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Biomedical subjects

N Kovacevic

Publications and source records attributed to N Kovacevic.

At least 19 recordsLinked to original sources
PubMed2005

Evaluation of the anti-inflammatory and cytotoxic activities of naphthazarine derivatives from Onosma leptantha.

The root extracts of Onosma leptanhtha were evaluated for their anti-iflammatory and cytotoxic activities. The cyclohexane extract, which appeared as the most active in both assays, has been further subjected to bioassay-directed fractionation to afford the naphthazarine derivatives: beta,beta-dimethylacrylshikonin (1), isovalerylshikonin (2) and acetylshikonin (3). The evaluation of the anti-inflammatory activity was performed on carrageenan-induced rat paw edema test. All the tested compounds proved to be active, while compound 3 showed the best anti-inflammatory effect. In addition, the cytotoxic activity of the extracts and isolated compounds, was also assayed against L1210 murine lymphoblastic leukemia cell line, and human fibrosarcoma HT-1080 cells. Compound 1 exhibited remarkable cytotoxic activity (390 nM for L1210 cells), which is superior to that of shikonin, which was used as control.

Animals↗
PubMed2004

Semiautomatic brain region extraction: a method of parcellating brain regions from structural magnetic resonance images.

Structural MR imaging has become essential to the evaluation of regional brain changes in both healthy aging and disease-related processes. Several methods have been developed to measure structure size and regional brain volumes, but many of these methods involve substantial manual tracing and/or landmark identification. We present a new technique, semiautomatic brain region extraction (SABRE), for the rapid and reliable parcellation of cortical and subcortical brain regions. We combine the SABRE parcellation with tissue compartment segmentation [NeuroImage 17 (2002) 1087] to produce measures of gray matter (GM), white matter (WM), ventricular CSF, and sulcal CSF for 26 brain regions. Because SABRE restricts user input to a few easily identified landmarks, inter-rater reliability is high for all volumes, with all coefficients between 0.91 and 0.99. To assess construct validity, we contrasted SABRE-derived volumetric data from healthy young and older adults. Results from the SABRE parcellation and tissue segmentation showed significant differences in multiple brain regions in keeping with regional atrophy described in the literature by researchers using lengthy manual tracing methods. Our findings show that SABRE is a reliable semiautomatic method for assessing regional tissue volumes that provides significant timesavings over purely manual methods, yet maintains information about individual cortical landmarks.

Adult↗
PubMed2002

A robust method for extraction and automatic segmentation of brain images.

A new protocol is introduced for brain extraction and automatic tissue segmentation of MR images. For the brain extraction algorithm, proton density and T2-weighted images are used to generate a brain mask encompassing the full intracranial cavity. Segmentation of brain tissues into gray matter (GM), white matter (WM), and cerebral spinal fluid (CSF) is accomplished on a T1-weighted image after applying the brain mask. The fully automatic segmentation algorithm is histogram-based and uses the Expectation Maximization algorithm to model a four-Gaussian mixture for both global and local histograms. The means of the local Gaussians for GM, WM, and CSF are used to set local thresholds for tissue classification. Reproducibility of the extraction procedure was excellent, with average variation in intracranial capacity (TIC) of 0.13 and 0.66% TIC in 12 healthy normal and 33 Alzheimer brains, respectively. Repeatability of the segmentation algorithm, tested on healthy normal images, indicated scan-rescan differences in global tissue volumes of less than 0.30% TIC. Reproducibility at the regional level was established by comparing segmentation results within the 12 major Talairach subdivisions. Accuracy of the algorithm was tested on a digital brain phantom, and errors were less than 1% of the phantom volume. Maximal Type I and Type II classification errors were low, ranging between 2.2 and 4.3% of phantom volume. The algorithm was also insensitive to variation in parameter initialization values. The protocol is robust, fast, and its success in segmenting normal as well as diseased brains makes it an attractive clinical application.

Adult↗
PubMed1996

Instrumented implant for measuring tibiofemoral forces.

Experimental measurement of loads occurring in the human knee joint will allow validation of analytical models and provide data for the design of total knee implants. A customized transducer was developed to measure the dynamic tibiofemoral force and center of pressure after total knee arthroplasty. The transducer consists of a standard tibial component to which four uniaxial load cells and an additional tibial tray have been added. The transducer was calibrated using a loading device traceable to the National Institute of Standards and Technology (NIST). The transducer was accurate to within 1% in magnitude, 0.07 mm in medial/lateral location and 0.24 m in anterior/posterior location.

Calibration↗
PubMed1987

Elevated somatostatin in pancreatic islets of adrenalectomized dogs.

We have observed both hyperglucagonemia and hypoinsulinemia in adrenalectomized (Adx) dogs. To determine whether these hormonal alterations are related to changes in distribution of islet hormones in the pancreas, we examined the concentration and total mass of insulin, glucagon, and somatostatin in the head, body, and tail of the pancreas by immunoassay and immunocytochemistry. We studied 6 normal dogs, 5 Adx dogs deprived of cortisol for 24 h (Adx I) and 5 for 48-72 h (Adx II). In normal dogs, single and double immunocytochemical staining showed that, in contrast to some other species, B (insulin) cells are mostly in the central region of islet, whereas A (glucagon) and D (somatostatin) cells are distributed randomly. This topographic distribution was not altered by adrenalectomy. In normal dogs, insulin concentration (micrograms per g) and total mass (micrograms) were higher in the tail (174 +/- 22, 2001 +/- 396) and body (165 +/- 22, 2850 +/- 600) than in the head (91 +/- 17, 668 +/- 156) of pancreas. Glucagon concentration (micrograms per g) and total mass (micrograms) were 17 +/- 2, 178 +/- 17 in the tail; 9.5 +/- 2, 158 +/- 32 in the body, and negligible (0.78 +/- 0.32, 7 +/- 3) in the head, whereas somatostatin concentration (micrograms per g) and total mass (micrograms) were 0.58 +/- 0.26, 4.20 +/- 1.5 in the T, 0.23 +/- 0.10, 3.9 +/- 1.6 in the B, and 0.22 +/- 0.05, 1.8 +/- 0.6 in the H. The striking finding was that adrenalectomy caused large increases in somatostatin in all three regions of pancreas in both Adx I and Adx II. The total mass of somatostatin in Adx I and Adx II increased 4-fold in the tail (P less than 0.02-0.005), 5-fold in the body (P less than 0.01-0.001), and 7-9-fold in the head (P less than 0.05-0.005) and concentration increased 6-fold in the body (P less than 0.005) and 7- to 8-fold in the head (P less than 0.01-0.001). There were no significant changes in the content of insulin and glucagon after adrenalectomy. Plasma concentration of glucagon increased by 50% in Adx I (P less than 0.005) and 70% in Adx II (P less than 0.02), insulin decreased by 39% (P less than 0.005), 23% (NS), respectively, and somatostatin increased by 258% (P less than 0.001) in Adx II. Thus the adrenal glands appear to play an important role in regulation of the content of somatostatin in pancreatic islets.

Adrenalectomy↗
PubMed1986

Glucoregulation in alloxan-diabetic dogs.

In order to establish whether a prolonged subnormal secretion of insulin may affect glucoregulation against hypoglycemic stimuli, the level of plasma glucose was decreased in alloxan-diabetic dogs by the infusion of either 50 micrograms/kg . min phlorizin (PHL), ie, reducing the concentration of plasma glucose without hyperinsulinemia; or with 7 mU/kg . min insulin (combined hyperinsulinemia and hypoglycemia). The concentration of glucose, immunoreactive glucagon (IRG), and insulin (IRI) and catecholamines were followed in the plasma. Hepatic glucose production (Ra) and the overall rate of glucose removal from the circulation were calculated by a tracer method. During a 200-minute infusion of PHL plasma glucose fell from 328 +/- 29 to 114 +/- 16 mg/dl, while IRG rose from a mean of 470 +/- 123 to 623 +/- 200 pg/mL, however this increase was significant only in 3 out of 6 dogs. There was no change in the plasma level of epinephrine. Plasma IRI decreased significantly, the IRI/IRG ratio remained low, and Ra did not increase. When the animals were treated with insulin for one week, plasma glucose was restored to normal, while plasma IRI and the IRI/IRG ratio were raised above the normal level. Under these circumstances the infusion of PHL increased plasma IRG significantly from 59 +/- 5 to 110 +/- 32 pg/mL, decreased IRI slightly, and increased Ra by an average of 50 +/- 16%. No measurable change in plasma glucose was observed indicating the restoration of nonhypoglycemic glucoregulation. In diabetic dogs during a 95-minute infusion of insulin, plasma glucose dropped from a mean of 338 +/- 5 to 74 +/- 24 mg/dL.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1985

Modification of the pattern of central neurons by sensory inputs from the reproductive organs in Aplysia depilans L.

In the abdominal ganglion of Aplysia a number of motoneurons regulating visceral organs reacted to the stimulation of the reproductive organs. The response was mostly biphasic and often delayed. The multifunctional interneuron I (cell L10) reacted to the stimulation of the reproductive organs with burst firing, followed by an inhibitory phase. The interneuron II, involved in the regulation of visceral functions, was also activated during stimulation of the reproductive organs and its burst-pattern could be identified on a number of other neurons. Several members of the neurosecretory cell group reacted to the stimulation of reproductive organs. The response was, as a rule, biphasic and similar to the hormone action, long-lasting. Three further cells (near the cell L12, above the cell L21, and the neuron between R2 and R7 with unknown function) showed a stereotyped response to the stimulation of the reproductive organs. All the neurons reacting to the stimulation of the reproductive organs also received inputs from the cardiorenal system. The data support the existence of common networks composing variable units in the regulation of visceral functions of gastropods.

Action Potentials↗
PubMed1983

Bending stiffness of unilateral and bilateral fixator frames.

The structural and geometric fixator properties that best neutralize the prevailing anteroposterior and transverse bending moments at a tibial fracture site were analyzed in anatomic specimens. Clinically and mechanically, anterior unilateral frames were most effective, particularly when applied with relatively stiff components with a maximal spread between the pins in each main bony fragment and with placement of the longitudinal rod close to the tibia.

Fracture Fixation↗
PubMed1981

Chromatographic pattern of extrapancreatic glucagon and glucagon-like immunoreactivity before and during stimulation by epinephrine and participation of glucagon in epinephrine-induced hepatic glucose overproduction.

To characterize the glucagon released in response to epineephrine in depancreatized dogs, plasma samples before and during epinephrine infusion were subjected to molecular-sieve chromatography on Bio-Gel P-30 columns. The chromatographic profile for extrapancreatic immunoreactive glucagon (eIRG) revealed two glucagon moieties of molecular weight 9,000 to 12,000. GLI of this molecular weight was released in response to epinephrine only under conditions of prevailing hyperglycemia. To determine if glucagon's participation in epinephrine-induced hepatic glucose overproduction in diabetes was dependent upon the degree of metabolic control, six conscious depancreatized dogs were infused with epinephrine or epinphrine plus somatostatin, under conditions of prevailing hyperglycemia or normoglycemia. Under normoglycemic conditions, epinephrine stimulated eIRG release, but there was a similar rise in hepatic glucose production (Ra) with or without glucagon suppression by somatostatin. Under hyperglycemic conditions, epinephrine stimulated eIRG and GLI release, and the rise in Ra was significantly greater with epinephrine than with epinephrine plus somatostatin infusion. Thus, under conditions of good metabolic control, epinephrine increased hepatic glucose production independently of glucagon, whereas with poor metabolic control, glucagon contributed to hepatic overproduction of glucose.

Animals↗
PubMed1977

Endocrine cells in oxyntic mucosa of a dog 5 years after pancreatectomy.

Immunofluorescence shows that the oxyntic mucosa of a dog depancreatized for 5 years and having a poorly-controlled diabetes has more glucagon- and somatostatin-containing cells than the mucosa of a control dog. At the ultrastructural level, 4 endocrine cell types are identified: A-, A-like, D- and enterochromaffin-like (ECL) cells, with increased numbers of A-, A-like and D-cells in gastric glands of the depancreatized dog, together with a higher concentration of immunoreactive glucagon in the gastric mucosa. The increase in A-, A-like and D-cells is compatible with: a) a change induced by the diabetic state itself; b) a hyperplasia secondary to the loss of corresponding pancreatic cells. At any rate, the fact that A-, A-like and D-cells increase parallely may indicate that these three cell types are functionally related one with another.

Animals↗
PubMed1976

Plasma glucagon in pups, decreased by fasting, unaffected by somatostatin or hypoglycemia.

In pups less than 4 days old, the mean basal plasma immunoreactive glucagon (IRG) level was about 3 times higher than in adult dogs. This high level decreased with age, and in pups older than 12 days the mean plasma IRG level did not differ from that in adults. Insulin-induced hypoglycemia did not raise plasma IRG concentration in young pups. Fasting decreased plasma IRG in young, but not in older pups. This decrease is consistent with the decrease in gluconeogenesis and in contrast to the metabolic adjustments observed in the adult organism. In pups less than 7 days old, both the pancreas and gastric mucosa contained considerably more IRG than the normal value reported for adult dogs. Gastroduodenal IRG was immunologically indistinguishable from pancreatic glucagon. In pups, somatostatin did not decrease the plasma concentration of either IRG or immunoreactive insulin (IRI) and caused no change in plasma glucose or in the rates of glucose production and utilization calculated from experiments with tracers. The experiments indicate that in pups the pancreatic and gastric alpha-cells are unresponsive to stimuli normally effective in grown dogs.

Age Factors↗