Stabilization of immature rice grain using infrared radiation.

Immature rice grain is one of the underutilized by-products of paddy milling process. Despite its high potential of use as a food ingredient, it is mainly utilized as feed due to the rancidity problem. In the present study, the composition of immature rice grain, the potential of using infrared (IR) radiation for stabilization, and the effects of IR stabilization on color, fatty acid composition, tocopherol and γ-oryzanol contents of the grain were investigated. The free fatty acid (FFA) value of the unprocessed immature rice grain was 5.49% and increased to 35.71% at the end of 3 months of storage at room temperature. However, FFA content of the grains stabilized with IR radiation at specific conditions remained unchanged throughout the storage period. Moreover, IR stabilization did not caused a negative effect on the noted components of the immature rice grain.

Mast cells: target and source of neuropeptides.

Mast cells, originating from bone marrow pluripotential cells are generally populated near to strategic locations of mammalian body. They store a wide variety of biologically active molecules in their granules and also can de novo synthesize an additional spectrum of mediators, depending on their microenvironment, phenotype and status. Mast cells have numerous receptors that can trigger a wide spectrum of cellular responses, some of them which can be preprogrammed against specific pathogens. Mast cells secrete mediators, go under total degranulation, or degranulate only some of the specific granules with required content according to the environmental conditions, pathogens or signaling molecules binding to their receptors. Mast cells are functionally multi faceted cells. A single cell can behave such as an immune cell, an endocrine cell and even as a sensorial neuron. In this context, mast cells can significantly influence inflammation, tissue remodeling, host defense and homeostasis. Specifically the mast cells proximal to nerve fibers, contain, secrete and respond to, several neuropeptides, suggesting many potential functions for mast cells in health and disease. Mast cells are target cells for neuropeptides and, they have distinct profiles of responsiveness to these molecules. This extends the flexibility of neurogenic signaling pathways via reciprocity. Those neuropeptides have direct and indirect effects on mast cells such as inducing or suppression of degranulation, triggering, modulation or amplification of mediator content and release. The exploration of interactions of mast cells and neurons is a promising field of study which may bring treatments to several diseases. Since mast cells seem to form the major link between neurons and inflammation via neuropeptides, mast cell and mast cell mediator connection may lead to a better understanding of the autocrine, paracrine, and neuro-immune-endocrine systems in physiology and physiopathology. Therefore, mast cell manipulator drug designs, capable of granular content modulation, with effects on, selective mediator release, activity and, ablation of mast cells, would be very beneficial for the treatment of various diseases that mast cells may be involved in.

Optimisation techniques in vaginal cuff brachytherapy.

The aim of this study was to explore whether an in-house dosimetry protocol and optimisation method are able to produce a homogeneous dose distribution in the target volume, and how often optimisation is required in vaginal cuff brachytherapy. Treatment planning was carried out for 109 fractions in 33 patients who underwent high dose rate iridium-192 (Ir(192)) brachytherapy using Fletcher ovoids. Dose prescription and normalisation were performed to catheter-oriented lateral dose points (dps) within a range of 90-110% of the prescribed dose. The in-house vaginal apex point (Vk), alternative vaginal apex point (Vk'), International Commission on Radiation Units and Measurements (ICRU) rectal point (Rg) and bladder point (Bl) doses were calculated. Time-position optimisations were made considering dps, Vk and Rg doses. Keeping the Vk dose higher than 95% and the Rg dose less than 85% of the prescribed dose was intended. Target dose homogeneity, optimisation frequency and the relationship between prescribed dose, Vk, Vk', Rg and ovoid diameter were investigated. The mean target dose was 99+/-7.4% of the prescription dose. Optimisation was required in 92 out of 109 (83%) fractions. Ovoid diameter had a significant effect on Rg (p = 0.002), Vk (p = 0.018), Vk' (p = 0.034), minimum dps (p = 0.021) and maximum dps (p<0.001). Rg, Vk and Vk' doses with 2.5 cm diameter ovoids were significantly higher than with 2 cm and 1.5 cm ovoids. Catheter-oriented dose point normalisation provided a homogeneous dose distribution with a 99+/-7.4% mean dose within the target volume, requiring time-position optimisation.

Changes in applicator positions and dose distribution between high dose rate brachytherapy fractions in cervix carcinoma patients receiving definitive radiotherapy.

This study examines the change of applicator geometry and its effect on rectal/rectum (R) and bladder (B) doses, and obtained radiobiological equivalent doses (RED), between each high dose rate (HDR) brachytherapy (BT) fraction in cervical carcinoma patients. BT using a tandem (T) and two ovoids (O) is included, and any discrepancies in applicator positions among the fractions were calculated. Whether the change of applicator position had an effect on the calculated R and B doses was analysed. Furthermore, the relationship between the size of tumour, the magnitude of displacement and the change in R and B doses was also investigated. Lastly, the changes in R and B RED were noted. The average magnitude of displacement was between 2.0 mm and 16.9 mm, showing time trend. There was no relationship between tumour size and the magnitude of discrepancy of Left O, Right O, T, R, B, and neither change in R and B doses (p>0.05). The mean differences of R and B doses were between 49-78 cGy, and 70-84 cGy, respectively. The magnitude of discrepancy and changes in doses showed no correlation (p>0.05). There were no significant differences in REDs for bladder (p = 0.8) and rectum (p = 0.2). In conclusion, there were significant differences in the applicator positions R and B and R and B doses among the fractions, which confirm the necessity of treatment planning in each HDR BT fraction. However, the total calculated R and B REDs did not show a remarkable difference.

Effects of sepsis on mast cells in rat dura mater: influence of L-NAME and VIP.

1. The influence of lipopolysaccharide (LPS)-induced sepsis on the various mast cell phenotypes of rat dura mater were examined both by immunohistochemical and biochemical methods. 2. Three different populations of mast cells were identified in control rats: connective tissue type mast cells (CTMC) which contain rat mast cell protease1 (RMCP1), histamine, serotonin and heparin, mucosal type mast cells (MMC) which contain RMCP2, histamine and serotonin, and intermediate type which contains both RMCP1 and RMCP2 and probably various proportions of amines and heparin. 3. LPS (25 mg kg(-1) i.p.) caused changes in the proportions of the various types of mast cells. The number of MMC and intermediate type mast cells significantly increased and the number of mast cells immunopositive for both heparin and serotonin significantly decreased. Biochemical analysis showed that the histamine concentration of dura increased while its serotonin concentration decreased. 4. While vasoactive intestinal peptide (VIP) (25 ng kg(-1) i.p.) appears to potentiate LPS effects on dura mater mast cells, non-selective inhibition of nitric oxide (NO) synthase by N(g)-nitro-L-arginine methyl ester (L-NAME) (30 mg kg(-1) i.p.) did not influence sepsis-induced mast cell changes. 5. These findings suggest that mast cells of dura mater may play a role in brain protection during sepsis.

Optimization in high dose rate brachytherapy for utero-vaginal applications.

BACKGROUND AND PURPOSE: High dose rate (HDR) remote afterloading intracavitary brachytherapy is an effective treatment modality which has some advantages over low dose rate (LDR) techniques for gynaecological cancer. Optimization is one of the possibilities of modern brachytherapy techniques, especially the stepping source technology. The use of the term 'optimization' implies achieving the desired optimum dose distribution by changing some parameters of the treatment. The aim of this study was to theoretically evaluate the optimization possibilities by modifying dwell times and dwell positions of the uterine and vaginal sources. MATERIALS AND METHODS: Working on a virtual utero-vaginal model, the dose distribution variations in the rectum, bladder, mean point B reference points and volume parameters were investigated whilst giving a standard dose to point A in the Manchester system. In this model, the intrauterine tandem consisted of 27 dwell positions for 2.5 mm steps and 14 dwell positions for 5 mm steps. Vaginal colpostats consisted of five dwell positions each for 2.5 mm steps. Using a Nucletron Plato treatment planning system and a Microselectron Ir-192 HDR stepping source unit, the dwell times of the intrauterine (T(u)) and vaginal sources (T(v)) were modified at the ratios of (T(u)/T(v)) 1:1; 1:2; 1:3; 1:4; 1:0.50; 1:0.33; and 1:0.25 for the two different dwell positions, 2.5 and 5 mm steps, of the intrauterine tandem. RESULTS: All evaluated parameters decreased with increasing dwell time ratios of uterine tandem to vaginal colpostats, with the greatest fall in the percentage of rectum reference dose (D(R) %), 23 and 28% for 2.5 and 5 mm dwell positions respectively; in addition, the reference isodose volume decreased by 14 and 17% for 2.5 and 5 mm dwell positions, respectively. All evaluated parameters increased with decreasing dwell time ratios of uterine tandem to vaginal colpostats for both dwell positions. The DR% of 1:1-1:4 (T(u)/T(v)) weightings showed an increase from 40.6 to 58.3 (44%) for 2.5 mm and from 49.2 to 67.5 (37%) for 5 mm dwell positions. The volume was increased by 27 and 37% for 2.5 and 5 mm dwell positions respectively. CONCLUSION: Modern brachytherapy techniques enable the individualization of treatments by optimization procedures in gynaecological brachytherapy applications. By altering the dwell time and position, some important changes in reference points, volume and treatment time can be achieved, whilst maintaining a standard dose to point A.

Effect of nitric oxide inhibition on rat liver ischemia reperfusion injury.

Objective: to determine the role of nitric oxide (NO) in rat liver ischemia reperfusion we examined the effects of competitive NO synthesis inhibitor L-nitro-arginine-methyl-ester (L-NAME) and NO precursor L-arginin. Methods: 46 Sprague-Dawley rats were divided into five groups. Group 1, sham operated; group 2, 30-min ischemia administered; group 3, 60-min reperfusion administered after ischemia; group 4, 50 mg/kg L-NAME was given i.v. immediately before reperfusion; group 5, 50 mg/kg L-NAME+250 mg/kg L-arginin was given i.v. immediately before reperfusion. At the end of the experiment, liver was removed and superoxide dismutase (SOD), catalase, and malondialdehyde (MDA) were measured, transaminases SGOT and SGPT were measured in sera. Liver was also evaluated histopathologically. Results: transaminase levels were the highest in ischemia reperfusion group. Transaminases in this group were high compared with sham, ischemia, L-NAME and L-arginin groups (***P<0.001, ***P<0.001, *P<0.05, *P<0.05, respectively). SOD activity was 29.8+4 U/mg protein in L-arginin group. This level was the lowest level in all groups. SOD activity in L-arginin group was lower than that of sham and ischemia reperfusion groups (**P<0.01, *P<0.05, respectively). There were no significant differences in catalase activity and MDA levels among groups. Tissue damage was significant in ischemia and ischemia reperfusion groups. Tissue damages in these groups were greater than that of sham group (***P<0.001). In L-NAME treated group, tissue damage was similar to sham group, and significantly less than ischemia reperfusion group and L-arginin group (**P<0.01). Conclusion: even though there was significant tissue damage, we have not observed oxidative stress in the length of ischemia reperfusion period that we have performed. Mechanism of this damage seems to be independent from lipid peroxidation. NO supplementation decreased SOD, but did not cause further tissue damage. NO may dispose O(2)(-) by formation of peroxynitrite. L-NAME did not change lipid peroxidation, but clearly reduced reperfusion injury.

Vasoactive intestinal peptide inhibits degranulation and changes granular content of mast cells: a potential therapeutic strategy in controlling septic shock.

Vasoactive intestinal peptide (VIP) has potent protective activity against sepsis and increases the survival rate of septic rats and mice. The present study was planned to evaluate the effect of VIP on mast cell activity, histamine and methylhistamine levels and oxidative stress in the liver and kidneys of septic rats. The effect of VIP was compared to that of nitric oxide synthesis inhibition, previously tested extensively in septic shock models, with doubtful benefit. The present study showed that endotoxic shock did not lead to oxidative stress in either liver or kidney of the rats. On the other hand, mast cells, based on their location, displayed functional heterogeneity to the septic insults. VIP possibly modulated the specific reactions of the tissues to mediators released from mast cells during septic shock. The most prominent effect of VIP as compared to nitric oxide synthesis inhibition was related to mast cells. In conclusion, the prevention of mast cell reactivity by VIP could be a potential therapeutic strategy in controlling septic shock.

The effect of stress and in vivo vasoactive intestinal peptide (VIP) treatment on the response of isolated rat aorta to norepinephrine, angiotensin II and vasopressin, and adventitial mast cells.

The effects of cold-restraint stress, repeated over 3 days, and treatment of rats with vasoactive intestinal peptide (VIP) on the contractile responses of isolated aorta to vasoconstrictors, and on aortic adventitial mast cells were investigated. Stress significantly reduced the contractile response of rat aorta smooth muscle to norepinephrine (NE), angiotensin II (Ang II) and vasopressin (VP). Decreased sensitivity to NE, Ang II and VP may result from decreased receptor density, and affinity or reduced effector efficacy. Stress induced degranulation, decreased the number and changed the granular content of mast cells; all degranulated mast cells were stained with alcian blue, and the percentage of safranin staining cells was decreased. Given prior to stress, VIP reversed the reduced contractile responses and sensitivity of aorta to NE and Ang II but had no effect on VP subsensitivity. VIP also inhibited stress-induced degranulation of mast cells, and after VIP only alcian blue-stained mast cells were seen. When VIP was given to non-stressed rats, the contractile response of the aorta to NE, but not Ang II or VP, was increased compared with control. Mast cell count was decreased in the adventitia of non-stressed VIP treated rats. The results indicate that stress decreases the heparin content of mast cells and VIP has an additive effect. In conclusion, VIP modulates both stress-induced mast cell activity and reduced sensitivity of aorta smooth muscle to NE and Ang II. It can be suggested that VIP may moderate some effects of stress on vascular pathophysiology.

Ovarian, uterine and brain mast cells in female rats: cyclic changes and contribution to tissue histamine.

Using histochemical techniques, we determined mast cell content in ovarian, uterine and brain tissues throughout the estrus cycle of the rat. In one series of experiments, 26 cycling female rats were used for the measurement of follicle stimulating hormone (FSH) in plasma and evaluation of mast cells in the tissues. In a second series, cycling female rats were used for the determination of tissue histamine. The number, degranulation pattern and staining characteristics of mast cells changed synchronously in rat ovarian, uterine and brain tissues during the estrus cycle. A great majority of mast cells in tissues were stained by Alcian blue at proestrus and metestrus. Safranin-stained mast cells were abundant in all tissues during estrus and diestrus. Alcian blue-stained mast cells contribute to the change of tissues histamine level. In ovarian tissue, histamine level increased significantly at proestrus and metestrus. The lowest ovarian histamine level was determined at estrus, in which virtually all mast cells were stained by safranin only. Mast cells in ovarian, uterine and brain tissues seem to change their histamine content throughout the estrus cycle. Mast cells are absent from the thalamus during proestrus and are present in the hypothalamus only during the estrus phase. Plasma FSH concentrations (mlU ml-1) did not significantly change throughout the estrus cycle (proestrus: 0.81 +/- 0.11, estrus: 0.69 +/- 0.07, metestrus: 0.82 +/- 0.13, diestrus: 0.67 +/- 0.19).

A phase II trial, feasibility of combination of daily cisplatinum and accelerated radiotherapy via concomitant boost in stage III non-small cell lung cancer.

PURPOSE: A prospective phase II trial was conducted by the Institute of Oncology, Istanbul University in December 1994 on patients with locally-advanced non-small cell lung cancer to assess acute toxicity and the feasibility of a combination of radiosensitizer and accelerated radiotherapy with concomitant boost. MATERIALS AND METHODS: Patients were irradiated using 'large' fields (primary tumour and locoregional lymph nodes) with 1.8 Gy per fraction, five fractions a week. Reduced 'boost' fields (primary and involved nodes only) were also irradiated twice-weekly 1.8 Gy per fraction in ten fractions concomitantly 6 h after the administration of large field. Total radiation dose was 63 Gy in 5 weeks (45 Gy 'large' fields and 18 Gy 'boost'). The maximum allowed dose to the spinal cord was 3750 cGy. Cisplatinum, 6 mg/m2 was given daily just before 'large' field irradiation. RESULTS: As of January 1997, 15 patients were evaluated (median follow-up of 12.5 months with a range of 5.5-23 months). The overall acute toxicity rate was 38% and Grade 3 acute toxicity was 8%. Grade 4 or greater acute toxicities were not observed. The overall rate of cisplatinum-induced nausea and vomiting was 80% (severe in 60%), but all were easily treated with antiemetics. Complete response rate (clinical and radiological) was 40% and an overall response rate was 73%. Median survival was 16 months and progression-free survival was 5.5 months (range of 2.5-21 months). CONCLUSIONS: Toxicity was well tolerated and no treatment-related death occurred with this combined treatment regimen. Although it appears that better local control rates can be achieved, additional phase II/III studies are needed.

The protective effect of vasoactive intestinal peptide (VIP) on stress-induced gastric ulceration in rats.

The pathogenesis of cold-restraint stress ulcer involves various factors and is not completely understood. Mast cell degranulation, increased gastric muscular contractility, diminished mucosal blood flow, release of several biogenic amines, activated polymorphonuclear leukocytes, and lipid peroxidation which results from toxic oxygen molecules were suggested to be related to the production of gastric damage by cold-restraint stress. Recent evidence strongly indicates that VIP has a modulatory effect on tissue injury. Sprague-Dawley rats were used in two series of experiments. One set of rats was exposed to cold-restraint stress with some of the rats pretreated with VIP. The second set of rats was exposed to cold-restraint stress and then was administered VIP for different durations. Cold-restraint stress induced gastric lesions and mast cell degranulation and also increased lipid peroxidation in gastric tissue. VIP prevented stress-induced ulcers and mast cell degranulation and protected gastric tissue from lipid peroxidation. When VIP was used after induction of stress ulcer it was therapeutically beneficial. Thanks to its antioxidant and anti-inflammatory activity, VIP can be valuable in the prevention of gastric mucosal damage induced by cold-restraint stress.

Ischemic-reperfused rat skeletal muscle: the effect of vasoactive intestinal peptide (VIP) on contractile force, oxygenation and antioxidant enzyme systems.

The effect of vasoactive intestinal peptide (VIP) on the nerve-stimulated contraction, tissue oxygenation, lipid peroxidation and antioxidant enzymes activities-superoxide dismutase and catalase was investigated in the rat gastrocnemius muscle exposed to 4 h ischemia-4hr reperfusion. Ischemia caused significant decrease in muscle contractile force, oxygenation and superoxide dismutase enzyme activity. Reperfusion of ischemic muscle increased the muscle contractile force and restored the tissue oxygenation to the baseline level. Superoxide dismutase and catalase activities of reperfused muscle increased significantly. However neither ischemia nor reperfusion affected gastrocnemius muscle malondialdehide (MDA) levels. VIP administration at the onset of reperfusion significantly increased skeletal muscle contractile force and tissue oxygenation even higher than baseline and reperfusion values. VIP also normalized the increased superoxide dismutase and catalase activities of reperfused skeletal muscle. In conclusion, VIP, acting as a powerful antioxidant and preserving contractile machinery seems to be a promising endogenous peptide that can salvage the skeletal muscle from severe ischemia-reperfusion injury.

The effect of vasoactive intestinal peptide (VIP) on the testicular tissue histamine level of immobilized + cold stressed rats.

The effects of VIP on testicular tissue histamine level of stressed (immobilization and cold) rats were investigated. Sixteen Sprague-Dawley adult male rats were used and divided into three groups. Testicular tissue histamine was measured by HPLC. Stress caused a significant increase in the testicular tissue histamine level. VIP treatment decreased histamine to baseline.

Relaxing effects of vasoactive intestinal peptide (VIP) on the contractile actions of endothelin-3, histamine, and acetylcholine in isolated guinea pig tracheal smooth muscle with or without epithelium.

The role of VIP on the contractile effects of endothelin-3 (ET-3) (10(-8) M) or a combination of ET-3 plus histamine (Hist) (10(-5) M) or ET-3 plus acetylcholine (Ach) (10(-5) M) were investigated in guinea pig isolated tracheal smooth muscle. Strips of guinea pig trachea, in some of which the epithelium had been removed mechanically, were suspended in organ chambers and isometric tension was recorded. ET-3 contracted the tracheal smooth muscle in a dose-dependent manner ranging from 2 x 10(-12) to 2 x 10(-8) M. The removal of the epithelium significantly potentiated the ET-3-induced contractions. VIP significantly relaxed ET-3 contractile responses about 46 +/- 12% for the intact trachea (p < 0.05) and 39 +/- 6% for the rubbed trachea (p < 0.05). The removal of the epithelium did not significantly change the relaxation effect of VIP on ET-3-induced contraction of guinea pig isolated tracheal smooth muscle. On the other hand, the presence of tracheal epithelium was required for VIP (10(-8)) relaxation in Hist (10(-5)) contracted trachea. Apart from this finding, other Hist and all Ach-induced contractions (10(-5)) of the trachea were not significantly affected by ET-3 (10(-8)) or VIP treatments with or without epithelium. These findings indicate that VIP may play a role in inhibiting the contractile actions of ET-3 in guinea pig trachea and that an intact epithelium is not required for the relaxation but it is required for the VIP relaxation of Hist-induced contraction.

The effect of vasoactive intestinal peptide (VIP) on mast cell invasion/degranulation in testicular interstitium of immobilized + cold stressed and beta-endorphin-treated rats.

The effect of VIP on mast cell invasion/degranulation in testicular interstitium of stressed (immobilization and cold) and beta-endorphin-treated rats were investigated. Fifty-three Wistar male rats were used in four series of experiments. Initially, the effect of immobilization and cold stress on mast cell invasion and degranulation in testicular interstitium was examined in three age group of rats: 15 (n = 6), 30 (n = 6), and 45 (n = 7) days of age. Five animals per age group were used as controls. Because the most obvious effect of the stress on mast cell invasion/degranulation in testicular interstitium was observed in 45-day-old rats, the action of VIP in stressed and beta-endorphin-treated rats was only investigated at this age group. Mast cells and Leydig cells were evaluated by using histochemical and light microscopic protocols. Stress caused mast cell accumulation and degranulation in the testicular interstitium. Stress decreased heparin synthesis and possibly increased histamine content of mast cells. The effect of beta-endorphin was not as high as seen with stress. In some areas of testicular interstitium of stressed rats, there were aplasic and/or inactive Leydig cells. VIP inhibited proliferation and degranulation of mast cells, increased heparin content of the cells, and protected Leydig cells. By way of mast cell accumulation and degranulation in the testicular interstitium, exposure to stress may lead to Leydig cell damage and infertility. VIP may be involved in the protection of normal testicular function under stress conditions.

The effect of vasoactive intestinal peptide (VIP) on superoxide dismutase and catalase activities in renal tissues of rats exposed to hemorrhagic ischemia-reperfusion.

The effect of vasoactive intestinal peptide (VIP) on the activities of superoxide dismutase and catalase was investigated in renal tissues of rats exposed to 30% hemorrhage followed by reperfusion. In addition to enzyme activities, renal tissues were also histologically evaluated. Thirty percent hemorrhage had no significant effect on the activity of either enzyme. Reperfusion altered the activity of renal catalase but not of superoxide dismutase. On the other hand, administration of VIP (25 ng.kg-1) together with shed blood retransfusion protected the renal tissue from hemorrhagic ischemia-reperfusion injury without increasing superoxide dismutase and catalase activity. These results seem to be related either to the inhibitory effect of VIP on production or quenching activity of some reactive oxygen species. In conclusion, VIP may be a novel promising therapeutic approach toward defenses against hemorrhagic ischemia-reperfusion injury as an antioxidant.