PubMed Health⌕ Search

Biomedical subjects

A Nadeem

Publications and source records attributed to A Nadeem.

10 recordsLinked to original sources
PubMed2005

A novel A1 adenosine receptor antagonist, L-97-1 [3-[2-(4-aminophenyl)-ethyl]-8-benzyl-7-{2-ethyl-(2-hydroxy-ethyl)-amino]-ethyl}-1-propyl-3,7-dihydro-purine-2,6-dione], reduces allergic responses to house dust mite in an allergic rabbit model of asthma.

Adenosine, an important signaling molecule in asthma, produces bronchoconstriction in asthmatics. Adenosine produces bronchoconstriction in allergic rabbits, primates, and humans by activating A1 adenosine receptors (ARs). Effects of L-97-1 [3-[2-(4-aminophenyl)-ethyl]-8-benzyl-7-{2-ethyl-(2-hydroxyethyl)-amino]-ethyl}-1-propyl-3,7-dihydro-purine-2,6-dione] a water-soluble, small molecule A1 AR antagonist were investigated on early and late phase allergic responses (EAR and LAR) in a hyper-responsive rabbit model of asthma. Rabbits were made allergic by intraperitoneal injections of house dust mite [HDM; 312 allergen units (AU)] extract within 24 h of their birth. Booster HDM injections were given weekly for 1 month, biweekly for 4 months, and continued monthly thereafter. Hyperresponsiveness was monitored by measuring lung dynamic compliance (Cdyn), after histamine or adenosine aerosol challenge in allergic rabbits. Hyper-responsive rabbits were subjected to aerosol of HDM (2500 AU), 1 h after intragastric administration of L-97-1 (10 mg/kg) solution or an equivalent volume of saline. Cdyn was significantly higher after treatment with L-97-1 compared with untreated controls (p < 0.05 n = 5). Histamine PC30 was significantly higher (p < 0.05; n = 5) after L-97-1 at 24 h compared with histamine PC30 at 24 h after HDM. Adenosine PC30 was significantly higher at 15 min and 6 h after L-97-1 compared with control (p < 0.05; n = 5). L-97-1 showed strong affinity for human A1 ARs in radioligand binding studies and no inhibition toward human phosphodiesterase II, III, IV, and V enzymes. These data suggest that L-97-1 produces a significant reduction of histamine or adenosine-induced hyper-responsiveness and HDM-induced EAR and LAR in allergic rabbits by blocking A1 ARs and may be beneficial as an oral therapy for human asthma.

Adenosine↗
PubMed2002

Binding of bilirubin with albumin-coupled liposomes: implications in the treatment of jaundice.

In the present study, we demonstrated the suitability of liposomes as a method of removing plasma bilirubin in hyperbilirubinemic rats. The liposomes have innate tendency to bind with bilirubin through hydrophobic interaction. Among different types of liposomes, the positively charged liposomes were found to have maximum affinity to free bilirubin. However, the entrapment or coupling of serum albumin on the surface of egg phosphatidylcholine liposomes can render a several-fold increase in their bilirubin binding capacity. The proteoliposomes were able to preferentially bind with bilirubin even in the presence of erythrocytes. Interestingly, these liposomes were found to displace bilirubin bound on the surface of erythrocytes as well. The results of the present study further demonstrate that albumin-bearing liposomes were equally effective in removing plasma bilirubin in experimental jaundiced animals. These observations indicate that liposome-mediated selective homing of excess plasma bilirubin to the liver cells (cf. hepatocytes) may help in the development of safer strategy for the treatment of hyperbilirubinemic conditions in the model animals.

Animals↗
PubMed2000

Stent-based gene therapy.

Delivery of gene therapy to inhibit intimal hyperplasia has been proposed to prevent postangioplasty restenosis. We sought to apply gene therapy by using a stent-based technique. There are several hurdles that must be overcome before gene-stent therapy can be applied successfully in clinical trials. These include increasing the efficiency of gene delivery through atherosclerotic plaque; increasing intramural retention times; preventing the inflammatory reaction that stents coated with biodegradable polymers can elicit; overcoming the risk of systemic gene delivery; and accessing the adventitia via percutaneous approach. We evaluated a gene-stent delivery mechanism based on microporous metal microneedles developed with nanotechnology in an attempt to overcome some of these problems. A novel approach to the transfection of genes by microfabricated technology was evaluated in smooth muscle cells in culture. We demonstrated that microneedles can deliver gene therapy to smooth muscle cells in culture and can produce controlled penetration of the IEL and intima. We conclude that taller microneedles need to be developed to reach the media in diseased human arteries and that this technology has the potential to be incorporated in a stent to deliver gene therapy in atherosclerotic plaque.

Angioplasty, Balloon, Coronary↗
PubMed2000

Meningococcal infection among pilgrims visiting Madinah Al-Munawarah despite prior A-C vaccination.

OBJECTIVE: To study the profile of meningococcal infection among pilgrims despite prior A-C vaccination. SETTING: King Abdul Aziz Hospital, Madinah Al-Munawarah, Saudi Arabia. SUBJECTS AND METHODS: Fifteen patients admitted to the hospital during the study period of April 1992 to June 1993 were evaluated prospectively regarding their clinical and laboratory features, culture and antibiotic sensitivity and meningococcal serotypes. RESULTS: Twelve cases presented as meningitis while 3 cases had meningococcaemia. Most (53.3%) were from Pakistan while rest were from 6 other countries. Clinical and laboratory features at presentation were similar as reported in the literature. In 13 cases where serotyping could be done, most belonged to group A (54%) and C (23%). Antimicrobial sensitivity showed the isolates to be sensitive to most of the antibiotics commonly used to treat this infection. Mortality was 33% with the poorest outcome in patients with W135 infection. CONCLUSION: This study underscores the need of further studies in Makkah and Madinah, Saudi Arabia to find out the serotypes and immunological factors responsible for meningococcal infection in A-C vaccinated pilgrims so as to explore the possibility of use of polyvalent meningococcal vaccine.

Adult↗
PubMed1998

Micromechanical devices for intravascular drug delivery.

Microfabrication technology, more commonly applied to the manufacture of integrated circuits, can be used to build devices useful for mechanical delivery of drugs and genes. Microprobes fabricated using silicon micromachining have been used to deliver DNA into cells as an alternative to bombardment and microinjection. This idea can be extended to intravascular stents with integrated microprobes capable of piercing compressed plaque and delivering anti-restenosis therapies into coronary arteries. Preliminary experiments using filleted rabbit arteries have demonstrated transection of the internal elastic lamina. New nonplanar microfabrication technologies are necessary for creating practical devices with cylindrical symmetry; a promising possibility is to use microfabricated structures of anodic metal oxides.

Animals↗
PubMed1997

Electrical defibrillation optimization: an automated, iterative parallel finite-element approach.

To date, optimization of electrode systems for electrical defibrillation has been limited to hand-selected electrode configurations. In this paper we present an automated approach which combines detailed, three-dimensional (3-D) finite-element torso models with optimization techniques to provide a flexible analysis and design tool for electrical defibrillation optimization. Specifically, a parallel direct search (PDS) optimization technique is used with a representative objective function to find an electrode configuration which corresponds to the satisfaction of a postulated defibrillation criterion with a minimum amount of power and a low possibility of myocardium damage. For adequate representation of the thoracic inhomogeneities, 3-D finite-element torso models are used in the objective function computations. The CPU-intensive finite-element calculations required for the objective function evaluation have been implemented on a message-passing parallel computer in order to complete the optimization calculations in a timely manner. To illustrate the optimization procedure, it has been applied to a representative electrode configuration for transmyocardial defibrillation, namely the subcutaneous patch-right ventricular catheter (SP-RVC) system. Sensitivity of the optimal solutions to various tissue conductivities has been studied. Results for the optimization of defibrillation systems are presented which demonstrate the feasibility of the approach.

Algorithms↗
PubMed1995

Three-dimensional uniform grid modeling of electrical defibrillation on a data parallel computer.

Finite element modeling has played an increasingly important role in the study of defibrillation. In order to model well the complex anatomical details, a large number of elements are required in the finite element grid, leading to a large set of equations that often cannot be solved effectively with the computational power of conventional computers. In this paper, we describe the use of a data parallel computer to provide the memory and reduction in solution time for solving these large finite element problems. Using a uniform grid and a nodal assembly technique, the discretized problem domain can be mapped efficiently to the parallel computer, allowing the solution of problems with over two million unknowns. The finite element algorithm for a three-dimensional inhomogeneous anisotropic body is described together with its parallel implementation. Test results for a canine torso model constructed from CT images are also presented.

Algorithms↗
PubMedDate not supplied

A gait-powered autologous battery charging system for artificial organs.

The quality of life of patients relying on electrically powered artificial organs is currently restricted by the limited energy availability provided by portable batteries. As these patients become increasingly ambulatory, and are developing more active lifestyles, this limitation grows more apparent. Coincidentally, these patients may themselves be capable of generating electrical power as a consequence of their physical activity. Extraction of this latent autologous energy could, in turn, be used to augment charging of internal batteries--thus untethering the patient from external power for extended periods of time. In this study, the viability of deriving energy associated with natural human ambulation has been evaluated. The kinematic components of gait were evaluated to identify the largest useful forces and moments that may be harnessed as an energy source, while presenting minimal "perceived" work for the patient. It was found that the ground reaction forces associated with the heel strike and toe-off phases of the gait represent the greatest potential for usable energy. This study uses a piezoelectric array within the midsole of the shoe for the conversion of mechanical to electric energy. This power could then be easily coupled in tandem with existing transcutaneous transformers for augmenting or temporarily replacing external power sources.

Artificial Organs↗