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Biomedical subjects

F Khan

Publications and source records attributed to F Khan.

At least 19 recordsLinked to original sources
PubMed2007

Mechanisms influencing the vasoactive effects of lidocaine in human skin.

The vasodilator properties of lidocaine are believed to be due mainly to the inhibition of action potentials via sodium channel blocking in vasoconstrictor sympathetic nerves. However, mechanisms involving the vascular endothelium may also play a role, and in this study we investigated the potential influences of nitric oxide release, the cyclo-oxygenase pathway and the beta-adrenoceptors of vascular smooth muscle. Laser Doppler imaging was used to measure microvascular blood flow responses to intradermal injection of lidocaine 2%, with or without the addition of preservatives, in eight healthy, male volunteers. Co-injection of the nitric-oxide-synthase inhibitor Nomega-nitro-L-arginine methyl ester caused a 60% reduction in the response after about 20 min, and this reduction was enhanced with the lidocaine solution containing the preservatives methylhydroxybenzoate and propylhydroxybenzoate. No reduction in response was seen after blocking the cyclo-oxygenase or beta-adrenoceptor pathways. Nitric oxide release contributes to the vasoactivity of lidocaine in human skin.

Adult↗
PubMed2006

Local delivery of angiotensin receptor blocker into the kidney ameliorates progression of experimental glomerulonephritis.

Intrarenally synthesized angiotensin II (Ang II) may be involved in the progression of glomerulonephritis, leading to irreversible glomerulosclerosis. There is increasing evidence that systemic angiotensin receptor blocker (ARB) treatment has beneficial effect on the prognosis of progressive glomerulonephritis and diabetic nephropathy. However, the cellular and molecular mechanisms behind this therapeutic effect of ARB remain unclear. In this study, we used a novel strategy of local ARB delivery via type-1 collagen sponge, to treat progressive glomerulonephritis that would result in irreversible glomerulosclerosis in our previously established rat model. At days 9 and 14 after disease induction, mild proteinuria, 20.7+/-4.7 and 10+/-1.3 mg/day, was found. Local ARB treatment reduced proteinuria significantly to 3.19+/-3.2 and 5.25+/-0.95 mg/day (P < 0.01), respectively. Scoring of glomerular matrix expansion and sclerotic index revealed that local ARB treatment significantly ameliorated glomerular pathology. Ang II type 1 receptor mRNA expression was remarkably enhanced in the Ang II group and ARB treatment reversed this effect at 14 days. Local delivery of ARB significantly improved glomerular blood flow levels, compared to the untreated disease control group, from 710+/-18.25 to 859.44+/-22.86 microm/s, respectively. Local delivery of ARB into the kidney affected local RAS and thus improved the renal injury and function in the potentially progressive glomerulosclerosis of rat model.

Angiotensin II↗
PubMed2006

Design, synthesis and in vivo anticonvulsant screening in mice of novel phenylacetamides.

A set of seven novel N-substituted 2-anilinophenylacetamides were designed by pharmacophore generation and using flexible alignment module of MOE software. The novel molecules were synthesized and screened for anticonvulsant activity in Swiss albino mice by MES and ScPTZ induced seizure tests. Test compounds were found to be potent in MES test. Compounds 12 and 14 were found to be more potent with ED(50) values 24.0 and 8.0 mg kg(-1), respectively, and their activity was comparable to standard drugs (Phenytoin, Carbamazepine). Test compounds did not show significant activity in ScPTZ test. Compounds 12 and 14 also exhibited higher protective indices (20.3 and 87.5, respectively) when assessed for neurotoxicity by rotarod test as compared to the standards.

Amides↗
PubMed2006

Measurement and significance of 3-nitrotyrosine in systemic lupus erythematosus.

Nitration of free and protein associated tyrosine represents, in vivo, a mechanism that can severely compromise the cell function. The detection of 3-nitrotyrosine (3-NT) in pathological tissues is suggestive of the occurrence of nitrating pathways and has been identified as a marker of inflammation and a stable end product of increased reactive nitrogen intermediate production. Protein nitration occurs in many disease conditions including systemic lupus erythematosus (SLE). In this study we show that the level of both free and protein bound 3-NT, which is produced by reactive nitrogen species (RNS)-dependent oxidative damage, is elevated in patients with SLE and that there is a possible role of RNS-modified epitopes in the aetiology of the disease. Commercially available poly L-tyrosine was exposed to nitrating species, inducing nitration in tyrosine residues. Immunoglobulin-G (IgG) purified on Protein-A-Sepharose matrix from 24 SLE patients was studied for their recognition of native and nitrated poly L-tyrosine by direct binding and competition enzyme-linked immunosorbent assay (ELISA). The formation of immune complex between SLE IgG and nitrated poly L-tyrosine was visualized by gel retardation assay. Free 3-NT in patients' sera was detected and quantitated by high performance liquid chromatography whereas protein-bound 3-NT was analysed by Western blotting and the concentration was calculated by sandwich ELISA. The concentration of free 3-NT was found to be 1.4 +/- 0.09 microm whereas the concentration of protein bound 3-NT was 96.52 +/- 21.12 microm nitrated bovine serum albumin equivalents/mg protein, which was significantly higher when compared with healthy controls. Elevated level of 3-NT was observed in SLE patients using two different techniques, when compared with healthy subjects confirms the overproduction of RNS in the pathogenesis of human SLE.

Adolescent↗
PubMed2006

Effects of poor glucose handling on arterial stiffness and left ventricular mass in normal children.

AIM: Cardiovascular risk factors can be present in children and young adults. We previously found abnormal microvascular function in children who had glucose intolerance and insulin resistance. The aim of the present study was to investigate whether they also have abnormalities in left ventricular mass (LVM) and arterial stiffness. METHODS: We measured heart dimensions and LVM using echocardiography, and arterial stiffness using pulse wave analysis in 23 children with good glucose handling (postfeeding glucose: 3.9 to 5 mmol/L) and 21 with poor glucose handling (7.7 to 11.4 mmol/L). RESULTS: The time to pulse reflection was slightly shorter in the poorer glucose handlers (mean+/-SD: 143+/-10 vs 153+/-20 ms, P=0.04), suggestive of increased arterial stiffness. Also in this group, there were significant relationships between intraventricular septal thickness, blood pressure and body mass index, but not in the normal glucose handlers. CONCLUSIONS: We have found that normal children who are in the lowest quintile of glucose tolerance in comparison with their peers are exhibiting the first signs of arterial stiffening. In addition, we have seen the beginnings of a relationship between blood pressure, body mass index and left ventricular enlargement in this group. While these changes may not yet be clinically significant, their emergence might be further evidence of early predisposition to cardiovascular disease.

Adolescent↗
PubMed2005

Vasoactive characteristics of bupivacaine and levobupivacaine with and without adjuvant epinephrine in peripheral human skin.

BACKGROUND: Epinephrine is added to local anaesthetic preparations to prolong their action and reduce their systemic absorption. Bupivacaine and levobupivacaine cause vasodilatation at clinical doses, but lower doses appear to cause vasoconstriction. The aim of this study was to characterize fully the vasoactive effects of these anaesthetics, using an objective measure of blood flow, and to assess the influence of adding epinephrine. METHODS: Laser Doppler imaging was used to measure the forearm skin blood flow responses to intradermal injection of eight doses of bupivacaine and levobupivacaine in 10 healthy male volunteers. The doses tested ranged from 0.008% to 0.75%, and the five highest doses were administered both with and without adjuvant epinephrine 2.5 microg ml(-1). RESULTS: The cumulative responses to the lower subclinical concentrations (0.008-0.0625%) of both anaesthetics were smaller than or similar to that produced by saline alone, indicating a net vasoconstrictive effect. Higher doses caused net vasodilatation, and the levobupivacaine responses were generally lower than the corresponding bupivacaine responses (P=0.022). Epinephrine 2.5 microg ml(-1) significantly reduced the responses to clinical doses of both drugs (P<0.001), producing net vasoconstriction. CONCLUSIONS: Bupivacaine and levobupivacaine have a biphasic vascular effect when injected intradermally, with subclinical doses causing net vasoconstriction. The addition of epinephrine 2.5 microg ml(-1) decreases these responses markedly.

Adjuvants, Anesthesia↗
PubMed2005

Endothelin-1 levels predict 3-year survival in patients who have amputation for critical leg ischaemia.

BACKGROUND: Most patients with critical leg ischaemia (CLI) have co-existing coronary heart disease, which is the main cause of their increased mortality rate. The aim of this study was to investigate whether any markers of endothelial function could predict death in these patients. METHODS: In a cohort of 39 patients with CLI who were scheduled for lower-limb amputation, blood levels of vascular endothelial growth factor, homocysteine, endothelin (ET) 1, von Willebrand factor and vascular cell adhesion molecule 1 were measured, as well as forearm vascular responses to the endothelium-dependent vasodilator acetylcholine. RESULTS: Levels of ET-1 were significantly higher in patients who subsequently died within 3 years than in those who were still alive (P = 0.002) and Cox proportional hazards regression analysis demonstrated that ET-1 was an independent predictor of all-cause mortality:hazard ratio 3.53 (95 per cent confidence interval (c.i.) 1.29 to 9.70; P = 0.007) and cardiovascular mortality:hazard ratio 4.15 (95 per cent c.i. 1.30 to 13.23); P = 0.014. CONCLUSION: ET-1 was an independent predictor of death in these patients with CLI.

Adult↗
PubMed2005

Pilot study of the effects of local pressure on microvascular function in the diabetic foot.

AIM: The aim of the study was to determine whether areas of the diabetic foot that experience high pressures during normal activity also demonstrate reductions in cutaneous microvascular flow and/or endothelial function. METHODS: Sixteen patients with diabetes mellitus and eight healthy, age-matched control subjects were recruited. Maps of dynamic pressure on the plantar aspect of both feet were recorded during a normal gait cycle, and the skin microvascular blood flow response to the endothelium-dependent vasodilator acetylcholine was assessed at the sites of highest and lowest plantar pressure over the metatarsal heads. RESULTS: Patients with diabetes had higher plantar pressures than control subjects (P = 0.002), but there were no significant differences in basal skin blood flow or acetylcholine response between the groups. In the patients, baseline flow was increased (P = 0.041) but the acetylcholine response reduced (P = 0.03) at the high-pressure compared with the low-pressure site; this was most apparent in those who were particularly at risk of ulceration due to high plantar pressures. CONCLUSIONS: Chronically raised plantar pressure in the diabetic foot is associated with increased basal skin blood flow, compared with lower pressure areas on the same foot. Further work is required to determine whether, and under what conditions, this additional hyperaemia is protective or maladaptive. In addition, high-pressure areas have a reduced responsiveness to an endothelium-dependent vasodilator, although the clinical significance of these changes is not clear.

Acetylcholine↗
PubMed2005

Enhanced recognition of hydroxyl radical modified plasmid DNA by circulating cancer antibodies.

Reactive oxygen species have been implicated in various human diseases which are also responsible for the elimination of invading pathogens. In disease state and inflammatory responses, the excess of these radicals damage cellular macromolecules. DNA is susceptible to attacks by OH-induced damage. Oxidative DNA damage is an important factor in mutagenesis and carcinogenesis. In the present study, purified plasmid Bluescript DNA was modified by hydroxyl radical. Modifications incurred in DNA were characterized by physico-chemical techniques. Sera from patients of cancer were studied for their binding to native and hydroxyl radical modified plasmid DNA. Direct binding ELISA and competition binding results indicated that autoantibodies in cancer showed higher recognition to ROS-plasmid DNA as compared to the native form. Retarded mobility of the immune complex formation between IgG isolated from cancer sera using native and ROS-plasmid DNA as antigens reiterated preferential recognition of modified plasmid DNA by cancer autoantibodies. Therefore, it can be concluded that circulating autoantibodies in cancer sera bind preferentially to ROS-plasmid DNA as compared to native polymer. The data presented in the present communication suggest a role of ROS in the etiology of cancer.

Antibodies, Neoplasm↗
PubMed2005

Angiotensin converting enzyme gene polymorphism in Indian children with steroid sensitive nephrotic syndrome.

CONTEXT: Nephrotic syndrome is one of the commonest renal problem encountered in children. It is difficult to predict at onset, the clinical course in terms of steroid responsiveness or resistance. Angiotensin converting enzyme (ACE) gene insertion/deletion (I/D) polymorphism has been studied as a predictor of clinical course in common multi-factorial diseases including focal segmental glomerulosclerosis. There is no study available from our country till date to find out any correlation of the steroid response in idiopathic nephrotic syndrome and ACE gene polymorphism. AIM: To study distribution and correlation of ACE gene I/D polymorphism in idiopathic steroid sensitive nephrotic syndrome. SETTINGS & DESIGN: Case-control retrospective study. SUBJECTS & METHODS: We studied ACE gene polymorphism in 90 consecutive patients (82% males, 18% females) with steroid sensitive idiopathic nephrotic syndrome and 300 normal controls (NC). STATISTICAL ANALYSIS: Chi-square test and Fisher's exact test (for cases with insufficient expected cell frequencies). RESULTS: The mean age of onset was 5.3 +/- 4 years. Steroid sensitive (SS) patients showed II (SS-48%, NC-26%) genotype was more frequent than normal controls (p=0.002). There was no significant difference in genotype frequencies among steroid SS subgroups. CONCLUSIONS: In our study II genotype was more frequent in steroid sensitive nephrotic syndrome children in comparison to normal controls. Further functional studies with large number of children are required to investigate the role of II genotype in steroid sensitive nephrotic syndrome. Comparison of the genotypic frequency with steroid resistant patients may provide information, which might be useful in clinical practice.

Child, Preschool↗
PubMed2004

Altered signal intensity in the posterior horn of the medial meniscus: an MR finding of questionable significance.

INTRODUCTION: MR imaging has emerged as an important modality in the non-invasive evaluation of osseous and soft-tissue structures in the post-traumatic knee. However, it is sometimes impossible to determine with confidence if a focus of high signal intensity in the meniscus is confined to the substance of the meniscus or if it extends to involve the joint surface. This is a critical differentiation because the latter represents meniscal tears that can be found and treated arthroscopically, whereas the former represents degeneration, intrasubstance tears or perhaps normal variants that are not amenable to arthroscopic intervention. The aim of this study was to investigate the occurrence of such borderline findings in relation to the posterior horn of the medial meniscus and to correlate the arthroscopic results. MATERIALS AND METHODS: Sixty-four patients with suspected post-traumatic internal derangements of the knee who underwent MR imaging prior to arthroscopy were evaluated retrospectively. There were 48 men and 16 women. Their mean age was 28.2 years. RESULTS: Tears of the posterior horn of the medial meniscus were diagnosed unequivocally (grade 3 signal) in 18 patients and equivocally (grade 2/3 signal) in 10 patients. Arthroscopic correlation revealed 16 tears (89%) in the unequivocal group and only 1 tear (10%) in the equivocal group. CONCLUSION: A meniscal tear is unlikely when MR shows a focus of high signal intensity in the posterior horn of the medial meniscus that does not unequivocally extend to involve the inferior or superior joint surface. An appropriate trial of conservative treatment is recommended in such questionable cases. MR is a useful diagnostic tool-however, it should be used selectively, and in conjunction with history and clinical examination in evaluating internal derangements of the knee.

Adolescent↗
PubMed2004

Osteoid osteoma: painful enlargement of the second toe.

Osteoid osteomas involving the phalanges of the toes are a rare occurrence. We report a case of an osteoid osteoma of the distal phalanx of the second toe which was treated successfully with surgical excision. Although soft-tissue swelling with a typical clinical history is suggestive of the diagnosis, differentiation from subacute infection is subtle and may ultimately depend on tissue analysis.

Adolescent↗
PubMed2004

Anatomy of the pelvic plexus and innervation of the prostate gland.

We have examined the anatomy of the pelvic (inferior hypogastric) plexus in six male cadavers, paying particular attention to gross anatomical landmarks that might aid in locating it and have used immunohistochemistry to study the small branches of the plexus that supply the prostate gland. The pelvic plexus was found two finger breadths lateral to the third anterior sacral foramina, lying deep to a line drawn from third sacral vertebra, the conventional level of the recto-sigmoid junction, and the palpable posterior superior surface of the pubic symphysis. Immunohistochemical staining showed small nerve branches from the pelvic plexus entering the prostate gland and the presence of ganglia within the prostate gland that contained both tyrosine hydroxylase positive and negative neuronal cell bodies. This information may be useful in nerve-sparing surgical procedures and in discussions of the functional implications of perturbations of prostate innervation.

Aged↗
PubMed2004

Acetylcholine mediated vasodilatation in the microcirculation of patients with chronic fatigue syndrome.

The aetiology of chronic fatigue syndrome (CFS) remains controversial and a number of hypotheses have been put forward to explain it. Research into the condition is hindered by the considerable heterogeneity seen across patients but several reports have highlighted disturbances to cholinergic mechanisms in terms of central nervous system activity, neuromuscular function and autoantibodies to muscarinic cholinergic receptors. This paper examines an altogether separate function for acetylcholine and that is its role as an important and generalized vasodilator. Most diseases are accompanied by a blunted response to acetylcholine but the opposite is true for CFS. Such sensitivity is normally associated with physical training so the finding in CFS is anomalous and may well be relevant to vascular symptoms that characterise many patients. There are several mechanisms that might lead to ACh endothelial sensitivity in CFS patients and various experiments have been designed to unravel the enigma. These are reported here.

Acetylcholine↗
PubMed2004

Significance of chimerism in hematopoietic stem cell transplantation: new variations on an old theme.

The main goal of post-transplantation monitoring in hematopoietic stem cell transplantation (HSCT) is to predict negative events, such as disease relapse, graft rejection and graft-versus-host disease, in order to intervene with appropriate therapy. In this context, chimerism analysis is an important method in monitoring post HSCT outcome. Mixed chimerism (MC) is mainly evaluated to define engraftment and relapse. Detection of MC is a prerequisite in both myeloablative and nonmyeloablative HSCT, in order to assess the graft status and decide later therapeutic strategies such as donor lymphocyte infusion. In this review, we discuss various techniques including erythrocyte phenotyping, cytogenetic analysis, fluorescent in situ hybridization, restriction fragment length polymorphism, STR/VNTR analysis and real-time quantitative PCR, along with the various methods used to detect minimal residual disease (MRD) in different diseases such as chronic myeloid leukemia, acute myelomonocytic leukemia or acute lymphoblastic leukemia. The review mainly highlights the optimal methodological approach, which needs to be informative, sensitive and quantitatively accurate for MC detection. Future of post HSCT graft monitoring lies in the selection of the most accurate and sensitive technique to determine both MC and MRD. Such an approach would be helpful in not only determining relapse or rejection, but also in ascertaining various responses to different treatment modalities.

Hematologic Neoplasms↗