222 resultados para capillary blood
Resumo:
To investigate the role of modified low-density lipoproteins (LDL) in the pathogenesis of diabetic retinopathy, we studied the cytotoxicity of normal and mildly modified human LDL to bovine retinal capillary endothelial cells and pericytes in vitro. Pooled LDL was incubated (in phosphate-buffered saline-EDTA, 3 days, 37 degrees C) under 1) nitrogen with additional chelating agents and 2) air, to prepare normal and minimally oxidized LDL, respectively. Similar conditions, but with the addition of 50 mM D-glucose, were used to prepare glycated and glycoxidized LDL. None of the LDL preparations was recognized by the macrophage scavenger receptor, confirming limited modification. Retinal capillary endothelial cells and pericytes were grown to confluence and then exposed for 2 or 3 days to serum-free medium (1% albumin) supplemented with normal or modified LDL (100 mg/l) or to serum-free medium alone. Cytotoxicity was assessed by cell counting (live and total cells) and by cell protein determination. Compared with normal LDL, modified LDL were cytotoxic to both cell types at both time points, causing highly significant decreases in live and total cell counts (P <0.001) (analysis of variance). Reductions in cell protein also were significant for pericytes at day 3 (P = 0.016) and of borderline significance for endothelial cells at day 2 (P = 0.05) and day 3 (P = 0.063). Cytotoxicity increased as follows: normal <glycated <or = minimally oxidized <glycoxidized LDL. We conclude that, in diabetes, mild modification of LDL resulting from separate or combined processes of glycation and oxidation may contribute to chronic retinal capillary injury and thus to the development of diabetic retinopathy.
Resumo:
Objective: To characterize the population pharmacokinetics of canrenone following administration of potassium canrenoate (K-canrenoate) in paediatric patients.
Methods: Data were collected prospectively from 37 paediatric patients (median weight 2.9?kg, age range 2 days–0.85 years) who received intravenous K-canrenoate for management of retained fluids, for example in heart failure and chronic lung disease. Dried blood spot (DBS) samples (n?=?213) from these were analysed for canrenone content and the data subjected to pharmacokinetic analysis using nonlinear mixed-effects modelling. Another group of patients (n?=?16) who had 71 matching plasma and DBS samples was analysed separately to compare canrenone pharmacokinetic parameters obtained using the two different matrices.
Results: A one-compartment model best described the DBS data. Significant covariates were weight, postmenstrual age (PMA) and gestational age. The final population models for canrenone clearance (CL/F) and volume of distribution (V/F) in DBS were CL/F (l/h)?=?12.86?×? (WT/70.0)0.75?×?e [0.066?×? (PMA?-?40]) and V/F (l)?=?603.30?×? (WT/70)?×?(GA/40)1.89 where weight is in kilograms. The corresponding values of CL/F and V/F in a patient with a median weight of 2.9?kg are 1.11?l/h and 20.48?l, respectively. Estimated half-life of canrenone based on DBS concentrations was similar to that based on matched plasma concentrations (19.99 and 19.37?h, respectively, in 70?kg patient).
Conclusion: The range of estimated CL/F in DBS for the study population was 0.12–9.62?l/h; hence, bodyweight-based dosage adjustment of K-canrenoate appears necessary. However, a dosing scheme that takes into consideration both weight and age (PMA/gestational age) of paediatric patients seems more appropriate.
Resumo:
A large body of research has highlighted practices and rituals that characterise injecting drug use and behavioural and environmental risks that can contribute to the transmission of blood-borne viruses. Compared with other injecting practices, considerably less is known about peer injecting, i.e. receiving or giving injections, particularly the social context in which it occurs. In this article, we explore peer injecting and injecting order at initiation into injecting drug user (IDU) and during subsequent injection episodes. Using data from semi-structured interviews, we highlight the experiences of 41 males and females who had received injections from other IDUs. Respondents were recruited through various strategies, largely chain referral. The results suggest gendered similarities as well as differences in terms of peer injecting, the order of injection and micro-risk contexts for blood-borne viruses. © 2013 Informa UK Ltd.
Resumo:
The purpose of this study was to define pathological abnormalities in the peripheral nerve of a large animal model of long-duration type 1 diabetes and also to determine the effects of treatment with sulindac. Detailed morphometric studies were performed to define nerve fiber and endoneurial capillary pathology in 6 control dogs, 6 type 1 diabetic dogs treated with insulin, and 6 type 1 diabetic dogs treated with insulin and sulindac for 4 years. Myelinated fiber and regenerative cluster density showed a non-significant trend toward a reduction in diabetic compared to control animals, which was prevented by treatment with sulindac. Unmyelinated fiber density did not differ among groups. However, diabetic animals showed a non-significant trend toward an increase in axon diameter (p <0.07), with a shift of the size frequency distribution towards larger axons, which was not prevented by treatment with sulindac. Endoneurial capillary density and luminal area showed a non-significant trend toward an increase in diabetic animals, which was prevented with sulindac treatment. Endoneurial capillary basement membrane area was significantly increased (p <0.05) in diabetic animals, but was not prevented with sulindac treatment. We conclude that the type 1 diabetic dog demonstrates minor structural abnormalities in the nerve fibers and endoneurial capillaries of the sciatic nerve, and treatment with sulindac ameliorates some but not all of these abnormalities.
Resumo:
The modern stereologic method of vertical sections was applied to the retina as a means of generating unbiased estimates of three-dimensional structure. The method is illustrated with real data on the volume and surface area of the capillary basement membrane from the central retina of the rat. Novel methods of estimating the volume of retina sampled and of creating accurate vertical sections are described. The advantages of using stereologic methods to generate quantitative information on the three-dimensional structure of the retina are discussed and compared to those of previous quantitative methods that provide data on two-dimensional structure only.
Resumo:
We produced choroidal neovascularization in the rhesus monkey by diminishing the blood supply to the inner retina and producing defects in Bruch's membrane by photocoagulation. The neovascular fronds which developed either infiltrated the subretinal space or proliferated through necrotic and gliotic retina into the vitreous cavity. Sequential electron microscopic sections of neovascular fronds in the subretinal space demonstrated that the advancing capillary sprouts were composed of primitive endothelial tubes surrounded by pericytes and enmeshed in a loose basement-membrane-like substance. More mature capillaris and displayed endothelial fenestrations and endothelial-pericyte membranous contacts. Large neovascular fronds developed major feeding vessels that closely resembled normal small choroidal arteries and veins. Retinal pigment epithelial cells in various guises were in constant association with proliferating neovascular networks.
Resumo:
When a subject is heated, the stimulation of temperature-sensitive nerve endings in the skin, and the raising of the central body temperature, results in the reflex release of sympathetic vasoconstrictor tone in the skin of the extremities, causing a measurable temperature increase at the site of release. In the sympathetic release test, the subject is gently heated by placing the feet and calves in a commercially available foot warming pouch or immersing the feet and calves in warm water and wrapping the subject in blankets. Skin blood flow is estimated from measurements of skin temperature in the fingers. Normally skin temperature of the fingers is 65-75 degrees F in cool conditions (environmental temperature: 59-68 degrees F) and rises to 85-95 degrees F during body heating. Deviations in this pattern may mean that there is abnormal sympathetic vasoconstrictor control of skin blood flow. Abnormal skin blood flow can substantially impair an individual's ability to thermoregulate and has important clinical implications. During whole body heating, the skin temperature from three different skin sites is monitored and oral temperature is monitored as an index of core temperature. Students determine the fingertip temperature at which the reflex release of sympathetic activity occurs and its maximal attainment, which reflects the vasodilating capacity of this cutaneous vascular bed. Students should interpret typical sample data for certain clinical conditions (Raynaud's disease, peripheral vascular disease, and postsympathectomy) and explain why there may be altered skin blood flow in these disorders.
Resumo:
The glycolytic enzyme triose phosphate isomerase from Schistosoma mansoni is a potential target for drugs and vaccines. Molecular modelling of the enzyme predicted that a Ser-Ala-Asp motif which is believed to be a helminth-specific epitope is exposed. The enzyme is dimeric (as judged by gel filtration and cross-linking), resistant to proteolysis and highly stable to thermal denaturation (melting temperature of 82.0°C). The steady-state kinetic parameters are high (Km for dihydroxyacetone phosphate is 0.51mM; Km for glyceraldehyde 3-phosphate is 1.1mM; kcat for dihydroxyacetone phosphate is 7800s(-1) and kcat for glyceraldehyde 3-phosphate is 6.9s(-1)).
Resumo:
Human B cell colonies were grown from peripheral blood of 12 patients with systemic lupus erythematosus (SLE) and from 12 healthy control subjects. The SLE group showed a large increase (p less than 0.001) in the number of colony forming cells (CFC) present in peripheral blood as compared with controls. The CFC were of the pre-B cell type. There was also a loss of OKT8+ cell inhibition of B cell colony growth in the SLE group compared with control subjects.
Resumo:
Hyperglycemia may contribute directly to pericyte loss and capillary leakage in early diabetic retinopathy. To elucidate relative contributions of glycation, glycoxidation, sugar autoxidation, osmotic stress and metabolic effects in glucose-mediated capillary damage, we tested the effects of D-glucose, L-glucose, mannitol and the potentially protective effects of aminoguanidine on cultured bovine retinal capillary pericytes and endothelial cells. Media (containing 5 mM D-glucose) were supplemented to increase the concentration of each sugar by 5, 10, or 20 mM. Subconfluent pericytes and endothelial cells were exposed to the supplemented media in the presence or absence of aminoguanidine (1 nM-100 µM) for three days. Cell counts, viability and protein were determined. For both cell types, all three sugars produced concentration-dependent decreases in cell counts and protein content (p
Resumo:
Experiments were undertaken to determine if nitric oxide (NO) plays a role in regulation of basal blood flow in the oral cavity of pentobarbital anesthetized cats and, if so, to quantify this effect using dose-response relationships. Blood flow was continuously measured from the surface of the tongue and mandibular gingiva (laser-Doppler flowmetry) and from the lingual artery (ultrasonic flowmetry). Cardiovascular parameters also were recorded. Administration of the nonselective inhibitor of nitric oxide synthase (NOS), L-NAME (0.08-20 mg/kg i.v.), produced a dose-related increase of blood pressure associated with decreases of blood flow at all three measurement sites. Maximal blood flow depression of 50-60% was seen 30-60 min after administration of 1.25 mg/kg of L-NAME. D-NAME (1.25 mg/kg i.v.) was inactive at all sites. Subsequent administration of L-arginine partially reversed effects of L-NAME in the lingual artery and tongue, but not in the gingival circulation. The neuronally selective NOS inhibitor, 7-nitroindazole (7-NI, 30 mg/kg i.p.), was devoid of effect on any of the measured parameters. These results suggest that endothelial (but not neuronally derived) NO plays an important role in control of basal blood flow in oral tissues of the cat.
Resumo:
Epidemiological studies show that elevated plasma levels of advanced glycation end products (AGEs) are associated with diabetes, kidney disease, and heart disease. Thus AGEs have been used as disease progression markers. However, the effects of variations in biological sample processing procedures on the level of AGEs in plasma/serum samples have not been investigated. The objective of this investigation was to assess the effect of variations in blood sample collection on measured Ne_(carboxy-methyl)lysine (CML), the best characterised AGE, and its homolog, Ne_(carboxyethyl)lysine (CEL). The investigation examined the effect on CML and CEL of different blood collection tubes, inclusion of a stabilising cocktail, effect of freeze thaw cycles, different storage times and temperatures, and effects of delaying centrifugation on a pooled sample from healthy volunteers. CML and CEL were measured in extracted samples by ultra_performance liquid chromatography-tandem mass spectrometry. Median CML and CEL ranged from 0.132 to 0.140 mM/M lys and from 0.053 to 0.060 mM/M lys, respectively. No significant difference was shown CML or CEL in plasma/serum samples. Therefore samples collected as part of epidemiological studies that do not undergo specific sample treatment at collection are suitable for measuring CML and CEL.