Significant Decrease In Blood Research Articles

Comparative analysis of robotic and laparoscopic surgery for mid and low rectal cancer in patients with varied body mass indexes: evaluating of short-term outcomes.

The main aim of this study was to evaluate and contrast the efficacy of robotic and laparoscopic surgical procedures in the treatment of low and mid rectal cancer in different BMI (body mass index) groups. The clinical records of patients who had laparoscopic or robotic proctectomy at a single center between December 2019 and August 2023 were analyzed. Then we utilized a classification framework to categorize individuals based on their BMI into three unique groups: non-obese, overweight, and obese. The short-term efficacy was evaluated. A consecutive sample of 1413 patients was included in this retrospective investigation. 1158 people out of the total sample chose laparoscopic surgery, whereas 255 people chose robotic surgery. In the group of obese people, robotic surgery showed a statistically significant decrease in blood losscompared to laparoscopic surgery (P = 0.026). People who were overweight or obese were in the hospital for a shorter amount of time after robotic surgery than after laparoscopic surgery (P = 0.033 and P = 0.031, respectively). People with different BMIs in the robotic surgery group took less time to have a flatus passage and oral intakethose in the laparoscopic surgery group. Oncological outcomes and the frequency of complicationswere comparable between the two treatments with different BMIs. Surgical resection of patients undergoing low-anterior surgery may benefit from a robotic approach, particularly in overweight and obese patients.

Increase in FeNO Levels Following IL5/IL5R-Targeting Therapies in Severe Asthma: A Case Series.

PurposeMonoclonal antibodies targeting interleukin-5 (IL5) and its receptor (IL5R), used for severe asthma treatment, reduce eosinophils to almost complete depletion. Fractional exhaled nitric oxide (FeNO), a surrogate marker of eosinophilic airway inflammation, is expected to decrease after their initiation. Our center noticed increased FeNO levels in a few patients in whom anti-IL5/IL5R therapy was initiated. Limited data are available on the kinetics of T2 inflammation biomarkers after initiation of a biologic in that population. This study aims to identify if a subgroup of severe asthma patients experiences increased FeNO levels after initiation of anti-IL5/IL5R therapy and to describe their clinical characteristics.Patients and MethodsThis is a retrospective case series of 5 patients on Benralizumab (4M:1F) and 8 on Mepolizumab (5M:3F) who showed a significant increase in FeNO (>20% AND >25 ppb) following initiation of an anti-IL5/IL5R treatment. Clinical data, expiratory flows, and inflammation were extracted from the patients’ chart at initiation of treatment (T0), 3 months (T1) and 12 months (T2) post-treatment. Descriptive statistics were used.ResultsIn patients treated with Benralizumab, the increase in FeNO was observed between T0 and T1 (mean delta = 82 ± 72 ppb) with a subsequent decrease (N = 3). In most patients taking Mepolizumab (N = 6), the FeNO increase was observed between T1 and T2 (mean delta = 57 ± 35 ppb). Under treatment, no Benralizumab patient experienced asthma exacerbation while two on Mepolizumab did. All patients had a significant decrease in blood eosinophils.ConclusionAlthough initiation of anti-IL5/IL5R may cause a transient rise in FeNO levels in a subgroup of patients, it does not appear to affect clinical outcomes. A compensatory mechanism involving other inflammatory pathways such as IL13 or IL4, both involved in FeNO production, could theoretically explain these findings. Further investigation is needed to elucidate the actual underlying mechanisms.

Propofol Infusion versus Combination of Isoflurane withNitroglycerine for Controlled Hypotensive Anesthesia in SpineSurgery: A Randomized Controlled Study

AbstractBackground: Several methods have been used to improvesurgical field clarity and decrease blood loss intraoperative;one of them is the usage of hypotensive anesthesia. Spinesurgery is one of the surgeries that need a clear field and adecreased amount of intraoperative bleeding which can impact on the ability of surgeons.Aim of Study: Current study was designed to evaluate theeffect of propofol versus isoflurane with nitroglycerine onblood loss, operative field clarity, extubation time and effectof both on tissue perfusion.Settings and Design: This study design was a prospectiverandomized controlled double blinded clinical study.Patients and Methods: 80 ASA or II patients undergoingelective spine surgery were randomly assigned to group P (n=40) that received propofol for induction and maintenancewhile group I (n=40) received thiopental for induction andisoflurane for maintenance with nitroglycerine. Heart rate,mean arterial pressure were recorded every 10min, amountof blood loss, grade of operative field clarity, extubation timeand effect of both on liver and kidney function were recorded.Results: Propofol group showed significant decrease inblood loss (p=0.01), better surgical field clarity (p=0.002)and shorter extubation time (p=0.001) than isoflurane groupbut there were no significant changes between the two groupsregarding their effect on tissue perfusion (liver and kidney).Conclusion: Propofol for elective spine surgery improvedsurgical condition and provided faster recovery compared toisoflurane even when we added an antihypertensive drug asnitroglycerine to isoflurane. Both of them had a comparableminor effect on liver and kidney functions.

Changes of basic hematological parameters in patients with generalized periodontitis depending on the blood group

Summary. General clinical blood test is widely used as one of the most important methods of examination in most diseases. The cellular composition of the blood of a healthy person is fairly constant, so various changes occurring in diseases may have important diagnostic value.
 The aim of the study – to analyze changes in the main hematological parameters in patients with generalized periodontitis associated with blood group.
 Materials and Methods. The studies were conducted in the clinic of Ternopil State Medical University and Ternopil Regional Blood Transfusion Station. 855 males aged 20–55 years were examined, who were divided into 2 groups: the main group consisted of 570 patients with generalized periodontitis of I – III severity. Complete blood count was determined using an automatic hematology analyzer “Sysmex KH - 21”. The morphological study of blood cells was performed using a Zeiss light microscope using a unified method. The erythrocyte sedimentation rate was determined using a Panchenkov unified micromethod.
 Results and Discussion. It was found that in patients with generalized periodontitis, a significant decrease in blood was determined: the number of red blood cells (by 17.53 %) and their volume (by 13.40 %), p <0.01. At the same time, hemoglobin decreased by 25.59 %, hematocrit – by 32.18 % against an increase in ESR by 2.7 times, p <0.01, relative to the corresponding data in the comparison group without periodontal pathology. At the same time, it was found that in patients with generalized periodontitis the number of leukocytes increased (by 52.87 %), neutrophils (by 25.47 %), p <0.01, stab (by 39.48%), segmented (by 18.32 %) leukocytes, p<0.05, relative to the corresponding parameters in the comparison group. At the same time, in patients with generalized periodontitis, the leukocyte index of intoxication was 2.9 times higher than in the examined group of comparison. It should be noted that in patients with generalized periodontitis, depending on the group membership of the blood, the dynamics of the values of the parameters studied was similar to the average, differed depending on the group membership, between the digital tannins.
 Conclusions. Our studies allowed us to obtain a block of new data revealing the biological variability of the cellular and molecular composition of blood, to identify features associated with blood group in patients with generalized periodontitis.

Effects of remifentanil with or without midazolam pretreatment on the 95% effective dose of propofol for loss of consciousness during induction: A randomized, clinical trial.

Background:Propofol is a rapid, efficient hypnotic agent with antiemetic effects. However, a high dosage is related to hemodynamic abnormalities such as hypotension and bradycardia. Pretreatment with remifentanil can decrease injection pain and stabilize hemodynamics during the induction period. Remifentanil or midazolam in combination with propofol can provide synergistic or additive effects during anesthesia induction. However, the hypnotic doses of propofol required in patients who receive pretreatment with remifentanil or midazolam remain unclear.Methods:Patients aged 20 to 50 years who were scheduled to undergo surgery under general anesthesia were enrolled in this study. The patients were randomized into 3 groups using a computer-generated randomization table. Patients in Group P (Propofol) received only propofol for loss of consciousness, those in Group PR (Propofol-Remifentanil) received remifentanil prior to propofol, and those in Group PMR (Propofol-Midazolam-Remifentanil) received remifentanil and midazolam prior to propofol. After propofol administration, loss of both the eyelash reflex and verbal response represented success. The 95% effective dose of propofol for loss of consciousness in each group, which was the primary outcome, was determined using a modified biased coin up-and-down method.Results:A total of 124 patients were initially enrolled. Of these, 4 were excluded, and the remaining 120 patients were randomized to each (n = 40) of the 3 groups. The 95% effective dose of propofol for loss of consciousness was 1.74 , 1.38, and 0.92 mg/kg in Groups P, PR, and PMR, respectively. Blood pressure decreased at 2 minutes after propofol administration in all the groups. However, compared with Group P, Groups PR and PMR exhibited a significant decrease in blood pressure.Conclusions:The effective dose of propofol for loss of consciousness could be decreased by 21% and 47% when remifentanil pretreatment was used without and with midazolam, respectively. However, the decrease in blood pressure was greater with pretreatment than sole propofol use. These findings suggest that the combination of remifentanil with or without midazolam may have no benefit on hemodynamic stability during induction using propofol.Trial registration:NCT02536690 (clinicaltrials.gov).

Peer Support Training Improved the Glycemic Control, Insulin Management, and Diabetic Behaviors of Patients with Type 2 Diabetes in Rural Communities of Central China: A Randomized Controlled Trial.

BackgroundThe efficacy of peer support in Chinese diabetes patients is still uncertain. The purpose of this study was to observe the effects of a peer support program on the outcomes of patients with type 2 diabetes who received community-based insulin therapy in rural communities of central China.Material/MethodsTwo hundred and eight eligible patients with type 2 diabetes were randomly assigned into the traditional training group (control group, n=111) and peer support intervention group (peer group, n=97) between June 2013 and January 2014 in 2 rural communities of Jingzhou area, China. Both groups received 3-month traditional training, followed by another 4-month traditional training or peer support training, respectively. At baseline and 7 months after treatment, the blood glycemic level was evaluated by biochemical detection. Capacities of self-management and knowledge related to insulin usage were assessed by questionnaire survey.ResultsNinety-seven and ninety patients completed this study in the control group and peer group, respectively. There was no significant difference in age, gender, diabetes duration, insulin usage time, and complications between the 2 groups at baseline (P>0.05). Compared with the control group, peer group patients achieved a more significant decrease in blood glycosylated hemoglobin levels (P<0.05), increase in knowledge related to insulin usage, and increase of diabetes self-management ability (P<0.05).ConclusionsPeer support intervention effectively improves outcomes of patients with type 2 diabetes in rural communities of central China.

Cytokine and clinical response to Saccharomyces boulardii therapy in diarrhea-dominant irritable bowel syndrome: a randomized trial.

This preliminary study aimed to investigate the effects of the probiotic Saccharomyces boulardii on proinflammatory and anti-inflammatory cytokines in patients with diarrhea-dominant irritable bowel syndrome (IBS-D). The other objectives were to document any clinical improvement as judged by symptoms, quality of life, and histology. This was a randomized, double blind, placebo-controlled trial in which S. boulardii, 750 mg/day, or placebo was administered for 6 weeks in IBS-D patients, in addition to ispaghula husk standard treatment. Thirty-seven patients received S. boulardii and 35 patients received the placebo. As compared with placebo, the S. boulardii group showed a significant decrease in blood and tissue levels of proinflammatory cytokines interleukin-8 (IL-8) and tumor necrosis factor-α (P<0.001) and an increase in anti-inflammatory IL-10 levels, as well as an increase in the tissue IL-10/IL-12 ratio (P<0.001). No significant change in the blood and tissue levels of cytokines was found in the placebo group. Bowel-related IBS-D symptoms reported in the patients' daily diary improved in both groups. However, overall improvement in the quality of life was more marked in the S. boulardii group. Although baseline histological findings were mild, an improvement was observed in the probiotic group in the lymphocyte and neutrophil infiltrates (P=0.017 and 0.018), epithelial mitosis (P=0.003), and intraepithelial lymphocytes (P=0.024). No serious adverse events were found in either group. S. boulardii with ispaghula husk was superior to placebo with ispaghula husk in improving the cytokine profile, histology, and quality of life of patients with IBS-D. These preliminary results need to be confirmed in a well-powered trial.

Evaluation of in vitro and in vivo antioxidant potential of polysaccharides from Aloe vera (Aloe barbadensis Miller) gel

In the present study, the antioxidant activity of the polysaccharides from aloe vera (Aloe barbadensis Miller) gel was evaluated, in vitro by five established methods, 1,1-diphenyl-2-picrylhydrazyl (DPPH–) radical scavenging, nitric oxide (NO) scavenging, hydrogen peroxide scavenging, superoxide radical (O-2) scavenging and reducing power assay, and in vivo against doxorubicin (DOX)-induced myocardial oxidative stress (OS) in albino wistar rats. The polysaccharides exhibited significant inhibitory activity against DPPH–, superoxide, NO and hydrogen peroxide scavenging assay with significant reducing activity at all concentrations used. DOX-induced (7.5 mg/kg, intravenously) cardiotoxicity manifested biochemically by a significant decrease in blood and tissue glutathione (GSH) along with elevated levels of serum lactate dehydrogenase and creatine phosphokinase. In addition, cardiotoxicity was further confirmed by the significant increase in lipid peroxidation expressed as thiobarbituric acid reactive substances (TBARS), catalase (CAT) and superoxide dismutase (SOD). Administration of aloe vera polysaccharides for 14 days produced a marked protection against cardiotoxicity induced by DOX evidenced by significant reductions in serum lactate dehydrogenase, serum creatine phosphokinase, cardiac TBARS, CAT and SOD along with increased levels of blood and tissue GSH in a dose-dependent manner. The present investigation is the first to establish the antioxidant potency of the polysaccharides from aloe vera against DOX-induced myocardial OS.

Abstract P4-10-01: High dose omega-3 fatty acid supplementation modulates breast tissue biomarkers in post-menopausal women at high risk for development of breast cancer

Abstract Background: We conducted a pilot study of high dose omega-3 fatty acid (FA) supplementation in post-menopausal women to determine if risk biomarkers for breast cancer in benign breast tissue sampled by random peri-areolar aspiration (RPFNA) could be favorably modulated and to acquire preliminary data on possible mechanism of action. Methods: 35 post-menopausal women at increased risk for breast cancer were accrued to a trial of 6-month intervention with 4 g daily of omega-3-acid ethyl esters [1.86 g eicosapentaenoic acid (EPA), 1.5 g docosahexaenoic acid (DHA)]. Subjects had RPFNA performed pre- and post-intervention and specimens evaluated for cytomorphology and proliferation (Ki-67). FA composition was determined in plasma, red blood cells, and RPFNA specimens. Additional specimens were frozen for assessment of hormones, a panel of 11 adipokines and cytokines by Luminex, and gene expression. Results: 34 subjects completed study with specimens evaluable for change in biomarkers. The ratio of (EPA+DHA):Arachidonic Acid (AA) levels in erythrocyte phospholipid increased significantly by a median of 2.7-fold. Although there was a significant decrease in blood EPA+DHA between discontinuation at 6 months and 2 weeks later when RPFNA was performed, all ratios were above the baseline value (median 1.6-fold). There was favorable but not statistically significant modulation for cytologic evidence of atypia (53% at baseline to 41% at off-study). However, favorable modulation was exhibited for Masood score (medians of 15 to 14; p = 0.014), number of epithelial cells recovered (p = 0.019) and Ki-67 expression (medians of 1.7% to 0.75%, p = 0.036, despite 8 subjects having no Ki-67 expression at baseline). Luminex assay of serum indicated a statistically significant increase (p = 0.003) for adiponectin and decrease (p = 0.016) for TNF-alpha between baseline and off-study. For RPFNA specimens, there was a significant decrease (P = 0.001) in MCP-1 levels adjusted for protein content. By ELISA, serum high molecular weight adiponection increased (p = 0.046) and molar ratio of IGF-1:IGFBP3 decreased (p = 0.006). Note that all analyses were exploratory and without correction for multiple analyses. Conclusion: Favorable modulation of a variety of blood and tissue risk biomarkers, including cytomorphology and proliferation, along with good tolerability suggests that high dose omega-3 FA esters should be tested further in a placebo-controlled trial. Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P4-10-01.

Acute NK1 receptor antagonist administration affects reward incentive anticipation processing in healthy volunteers

The primary brain structures of reward processing are mainly situated in the mid-brain dopamine system. The nucleus accumbens (NAc) receives dopaminergic projections from the ventral tegmental area and works as a key brain region for the positive incentive value of rewards. Because neurokinin-1 (NK₁) receptor, the cognate receptor for substance P (SP), is highly expressed in the NAc, we hypothesized that the SP/NK₁ receptor system might play a role in positive reward processing in the NAc in humans. Therefore, we conducted a functional MRI (fMRI) study to assess the effects of an NK₁ receptor antagonist on human reward processing through a monetary incentive delay task that is known to elicit robust activation in the NAc especially during gain anticipation. Eighteen healthy adults participated in two series of an fMRI study, taking either a placebo or the NK₁ receptor antagonist aprepitant. Behavioural measurements revealed that there was no significant difference in reaction time, hit rate, or self-reported effort for incentive cues between the placebo and aprepitant treatments. fMRI showed significant decrease in blood oxygenation-level-dependent signals in the NAc during gain anticipation with the aprepitant treatment compared to the placebo treatment. These results suggest that SP/NK₁ receptor system is involved in processing of positive incentive anticipation and plays a role in accentuating positive valence in association with the primary dopaminergic pathways in the reward circuit.

High-dose omega-3 fatty acid supplementation to modulate breast tissue biomarkers in premenopausal women at high risk for development of breast cancer.

1515 Background: We conducted a pilot study of high dose omega-3 fatty acid (FA) supplementation in pre-menopausal women to determine if risk biomarkers for breast cancer in benign breast tissue sampled by random peri-areolar aspiration (RPFNA) could be favorably modulated and to acquire preliminary data on possible mechanism of action. Methods: 36 pre-menopausal women at increased risk for breast cancer were accrued to a trial of 6-month intervention with 4 g daily of omega-3-acid ethyl esters [1.86 g eicosapentaenoic acid (EPA), 1.5 g docosahexaenoic acid (DHA)]. To date, 31 subjects have completed study with RPFNA performed pre- and post-intervention in the follicular phase of the menstrual cycle and specimens evaluated for cytomorphology and proliferation (Ki-67). FA composition was determined in plasma, red blood cells, and RPFNA specimens. Additional specimens were frozen for assessment of hormones, a panel of 11 adipokines and cytokines, and gene expression. Results: The ratio of (EPA+DHA):Arachidonic Acid (AA) levels increased significantly in plasma and erythrocytes by a median of three-fold. There was a significant decrease in blood EPA+DHA between discontinuation at 6 months and 2 weeks later when RPFNA was performed. Despite that, there was favorable modulation for cytologic evidence of atypia (81% at baseline to 42% at off-study; p=0.003), Masood score (medians of 15 to 14; p=0.001), number of epithelial cells recovered (p=0.004) and Ki-67 expression (p=0.025 for 30 women with any Ki-67 at baseline, medians of 1.9% to 0.9%). Serum assays have been completed for 24 subjects. No statistically significant changes were observed for estradiol, testosterone, progesterone, SHBG, IGF-1, IGFBP-3. There was a trend (p=0.056) towards a decrease in resistin. To date, only two subjects have discontinued the study early; grade 2 or greater gastrointestinal side effects have been reported by only two subjects. Conclusions: Favorable modulation of tissue risk biomarkers, cytologic atypia and proliferation along with good tolerability suggests that high dose omega-3 FA esters should be tested further in a placebo controlled trial. Clinical trial information: NCT01252277.

Hepatoprotective Effects of Thymus and Salvia Essential oils on Paracetamol-Induced Toxicity in Rats

Medicinal plants have been used traditionally worldwide for the prevention and treatment of liver disease. Thymus Capitatus and Salvia Officinal are used frequently as spices. The present investigation aimed to investigate the possible potential protective effect of Thymus and Salvia essential oils against Paracetamol induced hepatotoxicy. Administration of Paracetamol (500 mg/kg.b.wt) resulted in liver damage as manifested by significant increase in serum and hepatic lactate dehydrogenase (LDH) activity with a significant decrease in blood and hepatic glutathione (GSH) levels, as well as blood and hepatic superoxide dismutase (SOD), and glutathione peroxidase (GPx) activities. Rats pretreated orally with essential oil of Thymus Capitatus and Salvia Officinal (50 mg/kg b. wt. daily) for 15 days then intoxicated with paracetamol showed a significant protection against-induced increase in serum and hepatic LDH activities and inhibit reduce GSH levels and enhance increase SOD and GPx activities in blood and liver. These data indicate that essential oils of Thymus Capitatus and Salvia Officinalis possessed a hepatoprotective activity against hepatotoxicity induced by paracetamol model due to their antioxidant activity.

Protective effects of ebselen (Ebs) and para-aminosalicylic acid (PAS) against manganese (Mn)-induced neurotoxicity

Chronic, excessive exposure to manganese (Mn) may induce neurotoxicity and cause an irreversible brain disease, referred to as manganism. Efficacious therapies for the treatment of Mn are lacking, mandating the development of new interventions. The purpose of the present study was to investigate the efficacy of ebselen (Ebs) and para-aminosalicylic acid (PAS) in attenuating the neurotoxic effects of Mn in an in vivo rat model. Exposure biomarkers, inflammatory and oxidative stress biomarkers, as well as behavioral parameters were evaluated. Co-treatment with Mn plus Ebs or Mn plus PAS caused a significant decrease in blood and brain Mn concentrations (compared to rats treated with Mn alone), concomitant with reduced brain E 2 prostaglandin (PGE 2) and enhanced brain glutathione (GSH) levels, decreased serum prolactin (PRL) levels, and increased ambulation and rearing activities. Taken together, these results establish that both PAS and Ebs are efficacious in reducing Mn body burden, neuroinflammation, oxidative stress and locomotor activity impairments in a rat model of Mn-induced toxicity.

Direct and indirect effects of parathyroid hormone on circulating levels of fibroblast growth factor 23 in vivo

Fibroblastic growth factor 23 (FGF23) is a bone-derived hormone that has a pivotal role in the pathogenesis of mineral disorders in chronic kidney disease. To study the effect of parathyroid hormone (PTH) on FGF23, rats were parathyroidectomized for a week and then implanted with constant-delivery infusion pumps to provide vehicle, a physiological, or a threefold supraphysiological dose of parathyroid hormone. Parathyroidectomy resulted in a significant decrease in blood ionized calcium, FGF23, and calcitriol along with an increase in phosphorus concentrations. PTH replacement produced a dose-dependent increase in ionized calcium and FGF23 with decreased phosphorus. Calcitriol was also increased but there was no dose effect of PTH treatment. To maintain normal plasma calcitriol levels, two additional groups of parathyroidectomized rats were given calcitriol and temporarily treated with vehicle or the supraphysiological dose of PTH. FGF23 was significantly increased by calcitriol in the vehicle-treated rats but was not further increased above that in rats given the supraphysiological dose of PTH in the absence of calcitriol. Klotho expression in the kidney decreased after parathyroidectomy but was restored by hormone supplementation. Hence, our results show a direct and an indirect effect of PTH on FGF23 secretion, the latter through changes in calcitriol concentrations.

Phase IA/II Study of Oral LBH589, a Novel Deacetylase Inhibitor (DACi), Administered on 2 Schedules, in Patients with Advanced Hematologic Malignancies.

LBH589 is a novel cinnamic acid hydroxamate DACi which induces apoptosis in multiple hematologic tumor cell lines in vitro at nanomolar levels. LBH589 has been administered orally, once-a-day, on Monday/Wednesday/Friday, every week (Arm 1) or every other week (Arm 2), in cycles of 28 days, to adult pts with advanced hematologic malignancies. A 3-parameter Bayesian logistic regression model guided dose escalation. To date, 61 pts, median age 67 yrs (range 16–87), 40 male, 21 female, have been enrolled: 33 pts in Arm 1 at dose levels (mg/dose) of 20 (9 pts), 30 (12 pts), 40 (10 pts), and 60 (2 pts); 28 pts in Arm 2 at dose levels (mg/dose) of 30 (7 pts), 45 (12 pts), and 60 (9 pts). Diseases treated have included AML (36 pts), MDS (7 pts), MM (3 pts), NHL (3 pts), HL (3 pts), CML-BP (2 pts), CML-CP (1 pt), CMML (2 pts), Ph+ ALL (2 pts), CLL (1 pt), and chronic idiopathic myelofibrosis (CIMF) (1 pt). The MTD has not yet been determined for either schedule. In Arm 1, at the 40 mg dose level, 2 pts experienced G3 (dose-limiting) fatigue. No DLTs have been reported in Arm 2. The adverse event (AE) profile has been similar in both arms. The most common AEs (≥20%) include nausea (51%), diarrhea (43%), fatigue (39%), thrombocytopenia (31%), vomiting (30%), febrile neutropenia (28%), anorexia (26%), pyrexia (26%), dyspnea (23%), asthenia (21%), and peripheral edema (21%). The most common G3/4 AEs (≥10%) include thrombocytopenia (30%), febrile neutropenia (25%), fatigue (16%), and neutropenia (15%). Based on >2400 ECGs, no QTcF >500 msec has been recorded. In each arm, at the highest dose level explored to date, average QTcF change from baseline was <10 msec. PK has been evaluated on day 1 and at steady state by noncompartmental analysis. Mean terminal t1/2 ranged from 13–20 hrs. In Arm 1, Cmax and AUC0-inf increased linearly with dose after single and multiple doses. In Arm 2, Cmax did not increase with dose, whereas AUC0-inf increased linearly with dose only at steady state. However, the apparent differences between arms may be due to interpatient variability. Increased histone acetylation in peripheral blood leucocytes and bone marrow biopsies was observed at doses ≥20 mg. At higher dose levels, LBH589 has shown evidence of clinical activity in multiple indications, including HL (metabolic PR - Arm 1: 30mg [2 pts], Arm 2: 45mg [1 pt]); CD4+/56+ hematodermic neoplasm (PR - Arm 2: 45mg [1 pt]); CIMF (clinical improvement, transfusion independence - Arm 1: 30mg [1 pt]); and AML (CR [1 pt], significant decrease in blood and/or bone marrow blasts [3 pts] - all Arm 1: 40mg [total of 6 pts with AML in this cohort]). In both arms, the median number of cycles was 2 (range 1–11). LBH589 appears to be well tolerated and has shown evidence of clinical activity in multiple indications. Dose escalation is ongoing at 60mg (Arm 1) and 80mg (Arm 2).

Inhaled fluticasone propionate is effective as well as oral prednisone in reducing sputum eosinophilia during exacerbations of asthma which do not require hospitalization

The aim of this study was to evaluate whether fluticasone propionate (FP) is effective as well as prednisone (P) in reducing sputum eosinophilia and in improving airway obstruction due to asthma exacerbations not requiring hospitalization. We measured, in a parallel-group, double-blind double-dummy, randomized study, sputum and blood inflammatory cell counts and soluble mediators in 37 asthmatic subjects during a spontaneous exacerbation of asthma (Visit 1) and after a 2 week (Visit 2) treatment with inhaled FP (1000 μg bid) (Group A, n = 18 ) or a reducing course of oral P (Group B, n = 19 ). Asthma exacerbation was accompanied by sputum eosinophilia (eosinophils >2%) in almost all patients (95%). FP improved FEV 1 (from 53.9%±16.8 at Visit 1 to 76.4%±21.2 at Visit 2, p = 0.0001 ) and reduced the percentage of sputum eosinophils (from 38%[0–78] to 3%[1–31, p = 0.0008 ) as well as oral P (FEV 1: from 51.5%±14.4 to 83.6%±21.1, p = 0.0001 ; sputum eosinophils: from 52%[1–96] to 11%[0–64], p = 0.0003 ). At Visit 2, sputum eosinophils were significantly lower in Group A than in Group B. P but not FP induced significant decrease in blood and sputum ECP. Oxygen saturation, PEF variability, symptom score and use of rescue medication similarly improved in both groups. We conclude that FP is effective at least as well as P in reducing sputum eosinophilia and in improving airway obstruction due to asthma exacerbation. However, the cost/effectiveness ratio of this option should be further evaluated.

Changes in oxidative stress markers and NF-κB activation induced by sprint exercise

This study was aimed to investigate changes in blood markers of oxidative damage induced by short-term supramaximal anaerobic exercise and to determine whether oxidative stress was associated to activation of the redox-sensitive transcription factor nuclear factor-κB (NF-κB). Both a single Wingate test (WAnT) test and series of four WAnTs separated by 60 min rest intervals were carried out by eight professional cyclists. Leukocyte 8-OH-2-deoxyguanosine levels were significantly elevated 24 h after both exercise protocols. A significant decrease in blood reduced glutathione (GSH) concentration was observed immediately after and at 15, 60 and 120 min of the single WAnT, followed by a return to basal value after 24 h. This decrease was parallel to a significant increase of the oxidised/reduced glutathione (GSSG/GSH) ratio, to an activation of NF-κB and to a significant decrease in the protein level of its inhibitor IκB. GSH concentration and the GSSG/GSH ratio changed significantly for the first three of the WAnTs series and normalised thereafter. A significant activation of NF-κB and a decrease in the IκB protein level were also detected. We conclude that short-term supramaximal anaerobic exercise induces oxidative stress, as evidenced by non cumulative damage to macromolecules and changes in the glutathione status. Our data also indicate that high intensity anaerobic work gives rise to an activation of the transcription factor NF-κB accompanied by a degradation of IκB.

Modulatory influence of Adhatoda vasica Nees leaf extract against gamma irradiation in Swiss albino mice

The radiomodulatory influence of ethanolic extract of Adhatoda vasica Nees leaf extract against radiation-induced hematological alterations in peripheral blood of Swiss albino mice was studied at various post-irradiation intervals between 6 h to 30 days. Oral administration of A. vasica leaf extract (800 mg/kg body weight) prior to whole body irradiation showed a significant protection in terms of survival percentage and hematological parameters. Mice exposed to radiation (8.0 Gy) without A. vasica leaf extract pre-treatment exhibited signs of radiation sickness like anorexia, lethargicity, ruffled hairs and diarrhoea and such animals died within 25 days post-irradiation. The dose reduction factor (DRF = 1.6) for A. vasica leaf extract was calculated from LD50/30 values. A significant decline in hematological constituents (RBCs, WBCs, Hb and Hct) was evident till day 15 and no animal could survive beyond day 25. Conversely, animals pre-treated with A. vasica leaf extract showed 81.25% survival till 30 days after exposure and a gradual recovery was noted in the hematological values. However, these hematological values remained significantly below the normal even till day 30. A significant decrease in blood reduced glutathione (GSH) content and increase in lipid peroxidation (LPO) level was observed in control animals (Radiation alone). However, A. vasica leaf extract pretreated irradiated animals exhibited a significant increase in GSH content and decrease in LPO level. A significant increase in the serum alkaline phosphatase activity and decrease in acid phosphatase activity was observed in A. vasica leaf extract pretreated irradiated animals during the entire period of study.

Eotaxin-2 regulates newly produced and CD34 + airway eosinophils after allergen exposure

Eosinophils develop from CD34+ bone marrow progenitors, and evidence increasingly suggests that these progenitors are recruited to the airways in atopic asthmatics after allergen challenge. Moreover, it has been shown that the number of CD34+ progenitors in bronchial tissue correlates with asthma severity. To date, however, little is known about how these cells are recruited into the airways. Our aim was to evaluate the role of 2 chemokines, eotaxin-I and/or eotaxin-2, in the recruitment of newly produced and CD34+ eosinophils to the airways after allergen exposure. BALB/c mice sensitized and exposed to ovalbumin were pretreated intraperitoneally or intranasally with a neutralizing anti-eotaxin-1 and/or anti-eotaxin-2 antibody.A thymidine analogue, 5-bromo-2'-deoxyuridine (BrdU), was used to mark newly produced cells. Bronchoalveolar lavage (BAL), blood, and bone marrow were collected 24 hours after the final exposure. Anti-eotaxin-1 and/or anti-eotaxin-2 given intranasally(ie, locally to airways) significantly decreased BAL eosinophils. This decrease was paralleled with a decrease in both BrdU+and CD34+ eosinophils. In contrast, systemically administered(ie, intraperitoneally) anti-eotaxin-1 and/or anti-eotaxin-2 resulted in a significant decrease in BAL eosinophils only when the combined treatment was of a sufficiently high dosage to produce measurable concentrations in the airways.Furthermore, neither of the treated groups showed any significant decrease in blood or bone marrow eosinophils. Both eotaxin-1 and eotaxin-2 are involved locally within the airways in the regulation of the recruitment of newly produced and CD34+ eosinophils after allergen exposure.

The effect of Helicobacter pylori eradication on gastric juice and blood ammonia concentrations and on visual evoked potentials in cirrhotics.

The primary source of ammonia is the gut. Ammonia can also be generated by the urease activity of Helicobacter pylori in the gastric mucosa. The aim of this study was to investigate the effect of H. pylori eradication on blood and gastric juice ammonia levels and on visual evoked potential (VEP) recordings in cirrhotic patients. Male patients with cirrhosis and H. pylori infection were prospectively evaluated. All patients were given triple regimen for eradication for 10 days. Gastroscopy together with gastric juice sampling for ammonia and mucosal sampling for H. pylori status was performed before and after therapy. Gastric juice and blood ammonia levels were measured and VEP recordings were obtained before and after treatment. Twenty-seven patients were included in the study. Patients with overt clinical hepatic encephalopathy were excluded from the study. Twenty-four out of twenty-seven patients became H. pylori-negative after the treatment. Ammonia measurements and VEP recordings were evaluated in the 24 patients in whom eradication was successful. A slight but statistically significant decrease in blood and a considerable decrease in gastric juice ammonia levels were observed after treatment [from 44.23 micromol/l to 41.6 micromol/l compared with 3234 micromol/l to 2709 micromol/l, respectively (p <.05)] in patients in whom H. pylori was eradicated. VEP recordings were abnormal in 14 out of 24 patients before the treatment. Only four of these 14 patients with abnormal recordings showed improvement. (p > .05). Helicobacter pylori eradication in cirrhotics decreases blood and gastric juice ammonia concentrations whereas it does not provide an improvement in VEP recordings.