Microsurgical and fiber tract anatomy of the interthalamic adhesion.

OBJECTIVE: The authors of this study aimed to define the microanatomy of the interthalamic adhesion (ITA) using microfiber dissection, magnetic resonance (MR) tractography, and histological analysis. METHODS: Sagittal, coronal, and axial MR images from 160 healthy individuals 2-82 years of age were examined. The relationships between age range and ITA morphology as well as between gender and ITA morphology were evaluated statistically. Among these 160 individuals, 100 who had undergone MR tractography were examined. In this group, the presence of fiber tracts in the ITA and the relationship with ITA morphological types were examined. Thirty formalin-fixed human cadaveric brains were also examined endoscopically, and 6 hemispheres were dissected from the medial to lateral and superior to inferior directions under the microscope. Sections taken from one of the brains with an ITA type 2 with both thalami were examined histologically. Anti-neurofilament antibody was used in the histological examination. RESULTS: Four morphological types of ITA were observed. Type 1 had an adhesion/adherent appearance, type 2 had a bridge/commissure appearance, type 3 showed no adhesion, and type 4 had a double bridge. Tractographic examination revealed that 28% had no fiber tract transition in the ITA, 21% had a significant transition, and 51% had an indistinct transition. Statistically, the presence of the ITA was significantly higher in the pediatric (age) and female (gender) groups. In specimens with ITAs of a bridge/commissure appearance (type 2), fiber tracts showed clear transitions between thalami. In type 1 (adherent/adhesive appearance), fiber tracts were observed within the ITA, but a reciprocal transition was unclear. Dissection showed that these fiber tracts in the ITA reach the nucleus accumbens, caudate nucleus, and frontoorbital region anteriorly and the lateral habenula and posterior commissure posteriorly. Some fibers also joined the ansa peduncularis. In histological studies, axonal fibers moving in the ITA were observed with anti-neurofilament antibody staining. CONCLUSIONS: This is the first study to demonstrate fiber tracts of the ITA through fiber dissection and transillumination techniques as well as radiological and histological study. Statistical data were obtained by comparing the morphological group with age and gender groups. The anatomy of this structure, which has been neglected for many years, was reexamined. This study showed that the ITA has fibers connecting different parts of the brain, in contrast to previous studies suggesting that it was a simple massa.

Intake Duration of Anthocyanin-Rich New Zealand Blackcurrant Extract Affects Cardiovascular Responses during Moderate-Intensity Walking But Not at Rest.

We examined effects of intake duration of New Zealand blackcurrant (NZBC) extract on cardiovascular responses during supine rest and moderate-intensity walking. Recreationally active men (n = 15, age: 24 ± 6 yr, BMI: 24.7 ± 4.3 kg·m-2) volunteered in a randomized, cross-over design. One metabolic equivalent (1-MET) was measured (3.97 ± 0.66 mL·kg-1·min-1) and an incremental walking test was performed to individualize speed at 4 (n = 3) or 5 (n = 12) METs for the 30-min walk (5.7 ± 0.7 km·hr-1). NZBC extract (210 mg of anthocyanins) was taken with breakfast for 7 and 14 days, with a 14-days washout. The final dose was ingested 2-hr before recording of the cardiovascular responses (Portapres Model-2). At rest, %changes at 7- and 14-days intake were observed for stroke volume (+6.8% (trend), p = 0.065; +8.5%, p = 0.012), cardiac output (+10.1%, p = 0.007; +8.5%, p = 0.013), total peripheral resistance (-12.0%, p = 0.004; -13.1%, p = 0.011), diastolic (-5.7%, p = 0.045; -9.7%, p = 0.015) and mean arterial pressure (-4.4%, p = 0.040; -7.2%, p = 0.029), but without intake duration effect. During walking, %changes at 7- and 14-days intake were observed for stroke volume (+7.7% (trend), p = 0.063; +9.9%, p = 0.006), cardiac output (+8.7%, p = 0.037; +10.1%, p = 0.007), diastolic blood pressure (-6.2%, p = 0.042; -10.6%, p = 0.001), and total peripheral resistance (-9.6%, p = 0.042; -13.5%, p = 0.005) but without intake duration effect. During walking, %changes at 14-days were observed only for mean arterial pressure (-6.4%, p = 0.018) and arterio-venous oxygen difference (-7.9%, p = 0.019). NZBC extract affects cardiovascular responses at rest and during moderate-intensity exercise with 7- and 14-day intake. Only during moderate-intensity exercise, a longer intake of NZBC extract was required for an effect on some cardiovascular responses.

Comparison of the efficacy of silodosin and a terpene combination in the medical expulsive therapy of distal ureteral stones.

OBJECTIVE: We aimed to compare the efficacy of silodosin and a terpene combination in the treatment of distal ureteral stones. METHODOLOGY: The data of the patients admitted to the urology policlinic with renal colic, diagnosed with distal ureteral stones, and followed up with medical expulsive therapy between December 2017 and June 2018 were retrospectively reviewed. The patients were divided into two groups: Group 1 comprised 72 patients that received 8 mg/day silodosin and Group 2 consisted of 51 patients that were given three capsules of a terpene combination daily. The groups were compared in terms of the patients' demographic characteristics, medical history, localisation of the present stone, renal collecting system status, daily fluid intake, number of emergency service visits, number of additional analgesic applications needed, number of pain attacks, number of days off work, stone expulsion rate and time to stone expulsion. RESULTS: Of the total 123 patients, 98 (79.7%) were stone-free. The stone-free rate was 75.0% in Group 1 and 86.3% in Group 2, with no statistical difference between the two groups. However, the number of visits to the emergency service because of pain, number of additional analgesic applications required, number of days off work, and time to stone expulsion were statistically significantly lower in Group 2 than in Group 1. CONCLUSIONS: The treatment of distal ureteral stones with silodosin is as effective as the terpene combination. However, the terpene combination is more effective than silodosin in managing pain and accelerating stone expulsion.

No Effects of Different Doses of New Zealand Blackcurrant Extract on Cardiovascular Responses During Rest and Submaximal Exercise Across a Week in Trained Male Cyclists.

Supplementation with anthocyanin-rich blackcurrant increases blood flow, cardiac output, and stroke volume at rest. It is not known whether cardiovascular responses can be replicated over longer timeframes in fed trained cyclists. In a randomized, double-blind, crossover design, 13 male trained cyclists (age 39 ± 10 years, V˙O2max 55.3 ± 6.7 ml·kg-1·min-1) consumed two doses of New Zealand blackcurrant (NZBC) extract (300 and 600 mg/day for 1 week). Cardiovascular parameters were measured during rest and submaximal cycling (65% V˙O2max) on day 1 (D1), D4, and D7. Data were analyzed with an RM ANOVA using dose (placebo vs. 300 vs. 600 mg/day) by time point (D1, D4, and D7). Outcomes from placebo were averaged to determine the coefficient of variation within our experimental model, and 95% confidence interval (CI) was examined for differences between placebo and NZBC. There were no differences in cardiovascular responses at rest between conditions and between days. During submaximal exercise, no positive changes were observed on D1 and D4 after consuming NZBC extract. On D7, intake of 600 mg increased stroke volume (3.08 ml, 95% CI [-2.08, 8.26]; d = 0.16, p = .21), cardiac output (0.39 L/min, 95% CI [-1.39, .60]; d = 0.14, p = .40) (both +2.5%), and lowered total peripheral resistance by 6.5% (-0.46 mmHg·min/ml, 95% CI [-1.80, .89]; d = 0.18, p = .46). However, these changes were trivial and fell within the coefficient of variation of our study design. Therefore, we can conclude that NZBC extract was not effective in enhancing cardiovascular function during rest and submaximal exercise in endurance-trained fed cyclists.

Five-Year Efficacy of Transobturator Tape Treatment and Quality of Life in Women with Stress Urinary Incontinence.

BACKGROUND: We aimed to assess the results of first- and fifth-year outcomes and the effect on quality of life (QoL) of transobturator tape (TOT) treatment in patients with stress urinary incontinence (SUI). METHODS: The patients who underwent TOT surgery between January 2008 and June 2013 were screened retrospectively. The QoL was evaluated with Incontinence Impact Questionnaire (IIQ-7) and Urogenital Distress Inventory-Short Form (UDI-6). The subjective evaluation of patients in terms of incontinence outcome was classified as worsened (UDI-6 and IIQ-7 if pre-operative < postoperative), improved (UDI-6 and IIQ-7 if pre-operative > postoperative), or cured (UDI-6 and IIQ-7 postoperative <10). The first-year and fifth-year success rates were compared between the IIQ-7 and UDI-6 results. RESULTS: A total of 109 patients were included in the study. There was a significant improvement (P<0.001) in the patients' UDI-6 and IIQ-7 scores when the preoperative and postoperative first-year results were compared. Comparing the postoperative first-year and fifth-year total UDI-6 and IIQ-7 scores, a significant improvement was observed and the patients' complaints were significantly reduced (P<0.001). The results of the IIQ-7 and UDI-6 questionnaire revealed that the TOT surgery success rate was 93.3% at the end of the first year and 88.7% at the end of the fifth year. CONCLUSION: The postoperative first-year and fifth-year data reveal that TOT surgery has a high success rate and positive effects on QoL. Low complication rates and the ease of application make TOT a good alternative to other treatment modalities in surgical treatment of SUI.

Magnetic Field Exposure Modulates the Anti-Inflammatory Efficiency of Minocycline in Rats with Peripheral Acute Inflammation.

BACKGROUND AND OBJECTIVE: Microglial activation in spinal cord is key contributor and its inhibition by Minocycline (MCN) can result in anti-inflammatory actions. Effect of pulsed magnetic field (PMF) in living system is a very complex process and many biological and cellular processes can play key roles. In this study aimed to reveal the roles of PMF exposure on anti-inflammatory potentials of MCN treatment by evaluating the inflammatory profiles of either inflamed site or spinal cord. METHODS: In this study, we investigated the anti-inflammatory effects of PMF, MCN or their combination treatments in rats with carrageenan (CG)-induced peripheral inflammation by examining the cardinal signs, hyperalgesia, allodynia, edema and fever. The levels of various inflammation markers (tumor necrosis factor-α), interleukin (IL)-1ß, IL-6, IL-17, IL-4, IL-10, C-C motif chemokine ligand3 (CCL3), C-X-C motif chemokine ligand1 and myeloperoxidase were also measured in paw and spinal cord tissues. RESULTS: CG induced inflammation caused edema, fever, and hypersensitivities. MNC or PMF treatments ameliorated these responses by suppressing pro-inflammatory markers in both inflamed paw and spinal cord. Although anti-hypersensitive, anti-edematous and anti-pyretic actions of MCN or PMF, in combined treatments PMF exposure decreased the anti-hyperalgesic and anti-allodynic actions of MCN treatment. These may be associated with decreases in IL-4 and IL-10 levels and an increase in CCL3 level of spinal cord tissues. CONCLUSION: Present findings support that MCN or PMF has anti-inflammatory properties duo to the down-regulating central microglial and/or peripheral inflammatory markers. Our data showed here, for the first time, PMF exposure may suppress the anti-hypersensitive actions of MCN by modulating microglia function/phenotype and microglial markers.

Antiinflammatory properties of antiLy6G antibody disappear during magnetic field exposure in rats with carrageenan induced acute paw inflammation.

Antiinflammatory properties of pulsed magnetic field (PMF) treatments or administration of antiLy6G antibody have been previously reported. In this study, we hypothesized that, the combination of PMF treatments and antiLy6G administration may synergistically potentiate their antiinflammatory actions. The effects of the combination of PMF treatments and antiLy6G administration were investigated by examining the inflammatory signs, histopathological properties of the inflamed site, and measuring the macrophage inflammatory protein-1 alpha (MIP-1α/CCL3) and myeloperoxidase (MPO) levels of inflamed paw tissues in rats with carrageenan-induced acute paw inflammation. In this present study, PMF treatments alone or administration of antiLy6G alone ameliorated the acute inflammation. However, their combination exacerbated the inflammatory signs, hyperalgesia, allodynia, edema and fever, and aggravated the inflammatory conditions by excessive infiltration of inflammatory cells to the inflamed site. These opposing effects of the combined treatments may correlate with enhanced levels of MIP-1α and MPO in inflamed paws. Present results indicated that the combination of the PMF treatments and antiLy6G administration may not provide additional benefits and may actually cause an aggravation of the acute inflammatory process. Findings may also suggest that during neutrophil or immune cell-targeted treatments for inflammatory states, magnetic field exposure may cause unexpected negative consequences.

The impact of hyperbaric oxygen therapy on erectile functions and serum testosterone levels in patients with erectile dysfunction.

Objective: To evaluate the effects of hyperbaric oxygen therapy (HBOT) on erectile functions and serum testosterone levels in patients with erectile dysfunction (ED).Methods: The patients treated by HBOT for several diseases between July 2017-May 2018 and had erectile dysfunction were included in the study. All patients filled the International Index of Erectile Function (IIEF) questionnaire form; serum total testosterone (TT) and free testosterone (FT) levels were examined before the first day and after the last day of HBOT. The effects of demographic characteristics of patients on erectile functions were evaluated. Patients were categorized according to the risk factors. The IIEF scores, TT and FT levels of patients in first day and after last day of HBOT were compared.Results: Totally 43 patients were included in the study. The mean post-HBOT IIEF-EF score was significantly higher than the mean pre-HBOT IIEF-EF score of patients (25.4 ± 5.3 vs 20.6 ± 5.1; p < .001). There was no statistical difference between the pre-HBOT and post-HBOT serum TT and FT levels of patients (4.0 ± 2.3 ng/ml vs 4.1 ± 2.0 ng/ml, p = .797; 8.6 ± 3.8 pg/ml vs 8.9 ± 3.5 pg/ml, p = .658).Conclusions: HBOT improved the erectile functions in ED patients however we cannot detect any effect on testosterone levels in our study.

Predictive Factors of Ureterorenoscopy Outcomes in Proximal Ureteral Stones: A Multicenter Study of Aegean Study Group of the Society of Urological Surgery.

INTRODUCTION: We aimed to evaluate the predictive factors in a holistic manner for ureterorenoscopy (URS) outcomes in proximal ureteral stones by a multicenter study. MATERIALS AND METHODS: The data of patients who underwent URS for proximal ureteral stones between the years 2015 and 2018 in eight centers were recorded retrospectively. Patients were divided into two groups according to URS success: Group 1 consisted of patients with successful URS, and Group 2 consisted of patients with unsuccessful URS. The two groups were compared in terms of risk factors, stone, and clinical characteristics of patients. RESULTS: A total of 638 patients were included in the study. Group 1 consisted of 527 (82.6%) patients, and Group 2 consisted of 111 (17.4%) patients. In multivariate logistic analysis, the key risk factors for URS success was found to be age (OR = 0.980, 95% [CI] = 0.963-0.996, p = 0.018), stone area (OR = 0.993, 95% [CI] = 0.989-0.997, p = 0.002), and operation time (OR = 0.981, 95% [CI] = 0.968-0.994, p = 0.005). CONCLUSIONS: To make the treatment decision of proximal ureteral stones, it is necessary to examine several parameters including available equipment, stone, and patient characteristics. Physicians should keep these risk factors in mind in the decision of treatment options.

The Effect of Hyperbaric Oxygen Therapy on Erectile Functions: A Prospective Clinical Study.

INTRODUCTION: We aimed to evaluate the effects of hyperbaric oxygen therapy (HBOT) on erectile function in patients who had no cavernosal or urethral injury by using International Index of Erectile Function (IIEF) questionnaire. MATERIALS AND METHODS: The male patients who were treated by HBOT for several diseases between July 2017 and September 2017 were examined. All patients filled the IIEF questionnaire form before the first day and after the last day of HBOT and a questionnaire including demographic characteristics and medical history. The effects of demographic characteristics and risk factors on erectile function were evaluated, and the IIEF domain scores of patients in first day and last day of HBOT were compared. RESULTS: Totally, 50 patients were included in the study between July 2017 and September 2017 and the mean age was 59.38 ± 13.77. The mean post-HBOT IIEF-EF score of patients was significantly higher than the mean pre-HBOT IIEF-EF score of patients (15.74 ± 10.52 vs. 19.50 ± 10.91; p < 0.001). The mean post-HBOT IIEF scores of other domains including intercourse satisfaction, orgasmic function, sexual desire, and overall satisfaction were also significantly higher than pre-HBOT scores. CONCLUSIONS: HBOT may be a good alternative treatment or adjunctive treatment for erectile dysfunction.

Computational repositioning and preclinical validation of mifepristone for human vestibular schwannoma.

The computational repositioning of existing drugs represents an appealing avenue for identifying effective compounds to treat diseases with no FDA-approved pharmacotherapies. Here we present the largest meta-analysis to date of differential gene expression in human vestibular schwannoma (VS), a debilitating intracranial tumor, and use these data to inform the first application of algorithm-based drug repositioning for this tumor class. We apply an open-source computational drug repositioning platform to gene expression data from 80 patient tumors and identify eight promising FDA-approved drugs with potential for repurposing in VS. Of these eight, mifepristone, a progesterone and glucocorticoid receptor antagonist, consistently and adversely affects the morphology, metabolic activity, and proliferation of primary human VS cells and HEI-193 human schwannoma cells. Mifepristone treatment reduces VS cell viability more significantly than cells derived from patient meningiomas, while healthy human Schwann cells remain unaffected. Our data recommend a Phase II clinical trial of mifepristone in VS.

Matcha Green Tea Drinks Enhance Fat Oxidation During Brisk Walking in Females.

Intake of the catechin epigallocatechin gallate and caffeine has been shown to enhance exercise-induced fat oxidation. Matcha green tea powder contains catechins and caffeine and is consumed as a drink. We examined the effect of Matcha green tea drinks on metabolic, physiological, and perceived intensity responses during brisk walking. A total of 13 females (age: 27 ± 8 years, body mass: 65 ± 7 kg, height: 166 ± 6 cm) volunteered to participate in the study. Resting metabolic equivalent (1-MET) was measured using Douglas bags (1-MET: 3.4 ± 0.3 ml·kg-1·min-1). Participants completed an incremental walking protocol to establish the relationship between walking speed and oxygen uptake and individualize the walking speed at 5- or 6-MET. A randomized, crossover design was used with participants tested between Days 9 and 11 of the menstrual cycle (follicular phase). Participants consumed three drinks (each drink made with 1 g of Matcha premium grade; OMGTea Ltd., Brighton, UK) the day before and one drink 2 hr before the 30-min walk at 5- (n = 10) or 6-MET (walking speed: 5.8 ± 0.4 km/hr) with responses measured at 8-10, 18-20, and 28-30 min. Matcha had no effect on physiological and perceived intensity responses. Matcha resulted in lower respiratory exchange ratio (control: 0.84 ± 0.04; Matcha: 0.82 ± 0.04; p < .01) and enhanced fat oxidation during a 30-min brisk walk (control: 0.31 ± 0.10; Matcha: 0.35 ± 0.11 g/min; p < .01). Matcha green tea drinking can enhance exercise-induced fat oxidation in females. However, when regular brisk walking with 30-min bouts is being undertaken as part of a weight loss program, the metabolic effects of Matcha should not be overstated.

Involvement of TRPM2 and TRPV1 channels on hyperalgesia, apoptosis and oxidative stress in rat fibromyalgia model: Protective role of selenium.

Fibromyalgia (FM) results in pain characterized by low selenium (Se) levels, excessive Ca2+ influx, reactive oxygen species (ROS) production, and acidic pH. TRPM2 and TRPV1 are activated by ROS and acid; nevertheless, their roles have not been elucidated in FM. Therefore, we investigated the contribution of TRPM2 and TRPV1 to pain, oxidative stress, and apoptosis in a rat model of FM and the therapeutic potential of Se. Thirty-six rats were divided into four groups: control, Se, FM, and FM + Se. The Se treatment reduced the FM-induced increase in TRPM2 and TRPV1 currents, pain intensity, intracellular free Ca2+, ROS, and mitochondrial membrane depolarization in the sciatic (SciN) and dorsal root ganglion (DRGN) neurons. Furthermore, Se treatment attenuated the FM-induced decrease in cell viability in the DRGN and SciN, glutathione peroxidase, and reduced glutathione and α-tocopherol values in the DRGN, SciN, brain, muscle, and plasma; however, lipid peroxidation levels were decreased. Se also attenuated PARP1, caspase 3, and 9 expressions in the SciN, DRGN, and muscle. In conclusion, Se treatment decreased the FM-induced increase in hyperalgesia, ROS, apoptosis, and Ca2+ entry through TRPM2 and TRPV1 in the SciN and DRGN. Our findings may be relevant to the elucidation and treatment of FM.

Effects of Vitamin D Therapy on Quality of Life in Patients with Fibromyalgia.

OBJECTIVE: The role of vitamin D in the etiopathogenesis of fibromyalgia and non-specific musculoskeletal pain is controversial. In our study, we aimed to investigate the effect of vitamin D therapy on quality of life in patients with fibromyalgia. MATERIALS AND METHODS: Seventy patients diagnosed with fibromyalgia and 65 age- and sex-matched controls were included in the study. Patients were grouped as deficient (<20 ng/mL), inadequate (20-30 ng/mL), and sufficient (>30 ng/mL) according to the levels of vitamin D. Vitamin D replacement was performed for patients with deficiencies and inadequacies. Before and after vitamin D therapy, patients filled in the assessment tools, fibromyalgia impact questionnaire (FIQ), Arizona sexual experience scale (ASEX), Beck depression inventory (BDI), visual analog scale (VAS), and short form-36 (SF-36). RESULTS: Vitamin D deficiencies and inadequacies were observed in 60% of the patients (n=42). Among patients with low and normal levels of vitamin D, no statistically significant difference was observed in their values. In scales examined after vitamin D replacement therapy, statistically significant differences were observed in the FIQ, BDI, VAS, and SF-36 compared with pre-treatment. CONCLUSION: Vitamin D deficiency seems to be linked to the pathogenesis of fibromyalgia. Vitamin D supplementation may improve the quality of life in patients with fibromyalgia.

Effects of intraperitoneally administered folic acid on the healing of repaired tibial nerves in rats.

BACKGROUND: Complete nerve regeneration and clinical healing remain a challenge despite considerable advances in the treatment of peripheral nerve injuries. To improve nerve regeneration, several experimental molecular procedures have been attempted. This study aimed to investigate the effects of folic acid on peripheral nerve healing after transection and end-to-end suture repair of the tibial nerve in rats. METHODS: In this study, 20 adult male Wistar Albino rats weighing 225 to 250 g were used. The right tibial nerves of 20 rats were explored, transected, and sutured using the end-to-end technique. The rats were randomly allocated to either the intraperitoneally administered folic acid group (test group) or the control group. Preoperative and 6-week postoperative neurophysiological studies were performed by the same researcher. Myelin-sheathed axons were counted. RESULTS: The results demonstrated that the folic acid-treated group exhibited improved electromyographic results compared with the control group. Histological evaluation revealed that the axons were well preserved and that the axon quantity and density were increased in the test group compared with the control group. Quantitative results also increased in the test group compared with the control group (p = 0.001). CONCLUSION: In this study, 6-week intraperitoneal administration of 80 µg/kg of folic acid significantly improved peripheral nerve healing. Histological analysis of the group that received folic acid revealed increased axon myelination with little granular tissue or fibrosis. We propose that folic acid supplementation may be an effective component of peripheral nerve injury treatment.

Hypericum perforatum modulates apoptosis and calcium mobilization through voltage-gated and TRPM2 calcium channels in neutrophil of patients with Behcet's disease.

Behcet's disease (BD) is a chronic, inflammatory, and multisystemic condition although its pathogenesis is uncertain. Main component of St. John's wort (Hypericum perforatum, HP) is hyperforin and induces antiinflammatory and antioxidant properties. We aimed to investigate effects of HP on oxidative stress, apoptosis, and cytosolic-free Ca²âº [Ca²âº](i) concentration in neutrophil of BD patients. Nine new-diagnosed active patients with BD and nine control subjects were included in the study. Disease activity was considered by clinical findings. Neutrophil samples were obtained from the patients and controls. The neutrophils from patients were divided into three subgroups and were incubated with HP, voltage-gated calcium channel (VGCC) blockers, (verapamil+dilitiazem) and non-specific TRPM2 channel blocker (2-aminoethyl diphenylborinate, 2-APB), respectively. The neutrophils were stimulated by fMLP as a Ca²âº-concentration agonist and oxidative stress former. Caspase-3, caspase-9, apoptosis, lipid peroxidation, and [Ca²âº](i) values were high in the patient groups, although cell viability, glutathione (GSH), and glutathione peroxidase (GSH-Px) values were low in patient group. However, the [Ca²âº](i), caspase-3, and caspase-9 values decreased markedly in patient+HP group although GSH and GSH-Px values increased in the group. The [Ca²âº](i) concentration was also decreased in the patient group by V+D, 2-APB, and HP incubations. In conclusion, we observed the importance of neutrophil Ca²âº entry, apoptosis, and oxidative stress through gating VGCC and TRPM2 channels in the neutrophils in the pathogenesis and activation of the patients with BD. HP induced protective effects on oxidative stress by modulating Ca²âº influx in BD patients.

The apoptotic effect of a high dose of toluene on liver tissue during the acute phase: an experimental study.

The aim of this study is to investigate the acute toxic effects of high-dose toluene and its mechanisms on the liver tissue of toluene-treated rats. In this study, 16 adult male Wistar albino rats (200-220 g) were divided into two equal groups. Group I was used as a control group, while group II was exposed to high dose of toluene, 5200 mg/kg (6 ml/kg per gavage). After the 3-hour experimental period, blood samples and liver tissues were taken from the euthanized animals. Serum aspartate and alanine aminotransferase levels were assayed. Liver tissues were fixed in 10% neutral formalin, then embedded in paraffin and sectioned (5 µm thickness). Sections were stained with hematoxylin and eosin for histopathological examination. A terminal transferase dUTP nick end labeling assay was also done for the determination of apoptosis in liver tissues. For the determination of Bax and caspase-3 immunoreactivity, the sections were stained using avidin-biotin-peroxidase immunohistochemical method. The level of plasma transaminase was found to be increased in toluene administered rats. Additionally, slight degeneration of hepatocyte and mononuclear cell infiltration was observed in the liver tissue sections and a high (+++) immunoreactivity for Bax and caspase-3 protein was observed in the toluene group. This study showed that the high dose of toluene triggers apoptosis in the liver of rats via the mitochondrial pathway in acute period.

Proanthocyanidin prevents myocardial ischemic injury in adult rats.

BACKGROUND: Proanthocyanidin is a bioflavonoid known to have protective effect against oxidative injury. We investigated the cardioprotective effect of proanthocyanidin. MATERIAL/METHODS: Thirty-two Rattus Norvegicus rats were categorized equally as the control group (CG), proanthocyanidin group (PCG), ischemia group (IG) and proanthocyanidin-treated group (PCT). Rats in CG and IG were fed standard rat food and PCG and PCT were fed standard rat food plus proanthocyanidin (100 mg/kg/day twice a day by oral gavage) for 3 weeks. In CG and PCG the myocardial samples were prepared immediately, and in IG and PCT hearts were placed in transport solution and kept at 4°C for 5 hours, then prepared for evaluation. Malondialdehyde (MDA) level, superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx) activities were measured. RESULTS: MDA levels were significantly higher in IG and PCT than in CG and PCG. The activity of SOD was significantly lower in IG and higher in PCG than in the other groups. The activity of GPx was significantly lower in IG than in the other groups. The activities of CAT were significantly lower in IG and PCT than in the other groups and were significantly lower in IG than PCT. Histopathologic evaluation revealed normal findings in CG and PCG. While ischemic injury was observed in IG, the content of muscle fibers was better preserved in PCT. CONCLUSIONS: Proanthocyanidin may have a protective effect on myocardial ischemic injury.

KNK437, a benzylidene lactam compound, sensitises prostate cancer cells to the apoptotic effect of hyperthermia.

Hyperthermia is known to serve as a powerful tool in the treatment of prostate cancer which is commonly diagnosed in men. Quercetin and KNK437, Hsp70 inhibitors, play an important role in blocking thermotolerance in some cancer cells. In the present study we investigated the effects of KNK437 and quercetin on the acquisition of thermotolerance and heat-induced apoptosis. Also, it was examined whether the possible mechanism triggering apoptotic pathway included caspase-3 activation in prostate cancer cells. For this purpose, PC-3 and LNCaP cells were treated with hyperthermia following pretreatment with or without KNK437 or quercetin. Thermotolerance was investigated by colony formation assay in these cells, while Hsp70 mRNA levels were measured by real time RT-PCR. Sandwich ELISA was used for detection of Hsp70 protein levels. Apoptosis was detected by flow cytometric annexin V binding assay and by western blot analysis of procaspase-3 and cleaved poly (ADP-ribose) polymerase levels. In our study, KNK437 and quercetin inhibited thermotolerance in a dose-dependent manner in PC-3 cells. KNK437 and quercetin decreased heat-induced accumulation of Hsp70 mRNA and protein in PC-3 and LNCaP cells. KNK437 and quercetin pretreatment enhanced the apoptotic effect of hyperthermia in both cells. We found that KNK437 was more effective than quercetin in inducing apoptotic cell death, activation of caspase-3, and cleavage of PARP in prostate cancer cells. We suggest that KNK437 is a useful agent for enhancing the efficiency of hyperthermic therapy which has less toxic side-effects in prostate cancer.

Protective role of erdosteine on vancomycin-induced oxidative stress in rat liver.

Drug-induced liver toxicity is a common cause of liver injury. This study was designed to elucidate whether high dose vancomycin (VCM) induces oxidative stress in liver and to investigate the protective effects of erdosteine, an expectorant agent. Twenty-two young Wistar rats were divided into three groups as follows: control group, VCM, and VCM plus erdosteine. VCM was administered intraperitoneally in the dosage of 200 mg/kg twice daily for 7 days. Erdosteine was administered orally administered once a day at a dose of 10 mg/kg body weight. The activities of antioxidant enzymes such as superoxide dismutase and catalase as well as the concentration of malondialdehyde, as an indicator of lipid peroxidation, were measured to evaluate oxidative stress in homogenates of the liver. VCM administration increased malondialdehyde levels (p < 0.001), superoxide dismutase (p < 0.01) and catalase (p < 0.001) activities. Erdosteine co-administration with VCM injections caused significantly decreased malondialdehyde levels (p < 0.001), superoxide dismutase (p < 0.01) and catalase (p < 0.001) activities in liver tissue when compared with VCM alone. It can be concluded that erdosteine may prevent VCM-induced oxidative changes in liver by reducing reactive oxygen species.