PubMed Health⌕ Search

Biomedical subjects

A Ahluwalia

Publications and source records attributed to A Ahluwalia.

At least 19 recordsLinked to original sources
PubMed2007

Microfabrication of fractal polymeric structures for capillary morphogenesis: applications in therapeutic angiogenesis and in the engineering of vascularized tissue.

Microfabrication techniques were combined with fractal algorithms to realize polymeric scaffolds resembling capillary networks. The scaffolds were seeded with human endothelial cells in monoculture as well as in coculture with human fibroblasts. To enhance the process of angiogenesis, endothelial cells were transfected with an adenoviral vector carrying the gene for human tissue kallikrien. The results demonstrate that both the presence of a structured scaffold as well as fibroblasts in coculture contribute synergically to the promotion of a metabolically active network. The fractal scaffolds have several possible applications for example in vascularized tissue engineering and therapeutic angiogenesis. A broader implication of these results is that cell-extra cellular matrix and cell-cell interactions cooperate dynamically both at a biochemical as well as microstructural level.

Algorithms↗
PubMed2006

A composite sensor array impedentiometric electronic tongue Part II. Discrimination of basic tastes.

An impedentiometric electronic tongue based on the combination of a composite sensor array and chemometric techniques aimed at the discrimination of soluble compounds able to elicit different gustative perceptions is presented. A composite array consisting of chemo-sensitive layers based on carbon nanotubes or carbon black dispersed in polymeric matrices and doped polythiophenes was used. The electrical impedance of the sensor array was measured at a frequency of 150 Hz by means of an impedance meter. The experimental set-up was designed in order to allow the automatic selection of a test solution and dipping of the sensor array following a dedicated measurement protocol. Measurements were carried out on 15 different solutions eliciting 5 different tastes (sodium chloride, citric acid, glucose, glutamic acid and sodium dehydrocholate for salty, sour, sweet, umami and bitter, respectively) at 3 concentration levels comprising the human perceptive range. In order to avoid over-fitting, more than 100 repetitions for each sample were carried in a 4-month period. Principal component analysis (PCA) was used to detect and remove outliers. Classification was performed by linear discriminant analysis (LDA). A fairly good degree of discrimination was obtained.

Artificial Intelligence↗
PubMed2006

A composite sensor array impedentiometric electronic tongue Part I. Characterization.

A study aimed at the characterization of five compounds with different chemical characteristics and gustative perceptions by measuring the variations of the electrical impedance of a composite sensor array is presented. The array was composed of five sensors of three different types based on carbon nanotubes or carbon black dispersed in polymeric matrices and doped polythiophenes. Measurements were carried out by evaluating the electrical impedance of the sensor array at a frequency of 150 Hz, and the data acquisition process was automated; a mechanical arm and a rotating platform controlled by a data acquisition card and a dedicated software allowed the sequential dipping of sensors in the test solutions. Fifty different solutions eliciting the 5 basic tastes (sodium chloride, citric acid, glucose, glutamic acid and sodium dehydrocholate for salty, sour, sweet, umami and bitter, respectively) at 10 concentration levels comprising the human perceptive range were analysed. More than 100 measurements were carried for each sample in a 4-month period to evaluate the system repeatability and robustness. The impedentiometric composite sensor array is shown to be sensitive, selective and stable for use in an electronic tongue.

Biomimetic Materials↗
PubMed2006

Novel aspects of endothelium-dependent regulation of vascular tone.

The vascular endothelium plays a crucial role in the regulation of vascular homeostasis and in preventing the initiation and progress of cardiovascular disease by controlling mechanical functions of the underlying vascular smooth muscle. Three vasodilators: nitric oxide (NO), prostacyclin, and endothelium-derived hyperpolarizing factor, produced by the endothelium, underlie this activity. These substances act in a co-ordinated interactive manner to maintain normal endothelial function and operate as support mechanisms when one pathway malfunctions. In this review, we discuss recent advances in our understanding of how gender influences the interaction of these factors resulting in the vascular protective effects seen in pre-menopausal women. We also discuss how endothelial NO synthase (NOS) can act in both a pro- and anti-inflammatory action and therefore is likely to be pivotal in the initiation and time course of an inflammatory response, particularly with respect to inflammatory cardiovascular disorders. Finally, we review recent evidence demonstrating that it is not solely NOS-derived NO that mediates many of the beneficial effects of the endothelium, in particular, nitrite acts as a store of NO released during pathological episodes associated with NOS inactivity (ischemia/hypoxia). Each of these more recent findings has emphasized new pathways involved in endothelial biology, and following further research and understanding of the significance and mechanisms of these systems, it is likely that new and improved treatments for cardiovascular disease will result.

Adult↗
PubMed2006

Endothelial cell function on 2D and 3D micro-fabricated polymer scaffolds: applications in cardiovascular tissue engineering.

Polymeric structures of a polylactide-polycaprolactone blend were micro-fabricated using the Pressure Assisted Microsyringe (PAM) system. Human umbilical vein endothelial cells were cultured on the scaffolds, and apoptosis, cell adhesion, proliferation and metabolism were evaluated. In addition, more specific indicators of endothelial cell function, namely nitric oxide and endothelin production, were also assessed. Thin films of the blend, as well as gelatine-coated glass slides (as controls) were used. The results show that as far as adhesion, apoptosis and metabolism are concerned, the scaffolds do not interfere with cell function compared with gelatin controls. However, the nitric oxide/endothelin ratio was higher than that observed on the gelatin films, suggesting that the scaffolds could be used for engineering small diameter blood vessels without risk of occlusion.

Cardiovascular System↗
PubMed2005

An audit of patients investigated by Hysterosalpingo-Contrast-Sonography (HyCoSy) for infertility.

We reviewed 171 case notes of patients investigated by HyCoSy for sub-fertility in South Manchester University Hospital to assess HyCoSy as a screening test for tubal occlusion, in low risk infertile women and to evaluate the performance of HyCoSy in our unit by confirming its results with the results of laparoscopy & dye test in those patients who had both procedures. We also assessed the prognostic significance of HyCoSy, for fertility outcome over a follow-up period ranging from 12 to 63 months. An audit proforma was designed to collect data on maternal age, type of infertility (primary or secondary), duration of infertility and parity. History suggestive of ovulatory factors (PCO), pelvic inflammatory disease and endometriosis was noted. Findings of standard trans-vaginal scan, hysterosalpingography and HyCoSy were recorded. In total 333 tubes were examined in 171 patients. There were 121/171 diagnoses of bilateral patent tubes, 24/171 bilateral blocked tubes and 26/171 findings of one patent tube. In 15 (8.8%) women, laparoscopy and dye test was performed after HyCoSy and 19 patients had laparoscopy and dye test before HyCoSy. The findings in both investigations were similar. 70 additional uterine and adnexal pathologies were detected. Out of 171 40.9% (n=70) women conceived, 62 of these women had both tubes patent and 8 had one patent tube. In conclusion we have found that HyCoSy is a valuable cost effective screening test for low risk couples. Its results in our hands are as good as demonstrated by other studies. HyCoSy can be offered as a screening test for low risk infertile women as it is an effective alternative for laparoscopy and dye test.

Adolescent↗
PubMed2004

Microfabricated fractal branching networks.

In this article, we demonstrate how a combination of engineering and biological techniques could lead to the realization of branched microstructures that can be used for the repair of damaged vascularized tissue. Recursive "treelike" networks were first generated by using fractal algorithms based on Murray's equation for vascular branching as well as allometric scaling rules. Two- and three-dimensional branching patterns with different levels of complexity were then microfabricated from poly-lactide-co-glycolide (PLGA) by using the pressure-assisted microsyringe (PAM) system developed in our laboratory. Human endothelial cells isolated from umbilical cords were seeded on the microfabricated branched scaffolds to evaluate their effectiveness in supporting site-specific cell adhesion. The results show that cell densities on the networks increase with complexity up to the sixth level and are then constant independent of branching level. The implications of this finding are discussed in terms of contact inhibition of "capillaries."

Algorithms↗
PubMed2004

C-type natriuretic peptide: new candidate for endothelium-derived hyperpolarising factor.

Endothelium-derived hyperpolarising factor (EDHF) is an important regulator of vascular tone; however, its identity is still unclear. Several different molecules have been suggested, the most recent of which is the 22-amino acid peptide C-type natriuretic peptide (CNP). CNP induces hyperpolarisation and relaxation of rat mesenteric resistance artery vascular smooth muscle through activation of natriuretic peptide receptor subtype C (NPR-C) and the same potassium channels as EDHF. In addition, this peptide is released from endothelial cells of the perfused rat mesenteric bed in response to endothelium-dependent vasodilators. Thus, CNP is likely to play a vital role in regulation of vascular tone. In addition, since there is evidence that up-regulation of EDHF occurs where normal endothelium function has been compromised, modulation of this pathway represents a novel target for therapeutics in the treatment of inflammatory cardiovascular pathologies characterised by endothelial dysfunction.

Animals↗
PubMed2003

Protection against lipopolysaccharide-induced endothelial dysfunction in resistance and conduit vasculature of iNOS knockout mice.

Endothelial dysfunction is a characteristic of, and may be pathogenic in, inflammatory cardiovascular diseases, including sepsis. The mechanism underlying inflammation-induced endothelial dysfunction may be related to the expression and activity of inducible nitric oxide synthase (iNOS). This possibility was investigated in isolated resistance (mesenteric) and conduit (aorta) arteries taken from lipopolysaccharide (LPS)-treated (12.5 mg/kg i.v.) or saline-treated iNOS knockout (KO) and wild-type (WT) mice. LPS pretreatment (for 15 h, but not 4 h) profoundly suppressed responses to acetylcholine (ACh) and significantly reduced sensitivity to the NO donor spermine-NONOate (SPER-NO) in aorta and mesenteric arteries of WT mice. This effect was temporally associated with iNOS protein expression in both conduit and resistance arteries and with a 10-fold increase in plasma NOx levels. In contrast, no elevation of plasma NOx was observed in LPS-treated iNOS KO animals, and arteries dissected from these animals did not express iNOS or display hyporeactivity to ACh or SPER-NO. The mechanism underlying this phenomenon may be suppression of eNOS expression, as observed in arteries of WT animals, that was absent in arteries of iNOS KO animals. These results clearly demonstrate that iNOS induction plays an integral role in mediation of the endothelial dysfunction associated with sepsis in both resistance and conduit arteries.

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗
PubMed2002

Microsyringe-based deposition of two-dimensional and three-dimensional polymer scaffolds with a well-defined geometry for application to tissue engineering.

A technique for controlled deposition of biomaterials and cells in specific and complex architectures is described. It employs a highly accurate three-dimensional micropositioning system with a pressure-controlled syringe to deposit biopolymer structures with a lateral resolution of 5 microm. The pressure-activated microsyringe is equipped with a fine-bore exit needle and a wide variety of two- and three-dimensional patterns on which cells to be deposited can adhere. The system has been characterized in terms of deposition parameters such as applied pressure, motor speed, line width and height, and polymer viscosity, and a fluid dynamic model simulating the deposition process has been developed, allowing an accurate prediction of the topological characteristics of the polymer structures.

Biocompatible Materials↗
PubMed2001

DNA methylation in ovarian cancer. II. Expression of DNA methyltransferases in ovarian cancer cell lines and normal ovarian epithelial cells.

OBJECTIVE: The aim of this study was to investigate whether expression of the enzymes that catalyze cytosine CpG island methylation, DNA methyltransferases, DNMT1, DNMT3a, and DNMT3b is altered in human ovarian cancer. Aberrations in DNA methylation are common in cancer and have important roles in tumor initiation and progression. Tumors that display frequent and concurrent inactivation of multiple genes by methylation are designated as having a CpG Island methylator phenotype, or CIMP. To date, colon, gastric, and most recently ovarian cancers meet the CIMP criteria for cancer. We hypothesized that altered expression of DNA methyltransferases can result in hypermethylation events seen in CIMP cancers. METHODS: DNMT1, DNMT3a, and DNMT3b mRNA levels in eight ovarian cancer cells lines (Hey, HeyA8, HeyC2, OVCAR-3, SK-OV-3, PA-1, A2780, and A2780-P5) were compared to DNMT expression in normal ovarian surface epithelial cells using semi-quantitative reverse transcription-polymerase chain reaction. RESULTS: In HeyA8 and HeyC2 ovarian cancer cells, DNMT1 expression levels were up to threefold higher (P < 0.05) than in normal ovarian surface epithelial cells. SK-OV-3 and PA-1 displayed increased DNMT3b expression (P < 0.05) compared to normal ovarian surface epithelial cells. Transcript levels for DNMT3a, however, were similar in cancer and normal ovarian cells. CONCLUSIONS: We observed differential expression of the DNMT genes in some ovarian cancer cell lines and conclude that alterations in DNMT expression might contribute to the CIMP phenotype in ovarian cancer. However, based on the lack of aberrant DNMT expression in some of the cancer cell lines examined, we further suggest that another mechanism(s), in addition to DNMT overexpression, accounts for methylation anomalies commonly observed in ovarian cancer.

Adenocarcinoma↗
PubMed2001

DNA methylation and ovarian cancer. I. Analysis of CpG island hypermethylation in human ovarian cancer using differential methylation hybridization.

OBJECTIVE: The aim of this study was to examine CpG island methylation patterns in ovarian cancer and determine whether epigenetic information can be related to clinical data of patients. CpG island (CpGI) hypermethylation is commonly associated with cancer progression, but little is currently known about the role of methylation in ovarian cancer. METHODS: Differential methylation hybridization (DMH) analysis at 742 loci was performed to determine methylation signatures for 20 primary epithelial ovarian carcinomas (Stages II, III, and IV adenocarcinomas, serous papillary), 6 ovarian cancer cell lines, and normal ovarian surface epithelial cells. RESULTS: Between 23 and 108 methylated CpGIs were seen in the ovarian carcinomas. Fewer (P < 0.05) methylated CpGIs were observed in the ovarian cancer cell lines; however, a number of CpGIs were commonly hypermethylated in both the cell lines and the tumor samples. A methylation signature, consisting of frequently (P < 0.05) methylated CpGIs, was determined for the samples. The observed pattern of methylation in ovarian cancers included several (11) CpGI tags that were previously reported to be hypermethylated in human breast cancer. CONCLUSIONS: Epigenetic signatures in ovarian cancer were determined using DMH. This proof-of-concept study lays the foundation for genome-wide screening of methylation to examine epigenotype-phenotype relationships in ovarian cancer.

Adult↗