. In vitro studies revealed anthelmintic effects of crude aqueous (CAE) and methanol extracts (CME) of Artemisia brevifolia (whole plant) on live Haemonchus contortus as evident from their paralysis and/or mortality at 6 h post exposure. For in vivo studies, the whole plant of Artemisia brevifolia was administered as crude powder (CP), CAE and CME at graded doses (1, 2 and 3 g kg(-1) body weight (b.w.) to sheep naturally infected with mixed species of gastrointestinal nematodes. Maximum reduction (67.2%) in eggs per gram (EPG) of faeces was recorded on day 14 post treatment in sheep treated with Artemisia brevifolia CAE at 3 g kg(-1) b.w. It was found that, although, Artemisia brevifolia whole plant possesses anthelmintic activity against nematodes, it is not comparable with levamisole (99.2% reduction in EPG) at any of the doses tried in this study. However, increase in EPG reduction was noted with an increase in the dose of Artemisia brevifolia administered as CP, CAE and CME. The graded dose response suggested further studies on a larger number of animals on higher doses than those used in the current study.

Administration, Oral↗
PubMed2004

Hepatocyte growth factor prevents ventricular remodeling and dysfunction in mice via Akt pathway and angiogenesis.

This study determines the effect of hepatocyte growth factor (HGF) on post-infarction left ventricular (LV) remodeling and cardiac function. In mice, on day 1 after myocardial infarction (MI), HGF (0.45 mg/kg per day) was injected into the tail vein for 7 days (n = 12). In the control mice (n = 12), 0.9% sodium chloride was injected instead of HGF. Hemodynamic data were obtained in vehicle treated control and HGF-treated hearts 4 weeks after the onset of MI. In the HGF-treated group, cardiac function was well preserved as indicated by LV pressure-volume relationship. These mice exhibited better LV systolic and diastolic function. The infarcted LV wall in HGF-treated heart was thicker as compared to vehicle treated group. Fibrosis and infarct size of the ventricular wall was significantly reduced in the HGF-treated hearts. 5-Bromo-2'-deoxy-uridine (BrdU) and Ki67 positive cardiomyocytes were observed in the border area of the HGF-treated infarcted hearts. c-Met and c-kit positive cardiomyocytes were observed in the border area and epicardium. Angiogenesis was significantly enhanced in HGF-treated hearts as determined by vessel density per unit area. A significant reduction in apoptosis in the HGF-treated hearts was observed compared with control hearts, and was strongly associated with increased Akt activation. Treatment with HGF improved heart function through angiogenesis, ventricular wall thickening, and hypertrophy of cardiomyocytes. The antiapoptotic effect of HGF was mediated by activation of PI3-kinase/Akt pathway.

Animals↗
PubMed2003

Mice with a null mutation in the NHE1 Na+-H+ exchanger are resistant to cardiac ischemia-reperfusion injury.

Pharmacological studies indicate that Na+-H+ exchanger isoform 1 (NHE1) plays a central role in myocardial ischemia-reperfusion injury; however, confirmation by alternative methods is lacking. To address this issue, we examined the role of NHE1 in ischemia-reperfusion injury using gene-targeted NHE1-null mutant (Nhe1-/-) mice. Nhe1-/- and wild-type hearts were perfused in a Langendorff apparatus in both the absence and presence of the NHE1 inhibitor eniporide, subjected to 40 minutes of ischemia and 30 minutes of reperfusion, and the effects of genetic ablation or inhibition of NHE1 on hemodynamic, biochemical, and pathological changes were assessed. In the absence of eniporide, left ventricular developed pressure, end-diastolic pressure, and coronary flow were significantly less impaired in Nhe1-/- hearts relative to wild-type hearts, and release of lactate dehydrogenase, morphological damage, and ATP depletion were also significantly less. In the presence of eniporide, however, wild-type hearts were significantly protected and there were no significant differences between the two genotypes with respect to cardiac performance, lactate dehydrogenase release, or morphological damage. Furthermore, the presence or absence of eniporide had no apparent effect on the degree of cardioprotection observed in Nhe1-/- hearts. These data demonstrate that genetic ablation of NHE1 protects the heart against ischemia-reperfusion injury. In addition to providing direct evidence that confirms previous pharmacological studies indicating a role for NHE1 in ischemia-reperfusion injury, these results suggest that the long-term absence of NHE1 does not elicit major compensatory changes that might negate the cardioprotective effects of blocking its activity over the short-term.

Adenosine Triphosphate↗
PubMed2003

Implantation of bone marrow stem cells reduces the infarction and fibrosis in ischemic mouse heart.

Myocardial infarction may cause sudden cardiac death and heart failure. Adult cardiac myocytes do not replicate due to lack of a substantive pool of precursor, stem, or reserve cells in an adult heart. Ventricular myocytes following myocardial infarction are replaced by fibrous tissue and this leads to congestive heart failure in severe cases. Anversa et al. described that resident cardiac stem cells are present in the heart, and can repair the damaged mycardium by myocyte regeneration. Recent findings suggest the feasibility of cardiac repair using cell transplantation. However, it remains controversial which cell types are the best for cell transplantation in the ischemic heart. In this study, we demonstrate that cultured bone marrow stromal cells (MSCs) and Lin(-) bone marrow cells upon transplantation differentiate into myocytes and endothelial cells in the ischemic heart, eventually reducing both infarct size and fibrosis.

Animals↗
PubMed2003

Effects of resistance versus aerobic training on coronary artery disease risk factors.

Individuals exhibiting "the metabolic syndrome" have multiple coronary artery disease risk factors, including insulin resistance, hyperlipidemia, hypertension, and android obesity. We performed a randomized trial to compare the effects of aerobic and resistance training regimens on coronary risk factors. Twenty-six volunteers who exhibited android obesity and at least one other risk factor for coronary artery disease were randomized to aerobic or resistance training groups. Body mass index, waist-to-hip ratio, glucose, insulin, body composition, 24-hr urinary albumin, fibrinogen, blood pressure, and lipid profile were measured at baseline and after 10 weeks of exercise training. Both groups showed a significant reduction in waist-to-hip ratio and the resistance training group also showed a reduction in total body fat. There was no significant change in mean arterial blood pressure in either group. Fasting plasma glucose, insulin, total cholesterol, low-density lipoprotein (LDL) cholesterol, and triglycerides were unchanged in both groups. High-density lipoprotein (HDL) cholesterol increased (13%) with aerobic training only. Plasma fibrinogen was increased (28% and 34%, P < 0.02) in both groups and both groups showed a significant decrease (34% and 28%, P < 0.03) in microalbuminuria after their respective training regimen. In conclusion, resistance training was effective in improving body composition of middle-aged obese sedentary males. Only aerobic training was effective in raising HDL cholesterol. More studies are warranted to assess the effects of exercise on plasma fibrinogen and microalbuminuria.

Adult↗
PubMed2003

Pathogenesis and protection of ischemia and reperfusion injury in myocardium.

The important factors that influence the progress of ischemic cardiac lesion are blood flow condition and abnormal cardiac metabolism. Myocardial ischemia is promoted by either an increase in oxygen demand or a shortage of oxygen supply. The Na(+)-Ca(++) ion exchange mechanism is very important for myocardial contraction and cell damage. Na(+)-K(+)ATPase and Ca(++)ATPase are enzyme histochemically localized in subsarcolemmal cisterns, sarcolemmal reticulum and capillary endothelium, and keep myocardial function. These ATPases are impaired by anoxia, superoxides and free radicals. The reduction of O(2) results in the production of superoxides as well as hydrogen peroxide (H(2)O(2)). H(2)O(2) is highly diffusible and induces cell damage. H(2)O(2) appears to affect not only lipids but also intramembranous proteins embedded in the cell membrane. The hydroxyl radical (OH) also participates in lipid hyperoxidation. In the pathogenesis of ischemic and/or reperfused heart disease, ischemia induces rapid or gradual changes in all membrane systems and causes reversible or irreversible injury including necrotic and apoptotic cell death. Advanced glycation end products (AGEs) accumulation induced by diabetic conditioning is an etiologic factor inducing cardiomyopathy. The AGEs protein affects cell changes such as increased number, transformation, functional disturbance and cytokine elimination. In coronary arteries, the migration of smooth muscle cells caused by the taking up of AGEs proteins through the receptor (RAGE), and cytokine discharge are suggested. AGEs accumulation may induce diabetic macroangiopathy through RAGE, and the increase in the level of RAGE expression by endothelial cells could be a reason that diabetes mellitus accelerates atherosclerosis. On the other hand, we also reported that hyperglycemia was a promoting factor of ischemic heart injury in diabetic animals. Ischemic preconditioning is a useful phenomenon that limits myocardial damage. We foused on protein kinase C (PKC), mitogen-activated protein kinase (MAPK) and mitochondrial ATP-dependent potassium (mitoK(ATP)) channel as mediator or end which effector are necessary for adaptation. The opening of the mitoK(ATP) channel induces the depolarization of mitochondria, reducing Ca(++)overload during reperfusion. The regeneration of myocardial cells is confirmed using embryonic stem cells. Myocardial cells that exhibit self-pulsation are generated from mesenchymal stem cells in mesodermal tissues of the bone marrow.

Humans↗
PubMed2002

Melatonin protection against lethal myocyte injury induced by doxorubicin as reflected by effects on mitochondrial membrane potential.

Melatonin (MLT) is highly protective against cardiotoxicity caused by doxorubicin (DOX). DOX induces cardiac damage via production of reactive oxygen species. This study tests the hypothesis that oxygen radicals generated by DOX disrupt mitochondrial membrane potential (Delta(psi)(m)) prior to severe cell injury. Myocytes were incubated with 20 micromol/l DOX for 24 h. Myocyte damage was estimated by lactate dehydrogenase (LDH) release. Mitochondrial membrane potential was determined by staining myocytes with 5, 5', 6, 6'-tetrachloro-1, 1', 3, 3'-tetraethylbenzimidazolcarbocyanine iodide (JC-1) using confocal microscope. A significant amount of LDH was observed after 24 h of treatment with DOX. Mitochondria in DOX-treated myocytes exhibited a collapse of Delta(psi)(m). Pretreatment with melatonin (1 mmol/l) for one hour prevented the release of LDH and restored Delta(psi)(m). The data support the hypothesis that DOX induces damage to mitochondria through radicals, and this is reflected in depolarization of Delta(psi)(m), which was prevented by melatonin.

Animals↗
PubMed2002

Controlled-release naproxen using micronized ethyl cellulose by wet-granulation and solid-dispersion method.

This study has been undertaken to develop a controlled-release tablet dosage form of naproxen using ethocel (ethyl cellulose) as the rate-controlling polymer. The formulations were made by employing the conventional wet-granulation method and the solid-dispersion method. Tablets made by both methods were compared for their controlled-release dissolution profiles. Both methods were useful in developing the controlled-release formulations of naproxen with desirable properties. However, the amount of polymer required to make a formulation with the desired release profile was 33% less via solid dispersion than via wet granulation. A cumulative 88% of naproxen was released from the solid-dispersion formulation, compared with 84% from the wet-granulation formulation.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed2002

Adenosine A(1) receptor mediates late preconditioning via activation of PKC-delta signaling pathway.

Protein kinase C (PKC) plays a central role in both early and late preconditioning (PC) but its association with inducible nitric oxide synthase (iNOS) is not clear in late PC. This study investigates the PKC signaling pathway in the late PC induced by activation of adenosine A(1) receptor (A(1)R) with adenosine agonist 2-chloro-N(6)-cyclopentyladenosine (CCPA) and the effect on iNOS upregulation. Adult male mice were pretreated with saline or CCPA (100 microg/kg iv) or CCPA (100 microg/kg iv) with PKC-delta inhibitor rottlerin (50 microg/kg ip). Twenty-four hours later, the hearts were isolated and perfused in the Langendorff mode. Hearts were subjected to 40 min of ischemia, followed by 30 min reperfusion. After ischemia, the left ventricular end-diastolic pressure (LVEDP) was significantly improved and the rate-pressure product (RPP) was significantly higher in the CCPA group compared with the ischemia-reperfusion (I/R) control group. Creatine kinase release and infarct size were significantly lower in the CCPA group compared with the I/R control group. These salutary effects of CCPA were abolished in hearts pretreated with rottlerin. Immunoblotting of PKC showed that PKC-delta was upregulated (150.0 +/- 11.4% of control group) whereas other PKC isoforms remained unchanged, and iNOS was also significantly increased (146.2 +/- 9.0%, P < 0.05 vs. control group) after 24 h of treatment with CCPA. The data show that PKC is an important component of PC with adenosine agonist. It is concluded that activation of A(1)R induces late PC via PKC-delta and iNOS signaling pathways.

Acetophenones↗
PubMed2002

Two new rearranged taxoids from Taxus wallichiana ZUCC.

Two new rearranged taxane diterpenoids, 5alpha,7beta,10beta,13alpha-tetrahydroxy-2alpha,9alpha,15-triacetoxy-11(15-->1)-abeo-taxa-4(20), 11-diene (1) and 5alpha,9alpha,10beta,13alpha-tetraacetoxy-15-hydroxy-11(15-->1)-abeo-taxa-4(20), 11-diene (2) have been isolated from the barks of Taxus wallichiana. The structures of these compounds have been confirmed by modern spectroscopic techniques.

Bridged-Ring Compounds↗