Evaluation of in vivo biological activity profile of isoorientin

Anti-nociceptive, anti-inflammatory and gastroprotective activities of the known C-glycosyl flavonoid, isoorientin, were studied in rats and mice. For the anti-nociceptive activity assessment the p-benzoquinone-induced writing test, for the anti-inflammatory activity the carrageenan-induced hind paw edema model in mice, and for the gastroprotective activity the EtOH-induced ulcerogenesis model in rats were used. Isoorientin was shown to possess significant anti-nociceptive and anti-inflammatory activities at 15 mg/kg and 30 mg/kg doses, without inducing any apparent acute toxicity as well as gastric damage. However, the compound did not possess any significant gastroprotective activity against EtOH-induced ulcerogenesis.     

The effects of n-3 polyunsaturated fatty acids by gavage on some metabolic enzymes of rat liver

In this experimental study, the effect of fish n-3 fatty acids was studied on the some important enzymes of carbohydrate metabolism, hexokinase (HK), glucose-6-phosphate dehydrogenase (G6PD), 6-phosphogluconate dehydrogenase (6PGD), lactate dehydrogenase (LDH), and malate dehydrogenase (MDH) in rat liver. Wistar albino rats of experimental group (n= 9) were supplemented fish omega-3 fatty acids (n-3 PUFA) as 0.4 g/kg bw. by gavage for 30 days in addition to their normal diet. Isotonic solution was given to the control group (n= 8) by the same way. At 30th day, the rats were killed by decapitation under ether anesthesia, autopsied and liver was removed. Spectrophotometric methods were used to determine the activities of above-mentioned enzymes in the liver. The n-3 PUFA caused increases in the activities of HK, G6PD, LDH, and MDH in comparison with control. These increases were statistically significant (P < 0.01) except 6PGD activity. As a result, n-3 PUFA may regulate the metabolic function of liver effectively by increasing HK, G6PD, 6PGD, LDH, and MDH enzyme activities of rat liver when added in enough amounts to the regular diet.     

Evaluation of a new biosensor-based mushroom (Agaricus bisporus) tissue homogenate: investigation of certain phenolic compounds and some inhibitor effects

A biosensor based on mushroom tissue homogenate for detecting some phenolic compounds (PCs) and usage of the biosensor for quantifying certain substances that inhibit the polyphenol oxidase activity in mushroom (Agaricus bisporus) tissue homogenate is described. The mushroom tissue homogenate was immobilized to the top of a Clark-type oxygen electrode with gelatin and glutaraldehyde. Optimization of the experimental parameters was done by buffer system, pH, buffer concentration, and temperature. Besides, the detection range of eight phenolic compounds were obtained with the help of the calibration graphs. Thermal stability, storage stability, and repeatability of the biosensor were also investigated. A linear response was observed from 20 x 10(-3) to 200 x 10(-3) mM phenol. The biosensor retained approximately 74% of its original activity after 25 days of storage at 4 degrees C. In repeatability studies, variation coefficient (C.V.) and standard deviation (S.D.) were calculated as 2.44% and +/-0.002, respectively. Inhibition studies revealed that the proposed biosensor was applicable for monitoring benzoic acid and thiourea in soft drinks and fruit juices.     

Duration of diastole and its phases as a function of heart rate during supine bicycle exercise

The duration of diastole can be defined in terms of mechanical events. Mechanical diastolic duration (MDD) is comprised by the phases of early rapid filling (E wave), diastasis, and late atrial filling (A wave). The effect of heart rate (HR) on diastolic duration is predictable from kinematic modeling and known cellular physiology. To determine the dependence of MDD of each phase and the velocity time integral (VTI) on HR, simultaneous transmitral Doppler flow velocities and ECG were recorded during supine bicycle exercise in healthy volunteers. Durations, peak values, and VTI using triangular approximation for E- and A-wave shape were measured. MDD, defined as the interval from the start of the E wave to end of the A wave, was fit as an algebraic function of HR by MDD=BMDD + MLMDD.HR + MIMDD/HR, derivable from first principles, where BMDD is a constant, and MLMDD and MIMDD are the constant coefficients of the linear and inverse HR dependent terms. Excellent correlation was observed (r2=0.98). E- and A-wave durations were found to be very nearly independent of HR: 100% increase in HR generated only an 18% decrease in E-wave duration and 16% decrease in A-wave duration. VTI was similarly very nearly independent of HR. Diastasis duration closely tracked MDD as a function of HR. We conclude that the elimination of diastasis and merging of E and A waves of nearly fixed durations primarily govern changes in MDD. These observations support the perspective that E- and A-wave durations are primarily governed by the rules of mechanical oscillation that are minimally HR dependent.     

Molecular characterization of an Arabidopsis gene encoding a phospholipid-specific inositol polyphosphate 5-phosphatase

Phosphoinositides are important molecules that serve as second messengers and bind to a complex array of proteins modulating their subcellular location and activity. The enzymes that metabolize phosphoinositides can in some cases serve to terminate the signaling actions of phosphoinositides. The inositol polyphosphate 5-phosphatases (5PTases) comprise a large protein family that hydrolyzes 5-phosphates from a variety of inositol phosphate and phosphoinositide substrates. We previously reported the identification of 15 putative 5PTase genes in Arabidopsis and have shown that overexpression of the At5PTase1 gene can alter abscisic acid signaling. At5PTase1 and At5PTase2 have been shown to hydrolyze the 5-phosphate from inositol phosphate substrates. We have examined the substrate specificity of the At5PTase11 protein, which is one of the smallest predicted 5PTases found in any organism. We report here that the At5PTase11 gene encodes an active 5PTase enzyme that can only dephosphorylate phosphoinositide substrates containing a 5-phosphate. In addition to hydrolyzing known substrates of 5PTase enzymes, At5PTase11 also hydrolyzes the 5-phosphate from phosphatidylinositol (3,5) bisphosphate. We also show that the At5PTase11 gene is regulated by abscisic acid, jasmonic acid, and auxin, suggesting a role for phosphoinositide action in these signal transduction pathways.     

Long-term follow-up of total penile reconstruction with sensate osteocutaneous free fibula flap in 18 biological male patients

Surgical reconstruction of the penis is challenging because of the many cosmetic and functional (e.g., sexual intercourse and voiding) requirements that must be addressed. Since the free sensate osteocutaneous fibula flap was first described for total penile reconstruction in 1993 it has been widely accepted, with its advantages and minimal shortcomings. In this article, the authors present the longest follow-up of biologically male patients with free fibular phalloplasties. Since 1994, 18 biologically male patients with total penile losses for various reasons were treated with free sensate osteocutaneous fibula flaps. All patients were included in the study. The ages of the patients ranged between 20 and 26 years (mean, 22.2 years). The average follow-up period was 5.4 years (range, 1 to 9 years). Patient satisfaction was evaluated by a questionnaire regarding both quality of orgasm and daily activities. Conventional radiographic imaging, magnetic resonance imaging, and bone mineral densitometry were performed to evaluate the fate of the bony component of the flap. Also, sensibility was evaluated by bulbocavernous reflex and penile somatosensory evoked potentials testing in nine patients. Six patients married, and five of them had six children. Most patients and their partners reported pleasurable sexual intercourse and orgasm. Conventional radiographs of the fibular bone in neophalluses showed robust, calcified bone structure without any evidence of bone resorption or fracture. The magnetic resonance images showed the cortical substance and spongiosum of the bone marrow, which are characteristic signs of bone viability. After intravenous injection of gadolinium, the neophallus bone showed uptake of contrast medium. Viability of neophallus bone was shown even at 9-year follow-up (the longest follow-up in the literature). Dual energy x-ray absorptiometry measurements of the penile bone grafts showed that fibular components in the penis had bone mineral density values that were close to but lower than those of intact fibula in the same subjects. These results were considered as evidence of viability of bone grafts. Neural integrity was found between the nerves of the neophallus and the residual penile bodies by both bulbocavernous reflex and penile somatosensory evoked potentials tests. In conclusion, free sensate fibula flap phalloplasty provides the cosmetic and functional requirements that an ideal penis should have. All results put an end to the discussion that the fibular component of the neophallus could resorb. Constitution of neural integrity is important in terms of pleasurable sexual intercourse. The authors believe the free sensate osteocutaneous fibula flap should be considered as the standard in penile reconstruction.     

The descending branch of the superficial circumflex artery supplying anteromedial thigh skin

This report presents an extended groin flap design that consists of a conventional skin paddle in the groin region and a vertical extension in the anteromedial thigh region, based on the superficial iliac circumflex artery and an unnamed descending branch, respectively. The inferior branch of the superficial iliac circumflex artery that supplies the thigh extension of the flap, spanning approximately the upper half of the thigh region, was found to originate approximately 2 cm from the origin of the superficial iliac circumflex artery. A total of six free and four local flaps were used in 10 patients with ages ranging from 10 to 60 years (average, 45 years). There were six male and four female patients. The free flaps were required for total facial resurfacing, through-and-through cheek defect, and burn scar contractures and traumatic defects of the lower extremity. The local flaps were used for reconstruction of scrotum defect, trochanteric decubitus ulcer, and lower abdominal skin and fascia defects. All 10 flaps survived completely. The groin flap with anteromedial thigh extension offers the following advantages: (1) it is very easy and quick to elevate; (2) a significantly increased volume of tissue is available for reconstruction, based on one axial vessel and being completely reliable; (3) the flap offers two skin paddles that are independently mobile; (4) there is no need for positional change and a two-team approach is possible; and (5) it can be raised as a vertical skin island only. The authors conclude that the groin flap with anteromedial thigh extension is a useful modification for reconstruction of both distant and local defects.     

D-Serine as a putative glial neurotransmitter

Abundant recent evidence favors a neurotransmitter/neuromodulator role for D-serine. D-serine is synthesized from L-serine by serine racemase in astrocytic glia that ensheath synapses, especially in regions of the brain that are enriched in NMDA-glutamate receptors. D-serine is more potent than glycine at activating the 'glycine' site of these receptors. Moreover, selective degradation of D-serine but not glycine by D-amino acid oxidase markedly reduces NMDA neurotransmission. D-serine appears to be released physiologically in response to activation by glutamate of AMPA-glutamate receptors on D-serine-containing glia. This causes glutamate-receptor-interacting protein, which binds serine racemase, to stimulate enzyme activity and D-serine release. Thus, glutamate triggers the release of D-serine so that the two amino acids can act together on postsynaptic NMDA receptors. D-serine also plays a role in neural development, being released from Bergmann glia to chemokinetically enhance the migration of granule cell cerebellar neurons from the external to the internal granular layer.     

Thermodynamic phase plane analysis of ventricular contraction and relaxation

Background  

Ventricular function has conventionally been characterized using indexes of systolic (contractile) or diastolic (relaxation/stiffness) function. Systolic indexes include maximum elastance or equivalently the end-systolic pressure volume relation and left ventricular ejection fraction. Diastolic indexes include the time constant of isovolumic relaxation - and the end-diastolic pressure-volume relation. Conceptualization of ventricular contraction/relaxation coupling presents a challenge when mechanical events of the cardiac cycle are depicted in conventional pressure, P, or volume, V, terms. Additional conceptual difficulty arises when ventricular/vascular coupling is considered using P, V variables.     

Tumour necrosis factor alpha, lipid peroxidation and NO* are increased and associated with decreased free-radical scavenging enzymes in patients with Weill-Marchesani syndrome

AIM: Weill-Marchesani syndrome (WMS) is a rare systemic disorder with both autosomal recessive and dominant inheritances. Accumulation of reactive oxygen species such as O2*-, H2O2 and OH* causes lipid peroxidation (LPO), whereas antioxidant enzymes (superoxide dismutase (SOD), glutathione peroxidase (GSHPx)) mediate defence against oxidative stress. Excess tumour necrosis factor (TNF)-alpha and NO* react with O2*- and cause further antioxidant depletion with an increase in mutation frequency by H2O2. This study investigated the levels of SOD, GSHPx, catalase (CAT), TNF-alpha, NO and LPO in patients with WMS. METHODS: A group of 10 WMS patients (four males, six females; age, 26.5+/-19.0 years) and 10 age-matched and sex-matched controls (five males, five females; age, 27.3+/-18.2 years) were included. Serum TNF-alpha levels were determined by a spectrophotometer technique using immulite chemiluminescent immunometric assay. Malondialdehyde (MDA) was determined in plasma; CAT in red blood cells (RBCs), and SOD and GSHPx in both plasma and RBCs. Total serum NO* levels were evaluated by Griess reaction. RESULTS: Mean levels of TNF-alpha (8.3+/-0.6 pg/ml) in WMS patients were significantly (p<0.001) higher than controls (4.3+/-0.2 pg/ml). Plasma MDA levels in patients and controls were 5.4+/-0.8 and 1.8+/-0.6 micromol/l, respectively, and the difference was significant (p=0.0002). SOD and GSHPx activities were significantly lower in both RBCs and plasma of WMS than in controls (RBC-SOD, 3981.9+/-626.6 versus 5261.6+/-523.0 U/g haemoglobin (Hb), p=0.0005; plasma-SOD, 529.4+/-49.3 versus 713.4+/-55.7 U/g protein, p=0.0002; RBC-GSHPx, 682.7+/-42.0 versus 756.5+/-47.6 U/g Hb, p=0.0011; plasma-GSHPx, 107.3+/-15.0 versus 131.4+/-19.7 U/g protein, p=0.0113). In addition, serum NO (NO*-2 + NO*-3) levels were also significantly (p = 0.0002) increased in WMS patients (54.4+/-5.7 versus 26.9+/-6.7 micromol/l). RBC-CAT levels were similar between groups (125.6+/-21.3 versus 131.0+/-21.5 k/g Hb, p = 0.8798). CONCLUSIONS: The elevated LPO, TNF-alpha and NO* with decreased antioxidant enzyme activities indicated impaired antioxidative defence mechanisms with an oxidative injury and cell toxicity in WMS patients. The use of multiple antioxidants and free radical scavengers might be helpful in this genetic disorder.