Cardiac Troponin T and creatine kinase MB fraction levels among patients with acute ischemic stroke in Nigeria.

BACKGROUND: Stroke has been a global burden, with increasing morbidity and mortality. Serum cardiac troponin t (cTnT) and creatine kinase (CK-MB) fraction are reported to be elevated in patients admitted with acute ischaemic stroke and high level of these biomarkers indicated more severe stroke and neurologic deficit in some of the patients. OBJECTIVE: To evaluate the serum levels cardiac troponin t (cTnT) and creatine kinase MB fraction (CK-MB) in patients with acute ischaemic stroke and relate the analytes to severity of stroke. METHOD: Patients with clinical diagnosis of ischaemic stroke diagnosed, confirmed by brain Computerized Tomography scan and equal number of apparently healthy age and sex-matched were recruited. Serum cardiac troponin t (cTnT) and creatine kinase MB fraction (CK-MB) were analysed using ELISA method and Stroke severity was determined using National Institute of Health Stroke Score (NIHSS). RESULTS: Mean serum cardiac troponin t (cTnT) and creatine kinase MB fraction (CK-MB) in stroke patients were found to be higher than age sex matched control (p<0.05). NIHS Score of 12.2 ± 5.43 and 9.78 ± 3.97 were observed in Patients with elevated and normal cTnT respectively (p=0.009) while NIHS Score were similar in patients with elevated and normal CK-MB (p = 0.772). CONCLUSION: The mean values of serum cTnT and CK-MB were higher in acute ischaemic stroke patients compared to controls. Serum cardiac Troponin t level may be a significant biomarker of the severity of stroke.

Biochemical label-free tissue imaging with subcellular-resolution synchrotron FTIR with focal plane array detector.

The critical questions into the cause of neural degeneration, in Alzheimer disease and other neurodegenerative disorders, are closely related to the question of why certain neurons survive. Answers require detailed understanding of biochemical changes in single cells. Fourier transform infrared microspectroscopy is an excellent tool for biomolecular imaging in situ, but resolution is limited. The mid-infrared beamline IRENI (InfraRed ENvironmental Imaging) at the Synchrotron Radiation Center, University of Wisconsin-Madison, enables label-free subcellular imaging and biochemical analysis of neurons with an increase of two orders of magnitude in pixel spacing over current systems. With IRENI's capabilities, it is now possible to study changes in individual neurons in situ, and to characterize their surroundings, using only the biochemical signatures of naturally-occurring components in unstained, unfixed tissue. We present examples of analyses of brain from two transgenic mouse models of Alzheimer disease (TgCRND8 and 3xTg) that exhibit different features of pathogenesis. Data processing on spectral features for nuclei reveals individual hippocampal neurons, and neurons located in the proximity of amyloid plaque in TgCRND8 mouse. Elevated lipids are detected surrounding and, for the first time, within the dense core of amyloid plaques, offering support for inflammatory and aggregation roles. Analysis of saturated and unsaturated fatty acid ester content in retina allows characterization of neuronal layers. IRENI images also reveal spatially-resolved data with unprecedented clarity and distinct spectral variation, from sub-regions including photoreceptors, neuronal cell bodies and synapses in sections of mouse retina. Biochemical composition of retinal layers can be used to study changes related to disease processes and dietary modification.

Pore size prediction of polyethersulfone ultrafiltration membranes using artificial neural networks.

This paper reports the performance of two different artificial neural networks (ANN), Multi Layer Perceptron (MLP) and Radial Basis Function (RBF) compared to conventional software for prediction of the pore size of the asymmetric polyethersulfone (PES) ultrafiltration membranes. ANN has advantages such as incredible approximation, generalization and good learning ability. The MLP are well suited for multiple inputs and multiple outputs while RBF are powerful techniques for interpolation in multidimensional space. Three experimental data sets were used to train the ANN using polyethylene glycol (PEG) of different molecular weights as additives namely as PEG 200, PEG 400 and PEG 600. The values of the pore size can be determined manually from the graph and solve it using mathematical equation. However, the mathematical solution used to determine the pore size and pore size distribution involve complicated equations and tedious. Thus, in this study, MLP and RBF are applied as an alternative method to estimate the pore size of polyethersulfone (PES) ultrafiltration membranes. The raw data needed for the training are solute separation and solute diameter. Values of solute separation were obtained from the ultrafiltration experiments and solute diameters ware calculated using mathematical equation. With the development of this ANN model, the process to estimate membrane pore size could be made easier and faster compared to mathematical solutions.

Binding of 125I-insulin on capillary endothelial and myofiber cell membranes in normal and streptozotocin-induced diabetic perfused rat hearts.

A heart-perfusion technique was employed to measure 125I-insulin binding on capillary endothelial and myocyte cell membranes in Sprague-Dawley rats. Animals were anesthetized, and the anterior chest wall excised to expose the mediastinal contents. The right and left superior and inferior venae cavae were dissected and tied, and another tie was passed around the aorta. A polyethylene catheter was introduced into the aortic lumen from cephalad to caudad to sit with its tip above the aortic valve. Another catheter was introduced into the cavity of the right atrium and both were anchored by sutures. Oxygenated Ringer-Lock buffer containing 20 mM/L K+ and 125I-insulin was perfused at a rate of 1 mL/min via the aortic catheter. Concomitantly, the distal ascending aorta and venae cavae were ligated. The effluent was collected from the right atrial catheter at the same infusion rate. Animals were divided into two groups, the normal group and streptozotocin-induced diabetic group. Heart perfusion was done on both groups either without or after treatment with detergent (CHAPS) to remove the capillary endothelial lining. A physical model for 125I-insulin sequestration as a ligand to its receptors on endothelial and/or myocyte plasma membranes was proposed. The model described a reversible binding of ligand on cellular surface receptor concentration to fit a conservation equation and a first order Bessel function. The binding constants (kn), reversal constants (k-n), dissociation constants kd = k-n/kn, and residency time constants tau = 1/k-n of 125I-insulin in normal untreated, normal CHAPS-treated, diabetic untreated, and diabetic CHAPS-treated hearts were estimated using a theoretically generated curve-fit to the data. Since insulin receptor binding on the capillary endothelial cell surfaces may serve to transport insulin from the intravascular to the subendothelial space, and since streptozotocin-induced diabetes was shown to diminish receptor autophosphorylation and kinase activity and hence internalization of insulin, then one can conclude the following from the data. In the normal heart, removal of the capillary endothelial lining with CHAPS did not alter kn, k-n, kd, and tau of insulin binding as compared to the normal untreated, whereas in the diabetic untreated heart these constants were altered, compared to the diabetic treated. Furthermore, the kn and k-n values in the diabetic CHAPS-treated hearts were the same as for the normals untreated and CHAPS-treated, respectively. In conclusion, the dissociation constants and residency time constants of all groups indicated the possible existence of two types of insulin receptors: the capillary endothelial cell surface insulin receptors with lower residency time (low affinity receptor or combination of insulin and IGF-1 receptors) and the myocyte plasma membrane insulin receptors with higher residency times (high affinity).

Binding and distribution of three prototype calcium channel blockers in perfused rat liver.

This work represents a study of the binding and distribution of three different calcium channel blockers in the Sprague-Dawley rat liver, using an in situ perfusion technique. For this purpose, [3H] desmethoxyverapamil, [3H] PN200-110 (isradipine) and [3H] azidopine were used as binding probes interacting with calcium channels. The perfusion steps of the liver involved both portal vein and thoracic inferior vena cava cannulations as inlet and outlet respectively. The subhepatic inferior vena cava was ligated to prevent leakage of the perfusate. Buffer, containing the tracer drug, was administered via the portal vein at a rate of 1 mL/min and perfusate collected at the same rate within specified time intervals during 50 min. The concentration of the tracer solutes in the perfusate's outlet increased with time, and steady state was observed for all tracers at > or = 40 min. The effect of adding cold isradipine to tracer desmethoxyverapamil, or cold verapamil to tracer PN200-110 were also assessed. First order rate constants for hepatocellular influx, efflux and calcium channel binding of the tracer substances were obtained using a simplified model from Goresky et al. These constants were mathematically manipulated and changed into permeability constants, second order binding constants, and residency times. Tracer solute influx across hepatocellular membranes is solubility-diffusion controlled, is inversely related to the molecular weights and is different in value from the efflux constants. Cold isradipine reduced the binding constant of desmethoxyverapamil by 36%, while cold verapamil reduced the binding constant of PN200-110 by 23%. Azidopine cellular distribution was low, however, binding to its receptor was analogous to desmethoxyverapamil and PN200-110. Moreover, PN200-110 had the highest residency time with no effect of cold verapamil on its receptor binding, while desmethoxyverapamil had the lowest residency time which significantly increased in the presence of cold isradipine.

The mast cells of the multiple sclerosis brain.

Traditional staining methods, plus indirect immunoperoxidase techniques for IgE and mast cell tryptase (MCTr) were used to study the mast cells (MCs) of multiple sclerosis (MS) and normal brains. The MCs varied in number in MS amongst perivascular inflammatory cells as well as free in the parenchyma, especially inside and around "chronic active' plaques. Since MCs do not migrate, and rarely divide in maturity, they must have developed locally. Staining for IgE was moderately strong on and within MCs, and weak within some plasma cells. MCTr reacted strongly both within CNS and outside it. Being a strong neutral proteinase. MCTr, plus IgE, could conceivably have played some role in the pathogenesis of the MS plaques.

Explosive autotomy induced by simultaneous dorsal column lesion and limb denervation: a possible model for acute deafferentation pain.

We report on a new "explosive" form of self-mutilation behavior (autotomy) characterized by rapid onset (1-2 days), short duration (1-2 days), and unpredictable progression. The possible neural mechanism(s) underlying this novel behavior were examined in rats by combining at varying time intervals one leg denervation with a lesion to the dorsal columns (DC lesion) or to a dorsolateral funiculus (DLF lesion). DC lesion, followed immediately by leg denervation, resulted in explosive autotomy in 62% of the rats and regular autotomy in 25% of the rats. Regular autotomy was characterized by slow onset (2-3 weeks), prolonged duration (2-3 weeks), and stereotyped progression from distal to proximal parts of the leg. DC lesion, followed 1 week later by leg denervation, resulted in regular autotomy in 71% of the rats which was not different from autotomy resulting from denervation alone. DC lesion preceded 1 week earlier by leg denervation resulted in slightly accelerated regular autotomy in 77% of the rats. Simultaneous DC lesion and leg denervation immediately preceded by application of a local anesthetic (4% procaine) for 30 or 60 min to the exposed lumbar spinal cord resulted in regular autotomy in all rats. All rats in a sham group, in which the procaine was replaced by normal saline, exhibited explosive autotomy. DLF lesion, followed immediately by leg denervation, resulted in accelerated regular autotomy.(ABSTRACT TRUNCATED AT 250 WORDS)

The mast cells of the mammalian central nervous system. IX. Development of the mast cells in the brain of the young rat.

There are four potentially granular or frankly granular cells within the connective tissue compartment of the mammalian central nervous system, whether this is part of the surface leptomeninges or the leptomeningeal sleeves around parenchymal blood vessels larger than capillaries. These are: Cells that behave like macrophages, part of the mononuclear phagocyte system of the body; they are granular to varying degrees (containing lysosomes). Brown-pigmented granular cells which are mainly located on the surface but are also seen for varying distances along blood vessels as they pass inside the CNS of pigmented animals. Mast cells (MCs) which are granular and located especially prominently in surface leptomeninges of young mammals, and, in adults, are restricted to special parts of the CNS. Granular cells, referred to by me as neurolipomastocytoid cells (NLMs), are numerous, ubiquitously distributed, and seem to have morphological features in common with those of both MCs and macrophages. The exact identity of these NLMs still needs to established. One approach was to study the development of all three non-pigmented cells in the immature brain of the albino rat, especially at the ultrastructural level. This communication represents the findings regarding the MCs. The MCs appear to arise from a small mononuclear cell and to go through maturation stages identical to those described by others for MCs outside the CNS. The greatly flattened adjacent leptomeningeal cells are an easily identifiable entity especially due to their peculiar glycogen content in the young.

Correlation of urinary lactic dehydrogenase with polymorphonuclear leukocytes in urinary tract infections in patients with spinal cord injuries.

A number of indirect methods have been developed to determine the site of urinary tract infection, including the measurement of LDH in urine [1]. Although LDH has been thought to be from the kidneys, it has also been noted that leukocytes could contribute LDH isoenzymes 4 and 5 [2]. Seventeen patients with injured spinal cords and significant bacteriuria were included in this study. Urine specimens obtained by urethral catheter were cultured, and PMNLs identified with Sternheimer-Malbin stain were counted in a hemacytometer. A positive test for antibody-coated bacteria and the lack of patient response to five to 10 days of antibiotic therapy were used as an indication of upper urinary tract infection. Levels of LDH isoenzymes 4 and 5 (cathodal) correlated with the number of PMNLs in the urine (r = 0.63, P less than 0.01). There was no correlation of PMNLs with LDH isoenzymes 1 and 2 (r = 0.18). In addition, there was no correlation of LDH isoenzymes 4 and 5 with the level of urinary tract infection. These results suggest that the PMNLs in the urine are the source of the LDH isoenzymes 4 and 5.

The mast cells of the mammalian central nervous system. VI. Uptake of tritiated thymidine by mast cells, neurolipomastocytoid cells and other elements of the central nervous system.

The central nervous system (CNS) of two mammalian species was studied autoradiographically using tritium-labeled thymidine; the rat, whose brain contains few localized mast cells (MCs) but many ubiquitous neurolipomastocytoid cells (NLMs), and the guinea pig, whose brain contains only ubiquitous NLMs. A few guinea pigs were also injected with an MC discharger compound 48/80 and the response of the NLMs, which are thought to be allied to MCs, as well as of neuroglial and vascular endothelial cells, was noted. The rats were 3 days to 6 weeks old whereas all the guinea pigs were young adults. Both MCs and NLMs took up the label, and much more so in the babies, paralleling similar uptakes in only very small immature MCs outside the CNS. Neuroglial elements, especially subependymal and oligodendroglial, as well as endothelial, perivascular, leptomeningeal and ependymal cells demonstrated some uptake. This was considerably increased upon receipt of compound 48/80, especially in the case of the subependymal glia, the NLMs and the endothelial cells; capillary neoformations were seen in the spinal cords of guinea pigs that had shown signs of paralysis. The cause of this increase is discussed in terms of mild stress induced by that compound. The subependymal response is also discussed with reference to periventricular plaques seen in multiple sclerosis and lymphoreticular and glial tumors seen in that region. It is concluded that both MCs and NLMs are capable of DNA replication and mitosis in immature animals. The NLMs can also divide upon stimulation in adult CNS.

The mast cells of the mammalian central nervous system. V. The effect of compound 48/80 on the neurolipomastocytoid cells and related areas of the CNS: early changes.

The response of the neurolipomastocytoid cells (NLMs) and elements in their vicinity within the central nervous system of various animal species was studied following injection of the animals with the specific mast cell (MC)-discharger compound 48/80. The observed alterations were grouped into those occurring early (0--21 days) and later (up to 18 months). In the present report, only the acute changes are described, light and electron microscopically. Most experimental animals developed prostration, scratching, acral-type reaction, signs of respiratory distress and salivation, and, in the monkey, uncontrollable somnolence. Within about 2 weeks after the injection some animals (especially guinea pigs) manifested various degrees of limb paralysis. The NLMs, like MCs outside the CNS, responded to injection by various degrees of degranulation, vacuolation, marked variation in granule size, apparent cell loss and sometimes an increase in number. Electron microscopically, particulate breakdown products of the granules of the NLMs appeared in the cytoplasm; occasionally there was suggestive evidence that they had passed inward across the vessel wall to reach the lumen, and also outward through the outermost basal lamina. Perivascular astrocytic feet showed swelling and vacuolation shortly after the injection, which was followed by evidence of gliosis and later scarring; occasionally, alterations in the mitochondria were observed. In the spinal cord of the guinea pig, capillary neoformation was observed with endothelial cells and adjacent NLMs taking up tritiated thymidine. The discussion centers on the partial similarity of response to compound 48/80 of the NLMs to that of MCs outside the CNS, and the probable involvement of NLM-damage in the parenchymal changes.

The mast cells of the mammalian central nervous system. IV. Culture of neurolipomastocytoid cells from rabbit and rat leptomeninges.

Leptomeningeal cells of 1-3 day-old rabbits and rats were cultured in Hamm's complete medium or in Eagle's Basal Medium (BME); the latter proved to be favorable for the present research. Three types of granular cell could be differentiated and isolated from other mesenchymal, neuronal and neuroglial elements. These three closely resembled (i) mast cells (MCs), (ii) neurolipomastocytoid cells (NLMs), and (iii) typical macrophages. Because MCs are absent from adult rabbit leptomeninges but present in the rat, it was concluded that the MC-like elements in rabbit cultures were derived from precursor cells normally capable of producing NLMs. The macrophages appeared typical, but their cell of origin, as that of the MCs and NLMs, could not be determined conclusively; a small round mononuclear cell might have given rise to all three cell types. NLMS, like MCs but unlike macrophages, are sensitive to the MC-discharger compound 48/80. This finding, plus the peculiar morphological features of the NLMs, in addition to evidence of a strong phagocytic activity by the macrophages, distinguishes the mature NLMs from mature macrophages as distinct cellular entities. It is closely concluded that NLMs in culture resemble ordinary MCs more closely.

The mast cells of the mammalian central nervous system. III. Ultrastructural characteristics in the adult rat brain.

The brains of young adult male and female Sprague-Dawley rats were studied with the electron microscope to determine the full ultrastructural picture of two types of perivascular granular cell. One of these, referred to here as the type I cell and described by both light and electron microscopy by several authors, including ourselves, has been reported to be a mast cell (MC) almost identical to MCs outside the CNS. The other, referred to here as the type II cell and described by many authors under almost as many names, was dealt with fully by Ibrahim in several reports and regarded by him as a type of MC. It is felt that the results warrant the conclusions that the type I cells are indeed MCs, while the type II cells are closely allied to the type I cells and probably better adapted to the function they subserve in the CNS of mammals. The similarities between the two cell types probably outnumber the dissimilarities and even these have their counterparts in MCs outside the CNS. The problem of the possible confusion between the type II cells and macrophages, whether reportedly within vessel walls or in the form of modified or special 'pericytic' microglia, is discussed. It is concluded that there is no justification for regarding these cells as macrophages. Because of the similarity between the type II cells and MCs, and because of the high lipid content of the type II cells, it is suggested that these elements be called neurolipomastocytes or neurolipomastocytoid cells.